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Sample records for adapted human gastric

  1. Genome Sequence of Helicobacter bizzozeroniiStrain CIII-1, an Isolate from Human Gastric Mucosa ▿

    Science.gov (United States)

    Schott, Thomas; Rossi, Mirko; Hänninen, Marja-Liisa

    2011-01-01

    The canine-adapted Helicobacter bizzozeroniiis the only nonpylori Helicobacterspecies isolated from human gastric biopsy tissue. Here we present the genome sequence of strain CIII-1, isolated from a 45-year-old female patient with severe gastric symptoms. This is the first genome sequence of nonpylori gastric Helicobacterisolated from human gastritis. PMID:21705603

  2. Global regulation of virulence and the stress response by CsrA in the highly adapted human gastric pathogen Helicobacter pylori

    DEFF Research Database (Denmark)

    Barnard, F.M.; Loughlin, M.F.; Fainberg, H.P.

    2004-01-01

    Although successful and persistent colonization of the gastric mucosa depends on the ability to respond to changing environmental conditions and co-ordinate the expression of virulence factors during the course of infection, Helicobacter pylori possesses relatively few transcriptional regulators....... We therefore investigated the contribution of the regulatory protein CsrA to global gene regulation in this important human pathogen. CsrA was necessary for full motility and survival of H. pylori under conditions of oxidative stress. Loss of csrA expression deregulated the oxidant...... NapA protein was produced in the mutant strain. Finally, H. pylori strains deficient in the production of CsrA were significantly attenuated for virulence in a mouse model of infection. This work provides evidence that CsrA has a broad role in regulating the physiology of H. pylori in response...

  3. A changing gastric environment leads to adaptation of lipopolysaccharide variants in Helicobacter pylori populations during colonization.

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    Anna Skoglund

    2009-06-01

    Full Text Available The human gastric pathogen Helicobacter pylori colonizes the stomachs of half of the human population, and causes development of peptic ulcer disease and gastric adenocarcinoma. H. pylori-associated chronic atrophic gastritis (ChAG with loss of the acid-producing parietal cells, is correlated with an increased risk for development of gastric adenocarcinoma. The majority of H. pylori isolates produce lipopolysaccharides (LPS decorated with human-related Lewis epitopes, which have been shown to phase-vary in response to different environmental conditions. We have characterized the adaptations of H. pylori LPS and Lewis antigen expression to varying gastric conditions; in H. pylori isolates from mice with low or high gastric pH, respectively; in 482 clinical isolates from healthy individuals and from individuals with ChAG obtained at two time points with a four-year interval between endoscopies; and finally in isolates grown at different pH in vitro. Here we show that the gastric environment can contribute to a switch in Lewis phenotype in the two experimental mouse models. The clinical isolates from different human individuals showed that intra-individual isolates varied in Lewis antigen expression although the LPS diversity was relatively stable within each individual over time. Moreover, the isolates demonstrated considerable diversity in the levels of glycosylation and in the sizes of fucosylated O-antigen chains both within and between individuals. Thus our data suggest that different LPS variants exist in the colonizing H. pylori population, which can adapt to changes in the gastric environment and provide a means to regulate the inflammatory response of the host during disease progression.

  4. A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.

    Science.gov (United States)

    Aziz, Faisal; Yang, Xuesong; Wen, Qingping; Yan, Qiu

    2015-08-01

    At present, biopsy specimens, cancer cell lines and tissues obtained by gastric surgery are used in the study and analysis of gastric cancer, including the molecular mechanisms and proteomics. However, fibroblasts and other tissue components may interfere with these techniques. Therefore, the present study aimed to develop a procedure for the isolation of viable human gastric epithelial cells from gastric surgical tissues. A method was developed to culture human gastric epithelial cells using fresh, surgically excised tissues and was evaluated using immunocytochemistry, periodic acid-Schiff (PAS) staining and cell viability assays. Low cell growth was observed surrounding the gastric tissue on the seventh day of tissue explant culture. Cell growth subsequently increased, and at 12 days post-explant a high number of pure epithelial cells were detected. The gastric cancer cells exhibited rapid growth with a doubling time of 13-52 h, as compared to normal cells, which had a doubling time of 20-53 h. Immunocytochemical analyses of primary gastric cells revealed positive staining for cytokeratin 18 and 19, which indicated that the culture was comprised of pure epithelial cells and contained no fibroblasts. Furthermore, PAS staining demonstrated that the cultured gastric cells produced neutral mucin. Granulin and carbohydrate antigen 724 staining confirmed the purity of gastric cancer and normal cells in culture. This method of cell culture indicated that the gastric cells in primary culture consisted of mucin-secreting gastric epithelial cells, which may be useful for the study of gastric infection with Helicobacter pylori and gastric cancer.

  5. Honey and Apoptosis in Human Gastric Mucosa

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    Alireza Ostadrahimi

    2012-07-01

    Full Text Available Background: Gastric cancer is the fourth most common malignancy in the world. Honey is acomplex mixture of special biological active constituents. Honey possesses antioxidant and antitumorproperties. Nutritional studies have indicated that consumption of honey modulates therisk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisiverole in precancerous changes. Our chief study was conducted to assess the relationship betweenconsumption of honey and apoptosis in human gastric mucosa.Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred totwo hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire(FFQ and apoptosis was detected by TUNEL technique. We tested polynomial curve tofind the best fit between honey consumption and apoptosis.Results: A positive relation between honey consumption and apoptosis was found (P=0.024.Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honeyamount - 0.533(honey amount2 +1.833×10-5(honey amount7.Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis ingastric mucosa.

  6. Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

    DEFF Research Database (Denmark)

    Meier, Juris J; Goetze, Oliver; Anstipp, Jens

    2004-01-01

    . Gastric emptying was calculated from the (13)CO(2) exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA.......0, with GIP and placebo, respectively). The time pattern of gastric emptying was similar in the two groups (P = 0.98). Endogenous GIP secretion, as derived from the incremental area under the curve of plasma GIP concentrations in the placebo experiments, did not correlate to gastric half-emptying times (r(2...

  7. Alcohol and gastric acid secretion in humans: a short review.

    Science.gov (United States)

    Singer, M V; Leffmann, C

    1988-01-01

    The action of ethanol and alcoholic beverages on gastric acid secretion and release of gastrin in healthy, nonalcoholic humans is reviewed. Intravenous ethanol causes a dose-dependent stimulation of gastric acid output without releasing gastrin. The action of intragastric instillation of pure ethanol on gastric acid secretion is related to its concentration: concentrations of 1.4% and 4% (v/v) are moderate stimulants; concentrations of 5% to 40% (w/v) have no or rather an inhibitory effect. Oral, intragastric, and intraduodenal administrations of ethanol do not release gastrin, whereas beer and white and red wine but not whisky and cognac are potent stimulants of gastric acid secretion and release gastrin in humans. The stimulatory mechanism of low ethanol concentrations is unknown. Nonalcoholic constituents of beer and wine are most likely responsible for the strong stimulatory action of both beverages on gastric acid secretion and release of gastrin.

  8. Alcohol and gastric acid secretion in humans.

    Science.gov (United States)

    Chari, S; Teyssen, S; Singer, M V

    1993-06-01

    The secretory response of gastric acid to pure ethanol and alcoholic beverages may be different because the action of the non-ethanolic contents of the beverage may overwhelm that of ethanol. Pure ethanol in low concentrations (cognac) do not stimulate gastric acid secretion or release of gastrin. The powerful stimulants of gastric acid secretion present in beer, which are yet to be identified, are thermostable and anionic polar substances. The effect of chronic alcohol abuse on gastric acid secretion is not as predictable. Chronic alcoholic patients may have normal, enhanced, or diminished acid secretory capacity; hypochlorhydria being associated histologically with atrophic gastritis. There are no studies on the acute effect of alcohol intake on gastric acid secretion in chronic alcoholic patients. The acid stimulatory component of beer and wine needs to be characterised and its possible role in the causation of alcohol induced gastrointestinal diseases needs to be investigated.

  9. Translating Developmental Principles to Generate Human Gastric Organoids

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    Alexandra K. Eicher

    2018-01-01

    Full Text Available Gastric diseases, including peptic ulcer disease and gastric cancer, are highly prevalent in human beings. Despite this, the cellular biology of the stomach remains poorly understood relative to other gastrointestinal organs such as the liver, intestine, and colon. In particular, little is known about the molecular basis of stomach development and the differentiation of gastric lineages. Although animal models are useful for studying gastric development, function, and disease, there are major structural and physiological differences in human stomachs that render these models insufficient. To look at gastric development, function, and disease in a human context, a model system of the human stomach is imperative. This review details how this was achieved through the directed differentiation of human pluripotent stem cells in a 3-dimensional environment into human gastric organoids (HGOs. Similar to previous work that has generated human intestine, colon, and lung tissue in vitro, HGOs were generated in vitro through a step-wise differentiation designed to mimic the temporal-spatial signaling dynamics that control stomach development in vivo. HGOs can be used for a variety of purposes, including genetic modeling, drug screening, and potentially even in future patient transplantation. Moreover, HGOs are well suited to study the development and interactions of nonepithelial cell types, such as endothelial, neuronal, and mesenchymal, which remain almost completely unstudied. This review discusses the basics of stomach morphology, function, and developmental pathways involved in generating HGOs. We also highlight important gaps in our understanding of how epithelial and mesenchymal interactions are essential for the development and overall function of the human stomach.

  10. Helicobacter suis causes severe gastric pathology in mouse and mongolian gerbil models of human gastric disease.

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    Bram Flahou

    Full Text Available BACKGROUND: "Helicobacter (H. heilmannii" type 1 is the most prevalent gastric non-H. pylori Helicobacter species in humans suffering from gastric disease. It has been shown to be identical to H. suis, a bacterium which is mainly associated with pigs. To obtain better insights into the long-term pathogenesis of infections with this micro-organism, experimental infections were carried out in different rodent models. METHODOLOGY/PRINCIPAL FINDINGS: Mongolian gerbils and mice of two strains (BALB/c and C57BL/6 were infected with H. suis and sacrificed at 3 weeks, 9 weeks and 8 months after infection. Gastric tissue samples were collected for PCR analysis, histological and ultrastructural examination. In gerbils, bacteria mainly colonized the antrum and a narrow zone in the fundus near the forestomach/stomach transition zone. In both mice strains, bacteria colonized the entire glandular stomach. Colonization with H. suis was associated with necrosis of parietal cells in all three animal strains. From 9 weeks after infection onwards, an increased proliferation rate of mucosal epithelial cells was detected in the stomach regions colonized with H. suis. Most gerbils showed a marked lymphocytic infiltration in the antrum and in the forestomach/stomach transition zone, becoming more pronounced in the course of time. At 8 months post infection, severe destruction of the normal antral architecture at the inflamed sites and development of mucosa-associated lymphoid tissue (MALT lymphoma-like lesions were observed in some gerbils. In mice, the inflammatory response was less pronounced than in gerbils, consisting mainly of mononuclear cell infiltration and being most severe in the fundus. CONCLUSIONS/SIGNIFICANCE: H. suis causes death of parietal cells, epithelial cell hyperproliferation and severe inflammation in mice and Mongolian gerbil models of human gastric disease. Moreover, MALT lymphoma-like lesions were induced in H. suis-infected Mongolian gerbils

  11. Helicobacter suis causes severe gastric pathology in mouse and mongolian gerbil models of human gastric disease.

    Science.gov (United States)

    Flahou, Bram; Haesebrouck, Freddy; Pasmans, Frank; D'Herde, Katharina; Driessen, Ann; Van Deun, Kim; Smet, Annemieke; Duchateau, Luc; Chiers, Koen; Ducatelle, Richard

    2010-11-22

    "Helicobacter (H.) heilmannii" type 1 is the most prevalent gastric non-H. pylori Helicobacter species in humans suffering from gastric disease. It has been shown to be identical to H. suis, a bacterium which is mainly associated with pigs. To obtain better insights into the long-term pathogenesis of infections with this micro-organism, experimental infections were carried out in different rodent models. Mongolian gerbils and mice of two strains (BALB/c and C57BL/6) were infected with H. suis and sacrificed at 3 weeks, 9 weeks and 8 months after infection. Gastric tissue samples were collected for PCR analysis, histological and ultrastructural examination. In gerbils, bacteria mainly colonized the antrum and a narrow zone in the fundus near the forestomach/stomach transition zone. In both mice strains, bacteria colonized the entire glandular stomach. Colonization with H. suis was associated with necrosis of parietal cells in all three animal strains. From 9 weeks after infection onwards, an increased proliferation rate of mucosal epithelial cells was detected in the stomach regions colonized with H. suis. Most gerbils showed a marked lymphocytic infiltration in the antrum and in the forestomach/stomach transition zone, becoming more pronounced in the course of time. At 8 months post infection, severe destruction of the normal antral architecture at the inflamed sites and development of mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions were observed in some gerbils. In mice, the inflammatory response was less pronounced than in gerbils, consisting mainly of mononuclear cell infiltration and being most severe in the fundus. H. suis causes death of parietal cells, epithelial cell hyperproliferation and severe inflammation in mice and Mongolian gerbil models of human gastric disease. Moreover, MALT lymphoma-like lesions were induced in H. suis-infected Mongolian gerbils. Therefore, the possible involvement of this micro-organism in human gastric disease

  12. Human pathogen avoidance adaptations

    NARCIS (Netherlands)

    Tybur, J.M.; Lieberman, D.

    2016-01-01

    Over the past few decades, researchers have become increasingly interested in the adaptations guiding the avoidance of disease-causing organisms. Here we discuss the latest developments in this area, including a recently developed information-processing model of the adaptations underlying pathogen

  13. Differential growth factor induction and modulation of human gastric epithelial regeneration

    International Nuclear Information System (INIS)

    Tetreault, Marie-Pier; Chailler, Pierre; Rivard, Nathalie; Menard, Daniel

    2005-01-01

    While several autocrine/paracrine growth factors (GFs) can all stimulate epithelial regeneration in experimentally wounded primary gastric cultures, clinical relevance for their non-redundant cooperative actions in human gastric ulcer healing is suggested by the sequential pattern of GF gene induction in vivo. Using new HGE cell lines able to form a coherent monolayer with tight junctions as well as using primary human gastric epithelial cultures, we show that EGF, TGFα, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGFβ pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGFα exerts strong effects (even more than EGF) on cytoplasmic spreading and non-oriented protruding activity of bordering cells whereas HGF preferentially coordinates single lamella formation, cell elongation and migration into the wound. IGF-I and IGF-II rather induce the alignment of bordering cells and maintain a compact monolayer front. The number of mitotic cells maximally increases with EGF, followed by TGFα and IGF-I,-II. The current study demonstrates that GFs differentially regulate the regeneration of human gastric epithelial cells through specific modulation of cell shape adaptation, migration and proliferation, further stressing that a coordination of GF activities would be necessary for the normal progression of post-wounding epithelial repair

  14. Human whole body cold adaptation.

    NARCIS (Netherlands)

    Daanen, Hein A.M.; Van Marken Lichtenbelt, Wouter D.

    2016-01-01

    Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced

  15. An Anticancer Role of Hydrogen Sulfide in Human Gastric Cancer Cells

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    Li Zhang

    2015-01-01

    Full Text Available Hydrogen sulfide (H2S can be synthesized in mammalian cells by cystathionine γ-lyase (CSE and/or cystathionine β-synthase (CBS. Both CSE and CBS are expressed in rat gastric tissues but their role in human gastric neoplasia has been unclear. The aims of the present study were to detect CSE and CBS proteins in human gastric cancer and determine the effect of exogenous NaHS on the proliferation of gastric cancer cells. We found that both CSE and CBS proteins were expressed in human gastric cancer cells and upregulated in human gastric carcinoma mucosa compared with those in noncancerous gastric samples. NaHS induced apoptosis of gastric cancer cells by regulating apoptosis related proteins. Also, NaHS inhibited cancer cell migration and invasion. An antigastric cancer role of H2S is thus indicated.

  16. Terahertz spectroscopic investigation of human gastric normal and tumor tissues.

    Science.gov (United States)

    Hou, Dibo; Li, Xian; Cai, Jinhui; Ma, Yehao; Kang, Xusheng; Huang, Pingjie; Zhang, Guangxin

    2014-09-21

    Human dehydrated normal and cancerous gastric tissues were measured using transmission time-domain terahertz spectroscopy. Based on the obtained terahertz absorption spectra, the contrasts between the two kinds of tissue were investigated and techniques for automatic identification of cancerous tissue were studied. Distinctive differences were demonstrated in both the shape and amplitude of the absorption spectra between normal and tumor tissue. Additionally, some spectral features in the range of 0.2~0.5 THz and 1~1.5 THz were revealed for all cancerous gastric tissues. To systematically achieve the identification of gastric cancer, principal component analysis combined with t-test was used to extract valuable information indicating the best distinction between the two types. Two clustering approaches, K-means and support vector machine (SVM), were then performed to classify the processed terahertz data into normal and cancerous groups. SVM presented a satisfactory result with less false classification cases. The results of this study implicate the potential of the terahertz technique to detect gastric cancer. The applied data analysis methodology provides a suggestion for automatic discrimination of terahertz spectra in other applications.

  17. Population Genomics of Human Adaptation

    OpenAIRE

    Lachance, Joseph; Tishkoff, Sarah A.

    2013-01-01

    Recent advances in genotyping technologies have facilitated genome-wide scans for natural selection. Identification of targets of natural selection will shed light on processes of human adaptation and evolution and could be important for identifying variation that influences both normal human phenotypic variation as well as disease susceptibility. Here we focus on studies of natural selection in modern humans who originated ~200,000 years go in Africa and migrated across the globe ~50,000 – 1...

  18. Human Gastric Mucosal Hydrophobicity Does dot Decrease with Helicobacter Pylori Infection or Chronological Age

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    Mohammed S Al-Marhoon

    2005-01-01

    Full Text Available BACKGROUND AND AIMS: Infection with cytotoxin-associated gene A (cagA Helicobacter pylori is associated with severe gastric diseases. Previous studies in humans have reported a decreased gastric hydrophobicity with H pylori infection. The aim of the present study was to differentiate between the effect of cagA+ and cagA- strains on gastric mucus hydrophobicity.

  19. Magnetogastrographic detection of gastric electrical response activity in humans

    International Nuclear Information System (INIS)

    Irimia, Andrei; Richards, William O; Bradshaw, L Alan

    2006-01-01

    The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is characterized by spiking potentials during the plateau phase of the ECA. Whereas the ECA has been recorded in humans both invasively and non-invasively (magnetogastrography-MGG), the ERA has never been detected non-invasively in humans before. In this paper, we report on our progress towards the non-invasive detection of ERA from the human stomach using a procedure that involves the application of principal component analysis to MGG recordings, which were acquired in our case from ten normal human patients using a Superconducting QUantum Interference Device (SQUID) magnetometer. Both pre- and post-prandial recordings were acquired for each patient and 20 min of recordings (10 min of pre-prandial and 10 min of post-prandial data) were analysed for each patient. The mean percentage of ECA slow waves that were found to exhibit spikes of suspected ERA origin was 41% and 61% for pre- and post-prandial recordings, respectively, implying a 47% ERA increase post-prandially (P < 0.0001 at a 95% confidence level). The detection of ERA in humans is highly encouraging and points to the possible use of non-invasive ERA recordings as a valuable tool for the study of human gastric disorders

  20. Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori-infected human gastric epithelium.

    Science.gov (United States)

    Mihara, Hiroshi; Suzuki, Nobuhiro; Muhammad, Jibran Sualeh; Nanjo, Sohachi; Ando, Takayuki; Fujinami, Haruka; Kajiura, Shinya; Hosokawa, Ayumu; Sugiyama, Toshiro

    2017-04-01

    Helicobacter pylori (HP) infection induces methylation silencing of specific genes in gastric epithelium. Various stimuli activate the nonselective cation channel TRPV4, which is expressed in gastric epithelium where it detects mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are methylated in HP-infected gastric epithelium, we evaluated HP infection-dependent changes in TRPV4 expression in gastric epithelium. Human gastric biopsy samples, a human gastric cancer cell line (AGS), and a normal gastric epithelial cell line (GES-1) were used to detect TRPV4 mRNA and protein expression by RT-PCR and Western blotting, respectively. Ca 2+ imaging was used to evaluate TRPV4 ion channel activity. TRPV4 methylation status was assessed by methylation-specific PCR (MSP). ATP release was measured by a luciferin-luciferase assay. TRPV4 mRNA and protein were detected in human gastric biopsy samples and in GES-1 cells. MSP and demethylation assays showed TRPV4 methylation silencing in AGS cells. HP coculture directly induced methylation silencing of TRPV4 in GES-1 cells. In human samples, HP infection was associated with TRPV4 methylation silencing that recovered after HP eradication in a time-dependent manner. HP infection-dependent DNA methylation suppressed TRPV4 expression in human gastric epithelia, suggesting that TRPV4 methylation may be involved in HP-associated dyspepsia. © 2016 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  1. The role of the obestatin/GPR39 system in human gastric adenocarcinomas.

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    Alén, Begoña O; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S; Beiras, Andrés; Casanueva, Felipe F; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P; Pazos, Yolanda

    2016-02-02

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.

  2. Apoptosis induced by GanoPoly in human gastric cancer cell line ...

    African Journals Online (AJOL)

    In order to investigate polysaccharide effect on the cultured human gastric cancer cells (SGC7901), DNA ladder, flow cytometry and western blot were used to examine the morpholog, proliferation and apoptosis of human gastric cancer SGC-7901 cells when they were affected by polysaccharide. Results show that ...

  3. Effect of sialoadenectomy and synthetic human urogastrone on healing of chronic gastric ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of extirpation of the submandibular glands, an exocrine organ for epidermal growth factor/urogastrone (EGF/URO), and the effect of oral administration of synthetic human (EGF/URO) on healing of chronic gastric ulcers in rats has been investigated. Removal of the submandibular glands...... delayed healing of chronic gastric ulcers when examined after 50, 100, and 200 days. Oral administration of synthetic human EGF/URO stimulated gastric ulcer healing when examined after 25 and 50 days of treatment. The effect of synthetic human EGF/URO was comparable with that of cimetidine. The combined...... administration of synthetic human EGF/URO and cimetidine further increased healing of gastric ulcers compared with administration of each substance. Neither synthetic human EGF/URO, nor removal of the submandibular glands had any influence on gastric acid secretion. This study showed that the submandibular...

  4. Energy Adaptations Persist 2 Years After Sleeve Gastrectomy and Gastric Bypass.

    Science.gov (United States)

    Tam, Charmaine S; Rigas, Georgia; Heilbronn, Leonie K; Matisan, Tania; Probst, Yasmine; Talbot, Michael

    2016-02-01

    Non-surgical weight loss induces a greater than expected decrease in energy expenditure, a phenomenon known as 'metabolic adaptation'. The effects of different bariatric surgery procedures on metabolic adaptation are not yet known and may partially contribute to weight loss success. We compared resting energy expenditure (REE) in 35 subjects (nine males; age = 46 ± 11 years; BMI = 42.1 ± 6.5 kg/m(2)) undergoing gastric band, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) up to 2 years after surgery. We found a greater than expected reduction of 130-300 kcal/day at 6 weeks after sleeve and bypass surgery which was not explained by changes in body composition; this change was not seen in the band group. The suppression in REE after sleeve and RYGB remained up to 2 years, even after weight loss had plateaued. Our findings suggest that energy adaptation is not a contributing mechanism to medium-term weight maintenance after sleeve and RYGB bariatric surgeries.

  5. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Søndergaard, S B; Fuglsang, S

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans...... gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  6. The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?

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    Nardone, Gerardo; Compare, Debora

    2015-06-01

    Although long thought to be a sterile organ, due to its acid production, the human stomach holds a core microbiome. To provide an update of findings related to gastric microbiota and its link with gastric diseases. We conducted a systematic review of the literature. The development of culture-independent methods facilitated the identification of many bacteria. Five major phyla have been detected in the stomach: Firmicutes, Bacteroidites, Actinobacteria, Fusobacteria and Proteobacteria. At the genera level, the healthy human stomach is dominated by Prevotella, Streptococcus, Veillonella, Rothia and Haemophilus; however, the composition of the gastric microbiota is dynamic and affected by such factors as diet, drugs and diseases. The interaction between the pre-existing gastric microbiota and Helicobacter pylori infection might influence an individual's risk of gastric disease, including gastric cancer. The maintenance of bacterial homeostasis could be essential for the stomach's health and highlights the chance for therapeutic interventions targeting the gastric microbiota, even if gastric pH, peristalsis and the mucus layer may prevent bacteria colonization; and the definition of gastric microbiota of the healthy stomach is still an ongoing challenging task.

  7. Characterization of gastrins and their receptor in solid human gastric adenocarcinomas

    DEFF Research Database (Denmark)

    Goetze, Jens Peter; Eiland, Signe; Svendsen, Lars Bo

    2013-01-01

    of the progastrin-derived peptides in gastric cancer has not been reported. The authors therefore examined the molecular nature of gastrin and its receptor in human gastric carcinomas. MATERIALS AND METHODS: Twenty patients with adenocarcinoma underwent partial or total gastrectomy. In samples from each carcinoma...

  8. Effect of sialoadenectomy and synthetic human urogastrone on healing of chronic gastric ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of extirpation of the submandibular glands, an exocrine organ for epidermal growth factor/urogastrone (EGF/URO), and the effect of oral administration of synthetic human (EGF/URO) on healing of chronic gastric ulcers in rats has been investigated. Removal of the submandibular glands...... delayed healing of chronic gastric ulcers when examined after 50, 100, and 200 days. Oral administration of synthetic human EGF/URO stimulated gastric ulcer healing when examined after 25 and 50 days of treatment. The effect of synthetic human EGF/URO was comparable with that of cimetidine. The combined...

  9. ERC/mesothelin is expressed in human gastric cancer tissues and cell lines.

    Science.gov (United States)

    Ito, Tomoaki; Kajino, Kazunori; Abe, Masaaki; Sato, Koichi; Maekawa, Hiroshi; Sakurada, Mutsumi; Orita, Hajime; Wada, Ryo; Kajiyama, Yoshiaki; Hino, Okio

    2014-01-01

    ERC/mesothelin is expressed in mesothelioma and other malignancies. The ERC/mesothelin gene (MSLN) encodes a 71-kDa precursor protein, which is cleaved to yield 31-kDa N-terminal (N-ERC/mesothelin) and 40-kDa C-terminal (C-ERC/mesothelin) proteins. N-ERC/mesothelin is a soluble protein and has been reported to be a diagnostic serum marker of mesothelioma and ovarian cancer. Gastric cancer tissue also expresses C-ERC/mesothelin, but the significance of serum N-ERC levels for diagnosing gastric cancer has not yet been studied. We examined the latter issue in the present study as well as C-ERC/mesothelin expression in human gastric cancer tissues and cell lines. We immunohistochemically examined C-ERC/mesothelin expression in tissue samples from 50 cases of gastric cancer, and we also assessed the C-ERC/mesothelin expression in 6 gastric cancer cell lines (MKN-1, MKN-7, MKN-74, NUGC-3, NUGC-4 and TMK-1) using reverse transcription-polymerase chain reaction, flow cytometry, immunohistochemistry and immunoblotting. We also examined the N-ERC/mesothelin concentrations in the supernatants of cultured cells and in the sera of gastric cancer patients using an enzyme-linked immunosorbent assay (ELISA). N-ERC/mesothelin was detected in the supernatants of 3 gastric cancer cell lines (MKN-1, NUGC-4 and TMK-1) by ELISA, but its concentration in the sera of gastric cancer patients was almost same as that observed in the sera of the normal controls. In the gastric cancer tissues, C-ERC/mesothelin expression was associated with lymphatic invasion. N-ERC/mesothelin was secreted into the supernatants of gastric cancer cell lines, but does not appear to be a useful serum marker of gastric cancer.

  10. Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients.

    Science.gov (United States)

    Yu, Guoqin; Torres, Javier; Hu, Nan; Medrano-Guzman, Rafael; Herrera-Goepfert, Roberto; Humphrys, Michael S; Wang, Lemin; Wang, Chaoyu; Ding, Ti; Ravel, Jacques; Taylor, Philip R; Abnet, Christian C; Goldstein, Alisa M

    2017-01-01

    Helicobacter pylori ( Hp ) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.

  11. Co-lyophilized Aspirin with Trehalose Causes Less Injury to Human Gastric Cells and Gastric Mucosa of Rats.

    Science.gov (United States)

    Lin, Lee-Shuan; Kayasuga-Kariya, Yuko; Nakamura, Shugo; Shimohata, Nobuyuki; Sakai, Takamasa; Fujisawa, Ayano; Akagi, Yuki; Suzuki, Shigeki; Chung, Ung-Il; Sasaki, Nobuo; Mochizuki, Manabu

    2016-08-01

    Aspirin is one of the most popular NSAIDs worldwide because of its anti-inflammatory and anticoagulant effects, and however, gastrointestinal injury remains a major complication. We previously reported co-lyophilized aspirin/trehalose (Lyo A/T) decreased the aspirin-induced gastric lesions in dogs. This study investigated the mechanism of gastroprotective effects of trehalose in vitro and in vivo. The apoptotic assays were performed in a human gastric carcinoma cell line, which was treated with aspirin, mixed aspirin/trehalose (Mix A/T) or Lyo A/T. Gastric ulcer severity was examined after oral administration of drugs in rats. In addition, the mucosal tissue apoptotic status in drug-treated rats was evaluated. Molecular dynamics simulations and laser Raman spectroscopy were performed in order to examine the molecular properties of Lyo A/T. DNA fragmentation was detected in AGS cells that were treated with aspirin and Mix A/T, but not in the Lyo A/T-treated cells. There were fewer apoptotic cells in the Lyo A/T-treated cells than in the other cells. Gastric injury was reduced in rats that received oral Lyo A/T compared with the others, while PGE2 synthesis was equally decreased in all groups. TUNEL assay and immunohistochemistry of cleaved caspase-3 in the mucosal tissues also revealed that Lyo A/T treatment induced less apoptosis than the others. The Lyo A/T spectrum showed clear differences in several Raman bands compared with that of Mix A/T. Our data showed that co-lyophilization of aspirin with trehalose reduced gastric injury, potentially through suppression of aspirin-induced mucosal cell apoptosis while retaining its anti-inflammatory effects.

  12. Gastric helicobacters in domestic animals and nonhuman primates and their significance for human health.

    Science.gov (United States)

    Haesebrouck, Freddy; Pasmans, Frank; Flahou, Bram; Chiers, Koen; Baele, Margo; Meyns, Tom; Decostere, Annemie; Ducatelle, Richard

    2009-04-01

    Helicobacters other than Helicobacter pylori have been associated with gastritis, gastric ulcers, and gastric mucosa-associated lymphoid tissue lymphoma in humans. These very fastidious microorganisms with a typical large spiral-shaped morphology were provisionally designated "H. heilmannii," but in fact they comprise at least five different Helicobacter species, all of which are known to colonize the gastric mucosa of animals. H. suis, which has been isolated from the stomachs of pigs, is the most prevalent gastric non-H. pylori Helicobacter species in humans. Other gastric non-H. pylori helicobacters colonizing the human stomach are H. felis, H. salomonis, H. bizzozeronii, and the still-uncultivable "Candidatus Helicobacter heilmannii." These microorganisms are often detected in the stomachs of dogs and cats. "Candidatus Helicobacter bovis" is highly prevalent in the abomasums of cattle but has only occasionally been detected in the stomachs of humans. There are clear indications that gastric non-H. pylori Helicobacter infections in humans originate from animals, and it is likely that transmission to humans occurs through direct contact. Little is known about the virulence factors of these microorganisms. The recent successes with in vitro isolation of non-H. pylori helicobacters from domestic animals open new perspectives for studying these microorganisms and their interactions with the host.

  13. Effects of the H2-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J.L.; Graff, J.

    2008-01-01

    OBJECTIVE: Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist......, on gastric volume and gastric emptying after a liquid meal in healthy humans. MATERIAL AND METHODS: Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission......: Ranitidine did not change gastric volume before the meal, nor at 0 h or 1 h after it. Furthermore, ranitidine did not influence gastric retention of meal components after 0.5 h and 1 h. CONCLUSIONS: Intravenous bolus injection of 50 mg ranitidine does not modify gastric volume or gastric emptying after a 600...

  14. Effects of the H(2)-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Graff, J

    2008-01-01

    Objective. Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist......, on gastric volume and gastric emptying after a liquid meal in healthy humans. Material and methods. Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission....... Ranitidine did not change gastric volume before the meal, nor at 0 h or 1 h after it. Furthermore, ranitidine did not influence gastric retention of meal components after 0.5 h and 1 h. Conclusions. Intravenous bolus injection of 50 mg ranitidine does not modify gastric volume or gastric emptying after a 600...

  15. Synchrotron-radiation phase-contrast imaging of human stomach and gastric cancer: in vitro studies.

    Science.gov (United States)

    Tang, Lei; Li, Gang; Sun, Ying-Shi; Li, Jie; Zhang, Xiao-Peng

    2012-05-01

    The electron density resolution of synchrotron-radiation phase-contrast imaging (SR-PCI) is 1000 times higher than that of conventional X-ray absorption imaging in light elements, through which high-resolution X-ray imaging of biological soft tissue can be achieved. For biological soft tissue, SR-PCI can give better imaging contrast than conventional X-ray absorption imaging. In this study, human resected stomach and gastric cancer were investigated using in-line holography and diffraction enhanced imaging at beamline 4W1A of the Beijing Synchrotron Radiation Facility. It was possible to depict gastric pits, measuring 50-70 µm, gastric grooves and tiny blood vessels in the submucosa layer by SR-PCI. The fine structure of a cancerous ulcer was displayed clearly on imaging the mucosa. The delamination of the gastric wall and infiltration of cancer in the submucosa layer were also demonstrated on cross-sectional imaging. In conclusion, SR-PCI can demonstrate the subtle structures of stomach and gastric cancer that cannot be detected by conventional X-ray absorption imaging, which prompt the X-ray diagnosis of gastric disease to the level of the gastric pit, and has the potential to provide new methods for the imageology of gastric cancer.

  16. Oxygenated hemoglobin diffuse reflectance ratio for in vitro detection of human gastric pre-cancer

    Science.gov (United States)

    Li, L. Q.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Zhong, H. Q.; Li, X. Y.; Zhao, Q. L.; Guo, X.

    2010-07-01

    Oxygenated hemoglobin diffuse reflectance (DR) ratio (R540/R575) method based on DR spectral signatures is used for early diagnosis of malignant lesions of human gastric epithelial tissues in vitro. The DR spectra for four different kinds of gastric epithelial tissues were measured using a spectrometer with an integrating sphere detector in the spectral range from 400 to 650 nm. The results of measurement showed that the average DR spectral intensity for the epithelial tissues of normal stomach is higher than that for the epithelial tissues of chronic and malignant stomach and that for the epithelial tissues of chronic gastric ulcer is higher than that for the epithelial tissues of malignant stomach. The average DR spectra for four different kinds of gastric epithelial tissues show dips at 542 and 577 nm owing to absorption from oxygenated Hemoglobin (HbO2). The differences in the mean R540/R575 ratios of HbO2 bands are 6.84% between the epithelial tissues of normal stomach and chronic gastric ulcer, 14.7% between the epithelial tissues of normal stomach and poorly differentiated gastric adenocarcinoma and 22.6% between the epithelial tissues of normal stomach and undifferentiated gastric adenocarcinoma. It is evident from results that there were significant differences in the mean R540/R575 ratios of HbO2 bands for four different kinds of gastric epithelial tissues in vitro ( P < 0.01).

  17. Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities

    DEFF Research Database (Denmark)

    Pedersen, Pernille Barbre; Vilmann, Peter; Bar-Shalom, Daniel

    2013-01-01

    characterization of the aspirates was conducted on a TA AR-G2 rheometer, using cone and plate geometry. Lipase activity was measured by continuous titration of released free fatty acid from tributyrate. Further, pH, osmolality, buffer capacity, and surface tension were measured and the total protein content.......8 and 5.4, respectively. pH, surface tension, buffer capacity, bile salt concentration, and osmolality were measured and compared with literature data. CONCLUSION: The rheological behavior and the mean apparent viscosity of HGA are significantly different from that of water and should therefore...... be considered important during development of gastric simulated media. Further, the activity of the HGL is active even under fasted gastric conditions and might contribute to the digestion and emulsification of lipid-based drug delivery systems in the entire gastrointestinal tract. HGL should therefore...

  18. Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.

    Directory of Open Access Journals (Sweden)

    Zhi Xu

    Full Text Available Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7% in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.

  19. Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hu; Peng, Jun-Sheng [Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital (Gastrointestinal and Anal Hospital), Sun Yat-sen University, Guangzhou, Guangdong (China); Yao, Dong-Sheng [National Engineering Research Center of Genetic Medicine,Ji Nan University, Guangzhou, Guangdong (China); Yang, Zu-Li [Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital (Gastrointestinal and Anal Hospital), Sun Yat-sen University, Guangzhou, Guangdong (China); Liu, Huan-Liang [Institute of Gastroenterology,Sun Yat-sen University, Guangzhou, Guangdong (China); Zeng, Yi-Ke [Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital (Gastrointestinal and Anal Hospital), Sun Yat-sen University, Guangzhou, Guangdong (China); Shi, Xian-Ping; Lu, Bi-Yan [Institute of Gastroenterology,Sun Yat-sen University, Guangzhou, Guangdong (China)

    2011-11-25

    Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.

  20. Association between Increased Gastric Juice Acidity and Sliding Hiatal Hernia Development in Humans.

    Directory of Open Access Journals (Sweden)

    Hiroshi Kishikawa

    Full Text Available Several clinical factors; overweight, male gender and increasing age, have been implicated as the etiology of hiatal hernia. Esophageal shortening due to acid perfusion in the lower esophagus has been suggested as the etiological mechanism. However, little is known about the correlation between gastric acidity and sliding hiatus hernia formation. This study examined whether increased gastric acid secretion is associated with an endoscopic diagnosis of hiatal hernia.A total of 286 consecutive asymptomatic patients (64 were diagnosed as having a hiatal hernia who underwent upper gastrointestinal endoscopy were studied. Clinical findings including fasting gastric juice pH as an indicator of acid secretion, age, sex, body mass index, and Helicobacter pylori infection status determined by both Helicobacter pylori serology and pepsinogen status, were evaluated to identify predictors in subjects with hiatal hernia.Male gender, obesity with a body mass index >25, and fasting gastric juice pH were significantly different between subjects with and without hiatal hernia. The cut-off point of fasting gastric juice pH determined by receiver operating curve analysis was 2.1. Multivariate regression analyses using these variables, and age, which is known to be associated with hiatal hernia, revealed that increased gastric acid secretion with fasting gastric juice pH 25 (OR = 3.49, 95% CI: 1.77-6.91 and age >65 years (OR = 1.86, 95% CI: 1.00-3.45, were also significantly associated with hiatal hernia.This study suggests that increased gastric acid secretion independently induces the development of hiatal hernia in humans. These results are in accordance with the previously reported hypothesis that high gastric acid itself induces hiatal hernia development.

  1. Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

    International Nuclear Information System (INIS)

    Song, Hu; Peng, Jun-Sheng; Yao, Dong-Sheng; Yang, Zu-Li; Liu, Huan-Liang; Zeng, Yi-Ke; Shi, Xian-Ping; Lu, Bi-Yan

    2011-01-01

    Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms

  2. Effects of the H(2)-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Graff, J

    2008-01-01

    computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. Results......, on gastric volume and gastric emptying after a liquid meal in healthy humans. Material and methods. Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...

  3. Effects of the H2-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J.L.; Graff, J.

    2008-01-01

    computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. RESULTS......, on gastric volume and gastric emptying after a liquid meal in healthy humans. MATERIAL AND METHODS: Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...

  4. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2.

    Science.gov (United States)

    Zhang, Ping; Luo, He-Sheng; Li, Ming; Tan, Shi-Yun

    2015-01-01

    Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic

  5. Alcoholic beverages produced by alcoholic fermentation but not by distillation are powerful stimulants of gastric acid secretion in humans.

    OpenAIRE

    Teyssen, S; Lenzing, T; González-Calero, G; Korn, A; Riepl, R L; Singer, M V

    1997-01-01

    BACKGROUND: The effect of commonly ingested alcoholic beverages on gastric acid output and release of gastrin in humans is unknown. AIM AND METHODS: In 16 healthy humans the effect of some commonly ingested alcoholic beverages produced by fermentation plus distillation (for example, whisky, cognac, calvados, armagnac, and rum) or by alcoholic fermentation (beer, wine, champagne, martini, and sherry) on gastric acid output and release of gastrin was studied. Gastric acid output was determined ...

  6. Apoptosis induced by GanoPoly in human gastric cancer cell line ...

    African Journals Online (AJOL)

    use

    2011-12-12

    Dec 12, 2011 ... College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, People's Republic of China. Accepted 4 ... In order to investigate polysaccharide effect on the cultured human gastric cancer cells (SGC7901), DNA ladder, flow ... the kidney's function and soothe human's breath and also.

  7. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection

    NARCIS (Netherlands)

    Bartfeld, Sina; Bayram, Tülay; van de Wetering, Marc; Huch, Meritxell; Begthel, Harry; Kujala, Pekka; Vries, Robert|info:eu-repo/dai/nl/341413755; Peters, Peter J; Clevers, Hans|info:eu-repo/dai/nl/07164282X

    BACKGROUND & AIMS: We previously established long-term, 3-dimensional culture of organoids from mouse tissues (intestine, stomach, pancreas, and liver) and human intestine and pancreas. Here we describe conditions required for long-term 3-dimensional culture of human gastric stem cells. The

  8. Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

    Science.gov (United States)

    Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

    2008-09-01

    The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine.

  9. Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer.

    Directory of Open Access Journals (Sweden)

    Biao Fan

    Full Text Available BACKGROUND: Genomic instability with frequent DNA copy number alterations is one of the key hallmarks of carcinogenesis. The chromosomal regions with frequent DNA copy number gain and loss in human gastric cancer are still poorly defined. It remains unknown how the DNA copy number variations contributes to the changes of gene expression profiles, especially on the global level. PRINCIPAL FINDINGS: We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC arrays based comparative genomic hybridization (aCGH. Statistical analysis was applied to correlate previously published gene expression data obtained from cDNA microarrays with corresponding DNA copy number variation data to identify candidate oncogenes and tumor suppressor genes. We found that gastric cancer samples showed recurrent DNA copy number variations, including gains at 5p, 8q, 20p, 20q, and losses at 4q, 9p, 18q, 21q. The most frequent regions of amplification were 20q12 (7/72, 20q12-20q13.1 (12/72, 20q13.1-20q13.2 (11/72 and 20q13.2-20q13.3 (6/72. The most frequent deleted region was 9p21 (8/72. Correlating gene expression array data with aCGH identified 321 candidate oncogenes, which were overexpressed and showed frequent DNA copy number gains; and 12 candidate tumor suppressor genes which were down-regulated and showed frequent DNA copy number losses in human gastric cancers. Three networks of significantly expressed genes in gastric cancer samples were identified by ingenuity pathway analysis. CONCLUSIONS: This study provides insight into DNA copy number variations and their contribution to altered gene expression profiles during human gastric cancer development. It provides novel candidate driver oncogenes or tumor suppressor genes for human gastric cancer, useful pathway maps for the future understanding of the molecular pathogenesis of this malignancy, and the construction of new

  10. Comments on: The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study

    Directory of Open Access Journals (Sweden)

    Ekaterina A Pigarova

    2012-06-01

    Full Text Available Comments on: Stevens JE, Horowitz M, Deacon CF, Nauck M, Rayner CK, Jones KL. The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study. Aliment Pharmacol Ther. 2012 Jun 28. doi: 10.1111/j.1365-2036.2012.05198.x

  11. Apoptosis induced by GanoPoly in human gastric cancer cell line ...

    African Journals Online (AJOL)

    use

    2011-12-12

    Dec 12, 2011 ... among all cancers. Surgery and radiation therapy or conventional chemotherapy treatment saved a lot of lives, but too many people developed metastasic gastric can- ... It is widely used in China to strengthen the kidney's function and soothe human's breath and also for the treatment of alleviated fatigue, ...

  12. High K+-Induced Relaxation by Nitric Oxide in Human Gastric Fundus

    Science.gov (United States)

    Kim, Dae Hoon; Choi, Woong; Sung, Rohyun; Kim, Hun Sik; Kim, Heon; Yoo, Ra Young; Park, Seon-Mee; Yun, Sei Jin; Song, Young-Jin; Xu, Wen-Xie; Lee, Sang Jin

    2012-01-01

    This study was designed to elucidate high K+-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high K+ (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high K+-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 µM) and KT 5720 (1 µM) which block protein kinases (PKG and PKA) had no effect on high K+-induced relaxation. K+ channel blockers except 4-aminopyridine (4-AP), a voltage-dependent K+ channel (KV) blocker, did not affect high K+-induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High K+-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high K+-induced relaxation that was activated by the nitric oxide/sGC pathway through a KV channel-dependent mechanism. PMID:23118553

  13. Human leukocyte antigen (HLA)-E and HLA-F expression in gastric cancer.

    Science.gov (United States)

    Ishigami, Sumiya; Arigami, Takaaki; Okumura, Hiroshi; Uchikado, Yasuto; Kita, Yoshiaki; Kurahara, Hiroshi; Maemura, Kosei; Kijima, Yuko; Ishihara, Yuka; Sasaki, Ken; Uenosono, Yoshikazu; Natsugoe, Shoji

    2015-04-01

    Human leukocyte antigen (HLA)-E and HLA-F are classified as non-classical HLA class Ib antigens. Ectopic HLA-E and HLA-F expression was recently detected in cancer cells; however, the clinical implication of their expression remains unknown. A total of 209 patients with gastric cancer were enrolled in this study. Immunohistochemistry was used to evaluate the expression of HLA-E and HLA-F in gastric cancer specimens. HLA-E and HLA-F expression were seen in the cell membrane. HLA-E and HLA-F expression significantly correlated with depth of invasion, nodal involvement, lymphatic invasion, and venous invasion. No significant correlation between HLA-E and HLA-F expression was found (pHLA-E-positive group and HLA-F-positive group were significantly poorer than that of their respective negative groups. Combination of HLA-E and HLA-F made the p-value smaller than single analysis (pHLA-E and HLA-F expression simultaneously in gastric cancer. We identified that the HLA-E and HLA-F in gastric cancer independently affected clinical factors, including postoperative outcome. For HLA-E- or HLA-F-positive gastric cancer, we should settle on a treatment strategy that reinforces the host immune response. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Human Nature in the Adaptation of Trust

    NARCIS (Netherlands)

    Nooteboom, B.

    2006-01-01

    This chapter pleads for more inspiration from human nature, in agent-based modeling.As an illustration of an effort in that direction, it summarizes and discusses an agentbased model of the build-up and adaptation of trust between multiple producers and suppliers.The central question is whether, and

  15. Impact of human milk pasteurization on gastric digestion in preterm infants: a randomized controlled trial.

    Science.gov (United States)

    de Oliveira, Samira C; Bellanger, Amandine; Ménard, Olivia; Pladys, Patrick; Le Gouar, Yann; Dirson, Emelyne; Kroell, Florian; Dupont, Didier; Deglaire, Amélie; Bourlieu, Claire

    2017-02-01

    Holder pasteurization has been reported to modify human milk composition and structure by inactivating bile salt-stimulated lipase (BSSL) and partially denaturing some of its proteins, potentially affecting its subsequent digestion. We sought to determine the impact of human milk pasteurization on gastric digestion (particularly for proteins and lipids) in preterm infants who were fed their mothers' own milk either raw or pasteurized. In a randomized controlled trial, 12 hospitalized tube-fed preterm infants were their own control group in comparing the gastric digestion of raw human milk (RHM) with pasteurized human milk (PHM). Over a 6-d sequence, gastric aspirates were collected 2 times/d before and after RHM or PHM ingestion. The impact of milk pasteurization digestive kinetics and disintegration was tested with the use of a general linear mixed model. Despite inactivating BSSL, instantaneous lipolysis was not affected by pasteurization (mean ± SD at 90 min: 12.6% ± 4.7%; P > 0.05). Lipolysis occurred in milk before digestion and was higher for PHM than for RHM (mean ± SD: 3.2% ± 0.6% and 2.2% ± 0.8%, respectively; P impact on the gastric digestion of lipids and some proteins from human milk but did affect lactoferrin and α-lactalbumin proteolysis and emulsion disintegration. Freeze-thawing and pasteurization increased the milk lipolysis before digestion but did not affect gastric lipolysis. Possible consequences on intestinal digestion and associated nutritional outcomes were not considered in this study. This trial was registered at clinicaltrials.gov as NCT02112331. © 2017 American Society for Nutrition.

  16. β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis

    International Nuclear Information System (INIS)

    Liu, Jing; Zhang, Ye; Qu, Jinglei; Xu, Ling; Hou, Kezuo; Zhang, Jingdong; Qu, Xiujuan; Liu, Yunpeng

    2011-01-01

    β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved. β-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with β-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3-II protein. Further study showed that β-elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by β-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of β-elemene. Our data provides the first evidence that β-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of β-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer

  17. Opioid-induced delay in gastric emptying: a peripheral mechanism in humans.

    LENUS (Irish Health Repository)

    Murphy, D B

    2012-02-03

    BACKGROUND: Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this effect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylnaltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier. METHODS: In a randomized, double-blind, crossover placebo-controlled study, 11 healthy volunteers were given either placebo (saline), 0.09 mg\\/kg morphine, or 0.09 mg\\/kg morphine plus 0.3 mg\\/kg methylnaltrexone on three separate occasions before ingesting 500 ml deionized water. The rate of gastric emptying was measured by two methods: a noninvasive epigastric bioimpedance technique and the acetaminophen absorption test. RESULTS: The epigastric bioimpedance technique was sufficiently sensitive to detect opioid-induced changes in the rate of gastric emptying. The mean +\\/- SD time taken for the gastric volume to decrease to 50% (t0.5) after placebo was 5.5 +\\/- 2.1 min. Morphine prolonged gastric emptying to (t0.5) of 21 +\\/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly with morphine reversed the morphine-induced delay in gastric emptying to a t0.5 of 7.4 +\\/- 3.0 (P < 0.04). Maximum concentrations and area under the concentration curve from 0 to 90 min of serum acetaminophen concentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0.05). No difference in maximum concentration or area under the concentration curve from 0 to 90 min was noted between placebo and methylnaltrexone coadministered with morphine. CONCLUSIONS: The attenuation of morphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is

  18. Helicobacter pylori enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in human gastric epithelial cells

    Science.gov (United States)

    Wu, Yi-Ying; Tsai, Hwei-Fang; Lin, We-Cheng; Chou, Ai-Hsiang; Chen, Hui-Ting; Yang, Jyh-Chin; Hsu, Ping-I; Hsu, Ping-Ning

    2004-01-01

    AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori (H pylori) infection in apoptosis of gastric epithelial cells and to assess the expression of TRAIL on the surface of infiltrating T-cells in H pylori-infected gastric mucosa. METHODS: Human gastric epithelial cell lines and primary gastric epithelial cells were co-cultured with H pylori in vitro, then recombinant TRAIL proteins were added to the culture. Apoptosis of gastric epithelial cells was determined by a specific ELISA for cell death. Infiltrating lymphocytes were isolated from H pylori-infected gastric mucosa, and expression of TRAIL in T cells was analyzed by flow cytometry. RESULTS: The apoptosis of gastric epithelial cell lines and primary human gastric epithelial cells was mildly increased by interaction with either TRAIL or H pylori alone. Interestingly, the apoptotic indices were markedly elevated when gastric epithelial cells were incubated with both TRAIL and H pylori (Control vs TRAIL and H pylori: 0.51 ± 0.06 vs 2.29 ± 0.27, P = 0.018). A soluble TRAIL receptor (DR4-Fc) could specifically block the TRAIL-mediated apoptosis. Further studies demonstrated that infiltrating T-cells in gastric mucosa expressed TRAIL on their surfaces, and the induction of TRAIL sensitivity by H pylori was dependent upon direct cell contact of viable bacteria, but not CagA and VacA of H pylori. CONCLUSION: H pylori can sensitize human gastric epithelial cells and enhance susceptibility to TRAIL-mediated apoptosis. Modulation of host cell sensitivity to apoptosis by bacterial interaction adds a new dimension to the immunopathogenesis of H pylori infection. PMID:15285015

  19. Tissue metabolic profiling of human gastric cancer assessed by 1H NMR

    International Nuclear Information System (INIS)

    Wang, Huijuan; Zhang, Hailong; Deng, Pengchi; Liu, Chunqi; Li, Dandan; Jie, Hui; Zhang, Hu; Zhou, Zongguang; Zhao, Ying-Lan

    2016-01-01

    Gastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to identify the potential biomarkers for the early diagnosis of gastric cancer. In this study, we reported the metabolic profiling of tissue samples on a large cohort of human gastric cancer subjects (n = 125) and normal controls (n = 54) based on 1 H nuclear magnetic resonance ( 1 H NMR) together with multivariate statistical analyses (PCA, PLS-DA, OPLS-DA and ROC curve). The OPLS-DA model showed adequate discrimination between cancer tissues and normal controls, and meanwhile, the model excellently discriminated the stage-related of tissue samples (stage I, 30; stage II, 46; stage III, 37; stage IV, 12) and normal controls. A total of 48 endogenous distinguishing metabolites (VIP > 1 and p < 0.05) were identified, 13 of which were changed with the progression of gastric cancer. These modified metabolites revealed disturbance of glycolysis, glutaminolysis, TCA, amino acids and choline metabolism, which were correlated with the occurrence and development of human gastric cancer. The receiver operating characteristic diagnostic AUC of OPLS-DA model between cancer tissues and normal controls was 0.945. And the ROC curves among different stages cancer subjects and normal controls were gradually improved, the corresponding AUC values were 0.952, 0.994, 0.998 and 0.999, demonstrating the robust diagnostic power of this metabolic profiling approach. As far as we know, the present study firstly identified the differential metabolites in various stages of gastric cancer tissues. And the AUC values were relatively high. So these results suggest that the metabolic profiling of gastric cancer tissues has great potential in detecting this disease and helping

  20. Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

    Science.gov (United States)

    Cousin, Fabien J; Jouan-Lanhouet, Sandrine; Dimanche-Boitrel, Marie-Thérèse; Corcos, Laurent; Jan, Gwénaël

    2012-01-01

    Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

  1. Milk Fermented by Propionibacterium freudenreichii Induces Apoptosis of HGT-1 Human Gastric Cancer Cells

    Science.gov (United States)

    Cousin, Fabien J.; Jouan-Lanhouet, Sandrine; Dimanche-Boitrel, Marie-Thérèse; Corcos, Laurent; Jan, Gwénaël

    2012-01-01

    Background Gastric cancer is one of the most common cancers in the world. The “economically developed countries” life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. Methodology/Principal Findings A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. Conclusions/Significance Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments. PMID:22442660

  2. Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Fabien J Cousin

    Full Text Available Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate.A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy.Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

  3. EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

    Directory of Open Access Journals (Sweden)

    Rossella Terragni

    Full Text Available Epidermal growth factor receptor (EGFR or HER-1 and its analog c-erbB-2 (HER-2 are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7% carcinomas were classified as intestinal-type and 9 (64.3% as diffuse-type. EGFR was overexpressed (≥ 1+ in 8 (42.1% cases and HER-2 (3+ in 11 (57.9% cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80% than in the diffuse-type (11.1%, p = 0.023. KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R. EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

  4. Epistatic adaptive evolution of human color vision.

    Directory of Open Access Journals (Sweden)

    Shozo Yokoyama

    2014-12-01

    Full Text Available Establishing genotype-phenotype relationship is the key to understand the molecular mechanism of phenotypic adaptation. This initial step may be untangled by analyzing appropriate ancestral molecules, but it is a daunting task to recapitulate the evolution of non-additive (epistatic interactions of amino acids and function of a protein separately. To adapt to the ultraviolet (UV-free retinal environment, the short wavelength-sensitive (SWS1 visual pigment in human (human S1 switched from detecting UV to absorbing blue light during the last 90 million years. Mutagenesis experiments of the UV-sensitive pigment in the Boreoeutherian ancestor show that the blue-sensitivity was achieved by seven mutations. The experimental and quantum chemical analyses show that 4,008 of all 5,040 possible evolutionary trajectories are terminated prematurely by containing a dehydrated nonfunctional pigment. Phylogenetic analysis further suggests that human ancestors achieved the blue-sensitivity gradually and almost exclusively by epistasis. When the final stage of spectral tuning of human S1 was underway 45-30 million years ago, the middle and long wavelength-sensitive (MWS/LWS pigments appeared and so-called trichromatic color vision was established by interprotein epistasis. The adaptive evolution of human S1 differs dramatically from orthologous pigments with a major mutational effect used in achieving blue-sensitivity in a fish and several mammalian species and in regaining UV vision in birds. These observations imply that the mechanisms of epistatic interactions must be understood by studying various orthologues in different species that have adapted to various ecological and physiological environments.

  5. Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence.

    Science.gov (United States)

    Bugaytsova, Jeanna A; Björnham, Oscar; Chernov, Yevgen A; Gideonsson, Pär; Henriksson, Sara; Mendez, Melissa; Sjöström, Rolf; Mahdavi, Jafar; Shevtsova, Anna; Ilver, Dag; Moonens, Kristof; Quintana-Hayashi, Macarena P; Moskalenko, Roman; Aisenbrey, Christopher; Bylund, Göran; Schmidt, Alexej; Åberg, Anna; Brännström, Kristoffer; Königer, Verena; Vikström, Susanne; Rakhimova, Lena; Hofer, Anders; Ögren, Johan; Liu, Hui; Goldman, Matthew D; Whitmire, Jeannette M; Ådén, Jörgen; Younson, Justine; Kelly, Charles G; Gilman, Robert H; Chowdhury, Abhijit; Mukhopadhyay, Asish K; Nair, G Balakrish; Papadakos, Konstantinos S; Martinez-Gonzalez, Beatriz; Sgouras, Dionyssios N; Engstrand, Lars; Unemo, Magnus; Danielsson, Dan; Suerbaum, Sebastian; Oscarson, Stefan; Morozova-Roche, Ludmilla A; Olofsson, Anders; Gröbner, Gerhard; Holgersson, Jan; Esberg, Anders; Strömberg, Nicklas; Landström, Maréne; Eldridge, Angela M; Chromy, Brett A; Hansen, Lori M; Solnick, Jay V; Lindén, Sara K; Haas, Rainer; Dubois, Andre; Merrell, D Scott; Schedin, Staffan; Remaut, Han; Arnqvist, Anna; Berg, Douglas E; Borén, Thomas

    2017-03-08

    The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Educational Cognitive Technologies as Human Adaptation Strategies

    Directory of Open Access Journals (Sweden)

    Marja Nesterova

    2017-07-01

    Full Text Available Modernity is characterized by profound changes in all spheres of human life caused by the global transformations on macro and micro levels of social reality. These changes allow us to speak about the present as the era of civilizational transition in the mode of uncertainty. Therefore, this situation demands qualitative transformations of human adaptive strategies and educational technologies accordingly. The dominant role in the dynamics of pedagogics and andragogy’s landscape belongs to transformative learning. The transformative learning theory is considered as the relevant approach to education of the individual, which is able to become an autonomous communicative actor of the social complexity. The article considers the cognitive technologies of social cohesion development and perspectives of their implementation in the educational dimension. In addition to implementing the principles of inclusion, equity in education, an important factor for improving social cohesion, stability and unity of society is the development of cognitive educational technologies. The key factors and foundations for the cognitive educational technologies are transversal competencies. They create the conditions for civil, public dialogue, non-violent type of communication. These “21st century skills” are extremely important for better human adaptation. One of the aspects and roots of social adaptation is social cohesion. Mutual determinations and connections between social cohesion development and transversal competences have been shown. The perspective direction of further researches is to find a methodological base for the further development of cognitive education technologies and platform for realization of innovative services for educational programs. New educational paradigm offers the concept of human adaptation as cognitive effectiveness and how to reach it through educational technologies. The article includes topics of creative thinking, teambuilding

  7. Human postprandial gastric emptying of 1-3-millimeter spheres

    International Nuclear Information System (INIS)

    Meyer, J.H.; Elashoff, J.; Porter-Fink, V.; Dressman, J.; Amidon, G.L.

