PVA matches human liver in needle-tissue interaction.

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de Jong, Tonke L; Pluymen, Loes H; van Gerwen, Dennis J; Kleinrensink, Gert-Jan; Dankelman, Jenny; van den Dobbelsteen, John J

2017-05-01

Medical phantoms can be used to study needle-tissue interaction and to train medical residents. The purpose of this research is to study the suitability of polyvinyl alcohol (PVA) as a liver tissue mimicking material in terms of needle-tissue interaction. Insertions into ex-vivo human livers were used for reference. Six PVA samples were created by varying the mass percentage of PVA to water (4m% and 7m%) and the number of freeze-thaw cycles (1, 2 and 3 cycles, 16hours of freezing at -19°C, 8hours of thawing). The inner needle of an 18 Gauge trocar needle with triangular tip was inserted 13 times into each of the samples, using an insertion velocity of 5 mm/s. In addition, 39 insertions were performed in two ex-vivo human livers. Axial forces on the needle were captured during insertion and retraction and characterized by friction along the needle shaft, peak forces, and number of peak forces per unit length. The concentration of PVA and the number of freeze-thaw cycles both influenced the mechanical interaction between needle and specimen. Insertions into 4m% PVA phantoms with 2 freeze-thaw cycles were comparable to human liver in terms of estimated friction along the needle shaft and the number of peak forces. Therefore, these phantoms are considered to be suitable liver mimicking materials for image-guided needle interventions. The mechanical properties of PVA hydrogels can be influenced in a controlled manner by varying the concentration of PVA and the number of freeze-thaw cycles, to mimic liver tissue characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Affinity of 167Tm-citrate for tumor and liver tissue

International Nuclear Information System (INIS)

Ando, A.; Ando, I.; Hiraki, T.

1983-01-01

Strong affinity of 167 Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with 167 Tm-citrate because of its strong tumor affinity and because of the suitable physical characteristics of 167 Tm. A large amount of 167 Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. 167 Tm was not seen in necrotic tumor tissue. It was concluded that lysosomes did not play a major role in the tumor concentration of 167 Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumed that lysosomes played a considerably important role in the tumor concentration of 167 Tm, hepatoma AH109A possessing some residual features of the liver. 167 Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which 167 Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate). (orig.)

Radioligand assay for biotin in liver tissues

International Nuclear Information System (INIS)

Rettenmaier, R.

1979-01-01

A radioligand assay for biotin in liver tissue is described. 3 H-biotin is used as tracer and avidin as binder. The biotin-loaded avidin is separated from free biotin on dextran-coated charcoal, which leaves the avidin-biotin complex in the supernatant liquid. Thus, the avidin-biotin complex can easily be utilized for determination of the radioactivity. Calibration with known additions of biotin in the range 0.25-8.0 ng per assay sample yields a linear logit-log plot. The biotin is extracted from liver tissues by enzymatic proteolysis with papain. This treatment is optimized to liberate the bound forms of the vitamin. Microbiological parallel assays with Lactobacillus plantarum were in good agreement with the radioligand assay giving a regression coefficient of 0.974(n=44). The coefficient of variation was found to be 4.2% in the range 500-1200 ng of biotin per g of liver tissue (n=46). The method is simple and reliable and allows the simultaneous analysis of a considerable number of samples. (Auth.)

High intensity interval training improves liver and adipose tissue insulin sensitivity

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Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

Dynamic PET of human liver inflammation: impact of kinetic modeling with optimization-derived dual-blood input function.

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Wang, Guobao; Corwin, Michael T; Olson, Kristin A; Badawi, Ramsey D; Sarkar, Souvik

2018-05-30

The hallmark of nonalcoholic steatohepatitis is hepatocellular inflammation and injury in the setting of hepatic steatosis. Recent work has indicated that dynamic 18F-FDG PET with kinetic modeling has the potential to assess hepatic inflammation noninvasively, while static FDG-PET did not show a promise. Because the liver has dual blood supplies, kinetic modeling of dynamic liver PET data is challenging in human studies. The objective of this study is to evaluate and identify a dual-input kinetic modeling approach for dynamic FDG-PET of human liver inflammation. Fourteen human patients with nonalcoholic fatty liver disease were included in the study. Each patient underwent one-hour dynamic FDG-PET/CT scan and had liver biopsy within six weeks. Three models were tested for kinetic analysis: traditional two-tissue compartmental model with an image-derived single-blood input function (SBIF), model with population-based dual-blood input function (DBIF), and modified model with optimization-derived DBIF through a joint estimation framework. The three models were compared using Akaike information criterion (AIC), F test and histopathologic inflammation reference. The results showed that the optimization-derived DBIF model improved the fitting of liver time activity curves and achieved lower AIC values and higher F values than the SBIF and population-based DBIF models in all patients. The optimization-derived model significantly increased FDG K1 estimates by 101% and 27% as compared with traditional SBIF and population-based DBIF. K1 by the optimization-derived model was significantly associated with histopathologic grades of liver inflammation while the other two models did not provide a statistical significance. In conclusion, modeling of DBIF is critical for kinetic analysis of dynamic liver FDG-PET data in human studies. The optimization-derived DBIF model is more appropriate than SBIF and population-based DBIF for dynamic FDG-PET of liver inflammation. © 2018

Donor-derived infections among Chinese donation after cardiac death liver recipients.

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Ye, Qi-Fa; Zhou, Wei; Wan, Qi-Quan

2017-08-21

To investigate blood cultures of deceased donors and report the confirmed transmission of bacterial infection from donors to liver recipients. We retrospectively studied the results of blood cultures among our donation after cardiac death (DCD) donors and calculated the donor-derived bacterial infection rates among liver recipients. Study participants underwent liver transplantation between January 1, 2010 and February 1, 2017. The study involved a total of 67 recipients of liver grafts from 67 DCD donors. We extracted the data of donors' and patients' characteristics, culture results and clinical outcomes, especially the post-transplant complications in liver recipients, from electronic medical records. We analyzed the characteristics of the donors and the corresponding liver recipients with emphasis put on donor-derived infections. Head trauma was the most common origin of death among our 67 DCD donors (46.3%). Blood taken prior to the procurement operation was cultured for 53 of the donors, with 17 episodes of bloodstream infections developing from 13 donors. The predominant organism isolated from the blood of donors was Gram-positive bacteria (70.6%). Only three (4.5%) of 67 liver recipients developed confirmed donor-derived bacterial infections, with two isolates of multidrug-resistant Klebsiella pneumoniae and one isolate of multidrug-resistant Enterobacter aerogenes. The liver recipients with donor-derived infections showed relation to higher crude mortality and graft loss rates (33.3% each) within 3 mo post transplantation, as compared to those without donor-derived infections (9.4% and 4.7%, respectively). All three liver recipients received appropriate antimicrobial therapy. Liver recipients have high occurrence of donor-derived infections. The liver recipients with donor-derived multidrug-resistant Enterobacteriaceae infections can have good outcome if appropriate antimicrobial therapy is given.

Nuclear magnetic resonance (NMR): application to examine liver tissues during invasion of the Liver fluke in cattle

International Nuclear Information System (INIS)

Wranicz, M.; Podbielski, T.; Grabiec, S.

1989-01-01

The T 1 and T 2 relaxation times of protons of hydrogen in the liver parenchyma and biliary ducts in normal and parazitized by the Liver fluke cows were determined. A method of the NMR in which a lenght or relaxation time is an index was applied. The value of this index is characteristic for determined physiological and pathological states of cells and it reveals changes which developed in body cells. It was found that tissues of cows parazitized by the Liver fluke (parenchyma and biliary ducts) and healthy ones differ significantly by the lenght of relaxation times. Parazitized tissues show a longer relaxation time than tissues of normal cows. (author)

Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

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Ruchi Sharma

2010-01-01

Full Text Available The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

Affinity of /sup 167/Tm-citrate for tumor and liver tissue

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Ando, A; Ando, I; Hiraki, T; Sakamoto, K; Hisada, K; Takeshita, M

1983-10-07

Strong affinity of /sup 167/Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with /sup 167/Tm-citrate because of its strong tumor affinity and because of the suitable physical characteristics of /sup 167/Tm. A large amount of /sup 167/Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. /sup 167/Tm was not seen in necrotic tumor tissue. It was concluded that lysosomes did not play a major role in the tumor concentration of /sup 167/Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumed that lysosomes played a considerably important role in the tumor concentration of /sup 167/Tm, hepatoma AH109A possessing some residual features of the liver. /sup 167/Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which /sup 167/Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate).

Biomaterials and Culture Technologies for Regenerative Therapy of Liver Tissue.

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Perez, Roman A; Jung, Cho-Rok; Kim, Hae-Won

2017-01-01

Regenerative approach has emerged to substitute the current extracorporeal technologies for the treatment of diseased and damaged liver tissue. This is based on the use of biomaterials that modulate the responses of hepatic cells through the unique matrix properties tuned to recapitulate regenerative functions. Cells in liver preserve their phenotype or differentiate through the interactions with extracellular matrix molecules. Therefore, the intrinsic properties of the engineered biomaterials, such as stiffness and surface topography, need to be tailored to induce appropriate cellular functions. The matrix physical stimuli can be combined with biochemical cues, such as immobilized functional groups or the delivered actions of signaling molecules. Furthermore, the external modulation of cells, through cocultures with nonparenchymal cells (e.g., endothelial cells) that can signal bioactive molecules, is another promising avenue to regenerate liver tissue. This review disseminates the recent approaches of regenerating liver tissue, with a focus on the development of biomaterials and the related culture technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

POLARIZATION IMAGING AND SCATTERING MODEL OF CANCEROUS LIVER TISSUES

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DONGZHI LI

2013-07-01

Full Text Available We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI, degree of polarization imaging (DOPI and rotating linear polarization imaging (RLPI. Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.

Superoxide Dismutase (SOD Enzyme Activity Assay in Fasciola spp. Para-sites and Liver Tissue Extract

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M Assady

2011-09-01

Full Text Available Background: The purpose of this comparative study was to detect superoxide dismutase (SOD activities in Fasciola hepatica, F. gigantica parasites, infected and healthy liver tissues in order to determine of species effects and liver infection on SODs activity level.Methods: Fasciola spp. parasites and sheep liver tissues (healthy and infected liver tissues, 10 samples for each, were collected, homogenized and investigated for protein measurement, protein detection and SOD enzyme activity assay. Protein concentration was measured by Bradford method and SODs band protein was detected on SDS-PAGE. SODs activity was determined by iodonitrotetrazolium chloride, INT, and xanthine substrates. Independent samples t-test was conducted for analysis of SODs activities difference.Results: Protein concentration means were detected for F. hepatica 1.3 mg/ ml, F. gigantica 2.9 mg/ml, healthy liver tissue 5.5 mg/ml and infected liver tissue 1.6 mg/ml (with similar weight sample mass. Specific enzyme activities in the samples were obtained 0.58, 0.57, 0.51, 1.43 U/mg for F. hepatica, F. gigantica, healthy liver and infected liver respectively. Gel electrophoresis of Fasciola spp. and sheep liver tissue extracts revealed a band protein with MW of 60 kDa. The statistical analysis revealed significant difference between SOD activities of Fasciola species and also between SOD activity of liver tissues (P<.05.Conclusion: Fasciola species and liver infection are effective causes on SOD enzyme activity level.

Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

Energy Technology Data Exchange (ETDEWEB)

Meyer, Carsten [University of Bonn, Department of Radiology, Bonn (Germany); Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz [University of Bonn, Department of Radiology, Bonn (Germany); Ezziddin, Samer; Ahmadzadehfar, Hojjat [University of Bonn, Department of Nuclear Medicine, Bonn (Germany)

2014-02-15

To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with {sup 90}Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept {sup registered} S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and {sup 99m}Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with {sup 18}F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. {sup 99m}Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

International Nuclear Information System (INIS)

Meyer, Carsten; Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz; Ezziddin, Samer; Ahmadzadehfar, Hojjat

2014-01-01

To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with 90 Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept registered S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and 99m Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with 18 F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. 99m Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity

International Nuclear Information System (INIS)

Herraez, Elisa; Macias, Rocio I.R.; Vazquez-Tato, Jose; Hierro, Carlos; Monte, Maria J.; Marin, Jose J.G.

2009-01-01

Phalloidin causes severe liver damage characterized by marked cholestasis, which is due in part to irreversible polymerization of actin filaments. Liver uptake of this toxin through the transporter OATP1B1 is inhibited by the bile acid derivative BALU-1, which does not inhibit the sodium-dependent bile acid transporter NTCP. The aim of the present study was to investigate whether BALU-1 prevents liver uptake of phalloidin without impairing endogenous bile acid handling and hence may have protective effects against the hepatotoxicity induced by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased bile flow more than taurocholic acid (TCA). Phalloidin administration decreased basal (- 60%) and TCA-stimulated bile flow (- 55%) without impairing bile acid output. Phalloidin-induced cholestasis was accompanied by liver necrosis, nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced cholestasis was partially prevented. Moreover haematuria was not observed, which was consistent with histological evidences of BALU-1-prevented injury of liver and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile mainly in non-conjugated form, although a small proportion ( TCA > DHCA > UDCA. In conclusion, BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due to an inhibition of the liver uptake and an enhanced biliary secretion of this toxin.

Normal liver tissue sparing by intensity-modulated proton stereotactic body radiotherapy for solitary liver tumours

International Nuclear Information System (INIS)

Petersen, Joergen B. B.; Hansen, Anders T.; Lassen, Yasmin; Grau, Cai; Hoeyer, Morten; Muren, Ludvig P.

2011-01-01

Background. Stereotactic body radiotherapy (SBRT) is often the preferred treatment for the advanced liver tumours which owing to tumour distribution, size and multi-focality are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients with liver tumours may be candidates for conventional SBRT because of the limited radiation tolerance of normal liver, intestine and other normal tissues. Due to the favourable depth-dose characteristics of protons, intensity-modulated proton therapy (IMPT) may be a superior alternative to photon-based SBRT. The purpose of this treatment planning study was therefore to investigate the potential sparing of normal liver by IMPT compared to photon-based intensity-modulated radiotherapy (IMRT) for solitary liver tumours. Material and methods. Ten patients with solitary liver metastasis treated at our institution with multi-field SBRT were retrospectively re-planned with IMRT and proton pencil beam scanning techniques. For the proton plans, two to three coplanar fields were used in contrast to five to six coplanar and non-coplanar photon fields. The same planning objectives were used for both techniques. A risk adapted dose prescription to the PTV surface of 12.5-16.75 Gy x 3 was used. Results. The spared liver volume for IMPT was higher compared to IMRT in all 10 patients. At the highest prescription dose level, the median liver volume receiving less than 15 Gy was 1411 cm 3 for IMPT and 955 cm 3 for IMRT (p D 15 Gy > 700 cm 3 constraint. For the D mean = 15 Gy constraint, nine of 10 cases could be treated at the highest dose level using IMPT whereas with IMRT, only two cases met this constraint at the highest dose level and six at the lowest dose level. Conclusion. A considerable sparing of normal liver tissue can be obtained using proton-based SBRT for solitary liver tumours

Analysis of iron storage proteins in chicken liver and spleen tissues in comparison with human liver ferritin by Moessbauer spectroscopy

International Nuclear Information System (INIS)

Oshtrakh, M.I.; Milder, O.B.; Semionkin, V.A.; Malakheeva, L.I.; Prokopenko, P.G.

2006-01-01

Characterization of iron storage proteins in liver and spleen from normal chicken and chicken with lymphoid leukemia in comparison with human liver ferritin were considered by Moessbauer spectroscopy (preliminary results). Small differences in Moessbauer hyperfine parameters for both normal and lymphoid leukemia chicken liver and spleen were observed. The value of quadrupole splitting for human liver ferritin was higher than those for chicken tissues. A decrease of iron content in lymphoid leukemia chicken tissues was also found, however, the reason of this fact (pathology or feeding) was not clear yet. (author)

Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery.

Science.gov (United States)

Kizawa, Hideki; Nagao, Eri; Shimamura, Mitsuru; Zhang, Guangyuan; Torii, Hitoshi

2017-07-01

The liver plays a central role in metabolism. Although many studies have described in vitro liver models for drug discovery, to date, no model has been described that can stably maintain liver function. Here, we used a unique, scaffold-free 3D bio-printing technology to construct a small portion of liver tissue that could stably maintain drug, glucose, and lipid metabolism, in addition to bile acid secretion. This bio-printed normal human liver tissue maintained expression of several kinds of hepatic drug transporters and metabolic enzymes that functioned for several weeks. The bio-printed liver tissue displayed glucose production via cAMP/protein kinase A signaling, which could be suppressed with insulin. Bile acid secretion was also observed from the printed liver tissue, and it accumulated in the culture medium over time. We observed both bile duct and sinusoid-like structures in the bio-printed liver tissue, which suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct route. These results demonstrated that our bio-printed liver tissue was unique, because it exerted diverse liver metabolic functions for several weeks. In future, we expect our bio-printed liver tissue to be applied to developing new models that can be used to improve preclinical predictions of long-term toxicity in humans, generate novel targets for metabolic liver disease, and evaluate biliary excretion in drug development.

Aldolase A isoenzyme levels in serum and tissues of patients with liver diseases

International Nuclear Information System (INIS)

Asaka, M.; Nagase, K.; Miyazaki, T.; Alpert, E.

1983-01-01

A radioimmunoassay specific for human aldolase A was used to measure human aldolase A levels in human tissue and serum of patients with various liver diseases. The method was a double-antibody technique using radio-iodinated purified aldolase A, chicken antibody to aldolase A, and rabbit antibody to chicken immunoglobulin G. Normal liver tissue contains only a small amount of aldolase A. In contrast, aldolase A predominates in liver cell carcinoma tissue. Aldolase A levels in the sera of normal subjects were 171 +/- 39 ng/ml (mean +/- 2 SD). In almost all of the nonmalignant liver diseases, the aldolase A levels remained less than 210 ng/ml. The serum aldolase A levels increased remarkable only in fulminant hepatitis. in contrast, 32 of 34 patients with liver cell carcinoma and all of 29 patients with metastatic liver carcinoma showed clearly increased serum aldolase A levels. More patients with primary liver cell carcinoma had increased serum aldolase A levels than elevations of serum alpha-fetoprotein. These results suggest that the determination of aldolase A by radioimmunoassay may be useful to differentiate malignant form nonmalignant liver diseases

High intensity interval training improves liver and adipose tissue insulin sensitivity

Directory of Open Access Journals (Sweden)

Katarina Marcinko

2015-12-01

Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

Immunohistochemical examination of effects of kefir, koumiss and commercial probiotic capsules on platelet derived growth factor-c and platelet derived growth factor receptor-alpha expression in mouse liver and kidney.

Science.gov (United States)

Bakir, B; Sari, E K; Aydin, B D; Yildiz, S E

2015-04-01

We investigated using immunohistochemistry the effects of kefir, koumiss and commercial probiotic capsules on the expression of platelet derived growth factor-c (PDGF-C) and platelet derived growth factor receptor-alpha (PDGFR-α) in mouse liver and kidney. Mice were assigned to four groups: group 1 was given commercial probiotic capsules, group 2 was given kefir, group 3 was given koumiss and group 4 was untreated. After oral administration for 15 days, body weights were recorded and liver and kidney tissue samples were obtained. Hematoxylin and eosin staining was used to examine histology. PDGF-C and PDGFR-α in liver and kidney were localized using the streptavidin-biotin peroxidase complex method (ABC). We found that the weights of the mice in the kefir, koumiss and commercial probiotic capsules groups increased compared to the control group. No differences in liver and kidney histology were observed in any of the experimental groups. Kefir, koumiss and the commercial probiotic preparation increased PDGF-C and PDGFR-α expression.

Betatrophin: A liver-derived hormone for the pancreatic β-cell proliferation.

Science.gov (United States)

Raghow, Rajendra

2013-12-15

The pancreatic β-cell failure which invariably accompanies insulin resistance in the liver and skeletal muscle is a hallmark of type-2 diabetes mellitus (T2DM). The persistent hyperglycemia of T2DM is often treated with anti-diabetic drugs with or without subcutaneous insulin injections, neither of which mimic the physiological glycemic control seen in individuals with fully functional pancreas. A sought after goal for the treatment of T2DM has been to harness the regenerative potential of pancreatic β-cells that might obviate a need for exogenous insulin injections. A new study towards attaining this aim was reported by Yi et al, who have characterized a liver-derived protein, named betatrophin, capable of inducing pancreatic β-cell proliferation in mice. Using a variety of in vitro and in vivo methods, Yi et al, have shown that betatrophin was expressed mainly in the liver and adipose tissue of mice. Exogenous expression of betatrophin in the liver led to dramatic increase in the pancreatic β-cell mass and higher output of insulin in mice that also concomitantly elicited improved glucose tolerance. The authors discovered that betatrophin was also present in the human plasma. Surprisingly, betatrophin has been previously described by three other names, i.e., re-feeding-induced fat and liver protein, lipasin and atypical angiopoeitin-like 8, by three independent laboratories, as nutritionally regulated liver-enriched factors that control serum triglyceride levels and lipid metabolism. Yi et al demonstration of betatrophin, as a circulating hormone that regulates β-cell proliferation, if successfully translated in the clinic, holds the potential to change the course of current therapies for diabetes.

Detection and quantitation analysis of cocaine and metabolites in fixed liver tissue and formalin solutions.

Science.gov (United States)

Cingolani, Mariano; Cippitelli, Marcello; Froldi, Rino; Gambaro, Veniero; Tassoni, Giovanna

2004-01-01

This study reports the results of the detection and quantitation of cocaine and its metabolites in liver tissues fixed in formalin and in the formalin solutions in which the same tissues were fixed. Toxicological analyses were performed on formalin-fixed liver samples from four cases of death of cocaine abusers and on formalin solutions (10% buffered, pH 7) in which the samples were preserved. Analyses carried out at the time of autopsy on body fluids and tissues allowed identification of cocaine and the metabolite benzoylecgonine. Liver tissue samples were preserved in formalin solutions for four weeks before analysis. Results only showed the presence of benzoylecgonine in the studied materials. The mean levels of recovery of benzoylecgonine in fixed tissues were 12.31% in liver and 84.47% in formalin from liver. Results indicated that benzoylecgonine has good stability, even in biological specimens subjected to chemical fixation.

Differentiation of diffuse liver disease with computer-aided tissue echo quantification

International Nuclear Information System (INIS)

Cha, Joo Hee; Choi, Byung Ihm; Yun, Eun Joo; Ko, Young Hwan; Song, Chi Sung; Kim, Seung Hyup; Han, Joon Koo; Kim, Tae Kyoung; Lee, Dong Hyuk; Kim, Jong Hyo

1999-01-01

The purpose of this study was to evaluate the efficacy of computer-aided tissue echo quantification technique in the differentiation of diffuse liver diseases. Sixty-five patients with chronic liver disease including chronic hepatitis in 21 patients, fatty liver in 11, and liver cirrhosis in 33, and 55 normal volunteers were included in this study. The sonographic images by the Sono-PACS(MARO, Seoul) was recalled and the analysis was done for the hepatic parenchymal coarseness by the program using Visual C++. Difference histogram variation (DHV), edge density (ED) and intertia of concurrence matrix (ICM) were used as the coarseness index. These three indexes were statistically significant (p<0.05) in the differentiation of these four groups. The accuracy of the differentiation between any two of four groups was 83.0%. The accuracy of the differentiation of these four groups was 70.8% at the same time. The computer-aided tissue echo quantification technique is a complementary study for the differentiation of diffuse liver disease.

Effects of radiosensibilization by metronidazole on liver tissue in patients with gastric carcinomas

International Nuclear Information System (INIS)

D'yakova, A.M.; Stefani, N.V.; Zagrebin, V.M.; Senokosov, N.I.; Berdov, B.A.

1985-01-01

Metronidazole, used as radiosensitizer in preoperative radiotherapy of gastric carcinoma caused an increased glycogen accumulation in the left lobe of the liver with a radiation dose of 80-100 % of the isodose. The glycogen level was higher not only in comparison with the same liver area in patients without radiosensitizer but also with the right lobe of the own liver within in the area of stray radiation. The effect observed after radiation was considered as result of the sensitizing influence on liver tissue. The sensitizing effect of metronidazole depended on its concentration in the patient's serum. In the right lobe of the liver the glycogen level showed no alteration under metronidazole. Metronidazole reduced the activity of lactate dehydrogenase and cholinesterase in liver tissue independently of its concentration in the serum and of the radiation dose on particular parts of the liver. (author)

A Case of Hemorrhagic Necrosis of Ectopic Liver Tissue within the Gallbladder Wall.

LENUS (Irish Health Repository)

Nagar, Sapna

2012-02-01

Ectopic liver tissue is a rare clinical entity that is mostly asymptomatic and found incidentally. In certain situations, however, patients may present with symptoms of abdominal pain secondary to torsion, compression, obstruction of adjacent organs, or rupture secondary to malignant transformation. Herein, we report a case of a 25-year-old female that presented with acute onset of epigastric pain found to have ectopic liver tissue near the gallbladder complicated by acute hemorrhage necessitating operative intervention in the way of laparoscopic excision and cholecystectomy. The patient\\'s postoperative course was uneventful. Gross pathology demonstrated a 1.2 x 2.8 x 4.5 cm firm purple ovoid structure that histologically revealed extensive hemorrhagic necrosis of benign ectopic liver tissue.

Quantification of total mercury in liver and heart tissue of Harbor Seals (Phoca vitulina) from Alaska USA

International Nuclear Information System (INIS)

Marino, Kady B.; Hoover-Miller, Anne; Conlon, Suzanne; Prewitt, Jill; O'Shea, Stephen K.

2011-01-01

This study quantified the Hg levels in the liver (n=98) and heart (n=43) tissues of Harbor Seals (Phoca vitulina) (n=102) harvested from Prince William Sound and Kodiak Island Alaska. Mercury tissue dry weight (dw) concentrations in the liver ranged from 1.7 to 393 ppm dw, and in the heart from 0.19 to 4.99 ppm dw. Results of this study indicate liver and heart tissues' Hg ppm dw concentrations significantly increase with age. Male Harbor Seals bioaccumulated Hg in both their liver and heart tissues at a significantly faster rate than females. The liver Hg bioaccumulation rates between the harvest locations Kodiak Island and Prince William Sound were not found to be significantly different. On adsorption Hg is transported throughout the Harbor Seal's body with the partition coefficient higher for the liver than the heart. No significant differences in the bio-distribution (liver:heart Hg ppm dw ratios (n=38)) values were found with respect to either age, sex or geographic harvest location. In this study the age at which Hg liver and heart bioaccumulation levels become significantly distinct in male and female Harbor Seals were identified through a Tukey's analysis. Of notably concern to human health was a male Harbor Seal's liver tissue harvested from Kodiak Island region. Mercury accumulation in this sample tissue was determined through a Q-test to be an outlier, having far higher Hg concentrarion (liver 392 Hg ppm dw) than the general population sampled. - Highlights: ► Mercury accumulation in the liver and heart of seals exceed food safety guidelines. ► Accumulation rate is greater in males than females with age. ► Liver mercury accumulation is greater than in the heart tissues. ► Mercury determination by USA EPA Method 7473 using thermal decomposition.

Comparison of Different Double Immunostaining Protocols for Paraffin Embedded Liver Tissue

Directory of Open Access Journals (Sweden)

Alexander Schütz

1999-01-01

Full Text Available Most of the double immunostaining protocols that have been introduced so far have been developed for application on fresh frozen material or based on different species antibodies. In liver tissue, general problems of double immunostaining techniques are further complicated by tissue‐specific difficulties, such as necrosis or high intracellular protein content. To assess a reliable double immunostaining protocol for archived, paraffin embedded liver tissue, different protocols based on the use of same species primary antibodies were evaluated in terms of sensitivity, specificity and non‐specific background staining in pathological liver specimens. We compared peroxidase–anti‐peroxidase, alkaline phosphatase–anti‐alkaline phosphatase (PAP/APAP, labelled‐avidin–biotin (LAB/LAB and digoxigenin–anti‐digoxigenin (dig–a‐dig/PAP techniques using different cytokeratin antibodies and an antibody against PCNA. Comparison of the double immunostaining techniques revealed a high sensitivity and specificity in all procedures. Sections, which were stained employing PAP/APAP‐technique, displayed a higher background staining compared to sections which were treated with the LAB/LAB or dig–a‐dig/PAP protocol. In contrast to the dig–a‐dig/PAP protocol, the LAB/LAB technique provides a better time/cost relationship. Therefore, we would like to recommend a modified LAB/LAB protocol for simultaneous detection of different antigens in archived liver tissue.

IgA against gut-derived endotoxins: does it contribute to suppression of hepatic inflammation in alcohol-induced liver disease?

DEFF Research Database (Denmark)

Parlesak, Alexandr; Schäfer, C.; Bode, C.

2002-01-01

Endotoxins of intestinal origin are supposed to play an important role in the development of alcoholic hepatitis in man. To estimate the role of immunoglobulin response to gut-derived endotoxin in the development of alcohol-induced liver disease, serum levels of IgA and IgG against fecal endotoxin......, endotoxin, and acute-phase proteins were measured in patients with different stages of alcoholic liver disease and in healthy controls. Antibodies of type IgA, but not IgG, against fecal endotoxins were significantly increased in patients with alcohol-induced liver disease. IgA antibodies against fecal...... endotoxin were found to be closely correlated with the plasma concentrations of alanine aminotransferase, gamma-glutamyl transferase, and C-reactive protein in patients with alcoholic liver disease. In conclusion, as IgA located in body tissue was shown to suppress the inflammatory process, enhanced...

Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

Science.gov (United States)

Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

2017-07-01

Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

Influence of nanoparticles accumulation on optical properties of human normal and cancerous liver tissue in vitro estimated by OCT

International Nuclear Information System (INIS)

Zhou, Fang; Wei, Huajiang; Guo, Zhouyi; Ye, Xiangping; Hu, Kun; Wu, Guoyong; Yang, Hongqin; Xie, Shusen; He, Yonghong

2015-01-01

In this work, the potential use of nanoparticles as contrast agents by using spectral domain optical coherence tomography (SD-OCT) in liver tissue was demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in human normal and cancerous liver tissues in vitro, respectively. Each sample was monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring showed that, after application of gold nanoparticles, the OCT signal intensities of normal liver and cancerous liver tissue both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The results show that the values of attenuation coefficients have significant differences between normal liver tissue and cancerous liver tissue. In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm gold nanoparticles in liver tissues. (paper)

Accuracy of real-time shear wave elastography in the assessment of normal liver tissue in the guinea pig (cavia porcellus).

Science.gov (United States)

Glińska-Suchocka, K; Kubiak, K; Spużak, J; Jankowski, M; Borusewicz, P

2017-03-28

Shear wave elastography is a novel technique enabling real-time measurement of the elasticity of liver tissue. The color map is superimposed on the classic ultrasound image of the assessed tissue, which enables a precise evaluation of the stiffness of the liver tissue. The aim of the study was to assess the stiffness of normal liver tissue in the guinea pig using shear wave elastography. The study was carried out on 36 guinea pigs using the SuperSonic Imagine Aixplorer scanner, and a 1 to 6 MH convex SC6-1 transducer. An ultrasound guided Try-Cut liver core needle biopsy was carried out in all the studied animals and the collected samples were examined to exclude pathological lesions. The mean liver tissue stiffness ranged from 0.89 to 5.40 kPa. We found that shear wave elastography is an easy, non-invasive technique that can be used to assess the stiffness of liver tissue. The obtained results can be used in future studies to assess the types and changes of liver tissue in the course of various types of liver disease.

Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine.

Science.gov (United States)

Skeldon, Gregor; Lucendo-Villarin, Baltasar; Shu, Wenmiao

2018-07-05

Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of 'bio-inks' and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. © 2018 The Author(s).

Apoptotic Effects of Reduced Brain Derived Neurotrophic Factor (BDNF on Mouse Liver and Kidney

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Berna Tezcan

2017-12-01

Full Text Available Objective: Brainderived neurotrophic factor (BDNF promotes the development and differentiation of neurons and synapses, as well as neuronal survival, by acting on specific neuronal groups in the central and peripheral nervous systems. However, the direct effect of BDNF on apoptosis in peripheral tissues is not known. The aim of this study was to investigate the relationship between BDNF and apoptosis, and the density and distribution of BDNF receptors in liver and kidney tissues by histological and immunehistochemical methods. Methods: Seven wild-type and 7 BDNF heterozygous (reduced BDNF levels male mice were used in the study. Caspase-3 and TUNEL immunehistochemical stainings were performed in order to investigate the presence of apoptosis in the liver and kidney tissues of the studied groups. Apoptosis-entering cells were counted and the groups were compared. Concentration and distribution of BDNF receptors, tropomyosin-related kinase B (TrkB and nerve growth factor receptor p75 (NGFR p75, in liver and kidney tissues were also examined by immunehistochemical analyzes. Results: As a result of Caspase-3 and TUNEL immune histochemical staining, more cells were counted to enter the apoptotic process in sections of BDNF heterozygous group compared to control group (p<0.0001. In both groups TrkB and NGFR p75 receptors in liver and kidney tissues were determined in trace amounts, but there was no difference in intensity and distribution between the studied groups. Conclusion: According to our histological and immune histochemical stainings and statistical analysis of cell count between groups, it was found that BDNF is protect ive against apoptosis in liver and kidney. The lack of difference between the studied groups in terms of intensity and distribution of BDNF receptors, suggests that BDNF receptor distribution in the liver and kidney tissues may be different from the nervous system or that BDNF may differ in affinity for these receptors.

Ectopic Liver Tissue Formation in Rats with Induced Liver Fibrosis

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Bauyrzhan Umbayev

2014-12-01

�� engraftment, we conducted immunohistochemical staining against HepPar1.Results: We observed a 30% mortality rate among rats with LF within 1 week after NDMA exposure cessation, while 100% of animals with HT survived. ALT, AST, and GGT activities and bilirubin levels were markedly elevated in blood samples of LF rats compared to the control animals. However, HT significantly improved ALT, AST, and GGT activity as well as bilirubin levels. We also observed decreased levels of total protein and albumin in the blood serum of rats with LF, while HT normalized these parameters. At the same time, we have not detected any statistical differences of the studied parameters in the group 4, which was treated with Cyclosporine A only, compared with the intact animals. HepPar1 immunohistochemical staining of the different tissue sections demonstrated the presence of engrafted hepatocytes, mainly within enlarged Peyer's patches (aggregated lymphoid nodules in the lowest portion of the small intestine.Conclusion: The results of our study provide evidence that HT improves animal survival and liver functions. One potential reason for these results is that ectopic hepatic mass inside the Peyer's patches can rescue rats from liver failure.

Derangements of liver tissue bioenergetics in concanavalin A-induced hepatitis.

Science.gov (United States)

Al-Shamsi, Mariam; Shahin, Allen; Mensah-Brown, Eric P K; Souid, Abdul-Kader

2013-01-12

A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O2 consumption) in mice treated with concanavalin A (Con A). This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. C57Bl/6 and C57Bl/6 IFN-γ-/- mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ) and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O2 as function of time was used to evaluate respiration. In sealed vials, O2 concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, pactivity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ-/- mice treated with ConA. Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes.

Adipose tissue-derived stem cells in oral mucosa tissue engineering ...

African Journals Online (AJOL)

Jane

2011-10-10

Oct 10, 2011 ... stem cells (ADSCs) may play an important role in this field. In this research ..... Adipose tissue is derived from embryonic mesodermal precursors and .... Clonogenic multipotent stem cells in human adipose tissue differentiate ...

Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells.

Science.gov (United States)

Prasetyo, R Heru; Hestianah, Eka Pramyrtha

2017-06-01

This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v) honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1) expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Honey can improve the liver tissue based on: (1) Mobilization of endogenous stem cells (CD34 and CD45); (2) Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3) regeneration histologically of liver tissue.

Effects of gadolinium-based MRI contrast agents on liver tissue.

Science.gov (United States)

Mercantepe, Tolga; Tümkaya, Levent; Çeliker, Fatma Beyazal; Topal Suzan, Zehra; Çinar, Seda; Akyildiz, Kerimali; Mercantepe, Filiz; Yilmaz, Adnan

2018-04-01

MRI with contrast is often used clinically. However, recent studies have reported a high accumulation of gadolinium-based contrast agents (GBCAs) in kidney, liver, and spleen tissues in several mouse models. To compare the effects on liver tissue of gadolinium-based MRI contrast agents in the light of biochemical and histopathological evaluation. Institutional Review Board (IRB)-approved controlled longitudinal study. In all, 32 male Sprague-Dawley rats were divided into a healthy control group subjected to no procedure (Group 1), a sham group (Group 2), a gadodiamide group (Group 3), and a gadoteric acid group (Group 4). Not applicable. Liver tissues removed at the end of the fifth week and evaluated pathologically (scored Knodell's histological activity index [HAI] method by two histopathologists) immunohistochemical (caspase-3 and biochemical tests (AST, ALT, TAS, TOS, and OSI method by Erel et al) were obtained. Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by the Tamhane test, and one-way analysis of variance (ANOVA) followed by Turkey's HSD test. An increase was observed in histological activity scores in sections from rats administered gadodiamide and gadoteric acid, and in caspase-3, AST and ALT values (P total antioxidant and antioxidant capacity. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

The role of zinc supplementation in the inhibition of tissue damage caused by exposure to electromagnetic field in rat lung and liver tissues.

Science.gov (United States)

Baltaci, A K; Mogulkoc, R; Salbacak, A; Celik, I; Sivrikaya, A

2012-01-01

The objective of the present study was to examine the effects of zinc supplementation on the oxidant damage in lung and liver tissues in rats exposed to a 50-Hz frequency magnetic field for 5 minutes every other day over a period of 6 months. The study included 24 adult male Sprague-Dawley rats, which were divided into the three groups in equal numbers: Group 1, the control group (G1); Group 2, the group exposed to an electromagnetic field (G2); and Group 3, the group, which was exposed to an EMF and supplemented with zinc (G3). At the end of the 6-month procedures, the animals were decapitated to collect lung and liver tissue samples, in which MDA was analyzed using the "TBARS method (nmol/g/protein)", GSH by the "biuret method (mg/g/protein)" and zinc levels by atomic emission (µg/dl). MDA levels in lung and liver tissues in G2 were higher than those in G1 and G3, and the levels in G3 were higher than those in G1 (pelectromagnetic field caused cellular damage in lung and liver tissues and zinc supplementation inhibited the inflicted cellular damage. Another important result of this study that needs emphasis was that exposure to an electromagnetic field led to a significant decrease in zinc levels in lung and liver tissues (Tab. 3, Ref. 23).

Donor-derived metastatic melanoma in a liver transplant recipient established by DNA fingerprinting.

Science.gov (United States)

Bilal, Muhammad; Eason, James D; Das, Kanak; Sylvestre, Pamela B; Dean, Amanda G; Vanatta, Jason M

2013-10-01

Metastatic melanoma is a donor-derived malignancy that has rarely been reported in liver allograft recipients. We present a case of a transmitted donor-derived melanoma to a liver allograft recipient in whom the diagnosis was established by polymerase chain reaction-based DNA fingerprinting. A 52-year-old African-American man underwent a successful orthotropic liver transplant for alcohol-induced cirrhosis. One year after the orthotropic liver transplant, he presented at our institution with diffuse abdominal pain, and a computed tomography scan of the abdomen and chest showed innumerable masses diffusely involving the liver and multiple subcutaneous nodules in the abdominal and chest wall. A liver biopsy confirmed the diagnosis of metastatic melanoma. The origin of melanoma was traced to the donor by DNA fingerprinting of the native liver, the donor liver, and the donor gallbladder. Chemotherapy was initiated with temozolomide (75 mg/m² daily) and thalidomide (50 mg daily), to which he responded within 8 weeks with radiologic improvement in metastatic lesions. Tacrolimus was switched to sirolimus because of renal insufficiency as well as reported effectiveness against melanoma. Our patient survived for 9 months after the diagnosis of metastatic melanoma. He ultimately died of brain metastases. Donor-derived metastatic melanoma is a rare cancer with the highest transmission and mortality rates, which requires better recognition. Prompt diagnosis of donor-derived melanoma is critical and can be achieved reliably with polymerase chain reaction-based DNA analysis. Management options after diagnosis include de-escalation of immunosuppression, with or without urgent organ removal or retransplant. The roles of chemotherapy, immunotherapy, and radiotherapy require further study.

Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model.

Science.gov (United States)

Mohamed, Hoda E; Elswefy, Sahar E; Rashed, Laila A; Younis, Nahla N; Shaheen, Mohamed A; Ghanim, Amal M H

2016-03-01

Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM-MSCs) induce liver regeneration of fibrotic liver in rats. Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM-MSCs (3 × 10(6) cells /rat, once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and α-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA. © 2016 by the Society for Experimental Biology and Medicine.

Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats.

Science.gov (United States)

Tang, Wei-Ping; Akahoshi, Tomohiko; Piao, Jing-Shu; Narahara, Sayoko; Murata, Masaharu; Kawano, Takahito; Hamano, Nobuhito; Ikeda, Tetsuo; Hashizume, Makoto

2016-08-01

Clinical studies suggest that splenectomy improves liver function in cirrhotic patients, but the influence of splenectomy on stem cell transplantation is poorly understood. This study investigated the effect of splenectomy on stem cell infusion and elucidated its mechanism. Rat adipose tissue-derived mesenchymal stem cells were infused into cirrhosis rats with or without splenectomy, followed by the assessment of the in vivo distribution of stem cells and pathological changes. Stromal cell-derived factor-1 and hepatocyte growth factor expression were also investigated in splenectomized cirrhosis patients and rats. Splenectomy, prior to cell infusion, improved liver function and suppressed fibrosis progression more efficiently than cell infusion alone in the experimental cirrhosis model. Stromal cell-derived factor-1 and hepatocyte growth factor levels after splenectomy were increased in patients and rats. These upregulated cytokines significantly facilitated stem cell motility, migration and proliferation in vitro. C-X-C chemokine receptor type 4 neutralization weakened the promotion of cell migration by these cytokines. The infused cells integrated into liver fibrosis septa and participated in regeneration more efficiently in splenectomized rats. Direct coculture with stem cells led to inhibition of hepatic stellate cell proliferation. In addition, hepatocyte growth factor induced hepatic stellate cell apoptosis via the c-jun N-terminal kinase-p53 pathway. Splenectomy prior to cell infusion enhanced the therapeutic effect of stem cells on cirrhosis, which involved upregulation of stromal cell-derived factor-1 and hepatocyte growth factor after splenectomy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

International Nuclear Information System (INIS)

Lanza-Jacoby, S.; Tabares, A.