    1988-01-01

    Microspheres of pancreatin should empty from the stomachs of patients with pancreatic insufficiency as fast as food. The present study was undertaken in 26 healthy subjects to identify the size of spheres that would empty from the stomach with food and to determine whether different meals alter this size. Spheres of predefined sizes were labeled with /sup 113m/In or /sup 99m/Tc. Using a gamma-camera, we studied the concurrent gastric emptying of spheres labeled with /sup 113m/In and of chicken liver labeled with /sup 99m/Tc in 100-g, 154-kcal or 420-g, 919-kcal meals, or the concurrent emptying of 1-mm vs. larger spheres. One-millimeter spheres emptied consistently (p less than 0.01, paired t-test) faster than 2.4- or 3.2-mm spheres when ingested together with either the 420- or 100-g meals. Thus, in the 1-3-mm range of diameters, sphere size was a more important determinant of sphere emptying than meal size. Statistical analyses indicated that spheres 1.4 +/- 0.3 mm in diameter with a density of 1 empty at the same rate as /sup 99m/Tc-liver. Our data indicate some commercially marketed microspheres of pancreatin will empty too slowly to be effective in digestion of food

  8. Binding of Helocobacter pyori to Human Gastric Mucose: Identification and Characterization of a Lewis b Bingind Protein

    National Research Council Canada - National Science Library

    Biegel, Susan

    1995-01-01

    .... With the isolation of a Gram-negative, spiral shaped bacterium from human gastric mucosa, Helicobacter pylori, came the answers to many questions concerning peptic ulcer disease, including this one. Recently...

  9. Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum.

    Science.gov (United States)

    Thomsen, L L; Gavin, J B; Tasman-Jones, C

    1990-11-01

    The spatial relations between bacteria and the affected tissues can indicate pathogenic mechanisms. This study was undertaken to define the spatial relation of Helicobacter pylori to the human gastric mucosa. Antibodies against gastric mucus and ruthenium red were used to stabilise the glycoprotein structure of the mucus and glycocalyces in antral biopsy specimens from eight patients infected with H pylori. The location of organisms and ultrastructural features were assessed using systematic scanning and transmission electron microscopy: 92 (2)% (mean (SE] of H pylori were in the pit mucus, and 7 (3)% were in the surface mucus; 60 (12)% of H pylori were close to epithelial cells, with only 5 (2)% located near the epithelial intercellular junctions. Fine filamentous strands extended between organisms and nearby epithelial cells, with few organisms in membrane to membrane contact. H pylori were not observed between, beneath, or within cells of the gastric mucosa. The preferred location of H pylori in the gastric antrum is within the pit mucus close to the epithelial cell surface, with no evidence that they have a direct toxic effect on the mucosa.

  10. Clinical-pathological implication of human leukocyte antigen-F-positive gastric adenocarcinoma.

    Science.gov (United States)

    Ishigami, Sumiya; Arigami, Takaaki; Setoyama, Testuro; Okumura, Hiroshi; Sasaki, Ken; Uchikado, Yasuto; Kurahara, Hiroshi; Kijima, Yuko; Nishizono, Yuka; Nakajo, Akihiro; Natsugoe, Shoji

    2013-10-01

    Human leukocyte antigen (HLA)-F is a nonclassical HLA class I molecule that shows aberrant expression in cancer cells. Although the clinical implications of HLA-F expression in cancer patients have been described, the specific significance of this antigen in gastrointestinal cancer remains unclear. The present study examined the expression pattern and clinical implications of HLA-F in gastric adenocarcinoma. HLA-F expression was assessed in 179 patients by immunohistochemistry, and its association with clinical parameters including patient survival was analyzed. HLA-F expression was positive in 30.7% (55/179) of patients and in 50.0% (90/179) of peritumoral infiltrating lymphocytes. HLA-F expression in gastric adenocarcinoma was significantly correlated with the depth of invasion, nodal involvement, and lymphatic and venous invasions (P HLA-F positivity of infiltrating cells near the tumor showed no correlation with clinicopathological features. HLA-F-positive patients had a significantly worse prognosis than HLA-F-negative patients (P = 0.012). However, HLA-F expression was not an independent prognostic factor in multivariate analysis. The present study provides the first evidence that neo-HLA-F expression is of clinical significance in gastric adenocarcinoma. HLA-F expression in gastric adenocarcinoma may promote the aggressive behavior of tumors by suppressing the activity of antitumor immune effector cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Human epidermal growth factor receptor2 expression in unresectable gastric cancers: Relationship with CT characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Sub [Dept. of Radiology, Jeju National University Hospital, Jeju (Korea, Republic of); Kim, Se Hyung; Im, Seock Ah; Kim, Min A; Han, Joon Koo [Seoul National University Hospital, Seoul (Korea, Republic of)

    2017-09-15

    To retrospectively analyze the qualitative CT features that correlate with human epidermal growth factor receptor 2 (HER2)-expression in pathologically-proven gastric cancers. A total of 181 patients with pathologically-proven unresectable gastric cancers with HER2-expression (HER2-positive [n = 32] and negative [n = 149]) were included. CT features of primary gastric and metastatic tumors were reviewed. The prevalence of each CT finding was compared in both groups. Thereafter, binary logistic regression determined the most significant differential CT features. Clinical outcomes were compared using Kaplan-Meier method. HER2-postive cancers showed lower clinical T stage (21.9% vs. 8.1%; p = 0.015), hyperattenuation on portal phase (62.5% vs. 30.9%; p = 0.003), and was more frequently metastasized to the liver (62.5% vs. 32.2%; p = 0.001), than HER2-negative cancers. On binary regression analysis, hyperattenuation of the tumor (odds ratio [OR], 4.68; p < 0.001) and hepatic metastasis (OR, 4.43; p = 0.001) were significant independent factors that predict HER2-positive cancers. Median survival of HER2-positive cancers (13.7 months) was significantly longer than HER2-negative cancers (9.6 months) (p = 0.035). HER2-positive gastric cancers show less-advanced T stage, hyperattenuation on the portal phase, and frequently metastasize to the liver, as compared to HER2-negative cancers.

  12. Expression and Significances of Contactin-1 in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Ji-Wei Yu

    2013-01-01

    Full Text Available Background. This study aimed at determining the relationship between vascular endothelial growth factor-C (VEGF-C, vascular endothelial growth factor receptor-3 (VEGFR-3, and contactin-1 (CNTN-1 expression in gastric cancer (GC. Methods. The expression level of CNTN-1 mRNA and CNTN-1 protein of 33 cases was determined using RT-PCR and Western Blot. And 105 cases were immunohistochemically examined for VEGF-C, VEGFR-3, and CNTN-1 expressions. Assessment of lymphatic vessel density (LVD was also performed by D2-40 immunostaining. Then we analyzed the relationships between VEGF-C, VEGFR-3, and CNTN-1, as well as their correlations with clinicopathologic features, LVD, and survival time. Results. The positivity rate of VEGF-C, VEGFR-3, and CNTN-1 in primary tumor was 56.19%, 64.76%, and 58.09%. The expression of CNTN-1 significantly correlated with VEGF-C (P<0.001 and VEGFR-3 (P<0.001. All of them were closely related to TNM stage, lymphatic invasion, and lymph node involvement (P<0.05. LVD was significantly correlated with VEGF-C (P=0.001, VEGFR-3 (P=0.011, and CNTN-1 expression (P<0.001. VEGF-C, VEGFR-3, and CNTN-1 expression significantly associated with poorer prognosis (P<0.001, P=0.034, P=0.012, resp.. Conclusion. CNTN-1 associated with VEGF-C and VEGFR-3 expression in GC. All of them correlated with lymphatic metastasis, which might play an important role in the lymphatic invasion via lymphangiogenesis pathway in GC.

  13. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

    2006-01-01

    : To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...... of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean...... emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl...

  14. Efficacy of Sulforaphane in Eradicating Helicobacter pylori in Human Gastric Xenografts Implanted in Nude Mice

    OpenAIRE

    Haristoy, Xavier; Angioi-Duprez, Karine; Duprez, Adrien; Lozniewski, Alain

    2003-01-01

    Sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli sprouts, has shown in vitro activity against Helicobacter pylori. We evaluated the effect of sulforaphane in vivo against this bacterium by using human gastric xenografts in nude mice. H. pylori was completely eradicated in 8 of the 11 sulforaphane-treated grafts. This result suggests that sulforaphane might be beneficial in the treatment of H. pylori-infected individuals.

  15. Extracts of Opuntia humifusa Fruits Inhibit the Growth of AGS Human Gastric Adenocarcinoma Cells

    OpenAIRE

    Hahm, Sahng-Wook; Park, Jieun; Park, Kun-Young; Son, Yong-Suk; Han, Hyungchul

    2016-01-01

    Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF o...

  16. Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines.

    Science.gov (United States)

    Lin, Zu-Yau; Kuo, Chao-Hung; Wu, Deng-Chyang; Chuang, Wan-Long

    2016-02-01

    Colchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer effects on gastric cancer cells, and its possible anticancer mechanisms. Two human gastric cancer cell lines (i.e., AGS and NCI-N87) were investigated by proliferative assay, microarray, quantitative reverse transcriptase-polymerase chain reaction, and a nude mice study using clinically acceptable colchicine concentrations (2 ng/mL and 6 ng/mL for in vitro tests and 0.07 mg colchicine/kg/d for in vivo tests). Our results showed that colchicine had the same inhibitory effects on the proliferation of both cell lines. The antiproliferative effects of colchicine on both cell lines were achieved only at the concentration of 6 ng/mL (p colchicine, compared with 2 ng/mL colchicine. Among these genes, only the upregulated DUSP1 gene may contribute to the antiproliferative effects of colchicine on gastric cancer cells. The nude mice (BALB/c-nu) experiment showed that colchicine-treated mice after 14 days of treatment had lower increased tumor volume ratios (p = 0.0199) and tumor growth rates (p = 0.024) than the control mice. In conclusion, colchicine has potential for the palliative treatment of gastric cancer. However, the anticancer effects are achieved only at high clinically acceptable colchicine concentrations. Monitoring the colchicine plasma concentration is mandatory if this drug is applied for the palliative treatment of gastric cancer. Copyright © 2016. Published by Elsevier Taiwan.

  17. Effect of ethanol and some alcoholic beverages on gastric emptying in humans.

    Science.gov (United States)

    Franke, A; Teyssen, S; Harder, H; Singer, M V

    2004-07-01

    There is a paucity of detailed and controlled studies on the action of ethanol and alcoholic beverages on gastric emptying in humans. This study was designed to compare the effect of beer, red wine, whisky and their comparable pure ethanol solutions on gastric emptying in a controlled and randomized investigation. On separate days, 10 healthy, fasted subjects received the following solutions, in random order, through a gastric tube: 500 mL beer, red wine, comparable pure ethanol solutions (4% and 10% v/v), glucose (5.5% and 11.4% w/v) and water, 125 mL whisky and 40% (v/v) ethanol (both followed by 125 mL water) and 250 mL water. Gastric emptying of the test solutions was assessed using ultrasonography of the antrum. As measured by ultrasonography of the antrum, half emptying times of the ethanol solutions (4%, 10% and 40% v/v) were significantly (P beer (39.3 +/- 4.3 min) and red wine (72.6 +/- 7.6 min) were significantly longer than those of the corresponding ethanol concentrations, whereas whisky was emptied at nearly the same rate (26.4 +/- 5.9 min) as 40% (v/v) ethanol. Emptying of glucose 5.5% and 11.4% (w/v) was significantly and dose dependently slower (29.7 +/- 4.5 and 64.8 +/- 8.9 min) than water. 1) Pure ethanol in concentrations of 4%, 10% and 40% (v/v) inhibits gastric emptying. 2) The inhibitory effect of beer and red wine, but not of whisky, is stronger than that of their comparable ethanol concentrations. 3) Caloric content and non-alcoholic ingredients in alcoholic beverages produced by fermentation (beer and wine), but not in those produced by distillation (whisky), are most likely responsible for this effect.

  18. Alcoholic beverages produced by alcoholic fermentation but not by distillation are powerful stimulants of gastric acid secretion in humans.

    Science.gov (United States)

    Teyssen, S; Lenzing, T; González-Calero, G; Korn, A; Riepl, R L; Singer, M V

    1997-01-01

    The effect of commonly ingested alcoholic beverages on gastric acid output and release of gastrin in humans is unknown. In 16 healthy humans the effect of some commonly ingested alcoholic beverages produced by fermentation plus distillation (for example, whisky, cognac, calvados, armagnac, and rum) or by alcoholic fermentation (beer, wine, champagne, martini, and sherry) on gastric acid output and release of gastrin was studied. Gastric acid output was determined by the method of intragastric titration. Plasma gastrin was measured using a specific radioimmunoassay. None of the alcoholic beverages produced by fermentation plus distillation had any significant effect on gastric acid output and release of gastrin compared with control (isotonic glucose and distilled water). Alcoholic beverages produced only by fermentation significantly (p beer, wine, and sherry were distilled, only their remaining parts increased gastric acid output by 53% to 76% of MAO and increased release of gastrin up to 4.3-fold compared with control. (1) Alcoholic beverages produced by fermentation but not by distillation are powerful stimulants of gastric acid output and release of gastrin; (2) the alcoholic beverage constituents that stimulate gastric acid output and release of gastrin are most probably produced during the process of fermentation and removed during the following process of distillation.

  19. NOTCH1 and NOTCH2 regulate epithelial cell proliferation in mouse and human gastric corpus.

    Science.gov (United States)

    Demitrack, Elise S; Gifford, Gail B; Keeley, Theresa M; Horita, Nobukatsu; Todisco, Andrea; Turgeon, D Kim; Siebel, Christian W; Samuelson, Linda C

    2017-02-01

    The Notch signaling pathway is known to regulate stem cells and epithelial cell homeostasis in gastrointestinal tissues; however, Notch function in the corpus region of the stomach is poorly understood. In this study we examined the consequences of Notch inhibition and activation on cellular proliferation and differentiation and defined the specific Notch receptors functioning in the mouse and human corpus. Notch pathway activity was observed in the mouse corpus epithelium, and gene expression analysis revealed NOTCH1 and NOTCH2 to be the predominant Notch receptors in both mouse and human. Global Notch inhibition for 5 days reduced progenitor cell proliferation in the mouse corpus, as well as in organoids derived from mouse and human corpus tissue. Proliferation effects were mediated through both NOTCH1 and NOTCH2 receptors, as demonstrated by targeting each receptor alone or in combination with Notch receptor inhibitory antibodies. Analysis of differentiation by marker expression showed no change to the major cell lineages; however, there was a modest increase in the number of transitional cells coexpressing markers of mucous neck and chief cells. In contrast to reduced proliferation after pathway inhibition, Notch activation in the adult stomach resulted in increased proliferation coupled with reduced differentiation. These findings suggest that NOTCH1 and NOTCH2 signaling promotes progenitor cell proliferation in the mouse and human gastric corpus, which is consistent with previously defined roles for Notch in promoting stem and progenitor cell proliferation in the intestine and antral stomach. Here we demonstrate that the Notch signaling pathway is essential for proliferation of stem cells in the mouse and human gastric corpus. We identify NOTCH1 and NOTCH2 as the predominant Notch receptors expressed in both mouse and human corpus and show that both receptors are required for corpus stem cell proliferation. We show that chronic Notch activation in corpus stem

  20. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are 'Human Adaptive Mechatronics (HAM' and 'Human-System Modelling (HSM', are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operators' skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory-motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human-mechatronics systems are also mentioned.

  1. Evolution of Human Herpesvirus Type 8-associated Gastric Kaposi's Sarcoma Following Corticosteroid Treatment for Asthma

    Directory of Open Access Journals (Sweden)

    Cheng-Chuan Su

    2006-01-01

    Full Text Available The association of gastric Kaposi's sarcoma (KS with human herpesvirus type 8 (HHV-8 may be found in immunosuppressed patients such as those with AIDS or transplant recipients. A 64-year-old man with a 2-year history of corticosteroid treatment was admitted due to the impression of chronic obstructive pulmonary disease with secondary infection. Abdominal fullness and tarry stool led to the performance of panendoscopy, which revealed two hypertrophic gastric mucosal lesions. These lesions had transformed into a large polyp 2 months later. KS was not diagnosed until a third endoscopic biopsy was performed. The polyp further transformed into a flattened, elongated tumor within a month. The patient died from acute cardiopulmonary insufficiency 4 days after radical gastrectomy. Polymerase chain reaction study identified HHV-8 in all biopsied specimens and resected tumor lesions. Immunostaining further demonstrated the virus in the tumor cells. Both of these methods seemed more sensitive in diagnosing KS than histologic examination of small biopsied specimens. This case suggests the existence of a relationship between gastric KS and HHV-8 infection.

  2. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

  3. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    Full Text Available BACKGROUND: Roux-en-Y gastric bypass (RYGB surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. METHODOLOGY AND PRINCIPAL FINDINGS: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7. Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172 of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05, including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9 and obese/diabetic (n = 5 groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2, nervonic (C24:1 acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI and estimates for insulin resistance (HOMA-IR. Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55. CONCLUSIONS: Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.

  4. Plasma membrane proteomic analysis of human Gastric Cancer tissues: revealing flotillin 1 as a marker for Gastric Cancer

    International Nuclear Information System (INIS)

    Gao, Wen; Xu, Jing; Wang, Fuqiang; Zhang, Long; Peng, Rui; Shu, Yongqian; Wu, Jindao; Tang, Qiyun; Zhu, Yunxia

    2015-01-01

    Gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful early gastric cancer detection is hampered by lack of highly sensitive and specific biomarkers. Plasma membrane proteins participate and/or have a central role in the metastatic process of cancer cells and are potentially useful for cancer therapy due to easy accessibility of the targets. In the present research, TMT method followed by mass spectrometry analysis was used to compare the relative expression levels of plasma membrane proteins between noncancer and gastric cancer tissues. Of a total data set that included 501 identified proteins, about 35% of the identified proteins were found to be plasma membrane and associated proteins. Among them, 82 proteins were at least 1.5-fold up- or down-regulated in gastric cancer compared with the adherent normal tissues. A number of markers (e.g. annexin A6, caveolin 1, epidermal growth factor receptor, integrin beta 4) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in endocytosis pathway and integrin signaling pathways were firstly identified as differentially expressed proteins in GC samples. Our findings also supported the notion that flotillin 1 is a potential biomarker that could be exploited for molecular imaging-based detection of gastric cancer. Together, the results show that subcellular proteomics of tumor tissue is a feasible and promising avenue for exploring oncogenesis. The online version of this article (doi:10.1186/s12885-015-1343-5) contains supplementary material, which is available to authorized users

  5. Proliferative and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.

    Science.gov (United States)

    Li, Shu-Guang; Wang, Yuan-yu; Ye, Zai-yuan; Shao, Qing-shu; Tao, Hou-quan; Shu, Li-sha; Zhao, Yi-feng; Yang, Yong-jiang; Yang, Jing; Peng, Tao; Han, Bo; Huang, Di

    2013-01-01

    Andrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers. The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line. Cell proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay, and morphologic structure with transmission electron microscopy. Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2, Bax, and caspase-3 expressions. Andrographolide showed a time- and concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to controls, the number of cells in the G0-G1-phase increased significantly, S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and both early and late apoptotic rates increased significantly compared to the controls, all in a concentration-dependent manner. Bax and caspase-3 expressions were markedly increased, and Bcl-2 expression was decreased. Andrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression. Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.

  6. Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

    International Nuclear Information System (INIS)

    Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

    2015-01-01

    Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer

  7. Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Yuxin; Li, Yan [Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122 (China); Gu, Hui [Department of Key Laboratory of Health Ministry for Congenital Malformation Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004 (China); Wang, Chunyu [Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122 (China); Liu, Funan [Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001 (China); Shao, Yangguang; Li, Jiabin; Cao, Liu [Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122 (China); Li, Feng, E-mail: fli@mail.cmu.edu.cn [Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122 (China)

    2015-11-27

    ArgBP2 is an adapter protein that plays an important role in actin-dependent processes such as cell adhesion and migration. However, its function and regulation mechanisms in gastric cancer have not yet been investigated. Here, we showed the low expression of ArgBP2 mRNA level in gastric tumor samples and its repressive function in the proliferation, migration, and invasion of gastric cancer cells. Then, we cloned and identified ArgBP2 promoter and verified that MORC2 bound to the promoter. Moreover, we demonstrated that MORC2 enhanced the recruitment of EZH2, which promoted the tri-methylation of H3K27, leading to the transcriptional repression of ArgBP2. Our results might thus contribute to understanding the molecular mechanisms of ArgBP2 regulation and suggesting ArgBP2 as a potential therapeutic target for gastric cancer. - Highlights: • ArgBP2 inhibits proliferation, migration, and invasion of gastric cancer cells. • Identification of ArgBP2 promoter and its transcription factor MORC2. • EZH2 is required in MORC2 down-regulating ArgBP2 via histone methylation.

  8. Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells

    International Nuclear Information System (INIS)

    Tong, Yuxin; Li, Yan; Gu, Hui; Wang, Chunyu; Liu, Funan; Shao, Yangguang; Li, Jiabin; Cao, Liu; Li, Feng

    2015-01-01

    ArgBP2 is an adapter protein that plays an important role in actin-dependent processes such as cell adhesion and migration. However, its function and regulation mechanisms in gastric cancer have not yet been investigated. Here, we showed the low expression of ArgBP2 mRNA level in gastric tumor samples and its repressive function in the proliferation, migration, and invasion of gastric cancer cells. Then, we cloned and identified ArgBP2 promoter and verified that MORC2 bound to the promoter. Moreover, we demonstrated that MORC2 enhanced the recruitment of EZH2, which promoted the tri-methylation of H3K27, leading to the transcriptional repression of ArgBP2. Our results might thus contribute to understanding the molecular mechanisms of ArgBP2 regulation and suggesting ArgBP2 as a potential therapeutic target for gastric cancer. - Highlights: • ArgBP2 inhibits proliferation, migration, and invasion of gastric cancer cells. • Identification of ArgBP2 promoter and its transcription factor MORC2. • EZH2 is required in MORC2 down-regulating ArgBP2 via histone methylation.

  9. Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans

    DEFF Research Database (Denmark)

    Calbet, Jose A L; Holst, Jens Juul

    2004-01-01

    peptide hydrolysate (WHY) or casein hydrolysate (CAHY). All solutions were matched for volume (600 mL), nitrogen content (9.3 g/L), energy density (1069-1092 kJ/L), osmolality (288-306 mosmol/kg), pH (6.9-7.0) and temperature (37 degrees C). RESULTS: Solutions were emptied at similar rates, with mean half......BACKGROUND: The influence of protein fractionation on gastric emptying and rate of appearance of their constituent amino acids in peripheral blood remains unknown. AIM OF THE STUDY: To examine the influence of the degree of protein fractionation on gastric emptying, gastric secretion, amino acid......-times of (mean +/- SEM) 21.4 +/- 1.3, 19.3 +/- 2.2, 18.0 +/- 2.5 and 19.4 +/- 2.8 min, for the WHY, CAHY, C and W, respectively. The rates of intestinal absorption of water and amino acids were similar with the exception of the casein protein solution, for which the speed of intestinal amino acid absorption...

  10. Extracts of Opuntia humifusa Fruits Inhibit the Growth of AGS Human Gastric Adenocarcinoma Cells.

    Science.gov (United States)

    Hahm, Sahng-Wook; Park, Jieun; Park, Kun-Young; Son, Yong-Suk; Han, Hyungchul

    2016-03-01

    Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF on AGS cells was observed in a dose-dependent manner. Exposure to OHF (100 μg/mL) significantly induced (P<0.05) the G1 phase cell cycle arrest. Additionally, the apoptotic cell population was greater (P<0.05) in OHF (200 μg/mL) treated AGS cells when compared to the control. The expression of genes associated with cell cycle progression (Cdk4, Cdk2, and cyclin E) was significantly downregulated (P<0.05) by the OHF treatment. Moreover, the expression of Bax and caspase-3 in OHF treated cells was higher (P<0.05) than in the control. These findings suggest that OHF induces the G1 phase cell cycle arrest and activation of mitochondria-mediated apoptosis pathway in AGS human gastric cancer cells.

  11. Ghrelin stimulates gastric emptying and hunger in normal-weight humans

    DEFF Research Database (Denmark)

    Levin, F; Edholm, T; Schmidt, P T

    2006-01-01

    CONTEXT: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. MAIN OBJECTIVE: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion i...

  12. Nitrergic Pathway Is the Main Contributing Mechanism in the Human Gastric Fundus Relaxation: An In Vitro Study.

    Directory of Open Access Journals (Sweden)

    Yang Won Min

    Full Text Available Human gastric fundus relaxation is mediated by intrinsic inhibitory pathway. We investigated the roles of nitrergic and purinergic pathways, two known inhibitory factors in gastric motility, on spontaneous and nerve-evoked contractions in human gastric fundus muscles.Gastric fundus muscle strips (12 circular and 13 longitudinal were obtained from patients without previous gastrointestinal motility disorder who underwent gastrectomy for stomach cancer. Using these specimens, we examined basal tone, peak, amplitude, and frequency of spontaneous contractions, and peak and nadir values under electrical field stimulation (EFS, 150 V, 0.3 ms, 10 Hz, 20 s. To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine (muscarinic antagonist, 1 μM, MRS2500 (a purinergic P2Y1 receptor antagonist, 1 μM, and N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor, 100 μM were added sequentially for spontaneous and electrically-stimulated contractions. Tetrodotoxin was used to confirm any neuronal involvement.In spontaneous contraction, L-NNA increased basal tone and peak in both muscle layers, while amplitude and frequency were unaffected. EFS (up to 10 Hz uniformly induced initial contraction and subsequent relaxation in a frequency-dependent manner. Atropine abolished initial on-contraction and induced only relaxation during EFS. While MRS2500 showed no additional influence, L-NNA reversed relaxation (p = 0.012 in circular muscle, and p = 0.006 in longitudinal muscle. Tetrodotoxin abolished any EFS-induced motor response.The relaxation of human gastric fundus muscle is reduced by nitrergic inhibition. Hence, nitrergic pathway appears to be the main mechanism for the human gastric fundus relaxation.

  13. Lack of effect of synthetic human gastric inhibitory polypeptide and glucagon-like peptide 1 [7-36 amide] infused at near-physiological concentrations on pentagastrin-stimulated gastric acid secretion in normal human subjects

    DEFF Research Database (Denmark)

    Nauck, M A; Bartels, E; Orskov, C

    1992-01-01

    -stimulated (0.1 micrograms/kg/h from -90 to 120 min) gastric volume, acid and chloride output, on separate occasions, synthetic human GIP (1 pmol/kg/min) and/or GLP-1 [7-36 amide] (0.3 pmol/kg/min) or placebo (0.9% NaCl with 1% albumin) were infused intravenously (from -30 to 120 min) in 9 healthy volunteers...... secretion). In conclusion, (penta)gastrin-stimulated gastric acid secretion is not inhibited by physiological circulating concentrations of GIP or GLP-1 [7-36 amide]. Therefore, the insulinotropic action of these intestinal hormones is physiologically more important than their possible role...

  14. Various Statistical Methods in Use for Evaluating Human Malignant Gastric Specimens

    Directory of Open Access Journals (Sweden)

    Ventzeslav Enchev

    1998-01-01

    Full Text Available This paper presents the use of certain statistical methods (comparison of means – independent samples t‐test, multiple linear regression analysis, multiple logistic regression analysis, analysis of clusters, etc. included in the SPSS Statistical Package used to classify the patients quantitatively evaluated after a subtotal resection of their stomachs. The group consisted of 40 patients subdivided into two groups: primary neoplasia of the stomach (20 patients, and corresponding lymphogenic deposits in the abdominal perigastric lymph nodes (20 patients. Paraffin‐embedded tissue sections (thickness 4–5µm prepared as consecutive hematoxylin‐eosin‐stained slides were morphometrically measured by a rotation of a graduated eyepiece‐micrometer; thus, we obtained the minor and major axes’ lengths of the elliptic nuclear profiles and the minor and major caliper diameters of the corresponding cellular profiles. These four variables were used to determine the dynamic changes in quantitative features of human gastric lesions when passing from normal histological structures, through hyperplastic processes (chronic gastritis, gastric precancer (ulcers and polyps with or without malignancy till the development of primary carcinomas and their corresponding lymphogeneous metastases. Besides the increased cytomorphometrical measures, we also noted an opportunity to classify the patients according to these data as well as to add to the knowledge of our consultation system for clinical aid and use, recently published in the literature.

  15. The relationship of human milk leptin and macronutrients with gastric emptying in term breastfed infants.

    Science.gov (United States)

    Cannon, Anna M; Gridneva, Zoya; Hepworth, Anna R; Lai, Ching T; Tie, Wan J; Khan, Sadaf; Hartmann, Peter E; Geddes, Donna T

    2017-07-01

    BackgroundInfants breastfed on demand exhibit a variety of feeding patterns and self-regulate their nutrient intake, but factors influencing their gastric emptying (GE) are poorly understood. Despite research into appetite regulation properties of leptin, there is limited information about relationships between human milk leptin and infant GE.MethodsGastric volumes were calculated from ultrasound scans of infants' stomachs (n=20) taken before and after breastfeeding, and then every 12.5 min (median; range: 3-45 min) until the next feed. Skim milk leptin and macronutrient concentrations were measured and doses were calculated.ResultsThe leptin concentration was (mean±SD) 0.51±0.16 ng/ml; the leptin dose was 45.5±20.5 ng per feed. No relationships between both concentration and dose of leptin and time between the feeds (P=0.57; P=1, respectively) or residual stomach volumes before the subsequent feed (P=0.20; P=0.050) were found. Post-feed stomach volumes (GE rate) were not associated with leptin concentration (P=0.77) or dose (P=0.85).ConclusionGE in term breastfed infants was not associated with either skim milk leptin concentration or dose. Further investigation with inclusion of whole-milk leptin and other hormones that affect gastrointestinal activity is warranted.

  16. Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA, which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS, down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.

  17. Temporal dimensions of human environmental research: Adaptive ...

    African Journals Online (AJOL)

    For the past, oral histories were conducted with elderly people in four villages to acquire information about past adaptive strategies. For the future, focus groups and fuzzy cognitive maps (FCM) of household participants in a workshop setting were conducted so as to understand what adaptations they envisage. We found ...

  18. Characterization of human gastric carcinoma-related methylation of 9 miR CpG islands and repression of their expressions in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Du Yantao

    2012-06-01

    Full Text Available Abstract Background Many miR genes are located within or around CpG islands. It is unclear whether methylation of these CpG islands represses miR transcription regularly. The aims of this study are to characterize gastric carcinoma (GC-related methylation of miR CpG islands and its relationship with miRNA expression. Methods Methylation status of 9 representative miR CpG islands in a panel of cell lines and human gastric samples (including 13 normal biopsies, 38 gastritis biopsies, 112 pairs of GCs and their surgical margin samples was analyzed by bisulfite-DHPLC and sequencing. Mature miRNA levels were determined with quantitative RT-PCR. Relationships between miR methylation, transcription, GC development, and clinicopathological characteristics were statistically analyzed. Results Methylation frequency of 5 miR CpG islands (miR-9-1, miR-9-3, miR-137, miR-34b, and miR-210 gradually increased while the proportion of methylated miR-200b gradually decreased during gastric carcinogenesis (Ps miR-9-1 methylation was detected in 62%-64% of the GC samples and 4% of the normal or gastritis samples (18/28 versus 2/48; Odds ratio, 41.4; P miR-210 methylation showed high correlation with H. pylori infection. miR-375, miR-203, and miR-193b methylation might be host adaptation to the development of GCs. Methylation of these miR CpG islands was consistently shown to significantly decrease the corresponding miRNA levels presented in human cell lines. The inverse relationship was also observed for miR-9-1, miR-9-3, miR-137, and miR-200b in gastric samples. Among 112 GC patients, miR-9-1 methylation was an independent favourable predictor of overall survival of GC patients in both univariate and multivariate analysis (P  Conclusions In conclusion, alteration of methylation status of 6 of 9 tested miR CpG islands was characterized in gastric carcinogenesis. miR-210 methylation correlated with H. pylori infection. miR-9-1 methylation may be a GC

  19. Characterization of human gastric carcinoma-related methylation of 9 miR CpG islands and repression of their expressions in vitro and in vivo

    International Nuclear Information System (INIS)

    Du, Yantao; Liu, Zhaojun; Gu, Liankun; Zhou, Jing; Zhu, Bu-dong; Ji, Jiafu; Deng, Dajun

    2012-01-01

    Many miR genes are located within or around CpG islands. It is unclear whether methylation of these CpG islands represses miR transcription regularly. The aims of this study are to characterize gastric carcinoma (GC)-related methylation of miR CpG islands and its relationship with miRNA expression. Methylation status of 9 representative miR CpG islands in a panel of cell lines and human gastric samples (including 13 normal biopsies, 38 gastritis biopsies, 112 pairs of GCs and their surgical margin samples) was analyzed by bisulfite-DHPLC and sequencing. Mature miRNA levels were determined with quantitative RT-PCR. Relationships between miR methylation, transcription, GC development, and clinicopathological characteristics were statistically analyzed. Methylation frequency of 5 miR CpG islands (miR-9-1, miR-9-3, miR-137, miR-34b, and miR-210) gradually increased while the proportion of methylated miR-200b gradually decreased during gastric carcinogenesis (Ps < 0.01). More miR-9-1 methylation was detected in 62%-64% of the GC samples and 4% of the normal or gastritis samples (18/28 versus 2/48; Odds ratio, 41.4; P < 0.01). miR-210 methylation showed high correlation with H. pylori infection. miR-375, miR-203, and miR-193b methylation might be host adaptation to the development of GCs. Methylation of these miR CpG islands was consistently shown to significantly decrease the corresponding miRNA levels presented in human cell lines. The inverse relationship was also observed for miR-9-1, miR-9-3, miR-137, and miR-200b in gastric samples. Among 112 GC patients, miR-9-1 methylation was an independent favourable predictor of overall survival of GC patients in both univariate and multivariate analysis (P < 0.02). In conclusion, alteration of methylation status of 6 of 9 tested miR CpG islands was characterized in gastric carcinogenesis. miR-210 methylation correlated with H. pylori infection. miR-9-1 methylation may be a GC-specific event. Methylation of miR CpG islands may

  20. Sonic hedgehog pathway is essential for maintenance of cancer stem-like cells in human gastric cancer.

    Directory of Open Access Journals (Sweden)

    Zhou Song

    Full Text Available Abnormal activation of the Sonic hedgehog (SHH pathway has been described in a wide variety of human cancers and in cancer stem cells (CSCs, however, the role of SHH pathway in gastric CSCs has not been reported. In this study, we investigated the possibility that abnormal activation of the SHH pathway maintained the characteristics of gastric CSCs. First, we identified cancer stem-like cells (CSLCs from human gastric cancer cell lines (HGC-27, MGC-803 and MKN-45 using tumorsphere culture. Compared with adherent cells, the floating tumorsphere cells had more self-renewing capacity and chemoresistance. The cells expressing CSCs markers (CD44, CD24 and CD133 were also significantly more in tumorsphere cells than in adherent cells. More importantly, in vivo xenograft studies showed that tumors could be generated with 2 x 10⁴ tumorsphere cells, which was 100-fold less than those required for tumors seeding by adherent cells. Next, RT-PCR and Western blot showed that the expression levels of Ptch and Gli1 (SHH pathway target genes were significantly higher in tumorsphere cells than in adherent cells. The results of quantitative real-time PCR were similar to those of RT-PCR and Western blot. Further analysis revealed that SHH pathway blocked by cyclopamine or 5E1 caused a higher reduction in self-renewing capacity of HGC-27 tumorsphere cells than that of adherent cells. We also found that SHH pathway blocking strongly enhanced the efficacy of chemotherapeutic drugs in HGC-27 tumorsphere cells in vitro and in vivo but had no significant effect in adherent cells. Finally, we isolated the tumorspheres from gastric cancer specimen, these cells also had chemoresistance and tumorigenic capacity, and SHH pathway maintained the gastric CSLCs characteristics of tumorsphere cells from primary tumor samples. In conclusion, our data suggested that SHH pathway was essential for maintenance of CSLCs in human gastric cancer.

  1. In vitro anti-proliferative activity of clove extract on human gastric carcinoma

    Directory of Open Access Journals (Sweden)

    A. Karimi

    2017-10-01

    Full Text Available Background and objectives: Cancer cell resistance to common chemotherapy agents is on rise. Plants are considered valuable sources of herbal drugs for cancer therapy. The present study was conducted to investigate the in vitro antioxidant, anti-proliferative, and apoptosis-inducing properties of clove (Syzygium aromaticum L. extract in human gastric carcinoma (AGS. Methods: Crude ethanol extract of S. aromaticum dried buds was prepared and  in vitro anti-proliferative effects of the extract on AGS and normal Human dermal fibroblasts (HDF cell lines were studied by MTT assay. To examine apoptosis induction, AGS cells were incubated with IC50 concentrations of the extract, stained with propidium iodide (PI and annexin V-fluorescein isothiocyanate (FITC, and analyzed by flow cytometry. Antioxidant activity and total phenolics and flavonoids contents were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method, respectively. Results: The IC50 of DPPH and total phenolics and flavonoids contents of the extract were 10.05±1.93 μg/mL, 225.6±40 mg GAE/g, and 29.30±2.35 mgRUT/g, respectively. The IC50 of the extract against HDFs was 649 µg/mL, higher than AGS cells, which was 118.7 g/mL at 48 h after treatment. Flow cytometric analysis showed that the extract induced cell apoptosis. Conclusions: Crude ethanol S. aromaticum extract had high total phenolics content, and suppressed the proliferation of human gastric cancer cells, likely due to apoptosis induction. Further studies should be conducted to determine the mechanisms of its anticancer effects.

  2. WWC3 downregulation correlates with poor prognosis and inhibition of Hippo signaling in human gastric cancer

    Directory of Open Access Journals (Sweden)

    Hou J

    2017-06-01

    Full Text Available Jiabin Hou, Jin Zhou The First Affiliated Hospital, Harbin Medical University, Harbin, People’s Republic of China Abstract: The aim of this study was to investigate the clinicopathological significance and biological roles of WWC3 in human gastric cancer (GC. Clinical significance of WWC3 in human GCs was examined by using immunohistochemistry (IHC. WWC3 was downregulated in 48 of 111 human GCs, and its downregulation was associated with advanced stage, positive nodal status, and higher relapse rate. Importantly, WWC3 downregulation correlated with poor survival. It was also found that WWC3 protein expression was downregulated in GC cell lines compared with normal cell line GES-1. On one hand, WWC3 overexpression inhibited the cell growth rate and invading ability in HGC-27 cell line. On the other hand, depleting WWC3 by small interfering RNA (siRNA promoted proliferation rate and invading ability in the SGC-7901 cell line. In addition, cell cycle analysis showed that WWC3 overexpression inhibited while its depletion accelerated cell cycle progression at the G1/S transition. Western blot (WB analysis demonstrated that WWC3 repressed cyclin D1 and cyclin E while upregulated p27 expression. Luciferase reporter assay showed that WWC3 activated Hippo signaling pathway by suppressing TEAD transcription activity, with downregulation of total and nuclear YAP and its target CTGF. WWC3 siRNA depletion exhibited the opposite effects. In conclusion, this study indicates that WWC3 serves as a tumor suppressor in GC by activating Hippo signaling. Keywords: WWC3, gastric cancer, cell cycle, Hippo, YAP

  3. Human epidermal growth factor receptor 2 status of gastric cancer patients in Asia: results from a large, multicountry study.

    Science.gov (United States)

    Pathmanathan, Nirmala; Geng, Jing-Shu; Li, Wencai; Nie, Xiu; Veloso, Januario; Wang, John; Hill, Julie; Mccloud, Philip; Bilous, Michael

    2017-06-01

    Current estimates of the human epidermal growth factor receptor 2 (HER2)-positivity rate in gastric cancer vary widely in the literature, and there are limited data from countries in Asia. The primary aim of this study was to conduct a clinical audit of laboratories across seven countries in Asia to determine the incidence of HER2-positive gastric cancer in this region. Pathologists were asked to collect data on patient gender, age, cancer site, specimen type, tumor spread, type and grade, HER2 test results, including protein and/or gene copy enumeration, and final HER2 status on consecutive gastric cancer cases tested for HER2 in their laboratory over a 2-year period. HER2 results from 5,301 gastric cancers were submitted by 50 laboratories. The overall HER2-positivity rate was 9.7% which, after the exclusion of China, increased to 18.1%. The rate between countries ranged from 0% to 23.1%, and from 0% to 50.0% between laboratories. An equivocal HER2 result was recorded in 19.5% of cases. Despite the lack of centralized testing to confirm the accuracy of HER2 diagnoses, the incidence of HER2-positive gastric cancer observed here was comparable to that reported in the literature. Nevertheless, rates were highly variable between countries and laboratories, which suggests a lack of HER2 testing expertise in gastric cancer. Given that the mortality rates for gastric cancer in Eastern Asia are the highest in the world, efforts should focus on improving HER2 testing expertise in the region so that patients receive the appropriate treatment early in their disease. © 2016 The Authors. Asia-Pacific Journal of Clinical Oncology Published by John Wiley & Sons Australia, Ltd.

  4. Action of ethanol and some alcoholic beverages on gastric acid secretion and release of gastrin in humans.

    Science.gov (United States)

    Singer, M V; Leffmann, C; Eysselein, V E; Calden, H; Goebell, H

    1987-12-01

    The action of intragastric ethanol in various concentrations (1.4%-40% vol/vol) and of beer, white wine, cognac, and whisky on gastric acid secretion and release of gastrin was studied in healthy humans. Ethanol concentrations of 1.4% and 4% (vol/vol), but not higher, significantly (p less than 0.05) increased gastric acid secretion to 23% and 22%, respectively, of incremental maximal acid output [i.e., observed response to pentagastrin (6 micrograms/kg s.c.) minus basal acid output]. The 1-h incremental gastric acid responses to beer and wine were 96% and 61%, respectively, of incremental maximal acid output. Neither cognac nor whisky had any stimulatory effect. The 1-h incremental gastric acid response to an 8% peptone meal was 40% of incremental maximal acid output, and to peptone plus white wine 77%. Plasma gastrin levels were not altered by ethanol, cognac, and whisky. The 1-h integrated plasma gastrin responses to beer and white wine were 119% and 77%, respectively, of the response to the peptone meal. We conclude that (a) the action of pure ethanol on gastric acid secretion is related to its concentration: concentrations of 1.4% and 4% are moderate stimulants; concentrations of 5%-40% have no effect, or rather an inhibitory effect; (b) beer and white wine, but not whisky and cognac, are potent stimulants of gastric acid secretion; (c) the stimulatory mechanism of low ethanol concentrations is unknown; and (d) nonalcoholic constituents of beer and wine are most likely responsible for the stimulatory actions of both beverages on gastric acid secretion and release of gastrin.

  5. TXNL1-XRCC1 pathway regulates cisplatin-induced cell death and contributes to resistance in human gastric cancer

    Science.gov (United States)

    Xu, W; Wang, S; Chen, Q; Zhang, Y; Ni, P; Wu, X; Zhang, J; Qiang, F; Li, A; Røe, O D; Xu, S; Wang, M; Zhang, R; Zhou, J

    2014-01-01

    Cisplatin is a cytotoxic platinum compound that triggers DNA crosslinking induced cell death, and is one of the reference drugs used in the treatment of several types of human cancers including gastric cancer. However, intrinsic or acquired drug resistance to cisplatin is very common, and leading to treatment failure. We have recently shown that reduced expression of base excision repair protein XRCC1 (X-ray repair cross complementing group1) in gastric cancerous tissues correlates with a significant survival benefit from adjuvant first-line platinum-based chemotherapy. In this study, we demonstrated the role of XRCC1 in repair of cisplatin-induced DNA lesions and acquired cisplatin resistance in gastric cancer by using cisplatin-sensitive gastric cancer cell lines BGC823 and the cisplatin-resistant gastric cancer cell lines BGC823/cis-diamminedichloridoplatinum(II) (DDP). Our results indicated that the protein expression of XRCC1 was significantly increased in cisplatin-resistant cells and independently contributed to cisplatin resistance. Irinotecan, another chemotherapeutic agent to induce DNA damaging used to treat patients with advanced gastric cancer that progressed on cisplatin, was found to inhibit the expression of XRCC1 effectively, and leading to an increase in the sensitivity of resistant cells to cisplatin. Our proteomic studies further identified a cofactor of 26S proteasome, the thioredoxin-like protein 1 (TXNL1) that downregulated XRCC1 in BGC823/DDP cells via the ubiquitin-proteasome pathway. In conclusion, the TXNL1-XRCC1 is a novel regulatory pathway that has an independent role in cisplatin resistance, indicating a putative drug target for reversing cisplatin resistance in gastric cancer. PMID:24525731

  6. PIV and CFD studies on analyzing intragastric flow phenomena induced by peristalsis using a human gastric flow simulator.

    Science.gov (United States)

    Kozu, Hiroyuki; Kobayashi, Isao; Neves, Marcos A; Nakajima, Mitsutoshi; Uemura, Kunihiko; Sato, Seigo; Ichikawa, Sosaku

    2014-08-01

    This study quantitatively analyzed the flow phenomena in model gastric contents induced by peristalsis using a human gastric flow simulator (GFS). Major functions of the GFS include gastric peristalsis simulation by controlled deformation of rubber walls and direct observation of inner flow through parallel transparent windows. For liquid gastric contents (water and starch syrup solutions), retropulsive flow against the direction of peristalsis was observed using both particle image velocimetry (PIV) and computational fluid dynamics (CFD). The maximum flow velocity was obtained in the region occluded by peristalsis. The maximum value was 9 mm s(-1) when the standard value of peristalsis speed in healthy adults (UACW = 2.5 mm s(-1)) was applied. The intragastric flow-field was laminar with the maximum Reynolds number (Re = 125). The viscosity of liquid gastric contents hardly affected the maximum flow velocity in the applied range of this study (1 to 100 mPa s). These PIV results agreed well with the CFD results. The maximum shear rate in the liquid gastric contents was below 20 s(-1) at UACW = 2.5 mm s(-1). We also measured the flow-field in solid-liquid gastric contents containing model solid food particles (plastic beads). The direction of velocity vectors was influenced by the presence of the model solid food particle surface. The maximum flow velocity near the model solid food particles ranged from 8 to 10 mm s(-1) at UACW = 2.5 mm s(-1). The maximum shear rate around the model solid food particles was low, with a value of up to 20 s(-1).

  7. Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Ma, Ning; Adachi, Yukihiko; Hiraku, Yusuke; Horiki, Noriyuki; Horiike, Shinichirou; Imoto, Ichiro; Pinlaor, Somchai; Murata, Mariko; Semba, Reiji; Kawanishi, Shosuke

    2004-01-01

    Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2 ' -deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection

  8. Effects of the H(2)-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Graff, J

    2008-01-01

    Objective. Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist...

  9. Vascular adaption to physical inactivity in humans

    NARCIS (Netherlands)

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical

  10. Vascular adaptation to physical inactivity in humans.

    NARCIS (Netherlands)

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical

  11. Blueberry proanthocyanidins against human norovirus surrogates in model foods and under simulated gastric conditions.

    Science.gov (United States)

    Joshi, Snehal; Howell, Amy B; D'Souza, Doris H

    2017-05-01

    Blueberry proanthocyanidins (B-PAC) are known to decrease titers of human norovirus surrogates in vitro. The application of B-PAC as therapeutic or preventive options against foodborne viral illness needs to be determined using model foods and simulated gastric conditions in vitro. The objective of this study was to evaluate the antiviral effect of B-PAC in model foods (apple juice (AJ) and 2% reduced fat milk) and simulated gastrointestinal fluids against cultivable human norovirus surrogates (feline calicivirus; FCV-F9 and murine norovirus; MNV-1) over 24 h at 37 °C. Equal amounts of each virus (5 log PFU/ml) was mixed with B-PAC (1, 2 and 5 mg/ml) prepared either in AJ, or 2% milk, or simulated gastric fluids and incubated over 24 h at 37 °C. Controls included phosphate buffered saline, malic acid (pH 7.2), AJ, 2% milk or simulated gastric and intestinal fluids incubated with virus over 24 h at 37 °C. The tested viruses were reduced to undetectable levels within 15 min with B-PAC (1, 2 and 5 mg/ml) in AJ (pH 3.6). However, antiviral activity of B-PAC was reduced in milk. FCV-F9 was reduced by 0.4 and 1.09 log PFU/ml with 2 and 5 mg/ml B-PAC in milk, respectively and MNV-1 titers were reduced by 0.81 log PFU/ml with 5 mg/ml B-PAC in milk after 24 h. B-PAC at 5 mg/ml in simulated intestinal fluid reduced titers of the tested viruses to undetectable levels within 30 min. Overall, these results show the potential of B-PAC as preventive and therapeutic options for foodborne viral illnesses. Copyright © 2016. Published by Elsevier Ltd.

  12. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  13. Clinicopathological correlation and prognostic significance of sonic hedgehog protein overexpression in human gastric cancer.

    Science.gov (United States)

    Niu, Yanyang; Li, Fang; Tang, Bo; Shi, Yan; Hao, Yingxue; Yu, Peiwu

    2014-01-01

    This study investigated the expression of Sonic Hedgehog (Shh) protein in gastric cancer, and correlated it with clinicopathological parameters. The prognostic significance of Shh protein was analyzed. Shh protein expression was evaluated in 113 cases of gastric cancer and 60 cases of normal gastric mucosa. The immunoreactivity was scored semi quantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely non-overexpression group with score 0 or 1, and overexpression group with score 2 or 3. The overexpression of Shh protein was correlated with clinicopathological parameters. Survival analysis was then performed to determine the Shh protein prognostic significance in gastric cancer. In immunohistochemistry study, nineteen (31.7%) normal gastric mucosa revealed Shh protein overexpression, while eighty-one (71.7%) gastric cancer revealed overexpression. The expression of Shh protein were significantly higher in gastric cancer tissues than in normal gastric mucosa (P overexpression and non-expression groups P = 0.168 and 0.071). However, Shh overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 1.187, P = 0.041). Shh protein expression is upregulated and is statistically correlated with age, tumor differentiation, depth of invasion, pathologic staging, and nodal metastasis. The Shh protein overexpression is a significant independent prognostic factor in multivariate Cox regression analysis in gastric cancer.

  14. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Ming-Ming Tsai

    2016-06-01

    Full Text Available Human gastric cancer (GC is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

  15. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Gang [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Zou, Xi [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Zhou, Jin-Yong [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Sun, Wei [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Wu, Jian [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Xu, Jia-Li [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Wang, Rui-Ping, E-mail: ruipingwang61@hotmail.com [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    2013-09-20

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

  16. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    International Nuclear Information System (INIS)

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-01-01

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug

  17. Human Adaptations to Heat and Cold Stress

    Science.gov (United States)

    2002-04-01

    Fed.Proc. 22: 843-845, 1963. 36. Hilton, J. G. Acetylcholine stimulation of the sympathetic ganglia: effects of taurine and nicotinic and muscarinic...reduced performance. Heat acclimation results in biological adaptations that reduce these negative effects of heat stress. One becomes acclimated to the...Exercise in the heat is the most effective method for developing heat acclimation, however, even resting in the heat results in some acclimation. The full

  18. Vascular adaption to physical inactivity in humans

    OpenAIRE

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical inactivity, exercise decreases the risk for cardiovascular disease. This beneficial effect of exercise is partly due to changes in vascular function and structure. However, far less is known about vascular ...

  19. Adaptations to local environments in modern human populations.

    Science.gov (United States)

    Jeong, Choongwon; Di Rienzo, Anna

    2014-12-01

    After leaving sub-Saharan Africa around 50000-100000 years ago, anatomically modern humans have quickly occupied extremely diverse environments. Human populations were exposed to further environmental changes resulting from cultural innovations, such as the spread of farming, which gave rise to new selective pressures related to pathogen exposures and dietary shifts. In addition to changing the frequency of individual adaptive alleles, natural selection may also shape the overall genetic architecture of adaptive traits. Here, we review recent advances in understanding the genetic architecture of adaptive human phenotypes based on insights from the studies of lactase persistence, skin pigmentation and high-altitude adaptation. These adaptations evolved in parallel in multiple human populations, providing a chance to investigate independent realizations of the evolutionary process. We suggest that the outcome of adaptive evolution is often highly variable even under similar selective pressures. Finally, we highlight a growing need for detecting adaptations that did not follow the classical sweep model and for incorporating new sources of genetic evidence such as information from ancient DNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Additive effects of gastric volumes and macronutrient composition on the sensation of postprandial fullness in humans.

    Science.gov (United States)

    Marciani, L; Cox, E F; Pritchard, S E; Major, G; Hoad, C L; Mellows, M; Hussein, M O; Costigan, C; Fox, M; Gowland, P A; Spiller, R C

    2015-03-01

    Intake of food or fluid distends the stomach and triggers mechanoreceptors and vagal afferents. Wall stretch and tension produces a feeling of fullness. Duodenal infusion studies assessing gastric sensitivity by barostat have shown that the products of fat digestion have a greater effect on the sensation of fullness and also dyspeptic symptoms than carbohydrates. We tested here the hypothesis that fat and carbohydrate have different effects on gastric sensation under physiological conditions using non-invasive magnetic resonance imaging (MRI) to measure gastric volumes. Thirteen healthy subjects received a rice pudding test meal with added fat or added carbohydrate on two separate occasions and underwent serial postprandial MRI scans for 4.5 h. Fullness was assessed on a 100-mm visual analogue scale. Gastric half emptying time was significantly slower for the high-carbohydrate meal than for the high-fat meal, P=0.0327. Fullness significantly correlated with gastric volumes for both meals; however, the change from baseline in fullness scores was higher for the high-fat meal for any given change in stomach volume (P=0.0147), despite the lower energy content and faster gastric emptying of the high-fat meal. Total gastric volume correlates positively and linearly with postprandial fullness and ingestion of a high-fat meal increases this sensation compared with high-carbohydrate meal. These findings can be of clinical interest in patients presenting with postprandial dyspepsia whereby manipulating gastric sensitivity by dietary intervention may help to control digestive sensations.

  1. Cognitive adaptations for gathering-related navigation in humans.

    Science.gov (United States)

    Krasnow, Max M; Truxaw, Danielle; Gaulin, Steven J C; New, Joshua; Ozono, Hiroki; Uono, Shota; Ueno, Taiji; Minemoto, Kazusa

    2011-01-01

    Current research increasingly suggests that spatial cognition in humans is accomplished by many specialized mechanisms, each designed to solve a particular adaptive problem. A major adaptive problem for our hominin ancestors, particularly females, was the need to efficiently gather immobile foods which could vary greatly in quality, quantity, spatial location and temporal availability. We propose a cognitive model of a navigational gathering adaptation in humans and test its predictions in samples from the US and Japan. Our results are uniformly supportive: the human mind appears equipped with a navigational gathering adaptation that encodes the location of gatherable foods into spatial memory. This mechanism appears to be chronically active in women and activated under explicit motivation in men.

  2. Mitochondria-dependent apoptosis induced by nanoscale hydroxyapatite in human gastric cancer SGC-7901 cells.

    Science.gov (United States)

    Chen, Xiaojuan; Deng, Changsheng; Tang, Shengli; Zhang, Ming

    2007-01-01

    Nanoscale hydroxyapatite (nano-HAP) has been reported to exhibit anti-cancer effect on several human cancers, but the molecular mechanism of which remains unclear. The aim of this study was to explore the mechanisms by investigating the effects of nano-HAP on human gastric cancer SGC-7901 cells. Our results showed that nano-HAP significantly reduced cell viability, and induced apoptosis in SGC-7901 cells characterized by hypodiploid DNA contents, morphological changes and DNA fragmentation. The increase in apoptosis was accompanied with the increased expression of Bax, a pro-apoptotic protein, and decreased expression of Bcl-2, an anti-apoptotic protein, the decrease of mitochondrial membrane potential and the release of cytochrome c from mitochondria into cytosol. Furthermore, the activation of caspases-3, and -9, but not activation of caspases-8 was induced by nano-HAP. Z-VAD-fmk, a universal caspase inhibitor, dose-dependently inhibited nano-HAP-induced apoptosis. This study demonstrates that nano-HAP inhibits the proliferation of SGC-7901 cells by inducing apoptosis, and the apoptotic pathway of nano-HAP-induced apoptosis is mediated through the mitochondrial-dependent and caspase-dependent pathway.

  3. Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases

    Science.gov (United States)

    Gobert, Alain P.; Wilson, Keith T.

    2017-01-01

    The innate immune response is a critical hallmark of Helicobacter pylori infection. Epithelial and myeloid cells produce effectors, including the chemokine CXCL8, reactive oxygen species (ROS), and nitric oxide (NO), in response to bacterial components. Mechanistic and epidemiologic studies have emphasized that dysregulated and persistent release of these products leads to the development of chronic inflammation and to the molecular and cellular events related to carcinogenesis. Moreover, investigations in H. pylori-infected patients about polymorphisms of the genes encoding CXCL8 and inducible NO synthase, and epigenetic control of the ROS-producing enzyme spermine oxidase, have further proven that overproduction of these molecules impacts the severity of gastric diseases. Lastly, the critical effect of the crosstalk between the human host and the infecting bacterium in determining the severity of H. pylori-related diseases has been supported by phylogenetic analysis of the human population and their H. pylori isolates in geographic areas with varying clinical and pathologic outcomes of the infection. PMID:28124148

  4. Adaptive Variability in Skilled Human Movements

    Science.gov (United States)

    Kudo, Kazutoshi; Ohtsuki, Tatsuyuki

    Human movements are produced in variable external/internal environments. Because of this variability, the same motor command can result in quite different movement patterns. Therefore, to produce skilled movements humans must coordinate the variability, not try to exclude it. In addition, because human movements are produced in redundant and complex systems, a combination of variability should be observed in different anatomical/physiological levels. In this paper, we introduce our research about human movement variability that shows remarkable coordination among components, and between organism and environment. We also introduce nonlinear dynamical models that can describe a variety of movements as a self-organization of a dynamical system, because the dynamical systems approach is a major candidate to understand the principle underlying organization of varying systems with huge degrees-of-freedom.

  5. Release of prostaglandin E2 into gastric juice during stimulation of muscarinic- and gastrin receptors in dogs and in humans

    DEFF Research Database (Denmark)

    Madsen, Jørgen Rask; Bukhave, K; Hovendal, C P

    1981-01-01

    To investigate the causal relationship, if any, between gastric PG formation and gastric acid output, the release of PGE2 into gastric juice has been studied in eight beagle dogs with a gastric fistula, using sustained half-maximal stimulation by bethanechol and pentagastrin, and in eight duodenal...... ulcer patients, using the combined sham feeding/pentagastrin test. Immunoreactive PGE2 was determined by a method validated by gas chromatography-mass spectrometry and PGE2 values were normalized by expressing them as ng PGE2 released per meq H+ secreted. In the dogs "steady state" PGE2 output (0...... minutes significantly (p less than 0.01) higher (3.9-46 ng/meq H+) than in pentagastrin experiments (0.8-20 ng/meq H+). In humans the peak PGE2 output during sham feeding (3.4-41 ng/meq H+) was significantly (p less than 0.02) larger than following bolus stimulation (6/micrograms/kg) by pentagastrin (2...

  6. Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum.

    Science.gov (United States)

    Choi, Eunyoung; Roland, Joseph T; Barlow, Brittney J; O'Neal, Ryan; Rich, Amy E; Nam, Ki Taek; Shi, Chanjuan; Goldenring, James R

    2014-11-01

    The glands of the stomach body and antral mucosa contain a complex compendium of cell lineages. In lower mammals, the distribution of oxyntic glands and antral glands define the anatomical regions within the stomach. We examined in detail the distribution of the full range of cell lineages within the human stomach. We determined the distribution of gastric gland cell lineages with specific immunocytochemical markers in entire stomach specimens from three non-obese organ donors. The anatomical body and antrum of the human stomach were defined by the presence of ghrelin and gastrin cells, respectively. Concentrations of somatostatin cells were observed in the proximal stomach. Parietal cells were seen in all glands of the body of the stomach as well as in over 50% of antral glands. MIST1 expressing chief cells were predominantly observed in the body although individual glands of the antrum also showed MIST1 expressing chief cells. While classically described antral glands were observed with gastrin cells and deep antral mucous cells without any parietal cells, we also observed a substantial population of mixed type glands containing both parietal cells and G cells throughout the antrum. Enteroendocrine cells show distinct patterns of localisation in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Patient-Derived Gastric Carcinoma Xenograft Mouse Models Faithfully Represent Human Tumor Molecular Diversity.

    Directory of Open Access Journals (Sweden)

    Tianwei Zhang

    Full Text Available Patient-derived cancer xenografts (PDCX generally represent more reliable models of human disease in which to evaluate a potential drugs preclinical efficacy. However to date, only a few patient-derived gastric cancer xenograft (PDGCX models have been reported. In this study, we aimed to establish additional PDGCX models and to evaluate whether these models accurately reflected the histological and genetic diversities of the corresponding patient tumors. By engrafting fresh patient gastric cancer (GC tissues into immune-compromised mice (SCID and/or nude mice, thirty two PDGCX models were established. Histological features were assessed by a qualified pathologist based on H&E staining. Genomic comparison was performed for several biomarkers including ERBB1, ERBB2, ERBB3, FGFR2, MET and PTEN. These biomarkers were profiled to assess gene copy number by fluorescent in situ hybridization (FISH and/or protein expression by immunohistochemistry (IHC. All 32 PDGCX models retained the histological features of the corresponding human tumors. Furthermore, among the 32 models, 78% (25/32 highly expressed ERBB1 (EGFR, 22% (7/32 were ERBB2 (HER2 positive, 78% (25/32 showed ERBB3 (HER3 high expression, 66% (21/32 lost PTEN expression, 3% (1/32 harbored FGFR2 amplification, 41% (13/32 were positive for MET expression and 16% (5/32 were MET gene amplified. Between the PDGCX models and their parental tumors, a high degree of similarity was observed for FGFR2 and MET gene amplification, and also for ERBB2 status (agreement rate = 94~100%; kappa value = 0.81~1. Protein expression of PTEN and MET also showed moderate agreement (agreement rate = 78%; kappa value = 0.46~0.56, while ERBB1 and ERBB3 expression showed slight agreement (agreement rate = 59~75%; kappa value = 0.18~0.19. ERBB2 positivity, FGFR2 or MET gene amplification was all maintained until passage 12 in mice. The stability of the molecular profiles observed across subsequent passages within the

  8. Estimation of gastric residence time of the Heidelberg capsule in humans: effect of varying food composition

    International Nuclear Information System (INIS)

    Mojaverian, P.; Ferguson, R.K.; Vlasses, P.H.; Rocci, M.L. Jr.; Oren, A.; Fix, J.A.; Caldwell, L.J.; Gardner, C.

    1985-01-01

    In animal and human studies, the gastric emptying of large (greater than 1 mm) indigestible solids is due to the activity of the interdigestive migrating myoelectric complex. The gastric residence time (GRT) of an orally administered, nondigestible, pH-sensitive, radiotelemetric device (Heidelberg capsule) was evaluated in three studies in healthy volunteers. In 6 subjects, the GRT of the Heidelberg capsule was compared with the half-emptying time (t1/2) of diethylenetriaminepentaacetic acid labeled with technetium 99m after a 4-ml/kg liquid fatty meal. The mean (+/-SD) GRT (4.3 +/- 1.4 h) was significantly (p less than 0.001) longer than the mean t1/2 (1.1 +/- 0.3 h); the GRT was prolonged compared with the t1/2 in each subject. In a randomized, crossover trial in 10 subjects, frequent feeding caused a dramatic prolongation in mean GRT of the capsule compared with the fasting state (greater than 14.5 vs. 0.5 h, p less than 0.005). In another crossover study in 6 subjects, the GRT of the capsule was evaluated after an overnight fast, a standard breakfast including solid food, and a liquid meal (i.e., 200 ml of diluted light cream). The mean GRT was 2.6 +/- 0.9 h after the liquid meal vs. 1.2 +/- 0.8 h after fasting (p less than 0.025). The mean GRT after the breakfast was 4.8 +/- 1.5 h, which was significantly greater than that after fasting (p less than 0.001) and after the liquid meal (p less than 0.01). These data suggest that the GRT of the Heidelberg capsule is a marker of the interdigestive migrating myoelectric complex in humans, the interdigestive migrating myoelectric complex can be markedly delayed by frequent feedings with solids, and the interdigestive migrating myoelectric complex is delayed by both liquid and solid meals

  9. Estimation of gastric residence time of the Heidelberg capsule in humans: effect of varying food composition

    Energy Technology Data Exchange (ETDEWEB)

    Mojaverian, P.; Ferguson, R.K.; Vlasses, P.H.; Rocci, M.L. Jr.; Oren, A.; Fix, J.A.; Caldwell, L.J.; Gardner, C.

    1985-08-01

    In animal and human studies, the gastric emptying of large (greater than 1 mm) indigestible solids is due to the activity of the interdigestive migrating myoelectric complex. The gastric residence time (GRT) of an orally administered, nondigestible, pH-sensitive, radiotelemetric device (Heidelberg capsule) was evaluated in three studies in healthy volunteers. In 6 subjects, the GRT of the Heidelberg capsule was compared with the half-emptying time (t1/2) of diethylenetriaminepentaacetic acid labeled with technetium 99m after a 4-ml/kg liquid fatty meal. The mean (+/-SD) GRT (4.3 +/- 1.4 h) was significantly (p less than 0.001) longer than the mean t1/2 (1.1 +/- 0.3 h); the GRT was prolonged compared with the t1/2 in each subject. In a randomized, crossover trial in 10 subjects, frequent feeding caused a dramatic prolongation in mean GRT of the capsule compared with the fasting state (greater than 14.5 vs. 0.5 h, p less than 0.005). In another crossover study in 6 subjects, the GRT of the capsule was evaluated after an overnight fast, a standard breakfast including solid food, and a liquid meal (i.e., 200 ml of diluted light cream). The mean GRT was 2.6 +/- 0.9 h after the liquid meal vs. 1.2 +/- 0.8 h after fasting (p less than 0.025). The mean GRT after the breakfast was 4.8 +/- 1.5 h, which was significantly greater than that after fasting (p less than 0.001) and after the liquid meal (p less than 0.01). These data suggest that the GRT of the Heidelberg capsule is a marker of the interdigestive migrating myoelectric complex in humans, the interdigestive migrating myoelectric complex can be markedly delayed by frequent feedings with solids, and the interdigestive migrating myoelectric complex is delayed by both liquid and solid meals.

  10. Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without type 2 diabetes.

    Science.gov (United States)

    Chowdhury, Sara; Reeds, Dominic N; Crimmins, Dan L; Patterson, Bruce W; Laciny, Erin; Wang, Songyan; Tran, Hung D; Griest, Terry A; Rometo, David A; Dunai, Judit; Wallendorf, Michael J; Ladenson, Jack H; Polonsky, Kenneth S; Wice, Burton M

    2014-02-15

    Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10-14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol · kg(-1) · min(-1) was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions.

  11. Monaural adaptive mechanisms in human sound localization

    NARCIS (Netherlands)

    Wanrooij, M.M. van

    2007-01-01

    Human sound localization results primarily from the processing of binaural differences in sound level and arrival time for locations in the horizontal plane and of spectral shape cues generated by the head and pinnae for positions in the vertical plane. Both types of cues have to be weighted and

  12. From lifetime to evolution: timescales of human gut microbiota adaptation

    Directory of Open Access Journals (Sweden)

    Sara eQuercia

    2014-11-01

    Full Text Available Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gut microbiota is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The gut microbiota continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies.

  13. Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells.

    Science.gov (United States)

    Xu, Mei-Ying; Lee, Dong Hwa; Joo, Eun Ji; Son, Kun Ho; Kim, Yeong Shik

    2013-09-01

    In this study, we investigated the anticancer mechanism of akebia saponin PA (AS), a natural product isolated from Dipsacus asperoides in human gastric cancer cell lines. It was shown that AS-induced cell death is caused by autophagy and apoptosis in AGS cells. The apoptosis-inducing effect of AS was characterized by annexin V/propidium (PI) staining, increase of sub-G1 phase and caspase-3 activation, while the autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF1) decreased AS-induced cell death and caspase-3 activation, but caspase-3 inhibitor Ac-DEVD-CHO did not affect LC3-II accumulation or AS-induced cell viability, suggesting that AS induces autophagic cell death and autophagy contributes to caspase-3-dependent apoptosis. Furthermore, AS activated p38/c-Jun N-terminal kinase (JNK), which could be inhibited by BaF1, and caspase-3 activation was attenuated by both SB202190 and SP600125, indicating that AS-induced autophagy promotes mitogen-activated protein kinases (MAPKs)-mediated apoptosis. Taken together, these results demonstrate that AS induces autophagic and apoptotic cell death and autophagy plays the main role in akebia saponin PA-induced cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Quercetin Suppresses CYR61-Mediated Multidrug Resistance in Human Gastric Adenocarcinoma AGS Cells

    Directory of Open Access Journals (Sweden)

    Ho Bong Hyun

    2018-01-01

    Full Text Available Cysteine-rich angiogenic inducer 61 (CYR61 is an extracellular matrix-associated protein involved in survival, tumorigenesis, and drug resistance. Therefore, we examined the effects of flavones against CYR61-overexpressing human gastric adenocarcinoma AGS (AGS-cyr61 cells, which show remarkable resistance to 5-fluorouracil (5-FU, adriamycin (ADR, tamoxifen (TAM, paclitaxel (PAC, and docetaxel (DOC. Among the tested flavones, quercetin had the lowest 50% inhibitory concentration (IC50 and significantly reduced the viability of AGS-cyr61 cells compared with AGS cells. Quercetin: (1 reduced multidrug resistance-associated protein 1 and nuclear factor (NF-kappa B p65 subunit levels; (2 reversed multidrug resistance (MDR; (3 inhibited colony formation and induced caspase-dependent apoptosis; and (4 suppressed migration and down-regulated epithelial–mesenchymal transition-related proteins in AGS-cyr61. Moreover, AGS-cyr61 cells treated with quercetin concentrations close to the IC50 and simultaneously treated with 5-FU or ADR in the sub-lethal range showed strong synergism between quercetin and these two drugs. These findings indicate that CYR61 is a potential regulator of drug resistance and that quercetin may be a novel agent for improving the efficacy of anticancer drugs in AGS-cyr61 cells.

  15. Solubility of indium-tin oxide in simulated lung and gastric fluids: Pathways for human intake.

    Science.gov (United States)

    Andersen, Jens Christian Østergård; Cropp, Alastair; Paradise, Diane Caroline

    2017-02-01

    From being a metal with very limited natural distribution, indium (In) has recently become disseminated throughout the human society. Little is known of how In compounds behave in the natural environment, but recent medical studies link exposure to In compounds to elevated risk of respiratory disorders. Animal tests suggest that exposure may lead to more widespread damage in the body, notably the liver, kidneys and spleen. In this paper, we investigate the solubility of the most widely used In compound, indium-tin oxide (ITO) in simulated lung and gastric fluids in order to better understand the potential pathways for metals to be introduced into the bloodstream. Our results show significant potential for release of In and tin (Sn) in the deep parts of the lungs (artificial lysosomal fluid) and digestive tract, while the solubility in the upper parts of the lungs (the respiratory tract or tracheobronchial tree) is very low. Our study confirms that ITO is likely to remain as solid particles in the upper parts of the lungs, but that particles are likely to slowly dissolve in the deep lungs. Considering the prolonged residence time of inhaled particles in the deep lung, this environment is likely to provide the major route for uptake of In and Sn from inhaled ITO nano- and microparticles. Although dissolution through digestion may also lead to some uptake, the much shorter residence time is likely to lead to much lower risk of uptake. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice.

    Science.gov (United States)

    Song, Lin; Zhou, Xin; Jia, Hong-Jun; Du, Mei; Zhang, Jin-Ling; Li, Liang

    2016-08-01

    To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, mRNA expression of proliferation, invasion, EMT-related molecules were determined. 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of hGC-MSCs group were significantly higher than those of PBS group and the more the number of hGC-MSCs, the higher the tumor tissue volume; mRNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of hGC-MSCs group were higher than those of PBS group, and mRNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. hGC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  17. Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6 axis in human gastric adenocarcinoma AGS cells.

    Science.gov (United States)

    Lee, Hyun Sook; Hong, Ji Eun; Kim, Eun Ji; Kim, Sun Hyo

    2014-01-01

    Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has been reported to possess anticancer activity in many human cancer cells. However, the effect of escin on the metastasis has not been studied. The present study examined the effect of escin on the migration and invasion of AGS human gastric cancer cells. To examine the effects of escin on metastatic capacities of gastric cancer cells, AGS cells were cultured in the presence of 0-4 μmol/L escin. Escin inhibited cell migration and invasion in AGS cells. However, escin did not affect the viability of these cells at these concentrations. The chemokine receptor and its ligands play an important role in cancer metastasis. Escin decreased the production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6 was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced migration inhibition. In addition, escin inhibited the phosphorylation of focal adhesion kinase and Akt. These results demonstrate that escin inhibited the migration and invasion of AGS cells, which is associated with altered CXCL16/CXCR6 axis. These findings suggest that escin has potential as an antimetastatic agent in gastric cancer.

  18. Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans.

    Science.gov (United States)

    Little, Tanya J; Gupta, Nili; Case, R Maynard; Thompson, David G; McLaughlin, John T

    2009-09-01

    In cell line and animal models, sweet and bitter tastants induce secretion of signaling peptides (e.g., glucagon-like peptide-1 and cholecystokinin) and slow gastric emptying (GE). Whether human GE and appetite responses are regulated by the sweetness or bitterness per se of ingested food is, however, unknown. We aimed to determine whether intragastric infusion of "equisweet" (Study A) or "equibitter" (Study B) solutions slow GE to the same extent, and whether a glucose solution made sweeter by the addition of saccharin will slow GE more potently than glucose alone. Healthy nonobese subjects were studied in a single-blind, randomized fashion. Subjects received 500-ml intragastric infusions of predetermined equisweet solutions of glucose (560 mosmol/kgH(2)O), fructose (290 mosmol/kgH(2)O), aspartame (200 mg), and saccharin (50 mg); twice as sweet glucose + saccharin, water (volumetric control) (Study A); or equibitter solutions of quinine (0.198 mM), naringin (1 mM), or water (Study B). GE was evaluated using a [(13)C]acetate breath test, and hunger and fullness were scored using visual analog scales. In Study A, equisweet solutions did not empty similarly. Fructose, aspartame, and saccharin did not slow GE compared with water, but glucose did (P solution (P > 0.05, compared with glucose alone). In Study B, neither bitter tastant slowed GE compared with water. None of the solutions modulated perceptions of hunger or fullness. We conclude that, in humans, the presence of sweetness and bitterness taste per se in ingested solutions does not appear to signal to influence GE or appetite perceptions.

  19. Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans

    Science.gov (United States)

    Little, Tanya J.; Gupta, Nili; Case, R. Maynard; Thompson, David G.; McLaughlin, John T.

    2009-01-01

    In cell line and animal models, sweet and bitter tastants induce secretion of signaling peptides (e.g., glucagon-like peptide-1 and cholecystokinin) and slow gastric emptying (GE). Whether human GE and appetite responses are regulated by the sweetness or bitterness per se of ingested food is, however, unknown. We aimed to determine whether intragastric infusion of “equisweet” (Study A) or “equibitter” (Study B) solutions slow GE to the same extent, and whether a glucose solution made sweeter by the addition of saccharin will slow GE more potently than glucose alone. Healthy nonobese subjects were studied in a single-blind, randomized fashion. Subjects received 500-ml intragastric infusions of predetermined equisweet solutions of glucose (560 mosmol/kgH2O), fructose (290 mosmol/kgH2O), aspartame (200 mg), and saccharin (50 mg); twice as sweet glucose + saccharin, water (volumetric control) (Study A); or equibitter solutions of quinine (0.198 mM), naringin (1 mM), or water (Study B). GE was evaluated using a [13C]acetate breath test, and hunger and fullness were scored using visual analog scales. In Study A, equisweet solutions did not empty similarly. Fructose, aspartame, and saccharin did not slow GE compared with water, but glucose did (P 0.05, compared with glucose alone). In Study B, neither bitter tastant slowed GE compared with water. None of the solutions modulated perceptions of hunger or fullness. We conclude that, in humans, the presence of sweetness and bitterness taste per se in ingested solutions does not appear to signal to influence GE or appetite perceptions. PMID:19535679

  20. Sequencing of 50 human exomes reveals adaptation to high altitude

    DEFF Research Database (Denmark)

    Yi, Xin; Liang, Yu; Huerta-Sanchez, Emilia

    2010-01-01

    Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which...... difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus...

  1. Esculetin induces apoptosis in human gastric cancer cells through a cyclophilin D-mediated mitochondrial permeability transition pore associated with ROS.

    Science.gov (United States)

    Pan, Hui; Wang, Bao-Hui; Lv, Wang; Jiang, Yan; He, Lei

    2015-12-05

    Esculetin is a coumarin derivative from natural plants that has been commonly used as a folk medicine and has been reported to have beneficial pharmacological and biochemical activities; however, the mechanism by which esculetin prevents human gastric cancer cell growth is still largely unknown. In this study, we investigated the effect of esculetin on human gastric cancer cells and explored the cell death mechanism. Our data indicated that esculetin inhibited the growth of human gastric cancer cells in a dose- and time-dependent manner and apoptosis was the main cause of decreased cell viability in esculetin-treated cells. Additionally, esculetin treatment increased the activity of caspase-9 and caspase-3, and resulted in the appearance of the PARP cleavage product; and esculetin-induced cell death and apoptosis was decreased by pretreatment with CsA and NAC, but not BA; these results demonstrate that esculetin induced apoptosis via the caspase-dependent mitochondrial pathway in human gastric cancer cells in which cyclophilin D mediated the cytotoxic action by triggering the opening of the mitochondrial permeability transition pore; and the generation of ROS not only was a consequence of mitochondrial dysfunction, but also triggered esculetin-induced apoptosis. These results reveal a novel mechanism of esculetin on gastric cancer cells and suggest that esculetin could be a novel agent in the treatment of gastric cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand

    Directory of Open Access Journals (Sweden)

    Venu Venkatarame Gowda Saralamma

    2015-09-01

    Full Text Available Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma. The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose polymerase (PARP. Inhibitor studies’ results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm, pro-apoptotic proteins (Bax and Bak and anti-apoptotic protein (Bcl-xL in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.

  3. Therapeutic effects of lentivirus-mediated shRNA targeting of cyclin D1 in human gastric cancer

    International Nuclear Information System (INIS)

    Seo, Jin-Hee; Jeong, Eui-Suk; Choi, Yang-Kyu

    2014-01-01

    Gastric cancer is the second most common cause of cancer-related death in males and the fourth in females. Traditional treatment has poor prognosis because of recurrence and systemic side effects. Therefore, the development of new therapeutic strategies is an important issue. Lentivirus-mediated shRNA stably inhibits target genes and can efficiently transduce most cells. Since overexpressed cyclin D1 is closely related to human gastric cancer progression, inhibition of cyclin D1 using specific targeting could be an effective treatment method of human gastric cancer. The therapeutic effect of lentivirus-mediated shRNA targeting of cyclin D1 (ShCCND1) was analyzed both in vitro and in vivo experiments. In vitro, NCI-N87 cells with downregulation of cyclin D1 by ShCCND1 showed significant inhibition of cell proliferation, cell motility, and clonogenicity. Downregulation of cyclin D1 in NCI-N87 cells also resulted in significantly increased G1 arrest and apoptosis. In vivo, stable NCI-N87 cells expressing ShCCND1 were engrafted into nude mice. Then, the cancer-growth inhibition effect of lentivirus was confirmed. To assess lentivirus including ShCCND1 as a therapeutic agent, intratumoral injection was conducted. Tumor growth of the lentivirus-treated group was significantly inhibited compared to growth of the control group. These results are in accordance with the in vitro data and lend support to the mitotic figure count and apoptosis analysis of the tumor mass. The lentivirus-mediated ShCCND1 was constructed, which effectively inhibited growth of NCI-N87-derived cancer both in vitro and in vivo. The efficiency of shRNA knockdown and variation in the degree of inhibition is mediated by different shRNA sequences and cancer cell lines. These experimental results suggest the possibility of developing new gastric cancer therapies using lentivirus-mediated shRNA

  4. Sensorimotor adaptations to microgravity in humans

    Science.gov (United States)

    Edgerton, V. R.; McCall, G. E.; Hodgson, J. A.; Gotto, J.; Goulet, C.; Fleischmann, K.; Roy, R. R.

    2001-01-01

    Motor function is altered by microgravity, but little detail is available as to what these changes are and how changes in the individual components of the sensorimotor system affect the control of movement. Further, there is little information on whether the changes in motor performance reflect immediate or chronic adaptations to changing gravitational environments. To determine the effects of microgravity on the neural control properties of selected motor pools, four male astronauts from the NASA STS-78 mission performed motor tasks requiring the maintenance of either ankle dorsiflexor or plantarflexor torque. Torques of 10 or 50% of a maximal voluntary contraction (MVC) were requested of the subjects during 10 degrees peak-to-peak sinusoidal movements at 0.5 Hz. When 10% MVC of the plantarflexors was requested, the actual torques generated in-flight were similar to pre-flight values. Post-flight torques were higher than pre- and in-flight torques. The actual torques when 50% MVC was requested were higher in- and post-flight than pre-flight. Soleus (Sol) electromyographic (EMG) amplitudes during plantarflexion were higher in-flight than pre- or post-flight for both the 10 and 50% MVC tasks. No differences in medial gastrocnemius (MG) EMG amplitudes were observed for either the 10 or 50% MVC tasks. The EMG amplitudes of the tibialis anterior (TA), an antagonist to plantarflexion, were higher in- and post-flight than pre-flight for the 50% MVC task. During the dorsiflexion tasks, the torques generated in both the 10 and 50% MVC tasks did not differ pre-, in- and post-flight. TA EMG amplitudes were significantly higher in- than pre-flight for both the 10 or 50% MVC tasks, and remained elevated post-flight for the 50% MVC test. Both the Sol and MG EMG amplitudes were significantly higher in-flight than either pre- or post-flight for both the 10 and 50% MVC tests. These data suggest that the most consistent response to space flight was an elevation in the level of

  5. Switching Adaptability in Human-Inspired Sidesteps: A Minimal Model

    Directory of Open Access Journals (Sweden)

    Keisuke Fujii

    2017-06-01

    Full Text Available Humans can adapt to abruptly changing situations by coordinating redundant components, even in bipedality. Conventional adaptability has been reproduced by various computational approaches, such as optimal control, neural oscillator, and reinforcement learning; however, the adaptability in bipedal locomotion necessary for biological and social activities, such as unpredicted direction change in chase-and-escape, is unknown due to the dynamically unstable multi-link closed-loop system. Here we propose a switching adaptation model for performing bipedal locomotion by improving autonomous distributed control, where autonomous actuators interact without central control and switch the roles for propulsion, balancing, and leg swing. Our switching mobility model achieved direction change at any time using only three actuators, although it showed higher motor costs than comparable models without direction change. Our method of evaluating such adaptation at any time should be utilized as a prerequisite for understanding universal motor control. The proposed algorithm may simply explain and predict the adaptation mechanism in human bipedality to coordinate the actuator functions within and between limbs.

  6. Relational adaptivity - enacting human-centric systems design

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve

    2016-01-01

    Human centered design approaches places the experiencing human at the center of concern, situated in relation to the dynamics of the environmental condition and the variables of the system of control and sensing. Taking the approach of enacted design methods to enforce the experience...... of the inhabitant as core in human-centered design solutions, the intelligence of the connected sensors is suggested to be developed as an actual learning and self-adjusting adaptive environment, where the adaptive system is part of a negotiation with users on the qualities of the environment. We will present...... and activity, driven by detailed encounters with human centered investigations and experiential accounts. The sensor system is a test environment, using a very elaborate system design to enable extensive variations in the sensor and network parameters. But, the suggestion is, that by using this kind of high...

  7. Human Neutrophil Peptides 1–3 as Gastric Cancer Tissue Markers Measured by MALDI-Imaging Mass Spectrometry: Implications for Infiltrated Neutrophils as a Tumor Target

    Directory of Open Access Journals (Sweden)

    Chun-Chia Cheng

    2012-01-01

    Full Text Available Objective: Human neutrophil peptides (HNPs -1, -2 and -3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC. However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1, -2 and -3, and assess whether infiltrated neutrophils accumulate in gastric tumor.

  8. Event driven adaptation, land use and human coping strategies

    DEFF Research Database (Denmark)

    Reenberg, Anette; Birch-Thomsen, Torben; Fog, Bjarne

    The paper focuses on assessing the wider perspectives of adaptive resource management strategies in former subsistence agriculture societies in the SW Pacific. Firstly, we will briefly introduce the theoretical context related to the livelihood framework, adaptation to socio-environmental change ...... of main drivers of change, incl. climatic and socio-economic changes in the recent past.......The paper focuses on assessing the wider perspectives of adaptive resource management strategies in former subsistence agriculture societies in the SW Pacific. Firstly, we will briefly introduce the theoretical context related to the livelihood framework, adaptation to socio-environmental change...... and the concept of coupled human-environmental timelines. Secondly, with point of departure in a baseline characterization of Bellona Island derived from a comprehensive survey in the late 1960s and resent fieldwork in late 2006, we present the case of Bellona Island. Key issues addressed concern climatic events...

  9. Reasoning about Human Participation in Self-Adaptive Systems

    Science.gov (United States)

    2015-01-16

    these adaptation models as stochastic multiplayer games (SMGs) that can be used to analyze human-system-environment interactions. We illustrate our...models as stochastic multiplayer games (SMGs) that can be used to analyze human-system-environment interactions. To explore these issues, we propose...select a set of devices of size MAX DEVS PN (a constant that represents the maximum number of devices that can be attached to a processor node) among

  10. Wavefront sensorless adaptive optics ophthalmoscopy in the human eye

    Science.gov (United States)

    Hofer, Heidi; Sredar, Nripun; Queener, Hope; Li, Chaohong; Porter, Jason

    2011-01-01

    Wavefront sensor noise and fidelity place a fundamental limit on achievable image quality in current adaptive optics ophthalmoscopes. Additionally, the wavefront sensor ‘beacon’ can interfere with visual experiments. We demonstrate real-time (25 Hz), wavefront sensorless adaptive optics imaging in the living human eye with image quality rivaling that of wavefront sensor based control in the same system. A stochastic parallel gradient descent algorithm directly optimized the mean intensity in retinal image frames acquired with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). When imaging through natural, undilated pupils, both control methods resulted in comparable mean image intensities. However, when imaging through dilated pupils, image intensity was generally higher following wavefront sensor-based control. Despite the typically reduced intensity, image contrast was higher, on average, with sensorless control. Wavefront sensorless control is a viable option for imaging the living human eye and future refinements of this technique may result in even greater optical gains. PMID:21934779

  11. Knowing beans: Human mirror mechanisms revealed through motor adaptation

    Directory of Open Access Journals (Sweden)

    Arthur M Glenberg

    2010-11-01

    Full Text Available Human mirror mechanisms (MMs respond during both performed and observed action and appear to underlie action goal recognition. We introduce a behavioral procedure for discovering and clarifying functional MM properties: Blindfolded participants repeatedly move beans either toward or away from themselves to induce motor adaptation. Then, the bias for perceiving direction of ambiguous visual movement in depth is measured. Bias is affected by a number of beans moved, b movement direction, and c similarity of the visual stimulus to the hand used to move beans. This cross-modal adaptation pattern supports both the validity of human MMs and functionality of our testing instrument. We also discuss related work that extends the motor adaptation paradigm to investigate contributions of MMs to speech perception and language comprehension.

  12. Emigrating Beyond Earth Human Adaptation and Space Colonization

    CERN Document Server

    Smith, Cameron M

    2012-01-01

    For four million years humankind has been actively expanding geographically and in doing so has adapted to a wide variety of hostile environments. Now we are looking towards the ultimate adaptation - the colonization of space. Emigrating Beyond Earth illustrates that this is not a technocratic endeavor, but a natural continuation of human evolution; a journey not just for the engineer and rocket scientist, but for everyman. Based on the most current understanding of our universe, human adaptation and evolution, the authors explain why space colonization must be planned as an adaptation to, rather than the conquest of, space. Emigrating Beyond Earth argues that space colonization is an insurance policy for our species, and that it isn't about rockets and robots, it's about humans doing what we've been doing for four million years: finding new places and new ways to live. Applying a unique anthropological approach, the authors outline a framework for continued human space exploration and offer a glimpse of a po...

  13. Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli.

    NARCIS (Netherlands)

    Green, D.J.; Hopman, M.T.E.; Padilla, J.; Laughlin, M.H.; Thijssen, D.H.J.

    2017-01-01

    On the 400th anniversary of Harvey's Lumleian lectures, this review focuses on "hemodynamic" forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century

  14. The human endurance athlete: heterogeneity and adaptability of ...

    African Journals Online (AJOL)

    In human subjects, large variations between individuals (up to 3-fold) exist in the capacity for endurance exercise performance. In a heterogeneous population, endurance performance is strongly related to whole body maximal oxygen uptake (VO2 max). This is in part genotype dependent (~25%) but is adaptable with ...

  15. Genetic adaptation of the antibacterial human innate immunity network

    NARCIS (Netherlands)

    Casals, F.; Sikora, M.; Laayouni, H.; Montanucci, L.; Muntasell, A.; Lazarus, R.; Calafell, F.; Awadalla, P.; Netea, M.G.; Bertranpetit, J.

    2011-01-01

    BACKGROUND: Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune

  16. Endoscopic laser Doppler flowmetry in evaluation of human gastric blood flow

    International Nuclear Information System (INIS)

    Lunde, O.C.

    1988-01-01

    The aims of the present study were to evaluate laser Doppler flowmetry (LDF) for endoscopic mesasurement of gastric blood flow. The study gave the following results: LDF is a reliable method for continuous measurement of gastrointestinal blood perfusion. This technique can be used endoscopically for measurement of gastric blood flow in conscious man. By means of endoscopic technique, relative blood flow changes can be measured in all parts of the stomach. The recorded blood flow values usually represent blood perfusion in all layers in the gastric wall. A slight contact pressure between the measuring probe and the mucosa is necessary to obtain stable recordings. To heavy pressure provokes reduction of flow values. Angulation of the probe and moderate air insufflation do not interfere with a constant flow level. Endoscopic measurements should be performed with a recording band-width of 4 kHz, since this frequency limit reduces the disturbing signals. Within the range of flow levels recorded in patients and healthy subjects, relative blood flow changes are measured with this band-width. Endoscopic LDF is safe and easy to handle. However, peristalsis and uneasy patients may sometime provoke disturbances which render blood flow measurements impossible. Endoscopic LDF is suitable for clinical studies such as investigation of the effect of drugs on gastric blood flow and examination of local blood flow in patients with gastric diseases

  17. Endoscopic laser Doppler flowmetry in evaluation of human gastric blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Lunde, O.C. (Aker Sykehus, Oslo (Norway))

    1988-12-01

    The aims of the present study were to evaluate laser Doppler flowmetry (LDF) for endoscopic mesasurement of gastric blood flow. The study gave the following results: LDF is a reliable method for continuous measurement of gastrointestinal blood perfusion. This technique can be used endoscopically for measurement of gastric blood flow in conscious man. By means of endoscopic technique, relative blood flow changes can be measured in all parts of the stomach. The recorded blood flow values usually represent blood perfusion in all layers in the gastric wall. A slight contact pressure between the measuring probe and the mucosa is necessary to obtain stable recordings. To heavy pressure provokes reduction of flow values. Angulation of the probe and moderate air insufflation do not interfere with a constant flow level. Endoscopic measurements should be performed with a recording band-width of 4 kHz, since this frequency limit reduces the disturbing signals. Within the range of flow levels recorded in patients and healthy subjects, relative blood flow changes are measured with this band-width. Endoscopic LDF is safe and easy to handle. However, peristalsis and uneasy patients may sometime provoke disturbances which render blood flow measurements impossible. Endoscopic LDF is suitable for clinical studies such as investigation of the effect of drugs on gastric blood flow and examination of local blood flow in patients with gastric diseases. 64 refs.

  18. Clinicopathological correlation of keratinocyte growth factor and matrix metalloproteinase-9 expression in human gastric cancer.

    Science.gov (United States)

    Zhang, Qing; Wang, Ping; Shao, Ming; Chen, Shi-Wen; Xu, Zhi-Feng; Xu, Feng; Yang, Zhong-Yin; Liu, Bing-Ya; Gu, Qin-Long; Zhang, Wen-Jian; Li, Yong

    2015-01-01

    Keratinocyte growth factor (KGF) is reported to be implicated in the growth of some cancer cells. Matrix metalloproteinase 9 (MMP-9) is thought to enhance the tumor invasion and metastasis ability. This study was aimed at analyzing the relationship between KGF and MMP-9 expression and patients' clinicopathological characteristics to clarify the clinical significance of the expression of KGF and MMP-9 in gastric cancer. Tissue samples from 161 patients with primary gastric cancer were investigated using immunohistochemistry. The relationship between KGF and/or MMP-9 expression and clinicopathological characteristics was analyzed. KGF expression and MMP-9 expression in gastric cancer tissue were observed in 62 cases (38.5%) and 97 cases (60.2%), respectively. MMP-9 was significantly associated with depth of invasion, lymph node metastasis and TNM stage. The prognosis of MMP-9-positive patients was significantly poorer than that of MMP-9-negative patients (p = 0.009). KGF expression was positively correlated with MMP-9 expression in gastric cancer, and the prognosis of patients with both KGF- and MMP-9-positive tumors was significantly worse than that of patients with negative tumors for either factor (p = 0.045). Expression of MMP-9 was revealed to be an independent prognostic factor (p = 0.026). Coexpression of KGF and MMP-9 in gastric cancer could be a useful prognostic factor, and MMP-9 might also serve as a novel target for both prognostic prediction and therapeutics.

  19. Berberine modulates cisplatin sensitivity of human gastric cancer cells by upregulation of miR-203.

    Science.gov (United States)

    You, He-Yi; Xie, Xue-Meng; Zhang, Wei-Jian; Zhu, Heng-Liang; Jiang, Fei-Zhao

    2016-09-01

    Chemotherapeutic resistance is the main reason of the failure in clinical treatment of gastric cancer. Berberine (BER) is the active compound of traditional Chinese medicine Huang Lian. The aim of this present study is to evaluate the effect of BER on cisplatin resistance in gastric cancer cells and to investigate its possible mechanism. Gastric cancer cell lines SGC-7901 and BGC-823 and their respective cisplatin-resistant variants SGC-7901/DDP and BGC-823/DDP were used in this study. We found that BER treatment significantly reversed cisplatin sensitivity and induced caspase-dependent apoptosis in SGC-7901/DDP and BGC-823/DDP cells; BER treatment induced miR-203 expression, and overexpression of miR-203 mimicked the cisplatin-sensitizing effect of BER. Importantly, we showed that miR-203 was able to target the 3'UTR of Bcl-w. Therefore, we conclude that BER treatment reduces cisplatin resistance of gastric cancer cells by modulating the miR-203/Bcl-w apoptotic axis. BER may be a novel agent to enhance chemotherapeutic responses in cisplatin-resistant gastric cancer patients.

  20. Preventing gastric sieving by blending a solid/water meal enhances satiation in healthy humans.

    Science.gov (United States)

    Marciani, Luca; Hall, Nicholas; Pritchard, Susan E; Cox, Eleanor F; Totman, John J; Lad, Mita; Hoad, Caroline L; Foster, Tim J; Gowland, Penny A; Spiller, Robin C

    2012-07-01

    Separation of solids and liquids within the stomach allows faster gastric emptying of liquids compared with solids, a phenomenon known as sieving. We tested the hypothesis that blending a solid and water meal would abolish sieving, preventing the early rapid decrease in gastric volume and thereby enhancing satiety. We carried out 2 separate studies. Study 1 was a 2-way, crossover, satiety study of 22 healthy volunteers who consumed roasted chicken and vegetables with a glass of water (1008 kJ) or the same blended to a soup. They completed satiety visual analogue scales at intervals for 3 h. Study 2 was a 2-way, crossover, mechanistic study of 18 volunteers who consumed the same meals and underwent an MRI to assess gastric emptying, gallbladder contraction, and small bowel water content (SBWC) at intervals for 3 h. In Study 1, the soup meal was associated with reduced hunger (P = 0.02). In Study 2, the volume of the gastric contents after the soup meal decreased more slowly than after the solid/liquid meal (P = 0.0003). The soup meal caused greater gallbladder contraction (P solid/liquid meal was consumed (P solid/liquid meal to a soup delayed gastric emptying and increased the hormonal response to feeding, which may contribute to enhanced postprandial satiety.

  1. Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway

    Directory of Open Access Journals (Sweden)

    Yiwen Li

    2012-11-01

    Full Text Available Rhein is a primary anthraquinone found in the roots of a traditional Chinese herb, rhubarb, and has been shown to have some anticancer effects. The aim of the present study was to investigate the effect of rhein on the apoptosis of the human gastric cancer line SGC-7901 and to identify the mechanism involved. SGC-7901 cells were cultured and treated with rhein (0, 50, 100, 150, and 200 µM for 24, 48, or 72 h. Relative cell viability assessed by the MTT assay after treatment was 100, 99, 85, 79, 63% for 24 h; 100, 98, 80, 51, 37% for 48 h, and 100, 97, 60, 36, 15% for 72 h, respectively. Cell apoptosis was detected with TUNEL staining and quantified with flow cytometry using annexin FITC-PI staining at 48 h after 100, 200 and 300 µm rhein. The percentage of apoptotic cells was 7.3, 21.9, 43.5%, respectively. We also measured the mRNA levels of caspase-3 and -9 using real-time PCR. Treatment with 100 µM rhein for 48 h significantly increased mRNA expression of caspase-3 and -9. The levels of apoptosis-related proteins including Bcl-2, Bax, Bcl-xL, and pro-caspase-3 were evaluated in rhein-treated cells. Rhein increased the Bax:Bcl-2 ratio but decreased the protein levels of Bcl-xL and pro-caspase-3. Moreover, rhein significantly increased the expression of cytochrome c and apoptotic protease activating factor 1, two critical components involved in mitochondrial pathway-mediated apoptosis. We conclude that rhein inhibits SGC-7901 proliferation by inducing apoptosis and this antitumor effect of rhein is mediated in part by an intrinsic mitochondrial pathway.

  2. Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yiwen; Xu, Yuqing [Department of Oncology,Second Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, Heilongjiang (China); Lei, Bo [Department of Breast Surgery, Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang (China); Wang, Wenxiu [Department of Oncology,Second Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, Heilongjiang (China); Ge, Xin; Li, Jingrui [Department of General Surgery, Heilongjiang Province Hospital, Harbin, Heilongjiang (China)

    2012-08-03

    Rhein is a primary anthraquinone found in the roots of a traditional Chinese herb, rhubarb, and has been shown to have some anticancer effects. The aim of the present study was to investigate the effect of rhein on the apoptosis of the human gastric cancer line SGC-7901 and to identify the mechanism involved. SGC-7901 cells were cultured and treated with rhein (0, 50, 100, 150, and 200 µM) for 24, 48, or 72 h. Relative cell viability assessed by the MTT assay after treatment was 100, 99, 85, 79, 63% for 24 h; 100, 98, 80, 51, 37% for 48 h, and 100, 97, 60, 36, 15% for 72 h, respectively. Cell apoptosis was detected with TUNEL staining and quantified with flow cytometry using annexin FITC-PI staining at 48 h after 100, 200 and 300 µm rhein. The percentage of apoptotic cells was 7.3, 21.9, 43.5%, respectively. We also measured the mRNA levels of caspase-3 and -9 using real-time PCR. Treatment with 100 µM rhein for 48 h significantly increased mRNA expression of caspase-3 and -9. The levels of apoptosis-related proteins including Bcl-2, Bax, Bcl-xL, and pro-caspase-3 were evaluated in rhein-treated cells. Rhein increased the Bax:Bcl-2 ratio but decreased the protein levels of Bcl-xL and pro-caspase-3. Moreover, rhein significantly increased the expression of cytochrome c and apoptotic protease activating factor 1, two critical components involved in mitochondrial pathway-mediated apoptosis. We conclude that rhein inhibits SGC-7901 proliferation by inducing apoptosis and this antitumor effect of rhein is mediated in part by an intrinsic mitochondrial pathway.

  3. Accumulation of abasic sites induces genomic instability in normal human gastric epithelial cells during Helicobacter pylori infection.

    Science.gov (United States)

    Kidane, D; Murphy, D L; Sweasy, J B

    2014-11-24

    Helicobacter pylori infection of the human stomach is associated with inflammation that leads to the release of reactive oxygen and nitrogen species (RONs), eliciting DNA damage in host cells. Unrepaired DNA damage leads to genomic instability that is associated with cancer. Base excision repair (BER) is critical to maintain genomic stability during RONs-induced DNA damage, but little is known about its role in processing DNA damage associated with H. pylori infection of normal gastric epithelial cells. Here, we show that upon H. pylori infection, abasic (AP) sites accumulate and lead to increased levels of double-stranded DNA breaks (DSBs). In contrast, downregulation of the OGG1 DNA glycosylase decreases the levels of both AP sites and DSBs during H. pylori infection. Processing of AP sites during different phases of the cell cycle leads to an elevation in the levels of DSBs. Therefore, the induction of oxidative DNA damage by H. pylori and subsequent processing by BER in normal gastric epithelial cells has the potential to lead to genomic instability that may have a role in the development of gastric cancer. Our results are consistent with the interpretation that precise coordination of BER processing of DNA damage is critical for the maintenance of genomic stability.

  4. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L. in Human Gastric Epithelial Cells: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Chiara Di Lorenzo

    2016-07-01

    Full Text Available Raisins (Vitis vinifera L. are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL-8 and Nuclear Factor (NF-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD analysis and screened for their ability to inhibit Tumor necrosis factor (TNFα-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases.

  5. Genome-wide landscapes of human local adaptation in Asia.

    Directory of Open Access Journals (Sweden)

    Wei Qian

    Full Text Available Genetic studies of human local adaptation have been facilitated greatly by recent advances in high-throughput genotyping and sequencing technologies. However, few studies have investigated local adaptation in Asian populations on a genome-wide scale and with a high geographic resolution. In this study, taking advantage of the dense population coverage in Southeast Asia, which is the part of the world least studied in term of natural selection, we depicted genome-wide landscapes of local adaptations in 63 Asian populations representing the majority of linguistic and ethnic groups in Asia. Using genome-wide data analysis, we discovered many genes showing signs of local adaptation or natural selection. Notable examples, such as FOXQ1, MAST2, and CDH4, were found to play a role in hair follicle development and human cancer, signal transduction, and tumor repression, respectively. These showed strong indications of natural selection in Philippine Negritos, a group of aboriginal hunter-gatherers living in the Philippines. MTTP, which has associations with metabolic syndrome, body mass index, and insulin regulation, showed a strong signature of selection in Southeast Asians, including Indonesians. Functional annotation analysis revealed that genes and genetic variants underlying natural selections were generally enriched in the functional category of alternative splicing. Specifically, many genes showing significant difference with respect to allele frequency between northern and southern Asian populations were found to be associated with human height and growth and various immune pathways. In summary, this study contributes to the overall understanding of human local adaptation in Asia and has identified both known and novel signatures of natural selection in the human genome.

  6. Genome-wide landscapes of human local adaptation in Asia.

    Science.gov (United States)

    Qian, Wei; Deng, Lian; Lu, Dongsheng; Xu, Shuhua

    2013-01-01

    Genetic studies of human local adaptation have been facilitated greatly by recent advances in high-throughput genotyping and sequencing technologies. However, few studies have investigated local adaptation in Asian populations on a genome-wide scale and with a high geographic resolution. In this study, taking advantage of the dense population coverage in Southeast Asia, which is the part of the world least studied in term of natural selection, we depicted genome-wide landscapes of local adaptations in 63 Asian populations representing the majority of linguistic and ethnic groups in Asia. Using genome-wide data analysis, we discovered many genes showing signs of local adaptation or natural selection. Notable examples, such as FOXQ1, MAST2, and CDH4, were found to play a role in hair follicle development and human cancer, signal transduction, and tumor repression, respectively. These showed strong indications of natural selection in Philippine Negritos, a group of aboriginal hunter-gatherers living in the Philippines. MTTP, which has associations with metabolic syndrome, body mass index, and insulin regulation, showed a strong signature of selection in Southeast Asians, including Indonesians. Functional annotation analysis revealed that genes and genetic variants underlying natural selections were generally enriched in the functional category of alternative splicing. Specifically, many genes showing significant difference with respect to allele frequency between northern and southern Asian populations were found to be associated with human height and growth and various immune pathways. In summary, this study contributes to the overall understanding of human local adaptation in Asia and has identified both known and novel signatures of natural selection in the human genome.

  7. Stability of free and encapsulated Lactobacillus acidophilus ATCC 4356 in yogurt and in an artificial human gastric digestion system.

    Science.gov (United States)

    Ortakci, F; Sert, S

    2012-12-01

    The objective of this study was to determine the effect of encapsulation on survival of probiotic Lactobacillus acidophilus ATCC 4356 (ATCC 4356) in yogurt and during artificial gastric digestion. Strain ATCC 4356 was added to yogurt either encapsulated in calcium alginate or in free form (unencapsulated) at levels of 8.26 and 9.47 log cfu/g, respectively, and the influence of alginate capsules (1.5 to 2.5mm) on the sensorial characteristics of yogurts was investigated. The ATCC 4356 strain was introduced into an artificial gastric solution consisting of 0.08 N HCl (pH 1.5) containing 0.2% NaCl or into artificial bile juice consisting of 1.2% bile salts in de Man, Rogosa, and Sharpe broth to determine the stability of the probiotic bacteria. When incubated for 2h in artificial gastric juice, the free ATCC 4356 did not survive (reduction of >7 log cfu/g). We observed, however, greater survival of encapsulated ATCC 4356, with a reduction of only 3 log cfu/g. Incubation in artificial bile juice (6 h) did not significantly affect the viability of free or encapsulated ATCC 4356. Moreover, statistically significant reductions (~1 log cfu/g) of both free and encapsulated ATCC 4356 were observed during 4-wk refrigerated storage of yogurts. The addition of probiotic cultures in free or alginate-encapsulated form did not significantly affect appearance/color or flavor/odor of the yogurts. However, significant deficiencies were found in body/texture of yogurts containing encapsulated ATCC 4356. We concluded that incorporation of free and encapsulated probiotic bacteria did not substantially change the overall sensory properties of yogurts, and encapsulation in alginate using the extrusion method greatly enhanced the survival of probiotic bacteria against an artificial human gastric digestive system. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. c-Jun N-terminal kinase is required for thermotherapy-induced apoptosis in human gastric cancer cells.

    Science.gov (United States)

    Xiao, Feng; Liu, Bin; Zhu, Qing-Xian

    2012-12-28

    To investigate the role of c-Jun N-terminal kinase (JNK) in thermotherapy-induced apoptosis in human gastric cancer SGC-7901 cells. Human gastric cancer SGC-7901 cells were cultured in vitro. Following thermotherapy at 43°C for 0, 0.5, 1, 2 or 3 h, the cells were cultured for a further 24 h with or without the JNK specific inhibitor, SP600125 for 2 h. Apoptosis was evaluated by immunohistochemistry [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)] and flow cytometry (Annexin vs propidium iodide). Cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The production of p-JNK, Bcl-2, Bax and caspase-3 proteins was evaluated by Western blotting. The expression of JNK at mRNA level was determined by reverse transcription polymerase chain reaction. The proliferation of gastric carcinoma SGC-7901 cells was significantly inhibited following thermotherapy, and was 32.7%, 30.6%, 43.8% and 52.9% at 0.5, 1, 2 and 3 h post-thermotherapy, respectively. Flow cytometry analysis revealed an increased population of SGC-790l cells in G0/G1 phase, but a reduced population in S phase following thermotherapy for 1 or 2 h, compared to untreated cells (P thermotherapy for 0.5, 1, 2 or 3 h, compared to the untreated group (46.5% ± 0.23%, 39.9% ± 0.53%, 56.6% ± 0.35% and 50.4% ± 0.29% vs 7.3% ± 0.10%, P thermotherapy, compared to mock-inhibitor treatment, which was in line with the decreased rate of apoptosis. The expression of Bcl-2 was consistent with thermotherapy alone. Thermotherapy induced apoptosis in gastric cancer cells by promoting p-JNK at the mRNA and protein levels, and up-regulated the expression of Bax and caspase-3 proteins. Bcl-2 may play a protective role during thermotherapy. Activation of JNK via the Bax-caspase-3 pathway may be important in thermotherapy-induced apoptosis in gastric cancer cells.

  9. Localizing recent adaptive evolution in the human genome

    DEFF Research Database (Denmark)

    Williamson, Scott H; Hubisz, Melissa J; Clark, Andrew G

    2007-01-01

    -nucleotide polymorphism ascertainment, while also providing fine-scale estimates of the position of the selected site, we analyzed a genomic dataset of 1.2 million human single-nucleotide polymorphisms genotyped in African-American, European-American, and Chinese samples. We identify 101 regions of the human genome......, clusters of olfactory receptors, genes involved in nervous system development and function, immune system genes, and heat shock genes. We also observe consistent evidence of selective sweeps in centromeric regions. In general, we find that recent adaptation is strikingly pervasive in the human genome......Identifying genomic locations that have experienced selective sweeps is an important first step toward understanding the molecular basis of adaptive evolution. Using statistical methods that account for the confounding effects of population demography, recombination rate variation, and single...

  10. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans

    DEFF Research Database (Denmark)

    Nauck, M A; Niedereichholz, U; Ettler, R

    1997-01-01

    Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological and pharmacological doses of intravenous GLP-1-(7-36) amide and GLP-1-(7-37) on gastric emptying...... a significant effect, 3) despite the known insulinotropic actions of GLP-1-(7-36) amide and -(7-37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms)....

  11. ERC/mesothelin is expressed in human gastric cancer tissues and cell lines

    OpenAIRE

    ITO, TOMOAKI; KAJINO, KAZUNORI; ABE, MASAAKI; SATO, KOICHI; MAEKAWA, HIROSHI; SAKURADA, MUTSUMI; ORITA, HAJIME; WADA, RYO; KAJIYAMA, YOSHIAKI; HINO, OKIO

    2013-01-01

    ERC/mesothelin is expressed in mesothelioma and other malignancies. The ERC/mesothelin gene (MSLN) encodes a 71-kDa precursor protein, which is cleaved to yield 31-kDa N-terminal (N-ERC/mesothelin) and 40-kDa C-terminal (C-ERC/mesothelin) proteins. N-ERC/mesothelin is a soluble protein and has been reported to be a diagnostic serum marker of mesothelioma and ovarian cancer. Gastric cancer tissue also expresses C-ERC/mesothelin, but the significance of serum N-ERC levels for diagnosing gastric...

  12. Evidence of Recent Intricate Adaptation in Human Populations.

    Directory of Open Access Journals (Sweden)

    Leeyoung Park

    Full Text Available Recent human adaptations have shaped population differentiation in genomic regions containing putative functional variants, mostly located in predicted regulatory elements. However, their actual functionalities and the underlying mechanism of recent adaptation remain poorly understood. In the current study, regions of genes and repeats were investigated for functionality depending on the degree of population differentiation, FST or ΔDAF (a difference in derived allele frequency. The high FST in the 5´ or 3´ untranslated regions (UTRs, in particular, confirmed that population differences arose mainly from differences in regulation. Expression quantitative trait loci (eQTL analyses using lymphoblastoid cell lines indicated that the majority of the highly population-specific regions represented cis- and/or trans-eQTL. However, groups having the highest ΔDAFs did not necessarily have higher proportions of eQTL variants; in these groups, the patterns were complex, indicating recent intricate adaptations. The results indicated that East Asian (EAS and European populations (EUR experienced mutual selection pressures. The mean derived allele frequency of the high ΔDAF groups suggested that EAS and EUR underwent strong adaptation; however, the African population in Africa (AFR experienced slight, yet broad, adaptation. The DAF distributions of variants in the gene regions showed clear selective pressure in each population, which implies the existence of more recent regulatory adaptations in cells other than lymphoblastoid cell lines. In-depth analysis of population-differentiated regions indicated that the coding gene, RNF135, represented a trans-regulation hotspot via cis-regulation by the population-specific variants in the region of selective sweep. Together, the results provide strong evidence of actual intricate adaptation of human populations via regulatory manipulation.

  13. Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

    Science.gov (United States)

    Green, Daniel J.; Hopman, Maria T. E.; Padilla, Jaume; Laughlin, M. Harold; Thijssen, Dick H. J.

    2017-01-01

    On the 400th anniversary of Harvey's Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity. PMID:28151424

  14. The impact of reduced gastric acid secretion on dissolution of salts of weak bases in the fasted upper gastrointestinal lumen: Data in biorelevant media and in human aspirates.

    Science.gov (United States)

    Litou, Chara; Vertzoni, Maria; Xu, Wei; Kesisoglou, Filippos; Reppas, Christos

    2017-06-01

    To propose media for simulating the intragastric environment under reduced gastric acid secretion in the fasted state at three levels of simulation of the gastric environment and evaluate their usefulness in evaluating the intragastric dissolution of salts of weak bases. To evaluate the importance of bicarbonate buffer in biorelevant in vitro dissolution testing when using Level II biorelevant media simulating the environment in the fasted upper small intestine, regardless of gastric acid secretions. Media for simulating the hypochlorhydric and achlorhydric conditions in stomach were proposed using phosphates, maleates and bicarbonates buffers. The impact of bicarbonates in Level II biorelevant media simulating the environment in upper small intestine was evaluated so that pH and bulk buffer capacity were maintained. Dissolution data were collected using two model compounds, pioglitazone hydrochloride and semifumarate cocrystal of Compound B, and the mini-paddle dissolution apparatus in biorelevant media and in human aspirates. Simulated gastric fluids proposed in this study were in line with pH, buffer capacity, pepsin content, total bile salt/lecithin content and osmolality of the fasted stomach under partial and under complete inhibition of gastric acid secretion. Fluids simulating the conditions under partial inhibition of acid secretion were useful in simulating concentrations of both model compounds in gastric aspirates. Bicarbonates in Level III biorelevant gastric media and in Level II biorelevant media simulating the composition in the upper intestinal lumen did not improve simulation of concentrations in human aspirates. Level III biorelevant media for simulating the intragastric environment under hypochlorhydric conditions were proposed and their usefulness in the evaluation of concentrations of two model salts of weak bases in gastric aspirates was shown. Level II biorelevant media for simulating the environment in upper intestinal lumen led to

  15. Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans

    DEFF Research Database (Denmark)

    Meier, Juris J; Nauck, Michael A; Pott, Andrea

    2006-01-01

    BACKGROUND & AIMS: The gut-derived peptide glucagon-like peptide 2 (GLP-2) has been suggested as a potential drug candidate for the treatment of various intestinal diseases. However, the acute effects of GLP-2 on gastric functions as well as on glucose and lipid homeostasis in humans are less well...... emptying. The stimulation of glucagon secretion by GLP-2 may counteract the glucagonostatic effect of GLP-1. Changes in postprandial lipid excursions seem to reflect enhanced intestinal nutrient absorption during GLP-2 administration....

  16. Genomic dysregulation in gastric tumors.

    Science.gov (United States)

    Janjigian, Yelena Y; Kelsen, David P

    2013-03-01

    Gastric cancer is among the most common human malignancies and the second leading cause of cancer-related death. The different epidemiologic and histopathology of subtypes of gastric cancer are associated with different genomic patterns. Data suggests that gene expression patterns of proximal, distal gastric cancers-intestinal type, and diffuse/signet cell are well separated. This review summarizes the genetic and epigenetic changes thought to drive gastric cancer and the emerging paradigm of gastric cancer as three unique disease subtypes. Copyright © 2012 Wiley Periodicals, Inc.

  17. Mutations in the hedgehog pathway genes SMO and PTCH1 in human gastric tumors.

    Directory of Open Access Journals (Sweden)

    Xi-De Wang

    Full Text Available The causal role of the hedgehog pathway in cancer has been best documented in basal cell carcinoma of the skin. To assess potential DNA alterations of the hedgehog pathway in gastric cancer, we sequenced SMO and PTCH1 genes in a set of 39 gastric tumors. Tumors were classified by histology based on the Lauren classification and Sanger sequencing was performed to obtain full length coding sequences. Genomic instability was evident in these tumors as a number of silent or missense mutations were found. In addition to those that are potential germline polymorphisms, we found three SMO missense mutations, and one PTCH1 frameshift mutation that are novel and have not been documented in basal cell carcinoma. Mutations were found in both intestinal and diffuse type gastric tumors as well as in tumors that exhibit both intestinal and diffuse features. mRNA expression of hedgehog pathway genes was also examined and their levels do not indicate unequivocal higher pathway activity in tumors with mutations than those without. In summary, SMO and/or PTCH1 mutations are present at low frequency in different histologic subtypes of gastric tumors and these do not appear to be driver mutations.

  18. Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety

    DEFF Research Database (Denmark)

    Schmidt, P T; Näslund, E; Grybäck, P

    2003-01-01

    Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel to the circulation after a meal. Intravenous (IV) GLP-1 has an inhibitory effect on gastric emptying, hunger and food intake in man. In rodents, central administration of GLP-2 increases satiety similar...

  19. Different effect of Helicobacter pylori on the human gastric antral and body mucosal intracellular mucin.

    Science.gov (United States)

    Kawano, S; Tsujii, M; Nagano, K; Ogihara, T; Tanimura, H; Hayashi, N; Ito, T; Sato, N; Kamada, T; Tamura, K

    1990-10-01

    To elucidate the role of Helicobacter pylori infection in the pathogenesis of gastric ulcer, we investigated the intracellular mucin content by measuring the periodic acid-Schiff-Alcian blue (PAS-AB)-stained substances, by means of computer, in the biopsy sample of gastric mucosa from patients with and without H. pylori infection. In the antral mucosa the intracellular PAS-AB-stained mucin content was significantly smaller in patients with infection than in patients without infection, whereas in the oxyntic gland mucosa the intracellular mucin content showed no significant change between patients with and without infection. In an animal study we investigated the effect of ammonia, which might be produced by H. pylori in the presence of urea. The ammonia, administered orally, caused a greater decrease of intracellular PAS-AB-stained mucin content in the gastric antral mucosa than in the body mucosa, in a dose-dependent manner. The results suggested that H. pylori infection had a different effect on the gastric mucosal intracellular PAS-AB-stained mucin and lowered specifically the antral intracellular PAS-AB-stained mucin content, possibly due to generation of ammonia by H. pylori.

  20. In vitro anti-tumor activity in SGC-7901 human gastric cancer cells ...

    African Journals Online (AJOL)

    lymphoma 2 (Bcl2) mRNA). Conclusion: The results suggest that dandelion extract is a potent gastric cancer cell proliferation, ... This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and .... starvation medium, and added at a 5 x 104 cells per well density (0.3 ...

  1. A revised model of ex-vivo reduction of hexavalent chromium in human and rodent gastric juices

    Energy Technology Data Exchange (ETDEWEB)

    Schlosser, Paul M., E-mail: schlosser.paul@epa.gov; Sasso, Alan F.

    2014-10-15

    Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function of Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. - Highlights: • Hexavalent chromium (Cr-VI) reduction in gastric juices is a key detoxifying step. • pH-dependent Cr-VI reduction rates are explained using known chemical speciation. • Reduction in rodents appears to involve multiple pools of electron donors. • Reduction appears to continue after 60 min, although more slowly than initial rates.

  2. Correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistance in human gastric cancer

    Directory of Open Access Journals (Sweden)

    Hong-mei ZHANG

    2015-11-01

    Full Text Available Objective To investigate the correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistant gastric cancer in humans. Methods Fifty-two patients who were confirmed to have advanced gastric cancer with the aid of electronic endoscopy and pathology in the Department of Gastroenterology, Affiliated Hospital of Weifang Medical College, were enrolled in the study. According to the effect of FOL-FOX4 chemotherapy that these patients had experienced, they were divided into three groups: CR+PR (complete remission+partial remission group, SD (stable disease group and PD (progressive disease group. The expression levels of HIF-2α, ABCG2, and OCT-4 mRNA and protein were assessed in different groups by using RT-PCR and immunocytochemistry. Results Two patients achieved CR , 19 achieved PR , 25 showed SD, and 6 showed PD. In other words, CR+PR were seen in 21 patients (40.4%, SD in 25(48.1%, PD in 6(11.5%. In CR+PR group, the expression levels of HIF-2α, ABCG2 and OCT4 mRNA and protein were low, but the above mentioned expressions were significantly increased in SD group and PD group. The expression levels of HIF-2α, ABCG2 and Oct-4 mRNA and protein were highest in the PD group, lower in the SD group, and lowest in the CR + PR groups (all P<0.05. Conclusions The expression of the markers HIF-2α, ABCG2 and OCT4 in human tumor tissues is related to the effect of chemotherapy for gastric cancer. A high expression of tumor markers is perhaps the main reason for low efficacy of chemotherapy due to drug resistance. DOI: 10.11855/j.issn.0577-7402.2015.10.09

  3. Epigenetic stability, adaptability, and reversibility in human embryonic stem cells

    OpenAIRE

    Tompkins, Joshua D.; Hall, Christine; Chen, Vincent Chang-yi; Li, Arthur Xuejun; Wu, Xiwei; Hsu, David; Couture, Larry A.; Riggs, Arthur D.

    2012-01-01

    The stability of human embryonic stem cells (hESCs) is of critical importance for both experimental and clinical applications. We find that as an initial response to altered culture conditions, hESCs change their transcription profile for hundreds of genes and their DNA methylation profiles for several genes outside the core pluripotency network. After adaption to conditions of feeder-free defined and/or xeno-free culture systems, expression and DNA methylation profiles are quite stable for a...

  4. In vitro and in vivo studies on antitumor effects of gossypol on human stomach adenocarcinoma (AGS) cell line and MNNG induced experimental gastric cancer

    International Nuclear Information System (INIS)

    Gunassekaran, G.R.; Kalpana Deepa Priya, D.; Gayathri, R.; Sakthisekaran, D.