1990-01-01

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats

Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells

Directory of Open Access Journals (Sweden)

R. Heru Prasetyo

2017-06-01

Full Text Available Aim: This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Materials and Methods: Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1 expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. Results: There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Conclusion: Honey can improve the liver tissue based on: (1 Mobilization of endogenous stem cells (CD34 and CD45; (2 Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3 regeneration histologically of liver tissue.

Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

DEFF Research Database (Denmark)

Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard

2013-01-01

-specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...... of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including...

Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post Radioembolization 90Y PET

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Shyam Mohan Srinivas

2014-10-01

Full Text Available Background: Radioembolization with Yttrium-90 (90Y microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC. Using post-treatment 90Y PET/CT scans,the distribution of microspheres within the liver can be determined and quantitatively assessesed . We studied the radiation dose of 90Y delivered to liver and treated tumors.Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres® to the frequency of complications with mRECIST. 90Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL to an absorbed dose (Gy.Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90-120 Gy;range 0-570 Gy. Tumor response by mRECIST criteria was performed for 48 tumors that had follow up scans. There were 21 responders (mean dose 215 Gy and 27 nonresponders (mean dose 167 Gy. The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p=0.099. Normal liver tissue received a mean dose of 67 Gy (mode 60-70 Gy; range 10-120 Gy. There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p=0.036.Conclusion: Our cohort of patients showed a possible dose response trend for the tumors. Collateral dose to normal liver is nontrivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose which the tumor or normal liver received.

Peroxisome proliferator-activated receptor α (PPARα mRNA expression in human hepatocellular carcinoma tissue and non-cancerous liver tissue

Directory of Open Access Journals (Sweden)

Kurokawa Tsuyoshi

2011-12-01

Full Text Available Abstract Background Peroxisome proliferator-activated receptor α (PPARα regulates lipid metabolism in the liver. It is unclear, however, how this receptor changes in liver cancer tissue. On the other hand, mouse carcinogenicity studies showed that PPARα is necessary for the development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer have been the focus of considerable attention. There have been no reports, however, demonstrating that PPARα is involved in the development of human liver cancer. Methods The subjects were 10 patients who underwent hepatectomy for hepatocellular carcinoma. We assessed the expression of PPARα mRNA in human hepatocellular carcinoma tissue and non-cancerous tissue, as well as the expression of target genes of PPARα, carnitine palmitoyltransferase 1A and cyclin D1 mRNAs. We also evaluated glyceraldehyde 3-phosphate dehydrogenase, a key enzyme in the glycolytic system. Results The amounts of PPARα, carnitine palmitoyltransferase 1A and glyceraldehyde 3-phosphate dehydrogenase mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of cyclin D1 mRNA tends to be higher in cancerous than non-cancerous sections. Although there was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections. Conclusion The present investigation indicated increased expression of PPARα mRNA and mRNAs for PPARα target genes in human hepatocellular carcinoma. These results might be associated with its carcinogenesis and characteristic features of energy production.

Ultrasound imaging of Nd:YAG laser-induced tissue coagulation in porcine livers.

Science.gov (United States)

Ritzel, U; Wietzke-Braun, P; Brinck, U; Leonhardt, U; Ramadori, G

2001-12-01

Absorption of laser light energy induces denaturation of proteins and thermocoagulation of irradiated tissue. Recently, MRI-guided laser coagulation in combination with MR thermometry was reported as a treatment of liver tumours. In the present study ultrasonographic imaging was evaluated for its suitability in laser induced tissue thermocoagulation. Fresh porcine livers were used for ex vivo examinations. Placement of the laser catheter and tissue coagulation during laser light emission were online monitored by ultrasonography. Nd:YAG laser-induced tissue damage was evaluated by macroscopical and microscopical examinations of histological sections. During laser light emission a marked hyperdense signal enhancement was observed by ultrasonography which strongly correlated with the extent of macroscopic tissue damage. The size of laser-induced coagulation zone depended on both the power setting and total energy delivered. Carbonization of the tissue surrounding the laser tip is a limiting factor because of laser light absorption. However our data indicate that using appropriate laser energy and exposure time prevent carbonization although carbonization can not be visualized by ultrasonography. It is concluded from the present ex vivo studies that laser coagulation can be effectively performed under ultrasonographic guidance.

Difference in Uptake of Tetrodotoxin and Saxitoxins into Liver Tissue Slices among Pufferfish, Boxfish and Porcupinefish

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Yuji Nagashima

2018-01-01

Full Text Available Although pufferfish of the family Tetraodontidae contain high levels of tetrodotoxin (TTX mainly in the liver, some species of pufferfish, boxfish of the family Ostraciidae, and porcupinefish of the family Diodontidae do not. To clarify the mechanisms, uptake of TTX and saxitoxins (STXs into liver tissue slices of pufferfish, boxfish and porcupinefish was examined. Liver tissue slices of the pufferfish (toxic species Takifugu rubripes and non-toxic species Lagocephalus spadiceus, L. cheesemanii and Sphoeroides pachygaster incubated with 50 µM TTX accumulated TTX (0.99–1.55 µg TTX/mg protein after 8 h, regardless of the toxicity of the species. In contrast, in liver tissue slices of boxfish (Ostracion immaculatus and porcupinefish (Diodon holocanthus, D. liturosus, D. hystrix and Chilomycterus reticulatus, TTX content did not increase with incubation time, and was about 0.1 µg TTX/mg protein. When liver tissue slices were incubated with 50 µM STXs for 8 h, the STXs content was <0.1 µg STXs/mg protein, irrespective of the fish species. These findings indicate that, like the toxic species of pufferfish T. rubripes, non-toxic species such as L. spadiceus, L. cheesemanii and S. pachygaster, potentially take up TTX into the liver, while non-toxic boxfish and porcupinefish do not take up either TTX or STXs.

The experimental study of radiation injury on bile duct and liver tissue

International Nuclear Information System (INIS)

Cao Guiwen; Wang Bin; Sun Yequan; Shao Xueye; Ning Houfa; Sui Shouguang; Wang Xiuchun; Bai Xuming

2007-01-01

Objective: To investigate the safety, acceptance and the effective extent of 192 Ir-internal irradiation, providing theoretical guidelines for HC. Methods: Sixteen male healthy hybrid dogs enrolled in the experiment were divided into 4 groups of 4 each. The brachytherapy applicator was introduced from gall bladder into the convergence of cystic duct with common hepatic duct during the operation and a small chip of 1 cm 3 liver tissue was cut off and taken for control later on. The animals in group A-D were irradiated by 192 Ir-internal irradiation with 30 Gy, 40 Gy, 50 Gy arid 60 Gy at the correlative dose points respectively. Animals were put to death after 10 days subsequently, with sampling specimens obtained from radiation cystic duct and the in between liver tissue with the distant cystic duct. The radiation injury of the cystic duct and liver tissue near bile ducts were observed and studied by light microscope and transmission election microscope. Results: By the limit of the safest endurance dose(50 Gy) of Bile duct, unreversed injury of the nuclei of liver cells occurred at 0 to 15 mm from bile duct revealed by transmission electron microscope and light microscope. The whole biliary duct wall would be undergone necrosis with irradiation dose over 60 Gy. Conclusions: Normal bile duct possesses good endurance to 192 Ir-internal irradiation. Within the safest endurance limit of 50 Gy the effective irradiation field could reach 15 mm from the involved bile duct. (authors)

Tissue-specific bioaccumulation of human and veterinary antibiotics in bile, plasma, liver and muscle tissues of wild fish from a highly urbanized region

International Nuclear Information System (INIS)

Zhao, Jian-Liang; Liu, You-Sheng; Liu, Wang-Rong; Jiang, Yu-Xia; Su, Hao-Chang; Zhang, Qian-Qian; Chen, Xiao-Wen; Yang, Yuan-Yuan; Chen, Jun; Liu, Shuang-Shuang; Pan, Chang-Gui; Huang, Guo-Yong; Ying, Guang-Guo

2015-01-01

We investigated the bioaccumulation of antibiotics in bile, plasma, liver and muscle tissues of wild fish from four rivers in the Pearl River Delta region. In total, 12 antibiotics were present in at least one type of fish tissues from nine wild fish species in the four rivers. The mean values of log bioaccumulation factors (log BAFs) for the detected antibiotics in fish bile, plasma, liver, and muscle tissues were at the range of 2.06–4.08, 1.85–3.47, 1.41–3.51, and 0.48–2.70, respectively. As the digestion tissues, fish bile, plasma, and liver showed strong bioaccumulation ability for some antibiotics, indicating a different bioaccumulation pattern from hydrophobic organic contaminants. Human health risk assessment based on potential fish consumption indicates that these antibiotics do not appear to pose an appreciable risk to human health. To the best of our knowledge, this is first report of bioaccumulation patterns of antibiotics in wild fish bile and plasma. - Highlights: • We investigated the bioaccumulation of antibiotics in wild fish from the Pearl River Delta region. • Twelve antibiotics were found in fish bile, plasma, liver and muscle tissues. • High log bioaccumulation factors suggested strong bioaccumulation ability for some antibiotics in wild fish tissues. • The presence of antibiotics in fish bile and plasma tissues indicates a novel bioaccumulation pattern. • Potential adverse effects are possibly caused by the high internal antibiotic concentrations in tissues. - Fish bile and plasma displayed strong bioaccumulation ability for some antibiotics, indicating a novel bioaccumulation pattern for antibiotics in the contaminated environment

Iophenoxic acid derivatives as markers of oral baits to wildlife. New tools for their detection in tissues of a game species and safety considerations for human exposure.

Science.gov (United States)

Sage, Mickael; Fourel, Isabelle; Lahoreau, Jennifer; Siat, Vivien; Berny, Philippe; Rossi, Sophie

2013-05-01

The bait-marker iophenoxic acid (IPA) and its derivatives are increasingly used for evaluating and optimizing the cost-effectiveness of baiting campaigns on wildlife, particularly on game species such as the wild boar. We aimed to determine whether concentrations of the three main IPA derivatives ethyl, methyl and propyl-IPA measured on thoracic liquid extracts (TLE) of hunted wild boars may be representative of two exposure doses, 40 and 200 mg, from 20 to 217 days after ingestion. Then we developed a method of detection of the three IPA derivatives by LC/ESI-MS-MS in muscle and liver to evaluate the suitability of these two other tissues for monitoring the marked bait consumption and for measuring available residues in the meat of marked animals. Three semi-captive wild boars received 40 mg of each IPA derivative, three received 200 mg, and three, as controls, did not receive IPA. Blood serum was sampled 20, 197 or 217 days after IPA exposure according to animals and to the derivative. Wild boars were shot by gun after the different times of serum sampling times, and TLE, muscle and liver were sampled. Our results suggest that TLE is not a relevant tissue for quantitatively expressing IPA exposure. Due to interference, no analytical method was validated on TLE containing digestive material. On the other hand, quantifications in the muscle and particularly in the liver could discriminate wild boars that had ingested the two IPA doses from 20 days until 7 months after exposure, especially for the two long term markers ethyl and propyl-IPA. So IPA quantifications in the liver sampled on hunted animals appear to be a reliable tool for monitoring bait consumption in the field at a large scale. Nevertheless, whatever the ingested dose, ethyl- and propyl-IPA concentrations measured in the muscle and the liver of tested animals until 217 days after exposure, remained higher than 0.01 mg/kg, the Maximal Residue Limit (MRL) is recommended for molecules for which no

Derangements of liver tissue bioenergetics in Concanavalin A-induced hepatitis

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Al-Shamsi Mariam

2013-01-01

Full Text Available Abstract Background A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O2 consumption in mice treated with concanavalin A (Con A. This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. Methods C57Bl/6 and C57Bl/6 IFN-γ−/− mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O2 as function of time was used to evaluate respiration. Results In sealed vials, O2 concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, pp=0.005 was noted 12 hr after ConA treatment, and occurred in conjunction with deranged mitochondria, areas of necrosis, and prominent infiltrations with immune cells, most significantly, CD3+NKT+ cells. Increases in intracellular caspase activity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ−/− mice treated with ConA. Conclusions Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes.

Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics.

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Maryna Perepelyuk

Full Text Available Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G' and G" and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver.

A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes

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Iwamuro Masaya

2012-12-01

Full Text Available Abstract Background Bioartificial liver systems, designed to support patients with liver failure, are composed of bioreactors and functional hepatocytes. Immunological rejection of the embedded hepatocytes by the host immune system is a serious concern that crucially degrades the performance of the device. Induced pluripotent stem (iPS cells are considered a desirable source for bioartificial liver systems, because patient-derived iPS cells are free from immunological rejection. The purpose of this paper was to test the feasibility of a bioartificial liver system with iPS cell-derived hepatocyte-like cells. Methods Mouse iPS cells were differentiated into hepatocyte-like cells by a multi-step differentiation protocol via embryoid bodies and definitive endoderm. Differentiation of iPS cells was evaluated by morphology, PCR assay, and functional assays. iPS cell-derived hepatocyte-like cells were cultured in a bioreactor module with a pore size of 0.2 μm for 7 days. The amount of albumin secreted into the circulating medium was analyzed by ELISA. Additionally, after a 7-day culture in a bioreactor module, cells were observed by a scanning electron microscope. Results At the final stage of the differentiation program, iPS cells changed their morphology to a polygonal shape with two nucleoli and enriched cytoplasmic granules. Transmission electron microscope analysis revealed their polygonal shape, glycogen deposition in the cytoplasm, microvilli on their surfaces, and a duct-like arrangement. PCR analysis showed increased expression of albumin mRNA over the course of the differentiation program. Albumin and urea production was also observed. iPS-Heps culture in bioreactor modules showed the accumulation of albumin in the medium for up to 7 days. Scanning electron microscopy revealed the attachment of cell clusters to the hollow fibers of the module. These results indicated that iPS cells were differentiated into hepatocyte-like cells after culture

Full experimental modelling of a liver tissue mimicking phantom for medical ultrasound studies employing different hydrogels.

Science.gov (United States)

Casciaro, Sergio; Conversano, Francesco; Musio, Stefano; Casciaro, Ernesto; Demitri, Christian; Sannino, Alessandro

2009-04-01

Tissue mimicking phantoms have been widely reported to be an important tool for development, optimisation and performance testing of ultrasound-based diagnostic techniques. In particular, modern applications of tissue mimicking phantoms often include characterisation of the nonlinear behaviour of experimental ultrasound contrast agents. In such cases, the tissue-mimicking materials should be chosen not only based on the values of their density, speed of sound and attenuation coefficient, but also considering their effect on the appearance of "native harmonics" due to nonlinear distortion of ultrasound signal during propagation. In a previous paper it was demonstrated that a cellulose-based hydrogel is suitable to simulate nonlinear acoustical behaviour of liver tissue for thicknesses up to 8 cm. In this paper we present the experimental characterisation of the nonlinear acoustical behaviour of a different polyethylene glycol diacrylate (PEGDA)-based hydrogel, in order to assess whether and how it can improve the performances and overcome some limitations of the cellulose-based hydrogel as liver tissue-mimicking material. Samples of pig liver tissue, cellulose-based hydrogel and PEGDA-based hydrogel were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values. Second harmonic and first harmonic amplitudes were extracted from the spectra of received signals and their difference was then used to compare sample behaviours. Obtained results show how a new more accurate and combined experimental model of linear and nonlinear acoustical behaviour of liver tissue is feasible. In fact, a further confirmation of the cellulose-based hydrogel effectiveness to precisely simulate the liver tissue for penetration depths up to 8 cm was provided, and it was also shown that the employment of the PEGDA-based hydrogel can extend the range of useful tissue-mimicking material thicknesses up to 11 cm, moreover allowing a

Functional state of perfused liver tissue in X-ray irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Borovikova, G.V.; Dokshina, G.A.; Lapteva, T.A. (Tomskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Biologii i Biofiziki)

1981-01-01

The results of studying the functional state of perfused liver tissue isolated from rats after irradiation in the 18.06x10/sup -2/ Kl/kg dose, which has been estimated by transamination process rate catalized alanine-(KF 2.6x1.2, ALT and aspartate by aminotransferases (KF 2.6x1.1, ACT), gluconeogenesis and urea production intensity presented. When comparing the results obtained on the perfused liver deprived of homeostatic body effects it has been found that the liver isolated from the body for the first 24 hours of the radiation sickness development possesses a higher radiation activity which manifests itself in intensification of the processes of gluconeogenesis and transamination with substrate addition. The third 24 hours upon irradiation in the isolated liver the intensity of the gluconeogenesis and transamination processes is attenuated.

Liver-Derived Insulin-Like Growth Factor-I is Involved in the Regulation of Blood Pressure in Mice

DEFF Research Database (Denmark)

Tivesten, Asa; Bollano, Entela; Andersson, Irene

2002-01-01

IGF-I has been suggested to be of importance for cardiovascular structure and function, but the relative role of locally produced and liver-derived endocrine IGF-I remains unclear. Using the Cre-LoxP recombination system, we have previously created transgenic mice with a liver-specific, inducible...... IGF-I knockout (LI-IGF-I-/-). To examine the role of liver-derived IGF-I in cardiovascular physiology, liver-derived IGF-I was inactivated at 4 wk of age, resulting in a 79% reduction of serum IGF-I levels. At 4 months of age, systolic blood pressure (BP) was increased in LI-IGF-I-/- mice...... to endothelial dysfunction associated with increased expression of endothelin-1 and impaired vasorelaxation of resistance vessels. In conclusion, our findings suggest that liver-derived IGF-I is involved in the regulation of BP in mice....

Green tea extracts reduce leukocyte cell-Derived chemotaxin 2 and selenoprotein P levels in the livers of C57BL/6J mice fed a high-fat diet.

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Onishi, Shintaro; Kitazawa, Hidefumi; Meguro, Shinichi; Tokimitsu, Ichiro

2018-05-31

Epidemiological studies suggest that green tea extracts (GTEs), including catechins such as epigallocatechin gallate and epicatechin gallate, have a beneficial effect on obesity, hyperglycemia, insulin resistance, endothelial dysfunction, and inflammation. Although several studies have shown that catechins directly modulate the cellular and molecular alterations in the liver tissue, the contributions of indirect mechanisms underlying these systemic effects of catechins remain unclear. In this study, we report that, in the C57BL/6J mouse liver, GTEs reduce high-fat diet-induced increases in the levels of hepatokines, liver-derived secretary proteins such as leukocyte cell-derived chemotaxin 2 and selenoprotein P production, which have been shown to induce systemic adverse effects, including several metabolic diseases. These findings suggest that the systemic effects of GTEs involve the regulation of hepatokine production as an indirect mechanism.

Kupffer cells activation promoted binge drinking-induced fatty liver by activating lipolysis in white adipose tissues.

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Zhao, Yu-Ying; Yang, Rui; Xiao, Mo; Guan, Min-Jie; Zhao, Ning; Zeng, Tao

2017-09-01

Kupffer cells (KCs) have been suggested to play critical roles in chronic ethanol induced early liver injury, but the role of KCs in binge drinking-induced hepatic steatosis remains unclear. This study was designed to investigate the roles of KCs inhibitor (GdCl 3 ) and TNF-α antagonist (etanercept) on binge drinking-induced liver steatosis and to explore the underlying mechanisms. C57BL/6 mice were exposed to three doses of ethanol (6g/kg body weight) to mimic binge drinking-induced fatty liver. The results showed that both GdCl 3 and etanercept partially but significantly alleviated binge drinking-induced increase of hepatic triglyceride (TG) level, and reduced fat droplets accumulation in mice liver. GdCl 3 but not etanercept significantly blocked binge drinking-induced activation of KCs. However, neither GdCl 3 nor etanercept could affect binge drinking-induced decrease of PPAR-α, ACOX, FAS, ACC and SCD protein levels, or increase of the LC3 II/LC3 I ratio and p62 protein level. Interestingly, both GdCl 3 and etanercept significantly suppressed binge drinking-induced phosphorylation of HSL in epididymal adipose tissues. Results of in vitro studies with cultured epididymal adipose tissues showed that TNF-α could increase the phosphorylation of HSL in adipose tissues and upgrade the secretion of free fatty acid (FFA) in the culture medium. Taken together, KCs inhibitor and TNF-α antagonist could partially attenuate binge drinking-induced liver steatosis, which might be attributed to the suppression of mobilization of white adipose tissues. These results suggest that KCs activation may promote binge drinking-induced fatty liver by TNF-α mediated activation of lipolysis in white adipose tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Heavy metal concentrations in gill and liver tissues of Rutilus kutum and Chelon aurata in the coast of Babolsar, southern Caspian Sea

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Fatemeh Kardel

2016-04-01

Full Text Available Heavy metal accumulation in the aquatic ecosystems is a main concern which threats human health. In this study two commercial fish species, Rutilus kutum and Chelon aurata were selected for assessing heavy metal (Cd, Pb, Zn concentrations in gill and liver tissues at Babolsar’s coast, the southern Caspian Sea, Iran. Babolsar is one of the important fishery stations in the southern Caspian Sea. The results showed that liver tissue of C. aurata significantly accumulated higher concentration of Cd, Pb and Zn compared to that of R. kutum, but these results were not significant for gill tissue. Liver tissue accumulated higher concentration of Cd and Pb compared to gill tissue in C. aurata, but these results were not significant for R. kutum. It is concluded that the liver tissue of C. aurata has higher potential to accumulate heavy metal pollution compared to liver tissue of R. kutum

Altered morphology of liver and pancreas tissues of offsprings of ...

African Journals Online (AJOL)

The relationship between consumption of charred meat, which is believed to be rich in nitrosamine by pregnant mothers and the adverse effects on the growth of their offsprings, alterations in morphology of tissues like liver and pancreas were studied. Meat was subjected to charcoal fire roasting without curing and was ...

Experimental investigation and theoretical modelling of the nonlinear acoustical behaviour of a liver tissue and comparison with a tissue mimicking hydrogel.

Science.gov (United States)

Casciaro, Sergio; Demitri, Christian; Conversano, Francesco; Casciaro, Ernesto; Distante, Alessandro

2008-02-01

Native harmonics generated by nonlinear distortion of ultrasound during propagation in a medium may cause misinterpretations in spectral analysis when studying contrast agents. The aim of this paper is to quantitatively evaluate nonlinear propagation effects of diagnostic ultrasound pulses in biological tissues and to assess whether a cellulose-based hydrogel can be a suitable material for tissue mimicking purposes. Hydrogel and pig liver tissue samples of various thicknesses were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values (range 0.06-0.60). Second harmonic and first harmonic amplitudes were extracted from spectra of received signals and their ratio was then used to compare hydrogel and liver behaviours. Resulting trends are very similar for sample thicknesses up to 8 cm and highlight a significant increase in nonlinearity for MI > 0.3, for both liver and hydrogel. A numerical procedure was also employed to calculate pressure distribution along the beam axis: these theoretical results showed a very good agreement with experimental data in the low pressure range, though failed in predicting the MI threshold. In conclusion, the hydrogel resulted to be a suitable material for manufacturing tissue mimicking phantoms, in particular to study contrast agent behaviour with a "low power approach".

Decellularized Tissue and Cell-Derived Extracellular Matrices as Scaffolds for Orthopaedic Tissue Engineering

Science.gov (United States)

Cheng, Christina W.; Solorio, Loran D.; Alsberg, Eben

2014-01-01

The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic. PMID:24417915

MR-guided noninvasive thermal coagulation of in-vivo liver tissue using ultrasonic phased array

Science.gov (United States)

Daum, Douglas R.; Smith, Nadine; McDannold, Nathan; Hynynen, Kullervo H.

1999-05-01

Magnetic resonance (MR) imaging was used to guide and monitor the thermal tissue coagulation of in vivo porcine tissue using a 256 element ultrasonic phased array. The array could coagulate tissue volumes greater than 2 cm3 in liver and 0.5 cm3 in kidney using a single 20 second sonication. This sonication used multiple focus fields which were temporally cycled to heat large tissue volumes simultaneously. Estimates of the coagulated tissue using a thermal dose threshold compare well with T2-weighted images of post sonication lesions. The overlapping large focal volumes could aid in the treatment of large tumor volumes which require multiple overlapping sonications. The ability of MR to detect the presence and undesirable thermal increases at acoustic obstacle such as cartilaginous and bony ribs is demonstrated. This could have a significant impact on the ability to monitor thermal treatments of the liver and other organs which are acoustically blocked.

Metabolic Circuit Involving Free Fatty Acids, microRNA 122, and Triglyceride Synthesis in Liver and Muscle Tissues.

Science.gov (United States)

Chai, Chofit; Rivkin, Mila; Berkovits, Liav; Simerzin, Alina; Zorde-Khvalevsky, Elina; Rosenberg, Nofar; Klein, Shiri; Yaish, Dayana; Durst, Ronen; Shpitzen, Shoshana; Udi, Shiran; Tam, Joseph; Heeren, Joerg; Worthmann, Anna; Schramm, Christoph; Kluwe, Johannes; Ravid, Revital; Hornstein, Eran; Giladi, Hilla; Galun, Eithan

2017-11-01

Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of Luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines. We measured levels of microRNAs and mRNAs by quantitative real-time PCR analysis of RNA extracted from plasma, liver, muscle, and adipose tissues of C57BL/6 mice given the FFA-inducer CL316243. MIR122 was inhibited using an inhibitor of MIR122. Metabolic profiles of mice were determined using metabolic chambers and by histologic analyses of liver tissues. We performed RNA sequence analyses to identify metabolic pathways involving MIR122. We validated human Agpat1 and Dgat1 mRNAs, involved in triglyceride synthesis, as targets of MIR122. FFAs increased MIR122 expression in livers of mice by activating the retinoic acid-related orphan receptor alpha, and induced secretion of MIR122 from liver to blood. Circulating MIR122 entered muscle and adipose tissues of mice, reducing mRNA levels of genes involved in triglyceride synthesis. Mice injected with an inhibitor of MIR122 and then given CL316243, accumulated triglycerides in liver and muscle tissues, and had reduced rates of β-oxidation. There was a positive correlation between level of FFAs and level of MIR122 in plasma samples from 6 healthy individuals, collected before and during fasting. In biochemical and histologic studies of plasma, liver, muscle, and adipose tissues from mice, we found that FFAs increase hepatic expression and secretion of MIR122, which regulates energy storage vs expenditure in liver and peripheral tissues. Strategies to reduce

Effect of alpha-lipoic acid on the removal of arsenic from arsenic-loaded isolated liver tissues of rat

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Noor-E-Tabassum

2006-06-01

Full Text Available The patient of chronic arsenic toxicity shows oxidative stress. To overcome the oxidative stress, several antioxidants such as beta-carotene, ascorbic acid, α-tocopherol, zinc and selenium had been suggested in the treatment of chronic arsenic toxicity. In the present study universal antioxidant (both water and lipid soluble antioxidant α-lipoic acid was used to examine the effectiveness of reducing the amount of arsenic from arsenic-loaded isolated liver tissues of rat. Isolated liver tissues of Long Evans Norwegian rats were cut into small pieces and incubated first in presence or absence of arsenic and then with different concentrations of α-lipoic acid during the second incubation. α-Lipoic acid decreases the amount of arsenic and malondialdehyde (MDA in liver tissues as well as increases the reduced glutathione (GSH level in dose dependent manner. These results suggest that α-lipoic acid remove arsenic from arsenic-loaded isolated liver tissues of rat.

The functional state of perfused liver tissue in X-ray irradiated rats

International Nuclear Information System (INIS)

Borovikova, G.V.; Dokshina, G.A.; Lapteva, T.A.

1981-01-01

The results of studying the functional state of perfused liver tissue isolated from rates after irradiation in the 18.06x10 - 2 Kl/kg dose, which has been estimated by transamination process rate catalized alanine-(KF 2.6x1.2, ALT and aspartate by aminotransferases (KF 2.6x1.1, ACT), gluconeogenesis and urea production intensity presented. When comparing the results obtained on the perfused liver deprived of homeostatic body effects it has been found that the liver isolated from the body for the first 24 hours of the radiation sickness development possesses a higher radiation activity which manifests itself in intensification of the processes of gluconeogenesis and transamination with substrate addition. The third 24 hours upon irradiation in the isolated liver the intensity of the gluconeogenesis and transamination processes is attenuated

Comparison of Species and Cell-Type Differences in Fraction Unbound of Liver Tissues, Hepatocytes, and Cell Lines.

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Riccardi, Keith; Ryu, Sangwoo; Lin, Jian; Yates, Phillip; Tess, David; Li, Rui; Singh, Dhirender; Holder, Brian R; Kapinos, Brendon; Chang, George; Di, Li

2018-04-01

Fraction unbound ( f u ) of liver tissue, hepatocytes, and other cell types is an essential parameter used to estimate unbound liver drug concentration and intracellular free drug concentration. f u,liver and f u,cell are frequently measured in multiple species and cell types in drug discovery and development for various applications. A comparison study of 12 matrices for f u,liver and f u,cell of hepatocytes in five different species (mouse, rat, dog, monkey, and human), as well as f u,cell of Huh7 and human embryonic kidney 293 cell lines, was conducted for 22 structurally diverse compounds with the equilibrium dialysis method. Using an average bioequivalence approach, our results show that the average difference in binding to liver tissue, hepatocytes, or different cell types was within 2-fold of that of the rat f u,liver Therefore, we recommend using rat f u,liver as a surrogate for liver binding in other species and cell types in drug discovery. This strategy offers the potential to simplify binding studies and reduce cost, thereby enabling a more effective and practical determination of f u for liver tissues, hepatocytes, and other cell types. In addition, f u under hepatocyte stability incubation conditions should not be confused with f u,cell , as one is a diluted f u and the other is an undiluted f u Cell density also plays a critical role in the accurate measurement of f u,cell . Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Tissue specific MR contrast media role in the differential diagnosis of cirrhotic liver nodules.

Science.gov (United States)

Lupescu, Ioana Gabriela; Capsa, Razvan A; Gheorghe, Liana; Herlea, Vlad; Georgescu, Serban A

2008-09-01

State-of-the-art magnetic resonance (MR) imaging using tissue specific contrast media facilitates detection and characterization in most cases of hepatic nodules. According to the currently used nomenclature, in liver cirrhosis there are only two major types of hepatocellular nodular lesions: regenerative lesions and dysplastic or neoplastic lesions. The purpose of this clinical imaging review is to provide information on the properties of tissue-specific MR contrast agents and on their usefulness in the demonstration of the pathologic changes that take place at the level of the hepatobiliary and reticuloendothelial systems during the carcinogenesis in liver cirrhosis.

Non-invasive liver fibrosis score calculated by combination of virtual touch tissue quantification and serum liver functional tests in chronic hepatitis C patients.

Science.gov (United States)

Takaki, Shintaro; Kawakami, Yoshiiku; Miyaki, Daisuke; Nakahara, Takashi; Naeshiro, Noriaki; Murakami, Eisuke; Tanaka, Mio; Honda, Yohji; Yokoyama, Satoe; Nagaoki, Yuko; Kawaoka, Tomokazu; Hiramatsu, Akira; Tsuge, Masataka; Hiraga, Nobuhiko; Imamura, Michio; Hyogo, Hideyuki; Aikata, Hiroshi; Takahashi, Shoichi; Arihiro, Koji; Chayama, Kazuaki

2014-03-01

Acoustic radiation force impulse (ARFI) technology, involving the shear wave velocity (SWV) with virtual touch tissue quantification (VTTQ), are currently available for the assessment of liver fibrosis, while there is no index derived from the combination of SWV and blood tests. The aim of this study was to develop a new index for assessment of liver fibrosis. The subjects were 176 consecutive patients with hepatitis C (training set [n = 120] and validation set [n = 56]) who underwent liver biopsy in our institution. In the training set, SWV, international normalized ratio (INR) and alanine aminotransferase (ALT) correlated independently and significantly with fibrosis. According to this, we developed the VIA index = -1.282 + 0.965 × SWV + 1.785 INR + 0.00185 ALT. The areas under the receiver-operator curve (AUROC) of the VIA index were 0.838 for the diagnosis of significant fibrosis (≥F2), 0.904 for the severe fibrosis (≥F3) and 0.958 for the cirrhosis (F4) in the training set. While in the validation set, AUROC of the VIA index were 0.917 for F2 or higher, 0.906 for F3 or higher and 1.000 for F4, respectively. AUROC of the VIA index was improved compared to SWV alone, equivalent for VIA for the diagnosis of F2 or higher, and superior to that of FIB-4 index and aspartate aminotransferase-to-platelet ratio index for the diagnosis of F3 or higher and F4. The VIA index is potentially more useful for assessment of liver fibrosis than SWV alone, and easily and accurately measures liver fibrosis stage. © 2013 The Japan Society of Hepatology.

Contribution of Gut Bacteria to Liver Pathobiology

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Gakuhei Son

2010-01-01

Full Text Available Emerging evidence suggests a strong interaction between the gut microbiota and health and disease. The interactions of the gut microbiota and the liver have only recently been investigated in detail. Receiving approximately 70% of its blood supply from the intestinal venous outflow, the liver represents the first line of defense against gut-derived antigens and is equipped with a broad array of immune cells (i.e., macrophages, lymphocytes, natural killer cells, and dendritic cells to accomplish this function. In the setting of tissue injury, whereby the liver is otherwise damaged (e.g., viral infection, toxin exposure, ischemic tissue damage, etc., these same immune cell populations and their interactions with the infiltrating gut bacteria likely contribute to and promote these pathologies. The following paper will highlight recent studies investigating the relationship between the gut microbiota, liver biology, and pathobiology. Defining these connections will likely provide new targets for therapy or prevention of a wide variety of acute and chronic liver pathologies.

(13)Carbon and (15)nitrogen isotopes in autopsy liver tissue samples from Greenlandic Inuit and Danes: consumption of marine versus terrestrial food

DEFF Research Database (Denmark)

Milman, N.; Laursen, J.; Mulvad, G.

2010-01-01

in liver tissue from Greenlandic Inuit and Danes. Subjects/Methods: Normal liver tissue was obtained at autopsy in 1992-1994 from 60 Inuit with a median age of 61 years (range 25-83) and in 1986 from 15 ethnic Danes with a median age of 84 years (range 66-93). By sieving, liver tissue was separated...

Simulation and performance evaluation of fiber optic sensor for detection of hepatic malignancies in human liver tissues

Science.gov (United States)

Sharma, Anuj K.; Gupta, Jyoti; Basu, Rikmantra

2018-01-01

A fiber optic sensor is proposed for the identification of healthy and cancerous liver tissues through determination of their corresponding refractive index values. Existing experimental results describing variation of complex refractive index of liver tissues in near infrared (NIR) spectral region are considered for theoretical calculations. The intensity interrogation method with chalcogenide fiber is considered. The sensor's performance is closely analyzed in terms of its sensitivity at multiple operating wavelengths falling in NIR region. Operating at shorter NIR wavelengths leads to greater sensitivity. The effect of design parameters (sensing region length and fiber core diameter), different launching conditions, and fiber glass materials on sensor's performance is examined. The proposed sensor has the potential to provide high sensitivity of liver tissue detection.

Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering.

Science.gov (United States)

Jiang, Wei-Cheng; Cheng, Yu-Hao; Yen, Meng-Hua; Chang, Yin; Yang, Vincent W; Lee, Oscar K

2014-04-01

Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Correlation between the mechanical and histological properties of liver tissue.

Science.gov (United States)

Yarpuzlu, Berkay; Ayyildiz, Mehmet; Tok, Olgu Enis; Aktas, Ranan Gulhan; Basdogan, Cagatay

2014-01-01

In order to gain further insight into the mechanisms of tissue damage during the progression of liver diseases as well as the liver preservation for transplantation, an improved understanding of the relation between the mechanical and histological properties of liver is necessary. We suggest that this relation can only be established truly if the changes in the states of those properties are investigated dynamically as a function of post mortem time. In this regard, we first perform mechanical characterization experiments on three bovine livers to investigate the changes in gross mechanical properties (stiffness, viscosity, and fracture toughness) for the preservation periods of 5, 11, 17, 29, 41 and 53h after harvesting. Then, the histological examination is performed on the samples taken from the same livers to investigate the changes in apoptotic cell count, collagen accumulation, sinusoidal dilatation, and glycogen deposition as a function of the same preservation periods. Finally, the correlation between the mechanical and histological properties is investigated via the Spearman's Rank-Order Correlation method. The results of our study show that stiffness, viscosity, and fracture toughness of bovine liver increase as the preservation period is increased. These macroscopic changes are very strongly correlated with the increase in collagen accumulation and decrease in deposited glycogen level at the microscopic level. Also, we observe that the largest changes in mechanical and histological properties occur after the first 11-17h of preservation. © 2013 Elsevier Ltd. All rights reserved.

Heterogenic transplantation of bone marrow-derived rhesus macaque mesenchymal stem cells ameliorates liver fibrosis induced by carbon tetrachloride in mouse

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Xufeng Fu

2018-02-01

Full Text Available Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma. Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects. Although liver fibrosis improvements by MSC transplantation in preclinical experiments as well as clinical trials have been reported, the in vivo fate of MSCs after transportation and their therapeutic mechanisms remain unclear. In this present study, we isolated MSCs from the bone marrow of rhesus macaques. The cells exhibited typical MSC markers and could differentiate into chondrocytes, osteocytes, and adipocytes, which were not affected by labeling with enhanced green fluorescent protein (EGFP. The harvested MSCs respond to interferon-γ stimulation and have the ability to inhibit lymphocyte proliferation in vitro. EGFP-labeled MSCs (1 × 106 cells were transplanted into mice with carbon tetrachloride-induced liver fibrosis via tail vein injection. The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice was evaluated by a blood plasma chemistry index, pathological examination and liver fibrosis-associated gene expression. Additionally, a small number of MSCs that homed and engrafted in the mouse liver tissues were evaluated by immunofluorescence analysis. Our results showed that the transplantation of heterogenic MSCs derived from monkey bone marrow can be used to treat liver fibrosis in the mouse model and that the

Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients.

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Jansen, Henry J; Vervoort, Gerald M; van der Graaf, Marinette; Stienstra, Rinke; Tack, Cees J

2013-11-01

Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an association between inflammatory features of the adipose tissue and liver fat content. To analyse associations between inflammatory features of the adipose tissue and liver fat content. A cross-sectional study. Twenty-seven obese patients with insulin-treated T2DM were studied. LFAT content was measured by proton magnetic resonance spectroscopy. A subcutaneous (sc) fat biopsy was obtained to determine morphology and protein levels within adipose tissue. In addition to fat cell size, the percentage of macrophages and the presence of crown-like structures (CLSs) within sc fat were assessed by CD68-immunohistochemical staining. Mean LFAT percentage was 11·1 ± 1·7% (range: 0·75-32·9%); 63% of the patients were diagnosed with an elevated LFAT (upper range of normal ≤5·5%). Whereas adipocyte size did not correlate with LFAT, 3 of 4 subjects with CLSs in sc fat had elevated LFAT and the percentage of macrophages present in sc adipose tissue was positively associated with LFAT. Protein concentrations of adiponectin within adipose tissue negatively correlated with LFAT. Adipose tissue protein levels of the key inflammatory adipokine plasminogen activator inhibitor-1 (PAI-1) were positively associated with LFAT. Several pro-inflammatory changes in sc adipose tissue associate with increased LFAT content in obese insulin-treated patients with T2DM. These findings suggest that inflammatory changes at the level of the adipose tissue may drive liver fat accumulation. © 2012 John Wiley & Sons Ltd.

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

Science.gov (United States)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

Merlin, the product of NF2 gene, is associated with aromatase expression and estrogen formation in human liver tissues and liver cancer cells.

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Cocciadiferro, Letizia; Miceli, Vitale; Granata, Orazia M; Carruba, Giuseppe

2017-09-01

The product of neurofibromatosis type 2 (NF2) gene, also known as Merlin/neurofibromin 2, homeostatically regulates liver stem cells by controlling abundance and signaling of epidermal growth factor receptor (EGFR), with a mechanism independent of the Hippo pathway. We have reported that locally elevated estrogen formation, driven by abnormally high expression and function of aromatase, may be implicated in development and progression of human hepatocellular carcinoma (HCC) through activation of a rapid signaling pathway mediated by amphiregulin (AREG) and EGFR. We have recently presented a model by which the aromatase-estrogen-amphiregulin-EGFR axis is activated in response to tissue injury and/or inflammatory disease, with its alteration eventually leading to development of major human tumors (liver, breast, prostate) and other chronic diseases (diabetes, obesity, Alzheimer's and heart disease). In this study, we investigated NF2 expression in liver cancer cells and tissues in relation to aromatase expression/function, estrogen receptor (ER) status and amphiregulin. Our data indicate that NF2 expression is associated with aromatase and AREG expression, being elevated in HCC tissues and HepG2 cells, intermediate in cirrhotic tissues and Huh7 cells, and lower in nontumoral liver and HA22T cells. In addition, NF2 expression is inversely related to wild type hERα66 and proportional to the expression of the membrane-associated hERα36 splice variant, as measured by exon-specific RT-PCR analysis, both in vivo and in vitro. Furthermore, incubation with estradiol induced a significant decrease of NF2 expression in both HA22T and Huh7 cells (over 54% and 22%, respectively), while no change could be observed in HepG2 cells, this effect being inversely related to aromatase expression and activity in HCC cell lines. Based on the above combined evidence, we hypothesize that NF2 behaves as a protein sensing tissue damage and aromatase-driven local estrogen formation

Antioxidant Role of Pomegranates on Liver and Brain Tissues of Rats Exposed to an Organophosphorus Insecticide

International Nuclear Information System (INIS)

Abd Elmonem, H.A.

2014-01-01

Toxicities of organophosphorus insecticides cause oxidative damage on many organs such as the liver and brain due to generation of reactive oxygen species. Pomegranate is among the richest fruit in poly - phenols. The aim of this study was to compare between the antioxidant strength of pomegranate juice (PJ) and pomegranate molasses (PM) and their effects on alanine transferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and total protein (TP) in liver and levels of malondialdehyde (MAD), reduced glutathione (GSH) and nitric oxide (NO) in rat liver and brain tissues exposed to 1/10 LD 50 diazinon (DI). Six groups each of 6 male albino rats were used comprising control, DI, PJ, PM, PJ + DI and PM + DI for 15 days. The activities of ALT, AST, and TP concentration in liver have been increased due to treatment of rats with DI. These increases restored to normalcy when rats were supplemented with PJ or PM with DI. The results demonstrate that treatment with DI induced significant increase in MDA and NO concentrations and significant decrease in GSH levels of liver and brain tissues. The administration of PJ or PM along with DI significant decrease in MDA and NO levels and significant increase in GSH level compared to DI-group. The present study suggest that PJ or PM has a potential protective effect as it can elevate antioxidant defense system, lessens induced oxidative dam - ages and protect the brain and liver tissue against DI-induced toxicity. In addition, comaring PJ with PM it was noticed that PJ had higher antioxidant activity as evidenced by increased GSH content and decreased NO level in the liver by greater extend than PM.

Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

International Nuclear Information System (INIS)

Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

2012-01-01

Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

Multi-locus sequence subtypes of Campylobacter detected on the surface and from internal tissue of retail chicken livers

Science.gov (United States)

Foodborne campylobacteriosis has been traced to undercooked chicken liver. The objectives of this study were to measure prevalence of Campylobacter associated with chicken livers at retail and determine which subtypes are detected on the surface and inner tissue of livers. Fifteen packages of fres...

Liver-targeting of interferon-alpha with tissue-specific domain antibodies.

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Edward Coulstock

Full Text Available Interferon alpha (IFNα is used for the treatment of hepatitis C infection and whilst efficacious it is associated with multiple adverse events including reduced leukocyte, erythrocyte, and platelet counts, fatigue, and depression. These events are most likely caused by systemic exposure to interferon. We therefore hypothesise that targeting the therapeutic directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. We genetically fused IFN to a domain antibody (dAb specific to a hepatocyte restricted antigen, asialoglycoprotein receptor (ASGPR. Our results show that the murine IFNα2 homolog (mIFNα2 fused to an ASGPR specific dAb, termed DOM26h-196-61, could be expressed in mammalian tissue culture systems and retains the desirable biophysical properties and activity of both fusion partners when measured in vitro. Furthermore a clear increase in in vivo targeting of the liver by mIFNα2-ASGPR dAb fusion protein, compared to that observed with either unfused mIFNα2 or mIFNα2 fused to an isotype control dAb VHD2 (which does not bind ASGPR was demonstrated using microSPECT imaging. We suggest that these findings may be applicable in the development of a liver-targeted human IFN molecule with improved safety and patient compliance in comparison to the current standard of care, which could ultimately be used as a treatment for human hepatitis virus infections.

Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

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Ori Nov

Full Text Available The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers, Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4 that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin

Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization

NARCIS (Netherlands)

Mazza, G. (Giuseppe); Al-Akkad, W. (Walid); Telese, A. (Andrea); Longato, L. (Lisa); Urbani, L. (Luca); Robinson, B. (Benjamin); Hall, A. (Andrew); Kong, K. (Kenny); Frenguelli, L. (Luca); Marrone, G. (Giusi); Willacy, O. (Oliver); Shaeri, M. (Mohsen); A.J. Burns (Alan); Malago, M. (Massimo); Gilbertson, J. (Janet); Rendell, N. (Nigel); Moore, K. (Kevin); Hughes, D. (David); Notingher, I. (Ioan); Jell, G. (Gavin); Del Rio Hernandez, A. (Armando); P. de Coppi (Paolo); Rombouts, K. (Krista); Pinzani, M. (Massimo)

2017-01-01

textabstractThe development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of

Method for Processing Liver Spheroids Using an Automatic Tissue Processor

Science.gov (United States)

2016-05-01

alcohol dehydration and hot liquid wax infiltration. After the water in the tissue is replaced with wax and cooled, it then becomes possible to cut...effective for processing and preparing microscopy slides of liver spheroids. The general process involved formalin fixation, dehydration in a...DPBS);  formalin (37% neutral buffer formaldehyde);  series of alcohol solutions: 70, 80, 95, and 100% ethanol in water; 2  xylene

Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

Science.gov (United States)

Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

2018-01-01

Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

The Role of Liver in Determining Serum Colon-Derived Uremic Solutes.

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Cheng-Jui Lin

Full Text Available Evidence has shown that indoxyl sulfate (IS and p-cresyl sulfate (PCS may be alternative predictors of clinical outcomes in chronic kidney disease (CKD. Both toxins are derived from the gastrointestinal tract and metabolised in the liver. However, it is unclear whether the liver affects the production of IS and PCS. Here, we explore the association between IS and PCS levels in liver cirrhosis and a CKD-based cohort (N = 115. Liver and kidney function was assessed and classified by a Child-Pugh score (child A-C and a modified version of the Modification of Diet in Renal Disease (MDRD equation (Stages 1-4, respectively. An animal model was also used to confirm the two toxin levels in a case of liver fibrosis. In patients with early liver cirrhosis (child A, IS and PCS were significantly associated with CKD stages. In contrast, serum IS and PCS did not significantly change in advanced liver cirrhosis (child C. A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012. Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without (p<0.01, p<0.05 and p<0.01, p<0.05, respectively. These results indicated that in addition to the kidneys, the liver was an essential and independent organ in determining serum IS and PCS levels. The production rate of IS and PCS was lower in patients with advanced liver cirrhosis.

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

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Sulin Cheng

Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

MAIT cells: new guardians of the liver

OpenAIRE

Kurioka, Ayako; Walker, Lucy J; Klenerman, Paul; Willberg, Christian B

2016-01-01

The liver is an important immunological organ that remains sterile and tolerogenic in homeostasis, despite continual exposure to non-self food and microbial-derived products from the gut. However, where intestinal mucosal defenses are breached or in the presence of a systemic infection, the liver acts as a second 'firewall', because of its enrichment with innate effector cells able to rapidly respond to infections or tissue dysregulation. One of the largest populations of T cells within the h...

The protective effect of pomegranate extract against cisplatin toxicity in rat liver and kidney tissue.

Science.gov (United States)

Bakır, Salih; Yazgan, Ümit Can; İbiloğlu, İbrahim; Elbey, Bilal; Kızıl, Murat; Kelle, Mustafa

2015-01-01

The purpose of this study was to perform a histopathological investigation, at the light microscopy level, of the protective effects of pomegranate extract in cisplatin-induced liver and kidney damage in rats. Twenty-eight adult male Wistar albino rats were randomly divided into four groups of seven animals: Group 1: Control; Group 2: Treated for 10 consecutive days by gavage with pomegranate juice (2 ml/kg/day); Group 3: Injected intraperitoneally with cisplatin (8 mg/kg body weight, single dose) onset of the day 5, and Group 4: Treated by gavage with pomegranate juice 10 days before and after a single injection of cisplatin onset of the day 5. After 10 days, the animals were sacrificed and their kidneys and liver tissue samples were removed from each animal after experimental procedures. Cisplatin-induced renal and hepatic toxicity and the effect of pomegranate juice were evaluated by histopatological examinations. In the kidney tissue, pomegranate juice significantly ameliorated cisplatin-induced structural alterations when compared with the cisplatin alone group. But in the liver tissue, although pomegranate juice attenuated the cisplatin-induced toxicity only in two rats, significant improvement was not observed. In conclusion, these results demonstrate that the anti-oxidant pomegranate juice might have a protective effect against cisplatin-induced toxicity in rat kidney, but not in liver. Pomegranate juice could be beneficial as a dietary supplement in patients receiving chemotherapy medications.

Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

Science.gov (United States)

Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

2009-01-01

Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

Epicardial Adipose Tissue (EAT Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease.

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Anna Ludovica Fracanzani

Full Text Available Epicardial adipose tissue (EAT has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD. Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1 the association between EAT, the other metabolic parameters and the severity of steatosis 2 the relationship between cardiovascular (cIMT, cplaques, E/A, liver (presence of NASH and significant fibrosis damage and metabolic risk factors including EAT 3 the relationship between EAT and genetic factors strongly influencing liver steatosis.In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100. EAT, severity of steatosis, carotid intima-media thickness (cIMT and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm were female gender (p = 0.003, age (p = 0.001, BMI (p = 0.01, diastolic blood pressure (p = 0.009, steatosis grade 2 (p = 0.01 and 3 (p = 0.04, fatty liver index (p = 0.001 and statin use (p = 0.03. Variables independently associated with carotid IMT were age (p = 0.0001, hypertension (p = 0.009, diabetes (p = 0.04, smoking habits (p = 0.04 and fatty liver index (p = 0.02, with carotid plaques age (p = 0.0001, BMI (p = 0.03, EAT (p = 0.02, and hypertension (p = 0.02, and with E/A age (p = 0.0001, diabetes (p = 0.005, hypertension (p = 0.04 and fatty liver index (p = 0.004. In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH was independently associated with EAT (p = 0.04 and diabetes (p = 0.054 while significant fibrosis with EAT (p = 0.02, diabetes (p = 0.01 and waist circumference (p = 0.05. No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found.In patients with NAFLD, EAT is associated with the severity of liver and vascular damage besides with the known metabolic risk factors.

Model and methods to assess hepatic function from indocyanine green fluorescence dynamical measurements of liver tissue.

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Audebert, Chloe; Vignon-Clementel, Irene E

2018-03-30

The indocyanine green (ICG) clearance, presented as plasma disappearance rate is, presently, a reliable method to estimate the hepatic "function". However, this technique is not instantaneously available and thus cannot been used intra-operatively (during liver surgery). Near-infrared spectroscopy enables to assess hepatic ICG concentration over time in the liver tissue. This article proposes to extract more information from the liver intensity dynamics by interpreting it through a dedicated pharmacokinetics model. In order to account for the different exchanges between the liver tissues, the proposed model includes three compartments for the liver model (sinusoids, hepatocytes and bile canaliculi). The model output dependency to parameters is studied with sensitivity analysis and solving an inverse problem on synthetic data. The estimation of model parameters is then performed with in-vivo measurements in rabbits (El-Desoky et al. 1999). Parameters for different liver states are estimated, and their link with liver function is investigated. A non-linear (Michaelis-Menten type) excretion rate from the hepatocytes to the bile canaliculi was necessary to reproduce the measurements for different liver conditions. In case of bile duct ligation, the model suggests that this rate is reduced, and that the ICG is stored in the hepatocytes. Moreover, the level of ICG remains high in the blood following the ligation of the bile duct. The percentage of retention of indocyanine green in blood, which is a common test for hepatic function estimation, is also investigated with the model. The impact of bile duct ligation and reduced liver inflow on the percentage of ICG retention in blood is studied. The estimation of the pharmacokinetics model parameters may lead to an evaluation of different liver functions. Copyright © 2018 Elsevier B.V. All rights reserved.

Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

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RINI PUSPITANINGRUM

2010-09-01

Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxiatolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

Directory of Open Access Journals (Sweden)

RINI PUSPITANINGRUM

2010-09-01

Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxia-tolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

A protein-based set of reference markers for liver tissues and hepatocellular carcinoma

International Nuclear Information System (INIS)

Sun, Stella; Yi, Xin; Poon, Ronnie TP; Yeung, Chun; Day, Philip JR; Luk, John M

2009-01-01

During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify 'housekeeping' markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression. A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers. The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples. Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference

THE EFFECTS OF GLYCOL METHACRYLATE AS A DEHYDRATING AGENT ON THE DIMENSIONAL CHANGES OF LIVER-TISSUE

NARCIS (Netherlands)

GERRITS, PO; HOROBIN, RW; STOKROOS, [No Value

The dimensional changes of liver sections during the course of processing with glycol methacrylate (GMA) or with ethanol are described. Tissue processing with ethanol served as a control. During prolonged processing steps (24 h each), linear shrinkage of tissue specimens dehydrated with GMA at room

Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis.

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Choi, Youngshim; Abdelmegeed, Mohamed A; Song, Byoung-Joon

2018-05-01

Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver injury and study the protective mechanism(s) by using the well-established chronic-plus-binge alcohol exposure model. The preventive effects of I3C were evaluated by conducting various histological, biochemical, and real-time PCR analyses in mouse liver, adipose tissue, and colon, since functional alterations of adipose tissue and intestine can also participate in promoting EtOH-induced liver damage. Daily treatment with I3C alleviated EtOH-induced liver injury and hepatocyte apoptosis, but not steatosis, by attenuating elevated oxidative stress, as evidenced by the decreased levels of hepatic lipid peroxidation, hydrogen peroxide, CYP2E1, NADPH-oxidase, and protein acetylation with maintenance of mitochondrial complex I, II, and III protein levels and activities. I3C also restored the hepatic antioxidant capacity by preventing EtOH-induced suppression of glutathione contents and mitochondrial aldehyde dehydrogenase-2 activity. I3C preventive effects were also achieved by attenuating the increased levels of hepatic proinflammatory cytokines, including IL1β, and neutrophil infiltration. I3C also attenuated EtOH-induced gut leakiness with decreased serum endotoxin levels through preventing EtOH-induced oxidative stress, apoptosis of enterocytes, and alteration of tight junction protein claudin-1. Furthermore, I3C alleviated adipose tissue inflammation and decreased free fatty acid release. Collectively, I3C prevented EtOH-induced liver injury via attenuating the damaging effect of ethanol on the gut-liver-adipose tissue axis. Therefore, I3C may also have a high potential for translational research in treating or preventing other types of hepatic injury associated with oxidative stress and inflammation. Copyright © 2017 Elsevier Inc. All

REGENERATIVE PECULIARITIES OF LIVER TISSUE AFTER HEMOSTASIS BY NONEQUILIBRIUM PLASMA ON 90TH AND 180TH DAY (EXPERIMENTAL STUDY

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Ye. V. Semichev

2014-01-01

Full Text Available Liver damages occur to 17.8% of blunt abdominal trauma cases. Postoperative mortality in liver damage is a high. It amounts to 4–10% in case of stab wounds, to 30.4–35,2% in case of closed injury, to 39.3% in case of concomitant injury. Complete hemostasis without damage to organ parenchyma is needed for liver surgical operation.The aim of research is to evaluate the regenerative characteristics of liver tissue after hemostasis by nonequilibrium plasma in a long-term period.Material and methods. Research was performed on 20 laboratory rats, 3 experimental groups. 10 intact animals and 5 animals in groups on 90th and 180th day. Surgery is resection of liver left lobe and coagulation with cold plasma coagulator. The biochemical control (glucose, ALT, AST, total bilirubin, direct, alkaline phosphatase, total protein, urea, α-amylase, CRP, fibrinogen, aPTT, PTT, INR, morphological study of rat liver were performed.Results. After surgery with cold plasma hemostasis animals are active, early begin to eat. Fatal cases are not. Analysis of biochemical markers doesn't reveal statistically significant differences from the norm for the majority of indicators. Decrease of glucose concentration in the blood serum is observed in a long-term period. Histological analysis reveals an increase of the central and interlobular veins and moderate signs of edema on the 90th day. Hepatocytes with pronounced signs of protein and fatty degeneration are identified. Liver histology corresponds to the usual structure and is represented by liver lobules, separated by a small layer of connective tissue on the 180th day.Conclusion. Cold plasma coagulation in liver surgery showed effective hemostasis, minimal trauma of organ parenchyma, the lack of systemic effect and the subsequent complete regeneration of liver tissue in the treatment area.

Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice.

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Valenzuela, Rodrigo; Echeverria, Francisca; Ortiz, Macarena; Rincón-Cervera, Miguel Ángel; Espinosa, Alejandra; Hernandez-Rodas, María Catalina; Illesca, Paola; Valenzuela, Alfonso; Videla, Luis A

2017-04-11

Eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) are long-chain polyunsaturated fatty acids (LCPUFAs) with relevant roles in the organism. EPA and DHA are synthesized from the precursor alpha-linolenic acid (ALA, C18:3n-3), whereas AA is produced from linoleic acid (LA, C18:2n-6) through the action of Δ5 and Δ6-desaturases. High-fat diet (HFD) decreases the activity of both desaturases and LCPUFA accretion in liver and other tissues. Hydroxytyrosol (HT), a natural antioxidant, has an important cytoprotective effects in different cells and tissues. Male mice C57BL/6 J were fed a control diet (CD) (10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks. Animals were daily supplemented with saline (CD) or 5 mg HT (HFD), and blood and the studied tissues were analyzed after the HT intervention. Parameters studied included liver histology (optical microscopy), activity of hepatic desaturases 5 and 6 (gas-liquid chromatography of methyl esters derivatives) and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by spectrophotometry), oxidative stress indicators (glutathione, thiobarbituric acid reactants, and the antioxidant capacity of plasma), gene expression assays for sterol regulatory element-binding protein 1c (SREBP-1c) (qPCR and ELISA), and LCPUFA profiles in liver, erythrocyte, brain, heart, and testicle (gas-liquid chromatography). HFD led to insulin resistance and liver steatosis associated with SREBP-1c upregulation, with enhancement in plasma and liver oxidative stress status and diminution in the synthesis and storage of n-6 and n-3 LCPUFAs in the studied tissues, compared to animals given control diet. HT supplementation significantly reduced fat accumulation in liver and plasma as well as tissue metabolic alterations induced by HFD. Furthermore, a normalization of desaturase activities

Chronic Dietary Intake of Enniatin B in Broiler Chickens Has Low Impact on Intestinal Morphometry and Hepatic Histology, and Shows Limited Transfer to Liver Tissue

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Sophie Fraeyman

2018-01-01

Full Text Available The Fusarium mycotoxin enniatin B (ENN B is a so-called emerging mycotoxin frequently contaminating poultry feed. To investigate the impact of chronic ENN B exposure on animal health, broiler chickens were fed either a diet naturally contaminated with ENN B (2352 µg/kg or a control diet (135 µg/kg for 2, 7, 14, or 21 days. ENN B concentrations were determined in plasma and liver using a validated ultra-high performance liquid chromatography—tandem mass spectrometry UHPLC-MS/MS method. Liver was evaluated histologically, and the villus length and crypt depth of the duodenum, jejunum, and ileum were measured. Histopathology of the livers did not reveal major abnormalities. Feeding an ENN B-contaminated diet could possibly inhibit the proliferation of enterocytes in the duodenal crypts, but did not affect villus length, crypt depth, or villus length-crypt depth ratio of the jejunum and ileum. ENN B levels in plasma and liver were significantly higher in the ENN B-fed group and ranged between <25–264 pg/mL and <0.05–0.85 ng/g, respectively. ENN B carry-over rates from feed to liver tissue were 0.005–0.014% and 0.034–0.109% in the ENN B and control group, respectively. Carry-over rates were low and indicated a limited contribution of poultry tissue-derived products to the total dietary ENN B intake for humans. The above results support the opinion of the European Food Safety Authority stating that adverse health effects from ENN B in broiler chickens are unlikely.

Effects of Loud Noise on Oxidation and Lipid peroxidation Variations of Liver Tissue of Rabbit

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Mirzaei Ramazan

2009-06-01

Full Text Available Background: In today's world, noise is one of the major physical pollutants. The exact mechanism leading to tissue damage in loud noise is not clear. There are increasing evidences that show damage to cochlear tissue by noise is linked to cell injury induced by free radical species. The aim of this study was to investigate the relationship between change in liver tissue glutathione (anti- oxidant and malondialdehyde (one metabolite of lipid oxidation levels that occur in rabbits which were exposed to continuous loud noise.Materials and Methods: This experimental study was performed on 12 white Newzeland male rabbits in Tarbiat Modarres University in 2004. The rabbits were assigned to the following two groups: control, and exposed to continuous loud noise for 96 hours (8 h/day for 12 days, SPL=110dBA and 250Hz to 20 KHz. The concentration of malondialdehyde (MDA and glutathione (GSH in liver tissue samples were measured in rabbits after exposure to noise. Thiobarbituric acid reacting substance, Ellman's reagent and spectrophotometry techniques were used for this measurement. The data were statically analyzed by SPSS software and 2 groups were compared by t-test. Differences at the level of P<0.05 were considered statistically significant.Results: Comparison of the biochemical parameters of GSH and MDA measured in treated group with control indicated that antioxidant and lipid peroxidants parameters were suppressed in treated group compared to control group (p<0.05.Conclusion: Possible similarities between rabbit and human biological system indicate the possible role of noise in causation of oxidative stress in context with liver tissue impairm

Fuzzy logic algorithm for quantitative tissue characterization of diffuse liver diseases from ultrasound images.

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Badawi, A M; Derbala, A S; Youssef, A M

1999-08-01

Computerized ultrasound tissue characterization has become an objective means for diagnosis of liver diseases. It is difficult to differentiate diffuse liver diseases, namely cirrhotic and fatty liver by visual inspection from the ultrasound images. The visual criteria for differentiating diffused diseases are rather confusing and highly dependent upon the sonographer's experience. This often causes a bias effects in the diagnostic procedure and limits its objectivity and reproducibility. Computerized tissue characterization to assist quantitatively the sonographer for the accurate differentiation and to minimize the degree of risk is thus justified. Fuzzy logic has emerged as one of the most active area in classification. In this paper, we present an approach that employs Fuzzy reasoning techniques to automatically differentiate diffuse liver diseases using numerical quantitative features measured from the ultrasound images. Fuzzy rules were generated from over 140 cases consisting of normal, fatty, and cirrhotic livers. The input to the fuzzy system is an eight dimensional vector of feature values: the mean gray level (MGL), the percentile 10%, the contrast (CON), the angular second moment (ASM), the entropy (ENT), the correlation (COR), the attenuation (ATTEN) and the speckle separation. The output of the fuzzy system is one of the three categories: cirrhosis, fatty or normal. The steps done for differentiating the pathologies are data acquisition and feature extraction, dividing the input spaces of the measured quantitative data into fuzzy sets. Based on the expert knowledge, the fuzzy rules are generated and applied using the fuzzy inference procedures to determine the pathology. Different membership functions are developed for the input spaces. This approach has resulted in very good sensitivities and specificity for classifying diffused liver pathologies. This classification technique can be used in the diagnostic process, together with the history

A strain-hardening bi-power law for the nonlinear behaviour of biological soft tissues.

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Nicolle, S; Vezin, P; Palierne, J-F

2010-03-22

Biological soft tissues exhibit a strongly nonlinear viscoelastic behaviour. Among parenchymous tissues, kidney and liver remain less studied than brain, and a first goal of this study is to report additional material properties of kidney and liver tissues in oscillatory shear and constant shear rate tests. Results show that the liver tissue is more compliant but more strain hardening than kidney. A wealth of multi-parameter mathematical models has been proposed for describing the mechanical behaviour of soft tissues. A second purpose of this work is to develop a new constitutive law capable of predicting our experimental data in the both linear and nonlinear viscoelastic regime with as few parameters as possible. We propose a nonlinear strain-hardening fractional derivative model in which six parameters allow fitting the viscoelastic behaviour of kidney and liver tissues for strains ranging from 0.01 to 1 and strain rates from 0.0151 s(-1) to 0.7s(-1). Copyright (c) 2009 Elsevier Ltd. All rights reserved.

[Influence of FPS on the expression of LDL-R mRNA in the liver tissues of hyperlipidemic rats].

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Wu, Qing-he; Xing, Yan-hong; Rong, Xiang-lu; Huang, Ping

2007-08-01

To explore the effect of FPS on low-density lipoprotein acceptor (LDL-R) mRNA in the liver tissues of hyperlipidemic rats. Sixty healthy male SD rats were randomly divided into six groups: normal control, model control, Gynostemma pentaphyllum, FPS low dosage, FPS moderate dosage, and FPS high dosage group. Excepting the rats in the normal control group, the ones in other groups were all made rats' hyperlipidemic model by irrigating hyperlipidemic emulsion into the stomach and observed the expression of LDL-R mRNA in the liver tissues of rats of each group. Relative content of LDL-RmRNA in low and moderate dosage groups was notably higher than that inmodel group. The contents's difference was not remarkable between FPS moderate dosage group and Gynostemma pentaphyllum group. FPS can appreciably increase the expression of LDL-R mRNA in the liver tissues of hyperlipidemic rats and promote the elimination ofLDL-C to reduce serum cholesterol notably.

Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

International Nuclear Information System (INIS)

Devi, Sachin S.; Mehendale, Harihara M.

2005-01-01

Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G 0 to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G 1 to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes

Ineffectiveness of rat liver tissues in the screening of connective tissue disease

International Nuclear Information System (INIS)

Aziz, Khalil A.

2004-01-01

To assess the effectiveness of using rat liver tissue (RLT) for the screening of connective tissue disease (CTD). Results of patient samples submitted to the Clinical Immunology Laboratory, Brimingham Heartlands Hospital, Bordsley Green East, Brimingham, United Kingdom for the investigation of CTD between 2001 and 2002 were analyzed. Positive results for anti-double stranded DNA (dsDNA) antibodies and anti-extractable nuclear antigen (ENA) antibodies were correlated with the results of the corresponding antinuclear antibodies (ANA), obtained by indirect immunofluorescence (IIF) using RLT. In the second part of study samples that were previously tested positive for anti-ENA or anti-dsDNA antibodies were investigated prospectively for ANA using both RLTand human epithelial (Hep-2) cell line. The IIF method employing RLT for screening of CTD, failed to detect ANA patterns from 45% and 25%of patients sample know to contain antibodies to dsDNA and ENA.The anti -dsDNA antibodies that failed to be detected by the RLTwere of low avidity and their clinical significance is unknown. In contrast the antibodies to ENAwere mostly directed against the Ro antigen.In cotrast and like RLT, Hep-2 cell line failed to detect the low avidity anti-dsDNA antibdies.The present study has clearly shown that RLT are ineffective for screening of CTD. It is recommended that laboratories which ars still using these tissues should consider replacing them with the Hep-2 cell line. (author)

Effect of Phenanthrene on the Tissue Structure of Liver and Aminotransferase Enzymes in Yellowfin Seabream (Acanthopagrus latus

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Mehrnaz Shirmohammadi*

2017-06-01

Full Text Available Background: Polycyclic aromatic hydrocarbons (PAHs such as phenanthrene (Phe represent one of the most abundant forms of organic pollutants. The aim of this study was to assess changes in plasma levels of aminotransferase enzymes, total protein and liver tissue as biomarkers of yellowfin seabream (Acanthopagrus latus exposed to Phe for 14 d. Methods: The research was carried out in January 2016 at Khorramshahr University of Marine Sciences and Technology, Khorramshahr, Iran. Some 72 fish were injected with 2, 20, 40 and 70 mg/kg of Phe. Then tissue and blood samples were obtained at 1, 4, 7 and 14 d after injection. Results: Exposure of fish to Phe resulted in a significant increase of alanine aminotransferase (ALT, aspartate aminotransferase (AST and decrease of total protein after 7 d of the experiment (P<0.05. The main histopathological alteration was showed in different sampling days including nucleus margination, hypertrophy, vacuolation, melanomacrophages aggregates, sinusoid dilation, degeneration and picnotic nucleus. Degree of tissue change (DTC of liver was recorded in the Phe-exposed fish from normal range to moderate changes. Conclusion: The studied biomarkers such as changes in concentrations of ALT, AST and total protein as well as tissue damages in liver may be served as beneficial biomarker to assess Phe toxicity in yellowfin seabream.

Lesions in Porcine Liver Tissues Created by Continuous High Intensity Ultrasound Exposures in Vitro

International Nuclear Information System (INIS)

Zhang Zhe; Chen Tao; Zhang Dong

2013-01-01

Lesions in porcine liver tissues created by continuous high intensity focused ultrasound (HIFU) exposures in vitro are theoretically and experimentally investigated, with the transmitter moving along a linear path at a fixed speed. Numerical simulations of the lesion formation are performed based on the Khokhlov—Zabolotskaya—Kuznetov equation and the bio-heat equation. In order to verify the theoretical predictions, experiments are performed in the one-dimensional scanning mode to measure the cross-sectional area of lesions created in the in vitro porcine liver exposed to 1.01-MHz HIFU pulses with the acoustic power of 70 W. The results indicate that, compared to the traditional discrete treatment protocol, the application of a continuous scanning model can create more uniform lesions in tissues and significantly reduces the total treatment time from 47s to 30s

Nano scaffolds and stem cell therapy in liver tissue engineering

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Montaser, Laila M.; Fawzy, Sherin M.

2015-08-01

Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

Intrahepatic tissue pO2 during continuous or intermittent vascular inflow occlusion in a pig liver resection model

NARCIS (Netherlands)

van Wagensveld, B. A.; van Gulik, T. M.; Gabeler, E. E.; van der Kleij, A. J.; Obertop, H.; Gouma, D. J.

1998-01-01

BACKGROUND: Temporary vascular inflow occlusion of the liver (clamping of the hepatic pedicle) can prevent massive blood loss during liver resections. In this study, intrahepatic tissue pO2 was assessed as parameter of microcirculatory disturbances induced by ischemia and reperfusion (I/R) in the

Isolation and expansion of adipose-derived stem cells for tissue engineering

DEFF Research Database (Denmark)

Fink, Trine; Rasmussen, Jeppe Grøndahl; Lund, Pia

2011-01-01

For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs for subseq......For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs...

Gestational age dependent changes of the fetal brain, liver and adipose tissue fatty acid compositions in a population with high fish intakes

NARCIS (Netherlands)

Kuipers, Remko S.; Luxwolda, Martine F.; Offringa, Pieter J.; Boersma, E. Rudy; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

2012-01-01

Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes. Subjects and methods: We analyzed the brain (n = 18), liver (n = 14) and adipose tissue (n = 11) FA compositions of 20 stillborn

Thyroid hormone upregulates zinc-α2-glycoprotein production in the liver but not in adipose tissue.

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Rafael Simó

Full Text Available Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes and in vivo (C57BL6/mice experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not

Thyroid hormone upregulates zinc-α2-glycoprotein production in the liver but not in adipose tissue.

Science.gov (United States)

Simó, Rafael; Hernández, Cristina; Sáez-López, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M

2014-01-01

Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not related to weight

Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

International Nuclear Information System (INIS)

Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W; Emami, K; Wu, H

2011-01-01

The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

Energy Technology Data Exchange (ETDEWEB)

Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W [Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104 (United States); Emami, K; Wu, H, E-mail: sunwei@drexel.edu, E-mail: weisun@tsinghua.edu.cn [Radiation Biophysics Lab, NASA Johnson Space Center, Houston, TX 77586 (United States)

2011-09-15

The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

Tissue-Derived Extracellular Matrix Bioscaffolds: Emerging Applications in Cartilage and Meniscus Repair.

Science.gov (United States)

Monibi, Farrah A; Cook, James L

2017-08-01

Musculoskeletal injuries are a common problem in orthopedic practice. Given the long-term consequences of unaddressed cartilage and meniscal pathology, a number of treatments have been attempted to stimulate repair or to replace the injured tissue. Despite advances in orthopedic surgery, effective treatments for cartilage and meniscus injuries remain a significant clinical challenge. Tissue engineering is a developing field that aims to regenerate injured tissues with a combination of cells, scaffolds, and signals. Many natural and synthetic scaffold materials have been developed and tested for the repair and restoration of a number of musculoskeletal tissues. Among these, biological scaffolds derived from cell and tissue-derived extracellular matrix (ECM) have shown great promise in tissue engineering given the critical role of the ECM for maintaining the biological and biomechanical properties, structure, and function of native tissues. This review article presents emerging applications for tissue-derived ECM scaffolds in cartilage and meniscus repair. We examine normal ECM composition and the current and future methods for potential treatment of articular cartilage and meniscal defects with decellularized scaffolds.

Biodistribution of Liver-Derived Mesenchymal Stem Cells After Peripheral Injection in a Hemophilia A Patient.

Science.gov (United States)

Sokal, Etienne M; Lombard, Catherine Anne; Roelants, Véronique; Najimi, Mustapha; Varma, Sharat; Sargiacomo, Camillo; Ravau, Joachim; Mazza, Giuseppe; Jamar, François; Versavau, Julia; Jacobs, Vanessa; Jacquemin, Marc; Eeckhoudt, Stéphane; Lambert, Catherine; Stéphenne, Xavier; Smets, Françoise; Hermans, Cédric

2017-08-01

With the exception of liver transplantation, there is no cure for hemophilia, which is currently managed by preemptive replacement therapy. Liver-derived stem cells are in clinical development for inborn and acquired liver diseases and could represent a curative treatment for hemophilia A. The liver is a major factor VIII (FVIII) synthesis site, and mesenchymal stem cells have been shown to control joint bleeding in animal models of hemophilia. Adult-derived human liver stem cells (ADHLSCs) have mesenchymal characteristics and have been shown able to engraft in and repopulate both animal and human livers. Thus, the objectives were to evaluate the potency of ADHLSCs to control bleeding in a hemophilia A patient and assess the biodistribution of the cells after intravenous injection. A patient suffering from hemophilia A was injected with repeated doses of ADHLSCs via a peripheral vein (35 million In-oxine-labeled cells, followed by 125 million cells the next day, and 3 infusions of 250 million cells every 2 weeks thereafter; total infusion period, 50 days). After cell therapy, we found a temporary (15 weeks) decrease in the patient's FVIII requirements and severe bleeding complications, despite a lack of increase in circulating FVIII. The cells were safely administered to the patient via a peripheral vein. Biodistribution analysis revealed an initial temporary entrapment of the cells in the lungs, followed by homing to the liver and to a joint afflicted with hemarthrosis. These results suggest the potential use of ADHLSCs in the treatment of hemophilia A.

Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

Science.gov (United States)

Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J; Korangy, Firouzeh; Greten, Tim F

2014-01-01

Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

Energy Technology Data Exchange (ETDEWEB)

El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Katsuta, Hitoshi; Hollister-Lock, Jennifer; Qian, Weijun; Wagers, Amy J.; Kulkarni, Rohit N.

2013-02-21

Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation in ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.

Advances of mesenchymal stem cells derived from bone marrow and dental tissue in craniofacial tissue engineering.

Science.gov (United States)

Yang, Maobin; Zhang, Hongming; Gangolli, Riddhi

2014-05-01

Bone and dental tissues in craniofacial region work as an important aesthetic and functional unit. Reconstruction of craniofacial tissue defects is highly expected to ensure patients to maintain good quality of life. Tissue engineering and regenerative medicine have been developed in the last two decades, and been advanced with the stem cell technology. Bone marrow derived mesenchymal stem cells are one of the most extensively studied post-natal stem cell population, and are widely utilized in cell-based therapy. Dental tissue derived mesenchymal stem cells are a relatively new stem cell population that isolated from various dental tissues. These cells can undergo multilineage differentiation including osteogenic and odontogenic differentiation, thus provide an alternative source of mesenchymal stem cells for tissue engineering. In this review, we discuss the important issues in mesenchymal stem cell biology including the origin and functions of mesenchymal stem cells, compare the properties of these two types of mesenchymal cells, update recent basic research and clinic applications in this field, and address important future challenges.

Natural Killer cells and liver fibrosis

Directory of Open Access Journals (Sweden)

Frank eFasbender

2016-01-01

Full Text Available In the 40 years since the discovery of Natural Killer (NK cells it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue resident NK cells with distinct phenotypical and functional characteristics have been identified. Here we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects.

Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure

NARCIS (Netherlands)

Oedayrajsingh-Varma, M. J.; van Ham, S. M.; Knippenberg, M.; Helder, M. N.; Klein-Nulend, J.; Schouten, T. E.; Ritt, M. J. P. F.; van Milligen, F. J.

2006-01-01

Adipose tissue contains a stromal vascular fraction that can be easily isolated and provides a rich source of adipose tissue-derived mesenchymal stem cells (ASC). These ASC are a potential source of cells for tissue engineering. We studied whether the yield and growth characteristics of ASC were

A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging

International Nuclear Information System (INIS)

Behrens, Christopher B.; Langholz, Juliane H.; Eiler, Jessika; Jenewein, Raphael; Fuchs, Konstantin; Alzen, Gerhard F.P.; Naehrlich, Lutz; Harth, Sebastian; Krombach, Gabriele A.

2013-01-01

Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD. (orig.)

A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging

Energy Technology Data Exchange (ETDEWEB)

Behrens, Christopher B.; Langholz, Juliane H.; Eiler, Jessika; Jenewein, Raphael; Fuchs, Konstantin; Alzen, Gerhard F.P. [University Hospital Giessen, Department of Pediatric Radiology, Giessen (Germany); Naehrlich, Lutz [University Hospital Giessen, Department of Pediatrics, Giessen (Germany); Harth, Sebastian; Krombach, Gabriele A. [University Hospital Giessen, Department of Radiology, Giessen (Germany)

2013-03-15

Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD. (orig.)

Establishment and characterization of a unique 1 microm diameter liver-derived progenitor cell line.

Science.gov (United States)

Aravalli, Rajagopal N; Behnan Sahin, M; Cressman, Erik N K; Steer, Clifford J

2010-01-01

Liver-derived progenitor cells (LDPCs) are recently identified novel stem/progenitor cells from healthy, unmanipulated adult rat livers. They are distinct from other known liver stem/progenitor cells such as the oval cells. In this study, we have generated a LDPC cell line RA1 by overexpressing the simian virus 40 (SV40) large T antigen (TAg) in primary LDPCs. This cell line was propagated continuously for 55 passages in culture, after which it became senescent. Interestingly, following transformation with SV40 TAg, LDPCs decreased in size significantly and the propagating cells measured 1 microm in diameter. RA1 cells proliferated in vitro with a doubling time of 5-7 days, and expressed cell surface markers of LDPCs. In this report, we describe the characterization of this novel progenitor cell line that might serve as a valuable model to study liver cell functions and stem cell origin of liver cancers. Copyright 2009 Elsevier Inc. All rights reserved.

Poly (dopamine) coated superparamagnetic iron oxide nanocluster for noninvasive labeling, tracking, and targeted delivery of adipose tissue-derived stem cells

Science.gov (United States)

Liao, Naishun; Wu, Ming; Pan, Fan; Lin, Jiumao; Li, Zuanfang; Zhang, Da; Wang, Yingchao; Zheng, Youshi; Peng, Jun; Liu, Xiaolong; Liu, Jingfeng

2016-01-01

Tracking and monitoring of cells in vivo after transplantation can provide crucial information for stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be an effective and non-invasive technique for cell tracking in living bodies. However, commercial superparamagnetic iron oxide nanoparticles (SPIONs) applied to label cells suffer from shortages such as potential toxicity, low labeling efficiency, and low contrast enhancing. Herein, the adipose tissue-derived stem cells (ADSCs) were efficiently labeled with SPIONs coated with poly (dopamine) (SPIONs cluster@PDA), without affecting their viability, proliferation, apoptosis, surface marker expression, as well as their self-renew ability and multi-differentiation potential. The labeled cells transplanted into the mice through tail intravenous injection exhibited a negative enhancement of the MRI signal in the damaged liver-induced by carbon tetrachloride, and subsequently these homed ADSCs with SPIONs cluster@PDA labeling exhibited excellent repair effects to the damaged liver. Moreover, the enhanced target-homing to tissue of interest and repair effects of SPIONs cluster@PDA-labeled ADSCs could be achieved by use of external magnetic field in the excisional skin wound mice model. Therefore, we provide a facile, safe, noninvasive and sensitive method for external magnetic field targeted delivery and MRI based tracking of transplanted cells in vivo.

Poly (dopamine) coated superparamagnetic iron oxide nanocluster for noninvasive labeling, tracking, and targeted delivery of adipose tissue-derived stem cells.

Science.gov (United States)

Liao, Naishun; Wu, Ming; Pan, Fan; Lin, Jiumao; Li, Zuanfang; Zhang, Da; Wang, Yingchao; Zheng, Youshi; Peng, Jun; Liu, Xiaolong; Liu, Jingfeng

2016-01-05

Tracking and monitoring of cells in vivo after transplantation can provide crucial information for stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be an effective and non-invasive technique for cell tracking in living bodies. However, commercial superparamagnetic iron oxide nanoparticles (SPIONs) applied to label cells suffer from shortages such as potential toxicity, low labeling efficiency, and low contrast enhancing. Herein, the adipose tissue-derived stem cells (ADSCs) were efficiently labeled with SPIONs coated with poly (dopamine) (SPIONs cluster@PDA), without affecting their viability, proliferation, apoptosis, surface marker expression, as well as their self-renew ability and multi-differentiation potential. The labeled cells transplanted into the mice through tail intravenous injection exhibited a negative enhancement of the MRI signal in the damaged liver-induced by carbon tetrachloride, and subsequently these homed ADSCs with SPIONs cluster@PDA labeling exhibited excellent repair effects to the damaged liver. Moreover, the enhanced target-homing to tissue of interest and repair effects of SPIONs cluster@PDA-labeled ADSCs could be achieved by use of external magnetic field in the excisional skin wound mice model. Therefore, we provide a facile, safe, noninvasive and sensitive method for external magnetic field targeted delivery and MRI based tracking of transplanted cells in vivo.

Exercise-induced liver chemokine CXCL-1 expression is linked to muscle-derived interleukin-6 expression

DEFF Research Database (Denmark)

Pedersen, Line; Pilegaard, Henriette; Hansen, Jakob

2011-01-01

interleukin-6 (IL-6) and muscle IL-6 mRNA. In contrast, exercise-induced regulation of liver CXCL-1 mRNA expression was completely blunted in IL-6 knockout mice. Based on these findings, we examined the possible existence of a muscle-to-liver axis by overexpressing IL-6 in muscles. This resulted in increases...... in serum CXCL-1 (5-fold) and liver CXCL-1 mRNA expression (24-fold) compared with control. Because IL-6 expression and release are known to be augmented during exercise in glycogen-depleted animals, CXCL-1 and IL-6 expression were examined after exercise in overnight-fasted mice.We found that fasting...... significantly augmented serum CXCL-1, and CXCL-1 expression in liver and muscle. Taken together, these data indicate that liver is the main source of serum CXCL-1 during exercise in mice, and that the CXCL-1 expression in the liver is regulated by muscle-derived IL-6....

Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

Directory of Open Access Journals (Sweden)

Tobias Eggert

Full Text Available Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL, while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina

NARCIS (Netherlands)

Segarra, Nuria Garcia; Ballhausen, Diana; Crawford, Heather; Perreau, Matthieu; Campos-Xavier, Belinda; van Spaendonck-Zwarts, Karin; Vermeer, Cees; Russo, Michel; Zambelli, Pierre-Yves; Stevenson, Brian; Royer-Bertrand, Beryl; Rivolta, Carlo; Candotti, Fabio; Unger, Sheila; Munier, Francis L.; Superti-Furga, Andrea; Bonafé, Luisa

2015-01-01

We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting,

Glutathione protects liver and kidney tissue from cadmium- and lead-provoked lipid peroxidation

Directory of Open Access Journals (Sweden)

Jovanović Jasmina M.

2013-01-01

Full Text Available Cd and Pb represent a serious ecological problem due to their soluble nature, their mobility and ability to accumulate in the soil. The exposure to these heavy metals can originate from different sources (drinking water, food, air, and they can make their way into the human body through the respiratory and digestive system. We investigated the effects of glutathione on Cd and Pb accumulation and lipid peroxidation effects in the liver and kidneys of heavy metal intoxicated rats. The content of the marker of lipid peroxidation - malondialdehyde was increased several fold the in tissues of exposed animals, the effects being more pronounced in liver. The treatment of intoxicated animals with glutathione drastically suppressed lipid peroxidation. Our results imply that the application of glutathione may have protective role in heavy metal intoxication by inhibiting lipid peroxidation. However, precaution should be made when it comes to Cd, since it seems that glutathione promoted Cd accumulation in the liver.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

Science.gov (United States)

Firneisz, Gábor

2014-07-21

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

RNA deep sequencing reveals novel candidate genes and polymorphisms in boar testis and liver tissues with divergent androstenone levels.