    2011-01-01

    Highlights: → Gossypol is a well known polyphenolic compound used for anticancer studies but we are the first to report that gossypol has antitumor effect on MNNG induced gastric cancer in experimental animal models. → Our study shows that gossypol inhibits the proliferation of AGS (human gastric adenocarcinoma) cell line. → In animal models, gossypol extends the survival of cancer bearing animals and also protects the cells from carcinogenic effect. → So we suggest that gossypol would be a potential chemotherapeutic and chemopreventive agent for gastric cancer. -- Abstract: The present study has evaluated the chemopreventive effects of gossypol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and on human gastric adenocarcinoma (AGS) cell line. Gossypol, C 30 H 30 O 8 , is a polyphenolic compound that has anti proliferative effect and induces apoptosis in various cancer cells. The aim of this work was to delineate in vivo and in vitro anti-initiating mechanisms of orally administered gossypol in target (stomach) tissues and in human gastric adenocarcinoma (AGS) cell line. In vitro results prove that gossypol has potent cytotoxic effect and inhibit the proliferation of adenocarcinoma (AGS) cell line. In vivo results prove gossypol to be successful in prolonging the survival of MNNG induced cancer bearing animals and in delaying the onset of tumor in animals administrated with gossypol and MNNG simultaneously. Examination of the target (stomach) tissues in sacrificed experimental animals shows that administration of gossypol significantly reduces the level of tumor marker enzyme (carcino embryonic antigen) and pepsin. The level of Nucleic acid contents (DNA and RNA) significantly reduces, and the membrane damage of glycoprotein subsides, in the target tissues of cancer bearing animals, with the administration of gossypol. These data suggest that gossypol may create a beneficial effect in patients with gastric cancer.

  5. N-methyl-N-nitro-N-nitrosoguanidine-mediated ING4 downregulation contributed to the angiogenesis of transformed human gastric epithelial cells.

    Science.gov (United States)

    Chen, Yansu; Fu, Rui; Xu, Mengdie; Huang, Yefei; Sun, Guixiang; Xu, Lichun

    2018-04-15

    Angiogenesis is associated with the progression and mortality of gastric cancer. Epidemiological evidences indicate that long-term N-nitroso compounds (NOCs) exposure predominantly contributes to the mortality of gastric cancer. Therefore, further reduced mortality of gastric cancer demands to explore the exact mechanisms of NOCs induced angiogenesis. As a tumor suppressor gene, inhibitor of growth protein 4 (ING4) plays an important role in pathological angiogenesis. In this study, we will investigate ING4 expression level in human gastric epithelial cells after the long-term low dose exposure of N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and the pathological impact of MNNG-reduced ING4 on angiogenesis of transformed cells. The soft agar colony formation assay, Western blotting, immunofluorescence and wound healing assay were used to evaluate the characteristics of transformed cells. HUVEC growth and tube formation assays were performed to test the angiogenic abilities. EMSA, luciferase reporter gene assay, real-time PCR and Western blotting were used to explore the exact mechanism. By establishing transformed human gastric epithelial cells via chronic low dose treatment, a gradually ING4 downregulation was observed in the later-stage of MNNG-induced cell transformation. Moreover, we demonstrated that MNNG exposure-reduced ING4 expression significantly resulted into aggravating angiogenesis through increasing the phosphorylation level of NF-κB p65 and subsequently DAN binding activity and regulating the expressions of NF-κB p65 downstream pro-angiogenic genes, MMP-2 and MMP-9. Our findings provided a significant mechanistic insight into angiogenesis of MNNG-transformed human gastric epithelial cell and supported the concept that ING4 may be a relevant therapeutic target for gastric cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Adaptive multi-histogram equalization using human vision thresholding

    Science.gov (United States)

    Wharton, Eric; Panetta, Karen; Agaian, Sos

    2007-02-01

    Image enhancement is the task of applying certain alterations to an input image such as to obtain a more visually pleasing image. The alteration usually requires interpretation and feedback from a human evaluator of the output resulting image. Therefore, image enhancement is considered a difficult task when attempting to automate the analysis process and eliminate the human intervention. Furthermore, images that do not have uniform brightness pose a challenging problem for image enhancement systems. Different kinds of histogram equalization techniques have been employed for enhancing images that have overall improper illumination or are over/under exposed. However, these techniques perform poorly for images that contain various regions of improper illumination or improper exposure. In this paper, we introduce new human vision model based automatic image enhancement techniques, multi-histogram equalization as well as local and adaptive algorithms. These enhancement algorithms address the previously mentioned shortcomings. We present a comparison of our results against many current local and adaptive histogram equalization methods. Computer simulations are presented showing that the proposed algorithms outperform the other algorithms in two important areas. First, they have better performance, both in terms of subjective and objective evaluations, then that currently used algorithms on a series of poorly illuminated images as well as images with uniform and non-uniform illumination, and images with improper exposure. Second, they better adapt to local features in an image, in comparison to histogram equalization methods which treat the images globally.

  7. Construction of Gait Adaptation Model in Human Splitbelt Treadmill Walking

    Directory of Open Access Journals (Sweden)

    Yuji Otoda

    2009-01-01

    Full Text Available There are a huge number of studies that measure kinematics, dynamics, the oxygen uptake and so on in human walking on the treadmill. Especially in walking on the splitbelt treadmill where the speed of the right and left belt is different, remarkable differences in kinematics are seen between normal and cerebellar disease subjects. In order to construct the gait adaptation model of such human splitbelt treadmill walking, we proposed a simple control model and made a newly developed 2D biped robot walk on the splitbelt treadmill. We combined the conventional limit-cycle based control consisting of joint PD-control, cyclic motion trajectory planning and a stepping reflex with a newly proposed adjustment of P-gain at the hip joint of the stance leg. We showed that the data of robot (normal subject model and cerebellum disease subject model experiments had high similarities with the data of normal subjects and cerebellum disease subjects experiments carried out by Reisman et al. (2005 and Morton and Bastian (2006 in ratios and patterns. We also showed that P-gain at the hip joint of the stance leg was the control parameter of adaptation for symmetric gaits in splitbelt walking and P-gain adjustment corresponded to muscle stiffness adjustment by the cerebellum. Consequently, we successfully proposed the gait adaptation model in human splitbelt treadmill walking and confirmed the validity of our hypotheses and the proposed model using the biped robot.

  8. Differential acute and chronic responses in insulin action in cultured myotubes following from nondiabetic severely obese humans following gastric bypass surgery.

    Science.gov (United States)

    Hinkley, J Matthew; Zou, Kai; Park, Sanghee; Zheng, Donghai; Dohm, G Lynis; Houmard, Joseph A

    2017-11-01

    Roux-en-Y gastric bypass (RYGB) surgery has been shown to induce positive metabolic adaptations for individuals with severe obesity (body mass index ≥40 kg/m 2 ), including improved peripheral insulin action. Although a major site of insulin action, the time course changes in skeletal muscle glucose metabolism following RYGB is unclear. To investigate the acute and chronic effects of RYGB surgery on insulin-stimulated glucose metabolism in cultured human primary myotubes derived from nondiabetic severely obese humans. East Carolina University Bariatric Surgery Center and East Carolina Diabetes and Obesity Institute. Primary human skeletal muscle cells were isolated from biopsies obtained from 8 women with severe obesity before, 1 month, and 7 months following RYGB surgery. Glucose metabolism, glycogen content, and insulin signal transduction were determined in differentiated myotubes. Insulin-stimulated glycogen synthesis and glucose oxidation increased in human myotubes derived from patients with severe obesity at both 1 and 7 months post-RYGB. However, there were no alterations indicative of enhanced insulin signal transduction. At 1 month post-RYGB, muscle glycogen levels were lower (-23%) and phosphorylation of acetyl CoA carboxylase 2 (ACC2) was elevated (+16%); both returned to presurgery levels at 7 months after RYGB in myotubes derived from patients. At 7 months post-RYGB, there was an increase in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) protein content (+54%). These data indicate that insulin action intrinsically improves in cultured human primary myotubes derived from nondiabetic severely obese patients following RYGB surgery; however, the cellular alterations involved appear to consist of distinct acute and chronic components. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  9. Synergistic Effect of Zuo Jin Wan on DDP-Induced Apoptosis in Human Gastric Cancer SGC-7901/DDP Cells

    Directory of Open Access Journals (Sweden)

    Qing-Feng Tang

    2014-01-01

    Full Text Available A traditional Chinese medicine (TCM formula, Zuo Jin Wan (ZJW, has been found as an anticancer drug in human cancer. In this study, we investigated the synergistic effect of ZJW extracts on DDP-induced apoptosis in human gastric cancer SGC-7901/DDP cells. Our results demonstrated that ZJW extracts could increase the sensitivity of SGC-7901/DDP cells to DDP by increasing the concentration of DDP in cytoplasm and enhance the proapoptosis of DDP by upregulating the JNK and Bax expression, downregulating the Bcl-2 expression, increasing the accumulation of Cytochrome C in cytoplasm, and promoting the activities of caspase-3 and caspase-9. In vivo, ZJW extracts enhanced the inhibiting effect of DDP on tumor growth in SGC-7901/DDP xenograft model and upregulated the expression of p-JNK and Bax but downregulated the Bcl-2 expression in xenograft tumors. In conclusion, in vitro and in vivo, ZJW extracts could enhance the proapoptotic effect of DDP by promoting the activation of JNK and the expression of Bcl-2, inhibiting the Bax expression, followed by increasing the release of Cytochrome C from mitochondria to cytoplasm, and finally activating the caspase cade reaction. Our results implied that ZJW might serve as a synergistic drug with chemotherapeutic drugs DDP in the treatment of gastric cancer.

  10. Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene

    Science.gov (United States)

    Lu, Xiao-Guang; Zhan, Li-Bin; Feng, Bing-An; Qu, Ming-Yang; Yu, Li-Hua; Xie, Ji-Hong

    2004-01-01

    AIM: To investigate the effects and mechanism of d-limonene on the growth and metastasis of gastric cancer in vivo. METHODS: Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. One percent d-limonene was orally administered at dose of 15 ml/kg every other day for seven weeks. Eight weeks after implantation, tumor weight, inhibition rate, apoptotic index (AI), microvessel density (MVD), vascular endothelial growth factor (VEGF), variation of ultrastructure, and the presence of metastasis were evaluated, respectively, after the mice were sacrificed. RESULTS: The tumor weight was significantly reduced in 5-FU group (2.55 ± 0.28 g), d-limonene group (1.49 ± 0.09 g) and combined treatment group (1.48 ± 0.21 g) compared with the control group(2.73 ± 0.23 g, P limonene group, combined treatment group, the inhibition rates were 2.60%, 47.58% and 46.84% and 0, respectively; AI was (3.31 ± 0.33)%, (8.26 ± 1.21)%, (20.99 ± 1.84)% and (19.34 ± 2.19)%, respectively; MVD was (8.64 ± 2.81), (16.77 ± 1.39), (5.32 ± 4.26) and (5.86 ± 2.27), respectively; VEGF expression was (45.77 ± 4.79), (41.34 ± 5.41), (29.71 ± 8.92) and (28.24 ± 8.55), respectively. The incidences of peritoneal metastasis also decreased significantly in 5-FU group(77.8%), d-limonene group (20.0%) and combined group (22.2%) compared with control group (100%) versus 62.5%, 30% and 22.2%) (P limonene group and combined group than that in control group (87.5% vs 55.5%, 20.0% and 22.2% respectively) (P limonene group and combined group was 25.0%, 22.2%, 0, 0, respectively and 12.5%, 11.1% 0, 0, with respect to the metastasis rate to other organs. CONCLUSION: d-limonene has antiangiogenic and proapoptotic effects on gastric cancer, thereby inhibits tumor growth and metastasis. Combination of d-limonene with cytotoxic agents may be more effective. PMID:15237454

  11. Effects of salinomycin and 17-AAG on proliferation of human gastric cancer cells in vitro

    Science.gov (United States)

    Zhang, Zuwen; Zhao, Jumei; Mi, Zhikuan; Pang, Qiuxia; Wang, Aihong; Chen, Meini; Liu, Xiaobin; Wei, Xiaoli; Liu, Tao

    2017-01-01

    The aim of the present study was to investigate the effects and mechanisms of 17-AAG combined with salinomycin treatment on proliferation and apoptosis of the SGC-7901 gastric cancer cell line. An MTT assay was used to detect the proliferation of SGC-7901 cells. Morphological alterations of cells were observed under inverted phase-contrast and fluorescence microscopes. Cell cycle and apoptosis were assessed by flow cytometry analysis. The protein expression of nuclear factor (NF)-κB p65 and Fas-ligand (L) were evaluated by immunocytochemistry. Salinomycin with a concentration range of 1–32 µmol/l was demonstrated to inhibit growth of SGC-7901 cells effectively, affect the morphology and apoptosis rate of cells, and arrest SGC-7901 cells in S phase. Furthermore, salinomycin significantly increased the protein expression of Fas-L and decreased the protein expression of NF-κB p65. The alterations in SGC-7901 cells co-treated with salinomycin and 17-AAG were more significant compared with cells treated with one drug only. In conclusion, the individual use of salinomycin and combined use with 17-AAG may significantly inhibit SGC-7901 gastric cancer cell proliferation and induce cell apoptosis. The potential mechanisms may be associated with upregulation of Fas-L and downregulation of NF-κB. These results provide a basis for the potential use of salinomycin in gastric cancer treatment. PMID:28627587

  12. Adaptive specializations, social exchange, and the evolution of human intelligence

    Science.gov (United States)

    Cosmides, Leda; Barrett, H. Clark; Tooby, John

    2010-01-01

    Blank-slate theories of human intelligence propose that reasoning is carried out by general-purpose operations applied uniformly across contents. An evolutionary approach implies a radically different model of human intelligence. The task demands of different adaptive problems select for functionally specialized problem-solving strategies, unleashing massive increases in problem-solving power for ancestrally recurrent adaptive problems. Because exchange can evolve only if cooperators can detect cheaters, we hypothesized that the human mind would be equipped with a neurocognitive system specialized for reasoning about social exchange. Whereas humans perform poorly when asked to detect violations of most conditional rules, we predicted and found a dramatic spike in performance when the rule specifies an exchange and violations correspond to cheating. According to critics, people's uncanny accuracy at detecting violations of social exchange rules does not reflect a cheater detection mechanism, but extends instead to all rules regulating when actions are permitted (deontic conditionals). Here we report experimental tests that falsify these theories by demonstrating that deontic rules as a class do not elicit the search for violations. We show that the cheater detection system functions with pinpoint accuracy, searching for violations of social exchange rules only when these are likely to reveal the presence of someone who intends to cheat. It does not search for violations of social exchange rules when these are accidental, when they do not benefit the violator, or when the situation would make cheating difficult. PMID:20445099

  13. The epigenetic side of human adaptation: hypotheses, evidences and theories.

    Science.gov (United States)

    Giuliani, Cristina; Bacalini, Maria Giulia; Sazzini, Marco; Pirazzini, Chiara; Franceschi, Claudio; Garagnani, Paolo; Luiselli, Donata

    2015-01-01

    Epigenetics represents a still unexplored research field in the understanding of micro- and macro-evolutionary mechanisms, as epigenetic changes create phenotypic diversity within both individuals and populations. The purpose of this review is to dissect the landscape of studies focused on DNA methylation, one of the most described epigenetic mechanisms, emphasizing the aspects that could be relevant in human adaptations. Theories and results here considered were collected from the most recent papers published. The matter of DNA methylation inheritance is here described as well as the recent evolutionary theories regarding the role of DNA methylation-and epigenetics in a broader sense-in human evolution. The complex relation between (1) DNA methylation and genetic variability and (2) DNA methylation and the environmental stimuli crucial in shaping genetic and phenotypic variability through the human lineage-such as diet, climate and pathogens exposure-are described. Papers about population epigenetics are also illustrated due to their high relevance in this context. Genetic, epigenetic and phenotypic variations of the species, together with cultural ones, are considerably shaped by a vast range of environmental stimuli, thus representing the foundation of all human bio-cultural adaptations.

  14. Helicobacter pylori Activates IL-6-STAT3 Signaling in Human Gastric Cancer Cells: Potential Roles for Reactive Oxygen Species.

    Science.gov (United States)

    Piao, Juan-Yu; Lee, Hee Geum; Kim, Su-Jung; Kim, Do-Hee; Han, Hyeong-Jun; Ngo, Hoang-Kieu-Chi; Park, Sin-Aye; Woo, Jeong-Hwa; Lee, Jeong-Sang; Na, Hye-Kyung; Cha, Young-Nam; Surh, Young-Joon

    2016-10-01

    Recent studies have shown that Helicobacter pylori (H. pylori) activates signal transducer and activator of transcription 3 (STAT3) that plays an important role in gastric carcinogenesis. However, the molecular mechanism underlying H. pylori-mediated STAT3 activation is still not fully understood. In this study, we investigated H. pylori-induced activation of STAT3 signaling in AGS human gastric cancer cells and the underlying mechanism. AGS cells were cocultured with H. pylori, and STAT3 activation was assessed by Western blot analysis, electrophoretic mobility shift assay and immunocytochemistry. To demonstrate the involvement of reactive oxygen species (ROS) in H. pylori-activated STAT3 signaling, the antioxidant N-acetylcysteine was utilized. The expression and production of interleukin-6 (IL-6) were measured by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The interaction between IL-6 and IL-6 receptor (IL-6R) was determined by the immunoprecipitation assay. H. pylori activates STAT3 as evidenced by increases in phosphorylation on Tyr(705) , nuclear localization, DNA binding and transcriptional activity of this transcription factor. The nuclear translocation of STAT3 was also observed in H. pylori-inoculated mouse stomach. In the subsequent study, we found that H. pylori-induced STAT3 phosphorylation was dependent on IL-6. Notably, the increased IL-6 expression and the IL-6 and IL-6R binding were mediated by ROS produced as a consequence of H. pylori infection. H. pylori-induced STAT3 activation is mediated, at least in part, through ROS-induced upregulation of IL-6 expression. These findings provide a novel molecular mechanism responsible for H. pylori-induced gastritis and gastric carcinogenesis. © 2016 John Wiley & Sons Ltd.

  15. Hyperthermia combined with 5-fluorouracil promoted apoptosis and enhanced thermotolerance in human gastric cancer cell line SGC-7901

    Directory of Open Access Journals (Sweden)

    Liu T

    2015-05-01

    Full Text Available Tao Liu,* Yan-Wei Ye,* A-li Zhu, Zhen Yang, Yang Fu, Chong-Qing Wei, Qi Liu, Chun-Lin Zhao, Guo-Jun Wang, Xie-Fu Zhang Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China *These authors contributed equally to this work Abstract: This study was designed to investigate the proliferation inhibition and apo­ptosis-promoting effect under hyperthermia and chemotherapy treatment, at cellular level. Human gastric cancer cell line SGC-7901 was cultivated with 5-fluorouracil at different temperatures. Cell proliferation and apoptosis were determined, and expression of Bcl-2 and HSP70 was measured at different treatments. Cell survival rates and inhibition rates in chemotherapy group, thermotherapy group, and thermo-chemotherapy group were drastically lower than the control group (P<0.05. For tumor cells in the thermo-chemotherapy group, survival rates and inhibition rates at three different temperatures were all significantly lower than those in chemotherapy group and thermotherapy group (P<0.05. 5-Fluorouracil induced apoptosis of SGC-7901 cells with a strong temperature dependence, which increased gradually with increase in temperature. At 37°C and 43°C there were significant differences between the thermotherapy group and chemotherapy group and between the thermo-chemotherapy group and thermotherapy group (P<0.01. The expression of Bcl-2 was downregulated and HSP70 was upregulated, with increase in temperature in all groups. Cell apoptosis was not significant at 46°C (P>0.05, which was probably due to thermotolerance caused by HSP70 accumulation. These results suggested that hyperthermia combined with 5-fluorouracil had a synergistic effect in promoting apoptosis and enhancing thermotolerance in gastric cancer cell line SGC-7901. Keywords: gastric cancer, thermotherapy, 5-fluorouracil, Bcl-2, HSP70, thermotolerance

  16. Convergence of the innate and adaptive immunity during human aging

    Directory of Open Access Journals (Sweden)

    Branca Isabel Pereira

    2016-11-01

    Full Text Available Aging is associated with profound changes in the human immune system, a phenomenon referred to as immunosenescence. This complex immune remodeling affects the adaptive immune system and the CD8+ T cell compartment in particular, leading to the accumulation of terminally differentiated T cells, which can rapidly exert their effector functions at the expenses of a limited proliferative potential. In this review we will discuss evidence suggesting that senescent αβCD8+ T cells acquire the hallmarks of innate-like T cells and use recently acquired NK cell receptors as an alternative mechanism to mediate rapid effector functions. These cells concomitantly lose expression of co-stimulatory receptors and exhibit decreased TCR signaling suggesting a functional shift away from antigen specific activation. The convergence of innate and adaptive features in senescent T cells challenges the classic division between innate and adaptive immune systems. Innate-like T cells are particularly important for stress and tumor surveillance and we propose a new role for these cells in aging, where the acquisition of innate-like functions may represent a beneficial adaptation to an increased burden of malignancy with age, although it may also pose a higher risk of autoimmune disorders.

  17. HMM Adaptation for Improving a Human Activity Recognition System

    Directory of Open Access Journals (Sweden)

    Rubén San-Segundo

    2016-09-01

    Full Text Available When developing a fully automatic system for evaluating motor activities performed by a person, it is necessary to segment and recognize the different activities in order to focus the analysis. This process must be carried out by a Human Activity Recognition (HAR system. This paper proposes a user adaptation technique for improving a HAR system based on Hidden Markov Models (HMMs. This system segments and recognizes six different physical activities (walking, walking upstairs, walking downstairs, sitting, standing and lying down using inertial signals from a smartphone. The system is composed of a feature extractor for obtaining the most relevant characteristics from the inertial signals, a module for training the six HMMs (one per activity, and the last module for segmenting new activity sequences using these models. The user adaptation technique consists of a Maximum A Posteriori (MAP approach that adapts the activity HMMs to the user, using some activity examples from this specific user. The main results on a public dataset have reported a significant relative error rate reduction of more than 30%. In conclusion, adapting a HAR system to the user who is performing the physical activities provides significant improvement in the system’s performance.

  18. Bone loss and human adaptation to lunar gravity

    Science.gov (United States)

    Keller, T. S.; Strauss, A. M.

    1992-01-01

    Long-duration space missions and establishment of permanently manned bases on the Moon and Mars are currently being planned. The weightless environment of space and the low-gravity environments of the Moon and Mars pose an unknown challenge to human habitability and survivability. Of particular concern in the medical research community today is the effect of less than Earth gravity on the human skeleton, since the limits, if any, of human endurance in low-gravity environments are unknown. This paper provides theoretical predictions on bone loss and skeletal adaptation to lunar and other nonterrestrial-gravity environments based upon the experimentally derived relationship, density approximately (mass x gravity)(exp 1/8). The predictions are compared to skeletal changes reported during bed rest, immobilization, certrifugation, and spaceflight. Countermeasures to reduce bone losses in fractional gravity are also discussed.

  19. Adaptive Human aware Navigation based on Motion Pattern Analysis

    DEFF Research Database (Denmark)

    Tranberg, Søren; Svenstrup, Mikael; Andersen, Hans Jørgen

    2009-01-01

    Respecting people’s social spaces is an important prerequisite for acceptable and natural robot navigation in human environments. In this paper, we describe an adaptive system for mobile robot navigation based on estimates of whether a person seeks to interact with the robot or not. The estimates...... are based on run-time motion pattern analysis compared to stored experience in a database. Using a potential field centered around the person, the robot positions itself at the most appropriate place relative to the person and the interaction status. The system is validated through qualitative tests...... in a real world setting. The results demonstrate that the system is able to learn to navigate based on past interaction experiences, and to adapt to different behaviors over time....

  20. An adaptive approach to human motion tracking from video

    Science.gov (United States)

    Wu, Lifang; Chen, Chang Wen

    2010-07-01

    Vision based human motion tracking has drawn considerable interests recently because of its extensive applications. In this paper, we propose an approach to tracking the body motion of human balancing on each foot. The ability to balance properly is an important indication of neurological condition. Comparing with many other human motion tracking, there is much less occlusion in human balancing tracking. This less constrained problem allows us to combine a 2D model of human body with image analysis techniques to develop an efficient motion tracking algorithm. First we define a hierarchical 2D model consisting of six components including head, body and four limbs. Each of the four limbs involves primary component (upper arms and legs) and secondary component (lower arms and legs) respectively. In this model, we assume each of the components can be represented by quadrangles and every component is connected to one of others by a joint. By making use of inherent correlation between different components, we design a top-down updating framework and an adaptive algorithm with constraints of foreground regions for robust and efficient tracking. The approach has been tested using the balancing movement in HumanEva-I/II dataset. The average tracking time is under one second, which is much shorter than most of current schemes.

  1. Inhibition of neutrophil elastase and metalloprotease-9 of human adenocarcinoma gastric cells by chamomile (Matricaria recutita L.) infusion.

    Science.gov (United States)

    Bulgari, Michela; Sangiovanni, Enrico; Colombo, Elisa; Maschi, Omar; Caruso, Donatella; Bosisio, Enrica; Dell'Agli, Mario

    2012-12-01

    This study investigated whether the antiinflammatory effect of chamomile infusion at gastric level could be ascribed to the inhibition of metalloproteinase-9 and elastase. The infusions from capitula and sifted flowers (250-1500 µg/mL) and individual flavonoids (10 µM) were tested on phorbol 12-myristate 13-acetate-stimulated AGS cells and human neutrophil elastase. The results indicate that the antiinflammatory activity associated with chamomile infusions from both the capitula and sifted flowers is most likely due to the inhibition of neutrophil elastase and gastric metalloproteinase-9 activity and secretion; the inhibition occurring in a concentration dependent manner. The promoter activity was inhibited as well and the decrease of metalloproteinase-9 expression was found to be associated with the inhibition of NF-kB driven transcription. The results further indicate that the flavonoid-7-glycosides, major constituents of chamomile flowers, may be responsible for the antiinflammatory action of the chamomile infusion observed here. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

    Science.gov (United States)

    Wang, Hai-Jun; Liu, Yu; Zhou, Bao-Jun; Zhang, Zhan-Xue; Li, Ai-Ying; An, Ran; Yue, Bin; Fan, Li-Qiao; Li, Yong

    2018-01-01

    Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO 3 vehicle alone or CP dissolved in NaHCO 3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.

  3. Adaptive upregulation of gastric and hypothalamic ghrelin receptors and increased plasma ghrelin in a model of cancer chemotherapy-induced dyspepsia.

    Science.gov (United States)

    Malik, N M; Moore, G B T; Kaur, R; Liu, Y-L; Wood, S L; Morrow, R W; Sanger, G J; Andrews, P L R

    2008-06-05

    Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03+/-1.35% vs. 11.38+/-2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03+/-1.35% vs. 2.60+/-0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.

  4. Expression of BAGE, GAGE, and MAGE genes in human gastric carcinoma.

    Science.gov (United States)

    Li, J; Yang, Y; Fujie, T; Baba, K; Ueo, H; Mori, M; Akiyoshi, T

    1996-09-01

    The MAGE, BAGE, and GAGE genes code for distinct antigens that are recognized by autologous cytolytic T lymphocytes. We investigated the expression of these genes in both cell lines and surgical samples of gastric carcinoma, using reverse transcription-PCR. Furthermore, the induction of these genes by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, was also examined in several cell lines. Of 11 cell lines, BAGE, GAGE1-6, GAGE1-2, MAGE-1, and MAGE-3 were detected in 7 (64%), 4 (36%), 3 (27%), 8 (73%), and 8 (73%) cell lines, respectively. After the in vitro treatment of the negative cell lines with DAC, the expression of these genes became positive in 46 to 91% of these cell lines. No expression of these genes was seen in any of the 57 samples of normal gastric tissue. In contrast, the tumor tissue samples expressed BAGE, GAGE1-6, GAGE1-2, MAGE-1, and MAGE-3 in 13 (23%), 9 (16%), 6 (11%), 25 (44%), and 23 (40%) tissue samples, respectively. Thus, at least one of these genes was expressed in 35 (61%) of 57 carcinomas. An analysis of the relationship between clinicopathological factors and the expression of these genes revealed that either BAGE or one of these genes was more frequently expressed in histologically intestinal-type than in diffuse-type carcinomas. Our results suggest that, because of the higher expression of these genes and the possible induction of these genes by DAC, patients with gastric carcinoma may, therefore, be potential candidates for tumor-specific immunotherapy directed against these antigens.

  5. Clusters of adaptive evolution in the human genome.

    Science.gov (United States)

    Scheinfeldt, Laura B; Biswas, Shameek; Madeoy, Jennifer; Connelly, Caitlin F; Akey, Joshua M

    2011-01-01

    Considerable work has been devoted to identifying regions of the human genome that have been subjected to recent positive selection. Although detailed follow-up studies of putatively selected regions are critical for a deeper understanding of human evolutionary history, such studies have received comparably less attention. Recently, we have shown that ALMS1 has been the target of recent positive selection acting on standing variation in Eurasian populations. Here, we describe a careful follow-up analysis of genetic variation across the ALMS1 region, which unexpectedly revealed a cluster of substrates of positive selection. Specifically, through the analysis of SNP data from the HapMap and Human Genome Diversity Project-Centre d'Etude du Polymorphisme Humain samples as well sequence data from the region, we find compelling evidence for three independent and distinct signals of recent positive selection across this 3 Mb region surrounding ALMS1. Moreover, we analyzed the HapMap data to identify other putative clusters of independent selective events and conservatively discovered 19 additional clusters of adaptive evolution. This work has important implications for the interpretation of genome-scans for positive selection in humans and more broadly contributes to a better understanding of how recent positive selection has shaped genetic variation across the human genome.

  6. Localised cutaneous microvascular adaptation to exercise training in humans.

    Science.gov (United States)

    Atkinson, Ceri L; Carter, Howard H; Thijssen, Dick H J; Birk, Gurpreet K; Cable, N Timothy; Low, David A; Kerstens, Floortje; Meeuwis, Iris; Dawson, Ellen A; Green, Daniel J

    2018-02-07

    Exercise training induces adaptation in conduit and resistance arteries in humans, partly as a consequence of repeated elevation in blood flow and shear stress. The stimuli associated with intrinsic cutaneous microvascular adaptation to exercise training have been less comprehensively studied. We studied 14 subjects who completed 8-weeks cycle ergometer training, with partial cuff inflation on one forearm to unilaterally attenuate cutaneous blood flow responses during each exercise-training bout. Before and after training, bilateral forearm skin microvascular dilation was determined using cutaneous vascular conductance (CVC: skin flux/blood pressure) responses to gradual localised heater disk stimulation performed at rest (33, 40, 42 and 44 °C). Cycle exercise induced significant increases in forearm cutaneous flux and temperature, which were attenuated in the cuffed arm (2-way ANOVA interaction-effect; P < 0.01). We found that forearm CVC at 42 and 44 °C was significantly lower in the uncuffed arm following 8-weeks of cycle training (P < 0.01), whereas no changes were apparent in the contralateral cuffed arm (P = 0.77, interaction-effect P = 0.01). Lower limb exercise training in healthy young men leads to lower CVC-responses to a local heating stimulus, an adaptation mediated, at least partly, by a mechanism related to episodic increases in skin blood flow and/or skin temperature.

  7. Epigenetic stability, adaptability, and reversibility in human embryonic stem cells.

    Science.gov (United States)

    Tompkins, Joshua D; Hall, Christine; Chen, Vincent Chang-yi; Li, Arthur Xuejun; Wu, Xiwei; Hsu, David; Couture, Larry A; Riggs, Arthur D

    2012-07-31

    The stability of human embryonic stem cells (hESCs) is of critical importance for both experimental and clinical applications. We find that as an initial response to altered culture conditions, hESCs change their transcription profile for hundreds of genes and their DNA methylation profiles for several genes outside the core pluripotency network. After adaption to conditions of feeder-free defined and/or xeno-free culture systems, expression and DNA methylation profiles are quite stable for additional passaging. However, upon reversion to the original feeder-based culture conditions, numerous transcription changes are not reversible. Similarly, although the majority of DNA methylation changes are reversible, highlighting the plasticity of DNA methylation, a few are persistent. Collectively, this indicates these cells harbor a memory of culture history. For culture-induced DNA methylation changes, we also note an intriguing correlation: hypomethylation of regions 500-2440 bp upstream of promoters correlates with decreased expression, opposite to that commonly seen at promoter-proximal regions. Lastly, changes in regulation of G-coupled protein receptor pathways provide a partial explanation for many of the unique transcriptional changes observed during hESC adaptation and reverse adaptation.

  8. Event driven adaptation, land use and human coping strategies

    DEFF Research Database (Denmark)

    Reenberg, Anette; Birch-Thomsen, Torben; Fog, Bjarne

    and the concept of coupled human-environmental timelines. Secondly, with point of departure in a baseline characterization of Bellona Island derived from a comprehensive survey in the late 1960s and resent fieldwork in late 2006, we present the case of Bellona Island. Key issues addressed concern climatic events......, population, agricultural strategies, land use, livelihood strategies, non-agricultural activities, etc. Satellite imagery and aerial photos show relative stability in agricultural land despite an increase in de facto population (51% from 1966-2006). A questionnaire survey of 48 households provide data...... perceive cause-effect relationships between societal and environmental events and their individual and collective management of resources. The coupled human-environment timelines are used to discuss ways in which the local communities' adaptive resource management strategies have been employed in the face...

  9. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis.

    Science.gov (United States)

    Sampieri, Clara Luz; de la Peña, Sol; Ochoa-Lara, Mariana; Zenteno-Cuevas, Roberto; León-Córdoba, Kenneth

    2010-03-28

    To assess expression of matrix metalloproteinases 2 (MMP2) and MMP9 in gastric cancer, superficial gastritis and normal mucosa, and to measure metalloproteinase activity. MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction. Normalization was carried out using three different factors. Proteins were analyzed by quantitative gelatin zymography (qGZ). 18S ribosomal RNA (18SRNA) was very highly expressed, while hypoxanthine ribosyltransferase-1 (HPRT-1) was moderately expressed. MMP2 was highly expressed, while MMP9 was not detected or lowly expressed in normal tissues, moderately or highly expressed in gastritis and highly expressed in cancer. Relative expression of 18SRNA and HPRT-1 showed no significant differences. Significant differences in MMP2 and MMP9 were found between cancer and normal tissue, but not between gastritis and normal tissue. Absolute quantification of MMP9 echoed this pattern, but differential expression of MMP2 proved conflictive. Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2, total MMP-9, 250 and 110 kDa bands. MMP9 expression is enhanced in gastric cancer compared to normal mucosa; interpretation of differential expression of MMP2 is difficult to establish.

  10. Weight loss after gastric bypass surgery in human obesity remodels promoter methylation

    DEFF Research Database (Denmark)

    Barres, Romain; Kirchner, Henriette; Rasmussen, Morten

    2013-01-01

    DNA methylation provides a mechanism by which environmental factors can control insulin sensitivity in obesity. Here, we assessed DNA methylation in skeletal muscle from obese people before and after Roux-en-Y gastric bypass (RYGB). Obesity was associated with altered expression of a subset of ge...... is associated with hypermethylation at CpG shores and exonic regions close to transcription start sites. Our results provide evidence that obesity and RYGB-induced weight loss have a dynamic effect on the epigenome.......DNA methylation provides a mechanism by which environmental factors can control insulin sensitivity in obesity. Here, we assessed DNA methylation in skeletal muscle from obese people before and after Roux-en-Y gastric bypass (RYGB). Obesity was associated with altered expression of a subset...... observed in the normal-weight, healthy subjects. Using bisulfite sequencing, we show that promoter methylation of PGC-1a and PDK4 is altered with obesity and restored to nonobese levels after RYGB-induced weight loss. A genome-wide DNA methylation analysis of skeletal muscle revealed that obesity...

  11. Evaluation of the Expression of the Human Epithelial Receptor 2 (HER2 in Gastric Carcinoma

    Directory of Open Access Journals (Sweden)

    Roberto de Moraes Cordts Filho

    2016-01-01

    Full Text Available Objective. To evaluate the HER2 expression on gastric adenocarcinoma from a Brazilian population and also to analyze the relations between the receptor and clinical characteristics, as well as the survival status. Materials and Methods. A retrospective analysis was conducted from January of 2008 to July of 2012, considering only gastrectomies with curative intent. Tumors were tested for HER2 status using immunohistochemistry. The relation between HER2 status and clinical aspects, surgical findings, and survival were also analyzed. Results. 222 patients with gastric carcinoma were submitted to surgery during that period, but only 121 (54,5% were with curative intention. The immunohistochemistry revealed that 4 patients (3,3% were HER2-positive, 6 patients (4,9% HER2-undetermined, and 111 patients (91,7% HER2-negative. There was no statistical concordance between HER2 status and survival or the clinical aspects. Conclusion. The HER2 overexpression rate was very low in this Brazilian population sample and cannot be considered as a prognostic factor.

  12. A Cooperative Human-Adaptive Traffic Simulation (CHATS)

    Science.gov (United States)

    Phillips, Charles T.; Ballin, Mark G.

    1999-01-01

    NASA is considering the development of a Cooperative Human-Adaptive Traffic Simulation (CHATS), to examine and evaluate performance of the National Airspace System (NAS) as the aviation community moves toward free flight. CHATS will be specifically oriented toward simulating strategic decision-making by airspace users and by the service provider s traffic management personnel, within the context of different airspace and rules assumptions. It will use human teams to represent these interests and make decisions, and will rely on computer modeling and simulation to calculate the impacts of these decisions. The simulation objectives will be to examine: 1. evolution of airspace users and the service provider s strategies, through adaptation to new operational environments; 2. air carriers competitive and cooperative behavior; 3. expected benefits to airspace users and the service provider as compared to the current NAS; 4. operational limitations of free flight concepts due to congestion and safety concerns. This paper describes an operational concept for CHATS, and presents a high-level functional design which would utilize a combination of existing and new models and simulation capabilities.

  13. Lingual and gastric lipases.

    Science.gov (United States)

    Hamosh, M

    1990-01-01

    The 1973 discovery of lingual lipase, which is secreted by lingual serous glands and hydrolyzes medium- and long-chain triglycerides in the stomach, has renewed interest in the gastric phase of fat digestion. In humans, lipase is present in the serous (von Ebner) glands of the tongue, where it is localized in zymogen granules. In the stomach, the highest lipase activity is in the body. By immunocytochemistry, gastric lipase is confined to the chief cells of the fundic mucosa and is colocalized with pepsin. Human lipase purified from lingual serous glands or gastric juice has a MW of 45k to 51K but tends to aggregate (MW 270-300K and 500K) and is highly hydrophobic. Secretion of gastric lipase appears to be stimulated by at least two receptor mechanisms. It has been suggested that the products of gastric lipolysis maintain the sterility of the gastrointestinal tract. These enzymes are essential for the digestion of milk fat in the newborn because, contrary to other digestive lipases (pancreatic or milk digestive lipase), lingual and gastric lipases can penetrate into the milk fat globule and initiate the digestive process. Lingual and gastric lipase activity has been found in subjects with cystic fibrosis and appears to continue in the upper small intestine in these patients, perhaps replacing some of the missing pancreatic lipase. It is possible that lingual and gastric lipase supplements would be more effective in preventing steatorrhea in these patients than are the pancreatic enzyme supplements now given. The same therapeutic utility might be obtained in patients with alcoholic pancreatic insufficiency.

  14. MiR-99a and MiR-491 Regulate Cisplatin Resistance in Human Gastric Cancer Cells by Targeting CAPNS1.

    Science.gov (United States)

    Zhang, Yajie; Xu, Wenxia; Ni, Pan; Li, Aiping; Zhou, Jianwei; Xu, Shan

    2016-01-01

    Cisplatin is the first-line agent utilized for the clinical treatment of a wide variety of solid tumors including gastric cancer. However, the intrinsic or acquired cisplatin resistance is often occurred in patients with gastric cancer and resulted in failure of cisplatin therapy. In order to investigate if miRNA involves in cisplatin resistance of human gastric cancer, we first screened and compared the expression of miRNAs between cisplatin resistant gastric cancer cell lines SGC-7901/DDP and BGC-823/DDP and their sensitive parental cells by miRNAs microarray and followed by analysis of 2D-GE/MS to identify their target proteins. We found both miR-99a and miR-491 were upregulated while their target gene calpain small subunit 1 (CAPNS1) was downregulated in resistant gastric cancer cells. Dual-luciferase- reporter assays with wild-type and mutated CAPNS1 3'-UTR confirmed their specificity of targeting. Inhibition of miR-99a and miR-491, or overexpress CAPNS1 can enhance cisplatin sensitivity of the resistant cells while transfection of two miRNAs' mimics or si-CAPNS1 in the sensitive cells can induce their resistance. Moreover, our results demonstrated CAPNS1 positively regulated calpain1 and calpain2, the catalytic subunits of CAPNS1, and cleaved caspase3 which further cleaved PARP1 and directly induced apoptosis. Therefore, miR-99a and miR-491 might be work as novel molecules regulate cisplatin resistance by directly targeting CAPNS1 associated pathway in human gastric cancer cells.

  15. Ethyl nitrite is produced in the human stomach from dietary nitrate and ethanol, releasing nitric oxide at physiological pH: potential impact on gastric motility.

    Science.gov (United States)

    Rocha, Bárbara S; Gago, Bruno; Barbosa, Rui M; Cavaleiro, Carlos; Laranjinha, João

    2015-05-01

    Nitric oxide ((∙)NO), a ubiquitous molecule involved in a plethora of signaling pathways, is produced from dietary nitrate in the gut through the so-called nitrate-nitrite-NO pathway. In the stomach, nitrite derived from dietary nitrate triggers a network of chemical reactions targeting endogenous and exogenous biomolecules, thereby producing new compounds with physiological activity. The aim of this study was to ascertain whether compounds with physiological relevance are produced in the stomach upon consumption of nitrate- and ethanol-rich foods. Human volunteers consumed a serving of lettuce (source of nitrate) and alcoholic beverages (source of ethanol). After 15 min, samples of the gastric headspace were collected and ethyl nitrite was identified by GC-MS. Wistar rats were used to study the impact of ethyl nitrite on gastric smooth muscle relaxation at physiological pH. Nitrogen oxides, produced from nitrite in the stomach, induce nitrosation of ethanol from alcoholic beverages in the human stomach yielding ethyl nitrite. Ethyl nitrite, a potent vasodilator, is produced in vivo upon the consumption of lettuce with either red wine or whisky. Moreover, at physiological pH, ethyl nitrite induces gastric smooth muscle relaxation through a cGMP-dependent pathway. Overall, these results suggest that ethyl nitrite is produced in the gastric lumen and releases (∙)NO at physiological pH, which ultimately may have an impact on gastric motility. Systemic effects may also be expected if ethyl nitrite diffuses through the gastric mucosa reaching blood vessels, therefore operating as a (∙)NO carrier throughout the body. These data pinpoint posttranslational modifications as an underappreciated mechanism for the production of novel molecules with physiological impact locally in the gut and highlight the notion that diet may fuel compounds with the potential to modulate gastrointestinal welfare. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Correlation of particle properties with cytotoxicity and cellular uptake of hydroxyapatite nanoparticles in human gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Xinhui [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China); Liang, Tong [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Liu, Changsheng [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China); Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Yuan, Yuan, E-mail: yyuan@ecust.edu.cn [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Qian, Jiangchao, E-mail: jiangchaoqian@ecust.edu.cn [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2016-10-01

    Three types of hydroxyapatite nanoparticles (HAPNs) were synthesized employing a sonochemistry-assisted microwave method by changing microwave power (from 200 to 300 W) or using calcination treatment: L200 (200 W, lyophilization), L300 (300 W, lyophilization) and C200 (200 W, lyophilization & calcination). Their physiochemical properties were characterized and correlated with cytotoxicity to human gastric cancer cells (MGC80-3). The major differences among these HAPN preparations were their size and specific surface area, with the L200 showing a smaller size and higher specific surface area. Although all HAPNs inhibited cell proliferation and induced apoptosis of cancer cells, L200 exhibited the greatest toxicity. All types of HAPNs were internalized through energy-dependent pathways, but the L200 nanoparticles were more efficiently uptaken by MGC80-3 cells. Inhibitor studies with dynasore and methyl-β-cyclodextrin suggested that caveolae-mediated endocytosis and, to a much lesser extent, clathrin-mediated endocytosis, were involved in cellular uptake of the various preparations, whereas the inhibition of endocytosis was more obvious for L200. Using fluorescein isothiocyanate-labeled HAPNs and laser-scanning confocal microscopy, we found that all forms of nanoparticles were present in the cytoplasm, and some L200 HAPNs were even found within nuclei. Treatment with all HAPN preparations led to the increase in the intracellular calcium level with the highest level detected for L200. - Highlights: • Three types of HAPNs (L200, L300 and C200) were synthesized employing a sonochemistry-assisted microwave method. • L200 exhibited the greatest cytotoxicity to human gastric cancer (MGC80-3) cells. • L200 showed a smaller size and higher specific surface area. • The L200 nanoparticles were more efficiently uptaken by MGC80-3 cells through energy-dependent pathways. • L200 caused the most significant increase in the intracellular calcium level.

  17. Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric Tumor Cells.

    Science.gov (United States)

    Reis, Filipa S; Lima, Raquel T; Morales, Patricia; Ferreira, Isabel C F R; Vasconcelos, M Helena

    2015-09-29

    Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was not known if it induces autophagy or decreases the autophagic flux. The treatment of a gastric adenocarcinoma cell line (AGS) with the mushroom extract increased the formation of autophagosomes (vacuoles typical from autophagy). Moreover, the cellular levels of LC3-II were also increased, and the cellular levels of p62 decreased, confirming that the extract affects cellular autophagy. Treating the cells with the extract together with lysossomal protease inhibitors, the cellular levels of LC3-II and p62 increased. The results obtained proved that, in AGS cells, the methanolic extract of G. lucidum causes an induction of autophagy, rather than a reduction in the autophagic flux. To our knowledge, this is the first study proving that statement.

  18. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth; Bojsen-Moller, Kirstine N; Dirksen, Carsten

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose......-surgery when major weight loss was evident and occurred concomitantly with alterations in plasma adiponectin and in protein expression/signaling in peripheral tissues. In skeletal muscle, protein expression of GLUT4, phosphorylated levels of TBC1D4 as well as insulin-induced changes in phosphorylation of Akt...... and glycogen synthase activity were enhanced 12 months post-surgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4 and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC as well as insulin-induced changes in phosphorylation of Akt and TBC1D4 were enhanced...

  19. Calcium Promotes Human Gastric Cancer via a Novel Coupling of Calcium-Sensing Receptor and TRPV4 Channel.

    Science.gov (United States)

    Xie, Rui; Xu, Jingyu; Xiao, Yufeng; Wu, Jilin; Wan, Hanxing; Tang, Bo; Liu, Jingjing; Fan, Yahan; Wang, Suming; Wu, Yuyun; Dong, Tobias Xiao; Zhu, Michael X; Carethers, John M; Dong, Hui; Yang, Shiming

    2017-12-01

    Although dietary calcium intake has long been recommended for disease prevention, the influence of calcium in development of cancer in the upper gastrointestinal tract has not been explored. Here, we assess the roles of calcium and calcium-sensing receptor (CaSR) in gastric cancer development. CaSR expression was enhanced in gastric cancer specimens, which positively correlated with serum calcium concentrations, tumor progression, poor survival, and male gender in gastric cancer patients. CaSR and transient receptor potential cation channel subfamily V member 4 (TRPV4) were colocalized in gastric cancer cells, and CaSR activation evoked TRPV4-mediated Ca 2+ entry. Both CaSR and TRPV4 were involved in Ca 2+ -induced proliferation, migration, and invasion of gastric cancer cells through a Ca 2+ /AKT/β-catenin relay, which occurred only in gastric cancer cells or normal cells overexpressing CaSR. Tumor growth and metastasis of gastric cancer depended on CaSR in nude mice. Overall, our findings indicate that calcium may enhance expression and function of CaSR to potentially promote gastric cancer, and that targeting the novel CaSR/TRPV4/Ca 2+ pathway might serve as preventive or therapeutic strategies for gastric cancer. Cancer Res; 77(23); 6499-512. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. iTRAQ-Based Proteomic Analysis of Ginsenoside F2 on Human Gastric Carcinoma Cells SGC7901

    Directory of Open Access Journals (Sweden)

    Qian Mao

    2016-01-01

    Full Text Available Ginsenoside F2 (F2, a protopanaxdiol type of saponin, was reported to inhibit human gastric cancer cells SGC7901. To better understand the molecular mechanisms of F2, an iTRAQ-based proteomics approach was applied to define protein expression profiles in SGC7901 cells in response to lower dose (20 μM and shorter duration (12 hour of F2 treatment, compared with previous study. 205 proteins were screened in terms of the change in their expression level which met our predefined criteria. Further bioinformatics and experiments demonstrated that F2 treatment downregulated PRR5 and RPS15 and upregulated RPL26, which are implicated in ribosomal protein-p53 signaling pathway. F2 also inhibited CISD2, Bcl-xl, and NLRX1, which are associated with autophagic pathway. Furthermore, it was demonstrated that F2 treatment increased Atg5, Atg7, Atg10, and PUMA, the critical downstream effectors of ribosomal protein-p53 signaling pathway, and Beclin-1, UVRAG, and AMBRA-1, the important molecules in Bcl-xl/Beclin-1 pathway. The 6 differentially abundant proteins, PRR5, CISD2, Bcl-xl, NLRX1, RPS15, and RPL26, were confirmed by western blot. Taken together, ribosomal protein-p53 signaling pathway and Bcl-xl/Beclin-1 pathway might be the most significantly regulated biological process by F2 treatment in SGC7901 cells, which provided valuable insights into the deep understanding of the molecular mechanisms of F2 for gastric cancer treatment.

  1. Effects of a novel porphyrin-based photosensitizer on sensitive and multidrug-resistant human gastric cancer cell lines.

    Science.gov (United States)

    Chen, Jingjing; Mao, Lina; Liu, Shuping; Liang, Yanling; Wang, Sicheng; Wang, Yeyu; Zhao, Qiang; Zhang, Xiaojing; Che, Yanjun; Gao, Lijing; Liu, Tianjun

    2015-10-01

    Photodynamic therapy (PDT) has been considered to be a possible candidate approach in combating multidrug resistance (MDR) phenomenon during the treatment of cancer. To investigate the photocytotoxicity of a novel porphyrin-based photosensitizer, meso-5-[ρ-DTPA-aminophenyl]-10, 15, 20-triphenyl-porhyrin (DTP) (Fig. 1A), on MDR cells, the intracellular DTP uptake, phototoxicity and subcellular DTP localization were studied by using a human gastric cancer MGC803 cell line and its paclitaxel selected subline MGC803/PA expressing MDR phenotype. No significant difference was observed in intracellular DTP accumulation between sensitive and resistant cell lines after exposure to 1.56 μM concentration for 6h. DTP-PDT induced significant photocytotoxicity on both MGC803 and MGC803/PA cell lines and the photokilling was greater in MGC803 cell line in comparison to MGC803/PA. The fluence that caused 50% cell death was 4.42 and 6.29 J/cm(2) in MGC803 and MGC803/PA cell lines, respectively. The presence of Pgp inhibitors verapamil and cyclosporin A could not modify the intracellular DTP level in MGC803/PA cell line and the phototoxic effects. DTP was localized at lysosomes of MGC803 cell line but at lysosomes and mitochondria of MGC803/PA. Our results indicated that DTP-mediated PDT could eradicate gastric cancer cells whether or not they express MDR although the efficacy is slightly reduced in the MDR cells. The photokilling in MDR cells could not be altered by MDR inhibitor verapamil. The slightly different photocytotoxicity between sensitive and resistant cell lines could not explained by classical Pgp MDR and might be attributed to the differential intracellular DTP localization sites. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Synthesis and characterization of C@CdS dots in aqueous solution and their application in labeling human gastric carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Wei, E-mail: dongwei5873@126.com [Shenyang Medical College, Department of Chemistry (China); Zhou, Siqi [Fengtian Hospital Affiliated to Shenyang Medical College, ICU (China); Dong, Yan [Shenyang Pharmaceutical University, Experiment Center of Traditional Chinese Medicine Department (China); Wang, Jingwen; Liu, Shuang; Zhu, Pengxia [Shenyang Medical College, Department of Chemistry (China)

    2015-03-15

    Colloidal carbon spheres coated with cadmium sulfide nanoparticle quantum dots (C@CdS dots) with the particle size smaller than 50 nm were synthesized by an aqueous approach. The effects of different reaction times, temperatures, and pH values were carefully investigated to optimize the synthesis conditions. The as-prepared C@CdS dots were linked with mouse anti-human carcinoembryonic antigen antibody and goat anti-mouse immunoglobulin (IgG) to directly and indirectly label fixed human gastric carcinoma cells, respectively. The cytotoxicity of the C@CdS dots was also tested using the human gastric carcinoma cells. No apparent cytotoxicity was observed, which suggested the potential application of the as-prepared C@CdS dots in bioimaging.

  3. Synthesis and characterization of C@CdS dots in aqueous solution and their application in labeling human gastric carcinoma cells

    Science.gov (United States)

    Dong, Wei; Zhou, Siqi; Dong, Yan; Wang, Jingwen; Liu, Shuang; Zhu, Pengxia

    2015-03-01

    Colloidal carbon spheres coated with cadmium sulfide nanoparticle quantum dots (C@CdS dots) with the particle size smaller than 50 nm were synthesized by an aqueous approach. The effects of different reaction times, temperatures, and pH values were carefully investigated to optimize the synthesis conditions. The as-prepared C@CdS dots were linked with mouse anti-human carcinoembryonic antigen antibody and goat anti-mouse immunoglobulin (IgG) to directly and indirectly label fixed human gastric carcinoma cells, respectively. The cytotoxicity of the C@CdS dots was also tested using the human gastric carcinoma cells. No apparent cytotoxicity was observed, which suggested the potential application of the as-prepared C@CdS dots in bioimaging.

  4. Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells.

    Science.gov (United States)

    Stec, Małgorzata; Szatanek, Rafał; Baj-Krzyworzeka, Monika; Baran, Jarosław; Zembala, Maria; Barbasz, Jakub; Waligórska, Agnieszka; Dobrucki, Jurek W; Mytar, Bożenna; Szczepanik, Antoni; Siedlar, Maciej; Drabik, Grażyna; Urbanowicz, Barbara; Zembala, Marek

    2015-12-01

    Tumour cells release membrane micro(nano)fragments called tumour-derived microvesicles (TMV) that are believed to play an important role in cancer progression. TMV suppress/modify antitumour response of the host, but there is also some evidence for their direct interaction with cancer cells. In cancer patients TMV are present in body fluid and tumour microenvironment. The present study aimed at characterization of whole types/subpopulations, but not only exosomes, of TMV from newly established gastric cancer cell line (called GC1415) and to define their interactions with autologous cells. TMV were isolated from cell cultures supernatants by centrifugation at 50,000×g and their phenotype was determined by flow cytometry. The size of TMV was analysed by dynamic light scattering and nanoparticle tracking analysis, while morphology by transmission electron microscopy and atomic force microscopy. Interactions of TMV with cancer cells were visualized using fluorescence-activated cell sorter, confocal and atomic force microscopy, biological effects by xenografts in NOD SCID mice. Isolated TMV showed expression of CD44H, CD44v6 (hyaluronian receptors), CCR6 (chemokine receptor) and HER-2/neu molecules, exhibited different shapes and sizes (range 60-900 nm, highest frequency of particles with size range of 80-120 nm). TMV attached to autologous cancer cells within 2 h and then were internalized by them at 24 h. CD44H, CD44v6 and CCR6 molecules may play a role in attachment of TMV to cancer cells, while HER-2 associated with CD24 be involved in promoting cancer cells growth. Pre-exposure of cancer cells to TMV resulted in enhancement of tumour growth and cancer cell-induced angiogenesis in NOD SCID mice model. TMV interact directly with cancer cells serving as macro-messengers and molecular cargo transfer between gastric cancer cells resulting in enhancement of tumour growth. TMV should be considered in future as target of anticancer therapy.

  5. Amperometric microsensor for direct probing of ascorbic acid in human gastric juice

    Energy Technology Data Exchange (ETDEWEB)

    Hutton, Emily A.; Pauliukaite, Rasa; Hocevar, Samo B. [Analytical Chemistry Laboratory, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana (Slovenia); Ogorevc, Bozidar, E-mail: bogorevc@ki.s [Analytical Chemistry Laboratory, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana (Slovenia); Smyth, Malcolm R. [National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9 (Ireland)

    2010-09-30

    This article reports on a novel microsensor for amperometric measurement of ascorbic acid (AA) under acidic conditions (pH 2) based on a carbon fiber microelectrode (CFME) modified with nickel oxide and ruthenium hexacyanoferrate (NiO-RuHCF). This sensing layer was deposited electrochemically in a two-step procedure involving an initial galvanostatic NiO deposition followed by a potentiodynamic RuHCF deposition from solutions containing the precursor salts. Several important parameters were examined to characterize and optimize the NiO-RuHCF sensing layer with respect to its current response to AA by using cyclic voltammetry, and scanning electron microscopy-energy dispersive X-ray spectroscopy methods. With the NiO-RuHCF coated CFME, the AA oxidation potential under acidic conditions was shifted to a less positive value for about 0.2 V (E{sub p} of ca. 0.23 V vs. Ag/AgCl) as compared to a bare CFME, which greatly improves the electrochemical selectivity. Using the hydrodynamic amperometry mode, the current vs. AA concentration in 0.01 M HCl, at a selected operating potential of 0.30 V, was found to be linear over a wide range of 10-1610 {mu}M (n = 22, r = 0.999) with a calculated limit of detection of 1.0 {mu}M. The measurement repeatability was satisfactory with a relative standard deviation (r.s.d.) ranging from 4% to 5% (n = 6), depending on the AA concentration, and with a sensor-to-sensor reproducibility (r.s.d.) of 6.9% at 100 {mu}M AA. The long-term reproducibility, using the same microsensor for 112 consecutive measurements of 20 {mu}M AA over 11 h of periodic probing sets over 4 days, was 16.1% r.s.d., thus showing very good stability at low AA levels and suitability for use over a prolonged period of time. Moreover, using the proposed microsensor, additionally coated with a protective cellulose acetate membrane, the calibration plot obtained in the extremely complex matrix of real undiluted gastric juice was linear from 10 to 520 {mu}M (n = 14, r = 0

  6. Amperometric microsensor for direct probing of ascorbic acid in human gastric juice

    International Nuclear Information System (INIS)

    Hutton, Emily A.; Pauliukaite, Rasa; Hocevar, Samo B.; Ogorevc, Bozidar; Smyth, Malcolm R.

    2010-01-01

    This article reports on a novel microsensor for amperometric measurement of ascorbic acid (AA) under acidic conditions (pH 2) based on a carbon fiber microelectrode (CFME) modified with nickel oxide and ruthenium hexacyanoferrate (NiO-RuHCF). This sensing layer was deposited electrochemically in a two-step procedure involving an initial galvanostatic NiO deposition followed by a potentiodynamic RuHCF deposition from solutions containing the precursor salts. Several important parameters were examined to characterize and optimize the NiO-RuHCF sensing layer with respect to its current response to AA by using cyclic voltammetry, and scanning electron microscopy-energy dispersive X-ray spectroscopy methods. With the NiO-RuHCF coated CFME, the AA oxidation potential under acidic conditions was shifted to a less positive value for about 0.2 V (E p of ca. 0.23 V vs. Ag/AgCl) as compared to a bare CFME, which greatly improves the electrochemical selectivity. Using the hydrodynamic amperometry mode, the current vs. AA concentration in 0.01 M HCl, at a selected operating potential of 0.30 V, was found to be linear over a wide range of 10-1610 μM (n = 22, r = 0.999) with a calculated limit of detection of 1.0 μM. The measurement repeatability was satisfactory with a relative standard deviation (r.s.d.) ranging from 4% to 5% (n = 6), depending on the AA concentration, and with a sensor-to-sensor reproducibility (r.s.d.) of 6.9% at 100 μM AA. The long-term reproducibility, using the same microsensor for 112 consecutive measurements of 20 μM AA over 11 h of periodic probing sets over 4 days, was 16.1% r.s.d., thus showing very good stability at low AA levels and suitability for use over a prolonged period of time. Moreover, using the proposed microsensor, additionally coated with a protective cellulose acetate membrane, the calibration plot obtained in the extremely complex matrix of real undiluted gastric juice was linear from 10 to 520 μM (n = 14, r = 0.998). These

  7. Shear stress mediates endothelial adaptations to exercise training in humans.

    Science.gov (United States)

    Tinken, Toni M; Thijssen, Dick H J; Hopkins, Nicola; Dawson, Ellen A; Cable, N Timothy; Green, Daniel J

    2010-02-01

    Although episodic changes in shear stress have been proposed as the mechanism responsible for the effects of exercise training on the vasculature, this hypothesis has not been directly addressed in humans. We examined brachial artery flow-mediated dilation, an index of NO-mediated endothelial function, in healthy men in response to an acute bout of handgrip exercise and across an 8-week period of bilateral handgrip training. Shear stress responses were attenuated in one arm by cuff inflation to 60 mm Hg. Similar increases were observed in grip strength and forearm volume and girth in both limbs. Acute bouts of handgrip exercise increased shear rate (P<0.005) and flow-mediated dilation percentage (P<0.05) in the uncuffed limb, whereas no changes were evident in the cuffed arm. Handgrip training increased flow-mediated dilation percentage in the noncuffed limb at weeks 2, 4, and 6 (P<0.001), whereas no changes were observed in the cuffed arm. Brachial artery peak reactive hyperemia, an index of resistance artery remodeling, progressively increased with training in the noncuffed limb (P<0.001 and 0.004); no changes were evident in the cuffed arm. Neither acute nor chronic shear manipulation during exercise influenced endothelium-independent glyceryl trinitrate responses. These results demonstrate that exercise-induced changes in shear provide the principal physiological stimulus to adaptation in flow-mediated endothelial function and vascular remodeling in response to exercise training in healthy humans.

  8. Adaptive Ensemble with Human Memorizing Characteristics for Data Stream Mining

    Directory of Open Access Journals (Sweden)

    Yanhuang Jiang

    2015-01-01

    Full Text Available Combining several classifiers on sequential chunks of training instances is a popular strategy for data stream mining with concept drifts. This paper introduces human recalling and forgetting mechanisms into a data stream mining system and proposes a Memorizing Based Data Stream Mining (MDSM model. In this model, each component classifier is regarded as a piece of knowledge that a human obtains through learning some materials and has a memory retention value reflecting its usefulness in the history. The classifiers with high memory retention values are reserved in a “knowledge repository.” When a new data chunk comes, most useful classifiers will be selected (recalled from the repository and compose the current target ensemble. Based on MDSM, we put forward a new algorithm, MAE (Memorizing Based Adaptive Ensemble, which uses Ebbinghaus forgetting curve as the forgetting mechanism and adopts ensemble pruning as the recalling mechanism. Compared with four popular data stream mining approaches on the datasets with different concept drifts, the experimental results show that MAE achieves high and stable predicting accuracy, especially for the applications with recurring or complex concept drifts. The results also prove the effectiveness of MDSM model.

  9. Preliminary Exploration of Adaptive State Predictor Based Human Operator Modeling

    Science.gov (United States)

    Trujillo, Anna C.; Gregory, Irene M.

    2012-01-01

    Control-theoretic modeling of the human operator dynamic behavior in manual control tasks has a long and rich history. In the last two decades, there has been a renewed interest in modeling the human operator. There has also been significant work on techniques used to identify the pilot model of a given structure. The purpose of this research is to attempt to go beyond pilot identification based on collected experimental data and to develop a predictor of pilot behavior. An experiment was conducted to quantify the effects of changing aircraft dynamics on an operator s ability to track a signal in order to eventually model a pilot adapting to changing aircraft dynamics. A gradient descent estimator and a least squares estimator with exponential forgetting used these data to predict pilot stick input. The results indicate that individual pilot characteristics and vehicle dynamics did not affect the accuracy of either estimator method to estimate pilot stick input. These methods also were able to predict pilot stick input during changing aircraft dynamics and they may have the capability to detect a change in a subject due to workload, engagement, etc., or the effects of changes in vehicle dynamics on the pilot.

  10. Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells.

    Science.gov (United States)

    Jeong, Jin Boo; Hong, Se Chul; Jeong, Hyung Jin; Koo, Jin Suk

    2011-10-01

    Gastric cancer is a leading cause of cancer-related deaths, worldwide being second only to lung cancer as a cause of death. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms of arctigenin for anti-tumor effect on gastric cancer have not been examined. This study examined the biological effects of arctigenin on the human gastric cancer cell line SNU-1 and AGS. Cell proliferation was determined by MTT assay. In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by arctigenin in a time and dose dependent manner, as compared with SNU-1 and AGS cells cultured in the absence of arctigenin. Inhibition of cell proliferation by arctigenin was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bcl-2 to Bax by arctigenin. Also, arctigenin blocked cell cycle arrest from G(1) to S phase by regulating the expression of cell cycle regulatory proteins such as Rb, cyclin D1, cyclin E, CDK4, CDK2, p21Waf1/Cip1 and p15 INK4b. The antiproliferative effect of arctigenin on SNU-1 and AGS gastric cancer cells revealed in this study suggests that arctigenin has intriguing potential as a chemopreventive or chemotherapeutic agent. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  11. Probiotic and technological properties of Lactobacillus spp. strains from the human stomach in the search for potential candidates against gastric microbial dysbiosis.

    Science.gov (United States)

    Delgado, Susana; Leite, Analy M O; Ruas-Madiedo, Patricia; Mayo, Baltasar

    2014-01-01

    This work characterizes a set of lactobacilli strains isolated from the stomach of healthy humans that might serve as probiotic cultures. Ten different strains were recognized by rep-PCR and PFGE fingerprinting among 19 isolates from gastric biopsies and stomach juice samples. These strains belonged to five species, Lactobacillus gasseri (3), Lactobacillus reuteri (2), Lactobacillus vaginalis (2), Lactobacillus fermentum (2) and Lactobacillus casei (1). All ten strains were subjected to a series of in vitro tests to assess their functional and technological properties, including acid resistance, bile tolerance, adhesion to epithelial gastric cells, production of antimicrobial compounds, inhibition of Helicobacter pylori, antioxidative activity, antibiotic resistance, carbohydrate fermentation, glycosidic activities, and ability to grow in milk. As expected, given their origin, all strains showed good resistance to low pH (3.0), with small reductions in counts after 90 min exposition to this pH. Species- and strain-specific differences were detected in terms of the production of antimicrobials, antagonistic effects toward H. pylori, antioxidative activity and adhesion to gastric epithelial cells. None of the strains showed atypical resistance to a series of 16 antibiotics of clinical and veterinary importance. Two L. reuteri strains were deemed as the most appropriate candidates to be used as potential probiotics against microbial gastric disorders; these showed good survival under gastrointestinal conditions reproduced in vitro, along with strong anti-Helicobacter and antioxidative activities. The two L. reuteri strains further displayed appropriated technological traits for their inclusion as adjunct functional cultures in fermented dairy products.

  12. Gastric emptying

    International Nuclear Information System (INIS)

    Vitti, R.A.; Malmud, L.S.; Fisher, R.S.

    1986-01-01

    Radionuclide techniques appear to be the current method of choice for determining the rate and pattern of gastric emptying. Isotopic methods are quantitative, noninvasive in that they do not require intubation, may be used with solid meals for greater sensitivity, present a low radiation burden to the patient compared to the burden of radiographic techniques, and are suitable and acceptable to the patient for repetitive studies. By comparison, other methods are either invasive, nonquantitative, or nonphysiologic. Of the radionuclide methods currently available, the solid meals (either liver or egg) are best, and dual liquid-solid studies offer additional physiologic data. It is now known that gastric emptying abnormalities may result from common disorders such as diabetes mellitus or gastric or duodenal ulcer disease, may be caused by a variety of medications, may follow gastric surgery, or may result from less well understood disorders, such as Zollinger-Ellison syndrome. By helping to clarify these gastric emptying abnormalities, the physician's ability to treat disorders of gastric emptying with diet, medication, and surgery is enhanced in accuracy and precision. Using these newer radionuclide techniques will permit both the clinician and the investigator a better understanding than was previously possible of gastric physiology in both health and disease

  13. Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer

    Science.gov (United States)

    Yang, Zhe; Luo, Huiyan; Cao, Zhong; Chen, Ya; Gao, Jinbiao; Li, Yingqin; Jiang, Qing; Xu, Ruihua; Liu, Jie

    2016-06-01

    Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44.Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor

  14. Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

    International Nuclear Information System (INIS)

    Guo, Xianling; Zhang, Baihe; Wu, Mengchao; Wei, Lixin; Ma, Nannan; Wang, Jin; Song, Jianrui; Bu, Xinxin; Cheng, Yue; Sun, Kai; Xiong, Haiyan; Jiang, Guocheng

    2008-01-01

    Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the MDR1 gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the MDR1 gene. Overexpression of MDR1 gene has often been reported in primary gastric adenocarcinoma. This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining. The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (MDR1) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and MDR1 expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy. Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line

  15. Impact of climate change on human infectious diseases: Empirical evidence and human adaptation.

    Science.gov (United States)

    Wu, Xiaoxu; Lu, Yongmei; Zhou, Sen; Chen, Lifan; Xu, Bing

    2016-01-01

    Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events. It may lead to changes in health threat to human beings, multiplying existing health problems. This review examines the scientific evidences on the impact of climate change on human infectious diseases. It identifies research progress and gaps on how human society may respond to, adapt to, and prepare for the related changes. Based on a survey of related publications between 1990 and 2015, the terms used for literature selection reflect three aspects--the components of infectious diseases, climate variables, and selected infectious diseases. Humans' vulnerability to the potential health impacts by climate change is evident in literature. As an active agent, human beings may control the related health effects that may be effectively controlled through adopting proactive measures, including better understanding of the climate change patterns and of the compound disease-specific health effects, and effective allocation of technologies and resources to promote healthy lifestyles and public awareness. The following adaptation measures are recommended: 1) to go beyond empirical observations of the association between climate change and infectious diseases and develop more scientific explanations, 2) to improve the prediction of spatial-temporal process of climate change and the associated shifts in infectious diseases at various spatial and temporal scales, and 3) to establish locally effective early warning systems for the health effects of predicated climate change. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Probiotic and technological properties of Lactobacillus spp. strains from the human stomach in the search for potential candidates against gastric microbial dysbiosis

    OpenAIRE

    Delgado, Susana; Leite, Analy M. O.; Ruas-Madiedo, Patricia; Mayo, Baltasar

    2015-01-01

    This work characterizes a set of lactobacilli strains isolated from the stomach of healthy humans that might serve as probiotic cultures. Ten different strains were recognized by rep-PCR and PFGE fingerprinting among 19 isolates from gastric biopsies and stomach juice samples. These strains belonged to five species, Lactobacillus gasseri (3), Lactobacillus reuteri (2), Lactobacillus vaginalis (2), Lactobacillus fermentum (2) and Lactobacillus casei (1). All ten strains were subjected to a ser...

  17. Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender

    International Nuclear Information System (INIS)

    Grybaeck, P.; Naeslund, E.; Hellstroem, P.M.; Jacobsson, H.; Backman, L.

    1996-01-01

    It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies. (orig.). With 6 figs., 4 tabs

  18. Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender

    Energy Technology Data Exchange (ETDEWEB)

    Grybaeck, P. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden); Naeslund, E. [Department of Surgery, Karolinska Institute at Danderyd Hospital, Stockholm (Sweden); Hellstroem, P.M. [Department of Internal Medicine, Karolinska Hospital, Stockholm (Sweden); Jacobsson, H. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden)]|[Department of Nuclear Medicine, Karolinska Hospital, Stockholm (Sweden); Backman, L. [Department of Surgery, Karolinska Institute at Danderyd Hospital, Stockholm (Sweden)

    1996-12-01

    It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies. (orig.). With 6 figs., 4 tabs.

  19. Natural Gastric Infection with Helicobacter pylori in Monkeys: A Model for Spiral Bacteria Infection in Humans

    Science.gov (United States)

    1994-01-01

    Schoenknecht FD. Campytobacter pyloni isolated of H. pyfon from human faeces . Lancet 1992:340:1194-1195. from the stomachg of the monkey Maca nemestnina. J Clin...Helicobacter pylori in Monkeys: A Model for Spiral Bacteria Infection in Humans ANDRE DUBOIS,*’t NANCY FIALA,*’` LILLIE M. HEMAN-ACKAH,% E. SUSAN DRAZEK...model for Helicobacter pyloi Infection In humans . The of this infection has been primarily based on identifica- aim of this study was to examine the

  20. Survival of Helicobacter pylori in gastric acidic territory.

    Science.gov (United States)

    Ansari, Shamshul; Yamaoka, Yoshio

    2017-08-01

    Helicobacter pylori is well adapted to colonize the epithelial surface of the human gastric mucosa and can cause persistent infections. In order to infect the gastric mucosa, it has to survive in the gastric acidic pH. This organism has well developed mechanisms to neutralize the effects of acidic pH. This review article was designed to summarize the various functional and molecular aspects by which the bacterium can combat and survive the gastric acidic pH in order to establish the persistent infections. We used the keywords (acid acclimation, gastric acidic environment, H. pylori and survival) in combination or alone for pubmed search of recent scientific literatures. One hundred and forty one papers published between 1989 and 2016 were sorted out. The articles published with only abstracts, other than in English language, case reports and reviews were excluded. Many literatures describing the role of several factors in acid survival were found. Recently, the role of several other factors has been claimed to participate in acid survival. In conclusion, this organism has well characterized mechanisms for acid survival. © 2017 John Wiley & Sons Ltd.

  1. Detection of sentinel nodes by a novel red-fluorescent dye, ATX-S10Na (II), in an orthotopic xenograft rat model of human gastric carcinoma.

    Science.gov (United States)

    Koyama, Tomoki; Tsubota, Akihito; Nariai, Koichi; Yoshikawa, Tetsuya; Mitsunaga, Makoto; Sumi, Makoto; Nimura, Hiroshi; Yanaga, Katsuhiko; Yumoto, Yoko; Mabashi, Yasuo; Takahashi, Hiroshi

    2007-01-01

    We developed a new imaging system to detect sentinel nodes (SNs) using a novel fluorescent tracer, ATX-S10Na(II), and investigated its usefulness in an animal model. Human gastric carcinoma cells were implanted orthotopically into nude rats. ATX-S10Na(II) was injected subserosally into the primary tumor lesion, and visualized by a fluorescence spectro-laparoscope. Presence of tumor cells in lymph nodes (LNs) was determined by RT-PCR specific for human beta-actin. Injection of ATX-S10Na(II) was successful in 27 tumor-bearing rats. A red fluorescence was incorporated into the left gastric and hepatic LNs in 25 and 2 rats, respectively. Of note, human beta-actin was detected in most of these LNs. Fluorescence was not detected in LNs that did not contain cancer. ATX-S10Na(II) is useful for the detection of cancer-containing SNs in an animal model of gastric carcinoma, and may serve as a novel tracer in SN navigation surgery. (c) 2006 Wiley-Liss, Inc.

  2. Gastric schwannoma.

    Science.gov (United States)

    Lin, Chen-Sung; Hsu, Han-Shui; Tsai, Chien-Ho; Li, Wing-Yin; Huang, Min-Hsiung

    2004-11-01

    Gastrointestinal mesenchymal tumors are a group of tumors originated from the mesenchymal stem cells of the gastrointestinal tract, consisting of gastrointestinal stromal tumors (GIST), leiomyomas or leiomyosarcomas or schwannomas. Gastric schwannoma is a very rare gastrointestinal mesenchymal tumor, which represents only 0.2% of all gastric tumors and 4% of all benign gastric neoplasms. We report a 24-year-old girl who suffered from an episode of upper gastrointestinal bleeding. The endoscopic examination showed a round submucosal tumor with a central ulceration and bleeding over the high body of the stomach. Surgical resection of the tumor was performed. The pathological examination revealed a picture of spindle cell tumor that was strongly positive for S-100 protein stain, and non-reactive for CD34, CD117, actin, HHF-35, desmin, melan-A and HMB-45, consistent with gastric schwannoma. The literature is reviewed.

  3. Body weight setpoint, metabolic adaption and human starvation.

    Science.gov (United States)

    Kozusko, F P

    2001-03-01

    A biological setpoint for fatness has been proposed in the medical literature. This body weight setpoint functions as a point of stable equilibrium. In an underfed state, with resulting weight loss, the body will reduce the relative energy expenditure by metabolic adaption which reduces the rate of weight loss. Previous mathematical models of energy expenditure and weight loss dynamics have not addressed this setpoint mechanism. The setpoint model has been proposed to quantify this biological process and is unique in predicting energy expenditure during weight loss as a function of the setpoint fat-free mass ratio and setpoint energy expenditure, eliminating the various controlling characteristics such as age, gender and heredity. The model is applied to the seminal Minnesota human semistarvation experiment and is used to predict weight vs time on an individual basis and the caloric requirements for weight maintenance at the reduced weight. Comparison is made with the Harris-Benedict equations and the Brody-Kleiber (W3/4) law.

  4. Optical techniques to understand biofunctional adaptation in human dentine

    Science.gov (United States)

    Kishen, Anil; Asundi, Anand K.

    2004-08-01

    Human tooth structure in the oral environment is subjected to mechanical forces and thermal fluctuations. Dentine, the major component of the tooth structure, is a bio-composite, mainly composed of a highly mineralized phase and a collagenous phase. When subjected to changes in load and/or temperature, dentine will experience stresses and strains distribution within their structure. Though such effects are found to cause deleterious effects on artificial dental restorations, biological structures such as dentine seem to posses an inherent ability to adapt to functional thermo-mechanical loads. Optical techniques enable visualization and quantification of deformation, strain and stress on dental structures and provide a better understanding on their thermo-mechanical response. In this study 2-dimensional and 3-dimensional digital photoelasticity, digital moiré interferometry and Electronic Speckle Pattern Interferometry (ESPI) are all shown to be quite promising in this application. This paper will highlight these techniques and the corresponding applications. These experiments will aid in designing and development of better dental restorations and implants in clinical practice.

  5. Propofol inhibits hypoxia/reoxygenation-induced human gastric epithelial cell injury by suppressing the Toll-like receptor 4 pathway

    Directory of Open Access Journals (Sweden)

    Jiao-Li Zhang

    2013-06-01

    Full Text Available This study aimed to investigate the role of the Toll-like receptor 4 (TLR4 pathway in normal human gastric epithelial (GES-1 cells under hypoxia/reoxygenation (H/R in vitro, and the effect of propofol on injured GES-1 cells as well as its possible mechanism. Before H/R induction, GES-1 cells were preconditioned with fat emulsion, propofol, or epigallocatechin gallate. Then cell viability, cell apoptosis, and related molecules in the cells were analyzed under experimental conditions. We found that propofol 50 μmol/L markedly inhibited the H/R injury under hypoxia 1.5 h/reoxygenation 2 hours by promoting GES-1 cell viability and decreasing cell apoptosis. The TLR4 signal may be involved in the protective effect of propofol against H/R injury. The malondialdehyde contents and superoxide dismutase activities were recovered under propofol preconditioning. In summary, propofol preconditioning may exert a protective effect on H/R injury in GES-1 cells and the mechanism may be via inhibition of the activated TLR4 signal under H/R conditions.

  6. Decreased expression of microRNA let-7i and its association with chemotherapeutic response in human gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Kun

    2012-10-01

    Full Text Available Abstract Background MicroRNA let-7i has been proven to be down-regulated in many human malignancies and correlated with tumor progression and anticancer drug resistance. Our study aims to characterize the contribution of miRNA let-7i to the initiation and malignant progression of locally advanced gastric cancer (LAGC, and evaluate its possible value in neoadjuvant chemotherapeutic efficacy prediction. Methods Eighty-six previously untreated LAGC patients who underwent preoperative chemotherapy and radical resection were included in our study. Let-7i expression was examined for pairs of cancer tissues and corresponding normal adjacent tissues (NATs, using quantitative RT-PCR. The relationship of let-7i level to clinicopathological characteristics, pathologic tumor regression grades after chemotherapy, and overall survival (OS was also investigated. Results Let-7i was significantly down-regulated in most tumor tissues (78/86: 91% compared with paired NATs (P P =0.024 independently of other clinicopathological factors, including tumor node metastasis (TNM stage (HR = 3.226, P = 0.013, depth of infiltration (HR = 4.167, P P = 0.037. Conclusions These findings indicate that let-7i may be a good candidate for use a therapeutic target and a potential tissue marker for the prediction of chemotherapeutic sensitivity and prognosis in LAGC patients.

  7. Non-detection of Epstein-Barr virus and human papillomavirus in a region of high gastric cancer risk indicates a lack of a role for these viruses in gastric carcinomas

    Directory of Open Access Journals (Sweden)

    Xiao-yan Yuan

    2013-01-01

    Full Text Available Gastric mucosa tissue was collected from patients with gastroduodenal diseases in a region of norrteastern China showing a high risk of gastric cancer incidence. The presence of EBV and HPV were assayed to investigate the relationship between gastric carcinomas and virus infection. Neither EBV nor HPV DNA was detected in tissue from the patients. The role of EBV and HPV in gastric cancer is not well understood and still needs to be clarified.

  8. Time course of arterial vascular adaptations to inactivity and paralyses in humans.

    NARCIS (Netherlands)

    Groot, P.C.E. de; Kuppevelt, D. van; Pons, C.; Snoek, G.V.E.; Woude, L.H.V. van der; Hopman, M.T.E.

    2003-01-01

    PURPOSE: The aim of the present study was to assess the time course of vascular adaptations to inactivity and paralyses in humans. The spinal cord-injured (SCI) population offers a unique "human model of nature" to assess peripheral vascular adaptations and its time course to extreme inactivity and

  9. Time course of arterial vascular adaptations to inactivity and paralyses in humans

    NARCIS (Netherlands)

    de Groot, P.C.E.; van Kuppevelt, D.; Pons, C.; van der Woude, L.H.V.; Hopman, M.T.E.

    2003-01-01

    Purpose: The aim of the present study was to assess the time course of vascular adaptations to inactivity and paralyses in humans. The spinal cord-injured (SCI) population offers a unique "human model of nature" to assess peripheral vascular adaptations and its time course to extreme inactivity and

  10. Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming.

    Science.gov (United States)

    Hanna, Elizabeth G; Tait, Peter W

    2015-07-15

    Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses.

  11. Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming

    Directory of Open Access Journals (Sweden)

    Elizabeth G. Hanna

    2015-07-01

    Full Text Available Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses.

  12. Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming

    Science.gov (United States)

    Hanna, Elizabeth G.; Tait, Peter W.

    2015-01-01

    Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses. PMID:26184272

  13. Survival of lactic acid bacteria from fermented milks in an in vitro digestion model exploiting sequential incubation in human gastric and duodenum juice.

    Science.gov (United States)

    Faye, T; Tamburello, A; Vegarud, G E; Skeie, S

    2012-02-01

    In the present study, the survival of 9 lactic acid bacteria (5 Lactococcus strains, 3 Lactobacillus strains, and 1 strain of Enterococcus hirae), was investigated in vitro under conditions similar to human digestion using human gastric and duodenal juices. The tolerance of the bacteria was also tested with traditional methods using acidic conditions and bile salts. The strains were subjected to a model digestive system comprising sequential incubation in human gastric and duodenal juices, in a 2-step digestion assay at 37°C, simulating the human upper gastrointestinal tract with human gastric juices at pH 2.5 and human duodenal juices at pH 7. The bacterial strains were tested either as washed cells from culture media or in fermented milk. The initial in vitro testing in acid and bile salts showed that Lactobacillus strains and the E. hirae strain displayed a significantly higher acid tolerance than the lactococci. The lactobacilli and the Enterococcus numbers increased, whereas the lactococci decreased at least 1 log during the bile salt treatment. The Lactobacillus strains showed the highest survival rate in the model digestive system when washed bacterial cultures were used with a minor log reduction, whereas the lactococci numbers were reduced by at least log 4. However, when using fermented milks in the model digestion system it was demonstrated that the Enterococcus strain and 2 strains of Lactococcus lactis ssp. cremoris benefited significantly from the presence of the fermented milk as food matrix, with log numbers >log 7 and 5, respectively, after digestion of the fermented milk. The analyses reported comprise a comprehensive in vitro testing regimen suitable for evaluation of the survival of candidate probiotic bacteria in human digestion as an initial prescreen to clinical trials. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Gastric digestion of α-lactalbumin in adult human subjects using capsule endoscopy and nasogastric tube sampling.

    Science.gov (United States)

    Sullivan, Louise M; Kehoe, Joseph J; Barry, Lillian; Buckley, Martin J M; Shanahan, Fergus; Mok, K H; Brodkorb, André

    2014-08-28

    In the present study, structural changes in the milk protein α-lactalbumin (α-LA) and its proteolysis were investigated for the potential formation of protein-fatty acid complexes during in vivo gastric digestion. Capsule endoscopy allowed visualisation of the digestion of the test drinks, with nasogastric tubes allowing sampling of the gastric contents. A total of ten healthy volunteers had nasogastric tubes inserted into the stomach and ingested test drinks containing 50 g/l of sucrose and 25 g/l of α-LA with and without 4 g/l of oleic acid (OA). The samples of gastric contents were collected for analysis at 3 min intervals. The results revealed a rapid decrease in the pH of the stomach of the subjects. The fasting pH of 2·31 (SD 1·19) increased to a pH maxima of pH 6·54 (SD 0·29) after ingestion, with a subsequent decrease to pH 2·22 (SD 1·91) after 21 min (n 8). Fluorescence spectroscopy and Fourier transform IR spectroscopy revealed partial protein unfolding, coinciding with the decrease in pH below the isoelectric point of α-LA. The activity of pepsin in the fasting state was found to be 39 (SD 12) units/ml of gastric juice. Rapid digestion of the protein occurred: after 15 min, no native protein was detected using SDS-PAGE; HPLC revealed the presence of small amounts of native protein after 24 min of gastric digestion. Mirocam® capsule endoscopy imaging and video clips (see the online supplementary material) revealed that gastric peristalsis resulted in a heterogeneous mixture during gastric digestion. Unfolding of α-LA was observed during gastric transit; however, there was no evidence of a cytotoxic complex being formed between α-LA and OA.

  15. Stimulation of growth of the human gastric pathogen Helicobacter pylori by atmospheric level of oxygen under high carbon dioxide tension

    Directory of Open Access Journals (Sweden)

    Lee Na

    2011-05-01

    Full Text Available Abstract Background Helicobacter pylori (Hp, a human pathogen that is associated with gastritis, peptic ulcer, and gastric cancer, has been considered a microaerophile, but there is no general consensus about its specific O2 requirements. A clear understanding of Hp physiology is needed to elucidate the pathogenic mechanism(s of Hp infection. Results We cultured Hp under a range of O2 levels with or without 10% CO2 and evaluated growth profiles, morphology, intracellular pH, and energy metabolism. We found that, in the presence of 10% CO2, the normal atmospheric level of O2 inhibited Hp growth at low density but stimulated growth at a higher density. Field emission scanning electron microscopy and fluorescence microscopy of Hp cells cultured under 20% O2 tension revealed live spiral-shaped bacteria with outer membrane vesicles on a rugged cell surface, which became smooth during the stationary phase. Fermentation products including acetate, lactate, and succinate were detected in cell culture media grown under microaerobic conditions, but not under the aerobic condition. CO2 deprivation for less than 24 h did not markedly change cytoplasmic or periplasmic pH, suggesting that cellular pH homeostasis alone cannot account for the capnophilic nature of Hp. Further, CO2 deprivation significantly increased intracellular levels of ppGpp and ATP but significantly decreased cellular mRNA levels, suggesting induction of the stringent response. Conclusions We conclude, unlike previous reports, that H. pylori may be a capnophilic aerobe whose growth is promoted by atmospheric oxygen levels in the presence of 10% CO2. Our data also suggest that buffering of intracellular pH alone cannot account for the CO2 requirement of H. pylori and that CO2 deprivation initiates the stringent response in H. pylori. Our findings may provide new insight into the physiology of this fastidious human pathogen.

  16. Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery

    Science.gov (United States)

    Oestricker, Lauren; Wallendorf, Michael J; Patterson, Bruce W.; Reeds, Dominic N.; Wice, Burton M

    2016-01-01

    Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of enteroendocrine cells located in the proximal small intestine. Many effects of Xen are mediated by neurotensin receptor-1 on neurons. In healthy humans with normal glucose tolerance (NGT), Xen administration causes diarrhea and inhibits postprandial glucagon-like peptide-1 (GLP-1) release but not insulin secretion. This study determines i) if Xen has similar effects in humans with Roux-en-Y gastric bypass (RYGB) and ii) whether neural pathways potentially mediate effects of Xen on glucose homeostasis. Eight females with RYGB and no history of type 2 diabetes received infusions with 0, 4 or 12 pmoles Xen/kg/min with liquid meals on separate occasions. Plasma glucose and gastrointestinal hormone levels were measured and insulin secretion rates calculated. Pancreatic polypeptide and neuropeptide Y levels were surrogate markers for parasympathetic input to islets and sympathetic tone, respectively. Responses were compared to those in well-matched non-surgical participants with NGT from our earlier study. Xen similarly increased pancreatic polypeptide and neuropeptide Y responses in patients with and without RYGB. In contrast, the ability of Xen to inhibit GLP-1 release and cause diarrhea was severely blunted in patients with RYGB. With RYGB, Xen had no statistically significant effect on glucose, insulin secretory, GLP-1, glucose-dependent insulinotropic peptide, and glucagon responses. However, insulin and glucose-dependent insulinotropic peptide secretion preceded GLP-1 release suggesting circulating GLP-1 does not mediate exaggerated insulin release after RYGB. Thus, Xen has unmasked neural circuits to the distal gut that inhibit GLP-1 secretion, cause diarrhea, and are altered by RYGB. PMID:27288245

  17. Altered phenotypic and functional characteristics of CD3+CD56+ NKT-like cells in human gastric cancer.

    Science.gov (United States)

    Peng, Liu-Sheng; Mao, Fang-Yuan; Zhao, Yong-Liang; Wang, Ting-Ting; Chen, Na; Zhang, Jin-Yu; Cheng, Ping; Li, Wen-Hua; Lv, Yi-Pin; Teng, Yong-Sheng; Guo, Gang; Luo, Ping; Chen, Weisan; Zou, Quan-Ming; Zhuang, Yuan

    2016-08-23

    CD3+CD56+ natural killer T (NKT)-like cells are a group of CD3+ T cells sharing characteristics of NK and T cells and constitute a major component of host anti-tumor immune response in human cancer. However, the nature, function and clinical relevance of CD3+CD56+ NKT-like cells in human gastric cancer (GC) remain unclear. In this study, we showed that the frequencies of CD3+CD56+NKT-like cells in GC tumors were significantly decreased and low levels of tumor-infiltrating CD3+CD56+ NKT-like cells were positively correlated with poor survival and disease progression. Most CD3+CD56+NKT-like cells in GC tumors were CD45RA-CD27+/- central/effector-memory cells with decreased activity and lower expression levels of CD69, NKG2D and DNAM-1 than those in non-tumor tissues. We further observed that tumor-infiltrating CD3+CD56+ NKT-like cells had impaired effector function as shown by decreased IFN-γ, TNF-α, granzyme B and Ki-67 expression. Moreover, in vitro studies showed that soluble factors released from GC tumors could induce the functional impairment of CD3+CD56+ NKT-like cells. Collectively, our data indicate that decreased tumor-infiltrating CD3+CD56+ NKT-like cells with impaired effector function are associated with tumor progression and poor survival of GC patients, which may contribute to immune escape of GC.

  18. Pan-Genome Analysis of Human Gastric Pathogen H. pylori: Comparative Genomics and Pathogenomics Approaches to Identify Regions Associated with Pathogenicity and Prediction of Potential Core Therapeutic Targets

    DEFF Research Database (Denmark)

    Ali, Amjad; Naz, Anam; Soares, Siomar C.

    2015-01-01

    Helicobacter pylori is a human gastric pathogen implicated as the major cause of peptic ulcer and second leading cause of gastric cancer (similar to 70%) around the world. Conversely, an increased resistance to antibiotics and hindrances in the development of vaccines against H. pylori are observed......-genome approach; the predicted conserved gene families (1,193) constitute similar to 77% of the average H. pylori genome and 45% of the global gene repertoire of the species. Reverse vaccinology strategies have been adopted to identify and narrow down the potential core-immunogenic candidates. Total of 28 nonhost...... homolog proteins were characterized as universal therapeutic targets against H. pylori based on their functional annotation and protein-protein interaction. Finally, pathogenomics and genome plasticity analysis revealed 3 highly conserved and 2 highly variable putative pathogenicity islands in all...

  19. Developmental evidence for obstetric adaptation of the human female pelvis.

    Science.gov (United States)

    Huseynov, Alik; Zollikofer, Christoph P E; Coudyzer, Walter; Gascho, Dominic; Kellenberger, Christian; Hinzpeter, Ricarda; Ponce de León, Marcia S

    2016-05-10

    The bony pelvis of adult humans exhibits marked sexual dimorphism, which is traditionally interpreted in the framework of the "obstetrical dilemma" hypothesis: Giving birth to large-brained/large-bodied babies requires a wide pelvis, whereas efficient bipedal locomotion requires a narrow pelvis. This hypothesis has been challenged recently on biomechanical, metabolic, and biocultural grounds, so that it remains unclear which factors are responsible for sex-specific differences in adult pelvic morphology. Here we address this issue from a developmental perspective. We use methods of biomedical imaging and geometric morphometrics to analyze changes in pelvic morphology from late fetal stages to adulthood in a known-age/known-sex forensic/clinical sample. Results show that, until puberty, female and male pelves exhibit only moderate sexual dimorphism and follow largely similar developmental trajectories. With the onset of puberty, however, the female trajectory diverges substantially from the common course, resulting in rapid expansion of obstetrically relevant pelvic dimensions up to the age of 25-30 y. From 40 y onward females resume a mode of pelvic development similar to males, resulting in significant reduction of obstetric dimensions. This complex developmental trajectory is likely linked to the pubertal rise and premenopausal fall of estradiol levels and results in the obstetrically most adequate pelvic morphology during the time of maximum female fertility. The evidence that hormones mediate female pelvic development and morphology supports the view that solutions of the obstetrical dilemma depend not only on selection and adaptation but also on developmental plasticity as a response to ecological/nutritional factors during a female's lifetime.

  20. A Software Environment for an Adaptive Human-Aware Software Agent Supporting Attention-Demanding Tasks

    NARCIS (Netherlands)

    Bosse, T.; Memon, Z.A.; Oorburg, R.; Umair, M.; Treur, J.; de Vos, M.

    2011-01-01

    This paper presents a software environment providing human-aware ambient support for a human performing a task that demands substantial amounts of attention. The agent obtains human attention-awareness in an adaptive manner by use of a dynamical model of human attention, gaze sensoring by an

  1. Gastric and intestinal myiasis due to Ornidia obesa (Diptera: Syrphidae in humans. First report in colombia

    Directory of Open Access Journals (Sweden)

    Gustavo López V

    2017-01-01

    Full Text Available Myasis are parasitic infestations of animals and humans tissues and is caused by fly larvae. This kind of infestation has Public Health importance. In the Colombian biomedical literature the reports about myiasis in humans are scarce. In this paper, we report two cases of patients with gastrointestinal myiasis where the etiologic agents involved were Ornidia obesa and Ornidia sp (Diptera: Syrphidae. The taxonomic identification of the larvae was done at the Colombian Institute of Tropical Medicine and taxonomic confirmation was done at the laboratory of medicine veterinary and Zoology of Sao Pablo University. These two cases of myiasis are of first report in Colombia

  2. Adaptive Gait Pattern Generation of Biped Robot based on Human's Gait Pattern Analysis

    OpenAIRE

    Seungsuk Ha; Youngjoon Han; Hernsoo Hahn

    2007-01-01

    This paper proposes a method of adaptively generating a gait pattern of biped robot. The gait synthesis is based on human's gait pattern analysis. The proposed method can easily be applied to generate the natural and stable gait pattern of any biped robot. To analyze the human's gait pattern, sequential images of the human's gait on the sagittal plane are acquired from which the gait control values are extracted. The gait pattern of biped robot on the sagittal plane is adaptively generated by...

  3. Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

    Directory of Open Access Journals (Sweden)

    E.M. Lima

    2004-12-01

    Full Text Available Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0 originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.

  4. Synergistic inhibitory effect of berberine and d-limonene on human gastric carcinoma cell line MGC803.

    Science.gov (United States)

    Zhang, Xiu-Zhen; Wang, Ling; Liu, Dong-Wu; Tang, Guang-Yan; Zhang, Hong-Yu

    2014-09-01

    This study aims at evaluating the anticancer effects of berberine hydrochloride (berberine) and d-limonene, alone and in combination, on human gastric carcinoma cell line MGC803 to determine whether berberine and d-limonene work synergistically and elucidate their mechanisms. MGC803 cells were treated with berberine and d-limonene, alone and in combination, for 24-48 h. The inhibitory effects of these drugs on growth were determined by MTT assay. The combination index and drug reduction index were calculated with the Chou-Talalay method based on the median-effect principle. Flow cytometry and laser scanning confocal microscopy were employed to evaluate the effects of both drugs on cell-cycle perturbation and apoptosis, generation of reactive oxygen species (ROS), mitochondrial membrane potential, and expression of Bcl-2 and caspase-3 in MGC803 cells. Berberine or d-limonene alone can inhibit the growth of MGC803 cells in a dose- and time-dependent manner. Berberine and d-limonene at a combination ratio of 1:4 exhibited a synergistic effect on anti-MGC803 cells. The two drugs distinctly induced intracellular ROS generation, reduced the mitochondrial transmembrane potential (ΔΨm), enhanced the expression of caspase-3, and decreased the expression of Bcl-2. The combination of berberine and d-limonene showed more remarkable effects compared with drugs used singly in MGC803 cells. The combination of berberine and d-limonene exerted synergistic anticancer effects on MGC803 cells by cell-cycle arrest, ROS production, and apoptosis induction through the mitochondria-mediated intrinsic pathway.

  5. Killing effect of peripheral blood mononuclear cells irradiated by γ ray on human gastric cancer MKN-28 cell

    International Nuclear Information System (INIS)

    Wu Daocheng; Zhang Xianqing; Mu Shijie; Liu Zhongxiang; Xia Aijun; Huang Xiaofeng; An Qunxing

    2007-01-01

    Objective: To observe the killing effect of peripheral blood mononuclear cells (PBMCs) irradiated by γ ray on cultured human gastric cancer cell line MKN-28. Methods: The experiment were divided into MKN-28 tumor cell control group, PBMCs groups and MKN-28 cells with irradiated or non-irradiated PBMCs co-culture groups. Radidation dosage were from 0.5 to 3 Gy, acridine orange/ethidium bromide (AO/EB) staining were used to observe the kill effect of PBMCs on tumor cells in different period. Results: After culture for 144h, the dead cells of several dosage irradiated PBMCs are much more than those of non-irradiated PBMCs group. At 240 hours of culture, the alive PBMCs deareses in number in both irradiated and non-irradiared groups, but decreases in radiated groups are more obvious. After culture for 72 h in the co-cultured groups, the difference is not evident among all radiation dosage groups. After 96-240 h of co-culture, the killing effect of 0.5-2Gy irradiated PBMCs on tumor cells is very strong, especially in 1Gy group, but the killing effect of PBMCs irradiated by 2.5-3Gy on tumor cells were weaker than that of 0.5-2Gy irradiated groups. At 240 hours co-cultured groups irradiated by 2.5-3Gy, tumor cells still survive and proliferate. Conclusion: Gamma ray irradiation have killing effect to some PBMCs. The cytocidal effect of PBMCs irradiated by 0.5-2Gy on tumor cells were increased. Chemotaxis and cytocidal effect of tumor cells to postirradiated PBMCs were also found. The killing effect of PBMCs irradiated by 2.5 and 3 Gy on tumor cells were restrained. (authors)

  6. WISP-2 in human gastric cancer and its potential metastatic suppressor role in gastric cancer cells mediated by JNK and PLC-γ pathways.

    Science.gov (United States)

    Ji, Jiafu; Jia, Shuqin; Jia, Yongning; Ji, Ke; Hargest, Rachel; Jiang, Wen G

    2015-09-15

    It has recently been shown that WISP proteins (Wnt-inducted secreted proteins), a group of intra- and extra-cellular regulatory proteins, have been implicated in the initiation and progression of a variety of tumour types including colorectal and breast cancer. However, the role of WISP proteins in gastric cancer (GC) cells and their clinical implications have not yet been elucidated. The expression of WISP molecules in a cohort of GC patients was analysed using real-time quantitative PCR and immunohistochemistry. The expression of a panel of recognised epithelial-mesenchymal transition (EMT) markers was quantified using Q-PCR in paired tumour and normal tissues. WISP-2 knockdown (kd) sublines using ribozyme transgenes were created in the GC cell lines AGS and HGC27. Subsequently, several biological functions, including cell growth, adhesion, migration and invasion, were studied. Potential pathways for the interaction of EMT, extracellular matrix and MMP were evaluated. Overexpression of WISP-2 was detected in GC and significantly correlated with early tumour node-metastasis staging, differentiation status and positively correlated with overall survival and disease-free survival of the patients. WISP-2 expression was inversely correlated with that of Twist and Slug in paired samples. Kd of WISP-2 expression promoted the proliferation, migration and invasion of GC cells. WISP-2 suppressed GC cell metastasis through reversing EMT and suppressing the expression and activity of MMP9 and MMP2 via JNK and ERK. Cell motility analysis indicated that WISP-2 kd contributed to GC cells' motility and can be attenuated by PLC-γ and JNK small inhibitors. Increased expression of WISP-2 in GC is positively correlated with favourable clinical features and the survival of patients with GC and is a negative regulator of growth, migration and invasion in GC cells. These findings suggest that WISP-2 is a potential tumour suppressor in GC.

  7. Adaptation.

    Science.gov (United States)

    Broom, Donald M

    2006-01-01

    The term adaptation is used in biology in three different ways. It may refer to changes which occur at the cell and organ level, or at the individual level, or at the level of gene action and evolutionary processes. Adaptation by cells, especially nerve cells helps in: communication within the body, the distinguishing of stimuli, the avoidance of overload and the conservation of energy. The time course and complexity of these mechanisms varies. Adaptive characters of organisms, including adaptive behaviours, increase fitness so this adaptation is evolutionary. The major part of this paper concerns adaptation by individuals and its relationships to welfare. In complex animals, feed forward control is widely used. Individuals predict problems and adapt by acting before the environmental effect is substantial. Much of adaptation involves brain control and animals have a set of needs, located in the brain and acting largely via motivational mechanisms, to regulate life. Needs may be for resources but are also for actions and stimuli which are part of the mechanism which has evolved to obtain the resources. Hence pigs do not just need food but need to be able to carry out actions like rooting in earth or manipulating materials which are part of foraging behaviour. The welfare of an individual is its state as regards its attempts to cope with its environment. This state includes various adaptive mechanisms including feelings and those which cope with disease. The part of welfare which is concerned with coping with pathology is health. Disease, which implies some significant effect of pathology, always results in poor welfare. Welfare varies over a range from very good, when adaptation is effective and there are feelings of pleasure or contentment, to very poor. A key point concerning the concept of individual adaptation in relation to welfare is that welfare may be good or poor while adaptation is occurring. Some adaptation is very easy and energetically cheap and

  8. Human case of gastric infection by a fourth larval stage of Pseudoterranova decipiens (Nematoda, Anisakidae

    Directory of Open Access Journals (Sweden)

    Rubén Mercado

    1997-04-01

    Full Text Available Only three cases of human infection by anisakid nematodes have been reported in Chile since 1976. In the present case, an anisakid worm, identified as a fourth-stage Pseudoterranova decipiens larva, was removed with a gastroendoscopic biopsy clipper from the stomach of a 45 year-old man from southern Chile. The patient, who presented acute epigastric pain and a continuous sensation of having an empty stomach, reported having eaten smoked fish. The worm was fixed in 70% ethanol and cleaned in lactophenol for morphological study. The morphometric characteristics of the worm are described and drawn. Anisakid larvae in fish flesh can be killed by freezing or cooking.

  9. Gastric emptying

    International Nuclear Information System (INIS)

    Bonaz, B.; Hostein, J.; Caravel, J.P.

    1990-01-01

    Gastric emptying (GE) of nutriments is a major function of the stomach. GE disorders are observed after gastric surgery and with various diseases, either of a strictly gastroenterologic kind or interesting other specialities (especially diabetes mellitus). Scintigraphy, which has allowed a better knowledge of GE physiological and pathological mechanisms, has now become the reference method for studying the emptying of solids and liquids. In a near future, it could well have two major applications: a diagnostic approach of functional digestive disorders and an assessment of the various effects of pharmacological drugs with digestive affinity [fr

  10. Gastric cancer

    International Nuclear Information System (INIS)

    Mineur, L.; Jaegle, E.; Pointreau, Y.; Denis, F.

    2010-01-01

    Radio-chemotherapy Gastro-intestinal inter-group study have demonstrated a convincing local control and overall survival benefit. Oncologists and GI workshops have in the present not had a major interest in the radiotherapy treatment of gastric cancer due to a number of factors. Primary because toxicities may be severe, second physicians may have low experience in definition of clinical target volume and in third perioperative chemotherapy is widely used in this indication. In Summary this issue should be used as guides for defining appropriate radiation planning treatment for the adjuvant postoperative therapy of gastric cancer. (authors)

  11. [Gastric tuberculosis].

    Science.gov (United States)

    Oliveira, E; Oliveira, A; Costa, A; Sa, L; Vieira, A; Oliveira, A

    1994-12-01

    A 37 year old woman with duodenal ulcer not responsive to medical treatment was operated. Antrectomy, truncal vagotomy and Bilroth II gastrojejunostomy were performed. The histopathology revealed epithelioid cell granulomas with multinucleated cells and central ceseation, in the gastric side of the pylorus and in three isolated lymph nodes. With Ziehl-Neelsen staining there were multiple acid-fast bacilli. There was no evidence or previous history, personal or familial, or tuberculosis in an other localization. Epidemiology, pathology, diagnosis, and treatment of gastric tuberculosis are discussed according to the literature.

  12. PTSD in the combat veteran: using Roy's Adaptation Model to examine the combat veteran as a human adaptive system.

    Science.gov (United States)

    Nayback, Ann Marie

    2009-05-01

    Posttraumatic stress disorder (PTSD) is the most prevalent mental disorder arising from combat and is poised to be a considerable health risk for our military veterans. To date, there is a paucity of nursing research that examines PTSD in this vulnerable population. The purpose of this article is to demonstrate how Roy's Adaptation Model can be an effective framework for nurses to understand the phenomenon of posttraumatic stress disorder in the combat veteran population. Current research conducted on PTSD across other disciplines is highlighted within the context of Roy's model to elucidate the idea of the combat veteran as a human adaptive system and to identify gaps for future nursing research.

  13. Probiotic and technological properties of Lactobacillus spp. strains from the human stomach in the search for potential candidates against gastric microbial dysbiosis

    Directory of Open Access Journals (Sweden)

    Susana eDelgado

    2015-01-01

    Full Text Available This work characterizes a set of lactobacilli strains isolated from the stomach of healthy humans that might serve as probiotic cultures. Ten different strains were recognized by rep-PCR and PFGE fingerprinting among 19 isolates from gastric biopsies and stomach juice samples. These strains belonged to five species, Lactobacillus gasseri (3, Lactobacillus reuteri (2, Lactobacillus vaginalis (2, Lactobacillus fermentum (2 and Lactobacillus casei (1. All ten strains were subjected to a series of in vitro tests to assess their functional and technological properties, including acid resistance, bile tolerance, adhesion to epithelial gastric cells, production of antimicrobial compounds, inhibition of Helicobacter pylori, antioxidative activity, antibiotic resistance, carbohydrate fermentation, glycosidic activities, and ability to grow in milk. As expected, given their origin, all strains showed good resistance to low pH (3.0, with small reductions in counts after 90 min exposition to this pH. Species- and strain-specific differences were detected in terms of the production of antimicrobials, antagonistic effects towards H. pylori, antioxidative activity and adhesion to gastric epithelial cells. None of the strains showed atypical resistance to a series of 16 antibiotics of clinical and veterinary importance. Two L. reuteri strains were deemed as the most appropriate candidates to be used as potential probiotics against microbial gastric disorders; these showed good survival under gastrointestinal conditions reproduced in vitro, along with strong anti-Helicobacter and antioxidative activities. The two L. reuteri strains further displayed appropriated technological traits for their inclusion as adjunct functional cultures in fermented dairy products.

  14. Combination treatment of all-trans retinoic acid (ATRA) and γ-secretase inhibitor (DAPT) cause growth inhibition and apoptosis induction in the human gastric cancer cell line.

    Science.gov (United States)

    Patrad, Elham; Niapour, Ali; Farassati, Faris; Amani, Mojtaba

    2018-04-01

    Current medication for gastric cancer patients has a low success rate with resistance and side effects. According to recent studies, γ-secretase inhibitors is used as therapeutic drugs in cancer. Moreover, all-trans retinoic acid (ATRA) is a natural compound proposed for the treatment/chemo-prevention of cancers. The aim of this study was to explore the effects of ATRA in combination with N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT) as γ-secretase inhibitor on viability and apoptosis of the AGS and MKN-45 derived from human gastric cancer. AGS and MKN-45 gastric cancer cell lines were treated with different concentrations of ATRA or DAPT alone or ATRA plus DAPT. The viability, death detection and apoptosis of cells was examined by MTT assay and Ethidium bromide/acridine orange staining. The distribution of cells in different phases of cell cycle was also evaluated through flow cytometry analyses. In addition, caspase 3/7 activity and the expression of caspase-3 and bcl-2 were examined. DAPT and ATRA alone decreased gastric cancer cells viability in a concentration dependent manner. The combination of DAPT and ATRA exhibited significant synergistic inhibitory effects. The greater percentage of cells were accumulated in G0/G1 phase of cell cycle in combination treatment. The combination of DAPT and ATRA effectively increased the proportion of apoptotic cells and the level of caspase 3/7 activities compared to single treatment. Moreover, augmented caspase-3 up-regulation and bcl-2 down-regulation were found following combined application of DAPT and ATRA. The combination of DAPT and ATRA led to more reduction in viability and apoptosis in respect to DAPT or ATRA alone in the investigated cell lines.

  15. 13-Acetoxysarcocrassolide Induces Apoptosis on Human Gastric Carcinoma Cells Through Mitochondria-Related Apoptotic Pathways: p38/JNK Activation and PI3K/AKT Suppression

    Directory of Open Access Journals (Sweden)

    Ching-Chyuan Su

    2014-10-01

    Full Text Available 13-acetoxysarcocrassolide (13-AC, an active compound isolated from cultured Formosa soft coral Sarcophyton crassocaule, was found to possess anti-proliferative and apoptosis-inducing activities against AGS (human gastric adenocarcinoma cells gastric carcinoma cells. The anti-tumor effects of 13-AC were determined by MTT assay, colony formation assessment, cell wound-healing assay, TUNEL/4,6-Diamidino-2-phenylindole (DAPI staining, Annexin V-fluorescein isothiocyanate/propidium iodide (PI staining and flow cytometry. 13-AC inhibited the growth and migration of gastric carcinoma cells in a dose-dependent manner and induced both early and late apoptosis as assessed by flow cytometer analysis. 13-AC-induced apoptosis was confirmed through observation of a change in ΔΨm, up-regulated expression levels of Bax and Bad proteins, down-regulated expression levels of Bcl-2, Bcl-xl and Mcl-1 proteins, and the activation of caspase-3, caspase-9, p38 and JNK. Furthermore, inhibition of p38 and JNK activity by pretreatment with SB03580 (a p38-specific inhibitor and SP600125 (a JNK-specific inhibitor led to rescue of the cell cytotoxicity of 13-AC-treated AGS cells, indicating that the p38 and the JNK pathways are also involved in the 13-AC-induced cell apoptosis. Together, these results suggest that 13-AC induces cell apoptosis against gastric cancer cells through triggering of the mitochondrial-dependent apoptotic pathway as well as activation of the p38 and JNK pathways.

  16. Diffuse neonatal gastric infarction

    International Nuclear Information System (INIS)

    Johnson, J.F.; Woisard, K.K.; Cooper, G.L.

    1988-01-01

    Diffuse neonatal gastric infarction can be a devastating complication of invasion of the gastric wall and vessels by fungi colonizing the gastric mucosa. Even in the presence of extensive transmural necrosis, however, the radiographs do not necessarily show evidence of gastric mucosal abnormality. Instead, plain films and positive contrast studies may erroneously suggest a mechanical gastric outlet obstruction. Ancillary evidence of a devitalized viscus in a baby who appears to have complete gastric outlet obstruction should suggest the diagnosis of gastric infarction. (orig.)

  17. Diffuse neonatal gastric infarction

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J.F.; Woisard, K.K.; Cooper, G.L.

    1988-02-01

    Diffuse neonatal gastric infarction can be a devastating complication of invasion of the gastric wall and vessels by fungi colonizing the gastric mucosa. Even in the presence of extensive transmural necrosis, however, the radiographs do not necessarily show evidence of gastric mucosal abnormality. Instead, plain films and positive contrast studies may erroneously suggest a mechanical gastric outlet obstruction. Ancillary evidence of a devitalized viscus in a baby who appears to have complete gastric outlet obstruction should suggest the diagnosis of gastric infarction.

  18. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Rasmussen, S L; Linnet, J

    2004-01-01

    and gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were...... measured using scintigraphic and manometric techniques. Isosorbide dinitrate did not change the area under the curve of gastric retention versus time, and did not influence the frequency of antral contractions as assessed at 15-min intervals or the integrated duodenal motility index, as recorded over...... consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal....

  19. Possible human impacts on adaptive radiation: beak size bimodality in Darwin's finches

    OpenAIRE

    Hendry, Andrew P; Grant, Peter R; Rosemary Grant, B; Ford, Hugh A; Brewer, Mark J; Podos, Jeffrey

    2006-01-01

    Adaptive radiation is facilitated by a rugged adaptive landscape, where fitness peaks correspond to trait values that enhance the use of distinct resources. Different species are thought to occupy the different peaks, with hybrids falling into low-fitness valleys between them. We hypothesize that human activities can smooth adaptive landscapes, increase hybrid fitness and hamper evolutionary diversification. We investigated this possibility by analysing beak size data for 1755 Geospiza fortis...

  20. Adaptive response of human lymphocytes to low dose radiation on DNA synthesis

    International Nuclear Information System (INIS)

    Du Zeji; Su Liaoyuan; Tian Hailin

    1995-01-01

    Human peripheral blood lymphocytes PHA-stimulated in vitro for 24 h were exposed to low dose γ-ray irradiation (adaptive dose), they showed an adaptive response to the inhibition of DNA synthesis by subsequent higher acute doses of γ-ray (challenge dose). At the interval of 24 h between adaptive dose and challenge dose, the most obvious adaptive response induced by low dose irradiation was found. It was also found that the response induced by 1.0 cGy of adaptive dose was more obvious than that by other doses. In the challenge doses range of 1.0∼7.0 Gy, the adaptive response was observed and that 3.0 Gy was more obvious. The adaptive response disappeared with the challenge doses further increased

  1. Human Adaptation to Space: Space Physiology and Countermeasures

    Science.gov (United States)

    Fogarty, Jennifer

    2009-01-01

    This viewgraph presentation reviews human physiological responses to spaceflight, and the countermeasures taken to prevent adverse effects of manned space flight. The topics include: 1) Human Spaceflight Experience; 2) Human Response to Spaceflight; 3) ISS Expeditions 1-16; 4) Countermeasure; and 5) Biomedical Data;

  2. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells

    International Nuclear Information System (INIS)

    Yi, Ho-Keun; Kim, Sun-Young; Hwang, Pyoung-Han; Kim, Chan-Young; Yang, Doo-Hyun; Oh, Youngman; Lee, Dae-Yeol

    2005-01-01

    PTEN is a tumor suppressor gene that is frequently mutated or deleted in a variety of human cancers including human gastric cancer. PTEN functions primarily as a lipid phosphatase and plays a key role in the regulation of the PI3 kinase/Akt pathway, thereby modulating cell proliferation and cell survival. On the other hand, the IGF system plays an important role in cell proliferation and cell survival via the PI3 kinase/Akt and MAP kinase pathways in many cancer cells. To characterize the impact of PTEN on the IGF-IGFR-IGFBP axis in gastric cancer, we overexpressed PTEN using an adenovirus gene transfer system in human gastric adenocarcinoma cells, SNU-484 and SNU-663, which lack PTEN. Overexpression of PTEN inhibited serum-induced as well as IGF-I-induced cell proliferation as compared to control cells. PTEN overexpression resulted in a significant decrease in the expression of IGF-I, -II, and IGF-IR. Interestingly, amongst the six IGFBPs, only IGFBP-3 was upregulated by PTEN, whereas IGFBP-4 and -6 were reduced. The IGFBP-3 promoter activity assay and Western immunoblotting demonstrate that PTEN regulates IGFBP-3 at the transcriptional level. In addition, the PI3 kinase inhibitor, LY294002, upregulates IGFBP-3 expression but downregulates IGF-I and IGF-II, indicating that PTEN controls IGFBP-3 and IGFs by an Akt-dependent pathway. These findings suggest that PTEN may inhibit antiapoptotic IGF actions not only by blocking the IGF-IGFR-induced Akt activity, but also by regulating expression of components of the IGF system, in particular, upregulation of IGFBP-3, which is known to exert antiproliferative effects through IGF-dependent and IGF-independent mechanisms in cancer cells

  3. Pose Estimation and Adaptive Robot Behaviour for Human-Robot Interaction

    DEFF Research Database (Denmark)

    Svenstrup, Mikael; Hansen, Søren Tranberg; Andersen, Hans Jørgen

    2009-01-01

    ’s pose. The resulting pose estimates are used to identify humans who wish to be approached and interacted with. The interaction motion of the robot is based on adaptive potential functions centered around the person that respect the persons social spaces. The method is tested in experiments...... that demonstrate the potential of the combined pose estimation and adaptive potential function approach....

  4. Diversity of the Gastric Microbiota in Thoroughbred Racehorses Having Gastric Ulcer.

    Science.gov (United States)

    Dong, Hee-Jin; Ho, Hungwui; Hwang, Hyeshin; Kim, Yongbaek; Han, Janet; Lee, Inhyung; Cho, Seongbeom

    2016-04-28

    Equine gastric ulcer syndrome is one of the most frequently reported diseases in thoroughbred racehorses. Although several risk factors for the development of gastric ulcers have been widely studied, investigation of microbiological factors has been limited. In this study, the presence of Helicobacter spp. and the gastric microbial communities of thoroughbred racehorses having mild to severe gastric ulcers were investigated. Although Helicobacter spp. were not detected using culture and PCR techniques from 52 gastric biopsies and 52 fecal samples, the genomic sequences of H. pylori and H. ganmani were detected using nextgeneration sequencing techniques from 2 out of 10 representative gastric samples. The gastric microbiota of horses was mainly composed of Firmicutes (50.0%), Proteobacteria (18.7%), Bacteroidetes (14.4%), and Actinobacteria (9.7%), but the proportion of each phylum varied among samples. There was no major difference in microbial composition among samples having mild to severe gastric ulcers. Using phylogenetic analysis, three distinct clusters were observed, and one cluster differed from the other two clusters in the frequency of feeding, amount of water consumption, and type of bedding. To the best of our knowledge, this is the first study to investigate the gastric microbiota of thoroughbred racehorses having gastric ulcer and to evaluate the microbial diversity in relation to the severity of gastric ulcer and management factors. This study is important for further exploration of the gastric microbiota in racehorses and is ultimately applicable to improving animal and human health.

  5. Acute effect of oral sensation of sweetness on celiac artery blood flow and gastric myoelectrical activity in humans.

    Science.gov (United States)

    Eguchi, Kohei; Kashima, Hideaki; Yokota, Akiko; Miura, Kohei; Yamaoka Endo, Masako; Hirano, Harutoyo; Tsuji, Toshio; Fukuba, Yoshiyuki

    2016-05-01

    Little is known about the effect of sweet taste stimulus on gastrointestinal motility and splanchnic blood flow. We examined whether gastric myoelectrical activity and/or celiac artery blood flow (CABF), which perfuses the stomach, are increased following an oral sensation of sweetness. After overnight fasting, 11 subjects rested for 5min and sipped, but not swallowed, one of four solutions for 1min. The fluid was then spat out, and subjects remained at rest for a further 10min. Fluids were approximately 15ml of three glucose solutions (4, 16, or 48%) or distilled water. Subjects completed trials with all four solutions in a randomized order. During each trial, gastric myoelectrical activity and CABF were continuously measured using electrogastrography and pulsed Doppler ultrasonography, respectively. None of the four solutions affected gastric myoelectrical activity. CABF was significantly increased after oral stimuli by all three glucose solutions, but not by water. There were no significant differences in the increments in CABF among the three glucose solutions. These results suggest that a sweet taste stimulus above a certain level of intensity acutely increases CABF during cephalic phase, without augmentation of gastric myoelectrical activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

    2006-01-01

    BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM: ...

  7. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism

    NARCIS (Netherlands)

    Patti, Mary-Elizabeth; Houten, Sander M.; Bianco, Antonio C.; Bernier, Raquel; Larsen, P. Reed; Holst, Jens J.; Badman, Michael K.; Maratos-Flier, Eleftheria; Mun, Edward C.; Pihlajamaki, Jussi; Auwerx, Johan; Goldfine, Allison B.

    2009-01-01

    The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2

  8. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    . Dar es Salaam. Durban. Bloemfontein. Antananarivo. Cape Town. Ifrane ... program strategy. A number of CCAA-supported projects have relevance to other important adaptation-related themes such as disaster preparedness and climate.