Directory of Open Access Journals (Sweden)

Asep Gunawan

Full Text Available Boar taint is an unpleasant smell and taste of pork meat derived from some entire male pigs. The main causes of boar taint are the two compounds androstenone (5α-androst-16-en-3-one and skatole (3-methylindole. It is crucial to understand the genetic mechanism of boar taint to select pigs for lower androstenone levels and thus reduce boar taint. The aim of the present study was to investigate transcriptome differences in boar testis and liver tissues with divergent androstenone levels using RNA deep sequencing (RNA-Seq. The total number of reads produced for each testis and liver sample ranged from 13,221,550 to 33,206,723 and 12,755,487 to 46,050,468, respectively. In testis samples 46 genes were differentially regulated whereas 25 genes showed differential expression in the liver. The fold change values ranged from -4.68 to 2.90 in testis samples and -2.86 to 3.89 in liver samples. Differentially regulated genes in high androstenone testis and liver samples were enriched in metabolic processes such as lipid metabolism, small molecule biochemistry and molecular transport. This study provides evidence for transcriptome profile and gene polymorphisms of boars with divergent androstenone level using RNA-Seq technology. Digital gene expression analysis identified candidate genes in flavin monooxygenease family, cytochrome P450 family and hydroxysteroid dehydrogenase family. Moreover, polymorphism and association analysis revealed mutation in IRG6, MX1, IFIT2, CYP7A1, FMO5 and KRT18 genes could be potential candidate markers for androstenone levels in boars. Further studies are required for proving the role of candidate genes to be used in genomic selection against boar taint in pig breeding programs.

Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

Science.gov (United States)

Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

2013-05-01

The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

Sexually dimorphic effects of maternal nutrient reduction on expression of genes regulating cortisol metabolism in fetal baboon adipose and liver tissues.

Science.gov (United States)

Guo, Chunming; Li, Cun; Myatt, Leslie; Nathanielsz, Peter W; Sun, Kang

2013-04-01

Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabolic syndrome, but underlying mechanisms are unknown. Hexose-6-phosphate dehydrogenase (H6PD) generates NADPH, the cofactor for 11β-HSD1 reductase activity. CCAAT/enhancer binding proteins (C/EBPs) and the glucocorticoid receptor (GR) regulate 11β-HSD1 expression. We hypothesize that MNR increases expression of fetal C/EBPs, GR, and H6PD, thereby increasing expression of 11β-HSD1 and reductase activity in fetal liver and adipose tissues. Pregnant MNR baboons ate 70% of what controls ate from 0.16 to 0.9 gestation (term, 184 days). Cortisol levels in maternal and fetal circulations increased in MNR pregnancies at 0.9 gestation. MNR increased expression of 11β-HSD1; H6PD; C/EBPα, -β, -γ; and GR in female but not male perirenal adipose tissue and in male but not female liver at 0.9 gestation. Local cortisol level and its targets PEPCK1 and PPARγ increased correspondingly in adipose and liver tissues. C/EBPα and GR were found to be bound to the 11β-HSD1 promoter. In conclusion, sex- and tissue-specific increases of 11β-HSD1, H6PD, GR, and C/EBPs may contribute to sexual dimorphism in the programming of exaggerated cortisol regeneration in liver and adipose tissues and offsprings' susceptibility to metabolic syndrome.

Dietary pattern associated with selenoprotein P and MRI-derived body fat volumes, liver signal intensity, and metabolic disorders.

Science.gov (United States)

di Giuseppe, Romina; Plachta-Danielzik, Sandra; Koch, Manja; Nöthlings, Ute; Schlesinger, Sabrina; Borggrefe, Jan; Both, Marcus; Müller, Hans-Peter; Kassubek, Jan; Jacobs, Gunnar; Lieb, Wolfgang

2018-02-14

The association of complex dietary patterns with circulating selenoprotein P (SELENOP) levels in humans is unknown. In a general population sample, we aimed to identify a dietary pattern explaining inter-individual variation in circulating SELENOP concentrations and to study this pattern in relation to prevalent diabetes, metabolic syndrome (MetS), MRI-determined total volumes of visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, and liver signal intensity/fatty liver disease. In this cross-sectional study, serum SELENOP levels were measured in 853 individuals. In a subsample of 553 participants, whole-body MRI was performed to assess body fat distribution and liver fat. Dietary intake was assessed by a self-administered food frequency questionnaire and the dietary pattern identified using reduced-rank regression (RRR). Multivariable linear and logistic regressions were used to investigate associations between dietary pattern score and metabolic traits. Characterized by high intake of fruit, vegetables and antioxidant beverages, the RRR-derived dietary pattern displayed inverse associations with VAT, SAT, MetS, and prevalent diabetes in multivariable-adjusted restricted cubic splines. Each unit increase in dietary pattern score was associated with 31% higher SELENOP levels, 12% lower VAT (95% CI: - 19%; - 5%), 13% (95% CI: - 20%; - 6%) lower SAT values and 46% (95% CI: 27%; 60%) and 53% (95% CI: 22%; 72%) lower odds of having MetS or diabetes, respectively. No meaningful relations were observed between the dietary pattern and liver traits. Our observations propose diet-related regulation in SELENOP levels and that the identified dietary pattern is inversely related to VAT, SAT, MetS, and prevalent diabetes.

Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals.

Science.gov (United States)

Machado, Christiano Bittencourt; Pereira, Wagner Coelho de Albuquerque; Meziri, Mahmoud; Laugier, Pascal

2006-05-01

This work studied the periodicity of in vitro healthy and pathologic liver tissue, using backscattered ultrasound (US) signals. It utilized the mean scatterer spacing (MSS) as a parameter of tissue characterization, estimated by three methods: the spectral autocorrelation (SAC), the singular spectrum analysis (SSA) and the quadratic transformation method (SIMON). The liver samples were classified in terms of tissue status using the METAVIR scoring system. Twenty tissue samples were classified in four groups: F0, F1, F3 and F4 (five samples for each). The Kolmogorov-Smirnov test (applied on group pairs) resulted as nonsignificant (p > 0.05) for two pairs only: F1/F3 (for SSA) and F3/F4 (for SAC). A discriminant analysis was applied using as parameters the MSS mean (MSS) and standard deviation (sigmaMSS), the estimates histogram mode (mMSS), and the speed of US (mc(foie)) in the medium, to evaluate the degree of discrimination among healthy and pathologic tissues. The better accuracy (Ac) with SAC (80%) was with parameter group (MSS, sigmaMSS, mc(foie)), achieving a sensitivity (Ss) of 92.3% and a specificity (Sp) of 57.1%. For SSA, the group with all four parameters showed an Ac of 75%, an Ss of 78.6% and an Sp of 66.70%. SIMON obtained the best Ac of all (85%) with group (MSS, mMSS, mc(foie)), an Ss of 100%, but with an Sp of 50%.

Establishment and characterization of a unique 1 μm diameter liver-derived progenitor cell line

International Nuclear Information System (INIS)

Aravalli, Rajagopal N.; Behnan Sahin, M.; Cressman, Erik N.K.; Steer, Clifford J.

2010-01-01

Liver-derived progenitor cells (LDPCs) are recently identified novel stem/progenitor cells from healthy, unmanipulated adult rat livers. They are distinct from other known liver stem/progenitor cells such as the oval cells. In this study, we have generated a LDPC cell line RA1 by overexpressing the simian virus 40 (SV40) large T antigen (TAg) in primary LDPCs. This cell line was propagated continuously for 55 passages in culture, after which it became senescent. Interestingly, following transformation with SV40 TAg, LDPCs decreased in size significantly and the propagating cells measured 1 μm in diameter. RA1 cells proliferated in vitro with a doubling time of 5-7 days, and expressed cell surface markers of LDPCs. In this report, we describe the characterization of this novel progenitor cell line that might serve as a valuable model to study liver cell functions and stem cell origin of liver cancers.

Establishment and characterization of a unique 1 {mu}m diameter liver-derived progenitor cell line

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Aravalli, Rajagopal N., E-mail: arava001@umn.edu [Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455 (United States); Behnan Sahin, M. [Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455 (United States); Cressman, Erik N.K. [Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455 (United States); Steer, Clifford J., E-mail: steer001@umn.edu [Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455 (United States); Department of Genetics, Cell Biology, and Development, University of Minnesota Medical School, Minneapolis, MN 55455 (United States)

2010-01-01

Liver-derived progenitor cells (LDPCs) are recently identified novel stem/progenitor cells from healthy, unmanipulated adult rat livers. They are distinct from other known liver stem/progenitor cells such as the oval cells. In this study, we have generated a LDPC cell line RA1 by overexpressing the simian virus 40 (SV40) large T antigen (TAg) in primary LDPCs. This cell line was propagated continuously for 55 passages in culture, after which it became senescent. Interestingly, following transformation with SV40 TAg, LDPCs decreased in size significantly and the propagating cells measured 1 {mu}m in diameter. RA1 cells proliferated in vitro with a doubling time of 5-7 days, and expressed cell surface markers of LDPCs. In this report, we describe the characterization of this novel progenitor cell line that might serve as a valuable model to study liver cell functions and stem cell origin of liver cancers.

Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases

Directory of Open Access Journals (Sweden)

Irina V. Kholodenko

2017-01-01

Full Text Available The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role. Participation of blood-borne cells of the bone marrow origin in liver parenchyma regeneration has been proven but does not exceed 1-2% of newly formed hepatocytes. Liver regeneration is activated spontaneously after injury and can be further stimulated by cell therapy with hepatocytes, hematopoietic stem cells, or mesenchymal stem cells. Further studies aimed at improving the outcomes of cell therapy of liver diseases are underway. In case of liver failure, transplantation of engineered liver can become the best option in the foreseeable future. Engineering of a transplantable liver or its major part is an enormous challenge, but rapid progress in induced pluripotency, tissue engineering, and bioprinting research shows that it may be doable.

Cytokines and Liver Diseases

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Herbert Tilg

2001-01-01

Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

Effects of Puerariae Radix Extract on Endotoxin Receptors and TNF-α Expression Induced by Gut-Derived Endotoxin in Chronic Alcoholic Liver Injury

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Jing-Hua Peng

2012-01-01

Full Text Available Kudzu (Pueraria lobata is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine for more than a millennium. However, little is known about its effects on chronic alcoholic liver injury. Therefore, the present study observed the effects of puerariae radix extract (RPE on chronic alcoholic liver injury as well as Kupffer cells (KCs activation to release tumor necrosis factor alpha (TNF-α induced by gut-derived endotoxin in rats and macrophage cell line. RPE was observed to alleviate the pathological changes and lipids deposition in liver tissues as well as the serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, and hepatic gamma-glutamyl transpeptidase (GGT activity. Meanwhile, RPE inhibited KCs activation and subsequent hepatic TNF-α expression and downregulated the protein expression of endotoxin receptors, lipopolysaccharide binding protein (LBP, CD14, Toll-like receptor (TLR 2, and TLR4 in chronic alcohol intake rats. Furthermore, an in vitro study showed that RPE inhibited the expression of TNF-α and endotoxin receptors, CD14 and TLR4, induced by LPS in RAW264.7 cells. In summary, this study demonstrated that RPE mitigated liver damage and lipid deposition induced by chronic alcohol intake in rats, as well as TNF-α release, protein expression of endotoxin receptors in vivo or in vitro.

Differentiation between chronic hepatitis and normal liver of grayscale ultrasound tissue quantification using adobe photoshop(5.0)

International Nuclear Information System (INIS)

Choi, Jong Cheol; Oh, Jong Young; Lim, Jong Uk; Nam, Kyung Jin

2001-01-01

To evaluate whether was any difference in the brightness of echogenicity on gray scale ultrasound imaging between the liver with chronic hepatitis and the normal liver using Adobe photoshop 5.0 Seventy-five patients with pathologically proven chronic hepatitis and twenty normal volunteers were included in this study. Adobe photoshop 5.0 histogram was used to measure the brightness of image. The measured brightness of the liver was divided by the brightness of the kidney, and the radio was calculated and compared between patients with chronic hepatitis and the normal control groups. In addition, the degree of fibrosis was also evaluated. The difference in brightness between the normal liver and live with chronic hepatitis was statistically significant, but no statistically significant difference was observed between the brightness of the liver and the degree of fibrosis in the liver. Tissue echo quantification using Adobe Photoshop 5.0 may be a helpful diagnostic methods for the patients with chronic hepatitis.

Functional pitch of a liver: fatty liver disease diagnosis with photoacoustic spectrum analysis

Science.gov (United States)

Xu, Guan; Meng, Zhuoxian; Lin, Jiandie; Carson, Paul; Wang, Xueding

2014-03-01

To provide more information for classification and assessment of biological tissues, photoacoustic spectrum analysis (PASA) moves beyond the quantification of the intensities of the photoacoustic (PA) signals by the use of the frequency-domain power distribution, namely power spectrum, of broadband PA signals. The method of PASA quantifies the linear-fit to the power spectrum of the PA signals from a biological tissue with 3 parameters, including intercept, midband-fit and slope. Intercept and midband-fit reflect the total optical absorption of the tissues whereas slope reflects the heterogeneity of the tissue structure. Taking advantage of the optical absorption contrasts contributed by lipid and blood at 1200 and 532 nm, respectively and the heterogeneous tissue microstructure in fatty liver due to the lipid infiltration, we investigate the capability of PASA in identifying histological changes of fatty livers in mouse model. 6 and 9 pairs of normal and fatty liver tissues from rat models were examined by ex vivo experiment with a conventional rotational PA measurement system. One pair of rat models with normal and fatty livers was examined non-invasively and in situ with our recently developed ultrasound and PA parallel imaging system. The results support our hypotheses that the spectrum analysis of PA signals can provide quantitative measures of the differences between the normal and fatty liver tissues and that part of the PA power spectrum can suffice for characterization of microstructures in biological tissues. Experimental results also indicate that the vibrational absorption peak of lipid at 1200nm could facilitate fatty liver diagnosis.

Histopathological and Ultrastructural Studies of Liver Tissue from TCDD-Exposed Beach Mice (Peromyscus polionotus).

Science.gov (United States)

1980-03-01

TQuantitative ultrastructural studies were conducted on liver tissue f ran beach Lj mice, Per~ ascus polionotus, exposed to the toxin 2,3, 7f8...weights per se was not attempted since the ages of the beach mice were not known and the animals could only be classified by sex and treatment. The

Study on pharmacokinetics and tissue distribution of the isocorydine derivative (AICD) in rats by HPLC-DAD method

Institute of Scientific and Technical Information of China (English)

Yali Chen; Qian Yan; Mei Zhong; Quanyi Zhao; Junxi Liu; Duolong Di; Jinxia Liu

2015-01-01

A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid-liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative(8-acetaminoisocorydine) of isocorydine.According to the in vivo experiments data calculations by DAS 2.0 software,a two-compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetaminoisocorydine in rats.8-Acetamino-isocorydine was absorbed well after oral administration,and the absolute bioavailability was 76.5%.The half-life of 8-acetamino-isocorydine after intravenous and oral administration was 2.2 h and 2.0 h,respectively.In vivo,8-acetamino-isocorydine was highly distributed in the lungs,kidney and liver;however,relatively little entered the brain,suggesting that 8-acetaminoisocorydine could not easily pass through the blood brain barrier.Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-isocorydine.The acquired data will provide useful information for the in vivo pharmacology of 8-acetaminoisocorydine,and can be applied to new drug research.

[Determination of hydroxyproline in liver tissue by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry].

Science.gov (United States)

Liu, Wei; Qi, Shenglan; Xu, Ying; Xiao, Zhun; Fu, Yadong; Chen, Jiamei; Yang, Tao; Liu, Ping

2017-12-08

A method for the determination of hydroxyproline (Hyp) in liver tissue of mice by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (HILIC-HRMS) was developed. The liver tissue samples of normal mice and liver fibrosis mice induced by carbon tetrachloride were hydrolyzed by concentrated hydrochloric acid. After filtrated and diluted by solution, the diluent was separated on an Hypersil GOLD HILIC column (100 mm×2.1 mm, 3 μm). Water-acetonitrile (28:72, v/v)were used as the mobile phases with isocratic elution. Finally, the target analytes were detected in positive model by HRMS equipped with an electrospray ionization source. The linear range of hydroxyproline was from 0.78 to 100.00 μg/L with the correlation coefficient ( R 2 ) of 0.9983. The limit of quantification was 0.78 μg/L. By detecting the spiked samples, the recoveries were in the range of 97.4%-100.9% with the relative standard deviations (RSDs) between 1.4% and 2.0%. In addition, comparison of the measurement results by this method and the chloramine T method was proceeded. It was found that the linear correlation between the two methods was very good, and the Pearson correlation coefficient was 0.927. And this method had simpler operation procedure and higher accuracy than chloramine T method. This method can be used for the quick determination of hydroxyproline in liver tissue samples.

The metabolism of 32P-CP-PLLA seed implanted in the liver and its damage to the normal liver tissue: a study in the experimental dogs

International Nuclear Information System (INIS)

Tan Zhongbao; Liu Lu; Guo Jinhe; Zhu Guangyu; Wang Fuan; Nie Qi; Gao Hailin; Teng Gaojun

2010-01-01

Objective: To investigate the effects of intratumoral implantation of 32 P -CP-PLLA seeds on the normal canine liver tissue and to explore the metabolism of 32 P-CP-PLLA seeds implanted in the liver of experimental dogs. Methods: Twelve beagles were enrolled in this study. The dogs were randomly and equally divided into four groups: group A (185 MBq), group B (370 MBq), group C (740 MBq) and group D (0 MBq). By using laparotomy procedure 32 P-CP-PLLA seeds were implanted into dog's liver. CT scan was performed before operation as well as before the dog was sacrificed. All dogs were sacrificed three months after the implantation. Before the procedure and 1, 2, 4, 8 and 12 weeks after the procedure the blood tests and serum biochemical tests were conducted. One dog from group B and group C was selected respectively and was fed in a metabolic cage. Within one month after the procedure the cpm in feces and in urine was determined every 24 hours. One dog was picked out from each of the three groups and was punctured to get its liver tissue for pathologic exam each time at 1, 2, 4, 8 and 12 weeks after the implantation, and SPECT imaging was also performed at the same time. Pathologic study, both macroscopic and microscopic (including optical and electronic microscopy) was made to observe the liver damage after the dog was sacrificed. The statistical analysis was processed by using SPSS 13.0 software and the measuring data were expressed with mean ± standard deviation (x ± s). Results: Two months after the procedure, serological examination found that the serum alkaline phosphatase (BKP) in both group B and group C was significantly higher than that in other groups, the difference was statistically significant (P 32 P-CP-PLLA seeds was manifested as a spherical lesion which was encysted by a layer of fibrous tissue with an edematous zone peripherally. Conclusion: The implantation of 32 P-CP-PLLA seeds in dog's liver causes only localized hepatic damage with no general

CULTIVATION OF HUMAN LIVER CELLS AND ADIPOSE-DERIVED MESENCHYMAL STROMAL CELLS IN PERFUSION BIOREACTOR

Directory of Open Access Journals (Sweden)

Yu. В. Basok

2018-01-01

Full Text Available Aim: to show the progress of the experiment of cultivation of human liver cells and adipose-derived mesenchymal stromal cells in perfusion bioreactor.Materials and methods. The cultivation of a cell-engineered construct, consisting of a biopolymer microstructured collagen-containing hydrogel, human liver cells, adipose-derived mesenchymal stromal cells, and William’s E Medium, was performed in a perfusion bioreactor.Results. On the 7th day large cells with hepatocyte morphology – of a polygonal shape and a centrally located round nucleus, – were present in the culture chambers of the bioreactor. The metabolic activity of hepatocytes in cell-engineered constructs was confi rmed by the presence of urea in the culture medium on the seventh day of cultivation in the bioreactor and by the resorption of a biopolymer microstructured collagen-containing hydrogel.

Time-resolved computed tomography of the liver: retrospective, multi-phase image reconstruction derived from volumetric perfusion imaging

Energy Technology Data Exchange (ETDEWEB)

Fischer, Michael A.; Kartalis, Nikolaos; Aspelin, Peter; Albiin, Nils; Brismar, Torkel B. [Karolinska University Hospital, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm (Sweden); Leidner, Bertil; Svensson, Anders [Karolinska University Hospital, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm (Sweden); Karolinska University Hospital Huddinge, Department of Radiology, Stockholm (Sweden)

2014-01-15

To assess feasibility and image quality (IQ) of a new post-processing algorithm for retrospective extraction of an optimised multi-phase CT (time-resolved CT) of the liver from volumetric perfusion imaging. Sixteen patients underwent clinically indicated perfusion CT using 4D spiral mode of dual-source 128-slice CT. Three image sets were reconstructed: motion-corrected and noise-reduced (MCNR) images derived from 4D raw data; maximum and average intensity projections (time MIP/AVG) of the arterial/portal/portal-venous phases and all phases (total MIP/ AVG) derived from retrospective fusion of dedicated MCNR split series. Two readers assessed the IQ, detection rate and evaluation time; one reader assessed image noise and lesion-to-liver contrast. Time-resolved CT was feasible in all patients. Each post-processing step yielded a significant reduction of image noise and evaluation time, maintaining lesion-to-liver contrast. Time MIPs/AVGs showed the highest overall IQ without relevant motion artefacts and best depiction of arterial and portal/portal-venous phases respectively. Time MIPs demonstrated a significantly higher detection rate for arterialised liver lesions than total MIPs/AVGs and the raw data series. Time-resolved CT allows data from volumetric perfusion imaging to be condensed into an optimised multi-phase liver CT, yielding a superior IQ and higher detection rate for arterialised liver lesions than the raw data series. (orig.)

Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

International Nuclear Information System (INIS)

Sedlakova, A.; Ahlers, I.; Praslicka, M.

1981-01-01

Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1- 14 C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U- 14 C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime. (author)

Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

Energy Technology Data Exchange (ETDEWEB)

Sedlakova, A; Ahlers, I; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

1981-01-01

Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1-/sup 14/C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U-/sup 14/C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime.

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

Science.gov (United States)

Rodrigues, Angélica Heringer; Moreira, Carolina Campos Lima; Neves, Maria José; Botion, Leida Maria; Chaves, Valéria Ernestânia

2018-06-01

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets. Copyright © 2018. Published by Elsevier Inc.

Myocardial regeneration potential of adipose tissue-derived stem cells

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Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

2010-10-22

Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

Myocardial regeneration potential of adipose tissue-derived stem cells

International Nuclear Information System (INIS)

Bai, Xiaowen; Alt, Eckhard

2010-01-01

Research highlights: → Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. → For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. → This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying

Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

International Nuclear Information System (INIS)

Chen, Qi-Liang; Luo, Zhi; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

2013-01-01

Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

Energy Technology Data Exchange (ETDEWEB)

Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

2013-07-15

Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells.

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Lee, Sang Chul; Kim, Kee-Hwan; Kim, Ok-Hee; Lee, Sang Kuon; Hong, Ha-Eun; Won, Seong Su; Jeon, Sang-Jin; Choi, Byung Jo; Jeong, Wonjun; Kim, Say-June

2017-08-03

A hypoxic-preconditioned secretome from stem cells reportedly promotes the functional and regenerative capacity of the liver more effectively than a control secretome. However, the optimum oxygen partial pressure (pO 2 ) in the cell culture system that maximizes the therapeutic potential of the secretome has not yet been determined. We first determined the cellular alterations in adipose tissue-derived stem cells (ASCs) cultured under different pO 2 (21%, 10%, 5%, and 1%). Subsequently, partially hepatectomized mice were injected with the secretome of ASCs cultured under different pO 2 , and then sera and liver specimens were obtained for analyses. Of all AML12 cells cultured under different pO 2 , the AML12 cells cultured under 1% pO 2 showed the highest mRNA expression of proliferation-associated markers (IL-6, HGF, and VEGF). In the cell proliferation assay, the AML12 cells cultured with the secretome of 1% pO 2 showed the highest cell proliferation, followed by the cells cultured with the secretome of 21%, 10%, and 5% pO 2 , in that order. When injected into the partially hepatectomized mice, the 1% pO 2 secretome most significantly increased the number of Ki67-positive cells, reduced serum levels of proinflammatory mediators (IL-6 and TNF-α), and reduced serum levels of liver transaminases. In addition, analysis of the liver specimens indicated that injection with the 1% pO 2 secretome maximized the expression of the intermediate molecules of the PIP3/Akt and IL-6/STAT3 signaling pathways, all of which are known to promote liver regeneration. The data of this study suggest that the secretome of ASCs cultured under 1% pO 2 has the highest liver reparative and regenerative potential of all the secretomes tested here.

WE-AB-303-05: Breathing Motion of Liver Segments From Fiducial Tracking During Robotic Radiosurgery and Comparison with 4D-CT-Derived Fiducial Motion

International Nuclear Information System (INIS)

Sutherland, J; Pantarotto, J; Nair, V; Cook, G; Plourde, M; Vandervoort, E

2015-01-01

Purpose: To quantify respiratory-induced motion of liver segments using the positions of implanted fiducials during robotic radiosurgery. This study also compared fiducial motion derived from four-dimensional computed tomography (4D-CT) maximum intensity projections (MIP) with motion derived from imaging during treatment. Methods: Forty-two consecutive liver patients treated with liver ablative radiotherapy were accrued to an ethics approved retrospective study. The liver segment in which each fiducial resided was identified. Fiducial positions throughout each treatment fraction were determined using orthogonal kilovoltage images. Any data due to patient repositioning or motion was removed. Mean fiducial positions were calculated. Fiducial positions beyond two standard deviations of the mean were discarded and remaining positions were fit to a line segment using least squares minimization (LSM). For eight patients, fiducial motion was derived from 4D-CT MIPs by calculating the CT number weighted mean position of the fiducial on each slice and fitting a line segment to these points using LSM. Treatment derived fiducial trajectories were corrected for patient rotation and compared to MIP derived trajectories. Results: The mean total magnitude of fiducial motion across all liver segments in left-right, anteroposterior, and superoinferior (SI) directions were 3.0 ± 0.2 mm, 9.3 ± 0.4 mm, and 20.5 ± 0.5 mm, respectively. Differences in per-segment mean fiducial motion were found with SI motion ranging from 12.6 ± 0.8 mm to 22.6 ± 0.9 mm for segments 3 and 8, respectively. Large, varied differences between treatment and MIP derived motion at simulation were found with the mean difference for SI motion being 2.6 mm (10.8 mm standard deviation). Conclusion: The magnitude of liver fiducial motion was found to differ by liver segment. MIP derived liver fiducial motion differed from motion observed during treatment, implying that 4D-CTs may not accurately capture the

WE-AB-303-05: Breathing Motion of Liver Segments From Fiducial Tracking During Robotic Radiosurgery and Comparison with 4D-CT-Derived Fiducial Motion

Energy Technology Data Exchange (ETDEWEB)

Sutherland, J; Pantarotto, J; Nair, V; Cook, G; Plourde, M; Vandervoort, E [The Ottawa Hospital Cancer Centre, Ottawa, Ontario (Canada)

2015-06-15

Purpose: To quantify respiratory-induced motion of liver segments using the positions of implanted fiducials during robotic radiosurgery. This study also compared fiducial motion derived from four-dimensional computed tomography (4D-CT) maximum intensity projections (MIP) with motion derived from imaging during treatment. Methods: Forty-two consecutive liver patients treated with liver ablative radiotherapy were accrued to an ethics approved retrospective study. The liver segment in which each fiducial resided was identified. Fiducial positions throughout each treatment fraction were determined using orthogonal kilovoltage images. Any data due to patient repositioning or motion was removed. Mean fiducial positions were calculated. Fiducial positions beyond two standard deviations of the mean were discarded and remaining positions were fit to a line segment using least squares minimization (LSM). For eight patients, fiducial motion was derived from 4D-CT MIPs by calculating the CT number weighted mean position of the fiducial on each slice and fitting a line segment to these points using LSM. Treatment derived fiducial trajectories were corrected for patient rotation and compared to MIP derived trajectories. Results: The mean total magnitude of fiducial motion across all liver segments in left-right, anteroposterior, and superoinferior (SI) directions were 3.0 ± 0.2 mm, 9.3 ± 0.4 mm, and 20.5 ± 0.5 mm, respectively. Differences in per-segment mean fiducial motion were found with SI motion ranging from 12.6 ± 0.8 mm to 22.6 ± 0.9 mm for segments 3 and 8, respectively. Large, varied differences between treatment and MIP derived motion at simulation were found with the mean difference for SI motion being 2.6 mm (10.8 mm standard deviation). Conclusion: The magnitude of liver fiducial motion was found to differ by liver segment. MIP derived liver fiducial motion differed from motion observed during treatment, implying that 4D-CTs may not accurately capture the

Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

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Stephanie C Burke Schinkel

Full Text Available Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared. In blood, IL-7 receptor α (CD127 expression on bulk CD8+ T-cells in HCV infection was no different than controls yet was lower on central memory T-cells, and there were fewer naïve cells. IL-7-induced signalling through phosphorylated STAT5 was lower in HCV infection than in controls, and differed between CD8+ T-cell subsets. Production of Bcl-2 following IL-7 stimulation was also lower in HCV infection and inversely related to the degree of liver fibrosis. In liver-derived CD8+ T-cells, STAT5 activation could not be increased with cytokine stimulation and basal Bcl-2 levels of liver-derived CD8+ T-cells were lower than blood-derived counterparts in HCV infection. Therefore, generalized CD8+ T-cell impairment in HCV infection is characterized, in part, by impaired IL-7-mediated signalling and survival, independent of CD127 expression. This impairment is more pronounced in the liver and may be associated with an increased potential for apoptosis. This generalized CD8+ T-cell impairment represents an important immune dysfunction in chronic HCV infection that may alter patient health.

Fasting for 21days leads to changes in adipose tissue and liver physiology in juvenile checkered garter snakes (Thamnophis marcianus).

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Davis, Mary; Jessee, Renee; Close, Matthew; Fu, Xiangping; Settlage, Robert; Wang, Guoqing; Cline, Mark A; Gilbert, Elizabeth R

2015-12-01

Snakes often undergo periods of prolonged fasting and, under certain conditions, can survive years without food. Despite this unique phenomenon, there are relatively few reports of the physiological adaptations to fasting in snakes. At post-prandial day 1 (fed) or 21 (fasting), brain, liver, and adipose tissues were collected from juvenile checkered garter snakes (Thamnophis marcianus). There was greater glycerol-3-phosphate dehydrogenase (G3PDH)-specific activity in the liver of fasted than fed snakes (P=0.01). The mRNA abundance of various fat metabolism-associated factors was measured in brain, liver, and adipose tissue. Lipoprotein lipase (LPL) mRNA was greater in fasted than fed snakes in the brain (P=0.04). Adipose triglyceride lipase (ATGL; P=0.006) mRNA was greater in the liver of fasted than fed snakes. In adipose tissue, expression of peroxisome proliferator-activated receptor (PPAR)γ (P=0.01), and fatty acid binding protein 4 (P=0.03) was greater in fed than fasted snakes. Analysis of adipocyte morphology revealed that cross-sectional area (P=0.095) and diameter (P=0.27) were not significantly different between fed and fasted snakes. Results suggest that mean adipocyte area can be preserved during fasting by dampening lipid biosynthesis while not changing rates of lipid hydrolysis. In the liver, however, extensive lipid remodeling may provide energy and lipoproteins to maintain lipid structural integrity during energy restriction. Because the duration of fasting was not sufficient to change adipocyte size, results suggest that the liver is important as a short-term provider of energy in the snake. Copyright © 2015 Elsevier Inc. All rights reserved.

Increase of infiltrating monocytes in the livers of patients with chronic liver diseases.

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Huang, Rui; Wu, Hongyan; Liu, Yong; Yang, Chenchen; Pan, Zhiyun; Xia, Juan; Xiong, Yali; Wang, Guiyang; Sun, Zhenhua; Chen, Jun; Yan, Xiaomin; Zhang, Zhaoping; Wu, Chao

2016-01-01

Infiltrating monocytes have been demonstrated to contribute to tissue damage in experimental models of liver injury and fibrosis. However, less is known about monocyte infiltration in the livers of patients with chronic liver diseases (CLD). In the present study, we demonstrated that CD68+ hepatic macrophages and MAC387+ infiltrating monocytes were significantly increased in the livers of CLD patients with different etiologies as compared with normal liver tissue. In addition, CLD patients with higher inflammatory grading scores had more CD68+ macrophages and MAC387+ monocytes infiltration in their livers compared to those with lower scores. Significantly more MAC387+ infiltrating monocytes were found in the liver tissue of CLD patients with higher fibrotic staging scores compared to those with lower scores. Monocyte chemoattractant protein-1 (MCP-1) expression was significantly increased in the livers of CLD patients with different etiologies. MCP-1 staining scores were significantly positively associated with the numbers of MAC387+ infiltrating monocytes in CLD patients. Taken together, our results demonstrate that infiltrating monocytes may play a pathological role in exacerbating chronic liver inflammation and fibrosis in CLD. MCP-1 may be involved in the monocyte infiltration and progression of liver inflammation and fibrosis in CLD.

Study of Fe, Zn, Cu, Cd, Pb concentrations in liver, kidney and muscle tissue of cow and sheep marketed in Hamedan in 2011

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S Sobhanardakani

2012-11-01

Full Text Available Importance of heavy metals in food safety and detrimental effects of their high concentrations in food stuff is well documented. In this study, concentrations of Fe, Zn, Cu, Cd and Pb in kidney, liver and muscle tissues of cow and sheep at Hamedan retails were evaluated. A total number of 180 samples was assessed for the amount of heavy metals as ppb in wet weight. For this, wet-digestion method was used to determine the concentration of given elements by ICP (Varian ES-710. Results showed that the highest concentration of heavy metals was determined in the liver and kidney samples, while the lowest concentration was found in muscle tissue. Among the heavy metals, Fe in cow’s liver had the highest concentration (25507±879 ppb and Cd in muscle tissue of sheep has the lowest concentration (192±54 ppb. In overall, accumulation of heavy metals in tissues of cows was higher than sheep. Statistical comparison of accumulated metals concentration in various tissues of these two animal groups showed significant difference (P

Experimental study on ablating goat liver tissue with ultrasound imaging guided percutaneous irreversible electroporation

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Ying LIU

2011-03-01

Full Text Available Objective To investigate the proper method of percutaneous irreversible electroporation(IRE to ablate goat liver tissue under ultrasonic guidance,and observe the features of ultrasound imaging and histological changes.Methods The pulse electric fields(PEFs with permanent duration(100 μs,frequency(1Hz,voltage(2000V and pulses(120 pieces were applied to the electrodes,and the electrodes were placed into goats’ liver under ultrasound guidance through the animal skin to the target area.The treated area was observed by real-time ultrasound scanning,and the histopathological changes were assessed by hematoxylin and eosin(HE staining under light microscope at the time of 0h and 24h after IRE ablation.The circumscribed ablated area was compared with that of finite element modeling(FEM calculation method.Results Ultrasound imaging guidance was accurate in focusing on the target area.Imaging captured by the ultrasound after IRE procedure was quite different from that of the normal liver imaging.Complete hepatic cell death with a sharp demarcation between the ablated zone and the non-ablated zone was well visualized 24 hours after the procedure.Necrospy-based measurement demonstrated a high consistence with FEM-anticipated ablation zones.Conclusion With real-time monitoring by ultrasonography and well-controlled ablation of the target tissue,percutaneous IRE can provide a novel and unique ablative method for cancer treatment.The present paper provides a fundamental experimental work for future studies on clinical application of IRE.

Up-regulation of calreticulin in mouse liver tissues after long-term irradiation with low-dose-rate gamma rays.

Science.gov (United States)

Yi, Lan; Hu, Nan; Yin, Jie; Sun, Jing; Mu, Hongxiang; Dai, Keren; Ding, Dexin

2017-01-01

The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ≥ 1.5-fold changes in expression. Twenty-three proteins were selected based on ≥2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.

Soapwort extract supplementation alters antioxidant status of serum, liver and heart tissues in growing Japanese quails reared under chronic intermittent cold stress

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Bestami Dalkilic

2017-01-01

Full Text Available Antioxidant effect of dietary soapwort extract supplementation was studied in growing Japanese quails suffering from chronic intermittent cold stress. For this purpose, a total of ninety 15-d-old quails were divided into three groups with three replicates. Chronic intermittent cold stress was applied every night between 22.00 to 06.00 h; starting at 14 °C for the first week, and gradually weekly lowered to 8 °C. Three groups were fed with corn-soy based standard diets supplemented with 0, 50, and 100 ppm soapwort extract for four weeks. At the end of the study, three males and three females were slaughtered to determine total antioxidant and oxidant status of serum, malondialdehyde, glutathione, glutathione peroxidase activity, superoxide dismutase of liver and heart tissues. Although the dietary soapwort extract had no effect on serum total antioxidant capacity, it significantly lowered the total oxidant status of serum in cold stressed quails. Glutathione and superoxide dismutase enzyme activity of liver and heart tissues were similar among groups. While the dietary soapwort extract had no effect on glutathione peroxidase activity of the heart tissue, it significantly increased glutathione peroxidase activity in the liver tissue. In relation to the control group, malondialdehyde concentrations in the liver and heart tissues were significantly lower in soapwort extract groups. These data suggest that dietary soapwort extract could alleviate the detrimental effects of oxidative stress in growing Japanese quails exposed to cold stress.

Diagnostic value of real-time tissue elastography for liver fibrosis in patients with chronic hepatitis B

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ZHANG Guosheng

2014-07-01

Full Text Available ObjectiveTo investigate the diagnostic value of real-time tissue elastography (RTE in evaluating liver fibrosis in patients with chronic hepatitis B (CHB. MethodsEighty-six patients with CHB, who visited Beijing Tiantan Hospital and Beijing You′an Hospital from March to August, 2013, were grouped according to the pathological stages of liver fibrosis. They were examined by RTE, biochemical tests, and liver biopsy. Then, liver fibrosis index (LFI and aspartate aminotransferase-to-platelet ratio index (APRI were calculated. Comparison between groups was made by one-way analysis of variance, followed by LSD t-test for multiple comparisons. The correlation between LFI and pathological stage of liver fibrosis was analyzed by Spearman correlation test. The sensitivity and specificity of LFI for the diagnosis of liver fibrosis were calculated. Regarding S≥2 (significant liver fibrosis and S≥4 (early liver cirrhosis as the positive standards, the receiver operating characteristic (ROC curve was drawn and compared with APRI. ResultsLFI differed significantly across the groups (P=0.000, except the comparison between S0 and S1 (P=0.298. LFI was significantly correlated with pathological stage (r=0.831, P＜0.001. The areas under the ROC curve of LFI in diagnosing significant liver fibrosis and early liver cirrhosis were 0873 (P＜0.001 and 0.923 (P=0002, respectively; the diagnostic thresholds were 2.74 and 3.61, respectively; the sensitivity and specificity were 0.766/0.872 and 0.833/0.878, respectively. LFI was significantly superior to APRI. ConclusionRTE has high diagnostic values for significant liver fibrosis and early liver cirrhosis and is an important noninvasive diagnostic method for liver fibrosis in patients with CHB.

Marine-derived collagen biomaterials from echinoderm connective tissues

KAUST Repository

Ferrario, Cinzia; Leggio, Livio; Leone, Roberta; Di Benedetto, Cristiano; Guidetti, Luca; Coccè , Valentina; Ascagni, Miriam; Bonasoro, Francesco; La Porta, Caterina A.M.; Candia Carnevali, M. Daniela; Sugni, Michela

2016-01-01

The use of marine collagens is a hot topic in the field of tissue engineering. Echinoderms possess unique connective tissues (Mutable Collagenous Tissues, MCTs) which can represent an innovative source of collagen to develop collagen barrier-membranes for Guided Tissue Regeneration (GTR). In the present work we used MCTs from different echinoderm models (sea urchin, starfish and sea cucumber) to produce echinoderm-derived collagen membranes (EDCMs). Commercial membranes for GTR or soluble/reassembled (fibrillar) bovine collagen substrates were used as controls. The three EDCMs were similar among each other in terms of structure and mechanical performances and were much thinner and mechanically more resistant than the commercial membranes. Number of fibroblasts seeded on sea-urchin membranes were comparable to the bovine collagen substrates. Cell morphology on all EDCMs was similar to that of structurally comparable (reassembled) bovine collagen substrates. Overall, echinoderms, and sea urchins particularly, are alternative collagen sources to produce efficient GTR membranes. Sea urchins display a further advantage in terms of eco-sustainability by recycling tissues from food wastes.

Marine-derived collagen biomaterials from echinoderm connective tissues

KAUST Repository

Ferrario, Cinzia

2016-03-31

The use of marine collagens is a hot topic in the field of tissue engineering. Echinoderms possess unique connective tissues (Mutable Collagenous Tissues, MCTs) which can represent an innovative source of collagen to develop collagen barrier-membranes for Guided Tissue Regeneration (GTR). In the present work we used MCTs from different echinoderm models (sea urchin, starfish and sea cucumber) to produce echinoderm-derived collagen membranes (EDCMs). Commercial membranes for GTR or soluble/reassembled (fibrillar) bovine collagen substrates were used as controls. The three EDCMs were similar among each other in terms of structure and mechanical performances and were much thinner and mechanically more resistant than the commercial membranes. Number of fibroblasts seeded on sea-urchin membranes were comparable to the bovine collagen substrates. Cell morphology on all EDCMs was similar to that of structurally comparable (reassembled) bovine collagen substrates. Overall, echinoderms, and sea urchins particularly, are alternative collagen sources to produce efficient GTR membranes. Sea urchins display a further advantage in terms of eco-sustainability by recycling tissues from food wastes.

Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

NARCIS (Netherlands)

Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos.

Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

Science.gov (United States)

Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

2017-03-01

Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency. Copyright © 2017 Elsevier GmbH. All rights reserved.

Sequential use of human-derived medium supplements favours cardiovascular tissue engineering

NARCIS (Netherlands)

Riem Vis, P.W.; Sluijter, J.P.G.; Soekhradj - Soechit, R.S.; Herwerden, van L.A.; Kluin, J.; Bouten, C.V.C.

2012-01-01

For clinical application of tissue engineering strategies, the use of animal-derived serum in culture medium is not recommended, because it can evoke immune responses in patients. We previously observed that human platelet-lysate (PL) is favourable for cell expansion, but generates weaker tissue as

FT-IR imaging for quantitative determination of liver fat content in non-alcoholic fatty liver.

Science.gov (United States)

Kochan, K; Maslak, E; Chlopicki, S; Baranska, M

2015-08-07

In this work we apply FT-IR imaging of large areas of liver tissue cross-section samples (∼5 cm × 5 cm) for quantitative assessment of steatosis in murine model of Non-Alcoholic Fatty Liver (NAFLD). We quantified the area of liver tissue occupied by lipid droplets (LDs) by FT-IR imaging and Oil Red O (ORO) staining for comparison. Two alternative FT-IR based approaches are presented. The first, straightforward method, was based on average spectra from tissues and provided values of the fat content by using a PLS regression model and the reference method. The second one – the chemometric-based method – enabled us to determine the values of the fat content, independently of the reference method by means of k-means cluster (KMC) analysis. In summary, FT-IR images of large size liver sections may prove to be useful for quantifying liver steatosis without the need of tissue staining.

Proteinase activated receptor 1 mediated fibrosis in a mouse model of liver injury: a role for bone marrow derived macrophages.

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Yiannis N Kallis

Full Text Available Liver fibrosis results from the co-ordinated actions of myofibroblasts and macrophages, a proportion of which are of bone marrow origin. The functional effect of such bone marrow-derived cells on liver fibrosis is unclear. We examine whether changing bone marrow genotype can down-regulate the liver's fibrotic response to injury and investigate mechanisms involved. Proteinase activated receptor 1 (PAR1 is up-regulated in fibrotic liver disease in humans, and deficiency of PAR1 is associated with reduced liver fibrosis in rodent models. In this study, recipient mice received bone marrow transplantation from PAR1-deficient or wild-type donors prior to carbon tetrachloride-induced liver fibrosis. Bone marrow transplantation alone from PAR1-deficient mice was able to confer significant reductions in hepatic collagen content and activated myofibroblast expansion on wild-type recipients. This effect was associated with a decrease in hepatic scar-associated macrophages and a reduction in macrophage recruitment from the bone marrow. In vitro, PAR1 signalling on bone marrow-derived macrophages directly induced their chemotaxis but did not stimulate proliferation. These data suggest that the bone marrow can modulate the fibrotic response of the liver to recurrent injury. PAR1 signalling can contribute to this response by mechanisms that include the regulation of macrophage recruitment.

A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.

Science.gov (United States)

Sierro, Frederic; Evrard, Maximilien; Rizzetto, Simone; Melino, Michelle; Mitchell, Andrew J; Florido, Manuela; Beattie, Lynette; Walters, Shaun B; Tay, Szun Szun; Lu, Bo; Holz, Lauren E; Roediger, Ben; Wong, Yik Chun; Warren, Alessandra; Ritchie, William; McGuffog, Claire; Weninger, Wolfgang; Le Couteur, David G; Ginhoux, Florent; Britton, Warwick J; Heath, William R; Saunders, Bernadette M; McCaughan, Geoffrey W; Luciani, Fabio; MacDonald, Kelli P A; Ng, Lai Guan; Bowen, David G; Bertolino, Patrick

2017-08-15

The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

Top-Down and Bottom-Up Identification of Proteins by Liquid Extraction Surface Analysis Mass Spectrometry of Healthy and Diseased Human Liver Tissue

Science.gov (United States)

Sarsby, Joscelyn; Martin, Nicholas J.; Lalor, Patricia F.; Bunch, Josephine; Cooper, Helen J.

2014-09-01

Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15-25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies.

Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model.

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Jiamin Zhang

Full Text Available Liver damage caused by radiotherapy is associated with a high mortality rate, but no established treatment exists. Adipose-derived mesenchymal stem cells (ADSCs are capable of migration to injured tissue sites, where they aid in the repair of the damage. Hepatocyte growth factor (HGF is critical for damage repair due to its anti-apoptotic, anti-fibrotic and cell regeneration-promoting effects. This study was performed to investigate the therapeutic effects of HGF-overexpressing ADSCs on radiation-induced liver damage (RILD. ADSCs were infected with a lentivirus encoding HGF and HGF-shRNA. Sprague-Dawley (SD rats received 60Gy of irradiation to induce liver injury and were immediately given either saline, ADSCs, ADSCs + HGF or ADSCs + shHGF. Two days after irradiation, a significant reduction in apoptosis was observed in the HGF-overexpressing ADSC group compared with the RILD group, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. Scanning electron microscopy showed chromatin condensation after irradiation, which was ameliorated in the group that received ADSCs and was reversed in the group that received HGF-overexpressing ADSCs. HGF-overexpressing ADSCs ameliorated radiation- induced liver fibrosis through down regulation of α-SMA and fibronectin. Hepatocyte regeneration was significantly improved in rats treated with ADSCs compared with rats from the RILD group, as assessed by Ki-67 immunohistochemistry. Rats that received HGF-overexpressing ADSCs showed an even greater level of hepatocyte regeneration. HGF-overexpressing ADSCs completely blocked the radiation-induced increase in the enzymes ALT and AST. The effect of mitigating RILD was compromised in the ADSC + shHGF group compared with the ADSC group. Altogether, these results suggest that HGF-overexpressing ADSCs can significantly improve RILD in a rat model, which may serve as a valuable therapeutic alternative.

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

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Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

2013-01-01

Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

Tissue inhibitor of matrix metalloproteinase-1 expression in colorectal cancer liver metastases is associated with vascular structures

DEFF Research Database (Denmark)

Illemann, Martin; Eefsen, Rikke Helene Løvendahl; Bird, Nigel Charles

2016-01-01

several proteases, involved in the degradation of extracellular matrix components, are up-regulated. In liver metastases, their expression is growth pattern dependent. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is a strong prognostic marker in plasma from colorectal cancer patients...

Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink

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Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D.; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

2016-01-01

Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types. PMID:27166839

Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink.

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Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

2016-04-21

Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types.

MicroRNA-mediated suppression of oncolytic adenovirus replication in human liver.

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Erkko Ylösmäki

Full Text Available MicroRNAs (miRNAs are important and ubiquitous regulators of gene expression that can suppress their target genes by translational inhibition as well as mRNA destruction. Cell type-specific miRNA expression patterns have been successfully exploited for targeting the expression of experimental and therapeutic gene constructs, for example to reduce pathogenic effects of cancer virotherapy in normal tissues. In order to avoid liver damage associated with systemic or intrahepatic delivery of oncolytic adenoviruses we have introduced the concept of suppressing adenovirus replication in hepatic cells by inserting target elements for the liver-specific miR122 into the viral genome. Here we show using ex vivo cultured tissue specimens that six perfectly complementary miR122 target sites in the 3' untranslated region of the viral E1A gene are sufficient in the absence of any other genetic modifications to prevent productive replication of serotype 5 adenovirus (Ad5 in normal human liver. This modification did not compromise the replicative capacity of the modified virus in cancer tissue derived from a colon carcinoma liver metastasis or its oncolytic potency in a human lung cancer xenograft mouse model. Unlike wild-type Ad5, the modified virus did not result in increased serum levels of liver enzymes in infected mice. These results provide a strong preclinical proof of concept for the use of miR122 target sites for reducing the risk of liver damage caused by oncolytic adenoviruses, and suggest that ectopic miR122 target elements should be considered as an additional safety measure included in any therapeutic virus or viral vector posing potential hazard to the liver.

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

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Kasten, Annika; Siegmund, Birte J. [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany); Grüttner, Cordula [Micromod Partikeltechnologie GmbH, Warnemünde, D-18115 Rostock (Germany); Kühn, Jens-Peter [Department of Radiology and Neuroradiology, Greifswald University Medical Center, D-17475 Greifswald (Germany); Frerich, Bernhard, E-mail: bernhard.frerich@med.uni-rostock.de [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany)

2015-04-15

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation.

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

International Nuclear Information System (INIS)

Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

2015-01-01

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation

Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite Allograft Transplantation

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2017-10-01

AWARD NUMBER: W81XWH-16-2-0042 TITLE: Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite...2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Adult Tissue-Derived Stem Cells and Tolerance Induction...Distribution Unlimited 13. SUPPLEMENTARY NOTES The utilization of adult derived adipose stem cells administration in composite tissue transplantation

Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate

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Narayanan, Sampath; Grünler, Jacob; Sunkari, Vivekananda Gupta; Calissendorff, Freja S.; Ansurudeen, Ishrath; Illies, Christopher; Svensson, Johan; Jansson, John-Olov; Ohlsson, Claes; Brismar, Kerstin; Catrina, Sergiu-Bogdan

2018-01-01

Objective IGF-I is a growth factor, which is expressed in virtually all tissues. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in wounds with low regenerative potential such as diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown. Here we investigated the role of systemic IGF-I on wound healing rate in mice with deficiency of liver-derived IGF-I (LI-IGF-I-/- mice) during normal (normoglycemic) and impaired wound healing (diabetes). Methods LI-IGF-I-/- mice with complete inactivation of the IGF-I gene in the hepatocytes were generated using the Cre/loxP recombination system. This resulted in a 75% reduction of circulating IGF-I. Diabetes was induced with streptozocin in both LI-IGF-I-/- and control mice. Wounds were made on the dorsum of the mice, and the wound healing rate and histology were evaluated. Serum IGF-I and GH were measured by RIA and ELISA respectively. The expression of IGF-I, IGF-II and the IGF-I receptor in the skin were evaluated by qRT-PCR. The local IGF-I protein expression in different cell types of the wounds during wound healing process was analyzed using immunohistochemistry. Results The wound healing rate was similar in LI-IGF-I-/- mice to that in controls. Diabetes significantly delayed the wound healing rate in both LI-IGF-I-/- and control mice. However, no significant difference was observed between diabetic animals with normal or reduced hepatic IGF-I production. The gene expression of IGF-I, IGF-II and IGF-I receptor in skin was not different between any group of animals tested. Local IGF-I levels in the wounds were similar between of LI-IGF-I-/- and WT mice although a transient reduction of IGF-I expression in leukocytes in the wounds of LI-IGF-I-/- was observed seven days post wounding. Conclusion Deficiency in the liver-derived IGF-I does not affect wound healing in mice, neither in normoglycemic conditions nor in

Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice

NARCIS (Netherlands)

Braster, Quinte; Silvestre Roig, Carlos; Hartwig, Helene; Beckers, Linda; den Toom, Myrthe; Döring, Yvonne; Daemen, Mat J.; Lutgens, Esther; Soehnlein, Oliver

2016-01-01

Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of

NS3 protease resistance-associated substitutions in liver tissue and plasma samples from patients infected by hepatitis C virus genotype 1A or 1B.

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Morsica, Giulia; Andolina, Andrea; Merli, Marco; Messina, Emanuela; Hasson, Hamid; Lazzarin, Adriano; Uberti-Foppa, Caterina; Bagaglio, Sabrina

2017-08-01

The presence of naturally occurring resistance-associated substitutions (RASs) in the HCV-protease domain has been poorly investigated in the liver, the main site of HCV replication. We evaluated the natural resistance of the virus to NS3 protease inhibitors in liver tissue and plasma samples taken from HCV-infected patients. RASs were investigated by means of viral population sequencing in liver tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype 1b; plasma samples from 12 of these patients were also available for virological investigation. A discordant genotype was found in two of the 12 patients (16.6%) who provided samples from both compartments. Sequence analysis of the NS3 protease domain showed the presence of RASs in four of the 18 liver tissue samples (22.2%), two of which showed cross-resistance to protease inhibitors in clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and plasma samples excluded the presence of RASs in the plasma compartment. The dominance of discordant genotypes in the paired liver and plasma samples of some HCV-infected patients suggests mixed infection possibly leading to the selective advantage of different genotype in the two compartments. The presence of RASs at intra-hepatic level is not uncommon and may lead to the early emergence of cross-resistant strains.

Review fantastic medical implications of 3D-printing in liver surgeries, liver regeneration, liver transplantation and drug hepatotoxicity testing: A review.

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Wang, Jing-Zhang; Xiong, Nan-Yan; Zhao, Li-Zhen; Hu, Jin-Tian; Kong, De-Cheng; Yuan, Jiang-Yong

2018-06-07

The epidemiological trend in liver diseases becomes more serious worldwide. Several recent articles published by International Journal of Surgery in 2018 particularly emphasized the encouraging clinical benefits of hepatectomy, liver regeneration and liver transplantation, however, there are still many technical bottlenecks underlying these therapeutic approaches. Remarkably, a few preliminary studies have shown some clues to the role of three-dimensional (3D) printing in improving traditional therapy for liver diseases. Here, we concisely elucidated the curative applications of 3D-printing (no cells) and 3D Bio-printing (with hepatic cells), such as 3D-printed patient-specific liver models and devices for medical education, surgical simulation, hepatectomy and liver transplantation, 3D Bio-printed hepatic constructs for liver regeneration and artificial liver, 3D-printed liver tissues for evaluating drug's hepatotoxicity, and so on. Briefly, 3D-printed liver models and bioactive tissues may facilitate a lot of key steps to cure liver disorders, predictably bringing promising clinical benefits. This work further provides novel insights into facilitating treatment of hepatic carcinoma, promoting liver regeneration both in vivo and in vitro, expanding transplantable liver resources, maximizing therapeutic efficacy as well as minimizing surgical complications, medical hepatotoxicity, operational time, economic costs, etc. Copyright © 2018. Published by Elsevier Ltd.

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

OpenAIRE

Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

2017-01-01

AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was ...

Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

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Rigo, Federica; De Stefano, Nicola; Navarro-Tableros, Victor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

2018-05-01

The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

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Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

2017-01-01

Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

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Anna Kakehashi

2017-02-01

Full Text Available To uncover mechanisms of nonalcoholic steatohepatitis (NASH associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1, and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis.

Gene expression profiling and secretome analysis differentiate adult-derived human liver stem/progenitor cells and human hepatic stellate cells.

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Silvia Berardis

Full Text Available Adult-derived human liver stem/progenitor cells (ADHLSC are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC derived from the liver non-parenchymal fraction, present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity. ADHLSC and HSC were isolated from the liver of four different donors, expanded in vitro and followed from passage 5 until passage 11. Cell characterization was performed using immunocytochemistry, western blotting, flow cytometry, and gene microarray analyses. The secretion profile of the cells was evaluated using Elisa and multiplex Luminex assays. Both cell types expressed α-smooth muscle actin, vimentin, fibronectin, CD73 and CD90 in accordance with their mesenchymal origin. Microarray analysis revealed significant differences in gene expression profiles. HSC present high expression levels of neuronal markers as well as cytokeratins. Such differences were confirmed using immunocytochemistry and western blotting assays. Furthermore, both cell types displayed distinct secretion profiles as ADHLSC highly secreted cytokines of therapeutic and immuno-modulatory importance, like HGF, interferon-γ and IL-10. Our study demonstrates that ADHLSC and HSC are distinct liver fibroblastic cell populations exhibiting significant different expression and secretion profiles.

Testing an aflatoxin B1 gene signature in rat archival tissues.

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Merrick, B Alex; Auerbach, Scott S; Stockton, Patricia S; Foley, Julie F; Malarkey, David E; Sills, Robert C; Irwin, Richard D; Tice, Raymond R

2012-05-21

Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 μg of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ≤ 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and β-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced

Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

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Sabrina Le Bouter

2010-01-01

Full Text Available Rosiglitazone (RSG, developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d with untreated non-diabetic littermates (db/+. For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs and free fatty acids (FFAs in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.

Effect of selective hepatic inflow occlusion during liver cancer resection on liver ischemia-reperfusion injury

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Yin-Tian Deng

2016-11-01

Full Text Available Objective: To study the effect of selective hepatic inflow occlusion during liver cancer resection on liver ischemia-reperfusion injury. Methods: A total of 68 patients with primary liver cancer who underwent left liver resection in our hospital between May 2012 and August 2015 were selected for study and divided into group A (selective hepatic inflow occlusion of left liver and group B (Prignle hepatic inflow occlusion according to different intraoperative blood occlusion methods, serum was collected before and after operation to determine liver enzyme content, the removed liver tissue was collected to determine energy metabolism indexes, inflammation indexes and oxidative stress indexes. Results: 1 d, 3 d and 5 d after operation, GPT, GOT, GGT, LDH and ALP content in serum of both groups were significantly higher than those before operation, and GPT, GOT, GGT, LDH and ALP content in serum of group A 1 d, 3 d and 5 d after operation were significantly lower than those of group B; ATP, ADP, AMP, PI3K, AKT, GSK3β, T-AOC, PrxI and Trx content in liver tissue of group A were significantly higher than those of group B while PTEN, IL-12p40, MDA and MPO content were significantly lower than those of group B. Conclusions: Selective hepatic inflow occlusion during liver cancer resection can reduce the liver ischemia-reperfusion injury, improve the energy metabolism of liver cells and inhibit inflammation and oxidative stress in liver tissue.

The effects of comfrey derived pyrrolizidine alkaloids on rat liver.

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Yeong, M L; Clark, S P; Waring, J M; Wilson, R D; Wakefield, S J

1991-01-01

Three groups of young adult rats were fed pyrrolizidine alkaloids derived from Russian comfrey to study the effects of the herb on the liver. Group I animals received a single dose of 200 mg/kg body wt, Group II 100 mg/kg three times a week for 3 weeks and Group III 50 mg/kg three times a week for 3 weeks. All rats showed light and electron-microscopic evidence of liver damage, the severity of which was dose dependent. There was swelling of hepatocytes and hemorrhagic necrosis of perivenular cells. There was a concomitant loss of sinusoidal lining cells with disruption of sinusoidal wall and the sinusoids were filled with cellular debris, hepatocyte organelles and red blood cells. Extravasation of red blood cells was evident. Terminal hepatic venules were narrowed by intimal proliferation, and in Group II and III, reiculin fibres radiated from these vessels. These appearances have been described in veno-occlusive disease due to pyrrolizidine alkaloids from other plant sources such as Senecio and Crotalaria. The safety of comfrey, a widely used herb, in relation to human consumption requires further investigation.

The effect of ZnO Nps of 20 nm on changes of enzyme and liver tissues of pregnant NMRI mice

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bager Seyed Alipour

2015-01-01

Full Text Available Background :Nowadays, nanotechnology has been developing rapidly and may have considerable effects on industry, society and the environment. In this research the toxicity properties of zinc oxide nanoparticles with a size of 20 nm on enzyme and liver tissue of NMRI mice were studied. Materials and Methods: This experimental study was performed in standard conditions on 25 NMRI mice with an average weight of 30 ± 3 g so that they received different doses of zinc oxide nanoparticles, an a days, for 15 days intraperitoneally. Then, blood samples were taken on day 17 of NMRI mice. The collected tissues were washed with saline and fixed in Boin΄s fluied buffer and stained with hematoxylin and eosin for histopathology evaluation. After data collection, statistical analysis was done using SAS software. Results: The results showed that activity of ALT enzyme at concentrations 50, 100, 150 and 200 mg/kg ZnO Nps at a significant level (p<0.05 increased in comparison with the control group. Histopathological investigation showed that zinc oxide nanoparticles caused severe damage in liver. Damaged liver cells develop leaky membranes and escape of intracellular enzymes into the bloodstream. Conclusion: Our findings showed that using different concentration of zinc oxide nanoparticles could be caused undesirable effects on liver with damage to hepatocyte and level elevation of liver enzymes.

Blood cell oxidative stress precedes hemolysis in whole blood-liver slice co-cultures of rat, dog, and human tissues

International Nuclear Information System (INIS)

Vickers, Alison E.M.; Sinclair, John R.; Fisher, Robyn L.; Morris, Stephen R.; Way, William

2010-01-01

A novel in vitro model to investigate time-dependent and concentration-dependent responses in blood cells and hemolytic events is studied for rat, dog, and human tissues. Whole blood is co-cultured with a precision-cut liver slice. Methimazole (MMI) was selected as a reference compound, since metabolism of its imidazole thione moiety is linked with hematologic disorders and hepatotoxicity. An oxidative stress response occurred in all three species, marked by a decline in blood GSH levels by 24 h that progressed, and preceded hemolysis, which occurred at high MMI concentrations in the presence of a liver slice with rat (≥ 1000 μM at 48 h) and human tissues (≥ 1000 μM at 48 h, ≥ 750 μM at 72 h) but not dog. Human blood-only cultures exhibited a decline of GSH levels but minimal to no hemolysis. The up-regulation of liver genes for heme degradation (Hmox1 and Prdx1), iron cellular transport (Slc40a1), and GSH synthesis and utilization (mGST1 and Gclc) were early markers of the oxidative stress response. The up-regulation of the Kupffer cell lectin Lgals3 gene expression indicated a response to damaged red blood cells, and Hp (haptoglobin) up-regulation is indicative of increased hemoglobin uptake. Up-regulation of liver IL-6 and IL-8 gene expression suggested an activation of an inflammatory response by liver endothelial cells. In summary, MMI exposure led to an oxidative stress response in blood cells, and an up-regulation of liver genes involved with oxidative stress and heme homeostasis, which was clearly separate and preceded frank hemolysis.

Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

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Masoudi, E.A.; Ribas, J.; Kaushik, G.; Leijten, Jeroen Christianus Hermanus; Khademhosseini, A.

2016-01-01

Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives,

Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies

NARCIS (Netherlands)

Jurgens, W.J.F.M.; Oedayrajsingh-Varma, M.J.; Helder, M.N.; Zandieh Doulabi, B.; Schouten, T.E.; Kuik, D.J.; Ritt, M.J.P.F.; van Milligen-Kummer, F.J.

2008-01-01

The stromal vascular fraction (SVF) of adipose tissue contains an abundant population of multipotent adipose-tissue-derived stem cells (ASCs) that possess the capacity to differentiate into cells of the mesodermal lineage in vitro. For cell-based therapies, an advantageous approach would be to

Histopathological Study of Protective Effects of Honey on Subacute Toxicity of Acrylamide-Induced Tissue Lesions in Rats’ Brain and Liver

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Parichehr Ahrari Roodi

2018-04-01

Full Text Available Background: The therapeutic potential of honey is related to antioxidant activity against reactive oxygen species because it contains compounds such as polyphenols; therefore, we evaluated the potential protective effect of honey on subacute toxicity of ACR by histopathologic study on tissue lesions in rat. Methods: In Ferdowsi University of Mashhad, Mashhad, Iran, 2016, male Wistar rats were divided into 7 groups. To induce toxicity, ACR was injected (50 mg/kg for 11 d to rats in 5 groups. In treatment groups, rats received three doses of honey 1.25, 2.5, and 5 g/kg in addition to the ACR. The two remaining groups received vitamin E (200 IU/kg and normal saline as positive and negative control respectively. On the last day, after necropsy, tissue specimens from brain and liver were collected for histopathological studies. Results: Receiving of ACR caused tissue injuries including degeneration, necrosis, hyperemia, hemorrhage and inflammation in liver; ischemic cell change, hyperemia, hemorrhage and edema in brain tissue. Administration of honey considerably reduced tissue damages caused by ACR, particularly with dosage 5 g/kg. Conclusion: The severity of tissue lesions caused by the ACR can be reduced by honey, likely through its antioxidant activity. Increasing concentrations of honey will enhance its effectiveness.

Liver Fibrosis: Current Principles of Diagnosis

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A.K. Duda

2014-09-01

Full Text Available Liver fibrosis — a natural consequence of almost all liver diseases of any origin. We are faced with a number of standard stereotype processes that take place in the liver tissue. Mostly it is the processes of chronic inflammation, which oppose the processes of liver tissue regeneration. The basis of imbalance between the processes of fibrosis and regeneration is an accumulation of extracellular matrix. Liver fibrosis in its development leads to liver cirrhosis, hepatocellular carcinoma, and the increase in morbidity rate is observed worldwide. Furthermore, the process is genetically determined, but modifiable factors play an important role in the progression of this disease. Current data indicate the possibility of reversible liver fibrosis.

The Interleukin-20 Cytokine Family in Liver Disease

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Esther Caparrós

2018-05-01

Full Text Available The three main causes of inflammation and chronic injury in the liver are viral hepatitis, alcohol consumption, and non-alcoholic steatohepatitis, all of which can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma, which in turn may prompt the need for liver transplant. The interleukin (IL-20 is a subfamily part of the IL-10 family of cytokines that helps the liver respond to damage and disease, they participate in the control of tissue homeostasis, and in the immunological responses developed in this organ. The best-studied member of the family in inflammatory balance of the liver is the IL-22 cytokine, which on the one hand may have a protective role in fibrosis progression but on the other may induce liver tissue susceptibility in hepatocellular carcinoma development. Other members of the family might also carry out this dual function, as some of them share IL receptor subunits and signal through common intracellular pathways. Investigators are starting to consider the potential for targeting IL-20 subfamily members in liver disease. The recently explored role of miRNA in the transcriptional regulation of IL-22 and IL-24 opens the door to promising new approaches for controlling the local immune response and limiting organ injury. The IL-20RA cytokine receptor has also been classified as being under miRNA control in non-alcoholic steatohepatitis. Moreover, researchers have proposed combining anti-inflammatory drugs with IL-22 as a hepatoprotective IL for alcoholic liver disease (ALD treatment, and clinical trials of ILs for managing severe alcoholic-derived liver degeneration are ongoing. In this review, we focus on exploring the role of the IL-20 subfamily of cytokines in viral hepatitis, ALD, non-alcoholic steatohepatitis, and hepatocellular carcinoma, as well as delineating the main strategies explored so far in terms of therapeutic possibilities of the IL-20 subfamily of cytokines in liver disease.

NKT cells act through third party bone marrow-derived cells to suppress NK cell activity in the liver and exacerbate hepatic melanoma metastases.

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Sadegh, Leila; Chen, Peter W; Brown, Joseph R; Han, Zhiqiang; Niederkorn, Jerry Y

2015-09-01

Uveal melanoma (UM) is the most common intraocular tumor in adults and liver metastasis is the leading cause of death in UM patients. We have previously shown that NKT cell-deficient mice develop significantly fewer liver metastases from intraocular melanomas than do wild-type (WT) mice. Here, we examine the interplay between liver NKT cells and NK cells in resistance to liver metastases from intraocular melanomas. NKT cell-deficient CD1d(-/-) mice and WT C57BL/6 mice treated with anti-CD1d antibody developed significantly fewer liver metastases than WT mice following either intraocular or intrasplenic injection of B16LS9 melanoma cells. The increased number of metastases in WT mice was associated with reduced liver NK cytotoxicity and decreased production of IFN-γ. However, liver NK cell-mediated cytotoxic activity was identical in non-tumor bearing NKT cell-deficient mice and WT mice, indicating that liver metastases were crucial for the suppression of liver NK cells. Depressed liver NK cytotoxicity in WT mice was associated with production of IL-10 by bone marrow-derived liver cells that were neither Kupffer cells nor myeloid-derived suppressor cells and by increased IL-10 receptor expression on liver NK cells. IL-10(-/-) mice had significantly fewer liver metastases than WT mice, but were not significantly different from NKT cell-deficient mice. Thus, development of melanoma liver metastases is associated with upregulation of IL-10 in the liver and an elevated expression of IL-10 receptor on liver NK cells. This impairment of liver NK activity is NKT cell-dependent and only occurs in hosts with melanoma liver metastases. © 2015 UICC.

The tissue residues of sodium dehydroacetate used as feed preservative in swine.

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Liu, Hao; Han, Lingling; Xie, Jiayu; Wu, Yingchao; Xie, Yang; Zhang, Yumei

2018-01-01

Sodium dehydroacetate (Na-DHA) is a food and feed additive with antimicrobial effects. There is little information on Na-DHA residue levels in foods derived from animals. In this study, Na-DHA residue levels in swine tissues were determined by HLPC, and the pharmacokinetics of Na-DHA in tissues were determined. The Na-DHA residue levels in swine tissues were liver > muscle > fat. The pharmacokinetics of Na-DHA followed a binomial regression model, and the half-time of Na-DHA in swine tissues was 9.07 days for kidney, 7.19 days for liver, 6.66 days for muscle, and 5.39 days for fat tissue. The accuracy of the HPLC method for Na-DHA determination ranged from 80.18% to 91.33% recovery, with coefficients of variation swine diet is a safe feed additive based on residue elimination and ADI values reported. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Preventive effect of halofuginone on concanavalin A-induced liver fibrosis.

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Jie Liang

Full Text Available Halofuginone (HF is an active component of extracts derived from the plant alkaloid febrifugine and has shown therapeutic promise in animal models of fibrotic disease. Our main objectives were to clarify the suppressive effect of HF on concanavalin A (ConA-induced liver fibrosis. ConA injection into the tail vein caused a great increase in the serum aspartate aminotransferase (AST and alanine aminotransferase (ALT levels, while orally administration of HF significantly decreased the levels of the transaminases. In addition, the levels of hyaluronic acid (HA, procollagen III (PCIII and TGF-β1 in the serum and collagen I, α-SMA, tissue inhibitors of metalloproteinase 2 (TIMP2 and Smad3 in the liver tissue were significantly lowered with the treatment of HF. Histological examination also demonstrated that HF significantly reduced the severity of liver fibrosis. Since ConA-induced liver fibrosis is caused by the repeated activation of T cells, immunomodulatory substances might be responsible for the suppressive effect of HF. We found that the production of nuclear factor (NF-kB in the serum was increased in ConA-treated group, while decreased significantly with the treatment of HF. The changes of inflammatory cytokines tumor necrosis factor (TNF-α, IL-6 and IL-1β in the serum followed the same rhythm. All together, our findings indicate that orally administration HF (10ppm would attenuate the liver fibrosis by suppressing the synthesis of collagen I and inflammation-mediated liver injury.

Intra-Tissue Pressure Measurement in Ex Vivo Liver Undergoing Laser Ablation with Fiber-Optic Fabry-Perot Probe

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Daniele Tosi

2016-04-01

Full Text Available We report the first-ever intra-tissue pressure measurement performed during 1064 nm laser ablation (LA of an ex vivo porcine liver. Pressure detection has been performed with a biocompatible, all-glass, temperature-insensitive Extrinsic Fabry-Perot Interferometry (EFPI miniature probe; the proposed methodology mimics in-vivo treatment. Four experiments have been performed, positioning the probe at different positions from the laser applicator tip (from 0.5 mm to 5 mm. Pressure levels increase during ablation time, and decrease with distance from applicator tip: the recorded peak parenchymal pressure levels range from 1.9 kPa to 71.6 kPa. Different pressure evolutions have been recorded, as pressure rises earlier in proximity of the tip. The present study is the first investigation of parenchymal pressure detection in liver undergoing LA: the successful detection of intra-tissue pressure may be a key asset for improving LA, as pressure levels have been correlated to scattered recurrences of tumors by different studies.

Kojyl cinnamate ester derivatives promote adiponectin production during adipogenesis in human adipose tissue-derived mesenchymal stem cells.

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Rho, Ho Sik; Hong, Soo Hyun; Park, Jongho; Jung, Hyo-Il; Park, Young-Ho; Lee, John Hwan; Shin, Song Seok; Noh, Minsoo

2014-05-01

The subcutaneous fat tissue mass gradually decreases with age, and its regulation is a strategy to develop anti-aging compounds to ameliorate the photo-aging of human skin. The adipogenesis of human adipose tissue-mesenchymal stem cells (hAT-MSCs) can be used as a model to discover novel anti-aging compounds. Cinnamomum cassia methanol extracts were identified as adipogenesis-promoting agents by natural product library screening. Cinnamates, the major chemical components of Cinnamomum cassia extracts, promoted adipogenesis in hAT-MSCs. We synthesized kojyl cinnamate ester derivatives to improve the pharmacological activity of cinnamates. Structure-activity studies of kojyl cinnamate derivatives showed that both the α,β-unsaturated carbonyl ester group and the kojic acid moiety play core roles in promoting adiponectin production during adipogenesis in hAT-MSCs. We conclude that kojyl cinnamate ester derivatives provide novel pharmacophores that can regulate adipogenesis in hAT-MSCs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Concentrations of metallic elements in kidney, liver, and lung tissue of Indo-Pacific bottlenose dolphin Tursiops aduncus from coastal waters of Zanzibar, Tanzania.

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Mapunda, Edgar C; Othman, Othman C; Akwilapo, Leonard D; Bouwman, Hindrik; Mwevura, Haji

2017-09-15

Concentrations of metallic elements in kidney, liver and lung tissues of Indo-Pacific bottlenose dolphins Tursiops aduncus from coastal waters of Zanzibar were determined using inductively coupled plasma - optical emission spectroscopy. Cadmium, chromium, copper, and zinc were quantifiable in all tissues at concentration ranges of 0.10-150, 0.08-3.2, 1.1-88 and 14-210μg/g dry mass, respectively. Copper and zinc was significantly higher in liver, and females had significantly higher Cd in liver, and chromium in lung. Generally, T. aduncus dolphins from coastal waters around Zanzibar carry low concentrations of metals compared with dolphins from other areas. Cadmium increased significantly with age in kidney and lung. Copper decreased significantly with age in liver, probably due to foetal metallothionein. This study supplied baseline data against which future trends in marine mammals in the Indian Ocean, the world's third largest, can be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Proteomic Profiles of Adipose and Liver Tissues from an Animal Model of Metabolic Syndrome Fed Purple Vegetables

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Hala M Ayoub

2018-04-01

Full Text Available Metabolic Syndrome (MetS is a complex disorder that predisposes an individual to Cardiovascular Diseases and type 2 Diabetes Mellitus. Proteomics and bioinformatics have proven to be an effective tool to study complex diseases and mechanisms of action of nutrients. We previously showed that substitution of the majority of carbohydrate in a high fat diet by purple potatoes (PP or purple carrots (PC improved insulin sensitivity and hypertension in an animal model of MetS (obese Zucker rats compared to a control sucrose-rich diet. In the current study, we used TMT 10plex mass tag combined with LC-MS/MS technique to study proteomic modulation in the liver (n = 3 samples/diet and adipose tissue (n = 3 samples/diet of high fat diet-fed rats with or without substituting sucrose for purple vegetables, followed by functional enrichment analysis, in an attempt to elucidate potential molecular mechanisms responsible for the phenotypic changes seen with purple vegetable feeding. Protein folding, lipid metabolism and cholesterol efflux were identified as the main modulated biological themes in adipose tissue, whereas lipid metabolism, carbohydrate metabolism and oxidative stress were the main modulated themes in liver. We propose that enhanced protein folding, increased cholesterol efflux and higher free fatty acid (FFA re-esterification are mechanisms by which PP and PC positively modulate MetS pathologies in adipose tissue, whereas, decreased de novo lipogenesis, oxidative stress and FFA uptake, are responsible for the beneficial effects in liver. In conclusion, we provide molecular evidence for the reported metabolic health benefits of purple carrots and potatoes and validate that these vegetables are good choices to replace other simple carbohydrate sources for better metabolic health.

Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.

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Priglinger, Eleni; Schuh, Christina M A P; Steffenhagen, Carolin; Wurzer, Christoph; Maier, Julia; Nuernberger, Sylvia; Holnthoner, Wolfgang; Fuchs, Christiane; Suessner, Susanne; Rünzler, Dominik; Redl, Heinz; Wolbank, Susanne

2017-09-01

Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Elasticity-based development of functionally enhanced multicellular 3D liver encapsulated in hybrid hydrogel.

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Lee, Ho-Joon; Son, Myung Jin; Ahn, Jiwon; Oh, Soo Jin; Lee, Mihee; Kim, Ansoon; Jeung, Yun-Ji; Kim, Han-Gyeul; Won, Misun; Lim, Jung Hwa; Kim, Nam-Soon; Jung, Cho-Rock; Chung, Kyung-Sook

2017-12-01

Current in vitro liver models provide three-dimensional (3-D) microenvironments in combination with tissue engineering technology and can perform more accurate in vivo mimicry than two-dimensional models. However, a human cell-based, functionally mature liver model is still desired, which would provide an alternative to animal experiments and resolve low-prediction issues on species differences. Here, we prepared hybrid hydrogels of varying elasticity and compared them with a normal liver, to develop a more mature liver model that preserves liver properties in vitro. We encapsulated HepaRG cells, either alone or with supporting cells, in a biodegradable hybrid hydrogel. The elastic modulus of the 3D liver dynamically changed during culture due to the combined effects of prolonged degradation of hydrogel and extracellular matrix formation provided by the supporting cells. As a result, when the elastic modulus of the 3D liver model converges close to that of the in vivo liver (≅ 2.3 to 5.9 kPa), both phenotypic and functional maturation of the 3D liver were realized, while hepatic gene expression, albumin secretion, cytochrome p450-3A4 activity, and drug metabolism were enhanced. Finally, the 3D liver model was expanded to applications with embryonic stem cell-derived hepatocytes and primary human hepatocytes, and it supported prolonged hepatocyte survival and functionality in long-term culture. Our model represents critical progress in developing a biomimetic liver system to simulate liver tissue remodeling, and provides a versatile platform in drug development and disease modeling, ranging from physiology to pathology. We provide a functionally improved 3D liver model that recapitulates in vivo liver stiffness. We have experimentally addressed the issues of orchestrated effects of mechanical compliance, controlled matrix formation by stromal cells in conjunction with hepatic differentiation, and functional maturation of hepatocytes in a dynamic 3D

Diet - liver disease

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Proteins normally help the body repair tissue. They also prevent fatty buildup and damage to the liver cells. In people with badly damaged livers, proteins are not properly processed. Waste products may build up and affect the brain. Dietary ...

A Multiscale Agent-Based in silico Model of Liver Fibrosis Progression

International Nuclear Information System (INIS)

Dutta-Moscato, Joyeeta; Solovyev, Alexey; Mi, Qi; Nishikawa, Taichiro; Soto-Gutierrez, Alejandro; Fox, Ira J.; Vodovotz, Yoram

2014-01-01

Chronic hepatic inflammation involves a complex interplay of inflammatory and mechanical influences, ultimately manifesting in a characteristic histopathology of liver fibrosis. We created an agent-based model (ABM) of liver tissue in order to computationally examine the consequence of liver inflammation. Our liver fibrosis ABM (LFABM) is comprised of literature-derived rules describing molecular and histopathological aspects of inflammation and fibrosis in a section of chemically injured liver. Hepatocytes are modeled as agents within hexagonal lobules. Injury triggers an inflammatory reaction, which leads to activation of local Kupffer cells and recruitment of monocytes from circulation. Portal fibroblasts and hepatic stellate cells are activated locally by the products of inflammation. The various agents in the simulation are regulated by above-threshold concentrations of pro- and anti-inflammatory cytokines and damage-associated molecular pattern molecules. The simulation progresses from chronic inflammation to collagen deposition, exhibiting periportal fibrosis followed by bridging fibrosis, and culminating in disruption of the regular lobular structure. The ABM exhibited key histopathological features observed in liver sections from rats treated with carbon tetrachloride (CCl 4 ). An in silico “tension test” for the hepatic lobules predicted an overall increase in tissue stiffness, in line with clinical elastography literature and published studies in CCl 4 -treated rats. Therapy simulations suggested differential anti-fibrotic effects of neutralizing tumor necrosis factor alpha vs. enhancing M2 Kupffer cells. We conclude that a computational model of liver inflammation on a structural skeleton of physical forces can recapitulate key histopathological and macroscopic properties of CCl 4 -injured liver. This multiscale approach linking molecular and chemomechanical stimuli enables a model that could be used to gain translationally relevant insights into

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives.

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Volvert, Marie-Laure; Seyen, Sandrine; Piette, Marie; Evrard, Brigitte; Gangolf, Marjorie; Plumier, Jean-Christophe; Bettendorff, Lucien

2008-06-12

Lipid-soluble thiamine precursors have a much higher bioavailability than genuine thiamine and therefore are more suitable for therapeutic purposes. Benfotiamine (S-benzoylthiamine O-monophosphate), an amphiphilic S-acyl thiamine derivative, prevents the progression of diabetic complications, probably by increasing tissue levels of thiamine diphosphate and so enhancing transketolase activity. As the brain is particularly sensitive to thiamine deficiency, we wanted to test whether intracellular thiamine and thiamine phosphate levels are increased in the brain after oral benfotiamine administration. Benfotiamine that is practically insoluble in water, organic solvents or oil was solubilized in 200 mM hydroxypropyl-beta-cyclodextrin and the mice received a single oral administration of 100 mg/kg. Though thiamine levels rapidly increased in blood and liver to reach a maximum after one or two hours, no significant increase was observed in the brain. When mice received a daily oral administration of benfotiamine for 14 days, thiamine derivatives were increased significantly in the liver but not in the brain, compared to control mice. In addition, incubation of cultured neuroblastoma cells with 10 muM benfotiamine did not lead to increased intracellular thiamine levels. Moreover, in thiamine-depleted neuroblastoma cells, intracellular thiamine contents increased more rapidly after addition of thiamine to the culture medium than after addition of benfotiamine for which a lag period was observed. Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells

Hypoxia Enhances Differentiation of Adipose Tissue-Derived Stem Cells toward the Smooth Muscle Phenotype

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Fang Wang

2018-02-01

Full Text Available Smooth muscle differentiated adipose tissue-derived stem cells are a valuable resource for regeneration of gastrointestinal tissues, such as the gut and sphincters. Hypoxia has been shown to promote adipose tissue-derived stem cells proliferation and maintenance of pluripotency, but the influence of hypoxia on their smooth myogenic differentiation remains unexplored. This study investigated the phenotype and contractility of adipose-derived stem cells differentiated toward the smooth myogenic lineage under hypoxic conditions. Oxygen concentrations of 2%, 5%, 10%, and 20% were used during differentiation of adipose tissue-derived stem cells. Real time reverse transcription polymerase chain reaction and immunofluorescence staining were used to detect the expression of smooth muscle cells-specific markers, including early marker smooth muscle alpha actin, middle markers calponin, caldesmon, and late marker smooth muscle myosin heavy chain. The specific contractile properties of cells were verified with both a single cell contraction assay and a gel contraction assay. Five percent oxygen concentration significantly increased the expression levels of α-smooth muscle actin, calponin, and myosin heavy chain in adipose-derived stem cell cultures after 2 weeks of induction (p < 0.01. Cells differentiated in 5% oxygen conditions showed greater contraction effect (p < 0.01. Hypoxia influences differentiation of smooth muscle cells from adipose stem cells and 5% oxygen was the optimal condition to generate smooth muscle cells that contract from adipose stem cells.

Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.