  9. Nutrition and human physiological adaptations to space flight

    Science.gov (United States)

    Lane, H. W.; LeBlanc, A. D.; Putcha, L.; Whitson, P. A.

    1993-01-01

    Space flight provides a model for the study of healthy individuals undergoing unique stresses. This review focuses on how physiological adaptations to weightlessness may affect nutrient and food requirements in space. These adaptations include reductions in body water and plasma volume, which affect the renal and cardiovascular systems and thereby fluid and electrolyte requirements. Changes in muscle mass and function may affect requirements for energy, protein and amino acids. Changes in bone mass lead to increased urinary calcium concentrations, which may increase the risk of forming renal stones. Space motion sickness may influence putative changes in gastro-intestinal-hepatic function; neurosensory alterations may affect smell and taste. Some or all of these effects may be ameliorated through the use of specially designed dietary countermeasures.

  10. Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer

    OpenAIRE

    Miyo, Masaaki; Konno, Masamitsu; Nishida, Naohiro; Sueda, Toshinori; Noguchi, Kozo; Matsui, Hidetoshi; Colvin, Hugh; Kawamoto, Koichi; Koseki, Jun; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Gotoh, Noriko; Matsuda, Fumio; Satoh, Taroh

    2016-01-01

    Tumor cells respond to their microenvironment, which can include hypoxia and malnutrition, and adapt their metabolism to survive and grow. Some oncogenes are associated with cancer metabolism via regulation of the related enzymes or transporters. However, the importance of metabolism and precise metabolic effects of oncogenes in colorectal cancer remain unclear. We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions dep...

  11. Influence of age on adaptability of human mastication.

    Science.gov (United States)

    Peyron, Marie-Agnès; Blanc, Olivier; Lund, James P; Woda, Alain

    2004-08-01

    The objective of this work was to study the influence of age on the ability of subjects to adapt mastication to changes in the hardness of foods. The study was carried out on 67 volunteers aged from 25 to 75 yr (29 males, 38 females) who had complete healthy dentitions. Surface electromyograms of the left and right masseter and temporalis muscles were recorded simultaneously with jaw movements using an electromagnetic transducer. Each volunteer was asked to chew and swallow four visco-elastic model foods of different hardness, each presented three times in random order. The number of masticatory cycles, their frequency, and the sum of all electromyographic (EMG) activity in all four muscles were calculated for each masticatory sequence. Multiple linear regression analyses were used to assess the effects of hardness, age, and gender. Hardness was associated to an increase in the mean number of cycles and mean summed EMG activity per sequence. It also increased mean vertical amplitude. Mean vertical amplitude and mean summed EMG activity per sequence were higher in males. These adaptations were present at all ages. Age was associated with an increase of 0.3 cycles per sequence per year of life and with a progressive increase in mean summed EMG activity per sequence. Cycle and opening duration early in the sequence also fell with age. We concluded that although the number of cycles needed to chew a standard piece of food increases progressively with age, the capacity to adapt to changes in the hardness of food is maintained.

  12. Studying of the DNA DSBs repair in the adaptive response of human lymphocytes

    International Nuclear Information System (INIS)

    Wojewodzka, M.; Gradzka, I.; Buraczewska, I.

    2000-01-01

    Human lymphocytes exposed to very low doses of DNA damaging agents may become less sensitive to subsequent higher doses of the DNA damaging agent. This phenomenon is called the adaptive response. The aim of this project was to study the significance of DNA double-strand break (DSBs) repair in the adaptive response of human lymphocytes exposed to ionizing radiation. Human lymphocytes isolated from whole blood and stimulated with hemagglutynin (PHA) were irradiated with adaptive dose (5 cGy of X-rays) and then challenge dose of 2 Gy in case of micronuclei assay and 10 Gy in case of comet assay. The frequency of micronuclei in adapted lymphocytes was about 30% lower than expected for an additive effect of both, adaptive and challenge doses, applied separately. Estimation of DSBs was carried out with the use of single cell gel electrophoresis assay (comet assay) in neutral pH and to complement these results with pulse-field gel electrophoresis (PFGE). The use of both PFGE and comet assay allowed us to suggest that lower damage revealed in the adapted lymphocytes at the chromosomal level was unrelated to initial level of DSBs in DNA. The differences between kinetics of DNA repair in the adapted and non-adapted lymphocytes were not significant. (author)

  13. Effect of climate change on human health and some adaptive ...

    African Journals Online (AJOL)

    The impact of human-induced climate change and ozone depletion are now observed to compromise the sustainability of human development as it threatens the ecological support system on which life depends. Evidences abound to show that there is climate change and ozone layer depletion in the last 2-4 decades.

  14. effect of climate change on human health and some adaptive

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The impact of human-induced climate change and ozone depletion are now observed to compromise the sustainability of human development as it threatens the ecological support system on which life depends. Evidences abound to show that there is climate change and ozone layer depletion in the last 2-4 ...

  15. A Conceptual Framework for Planning Systemic Human Adaptation to Global Warming

    Science.gov (United States)

    Tait, Peter W.; Hanna, Elizabeth G.

    2015-01-01

    Human activity is having multiple, inter-related effects on ecosystems. Greenhouse gas emissions persisting along current trajectories threaten to significantly alter human society. At 0.85 °C of anthropogenic warming, deleterious human impacts are acutely evident. Additional warming of 0.5 °C–1.0 °C from already emitted CO2 will further intensify extreme heat and damaging storm events. Failing to sufficiently address this trend will have a heavy human toll directly and indirectly on health. Along with mitigation efforts, societal adaptation to a warmer world is imperative. Adaptation efforts need to be significantly upscaled to prepare society to lessen the public health effects of rising temperatures. Modifying societal behaviour is inherently complex and presents a major policy challenge. We propose a social systems framework for conceptualizing adaptation that maps out three domains within the adaptation policy landscape: acclimatisation, behavioural adaptation and technological adaptation, which operate at societal and personal levels. We propose that overlaying this framework on a systems approach to societal change planning methods will enhance governments’ capacity and efficacy in strategic planning for adaptation. This conceptual framework provides a policy oriented planning assessment tool that will help planners match interventions to the behaviours being targeted for change. We provide illustrative examples to demonstrate the framework’s application as a planning tool. PMID:26334285

  16. A Conceptual Framework for Planning Systemic Human Adaptation to Global Warming

    Directory of Open Access Journals (Sweden)

    Peter W. Tait

    2015-08-01

    Full Text Available Human activity is having multiple, inter-related effects on ecosystems. Greenhouse gas emissions persisting along current trajectories threaten to significantly alter human society. At 0.85 °C of anthropogenic warming, deleterious human impacts are acutely evident. Additional warming of 0.5 °C–1.0 °C from already emitted CO2 will further intensify extreme heat and damaging storm events. Failing to sufficiently address this trend will have a heavy human toll directly and indirectly on health. Along with mitigation efforts, societal adaptation to a warmer world is imperative. Adaptation efforts need to be significantly upscaled to prepare society to lessen the public health effects of rising temperatures. Modifying societal behaviour is inherently complex and presents a major policy challenge. We propose a social systems framework for conceptualizing adaptation that maps out three domains within the adaptation policy landscape: acclimatisation, behavioural adaptation and technological adaptation, which operate at societal and personal levels. We propose that overlaying this framework on a systems approach to societal change planning methods will enhance governments’ capacity and efficacy in strategic planning for adaptation. This conceptual framework provides a policy oriented planning assessment tool that will help planners match interventions to the behaviours being targeted for change. We provide illustrative examples to demonstrate the framework’s application as a planning tool.

  17. A Conceptual Framework for Planning Systemic Human Adaptation to Global Warming.

    Science.gov (United States)

    Tait, Peter W; Hanna, Elizabeth G

    2015-08-31

    Human activity is having multiple, inter-related effects on ecosystems. Greenhouse gas emissions persisting along current trajectories threaten to significantly alter human society. At 0.85 °C of anthropogenic warming, deleterious human impacts are acutely evident. Additional warming of 0.5 °C-1.0 °C from already emitted CO₂ will further intensify extreme heat and damaging storm events. Failing to sufficiently address this trend will have a heavy human toll directly and indirectly on health. Along with mitigation efforts, societal adaptation to a warmer world is imperative. Adaptation efforts need to be significantly upscaled to prepare society to lessen the public health effects of rising temperatures. Modifying societal behaviour is inherently complex and presents a major policy challenge. We propose a social systems framework for conceptualizing adaptation that maps out three domains within the adaptation policy landscape: acclimatisation, behavioural adaptation and technological adaptation, which operate at societal and personal levels. We propose that overlaying this framework on a systems approach to societal change planning methods will enhance governments' capacity and efficacy in strategic planning for adaptation. This conceptual framework provides a policy oriented planning assessment tool that will help planners match interventions to the behaviours being targeted for change. We provide illustrative examples to demonstrate the framework's application as a planning tool.

  18. Adapt

    Science.gov (United States)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  19. Exploring the physiologic role of human gastroesophageal reflux by analyzing time‐series data from 24‐h gastric and esophageal pH recordings

    OpenAIRE

    Lu, Luo; Mu, John C.; Sloan, Sheldon; Miner, Philip B.; Gardner, Jerry D.

    2014-01-01

    Abstract Our previous finding of a fractal pattern for gastric pH and esophageal pH plus the statistical association of sequential pH values for up to 2 h led to our hypothesis that the fractal pattern encodes information regarding gastric acidity and that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity by influencing gastric secretion of acid or bicarbonate. Under our hypothesis values of gastric pH should provide information regarding...

  20. Comparative Genomics of Helicobacter pylori and the human-derived Helicobacter bizzozeronii CIII-1 strain reveal the molecular basis of the zoonotic nature of non-pylori gastric Helicobacter infections in humans

    Directory of Open Access Journals (Sweden)

    Schott Thomas

    2011-10-01

    Full Text Available Abstract Background The canine Gram-negative Helicobacter bizzozeronii is one of seven species in Helicobacter heilmannii sensu lato that are detected in 0.17-2.3% of the gastric biopsies of human patients with gastric symptoms. At the present, H. bizzozeronii is the only non-pylori gastric Helicobacter sp. cultivated from human patients and is therefore a good alternative model of human gastric Helicobacter disease. We recently sequenced the genome of the H. bizzozeronii human strain CIII-1, isolated in 2008 from a 47-year old Finnish woman suffering from severe dyspeptic symptoms. In this study, we performed a detailed comparative genome analysis with H. pylori, providing new insights into non-pylori Helicobacter infections and the mechanisms of transmission between the primary animal host and humans. Results H. bizzozeronii possesses all the genes necessary for its specialised life in the stomach. However, H. bizzozeronii differs from H. pylori by having a wider metabolic flexibility in terms of its energy sources and electron transport chain. Moreover, H. bizzozeronii harbours a higher number of methyl-accepting chemotaxis proteins, allowing it to respond to a wider spectrum of environmental signals. In this study, H. bizzozeronii has been shown to have high level of genome plasticity. We were able to identify a total of 43 contingency genes, 5 insertion sequences (ISs, 22 mini-IS elements, 1 genomic island and a putative prophage. Although H. bizzozeronii lacks homologues of some of the major H. pylori virulence genes, other candidate virulence factors are present. In particular, we identified a polysaccharide lyase (HBZC1_15820 as a potential new virulence factor of H. bizzozeronii. Conclusions The comparative genome analysis performed in this study increased the knowledge of the biology of gastric Helicobacter species. In particular, we propose the hypothesis that the high metabolic versatility and the ability to react to a range of

  1. Crossing the “Uncanny Valley”: adaptation to cartoon faces can influence perception of human faces

    Science.gov (United States)

    Chen, Haiwen; Russell, Richard; Nakayama, Ken; Livingstone, Margaret

    2013-01-01

    Adaptation can shift what individuals identify to be a prototypical or attractive face. Past work suggests that low-level shape adaptation can affect high-level face processing but is position dependent. Adaptation to distorted images of faces can also affect face processing but only within sub-categories of faces, such as gender, age, and race/ethnicity. This study assesses whether there is a representation of face that is specific to faces (as opposed to all shapes) but general to all kinds of faces (as opposed to subcategories) by testing whether adaptation to one type of face can affect perception of another. Participants were shown cartoon videos containing faces with abnormally large eyes. Using animated videos allowed us to simulate naturalistic exposure and avoid positional shape adaptation. Results suggest that adaptation to cartoon faces with large eyes shifts preferences for human faces toward larger eyes, supporting the existence of general face representations. PMID:20465173

  2. Effect of ionizing radiation on gastric secretion and gastric motility in monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Danquechin Dorval, E.; Mueller, G.P.; Eng, R.R.; Durakovic, A.; Conklin, J.J.; Dubois, A.

    1985-08-01

    The prodromal syndrome of radiation sickness is characterized by nausea and vomiting but the pathophysiology and the treatment of this entity is largely unknown. The authors investigated this problem by determining the effects of ionizing radiation on gastric function with and without administration of the dopamine antagonist domperidone. They measured gastric electrical control activity (waves per minute), fractional emptying rate (percent per minute), acid output (microequivalents per minute), and plasma levels of immunoreactive beta-endorphin. Twelve conscious, chair-adapted rhesus monkeys were studied twice before, once immediately after, and once 2 days after a single 800-cGy (800 rads) /sup 60/Co total body irradiation. In addition to causing vomiting, total body irradiation transiently suppressed gastric electrical control activity, gastric emptying and gastric secretion, while increasing plasma levels of immunoreactive beta-endorphin. Domperidone had no effect on vomiting or gastric function either before or after irradiation, but it significantly increased plasma immunoreactive beta-endorphin.

  3. Effect of ionizing radiation on gastric secretion and gastric motility in monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Dorval, E.D.; Mueller, G.P.; Eng, R.R.; Durakovic, A.; Conklin, J.J.

    1985-08-01

    The prodromal syndrome of radiation sickness is characterized by nausea and vomiting but the pathophysiology and the treatment of this entity is largely unknown. The authors investigated this problem by determining the effects of ionizing radiation on gastric function with and without administration of the dopamine antagonist domperidone. They measured gastric electrical control activity (waves per minute), fractional emptying rate (percent per minute), acid output (microequivalents per minute), and plasma levels of immunoreactive Beta-endorphin. Twelve conscious, chair-adapted rhesus monkeys were studied twice before, once immediately after, and once 2 days after a single 800-cGy (800 rads) /sup 60/Co total-body irradiation. In addition to causing vomiting, total-body irradiation transiently suppressed gastric electrical control activity, gastric emptying and gastric secretion, while increasing plasma levels of immunoreactive Beta-endorphin. Domperidone had no effect on vomiting or gastric function either before or after irradiation, but it significantly increased plasma immunoreactive Beta endorphin.

  4. Spontaneaous linear gastric tears in a cat.

    Science.gov (United States)

    Gualtieri, M; Olivero, D; Costa Devoti, C

    2015-09-01

    An 11-year-old female cat presented for chronic vomiting. Endoscopy revealed an altered gastric mucosa and spontaneous formation of linear gastric tears during normal organ insufflations. The histopathological diagnosis was atrophic gastritis with Helicobacter pylori infection. Medical treatment permitted a complete resolution of clinical signs. The linear tears observed resembled gastric lesions rarely reported in humans, called "Mallory-Weiss syndrome". To the authors' knowledge this is the first report of spontaneous linear gastric tears in animals. © 2015 British Small Animal Veterinary Association.

  5. Cytotoxic effects of Urtica dioica radix on human colon (HT29) and gastric (MKN45) cancer cells mediated through oxidative and apoptotic mechanisms.

    Science.gov (United States)

    Ghasemi, S; Moradzadeh, M; Mousavi, S H; Sadeghnia, H R

    2016-10-15

    Defects in the apoptotic pathways are responsible for both the colorectal cancer pathogenesis and resistance to therapy. In this study, we examined the level of cellular oxidants, cytotoxicity and apoptosis induced by hydroalcoholic extract of U. dioica radix (0-2000 µg/mL) and oxaliplatin (0-1000 µg/mL, as positive control) in human gastric (MKN45) and colon (HT29) cancer, as well as normal human foreskin fibroblast (HFF) cells. Exposure to U. dioica or oxaliplatin showed a concentration dependent suppression in cell survival with IC50 values of 24.7, 249.9 and 857.5 µg/mL for HT29, MKN45 and HFF cells after 72 h treatment, respectively. ROS formation and lipid peroxidation were also concentration-dependently increased following treatment with U. dioica, similar to oxaliplatin. In addition, the number of apoptotic cells significantly increased concomitantly with concentration of U. dioica as compared with control cells, which is similar to oxaliplatin and serum-deprived cancer cells. In conclusion, the present study demonstrated that U. dioica inhibited proliferation of gastric and colorectal cancer cells while posing no significant toxic effect on normal cells. U. dioica not only increased levels of oxidants, but also induced concomitant increase of apoptosis. The precise signaling pathway by which U. dioica induce apoptosis needs further research.

  6. The interaction between Helicobacter pylori culture filtrate and indomethacin: effects on the integrity of human gastric antral mucosa and its prostaglandin E2 production in vitro.

    Science.gov (United States)

    Taha, A S; Kelly, R W; Gemmell, C G; Lee, F D; Russell, R I

    1990-06-01

    Histopathological methods and radioimmunoassay were used to assess the microstructure and prostaglandin E2 production by paired specimens of human gastric antral mucosa; the specimens were studied after 48 h of incubation in base-line tissue culture medium, Helicobacter pylori culture filtrate, H. pylori culture control fluid, indomethacin, and H. pylori culture filtrate plus indomethacin. When applied alone, the filtrate did not affect the structure of the mucosal tissue or its prostaglandin E2 synthesis. In the overall group (n = 21), specimens incubated with the mixture of H. pylori filtrate and indomethacin had a median histological grade of 1 and prostaglandin E2 of 29 pg/mg tissue, compared to 2 pg/mg (P = 0.04) and 60 pg/mg (P = 0.0007) respectively, in specimens incubated with indomethacin alone. These results indicate that an interaction may exist between indomethacin and a factor contained in H. pylori culture filtrate. Such interaction is damaging to the human gastric antral mucosa, and its understanding might have therapeutic implications.

  7. Human Adaptation of Ebola Virus during the West African Outbreak.

    Science.gov (United States)

    Urbanowicz, Richard A; McClure, C Patrick; Sakuntabhai, Anavaj; Sall, Amadou A; Kobinger, Gary; Müller, Marcel A; Holmes, Edward C; Rey, Félix A; Simon-Loriere, Etienne; Ball, Jonathan K

    2016-11-03

    The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa was the largest recorded. It began following the cross-species transmission of EBOV from an animal reservoir, most likely bats, into humans, with phylogenetic analysis revealing the co-circulation of several viral lineages. We hypothesized that this prolonged human circulation led to genomic changes that increased viral transmissibility in humans. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolate and introduced amino acid substitutions that defined viral lineages. Mutant GPs were used to generate a panel of pseudoviruses, which were used to infect different human and bat cell lines. These data revealed that specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells. Such increased infectivity may have enhanced the ability of EBOV to transmit among humans and contributed to the wide geographic distribution of some viral lineages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas

    International Nuclear Information System (INIS)

    Xiang, Shengyan; Liu, Zhaojun; Zhang, Baozhen; Zhou, Jing; Zhu, Bu-Dong; Ji, Jiafu; Deng, Dajun

    2010-01-01

    Alu methylation is correlated with the overall level of DNA methylation and recombination activity of the genome. However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized. This information is useful for understanding natural status of Alu in the genome and helpful for developing an optimal assay to quantify Alu hypomethylation. Bisulfite clone sequencing was carried out in 14 human gastric samples initially. A Cac8I COBRA-DHPLC assay was developed to detect methylated-Alu proportion in cell lines and 48 paired gastric carcinomas and 55 gastritis samples. DHPLC data were statistically interpreted using SPSS version 16.0. From the results of 427 Alu bisulfite clone sequences, we found that only 27.2% of CpG sites within Alu elements were preserved (4.6 of 17 analyzed CpGs, A ~ Q) and that 86.6% of remaining-CpGs were methylated. Deamination was the main reason for low preservation of methylation targets. A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). Comethylation of the sites H and J were used as an indicator of the proportion of methylated-Alu in a Cac8I COBRA-DHPLC assay. Validation studies showed that hypermethylation or hypomethylation of Alu elements in human cell lines could be detected sensitively by the assay after treatment with 5-aza-dC and M.SssI, respectively. The proportion of methylated-Alu copies in gastric carcinomas (3.01%) was significantly lower than that in the corresponding normal samples (3.19%) and gastritis biopsies (3.23%). Most Alu CpG sites are deaminated in the genome. 27% of Alu CpG sites represented in our amplification products. 87% of the remaining CpG sites are methylated. Alu hypomethylation in primary gastric carcinomas could be detected with the Cac8I COBRA-DHPLC assay quantitatively

  9. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    Nairobi, Kenya. 28 Adapting Fishing Policy to Climate Change with the Aid of Scientific and Endogenous Knowledge. Cap Verde, Gambia,. Guinea, Guinea Bissau,. Mauritania and Senegal. Environment and Development in the Third World. (ENDA-TM). Dakar, Senegal. 29 Integrating Indigenous Knowledge in Climate Risk ...

  10. Gastric Bezoar

    Directory of Open Access Journals (Sweden)

    Samer Assaf

    2017-01-01

    Full Text Available History of present illness: A 12-year-old female with no past medical history presented with abdominal pain for 3 months. The pain was intermittent, located at the epigastric region, non-radiating, fluctuating intensity up to 8/10, and had worsened over the past month. She did not have fever, nausea, vomiting, diarrhea, constipation, or blood in her stool. The patient also endorsed hair loss over the same time period and noted that her previously long hair was now short and thin. On exam, patient was noted to have shoulder-length hair, a soft, non-distended abdomen with mild tenderness to the epigastric region, and a 5cm hard mass palpated at the epigastrium. Significant findings: In the abdominal radiograph, a nonspecific and non-obstructive bowel gas pattern with no air-fluid level was noted, however the stomach was distended with soft tissue. The CT abdomen/pelvis revealed a distended stomach with undigested heterogeneous contents (presumed bezoar. Discussion: A bezoar is a mass of incompletely digested material typically originating in the stomach and consisting of vegetable fibers, hair, or drugs.1 Bezoars develop after ingested foreign material accumulates in the gastrointestinal tract due to indigestibility, gastric outlet obstruction, or intestinal stasis. Trichobezoars are comprised of hair and classically form in young females with an underlying psychiatric disorder resulting in the urge to pull one’s hair out (trichotillomania and swallow it (trichophagia.2,3 Gastric bezoars are rare with an approximate incidence of 0.3 percent of patients undergoing upper endoscopy.4 Patients tend to remain asymptomatic for long periods, but may develop abdominal pain, nausea/vomiting, early satiety, anorexia, and weight loss.5 Complications may include gastrointestinal ulcerations, perforations, intussusception, pancreatitis, obstructive jaundice, and death.6-8 The diagnosis of a gastric bezoar can be made using plain films, ultrasound, or CT, and

  11. Gastric diverticulosis and ulcerations in bitches

    African Journals Online (AJOL)

    ADEYEYE

    2014-01-08

    Jan 8, 2014 ... atrophies when placental nutrition replaces the yolk sac (Van Klaveren et al., 2008). True gastric diverticula may occur at any age though middle age individuals are more prone to the disease. Often the incidence of gastric diverticulum is evenly distributed between male and female in human (Rashid et al., ...

  12. Chemokines and antimicrobial peptides have a cag-dependent early response to Helicobacter pylori infection in primary human gastric epithelial cells.

    Science.gov (United States)

    Mustapha, Pascale; Paris, Isabelle; Garcia, Magali; Tran, Cong Tri; Cremniter, Julie; Garnier, Martine; Faure, Jean-Pierre; Barthes, Thierry; Boneca, Ivo G; Morel, Franck; Lecron, Jean-Claude; Burucoa, Christophe; Bodet, Charles

    2014-07-01

    Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer.

    Science.gov (United States)

    Miyo, Masaaki; Konno, Masamitsu; Nishida, Naohiro; Sueda, Toshinori; Noguchi, Kozo; Matsui, Hidetoshi; Colvin, Hugh; Kawamoto, Koichi; Koseki, Jun; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Gotoh, Noriko; Matsuda, Fumio; Satoh, Taroh; Mizushima, Tsunekazu; Shimizu, Hiroshi; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2016-12-07

    Tumor cells respond to their microenvironment, which can include hypoxia and malnutrition, and adapt their metabolism to survive and grow. Some oncogenes are associated with cancer metabolism via regulation of the related enzymes or transporters. However, the importance of metabolism and precise metabolic effects of oncogenes in colorectal cancer remain unclear. We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone. Metabolomic analysis demonstrated that those cells maintained tricarboxylic acid cycle activity and ATP production under such conditions. Furthermore, we identified pivotal roles of GLUD1 and SLC25A13 in nutritional stress. GLUD1 and SLC25A13 were associated with tumor aggressiveness and poorer prognosis of colorectal cancer. In conclusion, GLUD1 and SLC25A13 may serve as new targets in treating refractory colorectal cancer which survive in malnutritional microenvironments.

  14. The Cultural Historical Complexity of Human Personality Adaptation

    Directory of Open Access Journals (Sweden)

    Melissa E. Wynn

    2012-10-01

    Full Text Available Research on implicit intelligence has conceptualized students’ beliefs about the nature of intelligence as either fixed or malleable. This research has largely not included African American adolescents, a group for whom beliefs about intelligence have a cultural historical complexity related to both scientific racism and master narratives of race and intelligence. The purpose of this study was to investigate the nature of implicit theories of intelligence for 63 African American adolescents who are seventh and eighth graders in a public charter school. The two-way ANOVA revealed that these adolescents held a malleable view of intelligence, which did not vary by gender or grade. Exploratory correlation analysis showed some consistent relationships with achievement motivation variables found in other studies. These findings may be explained by African American cultural values and the personality characteristic adaptations that they make living within a racialized society.

  15. The human endurance athlete: heterogeneity and adaptability of ...

    African Journals Online (AJOL)

    1997-12-09

    Dec 9, 1997 ... In human subjects, large variations between individuals (up to 3-fold) exist in the capacity for endurance exer- cise performance. In a heterogeneous population, endurance performance is strongly related to whole body maximal oxygen uptake (VO,max). This is in part genotype dependent (-25%) but is ...

  16. Enhancing Perception with Tactile Object Recognition in Adaptive Grippers for Human-Robot Interaction.

    Science.gov (United States)

    Gandarias, Juan M; Gómez-de-Gabriel, Jesús M; García-Cerezo, Alfonso J

    2018-02-26

    The use of tactile perception can help first response robotic teams in disaster scenarios, where visibility conditions are often reduced due to the presence of dust, mud, or smoke, distinguishing human limbs from other objects with similar shapes. Here, the integration of the tactile sensor in adaptive grippers is evaluated, measuring the performance of an object recognition task based on deep convolutional neural networks (DCNNs) using a flexible sensor mounted in adaptive grippers. A total of 15 classes with 50 tactile images each were trained, including human body parts and common environment objects, in semi-rigid and flexible adaptive grippers based on the fin ray effect. The classifier was compared against the rigid configuration and a support vector machine classifier (SVM). Finally, a two-level output network has been proposed to provide both object-type recognition and human/non-human classification. Sensors in adaptive grippers have a higher number of non-null tactels (up to 37% more), with a lower mean of pressure values (up to 72% less) than when using a rigid sensor, with a softer grip, which is needed in physical human-robot interaction (pHRI). A semi-rigid implementation with 95.13% object recognition rate was chosen, even though the human/non-human classification had better results (98.78%) with a rigid sensor.

  17. Aging Affects Adaptation to Sound-Level Statistics in Human Auditory Cortex.

    Science.gov (United States)

    Herrmann, Björn; Maess, Burkhard; Johnsrude, Ingrid S

    2018-02-21

    Optimal perception requires efficient and adaptive neural processing of sensory input. Neurons in nonhuman mammals adapt to the statistical properties of acoustic feature distributions such that they become sensitive to sounds that are most likely to occur in the environment. However, whether human auditory responses adapt to stimulus statistical distributions and how aging affects adaptation to stimulus statistics is unknown. We used MEG to study how exposure to different distributions of sound levels affects adaptation in auditory cortex of younger (mean: 25 years; n = 19) and older (mean: 64 years; n = 20) adults (male and female). Participants passively listened to two sound-level distributions with different modes (either 15 or 45 dB sensation level). In a control block with long interstimulus intervals, allowing neural populations to recover from adaptation, neural response magnitudes were similar between younger and older adults. Critically, both age groups demonstrated adaptation to sound-level stimulus statistics, but adaptation was altered for older compared with younger people: in the older group, neural responses continued to be sensitive to sound level under conditions in which responses were fully adapted in the younger group. The lack of full adaptation to the statistics of the sensory environment may be a physiological mechanism underlying the known difficulty that older adults have with filtering out irrelevant sensory information. SIGNIFICANCE STATEMENT Behavior requires efficient processing of acoustic stimulation. Animal work suggests that neurons accomplish efficient processing by adjusting their response sensitivity depending on statistical properties of the acoustic environment. Little is known about the extent to which this adaptation to stimulus statistics generalizes to humans, particularly to older humans. We used MEG to investigate how aging influences adaptation to sound-level statistics. Listeners were presented with sounds drawn from

  18. Possible human impacts on adaptive radiation: beak size bimodality in Darwin's finches.

    Science.gov (United States)

    Hendry, Andrew P; Grant, Peter R; Rosemary Grant, B; Ford, Hugh A; Brewer, Mark J; Podos, Jeffrey

    2006-08-07

    Adaptive radiation is facilitated by a rugged adaptive landscape, where fitness peaks correspond to trait values that enhance the use of distinct resources. Different species are thought to occupy the different peaks, with hybrids falling into low-fitness valleys between them. We hypothesize that human activities can smooth adaptive landscapes, increase hybrid fitness and hamper evolutionary diversification. We investigated this possibility by analysing beak size data for 1755 Geospiza fortis measured between 1964 and 2005 on the island of Santa Cruz, Galápagos. Some populations of this species can display a resource-based bimodality in beak size, which mirrors the greater beak size differences among species. We first show that an historically bimodal population at one site, Academy Bay, has lost this property in concert with a marked increase in local human population density. We next show that a nearby site with lower human impacts, El Garrapatero, currently manifests strong bimodality. This comparison suggests that bimodality can persist when human densities are low (Academy Bay in the past, El Garrapatero in the present), but not when they are high (Academy Bay in the present). Human activities may negatively impact diversification in 'young' adaptive radiations, perhaps by altering adaptive landscapes.

  19. Security under Uncertainty: Adaptive Attackers Are More Challenging to Human Defenders than Random Attackers

    Directory of Open Access Journals (Sweden)

    Frédéric Moisan

    2017-06-01

    Full Text Available Game Theory is a common approach used to understand attacker and defender motives, strategies, and allocation of limited security resources. For example, many defense algorithms are based on game-theoretic solutions that conclude that randomization of defense actions assures unpredictability, creating difficulties for a human attacker. However, many game-theoretic solutions often rely on idealized assumptions of decision making that underplay the role of human cognition and information uncertainty. The consequence is that we know little about how effective these algorithms are against human players. Using a simplified security game, we study the type of attack strategy and the uncertainty about an attacker's strategy in a laboratory experiment where participants play the role of defenders against a simulated attacker. Our goal is to compare a human defender's behavior in three levels of uncertainty (Information Level: Certain, Risky, Uncertain and three types of attacker's strategy (Attacker's strategy: Minimax, Random, Adaptive in a between-subjects experimental design. Best defense performance is achieved when defenders play against a minimax and a random attack strategy compared to an adaptive strategy. Furthermore, when payoffs are certain, defenders are as efficient against random attack strategy as they are against an adaptive strategy, but when payoffs are uncertain, defenders have most difficulties defending against an adaptive attacker compared to a random attacker. We conclude that given conditions of uncertainty in many security problems, defense algorithms would be more efficient if they are adaptive to the attacker actions, taking advantage of the attacker's human inefficiencies.

  20. Adaptive response to 2 low doses of X-rays in human blood lymphocytes

    International Nuclear Information System (INIS)

    Fan, S.; Vijayalaxmi; Burkart, W.; Mindek, G.

    1990-01-01

    Human peripheral blood lymphocytes exposed to a single adaptive dose of 1 cGy X-rays or 2 adaptive doses, each of 1 cGy, were found to be equally resistant to the induction of chromosome damage by subsequent challenge with a high dose of 1 Gy X-rays, as compared to cells that were not pre-exposed. They responded with a significantly reduced incidence of chromatid and isochromatid breaks. These results indicate the presence of an inducible chromosomal repair mechanism in human blood lymphocytes and confirm the observations made by earlier investigators. The incidence of chromosome damage was found to be similar in the lymphocytes pre-exposed to a single or 2 adaptive doses, suggesting that, under the conditions tested, the second adaptive dose did not offer any additional protection against the chromosome damage induced by the challenge dose. (author). 14 refs.; 1 tab

  1. Developmental evidence for obstetric adaptation of the human female pelvis.

    OpenAIRE

    Huseynov Alik; Zollikofer Christoph P E; Coudyzer Walter; Gascho Dominic; Kellenberger Christian; Hinzpeter Ricarda; Ponce de León Marcia S

    2016-01-01

    The bony pelvis of adult humans exhibits marked sexual dimorphism, which is traditionally interpreted in the framework of the "obstetrical dilemma" hypothesis: Giving birth to large-brained/large-bodied babies requires a wide pelvis, whereas efficient bipedal locomotion requires a narrow pelvis. This hypothesis has been challenged recently on biomechanical, metabolic, and biocultural grounds, so that it remains unclear which factors are responsible for sex-specific differences in adult pelvic...

  2. Effect of progressive visual error amplification on human motor adaptation.

    Science.gov (United States)

    Sung, Cynthia; O'Malley, Marcia K

    2011-01-01

    Amplification of error has been shown to be an effective technique in increasing the rate and extent of learning for motor tasks and has the potential to accelerate rehabilitation following motor impairment. However, current error amplification methods suffer from reduced effectiveness towards the end of training. In this paper, we propose a new approach, progressive error amplification, in which error gains increase as a trainee's performance improves. We tested this approach against conventional error augmentation in a controlled experiment wherein 30 subjects adapted to a visually distorted environment by performing target-hitting tasks under one of three conditions (control, constant error amplification, progressive error amplification). Our results showed that compared with repeated practice, error amplification does not accelerate learning or result in improved task performance with respect to trajectory error, although progressive error amplification does produce lower trajectory errors when training conditions are in effect. These results indicate a need for further tuning of error augmentation methods in order to determine their true potential as a training method. © 2011 IEEE

  3. Characterization, Purification of Poncirin from Edible Citrus Ougan (Citrus reticulate cv. Suavissima) and Its Growth Inhibitory Effect on Human Gastric Cancer Cells SGC-7901

    Science.gov (United States)

    Zhu, Xiaoyan; Luo, Fenglei; Zheng, Yixiong; Zhang, Jiukai; Huang, Jianzhen; Sun, Chongde; Li, Xian; Chen, Kunsong

    2013-01-01

    Poncirin is a bitter flavanone glycoside with various biological activities. Poncirin was isolated from four different tissues (flavedo, albedo, segment membrane, and juice sac) of Ougan fruit (Citrus reticulate cv. Suavissima). The highest content of poncirin was found in the albedo of Ougan fruit (1.37 mg/g DW). High speed counter-current chromatography (HSCCC) combined with D101 resin chromatography was utilized for the separation and purification of poncirin from the albedo of Ougan fruit. After this two-step purification, poncirin purity increased from 0.14% to 96.56%. The chemical structure of the purified poncirin was identified by both HPLC-PDA and LC-MS. Poncirin showed a significant in vitro inhibitory effect on the growth of the human gastric cancer cells, SGC-7901, in a dose-dependent manner. Thus, poncirin from Ougan fruit, may be beneficial for gastric cancer prevention. The purification method demonstrated here will be useful for further studies on the pharmacological mechanism of poncirin activity, as well as for guiding the consumption of Ougan fruit. PMID:23615464

  4. Characterization, Purification of Poncirin from Edible Citrus Ougan (Citrus reticulate cv. Suavissima and Its Growth Inhibitory Effect on Human Gastric Cancer Cells SGC-7901

    Directory of Open Access Journals (Sweden)

    Xian Li

    2013-04-01

    Full Text Available Poncirin is a bitter flavanone glycoside with various biological activities. Poncirin was isolated from four different tissues (flavedo, albedo, segment membrane, and juice sac of Ougan fruit (Citrus reticulate cv. Suavissima. The highest content of poncirin was found in the albedo of Ougan fruit (1.37 mg/g DW. High speed counter-current chromatography (HSCCC combined with D101 resin chromatography was utilized for the separation and purification of poncirin from the albedo of Ougan fruit. After this two-step purification, poncirin purity increased from 0.14% to 96.56%. The chemical structure of the purified poncirin was identified by both HPLC-PDA and LC-MS. Poncirin showed a significant in vitro inhibitory effect on the growth of the human gastric cancer cells, SGC-7901, in a dose-dependent manner. Thus, poncirin from Ougan fruit, may be beneficial for gastric cancer prevention. The purification method demonstrated here will be useful for further studies on the pharmacological mechanism of poncirin activity, as well as for guiding the consumption of Ougan fruit.

  5. Flavonoids Isolated from Korea Citrus aurantium L. Induce G2/M Phase Arrest and Apoptosis in Human Gastric Cancer AGS Cells

    Directory of Open Access Journals (Sweden)

    Do-Hoon Lee

    2012-01-01

    Full Text Available Aim of the Study. Citrus species is used in traditional medicine as medicinal herb in several Asian countries including Korea. Flavonioids became known as various properties, such as anti-oxidants, anti-inflammation and anti-cancer, and so forth. The present study, the anti-cancer effect of flavonioids isolated from Citrus aurantium L. in human gastric cancer AGS cells has been investigated. Materials and Methods. The anti-proliferative activity was assayed using MTT assay. Cell cycle analysis was done using flow cytometry and apoptosis detection was done using by hoechst fluorescent staining and Annexin V-propidium iodide double staining. Western blot was used to detect the expression of protein related with cell cycle and apoptosis. Results. Flavonoids isolated from Citrus aurantium L. have the effect of anti proliferation on AGS cells with IC50 value of 99 μg/mL. Flavonoids inhibited cell cycle progression in the G2/M phase and decrease expression level of cyclin B1, cdc 2, cdc 25c. Flavonoids induced apoptosis through activate caspase and inactivate PARP. Conclusions. Flavonoids isolated from Citrus aurantium L. induced G2/M phase arrest through the modulation of cell cycle related proteins and apoptosis through activation caspase. These finding suggest flavonoids isolated from Citrus aurantium L. were useful agent for the chemoprevention of gastric cancer.

  6. Flavonoids Isolated from Korea Citrus aurantium L. Induce G2/M Phase Arrest and Apoptosis in Human Gastric Cancer AGS Cells.

    Science.gov (United States)

    Lee, Do-Hoon; Park, Kwang-Il; Park, Hyeon-Soo; Kang, Sang-Rim; Nagappan, Arulkumar; Kim, Jin-A; Kim, Eun-Hee; Lee, Won-Sup; Hah, Young-Sool; Chung, Hyon-Jong; An, Su-Jin; Kim, Gon-Sup

    2012-01-01

    Aim of the Study. Citrus species is used in traditional medicine as medicinal herb in several Asian countries including Korea. Flavonioids became known as various properties, such as anti-oxidants, anti-inflammation and anti-cancer, and so forth. The present study, the anti-cancer effect of flavonioids isolated from Citrus aurantium L. in human gastric cancer AGS cells has been investigated. Materials and Methods. The anti-proliferative activity was assayed using MTT assay. Cell cycle analysis was done using flow cytometry and apoptosis detection was done using by hoechst fluorescent staining and Annexin V-propidium iodide double staining. Western blot was used to detect the expression of protein related with cell cycle and apoptosis. Results. Flavonoids isolated from Citrus aurantium L. have the effect of anti proliferation on AGS cells with IC50 value of 99 μg/mL. Flavonoids inhibited cell cycle progression in the G2/M phase and decrease expression level of cyclin B1, cdc 2, cdc 25c. Flavonoids induced apoptosis through activate caspase and inactivate PARP. Conclusions. Flavonoids isolated from Citrus aurantium L. induced G2/M phase arrest through the modulation of cell cycle related proteins and apoptosis through activation caspase. These finding suggest flavonoids isolated from Citrus aurantium L. were useful agent for the chemoprevention of gastric cancer.

  7. Lanatoside C inhibits cell proliferation and induces apoptosis through attenuating Wnt/β-catenin/c-Myc signaling pathway in human gastric cancer cell.

    Science.gov (United States)

    Hu, Yudong; Yu, Kaikai; Wang, Gang; Zhang, Depeng; Shi, Chaoji; Ding, Yunhe; Hong, Duo; Zhang, Dan; He, Huiqiong; Sun, Lei; Zheng, Jun-Nian; Sun, Shuyang; Qian, Feng

    2018-04-01

    Gastric cancer is the third common cause of cancer mortality in the world with poor prognosis and high recurrence due to lack of effective medicines. Our studies revealed that lanatoside C, a FDA-approved cardiac glycoside, had an anti-proliferation effect on different human cancer cell lines (MKN-45; SGC-7901; HN4; MCF-7; HepG2) and gastric cell lines MKN-45 and SGC-7901 were the most sensitive cell lines to lanatoside C. MKN-45 cells treated with lanatoside C showed cell cycle arrest at G2/M phase and inhibition of cell migration. Meanwhile, upregulation of cleaved caspase-9 and cleaved PARP and downregulation of Bcl-xl were accompanied with the loss of mitochondrial membrane potential (MMP) and induction of intracellular reactive oxygen species (ROS). Lanatoside C inhibited Wnt/β-catenin signaling with downregulation of c-Myc, while overexpression of c-Myc reversed the anti-tumor effect of lanatoside C, confirming that c-Myc is a key drug target of lanatoside C. Furthermore, we discovered that lanatoside C prompted c-Myc degradation in proteasome-ubiquitin pathway with attenuating the binding of USP28 to c-Myc. These findings indicate that lanatoside C targeted c-Myc ubiquitination to inhibit MKN-45 proliferation and support the potential value of lanatoside C as a chemotherapeutic candidate. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Autism as an adaptive common variant pathway for human brain development

    Directory of Open Access Journals (Sweden)

    Mark H. Johnson

    2017-06-01

    Full Text Available While research on focal perinatal lesions has provided evidence for recovery of function, much less is known about processes of brain adaptation resulting from mild but widespread disturbances to neural processing over the early years (such as alterations in synaptic efficiency. Rather than being viewed as a direct behavioral consequence of life-long neural dysfunction, I propose that autism is best viewed as the end result of engaging adaptive processes during a sensitive period. From this perspective, autism is not appropriately described as a disorder of neurodevelopment, but rather as an adaptive common variant pathway of human functional brain development.

  9. Gastric secretion elicited by conditioning in rats.

    Science.gov (United States)

    Caboclo, José Liberato Ferreira; Cury, Francico de Assis; Borin, Aldenis Albanese; Caboclo, Luís Otávio Sales Ferreira; Ribeiro, Maria Fernanda Sales Caboclo; de Freitas, Pedro José; Andersson, Sven

    2009-01-01

    To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

  10. Radiation-induced adaptive response in human lymphoblast

    International Nuclear Information System (INIS)

    Yatagai, Fumio; Sugasawa, Kaoru

    2009-01-01

    Described are the genetic analysis of variant strains obtained by the optimal condition for radiation-induced adaptive response (AR), and molecular elucidation of the suppression of concomitant mutation. The TK6 cells (heterozygous thymidine kinase, +/-) were used for detection of mutation by loss of heterozygosity (LOH). The optimal conditions for reducing the mutation by subsequent irradiation (SI) to its rate of about 60% (vs control 100%, no PI) were found to be 5 cGy of pre-irradiation (PI) of X-ray and 2 Gy of SI with the interval of 6 hr, where mutated cells were of non-LOH type in around 25% and homo-LOH type by homologous recombination (HR) in 60%. By cDNA sequencing, the former cells having changed bases were found to be in variant strain ratio of 1/8 vs control 7/18, suggesting that the mutation was decreased mainly by suppression of base change. Expression of XPC protein, an important component for recognition of the base damage in global genome nucleotide excision repair, was studied by Western blotting as the possible mechanism of suppressing the mutation, which revealed different time dynamics of the protein in cells with PI+SI and SI alone (control). To see the effect of PI on the double strand break (DSB) repair, cells with PI were infected with restriction enzyme I-SceI vector to yield DSB instead of SI, which revealed more efficient repair (70% increase) by HR than control, without significant difference in non-homologous end-joining repair. Micro-array analysis to study the gene expression in the present experimental conditions for AR is in progress. The TK6 cells used here were thought useful for additional studies of the mechanism of AR as mutation by direct or indirect irradiation can be tested. (K.T.)

  11. Noninvasive optical imaging of resistance training adaptations in human muscle

    Science.gov (United States)

    Warren, Robert V.; Cotter, Joshua; Ganesan, Goutham; Le, Lisa; Agustin, Janelle P.; Duarte, Bridgette; Cutler, Kyle; O'Sullivan, Thomas; Tromberg, Bruce J.

    2017-12-01

    A quantitative and dynamic analysis of skeletal muscle structure and function can guide training protocols and optimize interventions for rehabilitation and disease. While technologies exist to measure body composition, techniques are still needed for quantitative, long-term functional imaging of muscle at the bedside. We evaluate whether diffuse optical spectroscopic imaging (DOSI) can be used for long-term assessment of resistance training (RT). DOSI measures of tissue composition were obtained from 12 adults before and after 5 weeks of training and compared to lean mass fraction (LMF) from dual-energy X-ray absorptiometry (DXA). Significant correlations were detected between DXA LMF and DOSI-measured oxy-hemo/myoglobin, deoxy-hemo/myoglobin, total-hemo/myoglobin, water, and lipid. RT-induced increases of ˜6% in oxy-hemo/myoglobin (3.4±1.0 μM, p=0.00314) and total-hemo/myoglobin (4.9±1.1 μM, p=0.00024) from the medial gastrocnemius were detected with DOSI and accompanied by ˜2% increases in lean soft tissue mass (36.4±12.4 g, p=0.01641) and ˜60% increases in 1 rep-max strength (41.5±6.2 kg, p = 1.9E-05). DOSI measures of vascular and/or muscle changes combined with correlations between DOSI and DXA suggest that quantitative diffuse optical methods can be used to evaluate body composition, provide feedback on long-term interventions, and generate new insight into training-induced muscle adaptations.

  12. Adaptation of group A Streptococcus to human amniotic fluid.

    Directory of Open Access Journals (Sweden)

    Izabela Sitkiewicz

    Full Text Available BACKGROUND: For more than 100 years, group A Streptococcus has been identified as a cause of severe and, in many cases, fatal infections of the female urogenital tract. Due to advances in hospital hygiene and the advent of antibiotics, this type of infection has been virtually eradicated. However, within the last three decades there has been an increase in severe intra- and post-partum infections attributed to GAS. METHODOLOGY: We hypothesized that GAS alters its transcriptome to survive in human amniotic fluid (AF and cause disease. To identify genes that were up or down regulated in response to growth in AF, GAS was grown in human AF or standard laboratory media (THY and samples for expression microarray analysis were collected during mid-logarithmic, late-logarithmic, and stationary growth phases. Microarray analysis was performed using a custom Affymetrix chip and normalized hybridization values derived from three biological replicates were collected at each growth point. Ratios of AF/THY above a 2-fold change and P-value <0.05 were considered significant. PRINCIPAL FINDINGS: The majority of changes in the GAS transcriptome involved down regulation of multiple adhesins and virulence factors and activation of the stress response. We observed significant changes in genes involved in the arginine deiminase pathway and in the nucleotide de novo synthesis pathway. CONCLUSIONS/SIGNIFICANCE: Our work provides new insight into how pathogenic bacteria respond to their environment to establish infection and cause disease.

  13. The long non-coding RNA H19-derived miR-675 modulates human gastric cancer cell proliferation by targeting tumor suppressor RUNX1

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Ming [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu (China); Gao, Wen; Xu, Jing; Wang, Ping [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Shu, Yongqian, E-mail: shuyongqian39000@163.com [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China)

    2014-06-06

    Graphical abstract: - Highlights: • H19 regulates gastric cancer cell proliferation phenotype via miR-675. • MiR-675 modulates cell proliferation of gastric cancer cells by targeting tumor suppressor RUNX1. • The H19/miR-675/RUNX1 axis plays an important role in the tumorigenesis of gastric cancer. - Abstract: The lncRNA H19 has been recently shown to be upregulated and play important roles in gastric cancer tumorigenesis. However, the precise molecular mechanism of H19 and its mature product miR-675 in the carcinogenesis of gastric cancer remains unclear. In this study, we found that miR-675 was positively expressed with H19 and was a pivotal mediator in H19-induced gastric cancer cell growth promotion. Subsequently, the tumor suppressor Runt Domain Transcription Factor1 (RUNX1) was confirmed to be a direct target of miR-675 using a luciferase reporter assay and Western blotting analyses. A series of rescue assays indicated that RUNX1 mediated H19/miR-67-induced gastric cancer cell phenotypic changes. Moreover, the inverse relationship between the expression of RUNX1 and H19/miR-675 was also revealed in gastric cancer tissues and gastric cancer cell lines. Taken together, our study demonstrated that the novel pathway H19/miR-675/RUNX1 regulates gastric cancer development and may serve as a potential target for gastric cancer therapy.

  14. Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

    Science.gov (United States)

    Őri, Zsolt P

    2017-05-01

    A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

  15. Metabolic adaptation of a human pathogen during chronic infections - a systems biology approach

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte

    modeling to uncover how human pathogens adapt to the human host. Pseudomonas aeruginosa infections in cystic fibrosis patients are used as a model system for under-­‐ standing these adaptation processes. The exploratory systems biology approach facilitates identification of important phenotypes...... by classical molecular biology approaches where genes and reactions typically are investigated in a one to one relationship. This thesis is an example of how mathematical approaches and modeling can facilitate new biologi-­‐ cal understanding and provide new surprising ideas to important biological processes....

  16. The effect of retinal image error update rate on human vestibulo-ocular reflex gain adaptation.

    Science.gov (United States)

    Fadaee, Shannon B; Migliaccio, Americo A

    2016-04-01

    The primary function of the angular vestibulo-ocular reflex (VOR) is to stabilise images on the retina during head movements. Retinal image movement is the likely feedback signal that drives VOR modification/adaptation for different viewing contexts. However, it is not clear whether a retinal image position or velocity error is used primarily as the feedback signal. Recent studies examining this signal are limited because they used near viewing to modify the VOR. However, it is not known whether near viewing drives VOR adaptation or is a pre-programmed contextual cue that modifies the VOR. Our study is based on analysis of the VOR evoked by horizontal head impulses during an established adaptation task. Fourteen human subjects underwent incremental unilateral VOR adaptation training and were tested using the scleral search coil technique over three separate sessions. The update rate of the laser target position (source of the retinal image error signal) used to drive VOR adaptation was different for each session [50 (once every 20 ms), 20 and 15/35 Hz]. Our results show unilateral VOR adaptation occurred at 50 and 20 Hz for both the active (23.0 ± 9.6 and 11.9 ± 9.1% increase on adapting side, respectively) and passive VOR (13.5 ± 14.9, 10.4 ± 12.2%). At 15 Hz, unilateral adaptation no longer occurred in the subject group for both the active and passive VOR, whereas individually, 4/9 subjects tested at 15 Hz had significant adaptation. Our findings suggest that 1-2 retinal image position error signals every 100 ms (i.e. target position update rate 15-20 Hz) are sufficient to drive VOR adaptation.

  17. Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations.

    Science.gov (United States)

    Bonelli, Patrizia; Tuccillo, Franca M; Federico, Antonella; Napolitano, Maria; Borrelli, Antonella; Melisi, Daniela; Rimoli, Maria G; Palaia, Raffaele; Arra, Claudio; Carinci, Francesco

    2012-01-01

    Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells. MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography-mass spectrometry. Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes. Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen.

  18. Measurement of the intracellular ph in human stomach cells: a novel approach to evaluate the gastric acid secretory potential of coffee beverages.

    Science.gov (United States)

    Weiss, Carola; Rubach, Malte; Lang, Roman; Seebach, Elisabeth; Blumberg, Simone; Frank, Oliver; Hofmann, Thomas; Somoza, Veronika

    2010-02-10

    As the consumption of coffee beverages sometimes is reported to cause gastric irritation, for which an increased stomach acid secretion is one of the promoting factors, different processing technologies such as steam-treatment have been developed to reduce putative stomach irritating compounds. There is evidence-based data neither on the effect of detailed processing variations nor on individual coffee components affecting the proton secretory activity (PSA). This work aimed at developing a screening model suitable for investigating the effects of commercial coffee beverages and components thereof on human parietal cells. Human gastric cancer cells (HGT-1) were treated with reconstituted freeze-dried coffee beverages prepared from customary coffee products such as regular coffee (RC, n = 4), mild bean coffee (MBC, n = 5), stomach friendly coffee (SFC, n = 4), and SFC decaffeinated (SFCD, n = 3). PSA was analyzed by flow cytometry using the pH-sensitive dye SNARF-AM. Treatment of the cells with MBC did not result in a PSA different from RC treatment (p

  19. Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

    Science.gov (United States)

    Bonelli, Patrizia; Tuccillo, Franca M; Federico, Antonella; Napolitano, Maria; Borrelli, Antonella; Melisi, Daniela; Rimoli, Maria G; Palaia, Raffaele; Arra, Claudio; Carinci, Francesco

    2012-01-01

    Purpose Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells. Methods MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry. Results Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes. Conclusion Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen. PMID:23180963

  20. Dietary Change and Adaptive Evolution of enamelin in Humans and Among Primates

    OpenAIRE

    Kelley, Joanna L.; Swanson, Willie J.

    2008-01-01

    Scans of the human genome have identified many loci as potential targets of recent selection, but exploration of these candidates is required to verify the accuracy of genomewide scans and clarify the importance of adaptive evolution in recent human history. We present analyses of one such candidate, enamelin, whose protein product operates in tooth enamel formation in 100 individuals from 10 populations. Evidence of a recent selective sweep at this locus confirms the signal of selection foun...

  1. High-speed adaptive optics line scan confocal retinal imaging for human eye.

    Science.gov (United States)

    Lu, Jing; Gu, Boyu; Wang, Xiaolin; Zhang, Yuhua

    2017-01-01

    Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye's optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss.

  2. Evidence for Human Adaptation and Foodborne Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus.

    Science.gov (United States)

    Larsen, Jesper; Stegger, Marc; Andersen, Paal S; Petersen, Andreas; Larsen, Anders R; Westh, Henrik; Agersø, Yvonne; Fetsch, Alexandra; Kraushaar, Britta; Käsbohrer, Annemarie; Feβler, Andrea T; Schwarz, Stefan; Cuny, Christiane; Witte, Wolfgang; Butaye, Patrick; Denis, Olivier; Haenni, Marisa; Madec, Jean-Yves; Jouy, Eric; Laurent, Frederic; Battisti, Antonio; Franco, Alessia; Alba, Patricia; Mammina, Caterina; Pantosti, Annalisa; Monaco, Monica; Wagenaar, Jaap A; de Boer, Enne; van Duijkeren, Engeline; Heck, Max; Domínguez, Lucas; Torres, Carmen; Zarazaga, Myriam; Price, Lance B; Skov, Robert L

    2016-11-15

    We investigated the evolution and epidemiology of a novel livestock-associated methicillin-resistant Staphylococcus aureus strain, which colonizes and infects urban-dwelling Danes even without a Danish animal reservoir. Genetic evidence suggests both poultry and human adaptation, with poultry meat implicated as a probable source. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  3. Evidence for Human Adaptation and Foodborne Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus

    NARCIS (Netherlands)

    Larsen, Jesper; Stegger, Marc; Andersen, Paal S.; Wagenaar, Jaap A.

    2016-01-01

    We investigated the evolution and epidemiology of a novel livestock-associated methicillin-resistant Staphylococcus aureus strain, which colonizes and infects urban-dwelling Danes even without a Danish animal reservoir. Genetic evidence suggests both poultry and human adaptation, with poultry meat

  4. Multivariate Dynamic Modeling to Investigate Human Adaptation to Space Flight: Initial Concepts

    Science.gov (United States)

    Shelhamer, Mark; Mindock, Jennifer; Zeffiro, Tom; Krakauer, David; Paloski, William H.; Lumpkins, Sarah

    2014-01-01

    The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in integrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach.

  5. Multivariate Dynamical Modeling to Investigate Human Adaptation to Space Flight: Initial Concepts

    Science.gov (United States)

    Shelhamer, Mark; Mindock, Jennifer; Zeffiro, Tom; Krakauer, David; Paloski, William H.; Lumpkins, Sarah

    2014-01-01

    The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in intergrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach.

  6. ERP Human Enhancement Progress Report : Use case and computational model for adaptive maritime automation

    NARCIS (Netherlands)

    Kleij, R. van der; Broek, J. van den; Brake, G.M. te; Rypkema, J.A.; Schilder, C.M.C.

    2015-01-01

    Automation is often applied in order to increase the cost-effectiveness, reliability and safety of maritime ship and offshore operations. Automation of operator tasks, has not, however, eliminated human error so much as created opportunities for new kinds of error. The ambition of the Adaptive

  7. Effects of human-machine interface design for intelligent speed adaptation on driving behavior and acceptance

    NARCIS (Netherlands)

    Rook, A.M.; Hogema, J.H.

    2005-01-01

    The effects of human-machine interface (HMI) design for intelligent speed adaptation (ISA) on driving behavior and acceptance were measured in a moving-base research driving simulator. Sixty-four experienced drivers participated in two simulator experiments (32 in each). During the simulated runs

  8. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

    DEFF Research Database (Denmark)

    Arora, Tulika; Velagapudi, Vidya; Pournaras, Dimitri J

    2015-01-01

    -surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery......Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were...... subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were...

  9. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Patti, Mary-Elizabeth; Houten, Sander M; Bianco, Antonio C

    2009-01-01

    The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2...... thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We...... performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI...

  10. Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

    Science.gov (United States)

    Tamboli, Robyn A; Antoun, Joseph; Sidani, Reem M; Clements, Austin; Harmata, Emily E; Marks-Shulman, Pam; Gaylinn, Bruce D; Williams, Brandon; Clements, Ronald H; Albaugh, Vance L; Abumrad, Naji N

    2017-09-01

    Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg -1  min -1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB. © 2017 John Wiley & Sons Ltd.

  11. Exploring the physiologic role of human gastroesophageal reflux by analyzing time-series data from 24-h gastric and esophageal pH recordings.

    Science.gov (United States)

    Lu, Luo; Mu, John C; Sloan, Sheldon; Miner, Philip B; Gardner, Jerry D

    2014-07-16

    Our previous finding of a fractal pattern for gastric pH and esophageal pH plus the statistical association of sequential pH values for up to 2 h led to our hypothesis that the fractal pattern encodes information regarding gastric acidity and that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity by influencing gastric secretion of acid or bicarbonate. Under our hypothesis values of gastric pH should provide information regarding values of esophageal pH and vice versa. We used vector autoregression, a theory-free set of inter-related linear regressions used to measure relationships that can change over time, to analyze data from 24-h recordings of gastric pH and esophageal pH. We found that in pH records from normal subjects, as well as from subjects with gastroesophageal reflux disease alone and after treatment with a proton pump inhibitor, gastric pH values provided important information regarding subsequent values of esophageal pH and values of esophageal pH provided important information regarding subsequent values of gastric pH. The ability of gastric pH and esophageal pH to provide information regarding subsequent values of each other was reduced in subjects with gastroesophageal reflux disease compared to normal subjects. Our findings are consistent with the hypothesis that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity, and that this ability is impaired in subjects with gastroesophageal reflux disease. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  12. Autoimmunity and Gastric Cancer

    Science.gov (United States)

    Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

    2018-01-01

    Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

  13. Autoimmunity and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Nicola Bizzaro

    2018-01-01

    Full Text Available Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms.

  14. Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Liying Hou

    Full Text Available Vitamin E succinate (VES, a potential cancer therapeutic agent, potently induces apoptosis and inhibits the growth of various cancer cells. Autophagy has been supposed to promote cancer cell survival or trigger cell death, depending on particular cancer types and tumor microenvironments. The role of autophagy in the growth suppressive effect of VES on gastric cancer cell is basically unknown. We aimed to determine whether and how autophagy affected the VES-induced inhibition of SGC-7901 human gastric carcinoma cell growth. SGC-7901 cells were treated with VES or pre-treated with autophagy inhibitor, chloroquine (CQ and 3-methyladenine (3-MA. Electron microscopy, fluorescence microscopy and Western blot were used to study whether VES induced autophagy reaction in SGC-7901 cells. Western blot evaluated the activities of the mammalian target of rapamycin (mTOR axis. Then we used 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and flow cytometry to detect the level of cell viability and apoptosis. Collectively, our data indeed strongly support our hypothesis that VES treatment produced cytological variations that depict autophagy, increased the amount of intracellular green fluorescent protein-microtubule associated protein 1 light chain 3 (GFP-LC3 punctate fluorescence and the number of autophagic vacuoles. It altered the expression of endogenous autophagy marker LC3. VES activated the suppression of mTOR through inhibiting upstream regulators p38 MAPK and Akt. mTOR suppression consequently inhibited the activation of mTOR downstream targets p70S6K and 4E-BP-1. The activation of the upstream mTOR inhibitor AMPK had been up-regulated by VES. The results showed that pre-treatment SGC-7901 with autophagy inhibitors before VES treatment could increase the capacity of VES to reduce cell viability and to provoke apoptosis. In conclusion, VES-induced autophagy participates in SGC-7901 cell protection by inhibiting mTOR axis

  15. The effect of aloe emodin–encapsulated nanoliposome-mediated r-caspase-3 gene transfection and photodynamic therapy on human gastric cancer cells

    International Nuclear Information System (INIS)

    Li, Kai-Ting; Duan, Qin-Qin; Chen, Qing; He, Juan-Wen; Tian, Si; Lin, Hai-Dan; Gao, Qing; Bai, Ding-Qun

    2015-01-01

    Gastric carcinoma (GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy (PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin (AE)–encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer (PS). AE-encapsulated nanoliposomes (nano-AE) were prepared by reverse evaporation method. Electron microscopy and nano-ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase-3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species (ROS) contents were measured by DCFH-DA staining. Outcomes demonstrated that the nano-AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r-caspase-3 was transfected had higher protein expression of the caspase-3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano-AE-mediated PDT in an energy-dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm 2 ). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano-AE PDT group had quadrupled in SGC-7901 cells as early as 1 h after PDT, while it is similar to the group of nano-AE transfection and PDT. Nano-AE-mediated r-caspase-3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human

  16. The adaptive nature of the human neurocognitive architecture: an alternative model.

    Science.gov (United States)

    La Cerra, P; Bingham, R

    1998-09-15

    The model of the human neurocognitive architecture proposed by evolutionary psychologists is based on the presumption that the demands of hunter-gatherer life generated a vast array of cognitive adaptations. Here we present an alternative model. We argue that the problems inherent in the biological markets of ancestral hominids and their mammalian predecessors would have required an adaptively flexible, on-line information-processing system, and would have driven the evolution of a functionally plastic neural substrate, the neocortex, rather than a confederation of evolutionarily prespecified social cognitive adaptations. In alignment with recent neuroscientific evidence, we suggest that human cognitive processes result from the activation of constructed cortical representational networks, which reflect probabilistic relationships between sensory inputs, behavioral responses, and adaptive outcomes. The developmental construction and experiential modification of these networks are mediated by subcortical circuitries that are responsive to the life history regulatory system. As a consequence, these networks are intrinsically adaptively constrained. The theoretical and research implications of this alternative evolutionary model are discussed.

  17. Asymmetric adaptation in human walking using the Tethered Pelvic Assist Device (TPAD).

    Science.gov (United States)

    Vashista, Vineet; Reisman, Darcy S; Agrawal, Sunil K

    2013-06-01

    Human nervous system is capable of modifying motor commands in response to alterations in walking conditions. Previous research has shown that external perturbations that induce gait asymmetry can lead to adaptation in gait parameters. Such strategies have also been shown to temporarily restore gait symmetry in subjects with post stroke hemiparesis. This work aims to develop an experimental paradigm to induce gait asymmetry in human subjects by applying external asymmetric forces on the pelvis through the Tethered Pelvic Assist Device (TPAD). These external forces on the pelvis have the potential to influence the swing and the stance phases of both legs. Eight healthy subjects participated in the experiment where a higher resistive force was applied on the pelvis during the swing phase of the left leg as compared to the right leg. We hypothesized that such asymmetrically applied forces on the pelvis will lead to asymmetric adaptation in the human walking.

  18. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

    International Nuclear Information System (INIS)

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

    2016-01-01

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

  19. Expression of matrix metalloprotease-2, -7 and -9 on human colon, liver and bile duct cell lines by enteric and gastric Helicobacter species.

    Science.gov (United States)

    Yanagisawa, Naoko; Geironson, Linda; Al-Soud, Waleed Abu; Ljungh, Sa

    2005-05-01

    Gastric and enteric Helicobacter species have been associated with malignant and inflammatory diseases of the stomach, liver, gall bladder and intestine. Matrix metalloproteinases (MMPs) participate in degradation of extracellular matrix, which allows bacteria to come in contact with and interact with the cells. Enhanced level of MMPs facilitates metastasis and cell invasion of tumor cells by removal of physical barriers, as well as modulation of biologic activities of the proteins residing in the extracellular matrix. The aim of this study was to evaluate the effect of gastric and enteric Helicobacter on induction of MMPs in hepatocytes and epithelial cells of gall bladder and colon. Human hepatocytes HepG2, gall bladder epithelial cells TFK-1, and colon epithelial cells HT29 were infected with strains of H. pylori cagA+, cagE+, H. pylori cagA-, cagE-, H. pullorum, H. cholecystus, H. bilis and H. hepaticus. Protein levels of MMPs were analyzed by enzyme-linked immunosorbent assay and immunohistochemistry. Reverse transcription-quantitative polymerase chain reaction was used to study mRNA levels. Increased expression of MMP-2 and MMP-9 was observed on HepG2, TFK-1 and HT29 infected with H. pylori cagA+, cagE+ and H. cholecystus strains. H. pylori cagA+, cagE+, H. cholecystus, H. pullorum, H. bilis and H. hepaticus strains increased expression of MMP-7 on HT29, compared to uninfected control cells. The effect of MMP upregulation on HepG2, TFK-1 and HT29 was bacterial dose dependent. H. pylori cagA-, cagE- strain did not increase expression of MMPs. Inducible MMPs on colon and bile duct epithelial cells as well as hepatocytes may play an important role in facilitating invasion and progression of cancer by Helicobacter species colonizing the hepatobiliary and gastrointestinal tract.

  20. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan, E-mail: moonsonlife@yahoo.com; Xian, Shulin; Lu, Yunfei, E-mail: doctorlife@126.com

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

  1. The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives in human gastric cancer cells.

    Science.gov (United States)

    Pawłowska, Natalia; Gornowicz, Agnieszka; Bielawska, Anna; Surażyński, Arkadiusz; Szymanowska, Anna; Czarnomysy, Robert; Bielawski, Krzysztof

    2018-03-17

    Objective The aim of the current study was to examine the anticancer activity and the detailed mechanism of novel diisoquinoline derivatives in human gastric cancer cells (AGS). Methods The viability of AGS cells was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell cycle analysis and apoptosis assay were performed by standard flow cytometric method. Confocal microscopy bioimaging was used to demonstrate the expression of pivotal proteins engaged in apoptosis (caspase-8, caspase-3, p53) and cell signaling (AKT, ERK1/2). Results All compounds decreased the number of viable cells in a dose-dependent manner after 24 and 48 h of incubation, although compound 2 was a more cytotoxic agent, with IC 50 values of 21 ± 2 and 6 ± 2 μM, compared to 80 ± 2 and 45 ± 2 μM for etoposide. The cytotoxic and antiproliferative effects of novel compounds were associated with the induction of apoptosis. The highest percentage of early and late apoptotic cells was observed after 48 h of incubation with compound 2 (89.9%). The value was higher compared to compound 1 (20.4%) and etoposide (24.1%). The novel diisoquinoline derivatives decreased the expression of AKT and ERK1/2. Their mechanism was associated with p53-mediated apoptosis, accumulation of cells in the G2/M phase of cell cycle and inhibition of topoisomerase II. Conclusion These data strongly support compound 2 as a promising molecule for treatment of gastric cancer.

  2. Feedback effect of human physical and psychological adaption on time period of thermal adaption in naturally ventilated building

    DEFF Research Database (Denmark)

    liu, weiwei; Huangfu, Hao; Xiong, Jing

    2014-01-01

    This study proposed a method to determine time period of thermal adaption for occupants in naturally ventilated building, and analyzed the synergistic and separate feedback effect of the physical and psychological adaption modes on the time period of thermal adaption. Using the method, the values...... of the time period of thermal adaption were obtained on the basis of the data from a long-term field survey conducted in two typical naturally ventilated offices located in Changsha, China. The results showed that the occupants need to take 4.25 days to fully adapt to a step-change in outdoor air temperature......, under the synergistic feedback effect of the physical and psychological adaption modes. The time period of thermal adaption increased to 13 days, if only the feedback effect of the physical adaption mode was accounted for. The difference between the two values of the time period of thermal adaption...

  3. Leading toward value: the role of strategic human resource management in health system adaptability.

    Science.gov (United States)

    Garman, Andrew N; Polavarapu, Nandakishor; Grady, Jane C; Canar, W Jeffrey

    2013-01-01

    Personnel costs typically account for 60% or more of total operating expenses in health systems, and as such become a necessary focus in most if not all substantive health reform adaptations. This study sought to assess whether strategic alignment of the human resource (HR) and learning functions was associated with greater adaptive capacity in U.S. health systems. Data were gathered using a survey that was distributed electronically to chief human resource officers from two U.S.-based associations. The survey included questions about organizational structure, strategic human resource management, strategic learning, and organizational response to health reform. Significant correlations were found between strategic alignment of HR and HR's involvement in responses related to cost control (r = 0.46, p strategic alignment of organizational learning and HR involvement with these responses. Results suggest that HR structure may affect an organization's capacity for adaptive response. Top-management teams in health systems should consider positioning HR as part of the core leadership team, with a reporting relationship that allows HR to maximally participate in formulating and implementing organizational adaptation.

  4. Experimental adaptation of wild-type canine distemper virus (CDV to the human entry receptor CD150.

    Directory of Open Access Journals (Sweden)

    Maria Bieringer

    Full Text Available Canine distemper virus (CDV, a close relative of measles virus (MV, is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2 pfu/ml in Vero cells expressing human CD150 (Vero-hSLAM. After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5 pfu/ml. Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L and Gly to Glu (G71E, and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

  5. Integrating human responses to climate change into conservation vulnerability assessments and adaptation planning.

    Science.gov (United States)

    Maxwell, Sean L; Venter, Oscar; Jones, Kendall R; Watson, James E M

    2015-10-01

    The impact of climate change on biodiversity is now evident, with the direct impacts of changing temperature and rainfall patterns and increases in the magnitude and frequency of extreme events on species distribution, populations, and overall ecosystem function being increasingly publicized. Changes in the climate system are also affecting human communities, and a range of human responses across terrestrial and marine realms have been witnessed, including altered agricultural activities, shifting fishing efforts, and human migration. Failing to account for the human responses to climate change is likely to compromise climate-smart conservation efforts. Here, we use a well-established conservation planning framework to show how integrating human responses to climate change into both species- and site-based vulnerability assessments and adaptation plans is possible. By explicitly taking into account human responses, conservation practitioners will improve their evaluation of species and ecosystem vulnerability, and will be better able to deliver win-wins for human- and biodiversity-focused climate adaptation. © 2015 New York Academy of Sciences.

  6. Stomach (Gastric) Cancer Screening

    Science.gov (United States)

    ... certain chronic conditions increase the risk of stomach cancer. Stomach cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about stomach cancer: Stomach (Gastric) Cancer Prevention Gastric Cancer Treatment Stomach cancer ...

  7. Multiconjugate adaptive optics applied to an anatomically accurate human eye model

    Science.gov (United States)

    Bedggood, P. A.; Ashman, R.; Smith, G.; Metha, A. B.

    2006-09-01

    Aberrations of both astronomical telescopes and the human eye can be successfully corrected with conventional adaptive optics. This produces diffraction-limited imagery over a limited field of view called the isoplanatic patch. A new technique, known as multiconjugate adaptive optics, has been developed recently in astronomy to increase the size of this patch. The key is to model atmospheric turbulence as several flat, discrete layers. A human eye, however, has several curved, aspheric surfaces and a gradient index lens, complicating the task of correcting aberrations over a wide field of view. Here we utilize a computer model to determine the degree to which this technology may be applied to generate high resolution, wide-field retinal images, and discuss the considerations necessary for optimal use with the eye. The Liou and Brennan schematic eye simulates the aspheric surfaces and gradient index lens of real human eyes. We show that the size of the isoplanatic patch of the human eye is significantly increased through multiconjugate adaptive optics.

  8. Adaptation to climate change: Using nighttime lights satellite data to explore human response to flood events

    Science.gov (United States)

    Mård, Johanna; Di Baldassarre, Giuliano

    2017-04-01

    To better understand the impact of climate change, we need to uncover how (and to what extent) societies respond and adapt to it. Yet the dynamics resulting from two-way feedbacks between nature and society remain largely unknown. Here we present an interdisciplinary study aiming to uncover one of the least quantified aspects of human-nature interactions, the spatial-temporal distribution of demographic changes following the occurrence of extreme events. To this end, we use nighttime light satellite data in four contrasting case studies in both low- and high-income countries (Lower Limpopo River in Mozambique, Mekong River in Vietnam and Cambodia, Brisbane River in Australia and Mississippi River at St. Louis in USA), and explore the interplay between flooding events and changes in population distribution in the period 1992-2013. Our study shows the challenges and opportunities of nighttime lights in unraveling the way humans adapt to climate change. Specific results show that population distribution of societies that strongly rely on structural measures ("fighting floods" policies) is not significantly affected by the occurrence of flood events. Conversely, learning dynamics emerge in societies that mainly rely on non-structural measures ("living with floods" policies) in terms of relative population in floodplain areas, i.e. reduced human proximity to rivers. Lastly, we propose the development of a novel approach to exploit the growing availability of worldwide information, such as nighttime lights satellite data, to uncover human adaptation to climate change across scales and along gradients of social and natural conditions.

  9. Gastric and intestinal surgery.

    Science.gov (United States)

    Fossum, Theresa W; Hedlund, Cheryl S

    2003-09-01

    Gastric surgery is commonly performed to remove foreign bodies and correct gastric dilatation-volvulus and is less commonly performed to treat gastric ulceration or erosion, neoplasia, and benign gastric outflow obstruction. Intestinal surgery, although commonly performed by veterinarians, should never be considered routine. The most common procedures of the small intestinal tract performed in dogs and cats include enterotomy and resection/anastomosis. Surgery of the large intestine is indicated for lesions causing obstruction, perforations, colonic inertia, or chronic inflammation.

  10. Rotational Kinematics Model Based Adaptive Particle Filter for Robust Human Tracking in Thermal Omnidirectional Vision

    Directory of Open Access Journals (Sweden)

    Yazhe Tang

    2015-01-01

    Full Text Available This paper presents a novel surveillance system named thermal omnidirectional vision (TOV system which can work in total darkness with a wild field of view. Different to the conventional thermal vision sensor, the proposed vision system exhibits serious nonlinear distortion due to the effect of the quadratic mirror. To effectively model the inherent distortion of omnidirectional vision, an equivalent sphere projection is employed to adaptively calculate parameterized distorted neighborhood of an object in the image plane. With the equivalent projection based adaptive neighborhood calculation, a distortion-invariant gradient coding feature is proposed for thermal catadioptric vision. For robust tracking purpose, a rotational kinematic modeled adaptive particle filter is proposed based on the characteristic of omnidirectional vision, which can handle multiple movements effectively, including the rapid motions. Finally, the experiments are given to verify the performance of the proposed algorithm for human tracking in TOV system.

  11. Controlling a virtual forehand prosthesis using an adaptive and affective Human-Machine Interface.

    Science.gov (United States)

    Rezazadeh, I Mohammad; Firoozabadi, S M P; Golpayegani, S M R Hashemi; Hu, H

    2011-01-01

    This paper presents the design of an adaptable Human-Machine Interface (HMI) for controlling virtual forearm prosthesis. Direct physical performance measures (obtained score and completion time) for the requested tasks were calculated. Furthermore, bioelectric signals from the forehead were recorded using one pair of electrodes placed on the frontal region of the subject head to extract the mental (affective) measures while performing the tasks. By employing the proposed algorithm and above measures, the proposed HMI can adapt itself to the subject's mental states, thus improving the usability of the interface. The quantitative results from 15 subjects show that the proposed HMI achieved better physical performance measures in comparison to a conventional non-adaptive myoelectric controller (p < 0.001).

  12. Do the actions of glucagon-like peptide-1 on gastric emptying, appetite, and food intake involve release of amylin in humans?

    DEFF Research Database (Denmark)

    Asmar, Meena; Bache, Michael; Knop, Filip K

    2010-01-01

    Amylin, cosecreted with insulin, has like glucagon-like peptide-1 (GLP-1) been reported to inhibit glucagon secretion, delay gastric emptying, and reduce appetite and food intake. We investigated whether the effects of GLP-1 on gastric emptying, appetite, and food intake are mediated directly or ...

  13. Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum.

    Science.gov (United States)

    Diederen, Kelly M J; Ziauddeen, Hisham; Vestergaard, Martin D; Spencer, Tom; Schultz, Wolfram; Fletcher, Paul C

    2017-02-15

    Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness. SIGNIFICANCE STATEMENT To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that

  14. Assessing employability capacities and career adaptability in a sample of human resource professionals

    Directory of Open Access Journals (Sweden)

    Melinde Coetzee

    2015-06-01

    Full Text Available Orientation: Employers have come to recognise graduates’ employability capacities and their ability to adapt to new work demands as important human capital resources for sustaining a competitive business advantage. Research purpose: The study sought (1 to ascertain whether a significant relationship exists between a set of graduate employability capacities and a set of career adaptability capacities and (2 to identify the variables that contributed the most to this relationship. Motivation for the study: Global competitive markets and technological advances are increasingly driving the demand for graduate knowledge and skills in a wide variety of jobs. Contemporary career theory further emphasises career adaptability across the lifespan as a critical skill for career management agency. Despite the apparent importance attached to employees’ employability and career adaptability, there seems to be a general lack of research investigating the association between these constructs. Research approach, design and method: A cross-sectional, quantitative research design approach was followed. Descriptive statistics, Pearson product-moment correlations and canonical correlation analysis were performed to achieve the objective of the study. The participants (N = 196 were employed in professional positions in the human resource field and were predominantly early career black people and women. Main findings: The results indicated positive multivariate relationships between the variables and showed that lifelong learning capacities and problem solving, decision-making and interactive skills contributed the most to explaining the participants’ career confidence, career curiosity and career control. Practical/managerial implications: The study suggests that developing professional graduates’ employability capacities may strengthen their career adaptability. These capacities were shown to explain graduates’ active engagement in career management

  15. Adaptive thermogenesis in human body weight regulation: more of a concept than a measurable entity?

    Science.gov (United States)

    Dulloo, A G; Jacquet, J; Montani, J-P; Schutz, Y

    2012-12-01

    According to Lavoisier, 'Life is combustion'. But to what extent humans adapt to changes in food intake through adaptive thermogenesis--by turning down the rate of heat production during energy deficit (so as to conserve energy) or turning it up during overnutrition (so as to dissipate excess calories)--has been one of the most controversial issues in nutritional sciences over the past 100 years. The debate nowadays is not whether adaptive thermogenesis exists or not, but rather about its quantitative importance in weight homoeostasis and its clinical relevance to the pathogenesis and management of obesity. Such uncertainties are likely to persist in the foreseeable future primarily because of limitations to unobtrusively measure changes in energy expenditure and body composition with high enough accuracy and precision, particularly when even small inter-individual variations in thermogenesis can, in dynamic systems and over the long term, be important in the determining weight maintenance in some and obesity and weight regain in others. This paper reviews the considerable body of evidence, albeit fragmentary, suggesting the existence of quantitatively important adaptive thermogenesis in several compartments of energy expenditure in response to altered food intake. It then discusses the various limitations that lead to over- or underestimations in its assessment, including definitional and semantics, technical and methodological, analytical and statistical. While the role of adaptive thermogenesis in human weight regulation is likely to remain more a concept than a strictly 'quantifiable' entity in the foreseeable future, the evolution of this concept continues to fuel exciting hypothesis-driven mechanistic research which contributes to advance knowledge in human metabolism and which is bound to result in improved strategies for the management of a healthy body weight. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

  16. Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma

    Directory of Open Access Journals (Sweden)

    Nicolai J. Wewer Albrechtsen

    2016-05-01

    Full Text Available Low-abundance regulatory peptides, including metabolically important gut hormones, have shown promising therapeutic potential. Here, we present a streamlined mass spectrometry-based platform for identifying and characterizing low-abundance regulatory peptides in humans. We demonstrate the clinical applicability of this platform by studying a hitherto neglected glucose- and appetite-regulating gut hormone, namely, oxyntomodulin. Our results show that the secretion of oxyntomodulin in patients with type 2 diabetes is significantly impaired, and that its level is increased by more than 10-fold after gastric bypass surgery. Furthermore, we report that oxyntomodulin is co-distributed and co-secreted with the insulin-stimulating and appetite-regulating gut hormone glucagon-like peptide-1 (GLP-1, is inactivated by the same protease (dipeptidyl peptidase-4 as GLP-1 and acts through its receptor. Thus, oxyntomodulin may participate with GLP-1 in the regulation of glucose metabolism and appetite in humans. In conclusion, this mass spectrometry-based platform is a powerful resource for identifying and characterizing metabolically active low-abundance peptides.

  17. A novel polysaccharide derived from algae extract induces apoptosis and cell cycle arrest in human gastric carcinoma MKN45 cells via ROS/JNK signaling pathway.

    Science.gov (United States)

    Xie, Peiyu; Fujii, Isao; Zhao, Jien; Shinohara, Makoto; Matsukura, Makoto

    2016-10-01

    In recent years, interest in biological activities of compounds from marine organisms has intensified. Cancer is the most principal enemy for human life and health. For the first time, to the best of our knowledge, we investigated a novel algae-derived polysaccharide for its role in inducing apoptosis and cell cycle arrest in human gastric carcinoma MKN45 cells. We found that the novel polysaccharide suppressed MKN45 cell proliferation, induced cell apoptosis and arrested the cells at G2/M phase. Furthermore, we observed that the generation of reactive oxygen species (ROS) and the phosphorylation of Jun N-terminal kinase (JNK), p53, caspase-9 and -3 were induced in the polysaccharide-treated MKN45 cells. In addition, pretreatment with N-acetyl-cysteine (NAC) and SP600125, the inhibitor of ROS and JNK, induced MKN45 cell proliferation, prevented the cell apoptosis and released the cells from cycle arrest. Finally, we found that pretreatment with NAC prevented the JNK, p53, caspase-9 and -3 protein phosphorylation induced by the polysaccharide, however, pretreatment with SP600125 did not affect the generation of ROS, suggesting that ROS is upstream of JNK. Taken together, the novel polysaccharide induced cancer cell apoptosis and arrested cell cycle via ROS/JNK signaling pathway.

  18. Adaptive working memory training improved brain function in human immunodeficiency virus-seropositive patients.

    Science.gov (United States)

    Chang, Linda; Løhaugen, Gro C; Andres, Tamara; Jiang, Caroline S; Douet, Vanessa; Tanizaki, Naomi; Walker, Christina; Castillo, Deborrah; Lim, Ahnate; Skranes, Jon; Otoshi, Chad; Miller, Eric N; Ernst, Thomas M

    2017-01-01

    We aimed to evaluate the effectiveness of an adaptive working memory (WM) training (WMT) program, the corresponding neural correlates, and LMX1A-rs4657412 polymorphism on the adaptive WMT, in human immunodeficiency virus (HIV) participants compared to seronegative (SN) controls. A total of 201 of 206 qualified participants completed baseline assessments before randomization to 25 sessions of adaptive WMT or nonadaptive WMT. A total of 74 of 76 (34 HIV, 42 SN) completed adaptive WMT and all 40 completed nonadaptive WMT (20 HIV, 20 SN) and were assessed after 1 month, and 55 adaptive WMT participants were also assessed after 6 months. Nontrained near-transfer WM tests (Digit-Span, Spatial-Span), self-reported executive functioning, and functional magnetic resonance images during 1-back and 2-back tasks were performed at baseline and each follow-up visit, and LMX1A-rs4657412 was genotyped in all participants. Although HIV participants had slightly lower cognitive performance and start index than SN at baseline, both groups improved on improvement index (>30%; false discovery rate [FDR] corrected p < 0.0008) and nontrained WM tests after adaptive WMT (FDR corrected, p ≤ 0.001), but not after nonadaptive WMT (training by training type corrected, p = 0.01 to p = 0.05) 1 month later. HIV participants (especially LMX1A-G carriers) also had poorer self-reported executive functioning than SN, but both groups reported improvements after adaptive WMT (Global: training FDR corrected, p = 0.004), and only HIV participants improved after nonadaptive WMT. HIV participants also had greater frontal activation than SN at baseline, but brain activation decreased in both groups at 1 and 6 months after adaptive WMT (FDR corrected, p < 0.0001), with normalization of brain activation in HIV participants, especially the LMX1A-AA carriers (LMX1A genotype by HIV status, cluster-corrected-p < 0.0001). Adaptive WMT, but not nonadaptive WMT, improved WM performance

  19. Adaptive working memory training improved brain function in human immunodeficiency virus–seropositive patients

    Science.gov (United States)

    Løhaugen, Gro C.; Andres, Tamara; Jiang, Caroline S.; Douet, Vanessa; Tanizaki, Naomi; Walker, Christina; Castillo, Deborrah; Lim, Ahnate; Skranes, Jon; Otoshi, Chad; Miller, Eric N.; Ernst, Thomas M.

    2016-01-01

    Objective We aimed to evaluate the effectiveness of an adaptive working memory (WM) training (WMT) program, the corresponding neural correlates, and LMX1A‐rs4657412 polymorphism on the adaptive WMT, in human immunodeficiency virus (HIV) participants compared to seronegative (SN) controls. Methods A total of 201 of 206 qualified participants completed baseline assessments before randomization to 25 sessions of adaptive WMT or nonadaptive WMT. A total of 74 of 76 (34 HIV, 42 SN) completed adaptive WMT and all 40 completed nonadaptive WMT (20 HIV, 20 SN) and were assessed after 1 month, and 55 adaptive WMT participants were also assessed after 6 months. Nontrained near‐transfer WM tests (Digit‐Span, Spatial‐Span), self‐reported executive functioning, and functional magnetic resonance images during 1‐back and 2‐back tasks were performed at baseline and each follow‐up visit, and LMX1A‐rs4657412 was genotyped in all participants. Results Although HIV participants had slightly lower cognitive performance and start index than SN at baseline, both groups improved on improvement index (>30%; false discovery rate [FDR] corrected p < 0.0008) and nontrained WM tests after adaptive WMT (FDR corrected, p ≤ 0.001), but not after nonadaptive WMT (training by training type corrected, p = 0.01 to p = 0.05) 1 month later. HIV participants (especially LMX1A‐G carriers) also had poorer self‐reported executive functioning than SN, but both groups reported improvements after adaptive WMT (Global: training FDR corrected, p = 0.004), and only HIV participants improved after nonadaptive WMT. HIV participants also had greater frontal activation than SN at baseline, but brain activation decreased in both groups at 1 and 6 months after adaptive WMT (FDR corrected, p < 0.0001), with normalization of brain activation in HIV participants, especially the LMX1A‐AA carriers (LMX1A genotype by HIV status, cluster‐corrected‐p < 0

  20. Human adaptation responses to a rapidly changing Arctic: A research context for building system resilience

    Science.gov (United States)

    Chapin, T.; Brinkman, T. J.

    2016-12-01

    Although human behavior accounts for more uncertainty in future trajectories in climate change than do biophysical processes, most climate-change research fails to include human actions in research design and implementation. This is well-illustrated in the Arctic. At the global scale, arctic processes strongly influence the strength of biophysical feedbacks between global human emissions and the rate of climate warming. However, most human actions in the arctic have little effect on these feedbacks, so research can contribute most effectively to reduction in arctic warming through improved understanding of the strength of arctic-global biophysical feedbacks, as in NASA's ABoVE program, and its effective communication to policy makers and the public. In contrast, at the local to regional scale within the arctic, human actions may influence the ecological and societal consequences of arctic warming, so research benefits from active stakeholder engagement in research design and implementation. Human communities and other stakeholders (government and NGOs) respond heterogeneously to socioeconomic and environmental change, so research that documents the range of historical and current adaptive responses to change provides insights on the resilience (flexibility of future options) of social-ecological processes in the arctic. Alaskan communities have attempted a range of adaptive responses to coastal erosion (e.g., seasonal migration, protection in place, relocation), wildfire (fire suppression to use of fire to manage wildlife habitat or landscape heterogeneity), declining sea ice (e.g., new hunting technology, sea ice observations and predictions), and changes in wildlife and fish availability (e.g., switch to harvest of alternative species, harvest times, or harvest locations). Research that draws on both traditional and western knowledge facilitates adaptation and predictions of the likely societal consequences of climate change in the Arctic. Effective inclusion of

  1. Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection.

    Directory of Open Access Journals (Sweden)

    Eun-Young Kim

    2014-07-01

    Full Text Available Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1 cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection.

  2. Adapting Human Videofluoroscopic Swallow Study Methods to Detect and Characterize Dysphagia in Murine Disease Models

    OpenAIRE

    Lever, Teresa E.; Braun, Sabrina M.; Brooks, Ryan T.; Harris, Rebecca A.; Littrell, Loren L.; Neff, Ryan M.; Hinkel, Cameron J.; Allen, Mitchell J.; Ulsas, Mollie A.

    2015-01-01

    This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research. Successful outcomes are dependent upon three critical components: test chambers that permit self-feeding while standing unrestrained in a confined space, recipes that mask the aversive taste/odor of commercially-available oral contrast agents, and a step-by-step test protocol that permits quantification of swallow physi...

  3. Human-Automation Interaction Design for Adaptive Cruise Control Systems of Ground Vehicles

    OpenAIRE

    Eom, Hwisoo; Lee, Sang Hun

    2015-01-01

    A majority of recently developed advanced vehicles have been equipped with various automated driver assistance systems, such as adaptive cruise control (ACC) and lane keeping assistance systems. ACC systems have several operational modes, and drivers can be unaware of the mode in which they are operating. Because mode confusion is a significant human error factor that contributes to traffic accidents, it is necessary to develop user interfaces for ACC systems that can reduce mode confusion. T...

  4. Adaptive Human-Aware Robot Navigation in Close Proximity to Humans

    DEFF Research Database (Denmark)

    Svenstrup, Mikael; Hansen, Søren Tranberg; Andersen, Hans Jørgen

    2011-01-01

    For robots to be able coexist with people in future everyday human environments, they must be able to act in a safe, natural and comfortable way. This work addresses the motion of a mobile robot in an environment, where humans potentially want to interact with it. The designed system consists...

  5. Adaptive interaction a utility maximization approach to understanding human interaction with technology

    CERN Document Server

    Payne, Stephen J

    2013-01-01

    This lecture describes a theoretical framework for the behavioural sciences that holds high promise for theory-driven research and design in Human-Computer Interaction. The framework is designed to tackle the adaptive, ecological, and bounded nature of human behaviour. It is designed to help scientists and practitioners reason about why people choose to behave as they do and to explain which strategies people choose in response to utility, ecology, and cognitive information processing mechanisms. A key idea is that people choose strategies so as to maximise utility given constraints. The frame

  6. Radiation-induced apoptosis in human tumor cell lines: adaptive response and split-dose effect.

    Science.gov (United States)

    Filippovich, I V; Sorokina, N I; Robillard, N; Lisbona, A; Chatal, J F

    1998-07-03

    Irradiation of human ovarian carcinoma cells (OVCAR 3) and myeloma cells (RPMI 8226) with graded doses of 137Cs-gamma-rays led to a 35-40% increase in time-dependent apoptosis 72 hr after 6-8 Gy irradiation. Large individual variations in sensitivity to radiation-induced apoptosis were noted in human lymphocytes obtained from 5 donors. Pretreatment of OVCAR 3 and RPMI 8226 cells with 0.01 Gy increased their resistance to apoptosis after subsequent 6 Gy irradiation several hours or 48 and 72 hr later. A dose of 4 or 8 Gy given in 2 equal fractions at an interval of a few hours produced a low level of apoptosis compared to that resulting from a single administration of the same total dose. Adaptive response was demonstrated in 2 out of 3 samples of human lymphocytes isolated from different donors, and no split-dose effect for apoptosis was noted in 2 other donors. In split-dose experiments, there was no correlation between the sensitivity of cells to apoptosis and their position in the cell cycle, after the first half-dose. No G1 block was observed in irradiated cell lines. Adaptive response and split-dose effect were prevented by 3-aminobenzamide and okadaic acid which inhibit poly(ADP-ribose)polymerase and protein phosphatase, respectively. These results imply a common mechanism for acquired resistance to radiation-induced apoptosis in adaptive response and the split-dose effect.

  7. Tumour gastrin expression and serum gastrin concentrations in dogs with gastric carcinoma are poor diagnostic indicators

    DEFF Research Database (Denmark)

    Seim-Wikse, T.; Kolbjørnsen, Ø.; Jörundsson, E.

    2014-01-01

    Hypergastrinaemia is observed commonly in human patients with gastric carcinoma and is associated with atrophic gastritis and Helicobacter pylori infection, both of which predispose to development of gastric tumours. Increased expression of gastrin is also described as a prognostic indicator...

  8. Prevalence of Helicobacter Pylori in Gastric Fluid in the Surgical Patient

    National Research Council Canada - National Science Library

    Mc

    1998-01-01

    Helicobacter pylori is a bacterium that infects the human gastric mucosa. It is well established as a primary factor in peptic ulcer disease and has been implicated in the pathogenesis of gastric adenocarcinoma...

  9. Soft Sweeps Are the Dominant Mode of Adaptation in the Human Genome.

    Science.gov (United States)

    Schrider, Daniel R; Kern, Andrew D

    2017-08-01

    The degree to which adaptation in recent human evolution shapes genetic variation remains controversial. This is in part due to the limited evidence in humans for classic "hard selective sweeps", wherein a novel beneficial mutation rapidly sweeps through a population to fixation. However, positive selection may often proceed via "soft sweeps" acting on mutations already present within a population. Here, we examine recent positive selection across six human populations using a powerful machine learning approach that is sensitive to both hard and soft sweeps. We found evidence that soft sweeps are widespread and account for the vast majority of recent human adaptation. Surprisingly, our results also suggest that linked positive selection affects patterns of variation across much of the genome, and may increase the frequencies of deleterious mutations. Our results also reveal insights into the role of sexual selection, cancer risk, and central nervous system development in recent human evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

    Science.gov (United States)

    Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

    2014-01-01

    Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

  11. Upregulation of autophagy-related gene-5 (ATG-5 is associated with chemoresistance in human gastric cancer.

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    Jie Ge

    Full Text Available Autophagy-related gene-5 (ATG-5 is one of the key regulators of autophagic cell death. It has been widely regarded as a protective molecular mechanism for tumor cells during the course of chemotherapy. In the present study, we investigated the expression pattern of ATG-5 and multidrug resistance-associated protein-1 (MRP-1 in 135 gastric cancers (GC patients who were treated with epirubicin, cisplatin and 5-FU adjuvant chemotherapy (ECF following surgical resection and explored their potential clinical significance. We found that both ATG-5 (77.78% and MRP-1 (79.26% were highly expressed in GC patients. ATG-5 expression was significantly associated with depth of wall invasion, TNM stages and distant metastasis of GC (P<0.05, whereas MRP-1 expression was significantly linked with tumor size, depth of wall invasion, lymph node metastasis, TNM stages and differentiation status (P<0.05. ATG-5 expression was positively correlated with MRP-1 (rp = 0.616, P<0.01. Increased expression of ATG-5 and MPR-1 was significantly correlated with poor overall survival (OS; P<0.01 and disease free survival (DFS; P<0.01 of our GC cohort. Furthermore, we demonstrated that ATG-5 was involved in drug resistant of GC cells, which was mainly through regulating autophagy. Our data suggest that upregulated expression of ATG-5, an important molecular feature of protective autophagy, is associated with chemoresistance in GC. Expression of ATG-5 and MRP-1 may be independent prognostic markers for GC treatment.

  12. Biocompatible curcumin loaded PMMA-PEG/ZnO nanocomposite induce apoptosis and cytotoxicity in human gastric cancer cells.

    Science.gov (United States)

    Dhivya, Raman; Ranjani, Jothi; Bowen, Patrick K; Rajendhran, Jeyaprakash; Mayandi, Jeyanthinath; Annaraj, Jamespandi

    2017-11-01

    Although curcumin is efficient in killing cancer cells, its poor water solubility and assocaited inadequate bioavailability remain major limitations to its therapeutic application. The formulation of curcumin micellar nanoparticles (NPs) encapsulated with a biodegradable polymer promises to significantly improve curcumin's solubility, stability, and bioavailability. The past decade has witnessed the development of nanoscale curcumin delivery systems: curcumin-loaded liposomes or nanoparticles, self-microemulsifying drug delivery systems (SMEDDS), cyclodextrin inclusions, solid dispersions, nanodisks, and nanotubes. The intention of the present investigation was to enhance the bioavailability and ultimately the efficacy of curcumin by developing a curcumin loaded PMMA-PEG/ZnO bionanocomposite utilizing insoluble curcumin and poorly soluble ZnO nanoparticles. Here, the drug (curcumin) may be carry and deliver the biomolecule(s) by polymer-encapsulated ZnO NPs. Physical characteristics of these novel nanomaterials have been studied with transmission electron microscopy (TEM) and powder X-ray diffraction (XRD) in conjunction with spectral techniques. Aqueous solubility of curcumin was augmented upon conjugation with the polymer-stabilized ZnO NPs. A narrow nanocomposite particle size distribution with an average value of 40 to 90nm was found via TEM. Most importantly, the pH-responsive release of curcumin from the nano-vehicle ensures safer, more controlled delivery of the drug at physiological pH. Cytotoxic potential and cellular uptake of curcumin loaded ZnO NPs were assessed by) cell viability assay, cell cycle assays along with the cell imaging studies have been done in addition to MTT using AGS cancer cells. Hence, these studies demonstrate that the clinical potential of the Curcumin Loaded PMMA-PEG/ZnO can induce the apoptosis of cancer cells through a cell cycle mediated apoptosis corridor, which raises its probability to cure gastric cancer cells. Copyright

  13. Serum Bile Acids Are Higher in Humans With Prior Gastric Bypass: Potential Contribution to Improved Glucose and Lipid Metabolism

    Science.gov (United States)

    Patti, Mary-Elizabeth; Houten, Sander M.; Bianco, Antonio C.; Bernier, Raquel; Larsen, P. Reed; Holst, Jens J.; Badman, Michael K.; Maratos-Flier, Eleftheria; Mun, Edward C.; Pihlajamaki, Jussi; Auwerx, Johan; Goldfine, Allison B.

    2015-01-01

    The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 ± 4.84 µmol/l) than in both overweight (3.59 ± 1.95, P = 0.005, Ov) and severely obese (3.86 ± 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids were all significantly higher in GB compared to Ov (P fasting triglycerides (r = −0.40, P = 0.05), and positively correlated with adiponectin (r = −0.48, P < 0.02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P < 0.003). Total bile acids strongly correlated inversely with thyrotropic hormone (TSH) (r = −0.57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB. PMID:19360006

  14. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission.

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    Tulika Arora

    Full Text Available Roux-en-Y gastric bypass (RYGB is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3, which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

  15. Study on the proliferation of human gastric cancer cell AGS by activation of EGFR in H2O2.

    Science.gov (United States)

    Wang, Q; Shen, W; Tao, G-Q; Sun, J; Shi, L-P

    2017-03-01

    This study is to investigate the effect of low concentration hydrogen peroxide (H2O2) on the proliferation of gastric cancer AGS cell line in vitro and the mechanism. AGS cells were treated with different low concentrations of H2O2 (1, 0.1, 0.01, and 0.001 μm) for 48 hours. The effect of H2O2 concentration gradient on the activity of AGS cell activities was detected by methyl thiazolyl tetrazolium (MTT) method. The expression of the epidermal growth factor receptor (EGFR) and its downstream signaling pathway extracellular signal-regulated kinase (ERK) protein in H2O2 was detected by Western blot method; moreover, the effect of H2O2 on intracellular reactive oxygen species (ROS) in AGS cells was observed under the fluorescence microscope and quantitative analysis by flow cytometry. The effect of H2O2 on the level of c-myc mRNA in AGS cells was also detected by reverse transcription polymerase chain reaction (RT-PCR). MTT detection results showed that 1 μm and 0.1 μm H2O2 at 48h can effectively promote the proliferation of AGS cells (pH2O2 treatment of AGS cells, the EGFR protein levels and ERK protein phosphorylation levels increased significantly (pH2O2 increased the intracellular reactive oxygen species (ROS). RT-PCR results showed the levels of c-myc mRNA in AGS cells treated with a low concentration of H2O2 were significantly increased (pH2O2 can significantly promote the proliferation of AGS cells by activating EGFR/ERK signaling pathway.

  16. Early humans' egalitarian politics: runaway synergistic competition under an adapted veil of ignorance.

    Science.gov (United States)

    Harvey, Marc

    2014-09-01

    This paper proposes a model of human uniqueness based on an unusual distinction between two contrasted kinds of political competition and political status: (1) antagonistic competition, in quest of dominance (antagonistic status), a zero-sum, self-limiting game whose stake--who takes what, when, how--summarizes a classical definition of politics (Lasswell 1936), and (2) synergistic competition, in quest of merit (synergistic status), a positive-sum, self-reinforcing game whose stake becomes "who brings what to a team's common good." In this view, Rawls's (1971) famous virtual "veil of ignorance" mainly conceals politics' antagonistic stakes so as to devise the principles of a just, egalitarian society, yet without providing any means to enforce these ideals (Sen 2009). Instead, this paper proposes that human uniqueness flourished under a real "adapted veil of ignorance" concealing the steady inflation of synergistic politics which resulted from early humans' sturdy egalitarianism. This proposition divides into four parts: (1) early humans first stumbled on a purely cultural means to enforce a unique kind of within-team antagonistic equality--dyadic balanced deterrence thanks to handheld weapons (Chapais 2008); (2) this cultural innovation is thus closely tied to humans' darkest side, but it also launched the cumulative evolution of humans' brightest qualities--egalitarian team synergy and solidarity, together with the associated synergistic intelligence, culture, and communications; (3) runaway synergistic competition for differential merit among antagonistically equal obligate teammates is the single politically selective mechanism behind the cumulative evolution of all these brighter qualities, but numerous factors to be clarified here conceal this mighty evolutionary driver; (4) this veil of ignorance persists today, which explains why humans' unique prosocial capacities are still not clearly understood by science. The purpose of this paper is to start lifting

  17. The first whole genome and transcriptome of the cinereous vulture reveals adaptation in the gastric and immune defense systems and possible convergent evolution between the Old and New World vultures.

    Science.gov (United States)

    Chung, Oksung; Jin, Seondeok; Cho, Yun Sung; Lim, Jeongheui; Kim, Hyunho; Jho, Sungwoong; Kim, Hak-Min; Jun, JeHoon; Lee, HyeJin; Chon, Alvin; Ko, Junsu; Edwards, Jeremy; Weber, Jessica A; Han, Kyudong; O'Brien, Stephen J; Manica, Andrea; Bhak, Jong; Paek, Woon Kee

    2015-10-21

    The cinereous vulture, Aegypius monachus, is the largest bird of prey and plays a key role in the ecosystem by removing carcasses, thus preventing the spread of diseases. Its feeding habits force it to cope with constant exposure to pathogens, making this species an interesting target for discovering functionally selected genetic variants. Furthermore, the presence of two independently evolved vulture groups, Old World and New World vultures, provides a natural experiment in which to investigate convergent evolution due to obligate scavenging. We sequenced the genome of a cinereous vulture, and mapped it to the bald eagle reference genome, a close relative with a divergence time of 18 million years. By comparing the cinereous vulture to other avian genomes, we find positively selected genetic variations in this species associated with respiration, likely linked to their ability of immune defense responses and gastric acid secretion, consistent with their ability to digest carcasses. Comparisons between the Old World and New World vulture groups suggest convergent gene evolution. We assemble the cinereous vulture blood transcriptome from a second individual, and annotate genes. Finally, we infer the demographic history of the cinereous vulture which shows marked fluctuations in effective population size during the late Pleistocene. We present the first genome and transcriptome analyses of the cinereous vulture compared to other avian genomes and transcriptomes, revealing genetic signatures of dietary and environmental adaptations accompanied by possible convergent evolution between the Old World and New World vultures.

  18. Adapting Preclinical Benchmarks for First-in-Human Trials of Human Embryonic Stem Cell-Based Therapies.

    Science.gov (United States)

    Barazzetti, Gaia; Hurst, Samia A; Mauron, Alexandre

    2016-08-01

    : As research on human embryonic stem cell (hESC)-based therapies is moving from the laboratory to the clinic, there is an urgent need to assess when it can be ethically justified to make the step from preclinical studies to the first protocols involving human subjects. We examined existing regulatory frameworks stating preclinical requirements relevant to the move to first-in-human (FIH) trials and assessed how they may be applied in the context of hESC-based interventions to best protect research participants. Our findings show that some preclinical benchmarks require rethinking (i.e., identity, purity), while others need to be specified (i.e., potency, viability), owing to the distinctive dynamic heterogeneity of hESC-based products, which increases uncertainty and persistence of safety risks and allows for limited predictions of effects in vivo. Rethinking or adaptation of how to apply preclinical benchmarks in specific cases will be required repeatedly for different hESC-based products. This process would benefit from mutual learning if researchers included these components in the description of their methods in publications. To design translational research with an eye to protecting human participants in early trials, researchers and regulators need to start their efforts at the preclinical stage. Existing regulatory frameworks for preclinical research, however, are not really adapted to this in the case of stem cell translational medicine. This article reviews existing regulatory frameworks for preclinical requirements and assesses how their underlying principles may best be applied in the context of human embryonic stem cell-based interventions for the therapy of Parkinson's disease. This research will help to address the question of when it is ethically justified to start first-in-human trials in stem cell translational medicine. ©AlphaMed Press.

  19. Correlation between pepsinogens and gastric cancer

    International Nuclear Information System (INIS)

    Jiang Mengjun; Xiao Zhijian; Yang Xizhen; Huang Xuquan; Yu Huixin; Zhang Rongjun; Tao Yonghui; Zhang Lianfen; Cai Gangming; Tan Cheng; Xiao Ye; Jin Jian; Wang Bocheng

    2001-01-01

    Pepsinogen I and Pepsinogen II (PG I and PG II) were purified from human gastric mucosa using DE-52 anion exchange chromatography, Gel filtration HPLC and Q-2 anion exchange fast pressure chromatography. The antiserums against at both PG I and PG II were established respectively by preparing 125 I-PG I and 125 I-PG II using the chloramine-T method. Serum Pepsinogen I and II levels were measured by RIA in 190 healthy controls and other gastric diseases. The results were analyzed by statistics method. Compared with healthy controls, the serum PG I levels of duodenal ulcer patients and gastric ulcer were significantly higher. The serum PG I levels of gastritis patients were significantly lower and the serum PG I levels and PG I/PG II ratio of gastric cancer patients were much more lower. After total gastrectomy, the serum PG I and PG II levels of patients with recurrence of gastric cancer were significantly higher than those without recurrence. The changes of serum PG I and PG II levels are valuable for the diagnosis of gastric cancer and detecting the recurrence of gastric cancer after total gastrectomy

  20. PTEN Gene Induces Cell Invasion and Migration via Regulating AKT/GSK-3β/β-Catenin Signaling Pathway in Human Gastric Cancer.

    Science.gov (United States)

    Ma, Jingjing; Guo, Xufeng; Zhang, Jixiang; Wu, Dandan; Hu, Xue; Li, Jiao; Lan, Qingzhi; Liu, Ya; Dong, Weiguo

    2017-12-01

    Abnormality of PTEN gene and Wnt/β-catenin signaling have been strongly implicated in various malignant cancers. Recently, it has been noted that a functional interaction/cross-talk was found between the PTEN/PI3K/AKT and Wnt/β-catenin, which plays a key role in the development of cancers. However, few related studies on gastric cancer are available. We examined the expression of PTEN and β-catenin in gastric cancer tissues and detected whether down-regulation of PTEN promotes the migration and invasion in gastric cancer cells along with its underlying mechanism. Immunocytochemistry, a wound healing assay, a Matrigel invasion assay, an immunofluorescence staining were performed to detect expression of PTEN and β-catenin in gastric cancer and adjacent normal tissues, cell migration, cell invasion, and the effects of PTEN knockdown on β-catenin in cells, respectively. Further, MMP-2 and MMP-9 activities were analyzed by zymography assay. The changes in related proteins were further quantified by western blotting. Low expression of PTEN was found in majority of gastric cancer tissues, which showed significant associations with differentiation grade in gastric cancer patients. Further, a negative correlation was revealed between PTEN and β-catenin protein expression in gastric cancer tissues (r = - 0.546, P PTEN knockdown promoted the migration and invasion of cells and caused an obvious increase in p-AKT, p-GSK-3β, β-catenin, E-cadherin, MMP-7, MMP-2, and MMP-9 in gastric cancer cells. Our results indicated PTEN gene might induce cell invasion and migration via regulating AKT/GSK-3β/β-catenin signaling pathway, playing a vital role in the progression of gastric cancer.

  1. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

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    Matteo Fumagalli

    2011-11-01

    Full Text Available Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the

  2. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

    Science.gov (United States)

    Fumagalli, Matteo; Sironi, Manuela; Pozzoli, Uberto; Ferrer-Admetlla, Anna; Ferrer-Admettla, Anna; Pattini, Linda; Nielsen, Rasmus

    2011-11-01

    Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some

  3. Role of lipase in the regulation of postprandial gastric acid secretion and emptying of fat in humans: a study with orlistat, a highly specific lipase inhibitor

    OpenAIRE

    Borovicka, J; Schwizer, W; Guttmann, G; Hartmann, D; Kosinski, M; Wastiel, C; Bischof-Delaloye, A; Fried, M

    2000-01-01

    BACKGROUND AND AIMS—To investigate the importance of lipase on gastric functions, we studied the effects of orlistat, a potent and specific inhibitor of lipase, on postprandial gastric acidity and gastric emptying of fat.
METHODS—Fourteen healthy volunteers participated in a double blind, placebo controlled, randomised study. In a two way cross over study with two test periods of five days, separated by at least 14 days, orlistat 120 mg three times daily or placebo was given with standardised...

  4. Overexpression of nuclear apoptosis-inducing factor 1 altered the proteomic profile of human gastric cancer cell MKN45 and induced cell cycle arrest at G1/S phase.

    Directory of Open Access Journals (Sweden)

    Mei Yang

    Full Text Available Nuclear apoptosis-inducing factor 1 (NAIF1 was previously reported to induce apoptosis. Moreover, the expression of NAIF1 was significantly down-regulated in human gastric cancer tissues compared to adjacent normal tissues. However, the mechanism by which the NAIF1 gene induces apoptosis is not fully understood. Our results show that NAIF1 was minimally expressed in all the tested gastric cancer cell lines. Our data also demonstrates that NAIF1 is localized in the nuclei of cells as detected by monitoring the green fluorescence of NAIF1-GFP fusion protein using fluorescent confocal microscopy. Next, a comparative proteomic approach was used to identify the differential expression of proteins between gastric cancer cell lines MKN45/NAIF1 (- and MKN45/NAIF1 (+. We found five proteins (proteasome 26S subunit 2, proteasome 26S subunit 13, NADH dehydrogenase Fe-S protein 1, chaperonin containing TCP1 subunit 3 and thioredoxin reductase 1 that were up-regulated and three proteins (ribonuclease inhibitor 1, 14-3-3 protein epsilon isoform and apolipoprotein A-I binding protein that were down-regulated in the MKN45 cells overexpressing NAIF1. We also discovered that NAIF1 could induce cell cycle arrest at G1/S phase by altering the expression of cell cycle proteins cyclinD1, cdc2 and p21. The differentially expressed proteins identified here are related to various cellular programs involving cell cycle, apoptosis, and signal transduction regulation and suggest that NAIF1 may be a tumor suppressor in gastric cancer. Our research provides evidence that elucidates the role of how NAIF1 functions in gastric cancer.

  5. Lack of adaptation to human tetherin in HIV-1 Group O and P

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    Haworth Kevin G

    2011-09-01

    Full Text Available Abstract Background HIV-1 viruses are categorized into four distinct groups: M, N, O and P. Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts. Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin. This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin. Results We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses. Furthermore, we found no evidence of anti-human tetherin activity in a fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus. Interestingly, an activity against primate tetherins was retained in the Nef proteins from both a group O and a group P virus. By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin. We further demonstrated the importance of residue alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions. Conclusions The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread.

  6. Colloquium paper: adaptive specializations, social exchange, and the evolution of human intelligence.

    Science.gov (United States)

    Cosmides, Leda; Barrett, H Clark; Tooby, John

    2010-05-11

    Blank-slate theories of human intelligence propose that reasoning is carried out by general-purpose operations applied uniformly across contents. An evolutionary approach implies a radically different model of human intelligence. The task demands of different adaptive problems select for functionally specialized problem-solving strategies, unleashing massive increases in problem-solving power for ancestrally recurrent adaptive problems. Because exchange can evolve only if cooperators can detect cheaters, we hypothesized that the human mind would be equipped with a neurocognitive system specialized for reasoning about social exchange. Whereas humans perform poorly when asked to detect violations of most conditional rules, we predicted and found a dramatic spike in performance when the rule specifies an exchange and violations correspond to cheating. According to critics, people's uncanny accuracy at detecting violations of social exchange rules does not reflect a cheater detection mechanism, but extends instead to all rules regulating when actions are permitted (deontic conditionals). Here we report experimental tests that falsify these theories by demonstrating that deontic rules as a class do not elicit the search for violations. We show that the cheater detection system functions with pinpoint accuracy, searching for violations of social exchange rules only when these are likely to reveal the presence of someone who intends to cheat. It does not search for violations of social exchange rules when these are accidental, when they do not benefit the violator, or when the situation would make cheating difficult.

  7. Shared Genetic Signals of Hypoxia Adaptation in Drosophila and in High-Altitude Human Populations

    Science.gov (United States)

    Jha, Aashish R.; Zhou, Dan; Brown, Christopher D.; Kreitman, Martin; Haddad, Gabriel G.; White, Kevin P.

    2016-01-01

    The ability to withstand low oxygen (hypoxia tolerance) is a polygenic and mechanistically conserved trait that has important implications for both human health and evolution. However, little is known about the diversity of genetic mechanisms involved in hypoxia adaptation in evolving populations. We used experimental evolution and whole-genome sequencing in Drosophila melanogaster to investigate the role of natural variation in adaptation to hypoxia. Using a generalized linear mixed model we identified significant allele frequency differences between three independently evolved hypoxia-tolerant populations and normoxic control populations for approximately 3,800 single nucleotide polymorphisms. Around 50% of these variants are clustered in 66 distinct genomic regions. These regions contain genes that are differentially expressed between hypoxia-tolerant and normoxic populations and several of the differentially expressed genes are associated with metabolic processes. Additional genes associated with respiratory and open tracheal system development also show evidence of directional selection. RNAi-mediated knockdown of several candidate genes’ expression significantly enhanced survival in severe hypoxia. Using genomewide single nucleotide polymorphism data from four high-altitude human populations—Sherpas, Tibetans, Ethiopians, and Andeans, we found that several human orthologs of the genes under selection in flies are also likely under positive selection in all four high-altitude human populations. Thus, our results indicate that selection for hypoxia tolerance can act on standing genetic variation in similar genes and pathways present in organisms diverged by hundreds of millions of years. PMID:26576852

  8. The cucurbitacins D, E, and I from Ecballium elaterium (L. upregulate the LC3 gene and induce cell-cycle arrest in human gastric cancer cell line AGS

    Directory of Open Access Journals (Sweden)

    Naser Jafargholizadeh

    2018-03-01

    Full Text Available Objective(s: Cucurbitacins exhibit a range of anti-cancer functions. We investigated the effects of cucurbitacins D, E, and I purified from Ecballium elaterium (L. A. Rich fruits on some apoptotic and autophagy genes in human gastric cancer cell line AGS. Materials and Methods: Using quantitative reverse transcription PCR (qRT-PCR, the expression of LC3, VEGF, BAX, caspase-3, and c-MYC genes were quantified in AGS cells 24 hr after treatment with cucurbitacins D, E, and I at concentrations 0.3, 0.1 and 0.5 μg/ml, respectively. Cell cycle and death were analyzed by flowcytometry. Results: Purified cucurbitacins induced sub-G1 cell-cycle arrest and cell death in AGS cells and upregulated LC3mRNA effectively, but showed a very low effect on BAX, caspase-3, and c-MYC mRNA levels. Also after treatment with cucurbitacin I at concentration 0.5 μg/ml, VEGF mRNA levels were increased about 4.4 times. Pairwise comparison of the effect of cucurbitacins D, E, and I on LC3 mRNA expression showed that the cucurbitacin I effect is 1.3 and 1.1 times that of cucurbitacins E and D, respectively; cucurbitacin D effect is 1.2 times that of cucurbitacin E (P-value

  9. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway.

    Science.gov (United States)

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87) Cell Line.

    Science.gov (United States)

    Atnip, Allison A; Sigurdson, Gregory T; Bomser, Joshua; Giusti, M Mónica

    2017-02-18

    Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87) has been used to study the behavior of anthocyanins at a pH range of 3.0-7.4. This work examines the effects of time (0-3 h), concentration (50-1500 µM), and pH (3.0, 5.0, 7.4) on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0.

  11. X irradiation combined with TNF alpha-related apoptosis-inducing ligand (TRAIL) reduces hypoxic regions of human gastric adenocarcinoma xenografts in SCID mice

    International Nuclear Information System (INIS)

    Takahashi, Momoko; Yasui, Hironobu; Ogura, Aki; Asanuma, Taketoshi; Inanami, Osamu; Kubota, Nobuo; Tsujitani, Michihiko; Kuwabara, Mikinori

    2008-01-01

    Our previous study showed that X irradiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines under not only normoxia but also hypoxia. X irradiation combined with TNF α-related apoptosis-inducing ligand (TRAIL), which is the ligand of DR5, induced apoptosis in vitro (Takahashi et al., (2007) Journal of Radiation Research, 48: 461-468). In this report, we examined the in vivo antitumor efficacy of X irradiation combined with TRAIL treatment in tumor xenograft models derived from human gastric adenocarcinoma MKN45 and MKN28 cells in severe combined immunodeficiency (SCID) mice. X irradiation combined with TRAIL synergistically suppressed the tumor growth rates in the xenograft models derived from MKN45 and MKN28 cells, which have wild type Tp53 and mutated Tp53, respectively, indicating that the antitumor effects occurred in a Tp53-independent manner. Histological analysis showed that the combination of X irradiation and TRAIL induced caspase-3-dependent apoptotic cell death. Moreover, the immunohistochemical detection of hypoxic regions using the hypoxic marker pimonidazole revealed that caspase-3-dependent apoptosis occurred in the hypoxic regions in the tumors. These results indicated that X irradiation combined with TRAIL may be a useful treatment to reduce tumor growth in not only normoxic but also hypoxic regions. (author)

  12. In vivo imaging of human photoreceptor mosaic with wavefront sensorless adaptive optics optical coherence tomography.

    Science.gov (United States)

    Wong, Kevin S K; Jian, Yifan; Cua, Michelle; Bonora, Stefano; Zawadzki, Robert J; Sarunic, Marinko V

    2015-02-01

    Wavefront sensorless adaptive optics optical coherence tomography (WSAO-OCT) is a novel imaging technique for in vivo high-resolution depth-resolved imaging that mitigates some of the challenges encountered with the use of sensor-based adaptive optics designs. This technique replaces the Hartmann Shack wavefront sensor used to measure aberrations with a depth-resolved image-driven optimization algorithm, with the metric based on the OCT volumes acquired in real-time. The custom-built ultrahigh-speed GPU processing platform and fast modal optimization algorithm presented in this paper was essential in enabling real-time, in vivo imaging of human retinas with wavefront sensorless AO correction. WSAO-OCT is especially advantageous for developing a clinical high-resolution retinal imaging system as it enables the use of a compact, low-cost and robust lens-based adaptive optics design. In this report, we describe our WSAO-OCT system for imaging the human photoreceptor mosaic in vivo. We validated our system performance by imaging the retina at several eccentricities, and demonstrated the improvement in photoreceptor visibility with WSAO compensation.

  13. Do calories or osmolality determine gastric emptying

    International Nuclear Information System (INIS)

    Shafer, R.B.; Levine, A.S.; Marlette, J.M.; Morley, J.E.