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Tanaka, Mitsuru; Yasuoka, Akihito; Shimizu, Manae; Saito, Yoshikazu; Kumakura, Kei; Asakura, Tomiko; Nagai, Toshitada

2017-01-01

To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

Alcohol, Adipose Tissue and Lipid Dysregulation

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Jennifer L. Steiner

2017-02-01

Full Text Available Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease. In addition to the recognition of the role of adipose tissue derived fatty acids in liver steatosis, alcohol also impacts other functions of adipose tissue and lipid metabolism. Lipid balance in response to long‐term alcohol intake favors adipose tissue loss and fatty acid efflux as lipolysis is upregulated and lipogenesis is either slightly decreased or unchanged. Study of the lipolytic and lipogenic pathways has identified several regulatory proteins modulated by alcohol that contribute to these effects. Glucose tolerance of adipose tissue is also impaired by chronic alcohol due to decreased glucose transporter‐4 availability at the membrane. As an endocrine organ, white adipose tissue (WAT releases several adipokines that are negatively modulated following chronic alcohol consumption including adiponectin, leptin, and resistin. When these effects are combined with the enhanced expression of inflammatory mediators that are induced by chronic alcohol, a proinflammatory state develops within WAT, contributing to the observed lipodystrophy. Lastly, while chronic alcohol intake may enhance thermogenesis of brown adipose tissue (BAT, definitive mechanistic evidence is currently lacking. Overall, both WAT and BAT depots are impacted by chronic alcohol intake and the resulting lipodystrophy contributes to fat accumulation in peripheral organs, thereby enhancing the pathological state accompanying chronic alcohol use disorder.

Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth.

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Anderson, D M; Ashby, P; Busuttil, A; Kempson, S A; Lawson, M E

1984-04-01

Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.

The Histopathological Characteristics Caused by Trionyx sinensis Hemorrhagic Syndrome Virus (TSHSV) and Comparative Proteomic Analysis of Liver Tissue in TSHSV-Infected Chinese Soft-Shelled Turtles (Pelodiscus sinensis).

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Liu, Li; Cao, Zheng; Lin, Feng; Ye, Xueping; Lu, Shujuan; Lyv, Sunjian

2017-01-01

Trionyx sinensis hemorrhagic syndrome virus (TSHSV) is a pathogen that causes severe hemorrhagic syndrome and irreversible damage to different infected tissues of Pelodis cus sinensis, ending in the death of affected organisms. In the present study, the histopathological characteristics of TSHSV-infected P. sinensis were analyzed and compared by HE staining. Relative and absolute quantification (iTRAQ)-based proteomic analysis was employed to explore the molecular pathology of liver injury. Anatomical features indicated that TSHSV caused obvious congestion in the liver, kidney, intestine, and other tissues of P. sinensis. The typical clinical symptoms included hepatomegaly, fragility, spotty and severe congestion in liver tissue, and also obvious intestinal bleeding. The histopathological studies corroborated such lesions in the liver and kidney, etc. iTRAQ-based proteomic analysis revealed that there were 252 differentially expressed proteins in the liver tissue between healthy and infected P. sinensis, of which 118 proteins were upregulated and 134 proteins were downregulated. GO enrichment analysis and KEGG pathway analysis initially revealed the molecular mechanism of pathological changes in P. sinensis by TSHSV infection. The expression of some differentially expressed proteins was further confirmed by qRT-PCR. These results provided important information for the pathological diagnosis of TSHSV-caused disease, as well as the mechanism underlying TSHSV-caused disease. © 2017 S. Karger AG, Basel.

Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues.

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Cohen, Shahar; Leshansky, Lucy; Zussman, Eyal; Burman, Michael; Srouji, Samer; Livne, Erella; Abramov, Natalie; Itskovitz-Eldor, Joseph

2010-10-01

The use of stem cells for tissue engineering (TE) encourages scientists to design new platforms in the field of regenerative and reconstructive medicine. Human embryonic stem cells (hESC) have been proposed to be an important cell source for cell-based TE applications as well as an exciting tool for investigating the fundamentals of human development. Here, we describe the efficient derivation of connective tissue progenitors (CTPs) from hESC lines and fetal tissues. The CTPs were significantly expanded and induced to generate tendon tissues in vitro, with ultrastructural characteristics and biomechanical properties typical of mature tendons. We describe a simple method for engineering tendon grafts that can successfully repair injured Achilles tendons and restore the ankle joint extension movement in mice. We also show the CTP's ability to differentiate into bone, cartilage, and fat both in vitro and in vivo. This study offers evidence for the possibility of using stem cell-derived engineered grafts to replace missing tissues, and sets a basic platform for future cell-based TE applications in the fields of orthopedics and reconstructive surgery.

Is the propagation speed of ultrasound in human organs a diagnostic parameter for tissue characterization? Evaluation using the liver parenchyma in children and adolescents as an example

International Nuclear Information System (INIS)

Born, M.; Franke, I.

2011-01-01

New sonographic machines permit the measurement of the propagation speed of ultrasound (PSU) in humans. The liver seems to be an appropriate organ for examining whether the PSU may be used as a diagnostic parameter for tissue characterization since the liver is easily accessible to sonography and its variable content of fat impacts the PSU. Purpose: To determine whether there is a measurable correlation between obesity and PSU in the liver. Methods: In 69 children and adolescents, the PSU in the liver was measured sonographically and correlated to BMI, age, size and weight of the children. Results: A strong correlation was found between the PSU in the liver and the BMI. The PSU was significantly lower in obese children (1507 m/s) than in children with normal body weight (1564 m/s). Conclusion: PSU seems to be promising as an additional diagnostic parameter for characterizing liver tissue. Further evaluation is necessary. (orig.)

Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue.

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Mohamed Asrih

Full Text Available Beside its beneficial effects on weight loss, ketogenic diet (KD causes dyslipidemia, a pro-inflammatory state involved in the development of hepatic steatosis, glucose intolerance and insulin resistance, although the latter is still being debated. Additionally, KD is known to increase fibroblast growth factor 21 (FGF21 plasma levels. However, FGF21 cannot initiate its beneficial actions on metabolism in these conditions. We therefore hypothesized and tested in the present study that KD may impair FGF21 signaling.Using indirect calorimetry, we found that KD-fed mice exhibited higher energy expenditure than regular chow (RC-fed mice associated with increased Ucp1 levels in white adipose tissue (WAT, along with increased plasma FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the liver and WAT. We found that Fgfr4 and Klb (β-klotho were downregulated in the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because inflammation could be one of the mechanisms linking KD to impaired FGF21 signaling, we measured the expression levels of inflammatory markers and macrophage accumulation in WAT and liver and found an increased inflammation and macrophage accumulation in the liver, but surprisingly, a reduction of inflammation in WAT.We also showed that KD enhances lipid accumulation in the liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb expression. In contrast, import of lipids from the circulation was significantly reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36. This was further associated with reduced inflammation in WAT.Altogether, these results indicate that KD could be beneficial for a given tissue but deleterious for another.

Lipasin/betatrophin is differentially expressed in liver and white adipose tissue without association with insulin resistance in Wistar and Goto-Kakizaki rats.

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Cahová, M; Habart, D; Olejár, T; Berková, Z; Papáčková, Z; Daňková, H; Lodererova, A; Heczková, M; Saudek, F

2017-05-04

Lipasin is a recently identified lipokine expressed predominantly in liver and in adipose tissue. It was linked to insulin resistance in mice and to type 1 and type 2 diabetes (T1D, T2D) in humans. No metabolic studies concerning lipasin were performed yet in rats. Therefore, we used rat model of T2D and insulin resistance, Goto-Kakizaki (GK) rats, to determine changes of lipasin expression in liver and in white adipose tissue (WAT) over 52 weeks in the relation to glucose tolerance, peripheral tissue insulin sensitivity and adiposity. GK rats were grossly glucose intolerant since the age of 6 weeks and developed peripheral insulin resistance at the age of 20 weeks. Expression of lipasin in the liver did not differ between GK and Wistar rats, declining with age, and it was not related to hepatic triacylglycerol content. In WAT, the lipasin expression was significantly higher in Wistar rats where it correlated positively with adiposity. No such correlation was found in GK rats. In conclusion, lipasin expression was associated neither with a mild age-related insulin resistance (Wistar), nor with severe genetically-based insulin resistance (GK).

Intravital imaging of the immune responses during liver-stage malaria infection: An improved approach for fixing the liver.

Science.gov (United States)

Akbari, Masoud; Kimura, Kazumi; Houts, James T; Yui, Katsuyuki

2016-10-01

The host-parasite relationship is one of the main themes of modern parasitology. Recent revolutions in science, including the development of various fluorescent proteins/probes and two-photon microscopy, have made it possible to directly visualize and study the mechanisms underlying the interaction between the host and pathogen. Here, we describe our method of preparing and setting-up the liver for our experimental approach of using intravital imaging to examine the interaction between Plasmodium berghei ANKA and antigen-specific CD8 + T cells during the liver-stage of the infection in four dimensions. Since the liver is positioned near the diaphragm, neutralization of respiratory movements is critical during the imaging process. In addition, blood circulation and temperature can be affected by the surgical exposure due to the anatomy and tissue structure of the liver. To control respiration, we recommend anesthesia with isoflurane inhalation at 1% during the surgery. In addition, our protocol introduces a cushion of gauze around the liver to avoid external pressure on the liver during intravital imaging using an inverted microscope, which makes it possible to image the liver tissue for long periods with minimal reduction in the blood circulation and with minimal displacement and tissue damage. The key point of this method is to reduce respiratory movements and external pressure on the liver tissue during intravital imaging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Study of chicken liver and spleen by Moessbauer spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru [Ural State Technical University-UPI, Division of Applied Biophysics, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University-UPI, Faculty of Experimental Physics (Russian Federation); Malakheeva, L. I. [Simbio Holding, Science Consultation Department (Russian Federation); Prokopenko, P. G. [Russian State Medical University, Faculty of Biochemistry (Russian Federation)

2005-09-15

A preliminary study of purified normal human liver ferritin, normal chicken liver and spleen tissues in lyophilized form showed differences in room temperature Moessbauer hyperfine parameters. An additional study of liver and spleen tissues with lower iron content from chicken with lymphoid leukemia indicated small differences between the quadrupole splittings in these samples compared with those in normal tissues.

Study of chicken liver and spleen by Moessbauer spectroscopy

International Nuclear Information System (INIS)

Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Malakheeva, L. I.; Prokopenko, P. G.

2005-01-01

A preliminary study of purified normal human liver ferritin, normal chicken liver and spleen tissues in lyophilized form showed differences in room temperature Moessbauer hyperfine parameters. An additional study of liver and spleen tissues with lower iron content from chicken with lymphoid leukemia indicated small differences between the quadrupole splittings in these samples compared with those in normal tissues.

Principles and clinical application of ultrasound elastography for diffuse liver disease

International Nuclear Information System (INIS)

Jeong, Woo Kyoung; Lim, Hyo K.; Lee, Hyoung Ki; Jo, Jae Moon; Kim, Yong Soo

2014-01-01

Accurate assessment of the degree of liver fibrosis is important for estimating prognosis and deciding on an appropriate course of treatment for cases of chronic liver disease (CLD) with various etiologies. Because of the inherent limitations of liver biopsy, there is a great need for non-invasive and reliable tests that accurately estimate the degree of liver fibrosis. Ultrasound (US) elastography is considered a non-invasive, convenient, and precise technique to grade the degree of liver fibrosis by measuring liver stiffness. There are several commercial types of US elastography currently in use, namely, transient elastography, acoustic radiation force impulse imaging, supersonic shear-wave imaging, and real-time tissue elastography. Although the low reproducibility of measurements derived from operator-dependent performance remains a significant limitation of US elastography, this technique is nevertheless useful for diagnosing hepatic fibrosis in patients with CLD. Likewise, US elastography may also be used as a convenient surveillance method that can be performed by physicians at the patients' bedside to enable the estimation of the prognosis of patients with fatal complications related to CLD in a non-invasive manner.

Principles and clinical application of ultrasound elastography for diffuse liver disease

Energy Technology Data Exchange (ETDEWEB)

Jeong, Woo Kyoung; Lim, Hyo K. [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Hyoung Ki; Jo, Jae Moon [Health Medical Equipment Business, Samsung Electronics, Seoul (Korea, Republic of); Kim, Yong Soo [Dept. of Radiology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri (Korea, Republic of)

2014-10-15

Accurate assessment of the degree of liver fibrosis is important for estimating prognosis and deciding on an appropriate course of treatment for cases of chronic liver disease (CLD) with various etiologies. Because of the inherent limitations of liver biopsy, there is a great need for non-invasive and reliable tests that accurately estimate the degree of liver fibrosis. Ultrasound (US) elastography is considered a non-invasive, convenient, and precise technique to grade the degree of liver fibrosis by measuring liver stiffness. There are several commercial types of US elastography currently in use, namely, transient elastography, acoustic radiation force impulse imaging, supersonic shear-wave imaging, and real-time tissue elastography. Although the low reproducibility of measurements derived from operator-dependent performance remains a significant limitation of US elastography, this technique is nevertheless useful for diagnosing hepatic fibrosis in patients with CLD. Likewise, US elastography may also be used as a convenient surveillance method that can be performed by physicians at the patients' bedside to enable the estimation of the prognosis of patients with fatal complications related to CLD in a non-invasive manner.

Honokiol Improves Liver Steatosis in Ovariectomized Mice

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Yeon-Hui Jeong

2018-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common liver disease, and is associated with the development of metabolic syndrome. Postmenopausal women with estrogen deficiency are at a higher risk of progression to NAFLD. Estrogen has a protective effect against the progression of the disease. Currently, there are no safe and effective treatments for these liver diseases in postmenopausal women. Honokiol (Ho, a bioactive natural product derived from Magnolia spp, has anti-inflammatory, anti-angiogenic, and anti-oxidative properties. In our study, we investigated the beneficial effects of Ho on NAFLD in ovariectomized (OVX mice. We divided the mice into four groups, as follows: SHAM, OVX, OVX+β-estradiol (0.4 mg/kg of bodyweight, and OVX+Ho (50 mg/kg of diet. Mice were fed diets with/without Ho for 12 weeks. The bodyweight, epidermal fat, and weights of liver tissue were lower in the OVX group than in the other groups. Ho improved hepatic steatosis and reduced proinflammatory cytokine levels. Moreover, Ho markedly downregulated plasma lipid levels. Our results indicate that Ho ameliorated OVX-induced fatty liver and inflammation, as well as associated lipid metabolism. These findings suggest that Ho may be hepatoprotective against NAFLD in postmenopausal women.

Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

Science.gov (United States)

Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Morris, Raymond G; Russ, Graeme R; Hesselink, Dennis A; Van Gelder, Teun; Sallustio, Benedetta C

2013-10-01

Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

Evaluating childhood obesity. Magnetic resonance-based quantification of abdominal adipose tissue and liver fat in children

International Nuclear Information System (INIS)

Raschpichler, M.C.; Leipzig Univ. Medical Center; Sorge, I.; Hirsch, W.; Mende, M.; Sergeyev, E.; Koerner, A.; Kruber, D.; Schick, F.

2012-01-01

The purpose of this study is to establish and validate a magnetic resonance (MR)-based fat quantification package that provides an accurate assessment of abdominal adipose tissue and liver fat in children. Ex vivo trials with a torso model and water-oil mixtures are conducted. Abdominal adipose tissue (AAT) is covered by magnetic resonance imaging (MRI) using a fat-selective sequence and is analyzed by a plug-in based on the open source software Image. Liver fat (LF) is measured with localized 1 H Magnetic Resonance Spectroscopy ( 1 H MRS) and the jMRUI (java-based Magnetic Resonance User Interface) software package. Evaluation of the clinical methodology involved a study of 10 children in this feasibility study (mean age and body mass index: 13.3 yr; 33.3 kg/m 2 ). To evaluate the method's validity, reference measurements were performed. Ex vivo trials with the torso model showed that adipose tissue was measured appropriately with a systematic underestimation by 9.3 ± 0.2 % (0.32 ± 0.064 kg). Coefficients of variation for both intra- and inter-observer measurements ranged between 0 - 2.7 % and repeated analyses showed significant equivalent results (p 1 H MRS ex vivo revealed significant equivalence with the predefined fat content in water-oil mixtures (p < 0.01). In vivo, the homemade plug-in significantly overestimated the AAT, with the visceral adipose tissue being most affected (+ 15.7 ± 8.4 %). Although an overestimation of the AAT by the presented plug-in should be taken into consideration, this children-friendly package enables the quantification of both LF and AAT within 30 min on a freeware-based platform. (orig.)

Elastin in the Liver

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Jiri Kanta

2016-10-01

Full Text Available A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs, microfibrillar-associated proteins (MFAPs and fibulins. Lysyl oxidase (LOX and lysyl oxidase-like proteins (LOXLs are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibres are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the backgound of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

Non-alcoholic fatty liver disease, to struggle with the strangle: Oxygen availability in fatty livers.

Science.gov (United States)

Anavi, Sarit; Madar, Zecharia; Tirosh, Oren

2017-10-01

Nonalcoholic fatty liver diseases (NAFLD) is one of the most common chronic liver disease in Western countries. Oxygen is a central component of the cellular microenvironment, which participate in the regulation of cell survival, differentiation, functions and energy metabolism. Accordingly, sufficient oxygen supply is an important factor for tissue durability, mainly in highly metabolic tissues, such as the liver. Accumulating evidence from the past few decades provides strong support for the existence of interruptions in oxygen availability in fatty livers. This outcome may be the consequence of both, impaired systemic microcirculation and cellular membrane modifications which occur under steatotic conditions. This review summarizes current knowledge regarding the main factors which can affect oxygen supply in fatty liver. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Alleviation of lipopolysaccharide/d-galactosamine-induced liver injury in leukocyte cell-derived chemotaxin 2 deficient mice

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Akinori Okumura

2017-12-01

Full Text Available Leukocyte cell-derived chemotaxin 2 (LECT2 is a secreted pleiotropic protein that is mainly produced by the liver. We have previously shown that LECT2 plays an important role in the pathogenesis of inflammatory liver diseases. Lipopolysaccharide/d-galactosamine (LPS/d-GalN-induced acute liver injury is a known animal model of fulminant hepatic failure. Here we found that this hepatic injury was alleviated in LECT2-deficient mice. The levels of TNF-α and IFN-γ, which mediate this hepatitis, had significantly decreased in these mice, with the decrease in IFN-γ production notably greater than that in TNF-α. We therefore analyzed IFN-γ-producing cells in liver mononuclear cells. Flow cytometric analysis showed significantly reduced IFN-γ production in hepatic NK and NKT cells in LECT2-deficient mice compared with in wild-type mice. We also demonstrated a decrease in IFN-γ production in LECT2-deficient mice after systemic administration of recombinant IL-12, which is known to induce IFN-γ in NK and NKT cells. These results indicate that a decrease of IFN-γ production in NK and NKT cells was involved in the alleviation of LPS/d-GalN-induced liver injury in LECT2-deficient mice.

A Multiscale Agent-Based in silico Model of Liver Fibrosis Progression

Energy Technology Data Exchange (ETDEWEB)

Dutta-Moscato, Joyeeta [Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, University of Pittsburgh, Pittsburgh, PA (United States); Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Solovyev, Alexey [Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Mathematics, University of Pittsburgh, Pittsburgh, PA (United States); Mi, Qi [Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA (United States); Nishikawa, Taichiro [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, Children’s Hospital of Pittsburgh, Pittsburgh, PA (United States); Soto-Gutierrez, Alejandro [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Pathology, University of Pittsburgh, Pittsburgh, PA (United States); Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA (United States); Fox, Ira J. [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, Children’s Hospital of Pittsburgh, Pittsburgh, PA (United States); Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA (United States); Vodovotz, Yoram, E-mail: vodovotzy@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA (United States); Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States)

2014-05-30

Chronic hepatic inflammation involves a complex interplay of inflammatory and mechanical influences, ultimately manifesting in a characteristic histopathology of liver fibrosis. We created an agent-based model (ABM) of liver tissue in order to computationally examine the consequence of liver inflammation. Our liver fibrosis ABM (LFABM) is comprised of literature-derived rules describing molecular and histopathological aspects of inflammation and fibrosis in a section of chemically injured liver. Hepatocytes are modeled as agents within hexagonal lobules. Injury triggers an inflammatory reaction, which leads to activation of local Kupffer cells and recruitment of monocytes from circulation. Portal fibroblasts and hepatic stellate cells are activated locally by the products of inflammation. The various agents in the simulation are regulated by above-threshold concentrations of pro- and anti-inflammatory cytokines and damage-associated molecular pattern molecules. The simulation progresses from chronic inflammation to collagen deposition, exhibiting periportal fibrosis followed by bridging fibrosis, and culminating in disruption of the regular lobular structure. The ABM exhibited key histopathological features observed in liver sections from rats treated with carbon tetrachloride (CCl{sub 4}). An in silico “tension test” for the hepatic lobules predicted an overall increase in tissue stiffness, in line with clinical elastography literature and published studies in CCl{sub 4}-treated rats. Therapy simulations suggested differential anti-fibrotic effects of neutralizing tumor necrosis factor alpha vs. enhancing M2 Kupffer cells. We conclude that a computational model of liver inflammation on a structural skeleton of physical forces can recapitulate key histopathological and macroscopic properties of CCl{sub 4}-injured liver. This multiscale approach linking molecular and chemomechanical stimuli enables a model that could be used to gain translationally relevant

Liver immunology and its role in inflammation and homeostasis.

Science.gov (United States)

Robinson, Mark W; Harmon, Cathal; O'Farrelly, Cliona

2016-05-01

The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the non-diseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear 'dangerous' stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.

Histochemical demonstration of two mercury pools in trout tissues: mercury in kidney and liver after mercuric chloride exposure

DEFF Research Database (Denmark)

Baatrup, E; Nielsen, M G; Danscher, G

1987-01-01

Juvenile rainbow trout (Salmo gairdneri) were exposed to 100 ppb mercury (as HgCl2) in the water for 14 days. Concentrations of mercury in water and fish organs were monitored using radiolabeled mercury. Tissues from kidney and liver were fixed, and sections were developed by autometallography......, a method whereby accumulations of mercury sulfides and/or mercury selenides are silver amplified. In the kidney, mercury was found within lysosomes and extracellularly in the basal lamina of proximal tubules. In the liver, mercury was found within lysosomes of the hepatocytes. Additional groups of mercury......-exposed trout were subjected to selenium (as Na2SeO3), administered intraperitoneally 2 hr before fixation. Following this treatment, additional mercury could be visualized in the kidney circulatory system, including glomeruli, and in the nucleus and endoplasmic reticulum of liver cells. It is suggested...

How preservation time changes the linear viscoelastic properties of porcine liver.

Science.gov (United States)

Wex, C; Stoll, A; Fröhlich, M; Arndt, S; Lippert, H

2013-01-01

The preservation time of a liver graft is one of the crucial factors for the success of a liver transplantation. Grafts are kept in a preservation solution to delay cell destruction and cellular edema and to maximize organ function after transplantation. However, longer preservation times are not always avoidable. In this paper we focus on the mechanical changes of porcine liver with increasing preservation time, in order to establish an indicator for the quality of a liver graft dependent on preservation time. A time interval of 26 h was covered and the rheological properties of liver tissue studied using a stress-controlled rheometer. For samples of 1 h preservation time 0.8% strain was found as the limit of linear viscoelasticity. With increasing preservation time a decrease in the complex shear modulus as an indicator for stiffness was observed for the frequency range from 0.1 to 10 Hz. A simple fractional derivative representation of the Kelvin Voigt model was applied to gain further information about the changes of the mechanical properties of liver with increasing preservation time. Within the small shear rate interval of 0.0001-0.01 s⁻¹ the liver showed Newtonian-like flow behavior.

Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver

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Kuai Xiao Ling

2016-01-01

Full Text Available The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs mobilization and migration to the liver was poorly understood. Stromal cell-derived factor-1 (SDF-1 participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver.

Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: a transcriptomic and metabolomic study.

Science.gov (United States)

Holvoet, Paul; Rull, Anna; García-Heredia, Anabel; López-Sanromà, Sílvia; Geeraert, Benjamine; Joven, Jorge; Camps, Jordi

2015-03-01

There is a close interaction between Type 2 Diabetes, obesity and liver disease. We have studied the effects of the two most abundant Stevia-derived steviol glycosides, stevioside and rebaudioside A, and their aglycol derivative steviol on liver steatosis and the hepatic effects of lipotoxicity using a mouse model of obesity and insulin resistance. We treated ob/ob and LDLR-double deficient mice with stevioside (10 mg⋅kg(-1)⋅day-1 p.o., n = 8), rebaudioside A (12 mg⋅kg(-1)⋅day-1 p.o., n = 8), or steviol (5 mg⋅kg(-1)⋅day(-1) p.o., n = 8). We determined their effects on liver steatosis and on the metabolic effects of lipotoxicity by histological analysis, and by combined gene-expression and metabolomic analyses. All compounds attenuated hepatic steatosis. This could be explained by improved glucose metabolism, fat catabolism, bile acid metabolism, and lipid storage and transport. We identified PPARs as important regulators and observed differences in effects on insulin resistance, inflammation and oxidative stress between Stevia-derived compounds. We conclude that Stevia-derived compounds reduce hepatic steatosis to a similar extent, despite differences in effects on glucose and lipid metabolism, and inflammation and oxidative stress. Thus our data show that liver toxicity can be reduced through several pathophysiological changes. Further identification of active metabolites and underlying mechanisms are warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

Macrophage-derived Wnt opposes notch signaling to specify hepatic progenitor cell fate in chronic liver disease

NARCIS (Netherlands)

Boulter, L.; Govaere, O.; Bird, T.G.; Radulescu, S.; Ramachandran, P.; Pellicoro, A.; Ridgway, R.; Seo, S.S.; Spee, B.|info:eu-repo/dai/nl/304830925; van Rooijen, N.; Sansom, O.J.; Iredale, J.P.; Lowell, S.; Roskams, T.A.; Forbes, S.J.

2012-01-01

Nat Med. 2012 Mar 4;18(4):572-9. doi: 10.1038/nm.2667. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, Ridgway RA, Seo SS, Spee B, Van Rooijen N, Sansom OJ,

Liver collagen in cirrhosis correlates with portal hypertension and liver dysfunction

DEFF Research Database (Denmark)

Nielsen, Kåre; Clemmesen, Jens Otto; Vassiliadis, Efstathios

2014-01-01

livers. In 20 of the livers, CPA was measured in more than one tissue sample. CPA showed significant correlations with HVPG and with various surrogate markers of hepatic dysfunction including albumin, bilirubin, INR, MELD score and Child-Pugh score. CPA reliably discriminated HVPG ≥10 mmHg, termed...

Chronic alcohol exposure disturbs lipid homeostasis at the adipose tissue-liver axis in mice: analysis of triacylglycerols using high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling.

Directory of Open Access Journals (Sweden)

Xiaoli Wei

Full Text Available A method of employing high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling was developed in this study to investigate the effects of alcohol exposure on lipid homeostasis at the white adipose tissue (WAT-liver axis in a mouse model of alcoholic fatty liver. In order to differentiate the liver lipids synthesized from the fatty acids that were transported back from adipose tissue and the lipids synthesized from other sources of fatty acids, a two-stage mouse feeding experiment was performed to incorporate deuterium into metabolites. Hepatic lipids extracted from mouse liver, epididymal white adipose tissue (eWAT and subcutaneous white adipose tissue (sWAT were analyzed. It was found that 13 and 10 triacylglycerols (TGs incorporated with a certain number of deuterium were significantly increased in alcohol induced fatty liver at two and four weeks of alcohol feeding periods, respectively. The concentration changes of these TGs ranged from 1.7 to 6.3-fold increase. A total of 14 deuterated TGs were significantly decreased in both eWAT and sWAT at the two and four weeks and the fold-change ranged from 0.19 to 0.77. The increase of deuterium incorporated TGs in alcohol-induced fatty liver and their decrease in both eWAT and sWAT indicate that alcohol exposure induces hepatic influx of fatty acids which are released from WATs. The results of time course analysis further indicate a mechanistic link between adipose fat loss and hepatic fat gain in alcoholic fatty liver.

A search for losses of chromium and other trace elements during lyophilization of human liver tissue

International Nuclear Information System (INIS)

Goeij, J.J.M. de; Volkers, K.J.; Tjioe, P.S.

1979-01-01

Human liver tissues were investigated for possible trace-element losses during lyophilization by comparison of concentrations of lyophilized and untreated (wet) samples. When destructive neutron activation analysis (n.a.a.) was used, no significant losses were observed for As, Br, Cd, Co, Cr, Cu, Fe, Hg, Mo, Sb, Se, and Zn. The advantages of n.a.a. over radio-tracer techniques for studies of trace-element volatility are discussed. (Auth.)

Carotenoid accumulation in the tissues of zebra finches: predictors of integumentary pigmentation and implications for carotenoid allocation strategies.

Science.gov (United States)

McGraw, Kevin J; Toomey, Matthew B

2010-01-01

Carotenoid pigments produce the bright yellow to red ornamental colors of many animals, especially birds, and must ultimately be derived from the diet. However, they are also valuable for many physiological functions (e.g., antioxidants, immunostimulants, photoprotection, visual tuning, yolk nourishment to embryos), and as a result they are present in numerous internal body tissues (e.g., liver, adipose tissue, retina) whose carotenoid types and amounts are rarely studied in the context of color acquisition. Because male and female animals typically place different priorities on fitness-enhancing activities (e.g., gametic investment in females, sexual attraction in males), carotenoid allocation may track such investment patterns in the two sexes, and we can test for such sex-specific priorities of carotenoids by assessing body-tissue distributions of these pigments. We used high-performance liquid chromatography to identify and quantify carotenoid pigments from the plasma, liver, adipose tissue, and retina as well as the beak and legs of male and female zebra finches (Taeniopygia guttata), a species in which males display sexually attractive, red, carotenoid-based beak coloration and females also display some (albeit a less rich orange) beak color. To our knowledge, this is the first study of the predictors of carotenoid-based leg coloration-another potentially important visual signal-in this species. The same suite of dietary (e.g., lutein, zeaxanthin, beta-cryptoxanthin) and metabolically derived (e.g., dehydrolutein, anhydrolutein) yellow and orange carotenoids was present in plasma, liver, and adipose tissue of both sexes. Retina contained two different metabolites (astaxanthin and galloxanthin) that serve specific functions in association with unique photoreceptor types in the eye. Beaks were enriched with four red ketocarotenoid derivatives in both sexes (alpha-doradexanthin, adonirubin, astaxanthin, and canthaxanthin), while the carotenoid profile of legs

Evaluating childhood obesity. Magnetic resonance-based quantification of abdominal adipose tissue and liver fat in children

Energy Technology Data Exchange (ETDEWEB)

Raschpichler, M.C. [Leipzig Univ. (Germany). Dept. of Paediatric Radiology; Leipzig Univ. Medical Center (Germany). IFB Adiposity Diseases; Sorge, I.; Hirsch, W. [Leipzig Univ. (Germany). Dept. of Paediatric Radiology; Mende, M. [Leipzig Univ. (Germany). Clinical Trial Centre Leipzig; Sergeyev, E.; Koerner, A. [Leipzig Univ. (Germany). University Hospital for Children and Adolescents; Kruber, D. [Leipzig Univ. (Germany). Dept. of Oral, Craniomaxillofacial and Facial Plastic Surgery; Schick, F. [Univ. Hospital Tuebingen (Germany). Section on Experimental Radiology

2012-04-15

The purpose of this study is to establish and validate a magnetic resonance (MR)-based fat quantification package that provides an accurate assessment of abdominal adipose tissue and liver fat in children. Ex vivo trials with a torso model and water-oil mixtures are conducted. Abdominal adipose tissue (AAT) is covered by magnetic resonance imaging (MRI) using a fat-selective sequence and is analyzed by a plug-in based on the open source software Image. Liver fat (LF) is measured with localized {sup 1}H Magnetic Resonance Spectroscopy ({sup 1}H MRS) and the jMRUI (java-based Magnetic Resonance User Interface) software package. Evaluation of the clinical methodology involved a study of 10 children in this feasibility study (mean age and body mass index: 13.3 yr; 33.3 kg/m{sup 2}). To evaluate the method's validity, reference measurements were performed. Ex vivo trials with the torso model showed that adipose tissue was measured appropriately with a systematic underestimation by 9.3 {+-} 0.2 % (0.32 {+-} 0.064 kg). Coefficients of variation for both intra- and inter-observer measurements ranged between 0 - 2.7 % and repeated analyses showed significant equivalent results (p < 0.01). The lipid content obtained by {sup 1}H MRS ex vivo revealed significant equivalence with the predefined fat content in water-oil mixtures (p < 0.01). In vivo, the homemade plug-in significantly overestimated the AAT, with the visceral adipose tissue being most affected (+ 15.7 {+-} 8.4 %). Although an overestimation of the AAT by the presented plug-in should be taken into consideration, this children-friendly package enables the quantification of both LF and AAT within 30 min on a freeware-based platform. (orig.)

Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats.

Science.gov (United States)

Duan, Yun-Fei; An, Yong; Zhu, Feng; Jiang, Yong

2017-08-15

Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all Pfatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting.

Science.gov (United States)

Ma, Xuanyi; Qu, Xin; Zhu, Wei; Li, Yi-Shuan; Yuan, Suli; Zhang, Hong; Liu, Justin; Wang, Pengrui; Lai, Cheuk Sun Edwin; Zanella, Fabian; Feng, Gen-Sheng; Sheikh, Farah; Chien, Shu; Chen, Shaochen

2016-02-23

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

Assessment of Energy Metabolic Changes in Adipose Tissue-Derived Stem Cells

NARCIS (Netherlands)

Hajmousa, Ghazaleh; Harmsen, Martin C; Di Nardo, Paolo; Dhingra, Sanjiv; Singla, Dinender K.

2017-01-01

Adipose tissue-derived stem cells (ADSC) are promising candidates for therapeutic applications in cardiovascular regenerative medicine. By definition, the phenotype ADSCs, e.g., the ubiquitous secretion of growth factors, cytokines, and extracellular matrix components is not met in vivo, which

Perioperative liver and spleen elastography in patients without chronic liver disease.

Science.gov (United States)

Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

2018-02-27

To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s ( P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more ( P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy ( n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin ( R 2 = 0.154, Pearson's r = 0.392, P = 0.032) and international normalized ratio ( R 2 = 0.285, Pearson's r = 0.534, P = 0.003). Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.

Extracellular vesicles from human liver stem cells restore argininosuccinate synthase deficiency.

Science.gov (United States)

Herrera Sanchez, Maria Beatriz; Previdi, Sara; Bruno, Stefania; Fonsato, Valentina; Deregibus, Maria Chiara; Kholia, Sharad; Petrillo, Sara; Tolosano, Emanuela; Critelli, Rossana; Spada, Marco; Romagnoli, Renato; Salizzoni, Mauro; Tetta, Ciro; Camussi, Giovanni

2017-07-27

Argininosuccinate synthase (ASS)1 is a urea cycle enzyme that catalyzes the conversion of citrulline and aspartate to argininosuccinate. Mutations in the ASS1 gene cause citrullinemia type I, a rare autosomal recessive disorder characterized by neonatal hyperammonemia, elevated citrulline levels, and early neonatal death. Treatment for this disease is currently restricted to liver transplantation; however, due to limited organ availability, substitute therapies are required. Recently, extracellular vesicles (EVs) have been reported to act as intercellular transporters carrying genetic information responsible for cell reprogramming. In previous studies, we isolated a population of stem cell-like cells known as human liver stem cells (HLSCs) from healthy liver tissue. Moreover, EVs derived from HLSCs were reported to exhibit regenerative effects on the liver parenchyma in models of acute liver injury. The aim of this study was to evaluate whether EVs derived from normal HLSCs restored ASS1 enzymatic activity and urea production in hepatocytes differentiated from HLSCs derived from a patient with type I citrullinemia. HLSCs were isolated from the liver of a patient with type I citrullinemia (ASS1-HLSCs) and characterized by fluorescence-activated cell sorting (FACS), immunofluorescence, and DNA sequencing analysis. Furthermore, their differentiation capabilities in vitro were also assessed. Hepatocytes differentiated from ASS1-HLSCs were evaluated by the production of urea and ASS enzymatic activity. EVs derived from normal HLSCs were purified by differential ultracentrifugation followed by floating density gradient. The EV content was analyzed to identify the presence of ASS1 protein, mRNA, and ASS1 gene. In order to obtain ASS1-depleted EVs, a knockdown of the ASS1 gene in HLSCs was performed followed by EV isolation from these cells. Treating ASS1-HLSCs with EVs from HLSCs restored both ASS1 activity and urea production mainly through the transfer of ASS1 enzyme

Metabolism of polybrominated diphenyl ethers and tetrabromobisphenol A by fish liver subcellular fractions in vitro.

Science.gov (United States)

Shen, Mengnan; Cheng, Jie; Wu, Ruohan; Zhang, Shenghu; Mao, Liang; Gao, Shixiang

2012-06-15

Polybrominated diphenyl ethers (PBDEs) and tetrabromobisphenol A (TBBPA) are two major flame retardants that accumulate in fish tissues and are potentially toxic. Their debrominated and oxidated derivatives were also reported in fish tissues although the sources of theses derivatives were unidentified. Our study was to determine whether PBDEs and TBBPA could be metabolized by fish liver subcellular fractions in vitro and to identify what types of metabolites were formed. Liver microsomes and S9 fractions of crucian carp (Carassius auratus) were exposed to 4,4'-dibromodiphenyl ether (BDE 15), 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) or TBBPA solutions for 4h. Exposure of liver subcellular fractions to BDE 15 resulted in the formation of bromophenol and two monohydroxylated dibromodiphenyl ether metabolites. Neither in microsomes nor in S9 studies has revealed the presence of hydroxylated metabolites with BDE 47 exposure which indicated that the oxidation reactions in vitro were hindered by the increased number of bromine substituents on the PBDEs. TBBPA underwent an oxidative cleavage near the central carbon of the molecule, which led to the production of 2,6-dibromo-4-isopropyl-phenol and three unidentified metabolites. Another metabolite of TBBPA characterized as a hexa-brominated compound with three aromatic rings was also found in the liver subcellular fractions. These results suggest that the biotransformation of BDE 15 and TBBPA in fish liver is mediated by cytochrome P450 (CYP450) enzymes, as revealed by the formation of hydroxylated metabolites and oxidative bond cleavage products. Moreover, further studies on the identification of specific CYP450 isozymes involved in the biotransformation revealed that CYP1A was the major enzyme responsible for the biotransformation of BDE 15 and TBBPA in fish liver subcellular fractions and CYP3A4 also played a major role in metabolism of TBBPA. Copyright © 2012 Elsevier B.V. All rights reserved.

Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss.

Science.gov (United States)

Schmitz, J; Evers, N; Awazawa, M; Nicholls, H T; Brönneke, H S; Dietrich, A; Mauer, J; Blüher, M; Brüning, J C

2016-05-01

Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as

Effects of hypoxia on the immunomodulatory properties of adipose tissue-derived mesenchymal stem cells

NARCIS (Netherlands)

M. Roemeling-Van Rhijn (Marieke); F.K.F. Mensah (Fane ); S.S. Korevaar (Sander); M.J.C. Leijs (Maarten J.C.); G.J.V.M. van Osch (Gerjo); J.N.M. IJzermans (Jan); M.G.H. Betjes (Michiel); C.C. Baan (Carla); W. Weimar (Willem); M.J. Hoogduijn (Martin)

2013-01-01

textabstractAdipose tissue-derived mesenchymal stem cells (ASC) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The function of ASC adapts to environmental conditions, such as oxygen tension. Oxygen levels within tissues are typically much lower

Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major.

Science.gov (United States)

Ghavamzadeh, Ardeshir; Sotoudeh, Masoud; Hashemi Taheri, Amir Pejman; Alimoghaddam, Kamran; Pashaiefar, Hossein; Jalili, Mahdi; Shahi, Farhad; Jahani, Mohammad; Yaghmaie, Marjan

2018-02-01

The aims of this study are to determine the replacement rate of damaged hepatocytes by donor-derived cells in sex-mismatched recipient patients with thalassemia major and to determine whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells (HSCs) can alleviate liver fibrosis. Ten sex-mismatched donor-recipient pairs who received co-transplantation of HSCs with mesenchymal stem cells were included in our study. Liver biopsy was performed before transplantation. Two other liver biopsies were performed between 2 and 5 years after transplantation. The specimens were studied for the presence of donor-derived epithelial cells or hepatocytes using fluorescence in situ hybridization by X- and Y-centromeric probes and immunohistochemical staining for pancytokeratin, CD45, and a hepatocyte-specific antigen. All sex-mismatched tissue samples demonstrated donor-derived hepatocyte independent of donor gender. XY-positive epithelial cells or hepatocytes accounted for 11 to 25% of the cells in histologic sections of female recipients in the first follow-up. It rose to 47-95% in the second follow-up. Although not statistically significant, four out of ten patients showed signs of improvement in liver fibrosis. Our results showed that co-transplantation of HSC with mesenchymal stem cells increases the rate of replacement of recipient hepatocytes by donor-derived cells and may improve liver fibrosis.

Gene targeting and cloning in pigs using fetal liver derived cells.

Science.gov (United States)

Waghmare, Sanjeev K; Estrada, Jose; Reyes, Luz; Li, Ping; Ivary, Bess; Sidner, Richard A; Burlak, Chris; Tector, A Joseph

2011-12-01

Since there are no pig embryonic stem cells, pig genetic engineering is done in fetal fibroblasts that remain totipotent for only 3 to 5 wk. Nuclear donor cells that remain totipotent for longer periods of time would facilitate complicated genetic engineering in pigs. The goal of this study was to test the feasibility of using fetal liver-derived cells (FLDC) to perform gene targeting, and create a genetic knockout pig. FLDC were isolated and processed using a human liver stem cell protocol. Single copy α-1,3-galactosyl transferase knockout (GTKO) FLDCs were created using electroporation and neomycin resistant colonies were screened using PCR. Homozygous GTKO cells were created through loss of heterozygosity mutations in single GTKO FLDCs. Double GTKO FLDCs were used in somatic cell nuclear transfer (SCNT) to create GTKO pigs. FLDCs grew for more than 80 population doublings, maintaining normal karyotype. Gene targeting and loss of heterozygosity mutations produced homozygous GTKO FLDCs. FLDCs used in SCNT gave rise to homozygous GTKO pigs. FDLCs can be used in gene targeting and SCNT to produce genetically modified pigs. The increased life span in culture compared to fetal fibroblasts may facilitate genetic engineering in the pig. Copyright © 2011 Elsevier Inc. All rights reserved.

Signal changes in liver and spleen after Endorem administration in patients with and without liver cirrhosis

International Nuclear Information System (INIS)

Hundt, W.; Helmberger, T.; Reiser, M.; Petsch, R.

2000-01-01

The goal of this study was to compare the effect of Endorem on the signal intensity of the spleen in patients with normal liver tissue and in patients with liver cirrhosis. Thirty patients with normal liver tissue and 47 with liver cirrhosis were examined before and after i. v. Endorem administration. The patients were examined with a 1.5-T magnet system (Magnetom Vision) using a semiflexible cp-array coil. Three different pulse sequences were used: a T1-weighted gradient-echo sequence, a T2-weighted fast spin-echo sequence with spectral fat suppression, and a T2 * -weighted gradient-echo sequence. The signal-to-noise ratios (SNRs) of two areas of the liver and spleen were determined. The mean SNRs of the liver and spleen in patients with and without liver cirrhosis were compared. For assessment of statistical significance, the t-test at a level of P * -weighted gradient-echo sequence, the SNRs of the liver and spleen in the noncirrhotic liver group, compared with the cirrhotic liver group, were 126.8 % and 45.6 % less, respectively. The effect of Endorem on the liver in patients with Child C-stage liver cirrhosis was 32.1 % less than in patients with Child B-stage liver cirrhosis. Likewise, the Endorem effect on the spleen was 27.1 % less in patients with Child C-stage compared with Child B-stage liver cirrhosis. Hepatic and splenic uptake of Endorem is significantly decreased in patients with liver cirrhosis. (orig.)

The Role of Oxidative Stress and Antioxidants in Liver Diseases

Directory of Open Access Journals (Sweden)

Sha Li

2015-11-01

Full Text Available A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

Directory of Open Access Journals (Sweden)

Götz Pilarczyk

2016-01-01

Full Text Available The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.

Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering

DEFF Research Database (Denmark)

Starokozhko, Viktoriia; Hemmingsen, Mette; Larsen, Layla

2018-01-01

and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis...... in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted...... in slightly lower activity of some of the Phase I metabolism enzymes. Gene expression data indicate that hiPSCs differentiated into both hepatic and biliary directions. In conclusion, the hiPSC differentiated under flow conditions towards hepatocytes express a wide spectrum of liver functions at levels...

Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering

DEFF Research Database (Denmark)

Starokozhko, Viktoriia; Hemmingsen, Mette; Larsen, Layla

2018-01-01

Hepatic differentiation of human-induced pluripotent stem cells (hiPSCs) under flow conditions in a 3D scaffold is expected to be a major step forward for construction of bioartificial livers. The aims of this study were to induce hepatic differentiation of hiPSCs under perfusion conditions...... and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis...... in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted...

A descriptive study to provide evidence of the teratogenic and cellular effects of sibutramine and ephedrine on cardiac- and liver-tissue of chick embryos.

Science.gov (United States)

Oberholzer, Hester Magdalena; Van Der Schoor, Ciska; Taute, Helena; Bester, Megan Jean

2015-08-01

Exposure to drugs during pregnancy is a major concern, as some teratogenic compounds can influence normal foetal development. Although the use of drugs during pregnancy should generally be avoided, exposure of the developing foetus to teratogens may occur unknowingly since these compounds may be hidden in products that are being marketed as "all natural." The aim of the current study was to investigate the possible teratogenic and cellular effects of sibutramine-a serotonin-norepinephrine reuptake inhibitor used in the treatment of obesity-on the heart and liver tissue of chick embryos. Ephedrine was used as a positive control. The chick embryo model was chosen because it has been used in studying developmental and experimental biology and teratology with great success. The embryos were exposed to three different concentrations of sibutramine and ephedrine respectively. The results obtained revealed that both compounds exhibited embryotoxicity when compared to the control groups. Liver and heart tissue of the exposed embryos was severely affected by these compounds in a dose-related manner. Morphology similar to that of muscle dystrophy was observed in the heart, where the muscle tissue was infiltrated by adipose and connective tissue. Severe liver steatosis was also noted. A more in-depth investigation into the molecular pathways involved might provide more information on the exact mechanism of toxicity of these products influencing embryonic development. © 2015 Wiley Periodicals, Inc.

Derivation of transplantable 7,12-dimethylbenz[a]anthracene-induced chicken fibrosarcoma lines: differences in metastasizing properties and organ specificity

International Nuclear Information System (INIS)

Galton, J.E.; Xue, B.; Hochwald, G.M.; Thorbecke, G.J.

1982-01-01

Transplantable 7,12-dimethylbenz[a]anthracene-induced SC chicken fibrosarcoma (CHCT-NYU) lines were studied for their ability to grow in internal organs after iv injection (artificial metastases) into 1- to 3-week-old chickens. Some tumor lines were recently derived, whereas others were studied after many serial subcutaneous transplantations. Artificial metastases were seen in the stomach, pancreas, lungs, heart, and muscle, and occasionally in the kidneys and liver. Agammaglobulinemic recipients showed more extensive organ involvement than normal recipients of the same age. Whole-body ν-irradiation enhanced the incidence of artificial metastases, particularly in lungs. Antibody from the serum of a primary tumor-bearing host reduced the growth of the corresponding tumor in many organs. The metastatic pattern of line CHCT-NYU4 was a relatively stable property. However, intravenous transplantation of tumor cells from line CHCT-NYU4 taken from the liver, lungs, and pancreas of a single recipient established sublines with changes in organ specificity. After a few such serial transplants of liver-derived tumor, a line was derived that grew virtually in the liver alone. A subline with preference for growth in lungs was also obtained, but its ability to grow in the pancreas persisted. A pancreas-derived tumor line also grew in the liver and lungs. Subcutaneous transplants of tissue fragments of the lung-derived tumor line caused the appearance of spontaneous metastases in lungs. The incidence of spontaneous metastases with the lung-derived line was much greater than that with the liver-derived line or with the original CHCT-NYU4 line

Liver tissue tolerance for irradiation : Experimental and clinical investigations

NARCIS (Netherlands)

Cromheecke, M; Konings, AWT; Szabo, BG; Hoekstra, HJ

2000-01-01

Radiation treatment of the liver for malignant disease has gained renewed interest due to newly developed treatment modalities. Still limited specific knowledge is available concerning liver damage following irradiation. Inconsistencies between reported animal experimental studies are largely due to

Orosomucoid expression profiles in liver, adipose tissues and serum of lean and obese domestic pigs, Göttingen minipigs and Ossabaw minipigs

DEFF Research Database (Denmark)

Højbøge, Tina Rødgaard; Stagsted, Jan; Christoffersen, Berit Ø.

2013-01-01

The acute phase protein orosomucoid (ORM) has anti-inflammatory and immunomodulatory effects, and may play an important role in the maintenance of metabolic homeostasis in obesity-induced low-grade inflammation. Even though the pig is a widely used model for obesity related metabolic symptoms......, the expression of ORM has not yet been characterized in such pig models. The objective of this study was to investigate the expression of ORM1 mRNA in liver, visceral adipose tissue, subcutaneous adipose tissue (SAT) from the abdomen or retroperitoneal abdominal adipose tissue (RPAT) and SAT from the neck...

Clinical value of MRI liver-specific contrast agents: a tailored examination for a confident non-invasive diagnosis of focal liver lesions

International Nuclear Information System (INIS)

Ba-Ssalamah, Ahmed; Uffmann, Martin; Bastati, Nina; Herold, Christian; Schima, Wolfgang; Saini, Sanjai

2009-01-01

Screening of the liver for hepatic lesion detection and characterization is usually performed with either ultrasound or CT. However, both techniques are suboptimal for liver lesion characterization and magnetic resonance (MR) imaging has emerged as the preferred radiological investigation. In addition to unenhanced MR imaging techniques, contrast-enhanced MR imaging can demonstrate tissue-specific physiological information, thereby facilitating liver lesion characterization. Currently, the classes of contrast agents available for MR imaging of the liver include non-tissue-specific extracellular gadolinium chelates and tissue-specific hepatobiliary or reticuloendothelial agents. In this review, we describe the MR features of the more common focal hepatic lesions, as well as appropriate imaging protocols. A special emphasis is placed on the clinical use of non-specific and liver-specific contrast agents for differentiation of focal liver lesions. This may aid in the accurate diagnostic workup of patients in order to avoid invasive procedures, such as biopsy, for lesion characterization. A diagnostic strategy that considers the clinical situation is also presented. (orig.)

The Application of Minimally Invasive Devices with Nanostructured Surface Functionalization: Antisticking Behavior on Devices and Liver Tissue Interface in Rat

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Li-Hsiang Lin

2015-01-01

Full Text Available This study investigated the thermal injury and adhesion property of a novel electrosurgery of liver using copper-doped diamond-like carbon (DLC-Cu surface treatment. It is necessary to reduce the thermal damage of surrounding tissues for clinical electrosurgeries. The surface morphologies of stainless steel (SS coated with DLC (DLC-Cu-SS films were characterized by scanning electron microscopy (SEM and transmission electron microscopy (TEM. Bionic liver models were reconstructed using magnetic resonance imaging (MRI to simulate electrosurgery. Cell cytotoxicity assays showed that the DLC-Cu thin film was nontoxic. The temperature of tissue decreased significantly with use of the electrosurgical device with nanostructured DLC-Cu films and increased with increasing thickness of the films. Thermography revealed that the surgical temperature in the DLC-Cu-SS electrosurgical device was significantly lower than that in the untreated device in the animal model. Moreover, compared to the SS electrosurgical device, the DLC-Cu-SS electrosurgical device caused a relatively small injury area and lateral thermal effect. The results indicate that the DLC-Cu-SS electrosurgical device decreases excessive thermal injury and ensures homogeneous temperature transformation in the tissues.

A gold nanoparticle coated porcine cholecyst-derived bioscaffold for cardiac tissue engineering.

Science.gov (United States)

Nair, Reshma S; Ameer, Jimna Mohamed; Alison, Malcolm R; Anilkumar, Thapasimuthu V

2017-09-01

Extracellular matrices of xenogeneic origin have been extensively used for biomedical applications, despite the possibility of heterogeneity in structure. Surface modification of biologically derived biomaterials using nanoparticles is an emerging strategy for improving topographical homogeneity when employing these scaffolds for sophisticated tissue engineering applications. Recently, as a tissue engineering scaffold, cholecyst derived extracellular matrix (C-ECM) has been shown to have several advantages over extracellular matrices derived from other organs such as jejunum and urinary bladder. This study explored the possibility of adding gold nanoparticles, which have a large surface area to volume ratio on C-ECM for achieving homogeneity in surface architecture, a requirement for cardiac tissue engineering. In the current study, gold nanoparticles (AuNPs) were synthesized and functionalised for conjugating with a porcine cholecystic extracellular matrix scaffold. The conjugation of nanoparticles to C-ECM was achieved by 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide/N-hydroxysuccinimide chemistry and further characterized by Fourier transform infrared spectroscopy, environmental scanning electron microscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. The physical properties of the modified scaffold were similar to the original C-ECM. Biological properties were evaluated by using H9c2 cells, a cardiomyoblast cell line commonly used for cellular and molecular studies of cardiac cells. The modified scaffold was found to be a suitable substrate for the growth and proliferation of the cardiomyoblasts. Further, the non-cytotoxic nature of the modified scaffold was established by direct contact cytotoxicity testing and live/dead staining. Thus, the modified C-ECM appears to be a potential biomaterial for cardiac tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

International Nuclear Information System (INIS)

Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

2004-01-01

The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16 INKa and DNA repair gene O 6 -methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16 INKa promoter methylation upon LDR exposure. In male liver tissue, p16 INKa promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16 INKa promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16 INKa and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure

Quantization of liver tissue in dual kVp computed tomography using linear discriminant analysis

Science.gov (United States)

Tkaczyk, J. Eric; Langan, David; Wu, Xiaoye; Xu, Daniel; Benson, Thomas; Pack, Jed D.; Schmitz, Andrea; Hara, Amy; Palicek, William; Licato, Paul; Leverentz, Jaynne

2009-02-01

Linear discriminate analysis (LDA) is applied to dual kVp CT and used for tissue characterization. The potential to quantitatively model both malignant and benign, hypo-intense liver lesions is evaluated by analysis of portal-phase, intravenous CT scan data obtained on human patients. Masses with an a priori classification are mapped to a distribution of points in basis material space. The degree of localization of tissue types in the material basis space is related to both quantum noise and real compositional differences. The density maps are analyzed with LDA and studied with system simulations to differentiate these factors. The discriminant analysis is formulated so as to incorporate the known statistical properties of the data. Effective kVp separation and mAs relates to precision of tissue localization. Bias in the material position is related to the degree of X-ray scatter and partial-volume effect. Experimental data and simulations demonstrate that for single energy (HU) imaging or image-based decomposition pixel values of water-like tissues depend on proximity to other iodine-filled bodies. Beam-hardening errors cause a shift in image value on the scale of that difference sought between in cancerous and cystic lessons. In contrast, projection-based decomposition or its equivalent when implemented on a carefully calibrated system can provide accurate data. On such a system, LDA may provide novel quantitative capabilities for tissue characterization in dual energy CT.

Liver regenerative medicine: advances and challenges.

Science.gov (United States)

Chistiakov, Dimitry A

2012-01-01

Liver transplantation is the standard care for many end-stage liver diseases. However, donor organs are scarce and some people succumb to liver failure before a donor is found. Liver regenerative medicine is a special interdisciplinary field of medicine focused on the development of new therapies incorporating stem cells, gene therapy and engineered tissues in order to repair or replace the damaged organ. In this review we consider the emerging progress achieved in the hepatic regenerative medicine within the last decade. The review starts with the characterization of liver organogenesis, fetal and adult stem/progenitor cells. Then, applications of primary hepatocytes, embryonic and adult (mesenchymal, hematopoietic and induced pluripotent) stem cells in cell therapy of liver diseases are considered. Current advances and challenges in producing mature hepatocytes from stem/progenitor cells are discussed. A section about hepatic tissue engineering includes consideration of synthetic and natural biomaterials in engineering scaffolds, strategies and achievements in the development of 3D bioactive matrices and 3D hepatocyte cultures, liver microengineering, generating bioartificial liver and prospects for fabrication of the bioengineered liver. Copyright © 2012 S. Karger AG, Basel.

Feasibility of computed tomography based thermometry during interstitial laser heating in bovine liver

International Nuclear Information System (INIS)

Pandeya, G.D.; Klaessens, J.H.G.M.; Greuter, M.J.W.; Oudkerk, M.; Schmidt, B.; Flohr, T.; Hillegersberg, R. van

2011-01-01

To assess the feasibility of computed tomography (CT) based thermometry during interstitial laser heating in the bovine liver. Four freshly exercised cylindrical blocks of bovine tissue were heated using a continuous laser of Nd:YAG (wavelength: 1064 nm, active length: 30 mm, power: 10-30 W). All tissues were imaged at least once before and 7 times during laser heating using CT and temperatures were simultaneously measured with 5 calibrated thermal sensors. The dependency of the average CT numbers as a function of temperature was analysed with regression analysis and a CT thermal sensitivity was derived. During laser heating, the growing hypodense area was observed around the laser source and that area showed an increase as a function of time. The formation of hypodense area was caused by declining in CT numbers at increasing temperatures. The regression analysis showed an inverse linear dependency between temperature and average CT number with -0.65 ± 0.048 HU/ C (R 2 = 0.75) for the range of 18-85 C in bovine liver. The non-invasive CT based thermometry during interstitial laser heating is feasible in the bovine liver. CT based thermometry could be further developed and may be of potential use during clinical LITT of the liver. (orig.)

Histochemical demonstration of two mercury pools in trout tissues: mercury in kidney and liver after mercuric chloride exposure

International Nuclear Information System (INIS)

Baatrup, E.; Nielsen, M.G.; Danscher, G.

1986-01-01

Juvenile rainbow trout (Salmo gairdneri) were exposed to 100 ppb mercury (as HgCl 2 ) in the water for 14 days. Concentrations of mercury in water and fish organs were monitored using radiolabeled mercury. Tissues from kidney and liver were fixed, and sections were developed by autometallography, a method whereby accumulations of mercury sulfides and/or mercury selenides are silver amplified. In the kidney, mercury was found within lysosomes and extracellularly in the basal lamina of proximal tubules. In the liver, mercury was found within lysosomes of the hepatocytes. Additional groups of mercury-exposed trout were subjected to selenium (as Na 2 SeO 3 ), administered intraperitoneally 2 hr before fixation. Following this treatment, additional mercury could be visualized in the kidney circulatory system, including glomeruli, and in the nucleus and endoplasmic reticulum of liver cells. It is suggested that the mercury visualized prior to selenium treatment represents inorganic mercury, while additional mercury visualized after selenium administration represents an organic form

In vitro proliferation of haemopoietic cells in the presence of adherent cell layers. II. Differential effect of adherent cell layers derived from various organs

NARCIS (Netherlands)

Reimann, J.; Burger, H.

1979-01-01

Mouse bone marrow-derived adherent cell populations promoted proliferation of haemopoietic cells in vitro in a liquid culture system for at least 4 weeks. Adherent cell layers derived from other haemopoietic organs (foetal liver, adult spleen) and fibroblasts from embryonic tissues did not maintain

Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues.

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Nicolas Christoforou

Full Text Available The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS cells, which once differentiated allow for the enrichment of Nkx2-5(+ cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+ cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors' ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological

A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro

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Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

2017-01-01

Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotransformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two-dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases. PMID:27959388

[Insulin-sensitizing agents: metformin and thiazolidinedione derivatives].

Science.gov (United States)

Satoh, Jo

2003-07-01

Both metformin and thiazolidinedione derivatives(TZDs) improve insulin resistance, a major pathogenesis of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion. Metformin inhibits glucose output from the liver, while TZDs increase glucose utilization in the peripheral tissues. In addition, there has been indicated that these agents ameliorate metabolic syndrome beyond glucose-level lowering. Molecular targets of these agents have recently been revealed; AMP-activated protein kinase (AMPK) for metformin and adiponectin, while PPAR gamma for TZDs which induce gene expression of adipocyte glycerol kinase and adiponectin. Insulin-sensitizing agents are clinically useful for obese diabetic patients with insulin resistance. However, periodical examinations are necessary to avoid serious adverse effects such as lactic acidosis, although rare, by metformin and liver injury by TZDs.

Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells

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Irit Meivar-Levy

2011-01-01

Full Text Available Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.

Mechanism of tumor and liver concentration of /sup 67/Ga: /sup 67/Ga binding substances in tumor tissues and liver

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Ando, I; Hiraki, T; Takeshita, M; Hisada, K

1983-01-01

Tumor-bearing animals were administered with /sup 67/Ga citrate and tumor homogenates, from which nuclear fraction was removed, and mitochondrial fraction of the host livers were digested with protease (pronase P). After digestion, the supernatants of the reaction mixtures were applied to a Sephadex G-100 column. Resultant eluates were analyzed for radioactivity, protein, uronic acid and sialic acids. Three peaks of radioactivity were obtained by gel filtration. The first peak eluted in the void volume contained a species whose molecular weight exceeded 40,000. The second peak consisted of substances with molecular weights of 9400-40,000. Radioactivity in the third peak was from liberated gallium-67. /sup 67/Ga in the second peak was bound to acid mucopolysaccharide and/or the sulfated carbohydrate chain of sulfated glycoprotein. It was thought that /sup 67/Ga in the first peak might be bound to some acid mucopolysaccharides. Considering the results of cellulose acetate electrophoresis, /sup 67/Ga in the second peak seemed to be bound to acid mucopolysaccharide which contained no uronic acids, and/or to the sulfated carbohydrate chain of sulfated glycoprotein. It was concluded that /sup 67/Ga was bound to the acid mucopolysaccharides and/or the sulfated carbohydrate chain of sulfated glycoprotein in tumor tissues and liver lysosomes.

Adipokines in Liver Cirrhosis.

Science.gov (United States)

Buechler, Christa; Haberl, Elisabeth M; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

2017-06-29

Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively.

The effect of aqueous extract of Avicennia marina (Forsk. Vierh. leaves on liver enzymes' activity, oxidative stress parameters and liver histopathology in male diabetic rats

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Akram Hamzevi

2017-12-01

Full Text Available Background: Avicennia marina has antioxidant and anti-diabetic properties. This study was conducted to examine the effect of aqueous extract of A. marina on liver enzymes' activity, oxidative stress parameters and liver histopathology in diabetic rats. Materials and Methods: In this experimental study, 28 male rats were allocated into the equal groups of control, diabetic control and experimental diabetic 1 and 2. The diabetes in diabetic control and experimental diabetic groups was induced using an intraperitoneal injection of 120 mg/kg alloxan. The experimental diabetic groups received the aqueous extract of A. marina (100 and 200 mg/kg, i.p. in alternate days for one month. Sterile distilled water was injected to the animals of control and diabetic control groups. At the end of the treatment period, serum levels of ALT, AST, GGT and ALP were measured. Then, levels of SOD, GST, CAT and MDA were measured in the liver tissue. The liver sections were prepared and examined by an optical microscope. Results: Results showed that administration of the A. marina extract (100 and 300 mg/kg, ip to the diabetic rats significantly decreased the serum levels of liver enzymes and tissue level of MDA. Also, the activity of the liver tissue's antioxidant enzymes was increased (P<0.05. The A. marina extract dose-dependently decreased liver damages in diabetic rats. Conclusion: Administration of the A. marina extract improves liver tissue oxidative stress indices and decreases the serum level of liver enzymes. Also, A. marina extract improves liver tissue injuries induced by diabetes.

Tissue ablation accelerated by peripheral scanning mode with high-intensity focused ultrasound: a study on isolated porcine liver perfusion.

Science.gov (United States)

Bu, Rui; Yin, Li; Yang, Han; Wang, Qi; Wu, Feng; Zou, Jian Zhong

2013-08-01

The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Hepatic stellate cell-targeted imatinib nanomedicine versus conventional imatinib: A novel strategy with potent efficacy in experimental liver fibrosis.

Science.gov (United States)

El-Mezayen, Nesrine S; El-Hadidy, Wessam F; El-Refaie, Wessam M; Shalaby, Th I; Khattab, Mahmoud M; El-Khatib, Aiman S

2017-11-28

Liver fibrosis is a global health problem without approved treatment. Imatinib inhibits two key profibrotic pathways; platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) and thus can be used to treat liver fibrosis. However, conventional imatinib therapy is hampered by low concentration at target tissue and increased toxicity to other tissues especially heart, lung and liver. Since hepatic stellate cells (HSCs) are the main contributors to liver fibrosis pathogenesis and sole hepatic vitamin A (V A ) storage cells, they can be actively targeted by coupling liposomes to V A . In this study, novel V A -coupled imatinib-loaded liposomes (ILC) were prepared and optimized regarding V A -coupling efficiency, imatinib entrapment efficiency, and particle size. Preferential accumulation of the selected formula in liver was proved by tracing intraperitoneally (i.p.)-injected V A -coupled liposomes loaded with Nile Red (LCNR) to rats with CCl 4 -induced liver fibrosis using live animal imaging. Co-localization of LCNR with immunofluorescently-labeled PDGFR-β in frozen liver tissue sections confirmed HSCs targeting. ILC bio-distribution, following single i.p. injection, revealed 13.5 folds higher hepatic accumulation than conventional imatinib in addition to limited bio-distribution to other organs including heart and lung reflecting diminished adverse effects. ILC therapy resulted in a potent inhibition of phosphorylated PDGFR-β expression when compared to conventional imatinib. Subsequently, there was a statistically significant improvement in liver function tests and reversal of hepatotoxicity along with liver fibrosis. Anti-fibrotic effect was evident from histopathologic Ishak score reduction as well as normalization of the level of profibrotic mediators (hydroxyproline, TGF-B and matrix metalloproteinase-2). Thus, HSC-targeted imatinib therapy shows outstanding anti-fibrotic effects with reduced cytotoxicity compared to conventional

Damage of rat liver tissue caused by repeated and sustained +Gz exposure and the mechanism thereof

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Wen-bing LI

2014-03-01

Full Text Available Objective 　To explore the mechanisms of positive acceleration (+Gz on the damage of rat liver tissue and the effect of +Gz on the expression of JNK/c-Jun in liver cells. Methods 　Twenty four male Wistar rats were randomly divided into 4 groups (n=6: control, +2Gz, +6Gz and +10Gz group. With prone position, the rats in control group were fixed to the turning arm of centrifuge with head towards the axis for 5 minutes. The fixation method in +2Gz, +6Gz and +10Gz group was the same as in the control group. The increase rate of acceleration was 1G/s with a peak-time of 3 minutes, and each +Gz exposure repeated 5 times with an interval of 30 minutes. HE staining was used to observe the morphological changes of liver tissue, fluorescence real-time quantitative PCR to detect the expression of hepatic c-Jun mRNA, and Western blotting to detect the hepatic protein expression of p-c-Jun, c-Jun, p-JNK and JNK. Plasma aspartate aminotransferase (AST and alanine aminotransferase (ALT were determined. Results 　The levels of serum ALT and AST increased significantly in +6Gz and, especially, the +10Gz group than in control group and +2Gz group (P<0.05. The same situation also existed in the increase of c-Jun mRNA expression (P<0.05. Hepatic c-jun and p-c-Jun (c-Jun activated form protein expression increased with the increase of G value. Compared with control group, no change was found in JNK protein expression in the other three groups, but the expression of p-JNK (activated form of JNK increased in +6Gz and +10Gz groups (P<0.05. HE staining showed the disorganized liver cells with irregular shapes, the unclear cell gap and the vacuolar changes in +6Gz and +10Gz groups. Conclusions 　Repeated and sustained +Gz may cause enhanced expression of c-Jun/ p-c-Jun and p-JNK in hepatic cells. JNK/c-Jun signaling pathway may play an important role in the process of hepatic stress injury. DOI: 10.11855/j.issn.0577-7402.2014.03.15

Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis staging.

Science.gov (United States)

Morisaka, Hiroyuki; Motosugi, Utaroh; Ichikawa, Shintaro; Nakazawa, Tadao; Kondo, Tetsuo; Funayama, Satoshi; Matsuda, Masanori; Ichikawa, Tomoaki; Onishi, Hiroshi

2018-05-01

Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy. To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard. A retrospective study at a single institution. In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle. 2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used. Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard. The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test. Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90-91% [108-9/120]), ≥F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017). MRE can be an alternative to liver biopsy for fibrosis staging. 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268-1275. © 2017

Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine.

Science.gov (United States)

Lee, Hyunsu; Park, Jae-Hyung; Seo, Incheol; Park, Sun-Hyun; Kim, Shin

2014-12-21

Mapping of tissue structure at the cellular, circuit, and organ-wide scale is important for understanding physiological and biological functions. A bio-electrochemical technique known as CLARITY used for three-dimensional anatomical and phenotypical mapping within transparent intact tissues has been recently developed. This method provided a major advance in understanding the structure-function relationships in circuits of the nervous system and organs by using whole-body clearing. Thus, in the present study, we aimed to improve the original CLARITY procedure and developed specific CLARITY protocols for various intact organs. We determined the optimal conditions for reducing bubble formation, discoloration, and depositing of black particles on the surface of tissue, which allowed production of clearer organ images. We also determined the appropriate replacement cycles of clearing solution for each type of organ, and convincingly demonstrated that 250-280 mA is the ideal range of electrical current for tissue clearing. We then acquired each type of cleared organs including brain, pancreas, liver, lung, kidney, and intestine. Additionally, we determined the images of axon fibers of hippocampal region, the Purkinje layer of cerebellum, and vessels and cellular nuclei of pancreas. CLARITY is an innovative biochemical technology for the structural and molecular analysis of various types of tissue. We developed improved CLARITY methods for clearing of the brain, pancreas, lung, intestine, liver, and kidney, and identified the appropriate experimental conditions for clearing of each specific tissue type. These optimized methods will be useful for the application of CLARITY to various types of organs.

[Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

Science.gov (United States)

Fischer, H-P

2005-05-01

High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases

Insertion of liver enriched transcription factor hepatocyte nuclear factor-4 (HNF-4) in a vector which contains simian virus (SV40) promoter

International Nuclear Information System (INIS)

Al-Nbaheen, M.; Pourzand, C.; Tyrrell, R.M.

2006-01-01

One way of targeting gene expression in vivo is to control transcription using a tissue-specific regulatory system. Tissue specific promoters or enhancers are in use in transgenic animals and could be utilized in medical for gene therapy. At present the usual method for selection of a tissue-specific promoter is to identify a gene, which is expressed at unusually high level in the target tissue, and then to use the promoter for this gene to drive expression of another therapeutic gene in the target tissue. This approach is logical but does not always lead to high levels of gene expression. A second approach is to investigate the scope for discovery of synthetic specific promoters using a target tissue. The objective of the work described in this paper was to use both approach to design plasmid DNA expression vectors that would carry liver-specific promoter/enhancer linked to reporter gene (i.e. luciferase). Then transfect these vectors to both liver-derived and non-liver cell lines. This is followed by evaluation of the liver-specificity of each construct by measuring the basal level expression of the reporter gene (i.e. luciferase activity) in both cell lines. Hepatocyte nuclear factor-4 (HNF-4) is liver-enriched transcription factor used to design new synthetic enhancers by inserting a tandem array of 1', 3' or 5' repeats of the HNF-4 binding site upstream of the SV40 promoter linked to the luciferase reporter gene within an Epstein-Barr virus (EBV)-based vector, p 706. The results of transfection revealed that unexpectedly the HNF-4 binding sites in these constructs act as a repressor rather than enhancer of the liver-specific expression of the luciferase gene. (author)

In vitro recapitulation of the urea cycle using murine embryonic stem cell-derived in vitro liver model.

Science.gov (United States)

Tamai, Miho; Aoki, Mami; Nishimura, Akihito; Morishita, Koji; Tagawa, Yoh-ichi

2013-12-01

Ammonia, a toxic metabolite, is converted to urea in hepatocytes via the urea cycle, a process necessary for cell/organismal survival. In liver, hepatocytes, polygonal and multipolar structures, have a few sides which face hepatic sinusoids and adjacent hepatocytes to form intercellular bile canaliculi connecting to the ductules. The critical nature of this three-dimensional environment should be related to the maintenance of hepatocyte function such as urea synthesis. Recently, we established an in vitro liver model derived from murine embryonic stem cells, IVL(mES), which included the hepatocyte layer and a surrounding sinusoid vascular-like network. The IVL(mES) culture, where the hepatocyte is polarized in a similar fashion to its in vivo counterpart, could successfully recapitulate in vivo results. L-Ornithine is an intermediate of the urea cycle, but supplemental L-ornithine does not activate the urea cycle in the apolar primary hepatocyte of monolayer culture. In the IVL(mES), supplemental L-ornithine could activate the urea cycle, and also protect against ammonium/alcohol-induced hepatocyte death. While the IVL(mES) displays architectural and functional properties similar to the liver, primary hepatocyte of monolayer culture fail to model critical functional aspects of liver physiology. We propose that the IVL(mES) will represent a useful, humane alternative to animal studies for drug toxicity and mechanistic studies of liver injury.

Human hepatocytes loaded in 3D bioprinting generate mini-liver.

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Zhong, Cheng; Xie, Hai-Yang; Zhou, Lin; Xu, Xiao; Zheng, Shu-Sen

2016-10-01

Because of an increasing discrepancy between the number of potential liver graft recipients and the number of organs available, scientists are trying to create artificial liver to mimic normal liver function and therefore, to support the patient's liver when in dysfunction. 3D printing technique meets this purpose. The present study was to test the feasibility of 3D hydrogel scaffolds for liver engineering. We fabricated 3D hydrogel scaffolds with a bioprinter. The biocompatibility of 3D hydrogel scaffolds was tested. Sixty nude mice were randomly divided into four groups, with 15 mice in each group: control, hydrogel, hydrogel with L02 (cell line HL-7702), and hydrogel with hepatocyte growth factor (HGF). Cells were cultured and deposited in scaffolds which were subsequently engrafted into livers after partial hepatectomy and radiation-induced liver damage (RILD). The engrafted tissues were examined after two weeks. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total bilirubin, CYP1A2, CYP2C9, glutathione S-transferase (a-GST), and UDP-glucuronosyl transferase (UGT-2) were compared among the groups. Hematoxylin-eosin (HE) staining and immunohistochemistry of cKit and cytokeratin 18 (CK18) of engrafted tissues were evaluated. The survival time of the mice was also compared among the four groups. 3D hydrogel scaffolds did not impact the viability of cells. The levels of ALT, AST, albumin, total bilirubin, CYP1A2, CYP2C9, a-GST and UGT-2 were significantly improved in mice engrafted with 3D scaffold loaded with L02 compared with those in control and scaffold only (P<0.05). HE staining showed clear liver tissue and immunohistochemistry of cKit and CK18 were positive in the engrafted tissue. Mice treated with 3D scaffold+L02 cells had longer survival time compared with those in control and scaffold only (P<0.05). 3D scaffold has the potential of recreating liver tissue and partial liver functions and can be used in the

ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE

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Juliana Ayres de Alencar Arrais GUERRA

2015-09-01

Full Text Available BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

Tumor and liver uptake models of /sup 67/Ga-citrate

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Ando, I; Sanada, S; Hiraki, T; Hisada, K

1985-03-01

After administration /sup 67/Ga concentrates with time in lysosomes from the cytoplasm of liver cells. The lysosomal role in the accumulation of /sup 67/Ga in the liver cell is weakened upon transformation of the liver cell into a malignant tumor cell. In malignant tumors (except for hepatoma) the lysosome does not play a major role in the tumor concentration of /sup 67/Ga. /sup 67/Ga is bound to acid mucopolysaccharides (keratan polysulfate, etc.) in both tumor and liver. In liver cells, large amounts of /sup 67/Ga are transported into lysosomes with these acid mucopolysaccharides, and in hepatoma cells, quite large amounts of /sup 67/Ga are transported into lysosomes with these acid mucopolysaccharides. In malignant tumor cells (except for hepatoma) the effect is much smaller, the acid mucopolysaccharides transporting very little /sup 67/Ga into lysosome. The /sup 67/Ga is concentrated in viable tumor tissue within malignant tissue but hardly at all in necrotic tumor tissue, and concentrates avidly in inflammatory infiltration around tumor cells. Plenty of /sup 67/Ga is found in liver but very little in connective tissue associated with the liver.

Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages

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Julian Buchrieser

2017-02-01

Full Text Available Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS progenitors generated before the emergence of hematopoietic stem cells (HSCs. Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.

Tissue refractometry using Hilbert phase microscopy.

Science.gov (United States)

Lue, Niyom; Bewersdorf, Joerg; Lessard, Mark D; Badizadegan, Kamran; Dasari, Ramachandra R; Feld, Michael S; Popescu, Gabriel

2007-12-15

We present, for the first time to our knowledge, quantitative phase images associated with unstained 5 mum thick tissue slices of mouse brain, spleen, and liver. The refractive properties of the tissue are retrieved in terms of the average refractive index and its spatial variation. We find that the average refractive index varies significantly with tissue type, such that the brain is characterized by the lowest value and the liver by the highest. The spatial power spectra of the phase images reveal power law behavior with different exponents for each tissue type. This approach opens a new possibility for stain-free characterization of tissues, where the diagnostic power is provided by the intrinsic refractive properties of the biological structure. We present results obtained for liver tissue affected by a lysosomal storage disease and show that our technique can quantify structural changes during this disease development.

Fatty Liver

International Nuclear Information System (INIS)

Filippone, A.; Digiovandomenico, V.; Digiovandomenico, E.; Genovesi, N.; Bonomo, L.

1991-01-01

The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a 'skip area', in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of 'Skip area'. Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between broght liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical 'skip area', by demonstrating normal density - which suggests that CT can characterize normal tissue in atypical 'skip area'

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis.

Science.gov (United States)

Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

2017-12-14

To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. A CCl 4 -induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo . Functionally, the transplantation of hUC-MSCs to CCl 4 -treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl 4 -induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

CT Perfusion Characteristics Identify Metastatic Sites in Liver

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Yuan Wang

2015-01-01

Full Text Available Tissue perfusion plays a critical role in oncology because growth and migration of cancerous cells require proliferation of new blood vessels through the process of tumor angiogenesis. Computed tomography (CT perfusion is an emerging functional imaging modality that measures tissue perfusion through dynamic CT scanning following intravenous administration of contrast medium. This noninvasive technique provides a quantitative basis for assessing tumor angiogenesis. CT perfusion has been utilized on a variety of organs including lung, prostate, liver, and brain, with promising results in cancer diagnosis, disease prognostication, prediction, and treatment monitoring. In this paper, we focus on assessing the extent to which CT perfusion characteristics can be used to discriminate liver metastases from neuroendocrine tumors from normal liver tissues. The neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow (BF, blood volume (BV, mean transit time (MTT, permeability (PS, and hepatic arterial fraction (HAF, for tumor and normal liver. The result reveals the potential of CT perfusion as a tool for constructing biomarkers from features of the hepatic vasculature for guiding cancer detection, prognostication, and treatment selection.

Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

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J. Schmitz

2016-05-01

Conclusions: These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.

Liver Immunology

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Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

2014-01-01

The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

Tissue-Engineered Vascular Rings from Human iPSC-Derived Smooth Muscle Cells

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Biraja C. Dash

2016-07-01

Full Text Available There is an urgent need for an efficient approach to obtain a large-scale and renewable source of functional human vascular smooth muscle cells (VSMCs to establish robust, patient-specific tissue model systems for studying the pathogenesis of vascular disease, and for developing novel therapeutic interventions. Here, we have derived a large quantity of highly enriched functional VSMCs from human induced pluripotent stem cells (hiPSC-VSMCs. Furthermore, we have engineered 3D tissue rings from hiPSC-VSMCs using a facile one-step cellular self-assembly approach. The tissue rings are mechanically robust and can be used for vascular tissue engineering and disease modeling of supravalvular aortic stenosis syndrome. Our method may serve as a model system, extendable to study other vascular proliferative diseases for drug screening. Thus, this report describes an exciting platform technology with broad utility for manufacturing cell-based tissues and materials for various biomedical applications.

PEPCK-C reexpression in the liver counters neonatal hypoglycemia in Pck1 del/del mice, unmasking role in non-gluconeogenic tissues.

Science.gov (United States)

Semakova, Jana; Hyroššová, Petra; Méndez-Lucas, Andrés; Cutz, Ernest; Bermudez, Jordi; Burgess, Shawn; Alcántara, Soledad; Perales, José C

2017-02-01

Whole body cytosolic phosphoenolpyruvate carboxykinase knockout (PEPCK-C KO) mice die early after birth with profound hypoglycemia therefore masking the role of PEPCK-C in adult, non-gluconeogenic tissues where it is expressed. To investigate whether PEPCK-C deletion in the liver was critically responsible for the hypoglycemic phenotype, we reexpress this enzyme in the liver of PEPCK-C KO pups by early postnatal administration of PEPCK-C-expressing adenovirus. This maneuver was sufficient to partially rescue hypoglycemia and allow the pups to survive and identifies the liver as a critical organ, and hypoglycemia as the critical pathomechanism, leading to early postnatal death in the whole-body PEPCK-C knockout mice. Pathology assessment of survivors also suggest a possible role for PEPCK-C in lung maturation and muscle metabolism.

Bio-inspired fabrication of fibroin cryogels from the muga silkworm Antheraea assamensis for liver tissue engineering

International Nuclear Information System (INIS)

Kundu, Banani; Kundu, S C

2013-01-01

Conventional scaffold fabrication techniques result in narrow pore architectures causing a limited interconnectivity and use of porogens, which affects the bio- or cyto-compatibility. To ameliorate this, cryogels are immensely explored due to their macro-porous nature, ease in fabrication, using ice crystals as porogens, the shape property, easy reproducibility and cost-effective fabrication technique. Cryogels in the present study are prepared from nonmulberry Indian muga silk gland protein fibroin of Antheraea assamensis using two different fabrication temperatures (−20 and −80 °C). Anionic surfactant sodium dodecyl sulfate is used to solubilize fibroin, which in turn facilitates gelation by accelerating the ß-sheet formation. Ethanol is employed to stabilize the 3D network and induces bimodal porosity. The gels thus formed demonstrate increased ß-sheet content (FTIR) and a considerable effect of pre-freezing temperatures on 3D micro-architectures. The cryogels are capable of absorbing large amounts of water and withstanding mechanical compression without structure deformation. Further, cell impregnated cryogels well support the viability of human hepatocarcinoma cells (live/dead assay). The formation of cellular aggregates (confocal laser and scanning electron microscope), derivation in metabolic activity and proliferation rate are obtained in constructs fabricated at different temperatures. In summary, the present work reveals promising insights in the development of a biomimetic functional template for biomedical therapeutics and liver tissue engineering. (paper)

Radioprotection of normal tissues in tumor-bearing mice by troxerutin

International Nuclear Information System (INIS)

Maurya, D.K.; Salvi, V.P.; Krishnan Nair, C.K.

2004-01-01

The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of γ-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from γ-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by intraperitoneal (ip) one hour prior to 4 Gy whole-body γ-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in γ-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals. (author)

Beneifcial effect of reifned red palm oil on lipid peroxidation and monocyte tissue factor in HCV-related liver disease：a randomized controlled study

Institute of Scientific and Technical Information of China (English)

Roberto Catanzaro; Nicola Zerbinati; Umberto Solimene; Massimiliano Marcellino; Dheeraj Mohania; Angelo Italia; Antonio Ayala; Francesco Marotta

2016-01-01

BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carot-enoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinlfammatory cytokines proifle, and monocyte tissue factor in patients with chronic liver disease. METHODS: The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices. RESULTS: Both treatments signiifcantly decreased erythro-cyte malondialdehyde and urinary isoprostane output, only RPO signiifcantly affected macrophage-colony stimulating fac-tor and monocyte tissue factor. Liver ultrasound imaging did not show any change. CONCLUSIONS: RPO beneifcially modulates oxidative stress and, not least, downregulates macrophage/monocyte inlfam-matory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chron-ic liver diseases.

Phytosterols, Lipid Administration, and Liver Disease During Parenteral Nutrition.

Science.gov (United States)

Zaloga, Gary P

2015-09-01

Phytosterols are plant-derived sterols that are structurally and functionally analogous to cholesterol in vertebrate animals. Phytosterols are found in many foods and are part of the normal human diet. However, absorption of phytosterols from the diet is minimal. Most lipid emulsions used for parenteral nutrition are based on vegetable oils. As a result, phytosterol administration occurs during intravenous administration of lipid. Levels of phytosterols in the blood and tissues may reach high levels during parenteral lipid administration and may be toxic to cells. Phytosterols are not fully metabolized by the human body and must be excreted through the hepatobiliary system. Accumulating scientific evidence suggests that administration of high doses of intravenous lipids that are high in phytosterols contributes to the development of parenteral nutrition-associated liver disease. In this review, mechanisms by which lipids and phytosterols may cause cholestasis are discussed. Human studies of the association of phytosterols with liver disease are reviewed. In addition, clinical studies of lipid/phytosterol reduction for reversing and/or preventing parenteral nutrition associated liver disease are discussed. © 2015 American Society for Parenteral and Enteral Nutrition.

Liver diseases and aging : friends or foes?

NARCIS (Netherlands)

Sheedfar, Fareeba; Di Biase, Stefano; Koonen, Debby; Vinciguerra, Manlio

2013-01-01

The liver is the only internal human organ capable of natural regeneration of lost tissue, as little as 25% of a liver can regenerate into a whole liver. The process of aging predisposes to hepatic functional and structural impairment and metabolic risk. Therefore, understanding how aging could

Adipose Tissue as an Endocrine Organ: An Update on Pro-inflammatory and Anti-inflammatory Microenvironment

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Kvido Smitka

2015-01-01

Full Text Available Adipose tissue is recognized as an active endocrine organ that produces a number of endocrine substances referred to as “adipokines” including leptin, adiponectin, adipolin, visfatin, omentin, tumour necrosis factor-alpha (TNF-α, interleukin-6 (IL-6, resistin, pigment epithelium-derived factor (PEDF, and progranulin (PGRN which play an important role in the food intake regulation and significantly influence insulin sensitivity and in some cases directly affect insulin resistance in skeletal muscle, liver, and adipose tissue. The review summarizes current knowledge about adipose tissue-derived hormones and their influence on energy homeostasis regulation. The possible therapeutic potential of these adipokines in the treatment of insulin resistance, endothelial dysfunction, a pro-inflammatory response, obesity, eating disorders, progression of atherosclerosis, type 1 diabetes, and type 2 diabetes is discussed.

Evaluation the effect of silver nanoparticles on oxidative stress biomarkers in blood serum and liver and kidney tissues

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Mahsa Tashakori Miyanroudi

2016-07-01

Full Text Available Objective(s: Silver nanoparticles (Ag-NPs are one of the most widely used nanomaterials recently. Despite the wide application of nanomaterials, there is limited information concerning their impact on human health and the environment. This study aimed to find the effects of Ag-NPs (40 nm on blood serum, liver and kidney tissues of homing pigeons (Columbia livia.Materials and Methods: Columba livia, in vivo model used in ecotoxicity experiments were gavaged 3 times daily with 75 and 150 ppm of Ag-NPs within 14 days. A group of 30 Pigeon were randomly divided into three groups: Ag-NPs exposed and control groups (n=10. Data analysis was counducted by performing one-way variance (ANOVA in SPSS.v.16.0                                                                         Results: The results of this study illustrated that in the enzyme activity of Glutathione S –transferase (GST, Aspartate amino transferase (AST, Alanine amino transferase (ALT and lactate dehydrogenas (LDH there is a significant difference between treatment groups with Ag-NPs and the control group. Also, lipid peroxidation (LPO analysis and catalase activity CAT suggest Ag-NPs cause the main damage to the liver tissue. On the other hand: Ag-NPs have toxic and harmful effects in both concentrations (75 and 150 ppm, and cause LPO induction, oxidative stress and increase of biomarkers of liver necrosis in under treatment pigeons.Conclusion: The results of this study show that the organism’s exposure to Ag-NPs cause toxicity that is dose-dependant. in this study, the highest damage was observed in the liver. However, this issue will have to be considered more extensively in further studies.

Age dependence of rat liver function measurements

DEFF Research Database (Denmark)

Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

1989-01-01

Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All...... liver function measurements increased from the age of 8 to 44 weeks when expressed in absolute values. In relation to body weight, these function measurements were unchanged or reduced from week 8 to week 20. At week 44, galactose elimination capacity and capacity of urea-N synthesis related to body...... weight were increased by 10% and 36%, respectively, and antipyrine plasma clearance was reduced to 50%. Liver tissue concentrations of microsomal cytochrome P-450 and microsomal protein increased with age when expressed in absolute values, but were unchanged per g liver, i.e., closely related to liver...

Treating fructose-induced metabolic changes in mice with high-intensity interval training: insights in the liver, white adipose tissue, and skeletal muscle.

Science.gov (United States)

Motta, Victor F; Bargut, Thereza L; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A

2017-10-01

Fructose-rich caloric sweeteners induce adverse changes in the metabolism of humans. The study evaluated the effects of high-intensity interval training (HIIT) on a fructose feeding model, focusing on the liver, white adipose tissue (WAT), skeletal muscle, and their interplay. Male C57BL/6 mice were fed for 18 wk one of the following diets: control (C; 5% of total energy from fructose) or fructose (F; 55% of total energy from fructose). In the 10th week, for an additional 8-wk period, the groups were divided into nontrained (NT) or HIIT groups, totaling four groups: C-NT, C-HIIT, F-NT, and F-HIIT. At the end of the experiment, fructose consumption in the F-NT group led to a high systolic blood pressure, high plasma triglycerides, insulin resistance with glucose intolerance, and lower insulin sensitivity. We also observed liver steatosis, adipocyte hypertrophy, and diminished gene expressions of peroxisome proliferator-activated receptor-γ coactivator 1-α and fibronectin type III domain containing 5 (FNDC5; irisin) in this F-NT group. These results were accompanied by decreased gene expressions of nuclear respiratory factor 1 and mitochondrial transcription factor A (markers of mitochondrial biogenesis), and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1 (markers of β-oxidation). HIIT improved all of these data in the C-HIIT and F-HIIT groups. In conclusion, in mice fed a fructose diet, HIIT improved body mass, blood pressure, glucose metabolism, and plasma triglycerides. Liver, WAT, and skeletal muscle were positively modulated by HIIT, indicating HIIT as a coadjutant treatment for diseases affecting these tissues. NEW & NOTEWORTHY We investigated the effects of high-intensity interval training (HIIT) in mice fed a fructose-rich diet and the resulting severe negative effect on the liver, white adipose tissue (WAT), and skeletal muscle, which reduced the expression of fibronectin type III domain containing 5 (FNDC5, irisin) and

Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS Horses

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Krzysztof Marycz

2018-01-01

Full Text Available Nowadays, endocrine disorders have become more frequent in both human and veterinary medicine. In horses, reduced physical activity combined with carbohydrate and sugar overload may result in the development of the so-called equine metabolic syndrome (EMS. EMS is characterized by insulin resistance, hyperinsulinemia, elevated blood triglyceride concentrations and usually obesity. Although the phenotypic features of EMS individuals are well known, the molecular mechanism underlying disease development remains elusive. Therefore, in the present study, we analyzed insulin-sensitive tissues, i.e., muscles, liver and adipose tissue in order to evaluate insulin resistance and apoptosis. Furthermore, we assessed mitochondrial dynamics and mitophagy in those tissues, because mitochondrial dysfunction is linked to the development of metabolic syndrome. We established the expression of genes related to insulin resistance, endoplasmic reticulum (ER stress and mitochondria clearance by mitophagy using RT-PCR and Western blot. Cell ultrastructure was visualized using electron transmission microscopy. The results indicated that adipose tissue and liver of EMS horses were characterized by increased mitochondrial damage and mitophagy followed by triggering of apoptosis as mitophagy fails to restore cellular homeostasis. However, in muscles, apoptosis was reduced, suggesting the existence of a protective mechanism allowing that tissue to maintain homeostasis.

Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells

OpenAIRE

Eirin, Alfonso; Zhu, Xiang-Yang; Puranik, Amrutesh S.; Woollard, John R.; Tang, Hui; Dasari, Surendra; Lerman, Amir; van Wijnen, Andre J.; Lerman, Lilach O.

2017-01-01

Background Mesenchymal stromal/stem cell (MSC) transplantation is a promising therapy for tissue regeneration. Extracellular vesicles (EVs) released by MSCs act as their paracrine effectors by delivering proteins and genetic material to recipient cells. To assess how their cargo mediates biological processes that drive their therapeutic effects, we integrated miRNA, mRNA, and protein expression data of EVs from porcine adipose tissue-derived MSCs. Methods Simultaneous expression profiles of m...

A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro.

Science.gov (United States)

Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

2017-01-01

Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotra-nsformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two‑dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases.

Human dental pulp stem cells derived from cryopreserved dental pulp tissues of vital extracted teeth with disease demonstrate hepatic-like differentiation.

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Chen, Y K; Huang, Anderson H C; Chan, Anthony W S; Lin, L M

2016-06-01

Reviewing the literature, hepatic differentiation of human dental pulp stem cells (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with disease has not been studied. This study is aimed to evaluate the hypothesis that hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease could possess potential hepatic differentiation. Forty vital extracted teeth with disease recruited for hDPSCs isolation, stem cell characterization and hepatic differentiation were randomly and equally divided into group A (liquid nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp tissues). Samples of hDPSCs isolated from groups A and B but without hepatic growth factors formed negative controls. A well-differentiated hepatocellular carcinoma cell line was employed as a positive control. All the isolated hDPSCs from groups A and B showed hepatic-like differentiation with morphological change from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated hDPSCs and the positive control expressed hepatic metabolic function genes and liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from day 7 of differentiation-medium culture. Positive immunofluorescence staining of low-density lipoprotein and albumin was observed from day 14 of differentiation-medium culture; urea production in the medium was noted from week 6. No hepatic differentiation was observed for any of the samples of the negative controls. We not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease but also indicated that the differentiated cells possessed normal karyotype and were functionally close to normal hepatic-like cells. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.

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Shirazi, Alireza; Mihandoost, Ehsan; Ghobadi, Ghazale; Mohseni, Mehran; Ghazi-Khansari, Mahmoud

2013-01-01

Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.

Ligament Tissue Engineering Using a Novel Porous Polycaprolactone Fumarate Scaffold and Adipose Tissue-Derived Mesenchymal Stem Cells Grown in Platelet Lysate.

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Wagner, Eric R; Bravo, Dalibel; Dadsetan, Mahrokh; Riester, Scott M; Chase, Steven; Westendorf, Jennifer J; Dietz, Allan B; van Wijnen, Andre J; Yaszemski, Michael J; Kakar, Sanjeev

2015-11-01

Surgical reconstruction of intra-articular ligament injuries is hampered by the poor regenerative potential of the tissue. We hypothesized that a novel composite polymer "neoligament" seeded with progenitor cells and growth factors would be effective in regenerating native ligamentous tissue. We synthesized a fumarate-derivative of polycaprolactone fumarate (PCLF) to create macro-porous scaffolds to allow cell-cell communication and nutrient flow. Clinical grade human adipose tissue-derived human mesenchymal stem cells (AMSCs) were cultured in 5% human platelet lysate (PL) and seeded on scaffolds using a dynamic bioreactor. Cell growth, viability, and differentiation were examined using metabolic assays and immunostaining for ligament-related markers (e.g., glycosaminoglycans [GAGs], alkaline phosphatase [ALP], collagens, and tenascin-C). AMSCs seeded on three-dimensional (3D) PCLF scaffolds remain viable for at least 2 weeks with proliferating cells filling the pores. AMSC proliferation rates increased in PL compared to fetal bovine serum (FBS) (p ligament and tenogenic growth factor fibroblast growth factor 2 (FGF-2), especially when cultured in the presence of PL (p engineering and ligament regeneration.

Dickkopf-3, a tissue-derived modulator of local T cell responses

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Michael eMeister

2015-02-01

Full Text Available The adaptive immune system protects organisms from harmful environmental insults. In parallel, regulatory mechanisms control immune responses in order to assure preservation of organ integrity. Yet, molecules involved in the control of T cell responses in peripheral tissues are poorly characterized. Here, we investigated the function of Dickkopf-3 in the modulation of local T cell reactivity. Dkk3 is a secreted, mainly tissue derived protein with highest expression in organs considered as immune privileged such as the eye, embryo, placenta and brain. While T cell development and activation status in naïve Dkk3 deficient mice was comparable to littermate controls, we found that Dkk3 contributes to the immunosuppressive microenvironment that protects transplanted, class-I mismatched embryoid bodies from T cell mediated rejection. Moreover, genetic deletion or antibody mediated neutralization of Dkk3 led to an exacerbated experimental autoimmune encephalomyelitis (EAE. This phenotype was accompanied by a change of T cell polarization displayed by an increase of IFNγ producing T cells within in the CNS. In the wild type situation, Dkk3 expression in the brain was up-regulated during the course of EAE in an IFNγ dependent manner. In turn, Dkk3 decreased IFNγ activity and served as part of a negative feedback mechanism. Thus, our findings suggest that Dkk3 functions as a tissue-derived modulator of local CD4+ and CD8+ T cell responses.

Xenon-133 hepatic retention ratio: A useful index for fatty liver quantification

International Nuclear Information System (INIS)

Yeh, S.H.; Wu, L.C.; Wang, S.J.; Lin, H.C.; Liu, R.S.; Lee, S.D.; Wu, J.C.

1989-01-01

Xenon-133 hepatic retention ratio was developed for quantifying fatty liver. Data were acquired in frame mode in the hepatic region and both lung bases for 5 min after rebreathing 20 mCi of gaseous 133 Xe and for another 5 min during washout. Static [ 99m Tc]sulfur colloid liver imaging was performed with the patient in the identical position immediately after the ventilation study and data were stored for liver localization. A hepatic time-activity curve corrected for background activity was generated. The 133Xe retention ratio was derived by dividing the activity at 3.5 min after washout by the peak activity. The data of 16 controls and 20 patients with fatty liver were analyzed. The retention ratio (mean +/- s.d.) was greatly increased in patients with fatty infiltration (0.43 +/- 0.20 vs. 0.04 +/- 0.08 in controls, p less than 0.001). There was a strong positive correlation between the 133 Xe retention ratios and percentage of fat on biopsy as assessed by the amount of the liver tissue occupied by fat globules on H ampersand E stained sections. The 133 Xe hepatic retention ratio is a simple, accurate and clinically useful index of detecting, quantifying and managing fatty infiltration of the liver

Hyperdensity liver tumor on plain CT

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Hirota, Shozo; Hanaguri, Katsuro [Kochi Municipal Central Hospital (Japan); Shimizu, Masahumi; Sako, Masao; Harada, Yasushi

1984-12-01

Most liver tumors on plain CT have been recognized as low density or iso-density masses. Sometimes calcified high density masses were shown on plain CT in case of cysts or metastatic liver tumors. However, hyperdensity mass of the liver on CT, of which the density was a little higher than surrounding tissues, was very rare. Recently 7 patients with hyperdensity liver masses on plain CT were experienced: 6 hepatocellular carcinomas and 1 hepatic cavernous hemangioma. A single hyperdensity mass was shown in 4 patients, a hyperdensity mass of multiple hepatic tumors was shown in 2 patients, and some hyperdensity masses of multiple hepatic tumors were shown in 1 patient. Lesions are classified in 3 types according to the appearance of hyperdensity masses: diffuse hyperdensity all over the mass, ring like hyperdensity, creascent like hyperdensity. Intravenous contrast enhancement was performed in 2 patients: one with a primary hepatocellular carcinoma, and another with a hepatic cavernous hemangioma. In the former case the tumor margin had changed unclear, in the latter case the tumor was markedly enhanced. Our results revealed that hyperdensity liver tumors were divided into 2 types: One type, shown in a cavernous hemangioma with fatty liver, demonstrated relative hyperdensity due to lower density of the surrounding tissue. Another type, shown in 6 hepatocellular carcinomas, showed hyperdensity since the density of the tumor was hyperdensity relative to the surrounding tissue of the liver. It was suggested that the tumor with the latter type had been strongly probable of malignant one, and been recommended to receive further examination. Cause of hyperdensity was thought to be due to hemorrhage, though microcalcification could not be denyed. In Japan, no hyperdensity liver tumor had been reported partly due to a wide window width with which CT photographs were taken.

Differential gene expression in liver tissues of streptozotocin-induced diabetic rats in response to resveratrol treatment.

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Gökhan Sadi

Full Text Available This study was conducted to elucidate the genome-wide gene expression profile in streptozotocin induced diabetic rat liver tissues in response to resveratrol treatment and to establish differentially expressed transcription regulation networks with microarray technology. In addition to measure the expression levels of several antioxidant and detoxification genes, real-time quantitative polymerase chain reaction (qRT-PCR was also used to verify the microarray results. Moreover, gene and protein expressions as well as enzymatic activities of main antioxidant enzymes; superoxide dismutase (SOD-1 and SOD-2 and glutathione S-transferase (GST-Mu were analyzed. Diabetes altered 273 genes significantly and 90 of which were categorized functionally which suggested that genes in cellular catalytic activities, oxidation-reduction reactions, co-enzyme binding and terpenoid biosynthesis were dominated by up-regulated expression in diabetes. Whereas; genes responsible from cellular carbohydrate metabolism, regulation of transcription, cell signal transduction, calcium independent cell-to-cell adhesion and lipid catabolism were down-regulated. Resveratrol increased the expression of 186 and decreased the expression of 494 genes in control groups. While cellular and extracellular components, positive regulation of biological processes, biological response to stress and biotic stimulants, and immune response genes were up-regulated, genes responsible from proteins present in nucleus and nucleolus were mainly down-regulated. The enzyme assays showed a significant decrease in diabetic SOD-1 and GST-Mu activities. The qRT-PCR and Western-blot results demonstrated that decrease in activity is regulated at gene expression level as both mRNA and protein expressions were also suppressed. Resveratrol treatment normalized the GST activities towards the control values reflecting a post-translational effect. As a conclusion, global gene expression in the liver tissues is

Bone Marrow-Derived Mesenchymal Stem Cells Attenuate Immune-Mediated Liver Injury and Compromise Virus Control During Acute Hepatitis B Virus Infection in Mice.

Science.gov (United States)

Qu, Mengmeng; Yuan, Xu; Liu, Dan; Ma, Yuhong; Zhu, Jun; Cui, Jun; Yu, Mengxue; Li, Changyong; Guo, Deyin

2017-06-01

Mesenchymal stem cells (MSCs) have been used as therapeutic tools not only for their ability to differentiate toward different cells, but also for their unique immunomodulatory properties. However, it is still unknown how MSCs may affect immunity during hepatitis B virus (HBV) infection. This study was designed to explore the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic natural killer (NK) cells in a mouse model of acute HBV infection. Mice were injected with 1 × 10 6 BM-MSCs, which stained with chloromethyl derivatives of fluorescein diacetate fluorescent probe, 24 h before hydrodynamic injection of viral DNA (pHBV1.3) through the tail vein. In vivo imaging system revealed that BM-MSCs were accumulated in the injured liver, and they attenuated immune-mediated liver injury during HBV infection, as shown by lower alanine aminotransferase levels, reduced proinflammatory cytokine production, and decreased inflammatory cell infiltration in the liver. Importantly, administration of BM-MSCs restrained the increased expression of natural-killer group 2, member D (NKG2D), an important receptor required for NK cell activation in the liver from HBV-infected mice. BM-MSCs also reduced NKG2D expression on NK cells and suppressed the cytotoxicity of NK cells in vitro. Furthermore, BM-MSC-derived transforming growth factor-β1 suppressed NKG2D expression on NK cells. As a consequence, BM-MSC treatment enhanced HBV gene expression and replication in vivo. These results demonstrate that adoptive transfer of BM-MSCs influences innate immunity and limits immune-mediated liver injury during acute HBV infection by suppressing NK cell activity. Meanwhile, the effect of BM-MSCs on prolonging virus clearance needs to be considered in the future.

Liver slices in in vitro pharmacotoxicology with special reference to the use of human liver tissue

NARCIS (Netherlands)

Olinga, Peter; Meijer, D.K F; Slooff, M.JH; Groothuis, Geny

In the early years of research in in vitro pharmacotoxicology liver slices have been used. After a decline in the application of slices in favour of the use of isolated hepatocytes and the isolated perfused liver preparation, the development of the Krumdieck slicer in the 1980s led to a 'comeback'

Quantitative PET of liver functions.

Science.gov (United States)

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

Quantitative PET of liver functions

Science.gov (United States)

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

Heterogeneity of the radiosensitivity and origins of tissue macrophage colony-forming cells

Energy Technology Data Exchange (ETDEWEB)

Oghiso, Yoichi; Yamada, Yutaka (National Inst. of Radiological Sciences, Chiba (Japan))

1992-12-01

Previous studies suggest that the radiosensitivity and origin of tissue macrophage precursors differ from those of hemopoietic macrophage colony-forming units (CFU-Ms) committed to macrophage-lineage cells. We assessed the origins of tissue macrophage colony-forming cells (M-CFCs) in mice by comparing their kinetics and radiosensitivities in the normal steady state and under the conditions of bone marrow depletion by [sup 89]Sr-administration and/or splenectomy. The results indicate that the radiosensitive peritoneal M-CFCs elicited by thioglycollate are derived from bone marrow macrophage precursors; where as alveolar M-CFCs, which are radioresistant, are self-sustained locally and independent of hemopoietic macrophage precursors. In contrast, highly radiosensitive liver M-CFCs are probably derived from CFU-Ms that appear to be propagated in the spleen in association with hemopoietic responses. (author).

Gastric cancer tissue-derived mesenchymal stem cells impact peripheral blood mononuclear cells via disruption of Treg/Th17 balance to promote gastric cancer progression.

Science.gov (United States)

Wang, Mei; Chen, Bin; Sun, Xiao-Xian; Zhao, Xiang-Dong; Zhao, Yuan-Yuan; Sun, Li; Xu, Chang-Gen; Shen, Bo; Su, Zhao-Liang; Xu, Wen-Rong; Zhu, Wei

2017-12-01

Gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) are important resident stromal cells in the tumor microenvironment (TME) and have been shown to play a key role in gastric cancer progression. Whether GC-MSCs exert a tumor-promoting function by affecting anti-tumor immunity is still unclear. In this study, we used GC-MSC conditioned medium (GC-MSC-CM) to pretreat peripheral blood mononuclear cells (PBMCs) from healthy donors. We found that GC-MSC-CM pretreatment markedly reversed the inhibitory effect of PBMCs on gastric cancer growth in vivo, but did not affect functions of PBMCs on gastric cancer cell proliferation, cell cycle and apoptosis in vitro. PBMCs pretreated with GC-MSC-CM significantly promoted gastric cancer migration and epithelial-mesenchymal transition in vitro and liver metastases in vivo. Flow cytometry analysis showed that GC-MSC-CM pretreatment increased the proportion of Treg cells and reduced that of Th17 cells in PBMCs. CFSE labeling and naïve CD4 + T cells differentiation analysis revealed that GC-MSC-CM disrupted the Treg/Th17 balance in PBMCs by suppressing Th17 cell proliferation and inducing differentiation of Treg cells. Overall, our collective results indicate that GC-MSCs impair the anti-tumor immune response of PBMCs through disruption of Treg/Th17 balance, thus providing new evidence that gastric cancer tissue-derived MSCs contribute to the immunosuppressive TME. Copyright © 2017 Elsevier Inc. All rights reserved.

European research and commercialisation activities in the field of tissue engineering and liver support in world wide competition.

Science.gov (United States)

Marx, U; Bushnaq, H; Yalcin, E

1998-02-01

Tissue engineering is seen as an interesting field of technology which could improve medical therapy and could also be considered as a commercial opportunity for the European biotechnological industry. Research in the state of the art of science using the MedLine and the Science Citation Index databases, in the patent situation and of the industry dealing with tissue engineering was done. A special method, based on the Science Citation Index Journal Citation Report 1993, for evaluating scientific work was defined. The main countries working in the field of tissue engineering were evaluated in regard to their scientific performance and their patents. The R&D of German industry was investigated as an exemplary European country. Out of all activities, different tissues were rated with respect to the attention received from research and industry and with regard to the frequency in which patents were applied for. USA, Germany and Japan rank first in most tissues, especially liver. After comparing German patents with the German scientific and industrial work, it seems that the potential in German patents and research is underestimated by German industry and inefficiently exploited.

Autologous Adipose-Derived Tissue Matrix Part I: Biologic Characteristics.

Science.gov (United States)

Schendel, Stephen A

2017-10-01

Autologous collagen is an ideal soft tissue filler and may serve as a matrix for stem cell implantation and growth. Procurement of autologous collagen has been limited, though, secondary to a sufficient source. Liposuction is a widely performed and could be a source of autologous collagen. The amount of collagen and its composition in liposuctioned fat remains unknown. The purpose of this research was to characterize an adipose-derived tissue-based product created using ultrasonic cavitation and cryo-grinding. This study evaluated the cellular and protein composition of the final product. Fat was obtained from individuals undergoing routine liposuction and was processed by a 2 step process to obtain only the connective tissue. The tissue was then evaluated by scanning electronic microscope, Western blot analysis, and flow cytometry. Liposuctioned fat was obtained from 10 individuals with an average of 298 mL per subject. After processing an average of 1 mL of collagen matrix was obtained from each 100 mL of fat. Significant viable cell markers were present in descending order for adipocytes > CD90+ > CD105+ > CD45+ > CD19+ > CD144+ > CD34+. Western blot analysis showed collagen type II, III, IV, and other proteins. Scanning electronic microscope study showed a regular pattern of cross-linked, helical collagen. Additionally, vital staing demonstrated that the cells were still viable after processing. Collagen and cells can be easily obtained from liposuctioned fat by ultrasonic separation without alteration of the overall cellular composition of the tissue. Implantation results in new collagen and cellular growth. Collagen matrix with viable cells for autologous use can be obtained from liposuctioned fat and may provide long term results. 5. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Heavy metal levels in the liver and muscle tissues of the four commercial fishes from Lake Balik, Kızılırmak Delta (Samsun, Turkey

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Levent Bat

2015-12-01

Full Text Available Objective: To determine the levels of some heavy metals in the liver and edible tissues of four fish species [Mugil cephalus L., 1758 (M. cephalus, Cyprinus carpio L., 1758 (C. carpio, Perca fluviatilis L., 1758 (P. fluviatilis and Stizostedion lucioperca L., 1758 (S. lucioperca] collected from Lake Balik, Kizilirmak Delta (Samsun for analysis of Cu, Co, Pb, Zn, Cd, Mn, Ni and Fe. These metals were chosen because at higher concentrations there might be toxic to the fish and by extension humans that depends on such fish as food. Methods: The concentrations of the metals were carried out by the flame atomic absorption spectrophotometer (UNICAM 929. Results: Large differences in heavy metal levels were observed between liver and muscle tissues within each fish. The results showed that the Fe concentrations were the highest and Cd concentrations were the lowest in livers and edible tissues of the four species. The muscles of C. carpio accumulated significant higher levels of Co, Zn and Ni than other species. Cu was higher in the muscles of S. lucioperca than those in other species, while M. cephalus showed more of Mn and Fe levels. The muscles of P. fluviatilis accumulated significant higher levels of Pb and Cd than other species. However, the liver of M. cephalus accumulated significant higher levels of Co, Mn and Fe than other species. The level of Cd was the highest in the liver of P. fluviatilis, while S. lucioperca showed more of Cu and Pb, and the higher levels of Zn and Ni was measured in the liver of C. carpio. Conclusions: The metal levels obtained were compared with the maximum permitted levels in food of the Turkish Food Codex and Commission Regulation (EC. The results of this study showed that estimated daily and weekly intakes of selected metals via consumption of fish were below the permissible tolerable daily intake and provisional tolerable weekly intake values established by Food and Agriculture Organization/World Health

Comparative studies on the distribution of rhodanese in different tissues of domestic animals.

Science.gov (United States)

Aminlari, M; Gilanpour, H

1991-01-01

1. The activity of rhodanese in different tissues of some domestic animals was measured. 2. Rhodanese was present in all tissues studied. 3. The activity of rhodanese in most tissues of sheep was higher than other animals studied. 4. In sheep and cattle the epithelium of rumen, omasum and reticulum were the richest sources of rhodanese. Significant activity of rhodanese was also present in liver and kidney. 5. In camel the liver contained the highest level of rhodanese followed by lung and rumen epithelium. Camel liver contained a third of the activity of sheep liver. 6. Equine liver had a third of the activity of sheep liver. Other tissues showed low levels of rhodanese activity. 7. Dog liver contained only 4% of the activity of sheep liver. In this animal, brain was the richest source of rhodanese. 8. The results are discussed in terms of efficacy of different tissues of animals in cyanide detoxification.

Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues.

Directory of Open Access Journals (Sweden)

Ashkan Maccabi

Full Text Available Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E, long term shear modulus (η, and time constant (τ in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research.

Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues.

Science.gov (United States)

Maccabi, Ashkan; Shin, Andrew; Namiri, Nikan K; Bajwa, Neha; St John, Maie; Taylor, Zachary D; Grundfest, Warren; Saddik, George N

2018-01-01

Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA) and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs) and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E), long term shear modulus (η), and time constant (τ) in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research.

Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage

Science.gov (United States)

Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe; Roberts, William; Cain, Charles; Xu, Zhen

2014-01-01

Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues.

The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

International Nuclear Information System (INIS)

Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

2015-01-01

Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57 Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the 57 Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues

The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

Science.gov (United States)

Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

2015-04-01

Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient's tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients' spleen and liver tissues.

Implications of human tissue studies

International Nuclear Information System (INIS)

Kathren, R.L.

1986-10-01

Through radiochemical analysis of voluntary tissue donations, the United States Transuranium and Uranium Registries are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole body contributions to the Transuranium Registry revealed an inverse proportionality between actinide concentration and bone ash fraction. The analysis of a whole body with a documented 241 Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies of the Registries are designed to evaluate in vivo estimates of actinide deposition with those derived from postmortem tissue analysis, compare results of animal experiments with human data, and reviw histopathologic slides for tissue toxicity that might be attributable to exposure to uranium and the transuranic elements. The implications of these recent findings and other work of the Registries are discussed from the standpoint of their potential impact on biokinetic modeling, internal dose assessment, safety standards, and operational health physics practices

Effects of Re-heating Tissue Samples to Core Body Temperature on High-Velocity Ballistic Projectile-tissue Interactions.

Science.gov (United States)

Humphrey, Caitlin; Henneberg, Maciej; Wachsberger, Christian; Maiden, Nicholas; Kumaratilake, Jaliya

2017-11-01

Damage produced by high-speed projectiles on organic tissue will depend on the physical properties of the tissues. Conditioning organic tissue samples to human core body temperature (37°C) prior to conducting ballistic experiments enables their behavior to closely mimic that of living tissues. To minimize autolytic changes after death, the tissues are refrigerated soon after their removal from the body and re-heated to 37°C prior to testing. This research investigates whether heating 50-mm-cube samples of porcine liver, kidney, and heart to 37°C for varying durations (maximum 7 h) can affect the penetration response of a high-speed, steel sphere projectile. Longer conditioning times for heart and liver resulted in a slight loss of velocity/energy of the projectile, but the reverse effect occurred for the kidney. Possible reasons for these trends include autolytic changes causing softening (heart and liver) and dehydration causing an increase in density (kidney). © 2017 American Academy of Forensic Sciences.

Ultrasound-based Liver Elastography: Recent Advances

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Lee, Jae Young; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of)

2011-12-15

The invasiveness and sampling errors of liver biopsies have prompted the development of diverse non-invasive methods for evaluating liver stiffness. Recently, shear wave-based ultrasound elastography, such as transient elastography (TE), acoustic radiation force impulse (ARFI) imaging and supersonic shear imaging (SSI), as well as quasi-static elastography, such as real-time tissue elastography, have been introduced as noninvasive techniques for evaluating liver stiffness. This editorial reviews each elastographic technique in terms of the principle and clinical applications for the liver diseases

Liver-resident NK cells and their potential functions.

Science.gov (United States)

Peng, Hui; Sun, Rui

2017-09-18

Natural killer (NK) cells represent a heterogeneous population of innate lymphocytes with phenotypically and functionally distinct subsets. In particular, recent studies have identified a unique subset of NK cells residing within the liver that are maintained as tissue-resident cells, confer antigen-specific memory responses and exhibit different phenotypical and developmental characteristics compared with conventional NK (cNK) cells. These findings have encouraged researchers to uncover tissue-resident NK cells at other sites, and detailed analyses have revealed that these tissue-resident NK cells share many similarities with liver-resident NK cells and tissue-resident memory T cells. Here, we present a brief historical perspective on the discovery of liver-resident NK cells and discuss their relationship to cNK cells and other emerging NK cell subsets and their potential functions.Cellular &Molecular Immunology advance online publication, 18 September 2017; doi:10.1038/cmi.2017.72.

Energy Metabolism in the Liver

Science.gov (United States)

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes.

Science.gov (United States)

Wen, Shu Wen; Sceneay, Jaclyn; Lima, Luize Goncalves; Wong, Christina S F; Becker, Melanie; Krumeich, Sophie; Lobb, Richard J; Castillo, Vanessa; Wong, Ke Ni; Ellis, Sarah; Parker, Belinda S; Möller, Andreas

2016-12-01

Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45 + bone marrow-derived cells. Subsequent long-term conditioning of naïve mice with exosomes from highly metastatic breast cancer cells revealed the accumulation of myeloid-derived suppressor cells in the lung and liver. This favorable immune suppressive microenvironment was capable of promoting metastatic colonization in the lung and liver, an effect not observed from exosomes derived from nonmetastatic cells and liposome control vesicles. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation and inhibited NK cell cytotoxicity, and hence likely suppressed the anticancer immune response in premetastatic organs. Together, our findings provide novel insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to immune suppression and promotion of metastases. Cancer Res; 76(23); 6816-27. ©2016 AACR. ©2016 American Association for Cancer Research.

Distribution of sterol carrier protein2 (SCP2) in rat tissues and evidence for slow turnover in liver and adrenal cortex

International Nuclear Information System (INIS)

Kharroubi, A.; Chanderbhan, R.; Fiskum, G.; Noland, B.J.; Scallen, T.J.; Vahouny, G.V.

1986-01-01

Sterol carrier protein 2 (SCP 2 ) has been implicated in the regulation of the terminal stages of hepatic cholesterol biosynthesis, and in sterol utilization for adrenal steroid hormone and hepatic bile acid synthesis. In the present studies, a highly sensitive radioimmunoassay, using [ 125 I] SCP 2 , has been developed. Highest levels of SCP 2 were found in rat liver with progressively lower levels in intestinal mucosa, adrenal, kidney, lung and testis. SCP 2 levels were low or absent in heart, brain, skeletal muscle and serum. Liver SCP 2 was largely (44%) associated with the microsomal fraction, while in adrenal, 46% was associated with mitochondria, a distribution which is consistent with the proposed roles for SCP 2 in these tissues. Levels of SCP 2 in AS 30D hepatoma cells were only 5% of those in normal liver. In liver there was no indication of diurnal rhythm of SCP 2 in the cytosol and only slight variation of the microsomal SCP 2 levels. Fasting has only slight effects on SCP 2 concentration of rat liver microsomes and cytosol. Neither ACTH nor cycloheximide treatment of rats had a significant effect on SCP 2 distribution in the adrenal. In general, these findings indicate that SCP 2 has a low turn-over rate

Cloning Changes the Response to Obesity of Innate Immune Factors in Blood, Liver, and Adipose Tissues in Domestic Pigs

DEFF Research Database (Denmark)

Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Stagsted, Jan

2013-01-01

The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune...... factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both...... upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls...

Relationship between liver tissue stiffness and histopathological findings analyzed by shear wave elastography and compression testing in rats with non-alcoholic steatohepatitis.

Science.gov (United States)

Ogawa, Saori; Moriyasu, Fuminori; Yoshida, Keiko; Oshiro, Hisashi; Kojima, Mayumi; Sano, Takatomo; Furuichi, Yoshihiro; Kobayashi, Yoshiyuki; Nakamura, Ikuo; Sugimoto, Katsutoshi

2016-07-01

The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings. Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings. Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033). Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities.

Laser-induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection.

Science.gov (United States)

Isbert, Christoph; Ritz, Jörg-Peter; Roggan, André; Schuppan, Detlef; Ajubi, Navid; Buhr, Heinz Johannes; Hohenberger, Werner; Germer, Christoph-Thomas

2007-01-01

Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24-96 hours and 14 days after intervention. Volumes of the untreated tumors prior to intervention were 38+/-8 mm(3) in group I (laser), 39 +/- 7 mm(3) in group II (resection), and 42 +/- 12 mm(3) in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor+/-SEM volume of untreated tumor in group I (laser) [223 +/- 36] was smaller than in group II (resection) [1233.28 +/- 181.52; P tumor growth in comparison to hepatic resection. Accelerated tumor growth after hepatic resection is associated with higher mRNA level of HGF and reduced tumor growth after LITT with higher mRNA level of CTGF. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT. (c) 2006 Wiley-Liss, Inc.

Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease

OpenAIRE

de Witte, Samantha F. H.; Merino, Ana M.; Franquesa, Marcella; Strini, Tanja; van Zoggel, Johanna A. A.; Korevaar, Sander S.; Luk, Franka; Gargesha, Madhu; O?Flynn, Lisa; Roy, Debashish; Elliman, Steve J.; Newsome, Philip N.; Baan, Carla C.; Hoogduijn, Martin J.

2017-01-01

Background Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. Methods MSC derived from human umbilical cords (ucMSC) were treated for 3?days in vitro with various inflammator...

Gene expression profiling of liver cancer stem cells by RNA-sequencing.

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David W Y Ho

Full Text Available BACKGROUND: Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90(+ liver cancer stem cells (CSCs in hepatocellular carcinoma (HCC. Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq to compare the gene expression profiling of CD90(+ cells sorted from tumor (CD90(+CSCs with parallel non-tumorous liver tissues (CD90(+NTSCs and elucidate the roles of putative target genes in hepatocarcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: CD90(+ cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90(+ cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90(+CSCs and CD90(+NTSCs, and validated by quantitative real-time PCR (qRT-PCR on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes between CD90(+CSCs and CD90(+NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90(+CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3, a member of glypican family, was markedly elevated in CD90(+CSCs compared to CD90(+NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90(+CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90(+CSCs in liver tumor tissues. CONCLUSIONS

Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

Science.gov (United States)

Lam, Chi Tat; Ng, Michael N. P.; Yu, Wan Ching; Lau, Joyce; Wan, Timothy; Wang, Xiaoqi; Yan, Zhixiang; Liu, Hang; Fan, Sheung Tat

2012-01-01

Background Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90+ liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90+ cells sorted from tumor (CD90+CSCs) with parallel non-tumorous liver tissues (CD90+NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis. Methodology/Principal Findings CD90+ cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90+ cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90+CSCs and CD90+NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90+CSCs and CD90+NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90+CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90+CSCs compared to CD90+NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90+CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90+CSCs in liver tumor tissues. Conclusions/Significance The identified genes

PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS.

Science.gov (United States)

Almeida, Gilberto S; Bawn, Carlo M; Galler, Martin; Wilson, Ian; Thomas, Huw D; Kyle, Suzanne; Curtin, Nicola J; Newell, David R; Maxwell, Ross J

2017-09-01

Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ( 1 H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD + ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild-type (WT) and PARP1 knock-out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. 1 H-MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD + levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD + levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD + levels in the temozolomide-treated group. The combination of rucaparib and temozolomide did not prevent the NAD + depletion caused by temozolomide treatment. The 1 H-MRS results show that NAD + levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD + would be valuable. Copyright © 2017 John Wiley & Sons, Ltd.

Enamel matrix derivative enhances tissue formation around scaffolds used for tissue engineering of ligaments.

Science.gov (United States)

Messenger, Michael P; Raïf, El M; Seedhom, Bahaa B; Brookes, Steven J

2010-02-01

The following in vitro translational study investigated whether enamel matrix derivative (EMD), an approved biomimetic treatment for periodontal disease (Emdogain) and hard-to-heal wounds (Xelma), enhanced synovial cell colonization and protein synthesis around a scaffold used clinically for in situ tissue engineering of the torn anterior cruciate ligament (ACL). Synovial cells were enzymatically extracted from bovine synovium and dynamically seeded onto polyethylene terephthalate (PET) scaffolds. The cells were cultured in low-serum medium (0.5% FBS) for 4 weeks with either a single administration of EMD at the start of the 4 week period or multiple administrations of EMD at regular intervals throughout the 4 weeks. Samples were harvested and evaluated using the Hoechst DNA assay, BCA protein assay, cresolphthalein complexone calcium assay, SDS-PAGE, ELISA and electron microscopy. A significant increase in cell number (DNA) (p < 0.01), protein content (p < 0.01) and TGFbeta1 synthesis (p < 0.01) was observed with multiple administrations of EMD. Additionally, SDS-PAGE showed an increase in high molecular weight proteins, characteristic of the fibril-forming collagens. Electron microscopy supported these findings, showing that scaffolds treated with multiple administrations of EMD were heavily coated with cells and extracellular matrix (ECM) that enveloped the fibres. Multiple administrations of EMD to synovial cell-seeded scaffolds enhanced the formation of tissue in vitro. Additionally, it was shown that EMD enhanced TGFbeta1 synthesis of synovial cells, suggesting a potential mode of action for EMD's capacity to stimulate tissue regeneration.

Comparison of acoustic radiation force impulse imaging (ARFI) to liver biopsy histologic scores in the evaluation of chronic liver disease: A pilot study.

Science.gov (United States)

Haque, Mazhar; Robinson, Charlotte; Owen, David; Yoshida, Eric M; Harris, Alison

2010-01-01

Acoustic Radiation Force Impulse Imaging (ARFI) is a novel non invasive technique studying the localized mechanical properties of tissue by utilising short, high intensity acoustic pulses (shear wave pulses) to assess the mechanical response (tissue displacement), providing a measure of tissue elasticity. The aim of this study is to investigate the feasibility of ARFI imaging as a non-invasive method for the assessment of liver fibrosis compared to liver biopsy scores. A prospective blind comparison study of ARFI elastography (Virtual Touch Imaging., ACUSON S2000 Ultrasound Unit, Siemens, Mountain View CA) in a consecutive series of patients who underwent liver biopsy for assessment of fibrosis in chronic liver disease. ARFI shear-wave propagation velocity was measured in meters per second. Mean ARFI velocities were compared with both Batts-Ludwig (F0 to F4) and Modified Ishak scores (F0 to F4) for fibrosis in liver biopsy findings. Twenty-one patients with chronic liver disease (Hepatitis C (HCV) =16, Hepatitis B (HBV) = 1, both HCV and HBV = 1 Alcoholic liver disease (ALD) = 1, others = 2) underwent ARFI and liver biopsy on the same day. The Spearman correlation coefficients between the median values of the ARFI measurements and the histological fibrosis stage of the Modified Ishak score and Batts-Lud- (3) wig score were both highly significant (p shak score in chronic liver disease. It.s accuracy in prediction of severe fibrosis and cirrhosis is maximal in comparison with earlier stages.