    1984-01-01

    Recent animal studies suggest that gastric emptying is dependent on the caloric and osmotic content of the ingested food. These studies have involved intubation with infusion of liquid meals into the stomach. Scintigraphic methods, which are non-invasive and do not alter normal physiology, are now available for precise quantitation of gastric emptying. To study the role of calories and osmolality on gastric emptying, the authors employed a standardized /sup 99m/Tc-scrambled egg meal washed with 50 cc tap water in 10 normal human volunteers. A variety of simple and complex sugars, non-absorbable complex carbohydrate (polycose), medium chain fatty acid (MCFA) and gluten were dissolved in water and ingested with the test meal. Each subject acted as his own control. Coefficient of variation in control tests in each subject 12 weeks apart was 9.9%. Results showed that incremental glucose (25-66 gm) produced a linear increase in gastric emptying (T/2 control 50 +- 3, 25 gm 60 +- 3, 50 gm 79 +- 3 and 66 gm 102 +- 3 minutes). 25 gm fructose (T/2 59 +- 3 minutes) and 25 gm polycose (T/2 59 +- 3 minutes) had similar effects to glucose. 25 gm sucrose and 25 gm gluten did not significantly differ from controls. MCFA had an effect similar to 50 gm glucose - suggesting that calories are important in gastric emptying. However, 25 gm xylose markedly prolonged gastric emptying to 80 +- 5 minutes. The rank order for osmolality for substances tested MCFA = gluten < polycose < polycose < fructose < sucrose = glucose < xylose defined no relationship to gastric emptying. The authors' results suggest that neither calories nor osmolality alone determine gastric emptying. A specific food does not necessarily have the same effect on gastric emptying in different individuals

  14. A Conceptual Architecture for Adaptive Human-Computer Interface of a PT Operation Platform Based on Context-Awareness

    Directory of Open Access Journals (Sweden)

    Qing Xue

    2014-01-01

    Full Text Available We present a conceptual architecture for adaptive human-computer interface of a PT operation platform based on context-awareness. This architecture will form the basis of design for such an interface. This paper describes components, key technologies, and working principles of the architecture. The critical contents covered context information modeling, processing, relationship establishing between contexts and interface design knowledge by use of adaptive knowledge reasoning, and visualization implementing of adaptive interface with the aid of interface tools technology.

  15. Role of Helicobacter pylori in gastric cancer: Updates

    Science.gov (United States)

    Khatoon, Jahanarah; Rai, Ravi Prakash; Prasad, Kashi Nath

    2016-01-01

    Helicobacter pylori (H. pylori) infection is highly prevalent in human, affecting nearly half of the world’s population; however, infection remains asymptomatic in majority of population. During its co-existence with humans, H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side, presence of H. pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer (GC). A complex combination of host genetics, environmental agents, and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world, they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis, the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC. PMID:26909129

  16. Detection of Human Impacts by an Adaptive Energy-Based Anisotropic Algorithm

    Directory of Open Access Journals (Sweden)

    Manuel Prado-Velasco

    2013-10-01

    Full Text Available Boosted by health consequences and the cost of falls in the elderly, this work develops and tests a novel algorithm and methodology to detect human impacts that will act as triggers of a two-layer fall monitor. The two main requirements demanded by socio-healthcare providers—unobtrusiveness and reliability—defined the objectives of the research. We have demonstrated that a very agile, adaptive, and energy-based anisotropic algorithm can provide 100% sensitivity and 78% specificity, in the task of detecting impacts under demanding laboratory conditions. The algorithm works together with an unsupervised real-time learning technique that addresses the adaptive capability, and this is also presented. The work demonstrates the robustness and reliability of our new algorithm, which will be the basis of a smart falling monitor. This is shown in this work to underline the relevance of the results.

  17. How do precision medicine and system biology response to human body's complex adaptability?

    Science.gov (United States)

    Yuan, Bing

    2016-12-01

    In the field of life sciences, although system biology and "precision medicine" introduce some complex scientifific methods and techniques, it is still based on the "analysis-reconstruction" of reductionist theory as a whole. Adaptability of complex system increase system behaviour uncertainty as well as the difficulties of precise identifification and control. It also put systems biology research into trouble. To grasp the behaviour and characteristics of organism fundamentally, systems biology has to abandon the "analysis-reconstruction" concept. In accordance with the guidelines of complexity science, systems biology should build organism model from holistic level, just like the Chinese medicine did in dealing with human body and disease. When we study the living body from the holistic level, we will fifind the adaptability of complex system is not the obstacle that increases the diffificulty of problem solving. It is the "exceptional", "right-hand man" that helping us to deal with the complexity of life more effectively.

  18. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

    Science.gov (United States)

    Parsons, Bryony N; Ijaz, Umer Z; D'Amore, Rosalinda; Burkitt, Michael D; Eccles, Richard; Lenzi, Luca; Duckworth, Carrie A; Moore, Andrew R; Tiszlavicz, Laszlo; Varro, Andrea; Hall, Neil; Pritchard, D Mark

    2017-11-01

    Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

  19. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

    Science.gov (United States)

    Eccles, Richard; Duckworth, Carrie A.; Varro, Andrea

    2017-01-01

    Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. PMID:29095917

  20. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

    Directory of Open Access Journals (Sweden)

    Bryony N Parsons

    2017-11-01

    Full Text Available Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq. Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

  1. Enterococcus faecalis Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A. B; Desler, Claus; Martin-Bertelsen, Tomas

    2013-01-01

    Background Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and ...... in gastric cell culture. Finally the bacteria induced an NF-κB inflammatory response as well as impaired DNA damage response and cell cycle control gene expression....

  2. Gastric emptying in patients with gastric ulcer

    International Nuclear Information System (INIS)

    Harding, L.K.; Anselmi, M.; Donovan, I.A.; Alexander-Williams, J.

    1982-01-01

    The estimated volume of meal in the stomach 30 mins after sup(113m)In-DTPA administration was determined in patients with gastric ulcer and normal controls by 1) relating counts in the stomach to those in the whole field of view of the gamma camera and 2) aspirations. In the normal controls there was no significant difference between the two methods but in the gastric ulcer patients, the gamma camera method predicted significantly more meal in the stomach than was recovered by aspiration. It was suggested that the large low lying stomach found in gastric ulcer disease causes extensive overlap of the small bowel and invalidates measurements of gastric emptying made by a gamma camera. (U.K.)

  3. Sensory-Motor Adaptation to Space Flight: Human Balance Control and Artificial Gravity

    Science.gov (United States)

    Paloski, William H.

    2004-01-01

    Gravity, which is sensed directly by the otolith organs and indirectly by proprioceptors and exteroceptors, provides the CNS a fundamental reference for estimating spatial orientation and coordinating movements in the terrestrial environment. The sustained absence of gravity during orbital space flight creates a unique environment that cannot be reproduced on Earth. Loss of this fundamental CNS reference upon insertion into orbit triggers neuro-adaptive processes that optimize performance for the microgravity environment, while its reintroduction upon return to Earth triggers neuro-adaptive processes that return performance to terrestrial norms. Five pioneering symposia on The Role of the Vestibular Organs in the Exploration of Space were convened between 1965 and 1970. These innovative meetings brought together the top physicians, physiologists, and engineers in the vestibular field to discuss and debate the challenges associated with human vestibular system adaptation to the then novel environment of space flight. These highly successful symposia addressed the perplexing problem of how to understand and ameliorate the adverse physiological effects on humans resulting from the reduction of gravitational stimulation of the vestibular receptors in space. The series resumed in 2002 with the Sixth Symposium, which focused on the microgravity environment as an essential tool for the study of fundamental vestibular functions. The three day meeting included presentations on historical perspectives, vestibular neurobiology, neurophysiology, neuroanatomy, neurotransmitter systems, theoretical considerations, spatial orientation, psychophysics, motor integration, adaptation, autonomic function, space motion sickness, clinical issues, countermeasures, and rehabilitation. Scientists and clinicians entered into lively exchanges on how to design and perform mutually productive research and countermeasure development projects in the future. The problems posed by long duration

  4. Efficacy of laser capture microdissection plus RT-PCR technique in analyzing gene expression levels in human gastric cancer and colon cancer

    International Nuclear Information System (INIS)

    Makino, Hiroshi; Uetake, Hiroyuki; Danenberg, Kathleen; Danenberg, Peter V; Sugihara, Kenichi

    2008-01-01

    Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase gene expressions are reported to be valid predictive markers for 5-fluorouracil sensitivity to gastrointestinal cancer. For more reliable predictability, their expressions in cancer cells and stromal cells in the cancerous tissue (cancerous stroma) have been separately investigated using laser capture microdissection. Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase mRNA in cancer cells and cancerous stroma from samples of 47 gastric and 43 colon cancers were separately quantified by reverse transcription polymerase chain reaction after laser capture microdissection. In both gastric and colon cancers, thymidylate synthase and orotate phosphoribosyltransferase mRNA expressions were higher (p < 0.0001, p <0.0001 respectively in gastric cancer and P = 0.0002, p < 0.0001 respectively in colon cancer) and dihydropyrimidine dehydrogenase mRNA expressions were lower in cancer cells than in cancerous stroma (P = 0.0136 in gastric cancer and p < 0.0001 in colon cancer). In contrast, thymidine phosphorylase mRNA was higher in cancer cells than in cancerous stroma in gastric cancer (p < 0.0001) and lower in cancer cells than in cancerous stroma in colon cancer (P = 0.0055). By using this method, we could estimate gene expressions separately in cancer cells and stromal cells from colon and gastric cancers, in spite of the amount of stromal tissue. Our method is thought to be useful for accurately evaluating intratumoral gene expressions

  5. Not My Problem: Vicarious Conflict Adaptation with Human and Virtual Co-Actors

    Directory of Open Access Journals (Sweden)

    Michiel M. Spapé

    2016-04-01

    Full Text Available The Simon effect refers to an incompatibility between stimulus and response locations resulting in a conflict situation and, consequently, slower responses. Like other conflict effects, it is commonly reduced after repetitions, suggesting an executive control ability, which flexibly rewires cognitive processing and adapts to conflict. Interestingly, conflict is not necessarily individually defined: the Social Simon effect refers to a scenario where two people who share a task show a conflict effect where a single person does not. Recent studies showed these observations might converge into what could be called vicarious conflict adaptation, with evidence indicating that observing someone else’s conflict may subsequently reduce one’s own. While plausible, there is reason for doubt: both the social aspect of the Simon Effect, and the degree to which executive control accounts for the conflict adaptation effect, have become foci of debate in recent studies. Here, we present two experiments that were designed to test the social dimension of the effect by varying the social relationship between the actor and the co-actor. In Experiment 1, participants performed a conflict task with a virtual co-actor, while the actor-observer relationship was manipulated as a function of the similarity between response modalities. In Experiment 2, the same task was performed both with a virtual and with a human co-actor, while heart-rate measurements were taken to measure the impact of observed conflict on autonomous activity. While both experiments replicated the interpersonal conflict adaptation effects, neither showed evidence of the critical social dimension. We consider the findings as demonstrating that vicarious conflict adaptation does not rely on the social relationship between the actor and co-actor.

  6. Human gastric signet ring carcinoma (KATO-III) cell apoptosis induced by Vitex agnus-castus fruit extract through intracellular oxidative stress.

    Science.gov (United States)

    Ohyama, Kunio; Akaike, Takenori; Imai, Masahiko; Toyoda, Hiroo; Hirobe, Chieko; Bessho, Toshio

    2005-07-01

    We have previously reported that an ethanol extract of the dried ripe fruit of Vitex agnus-castus (Vitex) displays cytotoxic activity against certain kinds of human cancer cell line resulting in the induction of apoptosis. In this paper, we investigate the molecular mechanism of apoptosis induced by Vitex using a human gastric signet ring carcinoma cell line, KATO-III. DNA fragmentation was observed in Vitex-treated KATO-III cells in a time- and dose-dependent manner. DNA fragmentation was accompanied by the following phenomena: elevation in the level of hemeoxygenase-1 protein and thioredoxin reductase mRNA; repression of Mn-superoxide dismutase and catalase mRNAs; release of cytochrome c from mitochondria into the cytosol; activation of caspases-8, -9 and -3; decrease in the level of Bcl-2, Bcl-XL and Bid protein; increase in the level of Bad protein. The intracellular oxidized state, measured using 2',7'-dichlorofluorescin diacetate, increased after Vitex treatment. While the amount of intracellular GSH decreased significantly after treatment with Vitex, the level of GSSG was unaffected. Furthermore, no significant perturbation in the amount of proteins/mRNAs related to glutathione metabolism could be detected. These apoptotic alterations induced by exposure to Vitex were blocked by the presence of an anti-oxidative reagent, N-acetyl-l-cysteine, or the addition of exogenous GSH. Our results demonstrate that intracellular oxidative stress and mitochondrial membrane damage is responsible for Vitex-induced apoptosis, which may be mediated by a diminution of reduced type glutathione within the cell.

  7. Weight-independent effects of roux-en-Y gastric bypass on glucose homeostasis via melanocortin-4 receptors in mice and humans.

    Science.gov (United States)

    Zechner, Juliet F; Mirshahi, Uyenlinh L; Satapati, Santhosh; Berglund, Eric D; Rossi, Jari; Scott, Michael M; Still, Christopher D; Gerhard, Glenn S; Burgess, Shawn C; Mirshahi, Tooraj; Aguirre, Vincent

    2013-03-01

    Roux-en-Y gastric bypass (RYGB) improves glucose homeostasis independently of changes in body weight by unknown mechanisms. Melanocortin-4 receptors (MC4R) have weight-independent effects on glucose homeostasis, via autonomic neurons, and also might contribute to weight loss after RYGB. We investigated whether MC4Rs mediate effects of RYGB, such as its weight-independent effects on glucose homeostasis, in mice and humans. We studied C57BL/6 mice with diet-induced obesity, MC4R-deficient mice, and mice that re-express MC4R specifically in autonomic neurons after RYGB or sham surgeries. We also sequenced the MC4R locus in patients undergoing RYGB to investigate diabetes resolution in carriers of rare MC4R variants. MC4Rs in autonomic brainstem neurons (including the parasympathetic dorsal motor vagus) mediated improved glucose homeostasis independent of changes in body weight. In contrast, MC4Rs in cholinergic preganglionic motor neurons (sympathetic and parasympathetic) mediated RYGB-induced increased energy expenditure and weight loss. Increased energy expenditure after RYGB is the predominant mechanism of weight loss and confers resistance to weight gain from a high-fat diet, the effects of which are MC4R-dependent. MC4R-dependent effects of RYGB still occurred in mice with Mc4r haplosufficiency, and early stage diabetes resolved at a similar rate in patients with rare variants of MC4R and noncarriers. However, carriers of MC4R (I251L), a rare variant associated with increased weight loss after RYGB and increased basal activity in vitro, were more likely to have early and weight-independent resolution of diabetes than noncarriers, indicating a role for MC4Rs in the effects of RYGB. MC4Rs in autonomic neurons mediate beneficial effects of RYGB, including weight-independent improved glucose homeostasis, in mice and humans. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Toosendanin suppresses oncogenic phenotypes of human gastric carcinoma SGC‑7901 cells partly via miR‑200a‑mediated downregulation of β-catenin pathway.

    Science.gov (United States)

    Wang, Ge; Huang, Yan-Xia; Zhang, Rui; Hou, Li-Dan; Liu, Hui; Chen, Xiao-Yu; Zhu, Jin-Shui; Zhang, Jing

    2017-11-01

    Aberrant activation of β-catenin signaling due to low expression of miR‑200a is found in gastric carcinoma (GC) tissues promoting GC evolution. Toosendanin (TSN) has exhibited antitumor effects on various human cancer cells, but its influence on GC is largely unidentified. The potential roles of TSN on GC cells were examined and it was found that TSN inhibited growth, migration, invasion and TGF‑β1-induced epithelial-mesenchymal transition (EMT) and induced cell cycle arrest and apoptosis in SGC‑7901 cells which were most sensitive to TSN among various GC cell lines. TSN also inactivated β-catenin pathway in SGC‑7901 cells and the above effects were reversed following induction of β-catenin overexpression. Moreover, TSN facilitated the level of miR‑200a which targets β-catenin and miR‑200a silencing attenuated the antitumor effects of TSN on SGC‑7901 cells. Nonetheless, knockdown of miR‑200a did not relieve the suppressive effects of TSN on p‑AKT, p‑ERK and p‑GSK3β which were upstream regulators of β-catenin. In addition, TSN administration inhibited growth and liver metastasis of orthotopically implanted SGC‑7901 tumors in vivo through miR‑200a‑mediated β-catenin pathway. Our data suggest that TSN may suppress oncogenic phenotypes of human GC cells partly via miR‑200a/β-catenin axis. Hence, TSN may have a promising chemotherapeutic activity for GC therapy.

  9. Antitumor effects of the flavone chalcone: inhibition of invasion and migration through the FAK/JNK signaling pathway in human gastric adenocarcinoma AGS cells.

    Science.gov (United States)

    Lin, Su-Hsuan; Shih, Yuan-Wei

    2014-06-01

    Chalcones (benzylideneacetophenone) are cancer-preventive food components found in a human diet rich in fruits and vegetables. In this study, we first report the chemopreventive effect of chalcone in human gastric adenocarcinoma cell lines: AGS. The results showed that chalcone could inhibit the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, Boyden chamber invasion/migration assay, and wound-healing assay. Molecular data showed that the effect of chalcone in AGS cells might be mediated via sustained inactivation of the phosphorylation of focal adhesion kinase (FAK) and c-Jun N-terminal kinase 1 and 2 (JNK1/2) signal involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Next, chalcone-treated AGS cells showed tremendous decrease in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), the nuclear level of NF-κB, and the binding ability of NF-κB to NF-κB response element. Furthermore, treating FAK small interfering RNA (FAK siRNA) and specific inhibitor for JNK (SP600125) to AGS cells could reduce the phosphorylation of JNK1/2 and the activity of MMP-2 and MMP-9. Our results revealed that chalcone significantly inhibited the metastatic ability of AGS cells by reducing MMP-2 and MMP-9 expressions concomitantly with a marked reduction on cell invasion and migration through suppressing and JNK signaling pathways. We suggest that chalcone may offer the application in clinical medicine.

  10. Attenuated gastric distress but no benefit to performance with adaptation to octanoate-rich esterified oils in well-trained male cyclists

    DEFF Research Database (Denmark)

    Thorburn, M.S.; Vistisen, Bodil; Thorp, R.M.

    2006-01-01

    We investigated the effects of modifying a normal dietary fatty acid composition and ingestion of high-fat exercise supplements on gastrointestinal distress, substrate oxidation. and endurance cycling performance. Nine well-trained male cyclists completed a randomized triple-crossover comprising...... a 2-wk diet high in octanoate-rich esterified oil (MCFA) or twice long-chain fatty acids (LCFA). Following the diets, participants performed 3-h of cycling at 50% of peak power followed by 10 maximal sprints while ingesting either 1) a carbohydrate (CHO)+MCFA-rich oil emulsion after the 2-wk MCFA......-rich dietary condition (MC-MC, Intervention) and 2) after one of the LCFA-rich dietary conditions (LC-MC. Placebo) or 3) CHO only following a LCFA-rich diet (LC-CHO, Control). During the 3-h ride MCFA-adaptation decreased octanoic-acid oxidation by 24% (90% confidence interval: 14-34%). The CHO+MCFA-rich oil...

  11. A test of maternal human chorionic gonadotropin during pregnancy as an adaptive filter of human gestations

    OpenAIRE

    Bruckner, Tim A.; Saxton, Katherine B.; Pearl, Michelle; Currier, Robert; Kharrazi, Martin

    2012-01-01

    The risk of abnormalities and morbidity among live births increases with advanced maternal age. Explanations for this elevated morbidity invoke several maternal mechanisms. The relaxed filter stringency (RFS) hypothesis asserts that mothers, nearing the end of their reproductive lifespan, reduce the stringency of a screen of offspring quality in utero based on life-history traits of parity and interbirth interval (IBI). A separate line of research implicates human chorionic gonadotropin (hCG)...

  12. RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses

    Science.gov (United States)

    Akirav, Eitan M.; Preston-Hurlburt, Paula; Garyu, Justin; Henegariu, Octavian; Clynes, Raphael; Schmidt, Ann Marie; Herold, Kevan C.

    2012-01-01

    The Receptor for Advanced Glycation Endproducts (RAGE) is a scavenger ligand that binds glycated endproducts as well as molecules released during cell death such as S100b and HMGB1. RAGE is expressed on antigen presenting cells where it may participate in activation of innate immune responses but its role in adaptive human immune responses has not been described. We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes. The levels of RAGE on T cells from patients with diabetes are not related to the level of glucose control. It co-localizes to the endosomes. Its expression increases in activated T cells from healthy control subjects but bystander cells also express RAGE after stimulation of the antigen specific T cells. RAGE ligands enhance RAGE expression. In patients with T1D, the level of RAGE expression decreases with T cell activation. RAGE+ T cells express higher levels of IL-17A, CD107a, and IL-5 than RAGE− cells from the same individual with T1D. Our studies have identified the expression of RAGE on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses. PMID:22509345

  13. TCA cycle rewiring fosters metabolic adaptation to oxygen restriction in skeletal muscle from rodents and humans.

    Science.gov (United States)

    Capitanio, Daniele; Fania, Chiara; Torretta, Enrica; Viganò, Agnese; Moriggi, Manuela; Bravatà, Valentina; Caretti, Anna; Levett, Denny Z H; Grocott, Michael P W; Samaja, Michele; Cerretelli, Paolo; Gelfi, Cecilia

    2017-08-29

    In mammals, hypoxic stress management is under the control of the Hypoxia Inducible Factors, whose activity depends on the stabilization of their labile α subunit. In particular, the skeletal muscle appears to be able to react to changes in substrates and O 2 delivery by tuning its metabolism. The present study provides a comprehensive overview of skeletal muscle metabolic adaptation to hypoxia in mice and in human subjects exposed for 7/9 and 19 days to high altitude levels. The investigation was carried out combining proteomics, qRT-PCR mRNA transcripts analysis, and enzyme activities assessment in rodents, and protein detection by antigen antibody reactions in humans and rodents. Results indicate that the skeletal muscle react to a decreased O 2 delivery by rewiring the TCA cycle. The first TCA rewiring occurs in mice in 2-day hypoxia and is mediated by cytosolic malate whereas in 10-day hypoxia the rewiring is mediated by Idh1 and Fasn, supported by glutamine and HIF-2α increments. The combination of these specific anaplerotic steps can support energy demand despite HIFs degradation. These results were confirmed in human subjects, demonstrating that the TCA double rewiring represents an essential factor for the maintenance of muscle homeostasis during adaptation to hypoxia.

  14. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes

    KAUST Repository

    Moon, Robert

    2012-12-24

    Research into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen.

  15. Impact, adaptation and vulnerability of natural and human systems in Europe

    International Nuclear Information System (INIS)

    Martin, Eric; Salas y Melia, David; Delire, Christine; Lemonsu, Aude; Masson, Valery; Badeau, Vincent; Gattuso, Jean-Pierre; Pigeon, Gregoire; Regimbeau, Mathieu; Viguie, Vincent

    2015-01-01

    This article analyses the observed and projected impacts of climate change on human and natural systems, their vulnerability and adaptation options. It provides insight into the main results related to hydrology, agriculture, natural ecosystems, transport, energy, tourism, infrastructures, health and social aspects. This article presents the main results concerning Europe that were compiled in the contribution of Working Group II to the IPCC fifth assessment report published in 2014. Several studies focused on mainland France are also presented, without claiming to be exhaustive. (authors)

  16. [Research progression of translational medicine in gastric cancer].

    Science.gov (United States)

    Li, Maoran; Zhao, Gang; Zhu, Chunchao

    2014-02-01

    Gastric cancer is one of the most common malignant tumors which is a great threat to human health. In recent years, the reform of surgical mordalities and the optimization of radiation and chemotherapy is still far from reducing morbidity and mortality of gastric cancer. As a new research pattern, translational medicine has emerged in various clinical subjects, which leads to remarkable effects. In this paper, the definition and development of translational medicine, molecular markers and drug treatment of gastric cancer will be discussed and the feasibility of translational medicine in the treatment of gastric cancer will be explained. In our opinion, the intervention of translational medicine could change the current situation that scientific researches is severely disconnected with clinical practice and increase the detection rate of gastric cancer and the effective rate of adjuvant therapy after surgery to improve the prognosis of patients with gastric cancer.

  17. Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond

    Directory of Open Access Journals (Sweden)

    Tetsuya Tsukamoto

    2017-08-01

    Full Text Available Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

  18. Lobaplatin inhibits growth of gastric cancer cells by inducing apoptosis

    Science.gov (United States)

    Yin, Chu-Yang; Lin, Xiao-Lin; Tian, Lei; Ye, Ming; Yang, Xin-Ying; Xiao, Xiu-Ying

    2014-01-01

    AIM: To assess the anti-cancer effect of lobaplatin on human gastric cancer cells, and to explore the underlying molecular mechanisms. METHODS: The human gastric cancer cell lines MKN-28, AGS and MKN-45 were used. The cytotoxicity of lobaplatin was detected using an MTS cell proliferation assay. Flow cytometry was used to detect cell apoptosis using Annexin V-FITC Apoptosis Detection Kit. The expression of apoptosis-regulated genes was examined at the protein level using Western blot. RESULTS: Lobaplatin inhibited the proliferation of human gastric cancer cells and induced apoptosis, which may be associated with the up-regulation of Bax expression, poly(ADP-ribose) polymerase (PARP) cleavage, p53 expression and the reduction of Bcl-2 expression. CONCLUSION: The cytotoxicity of lobaplatin may be due to its ability of inducing apoptosis of gastric cancer cells, which would support the potential use of lobaplatin for the therapy of gastric cancer. PMID:25516654

  19. The Critical Impact of HIF-1α on Gastric Cancer Biology

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, Yoshihiko, E-mail: kitajiy@esaga.hosp.go.jp [Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501 (Japan); Department of Surgery, NHO Higashisaga Hospital, Saga 849-0101 (Japan); Miyazaki, Kohji [Saga University Faculty of Medicine, Saga 849-8501 (Japan)

    2013-01-10

    Hypoxia inducible factor-1 (HIF-1) monitors the cellular response to the oxygen levels in solid tumors. Under hypoxia conditions, HIF-1α protein is stabilized and forms a heterodimer with the HIF-1β subunit. The HIF-1 complex activates the transcription of numerous target genes in order to adapt the hypoxic environment in human cancer cells. In gastric cancer patients, HIF-1α activation following extended hypoxia strongly correlates with an aggressive tumor phenotype and a poor prognosis. HIF-1α activation has been also reported to occur via hypoxia-independent mechanisms such as PI3K/AKT/mTOR signaling and ROS production. This article argues for the critical roles of HIF-1α in glucose metabolism, carcinogenesis, angiogenesis, invasion, metastasis, cell survival and chemoresistance, focusing on gastric cancer.

  20. Composition and adaptation of human myotendinous junction and neighboring muscle fibers to heavy resistance training

    DEFF Research Database (Denmark)

    Jakobsen, Johannes; Mackey, A L; Knudsen, A B

    2017-01-01

    The myotendinous junction (MTJ) is a common site of strain injury and yet understanding of its composition and ability to adapt to loading is poor. The main aims of this study were to determine the profile of selected collagens and macrophage density in human MTJ and adjoining muscle fibers......, and to investigate whether heavy exercise loading would alter this profile. Fifteen individuals scheduled for anterior cruciate ligament repair surgery were randomized into three groups: control, acute or 4 weeks heavy resistance training. MTJ samples were collected from the semitendinosus and gracilis muscles...... collagens were abundant at the MTJ and in muscle perimysium or endomysium. The endomysial content of collagen XIV, macrophages and Tenascin-C increased following 4 weeks of training. These findings illustrate the heterogeneity of collagen type composition of human MTJ. The increase in collagen XIV following...

  1. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts

    KAUST Repository

    Otto, Thomas D.

    2014-09-09

    Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host–parasite interface may have mediated host switching.

  2. Postprandial proximal gastric acid pocket and gastric pressure in patients after gastric surgery

    OpenAIRE

    Herbella, F. A. M. [UNIFESP; Vicentine, F. P. P. [UNIFESP; Del Grande, J. C. [UNIFESP; Patti, M. G.

    2011-01-01

    BackgroundAn unbuffered postprandial proximal gastric acid pocket (PPGAP) has been demonstrated in normal individuals (NI) and patients with gastro-esophageal reflux disease (GERD). the role of gastric anatomy and gastric motility in the physiology of the PPGAP remains elusive. This study aims to analyze the correlation of PPGAP with proximal gastric pressure after gastric surgery.MethodsA total of 26 individuals were studied: eight patients after open Roux-en-Y gastric bypass (RYGB) for morb...

  3. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    Science.gov (United States)

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

  4. p53-dependent adaptive responses in human cells exposed to space radiations.

    Science.gov (United States)

    Takahashi, Akihisa; Su, Xiaoming; Suzuki, Hiromi; Omori, Katsunori; Seki, Masaya; Hashizume, Toko; Shimazu, Toru; Ishioka, Noriaki; Iwasaki, Toshiyasu; Ohnishi, Takeo

    2010-11-15

    It has been reported that priming irradiation or conditioning irradiation with a low dose of X-rays in the range of 0.02-0.1 Gy induces a p53-dependent adaptive response in mammalian cells. The aim of the present study was to clarify the effect of space radiations on the adaptive response. Two human lymphoblastoid cell lines were used; one cell line bears a wild-type p53 (wtp53) gene, and another cell line bears a mutated p53 (mp53) gene. The cells were frozen during transportation on the space shuttle and while in orbit in the International Space Station freezer for 133 days between November 15, 2008 and March 29, 2009. After the frozen samples were returned to Earth, the cells were cultured for 6 h and then exposed to a challenging X-ray-irradiation (2 Gy). Cellular sensitivity, apoptosis, and chromosome aberrations were scored using dye-exclusion assays, Hoechst33342 staining assays, and chromosomal banding techniques, respectively. In cells exposed to space radiations, adaptive responses such as the induction of radioresistance and the depression of radiation-induced apoptosis and chromosome aberrations were observed in wtp53 cells but not in mp53 cells. These results have confirmed the hypothesis that p53-dependent adaptive responses are apparently induced by space radiations within a specific range of low doses. The cells exhibited this effect owing to space radiations exposure, even though the doses in space were very low. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Epstein-Barr Virus in Gastric Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, Jun, E-mail: junnis@yamaguchi-u.ac.jp [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Yoshiyama, Hironori; Iizasa, Hisashi; Kanehiro, Yuichi [Department of Microbiology, Shimane University Faculty of Medicine, 89-1 Enyacho, Izumo City, Shimane 693-8501 (Japan); Nakamura, Munetaka; Nishimura, Junichi; Saito, Mari; Okamoto, Takeshi [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Sakai, Kouhei; Suehiro, Yutaka; Yamasaki, Takahiro [Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Oga, Atsunori [Department of Pathology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Yanai, Hideo [Department of Clinical Research, National Hospital Organization Kanmon Medical Center, 1-1 Sotoura, Chofu, Shimonoseki, Yamaguchi 752-8510 (Japan); Sakaida, Isao [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan)

    2014-11-07

    The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation.

  6. Adaptation to different human populations by HIV-1 revealed by codon-based analyses.

    Directory of Open Access Journals (Sweden)

    Sergei L Kosakovsky Pond

    2006-06-01

    Full Text Available Several codon-based methods are available for detecting adaptive evolution in protein-coding sequences, but to date none specifically identify sites that are selected differentially in two populations, although such comparisons between populations have been historically useful in identifying the action of natural selection. We have developed two fixed effects maximum likelihood methods: one for identifying codon positions showing selection patterns that persist in a population and another for detecting whether selection is operating differentially on individual codons of a gene sampled from two different populations. Applying these methods to two HIV populations infecting genetically distinct human hosts, we have found that few of the positively selected amino acid sites persist in the population; the other changes are detected only at the tips of the phylogenetic tree and appear deleterious in the long term. Additionally, we have identified seven amino acid sites in protease and reverse transcriptase that are selected differentially in the two samples, demonstrating specific population-level adaptation of HIV to human populations.

  7. Health Belief Model Scale for Human Papilloma Virus and its Vaccination: Adaptation and Psychometric Testing.

    Science.gov (United States)

    Guvenc, Gulten; Seven, Memnun; Akyuz, Aygul

    2016-06-01

    To adapt and psychometrically test the Health Belief Model Scale for Human Papilloma Virus (HPV) and Its Vaccination (HBMS-HPVV) for use in a Turkish population and to assess the Human Papilloma Virus Knowledge score (HPV-KS) among female college students. Instrument adaptation and psychometric testing study. The sample consisted of 302 nursing students at a nursing school in Turkey between April and May 2013. Questionnaire-based data were collected from the participants. Information regarding HBMS-HPVV and HPV knowledge and descriptive characteristic of participants was collected using translated HBMS-HPVV and HPV-KS. Test-retest reliability was evaluated and Cronbach α was used to assess internal consistency reliability, and exploratory factor analysis was used to assess construct validity of the HBMS-HPVV. The scale consists of 4 subscales that measure 4 constructs of the Health Belief Model covering the perceived susceptibility and severity of HPV and the benefits and barriers. The final 14-item scale had satisfactory validity and internal consistency. Cronbach α values for the 4 subscales ranged from 0.71 to 0.78. Total HPV-KS ranged from 0 to 8 (scale range, 0-10; 3.80 ± 2.12). The HBMS-HPVV is a valid and reliable instrument for measuring young Turkish women's beliefs and attitudes about HPV and its vaccination. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  8. Gastric Autoantigenic Proteins in Helicobacter Pylori Infection

    Science.gov (United States)

    Park, Ji Sook; Lee, Su-Jin; Kim, Tae Hyo; Yeom, Jeongsuk; Park, Eun-Sil; Seo, Ji-Hyun; Jun, Jin-Su; Lim, Jae-Young; Park, Chan-Hoo; Woo, Hyang-Ok; Ko, Gyung-Hyuck; Kang, Hyung-Lyun; Baik, Seung-Chul; Lee, Woo-Kon; Cho, Myung-Je; Rhee, Kwang-Ho

    2013-01-01

    Purpose This study tried to identify novel gastric autoimmune antigens that might be involved in aggravating the atrophic gastritis among patients with Helicobacter pylori infection using two-dimensional immunoblotting analysis. Materials and Methods Proteins from gastric mucosal antrectomy specimens and AGS cells (gastric adenocarcinoma cell lines derived from a Caucasian patient who had received no prior therapy) were 2-dimensionally immunoblotted separately with a pool of 300 sera from H. pylroi-infected patients at Gyeongsang National University Hospital. Results Thirty-eight autoantigenic proteins including alcohol dehydrogenase [NADP+], alpha enolase, gastrokine-1, gastric triacylglycerol lipase, heat shock 70 kDa protein 1, and peroxiredoxin-2 were identified in the gastric mucosal tissue. Fourteen autoantigenic proteins including programmed cell death 6-interacting protein, serum albumin and T-complex protein 1 subunit gamma were identified in the AGS cells. Albumin, alpha-enolase, annexin A3, cytoplasmic actin 1, heat shock cognate 71 kDa protein and leukocyte elastase inhibitor were commonly observed autoantigenic proteins in both gastric mucosal tissue and AGS cells. Alpha-enolase, glutathione S-transferase P, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1, human mitochondrial adenosine triphosphate synthase (ATP) subunit beta, mitochondrial 60 kDa heat shock protein, peroxiredoxin-2, 78 kDa glucose-regulated protein precursor, tyrosine-protein phosphatase non-receptor type 11 and Tryptophan-Aspartic acid (WD) repeat-containing protein 1 showed 60% or higher amino acid positivity. Conclusion These newly identified gastric autoimmune antigens might be useful in the control and prevention of gastroduodenal disorders, and might be valuable in breaking the vicious circle that exists in gastroduodenal disorders if their pathophysiological roles could be understood in the progress of chronic atrophic gastritis, gastroduodenal ulcers, intestinal

  9. Effect of Human Milk Appetite Hormones, Macronutrients, and Infant Characteristics on Gastric Emptying and Breastfeeding Patterns of Term Fully Breastfed Infants

    Directory of Open Access Journals (Sweden)

    Zoya Gridneva

    2016-12-01

    Full Text Available Human milk (HM components influence infant feeding patterns and nutrient intake, yet it is unclear how they influence gastric emptying (GE, a key component of appetite regulation. This study analyzed GE of a single breastfeed, HM appetite hormones/macronutrients and demographics/anthropometrics/body composition of term fully breastfed infants (n = 41, 2 and/or 5 mo. Stomach volumes (SV were calculated from pre-/post-feed ultrasound scans, then repeatedly until the next feed. Feed volume (FV was measured by the test-weigh method. HM samples were analyzed for adiponectin, leptin, fat, lactose, total carbohydrate, lysozyme, and total/whey/casein protein. Linear regression/mixed effect models were used to determine associations between GE/feed variables and HM components/infant anthropometrics/adiposity. Higher FVs were associated with faster (−0.07 [−0.10, −0.03], p < 0.001 GE rate, higher post-feed SVs (0.82 [0.53, 1.12], p < 0.001, and longer GE times (0.24 [0.03, 0.46], p = 0.033. Higher whey protein concentration was associated with higher post-feed SVs (4.99 [0.84, 9.13], p = 0.023. Longer GE time was associated with higher adiponectin concentration (2.29 [0.92, 3.66], p = 0.002 and dose (0.02 [0.01, 0.03], p = 0.005, and lower casein:whey ratio (−65.89 [−107.13, −2.66], p = 0.003. FV and HM composition influence GE and breastfeeding patterns in term breastfed infants.

  10. Silkworm Pupa Protein Hydrolysate Induces Mitochondria-Dependent Apoptosis and S Phase Cell Cycle Arrest in Human Gastric Cancer SGC-7901 Cells

    Directory of Open Access Journals (Sweden)

    Xiaotong Li

    2018-03-01

    Full Text Available Silkworm pupae (Bombyx mori are a high-protein nutrition source consumed in China since more than 2 thousand years ago. Recent studies revealed that silkworm pupae have therapeutic benefits to treat many diseases. However, the ability of the compounds of silkworm pupae to inhibit tumourigenesis remains to be elucidated. Here, we separated the protein of silkworm pupae and performed alcalase hydrolysis. Silkworm pupa protein hydrolysate (SPPH can specifically inhibit the proliferation and provoke abnormal morphologic features of human gastric cancer cells SGC-7901 in a dose- and time-dependent manner. Moreover, flow cytometry indicated that SPPH can induce apoptosis and arrest the cell-cycle in S phase. Furthermore, SPPH was shown to provoke accumulation of reactive oxygen species (ROS and depolarization of mitochondrial membrane potential. Western blotting analysis indicated that SPPH inhibited Bcl-2 expression and promoted Bax expression, and subsequently induced apoptosis-inducing factor and cytochrome C release, which led to the activation of initiator caspase-9 and executioner caspase-3, cleavage of poly (ADP-ribose polymerase (PARP, eventually caused cell apoptosis. Moreover, SPPH-induced S-phase arrest was mediated by up-regulating the expression of E2F1 and down-regulating those of cyclin E, CDK2 and cyclin A2. Transcriptome sequencing and gene set enrichment analysis (GSEA also revealed that SPPH treatment could affect gene expression and pathway regulation related to tumourigenesis, apoptosis and cell cycle. In summary, our results suggest that SPPH could specifically suppress cell growth of SGC-7901 through an intrinsic apoptotic pathway, ROS accumulation and cell cycle arrest, and silkworm pupae have a potential to become a source of anticancer agents in the future.

  11. Effect of Human Milk Appetite Hormones, Macronutrients, and Infant Characteristics on Gastric Emptying and Breastfeeding Patterns of Term Fully Breastfed Infants.

    Science.gov (United States)

    Gridneva, Zoya; Kugananthan, Sambavi; Hepworth, Anna R; Tie, Wan J; Lai, Ching T; Ward, Leigh C; Hartmann, Peter E; Geddes, Donna T

    2016-12-28

    Human milk (HM) components influence infant feeding patterns and nutrient intake, yet it is unclear how they influence gastric emptying (GE), a key component of appetite regulation. This study analyzed GE of a single breastfeed, HM appetite hormones/macronutrients and demographics/anthropometrics/body composition of term fully breastfed infants ( n = 41, 2 and/or 5 mo). Stomach volumes (SV) were calculated from pre-/post-feed ultrasound scans, then repeatedly until the next feed. Feed volume (FV) was measured by the test-weigh method. HM samples were analyzed for adiponectin, leptin, fat, lactose, total carbohydrate, lysozyme, and total/whey/casein protein. Linear regression/mixed effect models were used to determine associations between GE/feed variables and HM components/infant anthropometrics/adiposity. Higher FVs were associated with faster (-0.07 [-0.10, -0.03], p < 0.001) GE rate, higher post-feed SVs (0.82 [0.53, 1.12], p < 0.001), and longer GE times (0.24 [0.03, 0.46], p = 0.033). Higher whey protein concentration was associated with higher post-feed SVs (4.99 [0.84, 9.13], p = 0.023). Longer GE time was associated with higher adiponectin concentration (2.29 [0.92, 3.66], p = 0.002) and dose (0.02 [0.01, 0.03], p = 0.005), and lower casein:whey ratio (-65.89 [-107.13, -2.66], p = 0.003). FV and HM composition influence GE and breastfeeding patterns in term breastfed infants.

  12. Comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma and normal lung fibroblast cell lines

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Rashmezad

    2015-03-01

    Full Text Available Background: Biosynthesis of nanoparticles has attracted the attention of the scientific community in nanotechnology and biotechnology due to their extensive application in the area of material sciences and medicine. Nowadays, despite a various application of nanomaterial’s, there is a little information about their impact on human health. In this study, we investigated the comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma (AGS and normal lung fibroblast (MRC-5 cell lines. Methods: The current experimental study was carried out in Islamic Azad University, East Tehran Branch, from April to November 2014. The biological synthesis of nanosilver was obtained from Eucalyptus plant extract as a reducing agent. Further to more analysis, morphological study on size and shape of developed biological nanosilver was characterized by performing scanning electron microscopy and dynamic light scattering. AGS and MCR-5 cell lines were treated with various concentration of nanosilver for 24, 48 and 72 hours. Finally, the cell viability was evaluated by using MTT assay. Results: The results show that the nanosilver exerts a dose-dependent inhibitory effect on viability of cells. At 100µg/mL of commercial and biological synthesized nanosilver, the viability of AGS was reduced to 7.47±0.002% (P=0.002 and 3.65±0.01% (P=0.003 after 72 hours, respectively. In addition, the viability of MRC-5 at the same condition was reduced to 10.27±0.19% (P=0.001 and 9.16±1.53% (P=0.002, respectively. Conclusion: Based on a thorough literature surveys, the present study is the first research about biosynthesis of nanosilver using Eucalyptus plant extract. This eco-friendly and cost effective method can be used for large scale production of silver nanoparticle. In addition, based on the current obtained data, commercial and biological synthesized nanosilver can more inhibitory effect on cancer cells compared

  13. Fed and fasted gastric pH and gastric residence time in conscious beagle dogs.

    Science.gov (United States)

    Sagawa, Kazuko; Li, Fasheng; Liese, Ryan; Sutton, Steven C

    2009-07-01

    The gastric pH values are controversial in the literature. Some suggest the dog gastric pH is higher than human and dog gastric pH after fed with particular diet is uncertain. Gastric pH in 16 male beagle dogs was measured using Bravo pH telemetry system. For the fed study, the dogs received 10 or 200 g of dog dry food (5L18) 15 min before dosing the Bravo pH capsule, followed by a 50 mL of water to aid in swallowing. It was surprising to find a small, but statistically significantly lower pH in the fed compared to the fasted stomach. The average gastric pH in fasted dogs was 2.05 and 1.08 and 1.26 for 10 and 200 g fed dogs. The average gastric emptying time of the capsule was 1.4, 9.4 and 20 h for fasted, 10 g fed and 200 g fed dogs, respectively. The inter-individual variability was higher in fasted dogs than in fed dogs. The results showed the gastric pH in each colony of dogs can be different from reported values in the literature. It emphasizes that the importance of measuring the pH in each colony when dogs are used to evaluate pharmacokinetics of pH sensitive drugs or formulations.

  14. Shared and Unique Proteins in Human, Mouse and Rat Saliva Proteomes: Footprints of Functional Adaptation

    Directory of Open Access Journals (Sweden)

    Robert C. Karn

    2013-12-01

    Full Text Available The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with saliva collected from the genome mouse (C57BL/6 and the genome rat (BN/SsNHsd/Mcwi. Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals, as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals, because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals.

  15. Human adaptation to isolated and confined environments: Preliminary findings of a seven month Antarctic winter-over human factors study

    Science.gov (United States)

    Evans, Gary W.; Stokols, Daniel; Carrere, Sybil

    1988-01-01

    This field study was conducted during the last decade of an austral winter-over at Palmer Station in the Antarctic. The purpose of the study was to understand temporal patterns in physiological arousal and psychological mood over the course of the mission. The investigators were principally interested in how people adapted over time to chronic and acute stressors, and how people use and modify their built environment. Physiological and psychological data were collected several times a week, and information on behavior and the use of physical facilities was collected monthly. Physiological and psychological data were compared with social changes in the setting toward the development of a sequential model of human-environment transactional relationships. Based on the study results, guidelines for design of future isolated and confined environments (ICEs) included: plan space for items which make people feel at home, provide materials to allow people to personalize their environment, allow for flexible environments, provide areas for visual and auditory privacy, equip areas for socializing and remove them from private areas, and provide facilities for exercise and for projects involving physical activity. The study offers guidelines about patterns of adaption that could be expected in an ICE, discusses how these settings can be programmed to facilitate successful adjustment, and provides information about how to design future ICE habitats to maximize a healthy living environment.

  16. The identification of gene pathways involved in vascular adaptations after physical deconditioning versus exercise training in humans

    NARCIS (Netherlands)

    Lammers, G.; van Duijnhoven, T.L.; Hoenderop, J.G.; Horstman, A.M.H.; de Haan, A.; Janssen, T.W.J.; de Graaf, M.; Pardoel, E.M.; Verwiel, E.T.P.; Thijssen, D.H.J.; Hopman, M.T.E.

    2013-01-01

    New Findings: • What is the central question of this study? The aim of this study is to identify genes that are involved in vascular adaptations after physical deconditioning and exercise training in humans. • What is the main finding and its importance? Using unique human in vivo models for local

  17. Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2α-ATF4-xCT pathway

    Science.gov (United States)

    Wang, Sheng-Fan; Chen, Meng-Shian; Chou, Yueh-Ching; Ueng, Yune-Fang; Yin, Pen-Hui; Yeh, Tien-Shun; Lee, Hsin-Chen

    2016-01-01

    Mitochondrial DNA mutations and defects in mitochondrial enzymes have been identified in gastric cancers, and they might contribute to cancer progression. In previous studies, mitochondrial dysfunction was induced by oligomycin-enhanced chemoresistance to cisplatin. Herein, we dissected the regulatory mechanism for mitochondrial dysfunction-enhanced cisplatin resistance in human gastric cancer cells. Repeated cisplatin treatment-induced cisplatin-resistant cells exhibited high SLC7A11 (xCT) expression, and xCT inhibitors (sulfasalazine or erastin), xCT siRNA, or a GSH synthesis inhibitor (buthionine sulphoximine, BSO) could sensitize these cells to cisplatin. Clinically, the high expression of xCT was associated with a poorer prognosis for gastric cancer patients under adjuvant chemotherapy. Moreover, we found that mitochondrial dysfunction enhanced cisplatin resistance and up-regulated xCT expression, as well as intracellular glutathione (GSH). The xCT inhibitors, siRNA against xCT or BSO decreased mitochondrial dysfunction-enhanced cisplatin resistance. We further demonstrated that the upregulation of the eIF2α-ATF4 pathway contributed to mitochondrial dysfunction-induced xCT expression, and activated eIF2α kinase GCN2, but not PERK, stimulated the eIF2α-ATF4-xCT pathway in response to mitochondrial dysfunction-increased reactive oxygen species (ROS) levels. In conclusion, our results suggested that the ROS-activated GCN2-eIF2α-ATF4-xCT pathway might contribute to mitochondrial dysfunction-enhanced cisplatin resistance and could be a potential target for gastric cancer therapy. PMID:27708226

  18. The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia.

    Science.gov (United States)

    Deng, Lian; Hoh, Boon Peng; Lu, Dongsheng; Fu, Ruiqing; Phipps, Maude E; Li, Shilin; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Ismail, Endom; Mokhtar, Siti Shuhada; Jin, Li; Zilfalil, Bin Alwi; Marshall, Christian R; Scherer, Stephen W; Al-Mulla, Fahd; Xu, Shuhua

    2014-09-01

    Peninsular Malaysia is a strategic region which might have played an important role in the initial peopling and subsequent human migrations in Asia. However, the genetic diversity and history of human populations--especially indigenous populations--inhabiting this area remain poorly understood. Here, we conducted a genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito), and made comparisons of 17 world-wide populations. Our data revealed that Peninsular Malaysia has greater genetic diversity corresponding to its role as a contact zone of both early and recent human migrations in Asia. However, each single Orang Asli (indigenous) group was less diverse with a smaller effective population size (N(e)) than a European or an East Asian population, indicating a substantial isolation of some duration for these groups. All four MEGs were genetically more similar to Asian populations than to other continental groups, and the divergence time between MEGs and East Asian populations (12,000--6,000 years ago) was also much shorter than that between East Asians and Europeans. Thus, Malaysian Orang Asli groups, despite their significantly different features, may share a common origin with the other Asian groups. Nevertheless, we identified traces of recent gene flow from non-Asians to MEGs. Finally, natural selection signatures were detected in a batch of genes associated with immune response, human height, skin pigmentation, hair and facial morphology and blood pressure in MEGs. Notable examples include SYN3 which is associated with human height in all Orang Asli groups, a height-related gene (PNPT1) and two blood pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long isolation period, subsequent gene flow and local adaptations have jointly shaped the genetic architectures of MEGs, and this study provides insight into the peopling and human migration

  19. Benign gastric filling defect

    Energy Technology Data Exchange (ETDEWEB)

    Oh, K. K.; Lee, Y. H.; Cho, O. K.; Park, C. Y. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  20. Benign gastric filling defect

    International Nuclear Information System (INIS)

    Oh, K. K.; Lee, Y. H.; Cho, O. K.; Park, C. Y.

    1979-01-01

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  1. Suppression of gastric acid increases the risk of developing immunoglobulin E-mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model.

    Science.gov (United States)

    Riemer, A B; Gruber, S; Pali-Schöll, I; Kinaciyan, T; Untersmayr, E; Jensen-Jarolim, E

    2010-03-01

    Hypersensitivity reactions towards non-steroidal anti-inflammatory drugs (NSAID) are common, although true allergies are detectable only in a subgroup of patients. The current study was prompted by a case observation, where a patient experienced generalized urticaria following his second course of diclofenac and proton pump inhibitor medication, and was found to have diclofenac-specific IgE. During recent years, our group has been investigating the importance of gastric digestion in the development of food allergies, demonstrating anti-acid medication as a risk factor for sensitization against food proteins. Here, we aimed to investigate whether the mechanism of food allergy induction described can also be causative in NSAID allergy, using diclofenac as a paradigm. We subjected BALB/c mice to several oral immunization regimens modelled after the patient's medication intake. Diclofenac was applied with or without gastric acid suppression, in various doses, alone or covalently coupled to albumin, a protein abundant in gastric juices. Immune responses were assessed on the antibody level, and functionally examined by in vitro and in vivo crosslinking assays. Only mice receiving albumin-coupled diclofenac under gastric acid suppression developed anti-diclofenac IgG1 and IgE, whereas no immune responses were induced by the drug alone or without gastric acid suppression. Antibody induction was dose dependent with the group receiving the higher dose of the drug showing sustained anti-diclofenac titres. The antibodies induced triggered basophil degranulation in vitro and positive skin tests in vivo. Gastric acid suppression was found to be a causative mechanism in the induction of IgE-mediated diclofenac allergy.

  2. Pathobiology of Helicobacter pylori-induced Gastric Cancer

    Science.gov (United States)

    Amieva, Manuel; Peek, Richard M.

    2015-01-01

    Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

  3. Air trapping and arboreal locomotor adaptation in primates: a review of experiments on humans.

    Science.gov (United States)

    Hayama, Sugio; Honda, Kiyoshi; Oka, Hideo; Okada, Morihiko

    2002-03-01

    A review was made of experiments on humans in which air trapping by glottis closure during three-dimensional movements were examined in four subjects including former Olympic gymnasts. In brachiation and horizontal bar exercises, the behaviour of the larynx was monitored with a fiberoptic endoscope, and EMG-data were recorded from shoulder muscles. The results revealed that immobilization of the polyaxial connection between the shoulder girdle and the thorax by air trapping occurs in phases of extreme loading of the upper limbs. The closure of the airway by the larynx in humans serves three functions: first, the prevention of errors in deglutition; second, the production of vocal sounds; third, the retention of air inside the thoracic cavity. The latter function, air trapping, allows the immobilization of the rib cage for the muscular fixation of the shoulder blade on the trunk in movements that imply unusually high external forces acting on the upper limbs. This morphological-functional innovation probably has been made when early mammals invaded the three dimensional arboreal habitat, because it gave the tree-dwelling early primates the device to anchor themselves by the arms alone and to avoid falling out of trees. The specific functional characteristic of primates is the hermetic closure of the vocal and vestibular folds by rapidly contracting muscles in the folds. So the closure of the glottis, which in humans seems primarily an adaptation to the production of vocal tones, seems to go back to the adaptation of Tertiary arboreal primates to movements in a three-dimensional environment. Our conclusions are in agreement with the results of other contributions to this volume.

  4. Space Weather and a State of Cardiovascular System of Human Being with a Weakened Adaptation System

    Science.gov (United States)

    Samsonov, S. N.

    As has been shown in [Samsonov et al., 2013] even at the considerable disturbances of space weather parameters a healthy human being did not undergo painful symptoms although measurements of objective physiological indices showed their changes. At the same time the state of health of people with the weakened adaptation system under the same conditions can considerably be deteriorated up to fatal outcome. The analysis of results of the project "Heliomed" and the number of calls for the emergency medical care (EMC) around Yakutsk as to cardiovascular diseases (CVD) has shown:- the total number of calls for EMC concerning myocardial infarction (MI) per year near the geomagnetic disturbance maximum (1992) exceeds the number of calls per year near the geomagnetic activity minimum (1998) by a factor of 1,5 and concerning to strokes - by a factor of 1,8.- maxima of MI are observed during spring and autumn periods coinciding with maxima of geophysical disturbance;- the coincidence of 30-32 daily periods in a power spectrum of MI with the same periods in power spectra of space weather parameters (speeds and density of the solar wind, interplanetary magnetic field, geophysical disturbance);- the existence of 3 maxima of the number of calls for EMC: a) at the moment of disturbance on the Sun; during a geophysical disturbance (in 2-4 days after a disturbance on the Sun); in 2-4 days after a geophysical disturbance;- the availability of coincidence of insignificant disturbances of space weather parameters with changes of the functional state of cardiovascular system of a human being with the weakened adaptation system and the occurrence of MI and strokes at considerable values of such disturbances is explained by a quasi-logarithmic dependence of the response of human being organisms to the environment disturbance intensity.

  5. Adaptive Changes in Basal Metabolic Rate in Humans in Different Eco-Geographical Areas.

    Science.gov (United States)

    Maximov, Arkady L; Belkin, Victor Sh; Kalichman, Leonid; Kobyliansky, Eugene D

    2015-12-01

    Our aim was to establish whether the human basal metabolic rate (BMR) shifts towards the reduction of vital functions as an adaptation response to extreme environmental conditions. Data was collected in arid and Extreme North zones. The arid zone samples included Bedouins living in the Sinai Peninsula in Egypt, Turkmen students, the Pedagogical University of Chardzhou, Turkmenistan born Russians and Russian soldiers. Soldiers were divided into 3 groups according to the length of their tour of duty in the area: 1st group: up to six months, 2nd group: up to 2 years and the 3rd group: 3-5 years. The Extreme North samples comprised Chukchi natives, 1st generation Russian immigrants born in the area and 3 groups of soldiers comparable to the soldiers from Turkmenistan. BMR values of the new recruits had the highest values of total and relative BMR (1769 ± 16 and 28.3 ± 0.6, correspondingly). The total and relative BMR tended to decrease within a longer adaptation period. The BMR values of officers who served >3 years in Turkmenistan were very similar to the Turkmenistan born Russians (1730 ± 14 vs. 1726 ± 18 and 26.5 ± 0.6 vs. 27.3 ± 0.7, correspondingly). Similarly, in Chukotka, the highest relative BMR was found in the new recruits, serving up to 6 months (28.1 ± 0.7) and was significantly (p BMR was virtually similar in Russian officers serving > 3 years, compared to the middle-aged Chukchi or Chukotka-born Russians (25.8 ± 0.5 vs. 25.6 ± 0.5 and 25.5 ± 0.6, correspondingly). The BMR parameters demonstrated a stronger association with body weight than with age. In extreme environmental conditions, migrant populations showed a decrease in BMR, thus reducing its vital functions. The BMR reduction effect with the adequate adaptive transformation is likely to be the key strategy for developing programs to facilitate human and animal adaptation to extreme factors. This process is aimed at preserving the optimum energy balance and homeostasis while minimizing

  6. Epidermal growth factor receptor structural alterations in gastric cancer

    International Nuclear Information System (INIS)

    Moutinho, Cátia; Mateus, Ana R; Milanezi, Fernanda; Carneiro, Fátima; Seruca, Raquel; Suriano, Gianpaolo

    2008-01-01

    EGFR overexpression has been described in many human tumours including gastric cancer. In NSCLC patients somatic EGFR mutations, within the kinase domain of the protein, as well as gene amplification were associated with a good clinical response to EGFR inhibitors. In gastric tumours data concerning structural alterations of EGFR remains controversial. Given its possible therapeutic relevance, we aimed to determine the frequency and type of structural alterations of the EGFR gene in a series of primary gastric carcinomas. Direct sequencing of the kinase domain of the EGFR gene was performed in a series of 77 primary gastric carcinomas. FISH analysis was performed in 30 cases. Association studies between EGFR alterations and the clinical pathological features of the tumours were performed. Within the 77 primary gastric carcinomas we found two EGFR somatic mutations and several EGFR polymorphisms in exon 20. Six different intronic sequence variants of EGFR were also found. Four gastric carcinomas showed balanced polysomy or EGFR gene amplification. We verified that gastric carcinoma with alterations of EGFR (somatic mutations or copy number variation) showed a significant increase of tumour size (p = 0.0094) in comparison to wild-type EGFR carcinomas. We demonstrate that EGFR structural alterations are rare in gastric carcinoma, but whenever present, it leads to tumour growth. We considered that searching for EGFR alterations in gastric cancer is likely to be clinically important in order to identify patients susceptible to respond to tyrosine kinase inhibitors

  7. [Effects of HSP90 inhibitor 17-AAG on cell cycle and apoptosis of human gastric cancer cell lines SGC-7901].

    Science.gov (United States)

    Chen, Meini; Xu, Jinghong; Zhao, Jumei

    2013-02-01

    To study the effect of the HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), on cell proliferation and apoptosis of human cancer SGC-7901 cells and explore the mechanisms. The inhibitory effect of 17-AAG on the proliferation and morphology of SGC-7901 cells was assessed with MTT assay and DNA-PI staining, respectively. Flow cytometry was employed to analyze the changes in cell cycle and apoptosis of the cells following 17-AAG exposure. The cellular expression of Fas protein was detected by immunohistochemistry. 17-AAG significantly suppressed the proliferation of SGC-7901 cells in a time- and dose-dependent manner. After treatment with 17-AAG for 48 h, SGC-7901 cells showed cell cycle arrested at G(2)/M stage, and the cell apoptosis rate increased with the 17-AAG concentration. The expression of Fas protein in the cytoplasm of SGC-7901 cells increased gradually with the increase of 17-AAG concentration. 17-AAG can induce apoptosis, alters the cell cycle distribution and up-regulates the expression of Fas protein in SGC-7901 cells to suppress the cell proliferation.

  8. gastric pneumatosis of emphysematous gastritis?

    African Journals Online (AJOL)

    gastric pneumatosis (also known as gastric emphysema) or emphysematous gastritis. We present the case of a 27-year-old white female patient with a history of thoracic and abdominal surgery who presented with intractable vomiting, clinically suspected to be as a result of gastric outlet obstruction. Intramural gastric air was ...

  9. Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule

    DEFF Research Database (Denmark)

    Jessen, H; Jacobsen, Christian

    1997-01-01

    1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine...... homeostasis occurs predominantly via changes in the activity of the high-affinity taurine transport system by alterations in the uptake capacity and with an unaffected half-saturation constant. An adaptive response was not observed for the structurally related beta-alanine. 3. Only colchicine, which...... interferes with microtubule organization, was capable of blocking the response to alterations of taurine in cell medium, whereas inhibition of protein and nucleic acid synthesis by cycloheximide and actinomycin D, respectively, did not change the adaptive pattern. 4. Phorbol 12-myristate 13-acetate (PMA...

  10. Gastric Lipase Secretion in Children with Gastritis

    Directory of Open Access Journals (Sweden)

    Krystyna Sztefko

    2013-07-01

    Full Text Available Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL in