Centipede Venoms and Their Components: Resources for Potential Therapeutic Applications

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Md Abdul Hakim

2015-11-01

Full Text Available Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components.

Medicinal plants growing in the Judea region: network approach for searching potential therapeutic targets

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Arie Budovsky

2012-09-01

Full Text Available Plants growing in the Judea region are widely used in traditional medicine of the Levant region. Nevertheless, they have not so far been sufficiently analyzed and their medicinal potential has not been evaluated. This study is the first attempt to fill the gap in the knowledge of the plants growing in the region. Comprehensive data mining of online botanical databases and peer-reviewed scientific literature including ethno-pharmacological surveys from the Levant region was applied to compile a full list of plants growing in the Judea region, with the focus on their medicinal applications. Around 1300 plants growing in the Judea region were identified. Of them, 25% have medicinal applications which were analyzed in this study. Screening for chemical-protein interactions, together with the network-based analysis of potential targets, will facilitate discovery and therapeutic applications of the Judea region plants. Such an approach could also be applied as an integrative platform for further searching the potential therapeutic targets of plants growing in other regions of the world.

Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

International Nuclear Information System (INIS)

Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

2007-01-01

It has been six decades since synthesis of organophosphates, but this chapter has not yet come to a closure. Toxic effects of organophosphates are well known and the current therapeutic scheme includes supportive therapy and antidotes. There is a dilemma on whether and when to apply gastric lavage and activated charcoal. According to Position Statement (by EAPCCT) it should be applied only if the patient presents within one hour of ingestion, with potentially lethal ingested dose. Atropine, a competitive antagonist of acetylcholine at m-receptors, which antagonizes bronchosecretion and bronchoconstriction, is the corner stone of acute organophosphate poisoning therapy. There were many attempts to find a more efficient drug, including glycopyrrolate which has been used even in clinical trials, but it still can not replace atropine. The only dilemma about atropine usage which still exists, concerns usage of high atropine dose and scheme of application. The most efficient atropinization is achieved with bolus doses of 1-2mg of atropine i.v push, with repeating the dose on each 5 minutes until signs of atropinization are registered. Diazepam, with its GABA stabilizing effect, reduces central nervous system damage and central respiratory weakness. Oximes reactivate phosphorylated acetylcholinesterase, which still has not gone ageing, reducing acetylcholine concentration and cholinergic crisis. These effects are clearly demonstrated in experimental conditions, but the clinical significance of oximes is still unclear and there are still those who question oxime therapy. For those who approve it, oxime dosage, duration of therapy, the choice of oxime for certain OP is still an open issue. We need new, more efficient antidotes, and those that are in use are only the small part of the therapy which could be used. Experimental studies show favorable therapeutic effect of many agents, but none of them has been introduced in standard treatment of OPI poisoning in the last 30

Dendrimers as Potential Therapeutic Tools in HIV Inhibition

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Xiangbo Li

2013-07-01

Full Text Available The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. On the one hand, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. Some of the dendrimers are capable of intruding into the cell and interfere with the later stages of HIV replication as well. On the other hand, dendrimers are also able to transfer chemical drugs and genes into the host cells, which conspicuously increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection.

Therapeutic potential of curcumin in gastrointestinal diseases

OpenAIRE

Rajasekaran, Sigrid A

2011-01-01

Curcumin, also known as diferuloylmethane, is derived from the plant Curcuma longa and is the active ingredient of the spice turmeric. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. More recently, curcumin’s therapeutic potential for preventing and treating various cancers is being recognized. As curcumin’s therapeutic promise is being explored more system...

Therapeutic potential of adult stem cells

DEFF Research Database (Denmark)

Serakinci, Nedime; Keith, W. Nicol

2006-01-01

is the necessity to be able to identify, select, expand and manipulate cells outside the body. Recent advances in adult stem cell technologies and basic biology have accelerated therapeutic opportunities aimed at eventual clinical applications. Adult stem cells with the ability to differentiate down multiple...... lineages are an attractive alternative to human embryonic stem cells (hES) in regenerative medicine. In many countries, present legislation surrounding hES cells makes their use problematic, and indeed the origin of hES cells may represent a controversial issue for many communities. However, adult stem...... cells are not subject to these issues. This review will therefore focus on adult stem cells. Based on their extensive differentiation potential and, in some cases, the relative ease of their isolation, adult stem cells are appropriate for clinical development. Recently, several observations suggest...

Therapeutic Applications of Rose Hips from Different Rosa Species.

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Mármol, Inés; Sánchez-de-Diego, Cristina; Jiménez-Moreno, Nerea; Ancín-Azpilicueta, Carmen; Rodríguez-Yoldi, María Jesús

2017-05-25

Rosa species, rose hips, are widespread wild plants that have been traditionally used as medicinal compounds for the treatment of a wide variety of diseases. The therapeutic potential of these plants is based on its antioxidant effects caused by or associated with its phytochemical composition, which includes ascorbic acid, phenolic compounds and healthy fatty acids among others. Over the last few years, medicinal interest in rose hips has increased as a consequence of recent research that has studied its potential application as a treatment for several diseases including skin disorders, hepatotoxicity, renal disturbances, diarrhoea, inflammatory disorders, arthritis, diabetes, hyperlipidaemia, obesity and cancer. In this review, the role of different species of Rosa in the prevention of treatment of various disorders related to oxidative stress, is examined, focusing on new therapeutic approaches from a molecular point of view.

Garlic: a review of potential therapeutic effects

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Bayan, Leyla; Koulivand, Peir Hossain; Gorji, Ali

2014-01-01

Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases. PMID:25050296

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

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Etame, Arnold B.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

The chicken TH1 response: potential therapeutic applications of ChIFN-γ.

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Guo, Pengju; Thomas, Jesse D; Bruce, Matthew P; Hinton, Tracey M; Bean, Andrew G D; Lowenthal, John W

2013-11-01

The outcomes of viral infections are costly in terms of human and animal health and welfare worldwide. The observed increase in the virulence of some viruses and failure of many vaccines to stop these infections has lead to the apparent need to develop new anti-viral strategies. One approach to dealing with viral infection may be to employ the therapeutic administration of recombinant cytokines to act as 'immune boosters' to assist in augmenting the host response to virus. With this in mind, a greater understanding of the immune response, particularly cell mediated T-helper-1 (TH1) type responses, is imperative to the development of new anti-viral and vaccination strategies. Following the release of the chicken genome, a number of TH1-type cytokines have been identified, including chicken interleukin-12 (ChIL-12), ChIL-18 and interferon-γ ChIFN-γ), highlighting the nature of the TH1-type response in this non-mammalian vertebrate. To date a detailed analysis of the in vivo biological function of these cytokines has been somewhat hampered by access to large scale production techniques. This review describes the role of TH-1 cytokines in immune responses to viruses and explores their potential use in enhancing anti-viral treatment strategies in chickens. Furthermore, this review focuses on the example of ChIFN-γ treatment of Chicken Anemia Virus (CAV) infection. CAV causes amongst other things thymocyte depletion and thymus atrophy, as well as immunosuppression in chickens. However, due to vaccination, clinical disease appears less often, nevertheless, the subclinical form of the disease is often associated with secondary complicating infections due to an immunocompromised state. Since CAV-induced immunosuppression can cause a marked decrease in the immune response against other pathogens, understanding this aspect of the disease is critically important, as well as providing insights into developing new control approaches. With increasing emphasis on developing

Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential.

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Kuche, Kaushik; Maheshwari, Rahul; Tambe, Vishakha; Mak, Kit-Kay; Jogi, Hardi; Raval, Nidhi; Pichika, Mallikarjuna Rao; Kumar Tekade, Rakesh

2018-05-17

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

A readily applicable strategy to convert peptides to peptoid-based therapeutics.

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Minyoung Park

Full Text Available Incorporation of unnatural amino acids and peptidomimetic residues into therapeutic peptides is highly efficacious and commonly employed, but generally requires laborious trial-and-error approaches. Previously, we demonstrated that C20 peptide has the potential to be a potential antiviral agent. Herein we report our attempt to improve the biological properties of this peptide by introducing peptidomimetics. Through combined alanine, proline, and sarcosine scans coupled with a competitive fluorescence polarization assay developed for identifying antiviral peptides, we enabled to pinpoint peptoid-tolerant peptide residues within C20 peptide. The synergistic benefits of combining these (and other commonly employed methods could lead to a easily applicable strategy for designing and refining therapeutically-attractive peptidomimetics.

Insights into the Antimicrobial Properties of Hepcidins: Advantages and Drawbacks as Potential Therapeutic Agents

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Lisa Lombardi

2015-04-01

Full Text Available The increasing frequency of multi-drug resistant microorganisms has driven research into alternative therapeutic strategies. In this respect, natural antimicrobial peptides (AMPs hold much promise as candidates for the development of novel antibiotics. However, AMPs have some intrinsic drawbacks, such as partial degradation by host proteases or inhibition by host body fluid composition, potential toxicity, and high production costs. This review focuses on the hepcidins, which are peptides produced by the human liver with a known role in iron homeostasis, as well by numerous other organisms (including fish, reptiles, other mammals, and their potential as antibacterial and antifungal agents. Interestingly, the antimicrobial properties of human hepcidins are enhanced at acidic pH, rendering these peptides appealing for the design of new drugs targeting infections that occur in body areas with acidic physiological pH. This review not only considers current research on the direct killing activity of these peptides, but evaluates the potential application of these molecules as coating agents preventing biofilm formation and critically assesses technical obstacles preventing their therapeutic application.

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

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Sathish Sundar Dhilip Kumar

2018-04-01

Full Text Available Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

Science.gov (United States)

Sundar Dhilip Kumar, Sathish; Houreld, Nicolette Nadene; Abrahamse, Heidi

2018-04-05

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric ( Curcuma longa ) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

Therapeutic potential of fecal microbiota transplantation

NARCIS (Netherlands)

Smits, Loek P.; Bouter, Kristien E. C.; de Vos, Willem M.; Borody, Thomas J.; Nieuwdorp, Max

2013-01-01

There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal

Recent progress in the therapeutic applications of nanotechnology.

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Solomon, Melani; D'Souza, Gerard G M

2011-04-01

The field of pharmaceutical and medical nanotechnology has grown rapidly in recent decades and offers much promise for therapeutic advances. This review is intended to serve as a quick summary of the major areas in the therapeutic application of nanotechnology. Nanotechnology for therapeutic application falls into two broad categories of particulate systems and nanoengineered devices. Recent studies appear to focus on the development of multifunctional particles for drug delivery and imaging and the development of nanotechnology-based biosensors for diagnostic applications. Cancer treatment and diagnosis appears to be the principal focus of many of these applications, but nanotechnology is also finding application in tissue engineering and surface engineering of medical implants. Particulate drug delivery systems in general appear to be poised for increased use in the clinic, whereas nanoengineered implants and diagnostic sensors might well be the next major wave in the medical use of nanotechnology.

Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes

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Shih-Chang Chien

2015-01-01

Full Text Available Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes.

Inflammatory bowel disease: potential therapeutic strategies

DEFF Research Database (Denmark)

Nielsen, O H; Vainer, B; Bregenholt, S

1997-01-01

This review deals with potential and possibly primary therapeutics that, through insight into the inflammatory cascade, result in more rational treatment principles replacing the classical therapy of inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC). These ne...

Frontiers in nano-therapeutics

CERN Document Server

Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

2017-01-01

This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

Investigating Therapeutic Potential of Trigonella foenum-graecum L. as Our Defense Mechanism against Several Human Diseases

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Shivangi Goyal

2016-01-01

Full Text Available Current lifestyle, stress, and pollution have dramatically enhanced the progression of several diseases in human. Globally, scientists are looking for therapeutic agents that can either cure or delay the onset of diseases. Medicinal plants from time immemorial have been used frequently in therapeutics. Of many such plants, fenugreek is one of the oldest herbs which have been identified as an important medicinal plant by the researchers around the world. It is potentially beneficial in a number of diseases such as diabetes, hypercholesterolemia, and inflammation and probably in several kinds of cancers. It has industrial applications such as synthesis of steroidal hormones. Its medicinal properties and their role in clinical domain can be attributed to its chemical constituents. The 3 major chemical constituents which have been identified as responsible for principle health effects are galactomannan, 4-OH isoleucine, and steroidal saponin. Numerous experiments have been carried out in vivo and in vitro for beneficial effects of both the crude chemical and of its active constituent. Due to its role in health care, the functional food industry has referred to it as a potential nutraceutical. This paper is about various medicinal benefits of fenugreek and its potential application as therapeutic agent against several diseases.

Nanoparticles for therapeutic and diagnostic applications

OpenAIRE

Chiu, Yin To

2014-01-01

Nanomedicine focuses on the development and engineering of novel and unique therapeutic and diagnostic agents that can overcome the challenges associated with using traditional modalities. Nanoparticles (NPs) in the size range between 1 and 1000 nm have many advantages for use in these applications, such as, low polydispersity, established characterization methodologies, and the ability to be loaded with therapeutics for diseases, conjugated to targeting ligands to enhance specificity, and co...

Therapeutic potential of Aegle marmelos (L.-An overview

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Shahedur Rahman

2014-02-01

Full Text Available Medicinal plants are used in herbalism. They form the easily available source for healthcare purposes in rural and tribal areas. In the present review, an attempt has been made to congregate the phytochemical and pharmacological studies done on an important medicinal plant Aegle marmelos. Extensive experimental and clinical studies prove that Aegle marmelos possesses antidiarrhoeal, antimicrobial, antiviral, radioprotective, anticancer, chemopreventive, antipyretic, ulcer healing, antigenotoxic, diuretic, antifertility and anti-inflammatory properties, which help it to play role in prevention and treatment of many disease. Therefore, it is worthwhile to review its therapeutic properties to give an overview of its status to scientist both modern and ancient. This review also encompasses on the potential application of the above plant in the pharmaceutical field due to its wide pharmacological activities.

Engineered magnetic core shell nanoprobes: Synthesis and applications to cancer imaging and therapeutics.

Science.gov (United States)

Mandal, Samir; Chaudhuri, Keya

2016-02-26

Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.

The human gut microbiota and virome: Potential therapeutic implications.

Science.gov (United States)

Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio

2015-12-01

Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

X-ray application in diagnostics and therapeutics

International Nuclear Information System (INIS)

Braun, H.

1975-01-01

The lecture gives a general survey on the present possibilities of application of X-rays and radio-isotopes in medical diagnostics and therapeutics. The possibility of decreasing the radiation exposure by using image intensifiers and television is particularly indicated. The advantages of scintiscanning in diagnostics are presented by means of a series of examples. The increasing significance of telecurie equipment and particle accelerators are refered to in therapeutics. Finally, the radiation risk due to the medical application of radiation to the patient and the personnel is discussed and compared to the natural radiation exposure. (ORU/LH) [de

The causative role and therapeutic potential of the kynurenine pathway in neurodegenerative disease.

Science.gov (United States)

Amaral, Marta; Outeiro, Tiago F; Scrutton, Nigel S; Giorgini, Flaviano

2013-06-01

Metabolites of the kynurenine pathway (KP), which arise from the degradation of tryptophan, have been studied in detail for over a century and garnered the interest of the neuroscience community in the late 1970s and early 1980s with work uncovering the neuromodulatory potential of this pathway. Much research in the following decades has found that perturbations in the levels of KP metabolites likely contribute to the pathogenesis of several neurodegenerative diseases. More recently, it has become apparent that targeting KP enzymes, in particular kynurenine 3-monooxygenase (KMO), may hold substantial therapeutic potential for these disorders. Here we provide an overview of the KP, the neuroactive properties of KP metabolites and their role in neurodegeneration. We also discuss KMO as a therapeutic target for these disorders, and our recent resolution of the crystallographic structure of KMO, which will permit the development of new and improved KMO inhibitors which may ultimately expedite clinical application of these compounds.

Asparagus racemosus: a review on its phytochemical and therapeutic potential.

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Singh, Ram

2016-09-01

Asparagus racemosus (Willd.) is a widely found medicinal plant in tropical and subtropical parts of India. The therapeutic applications of this plant have been reported in Indian and British Pharmacopoeias and in traditional system of medicine, such as Ayurveda, Unani and Siddha. The crude, semi-purified and purified extracts obtained from different parts of this plant have been useful in therapeutic applications. Numerous bioactive phytochemicals mostly saponins and flavonoids have been isolated and identified from this plant which are responsible alone or in combination for various pharmacological activities. This review aims to give a comprehensive overview of traditional applications, current knowledge on the phytochemistry, pharmacology and overuse of A. racemosus.

Therapeutic Applications of Herbal Medicines for Cancer Patients

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Shu-Yi Yin

2013-01-01

Full Text Available Medicinal herbs and their derivative phytocompounds are being increasingly recognized as useful complementary treatments for cancer. A large volume of clinical studies have reported the beneficial effects of herbal medicines on the survival, immune modulation, and quality of life (QOL of cancer patients, when these herbal medicines are used in combination with conventional therapeutics. Here, we briefly review some examples of clinical studies that investigated the use of herbal medicines for various cancers and the development of randomized controlled trials (RCTs in this emerging research area. In addition, we also report recent studies on the biochemical and cellular mechanisms of herbal medicines in specific tumor microenvironments and the potential application of specific phytochemicals in cell-based cancer vaccine systems. This review should provide useful technological support for evidence-based application of herbal medicines in cancer therapy.

Aptamer nanomedicine for cancer therapeutics: barriers and potential for translation.

Science.gov (United States)

Lao, Yeh-Hsing; Phua, Kyle K L; Leong, Kam W

2015-03-24

Aptamer nanomedicine, including therapeutic aptamers and aptamer nanocomplexes, is beginning to fulfill its potential in both clinical trials and preclinical studies. Especially in oncology, aptamer nanomedicine may perform better than conventional or antibody-based chemotherapeutics due to specificity compared to the former and stability compared to the latter. Many proof-of-concept studies on applying aptamers to drug delivery, gene therapy, and cancer imaging have shown promising efficacy and impressive safety in vivo toward translation. Yet, there remains ample room for improvement and critical barriers to be addressed. In this review, we will first introduce the recent progress in clinical trials of aptamer nanomedicine, followed by a discussion of the barriers at the design and in vivo application stages. We will then highlight recent advances and engineering strategies proposed to tackle these barriers. Aptamer cancer nanomedicine has the potential to address one of the most important healthcare issues of the society.

Biomedical and therapeutic applications of biosurfactants

OpenAIRE

Rodrigues, L. R.; Teixeira, J. A.

2010-01-01

During the last years, several applications of biosurfactants with medical purposes have been reported. Biosurfactants are considered relevant molecules for applications in combating many diseases and as therapeutic agents due to their antibacterial, antifungal and antiviral activities. Furthermore, their role as anti-adhesive agents against several pathogens illustrate their utility as suitable anti-adhesive coating agents for medical insertional materials leading to a reduction of a large n...

Tunable resistive pulse sensing: potential applications in nanomedicine.

Science.gov (United States)

Sivakumaran, Muttuswamy; Platt, Mark

2016-08-01

An accurate characterization of nanomaterials used in clinical diagnosis and therapeutics is of paramount importance to realize the full potential of nanotechnology in medicine and to avoid unexpected and potentially harmful toxic effects due to these materials. A number of technical modalities are currently in use to study the physical, chemical and biological properties of nanomaterials but they all have advantages and disadvantages. In this review, we discuss the potential of a relative newcomer, tunable resistive pulse sensing, for the characterization of nanomaterials and its applications in nanodiagnostics.

Therapeutic potential of cannabis-related drugs.

Science.gov (United States)

Alexander, Stephen P H

2016-01-04

In this review, I will consider the dual nature of Cannabis and cannabinoids. The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the 'abuse' of Cannabis outside the clinic. The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma. As with every other medicinal drug of course, the 'trick' will be to maximise the benefit and minimise the cost. After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit. Copyright © 2015 Elsevier Inc. All rights reserved.

RBC micromotors carrying multiple cargos towards potential theranostic applications

Science.gov (United States)

Wu, Zhiguang; Esteban-Fernández de Ávila, Berta; Martín, Aída; Christianson, Caleb; Gao, Weiwei; Thamphiwatana, Soracha Kun; Escarpa, Alberto; He, Qiang; Zhang, Liangfang; Wang, Joseph

2015-08-01

Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic resonance imaging. The simultaneous encapsulation of the imaging nanoparticles and therapeutic payloads within the same RBC micromotor has a minimal effect upon its propulsion behavior. The ability of the RBC micromotors to transport imaging and therapeutic agents at high speed and spatial precision through a complex microchannel network is also demonstrated. Such ability to load and transport diagnostic imaging agents and therapeutic drugs within a single cell-based motor, in addition to a lower toxicity observed once the drug is encapsulated within the multicargo RBC motor, opens the door to the development of theranostic micromotors that may simultaneously treat and monitor diseases.Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic

Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells.

Science.gov (United States)

Kang, N-H; Hwang, K-A; Kim, S U; Kim, Y-B; Hyun, S-H; Jeung, E-B; Choi, K-C

2012-08-01

As stem cells are capable of self-renewal and can generate differentiated progenies for organ development, they are considered as potential source for regenerative medicine and tissue replacement after injury or disease. Along with this capacity, stem cells have the therapeutic potential for treating human diseases including cancers. According to the origins, stem cells are broadly classified into two types: embryonic stem cells (ESCs) and adult stem cells. In terms of differentiation potential, ESCs are pluripotent and adult stem cells are multipotent. Amnion, which is a membranous sac that contains the fetus and amniotic fluid and functions in protecting the developing embryo during gestation, is another stem cell source. Amnion-derived stem cells are classified as human amniotic membrane-derived epithelial stem cells, human amniotic membrane-derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They are in an intermediate stage between pluripotent ESCs and lineage-restricted adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti-inflammation. Furthermore, they are easily available and do not cause any controversial issues in their recovery and applications. Not only are amnion-derived stem cells applicable in regenerative medicine, they have anticancer capacity. In non-engineered stem cells transplantation strategies, amnion-derived stem cells effectively target the tumor and suppressed the tumor growth by expressing cytotoxic cytokines. Additionally, they also have a potential as novel delivery vehicles transferring therapeutic genes to the cancer formation sites in gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous properties, amnion-derived stem cells are emerging as a new candidate in anticancer therapy.

The Prognostic, Diagnostic, and Therapeutic Potential of Tumor Antigens

DEFF Research Database (Denmark)

Olsen, Lars Rønn

or abundance in cancer cells is often unique and their roles and functions in tumorigenesis are, in many cases, studied extensively. They, therefore, have the potential to be highly specific biomarkers as well as therapeutic targets, but complex analysis combining basic science, high-throughput methods...... of genomics and proteomics, and clinical studies need to be combined. These analyses produce large amounts of data that require advanced bioinformatics methods for collection, management, integration and interpretation. In this thesis, I have explored the potential of tumor antigens as biomarkers...... and therapeutic agents, by developing and implementing several computational tools and databases for immunotherapy target discovery, and have analyzed the potential of tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas. In this analysis I have shown that the combination of proteomics...

Potential Therapeutic Benefits of Green and Fermented Rooibos (Aspalathus linearis) in Dermal Wound Healing.

Science.gov (United States)

Pringle, Nadine A; Koekemoer, Trevor C; Holzer, Andrea; Young, Carly; Venables, Luanne; van de Venter, Maryna

2018-02-28

The process of wound healing constitutes an ordered sequence of events that provides numerous opportunities for therapeutic intervention to improve wound repair. Rooibos, Aspalathus linearis , is a popular ingredient in skin care products, however, little scientific data exists exploring its therapeutic potential. In the present study, we evaluated the effects of fermented and aspalathin-enriched green rooibos in various in vitro models representative of dermal wound healing. Treatment of RAW 264.7 macrophages with fermented rooibos resulted in increased nitric oxide production as well as increased levels of cellular inducible nitric oxide synthase and cyclooxygenase-2, which are typical markers for classically activated macrophages. In contrast, the green extract was devoid of such activity. Using glycated gelatin as a model to mimic diabetic wounds, only the green extract showed potential to reduce cyclooxygenase-2 levels. Considering the role of reactive oxygen species in wound healing, the effects of rooibos on oxidative stress and cell death in human dermal fibroblasts was evaluated. Both fermented and green rooibos decreased cellular reactive oxygen species and attenuated apoptotic/necrotic cell death. Our findings highlight several properties that support the therapeutic potential of rooibos, and demonstrate that green and fermented rooibos present distinctly different properties with regards to their application in wound healing. The proinflammatory nature of fermented rooibos may have therapeutic value for wounds characterised with a delayed initial inflammatory phase, such as early diabetic wounds. The green extract is more suited to wounds burdened with excessive inflammation as it attenuated cyclooxygenase-2 levels and effectively protected fibroblasts against oxidative stress. Georg Thieme Verlag KG Stuttgart · New York.

Commercially available interactive video games in burn rehabilitation: therapeutic potential.

Science.gov (United States)

Parry, Ingrid S; Bagley, Anita; Kawada, Jason; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

2012-06-01

Commercially available interactive video games (IVG) like the Nintendo Wii™ (NW) and PlayStation™II Eye Toy (PE) are increasingly used in the rehabilitation of patients with burn. Such games have gained popularity in burn rehabilitation because they encourage range of motion (ROM) while distracting from pain. However, IVGs were not originally designed for rehabilitation purposes but rather for entertainment and may lack specificity for achieving rehabilitative goals. Objectively evaluating the specific demands of IVGs in relation to common burn therapy goals will determine their true therapeutic benefit and guide their use in burn rehabilitation. Upper extremity (UE) motion of 24 normal children was measured using 3D motion analysis during play with the two types of IVGs most commonly described for use after burn: NW and PE. Data was analyzed using t-tests and One-way Analysis of Variance. Active range of motion for shoulder flexion and abduction during play with both PE and NW was within functional range, thus supporting the idea that IVGs offer activities with therapeutic potential to improve ROM. PE resulted in higher demands and longer duration of UE motion than NW, and therefore may be the preferred tool when UE ROM or muscular endurance are the goals of rehabilitation. When choosing a suitable IVG for application in rehabilitation, the user's impairment together with the therapeutic attributes of the IVG should be considered to optimize outcome. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Ming-Ming Tsai

2016-06-01

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

Ayahuasca: Pharmacology, neuroscience and therapeutic potential.

Science.gov (United States)

Domínguez-Clavé, Elisabet; Soler, Joaquim; Elices, Matilde; Pascual, Juan C; Álvarez, Enrique; de la Fuente Revenga, Mario; Friedlander, Pablo; Feilding, Amanda; Riba, Jordi

2016-09-01

Ayahuasca is the Quechua name for a tea obtained from the vine Banisteriopsis caapi, and used for ritual purposes by the indigenous populations of the Amazon. The use of a variation of the tea that combines B. caapi with the leaves of the shrub Psychotria viridis has experienced unprecedented expansion worldwide for its psychotropic properties. This preparation contains the psychedelic 5-HT 2A receptor agonist N,N-dimethyltryptamine (DMT) from P. viridis, plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties from B. caapi. Acute administration induces a transient modified state of consciousness characterized by introspection, visions, enhanced emotions and recollection of personal memories. A growing body of evidence suggests that ayahuasca may be useful to treat substance use disorders, anxiety and depression. Here we review the pharmacology and neuroscience of ayahuasca, and the potential psychological mechanisms underlying its therapeutic potential. We discuss recent findings indicating that ayahuasca intake increases certain mindfulness facets related to acceptance and to the ability to take a detached view of one's own thoughts and emotions. Based on the available evidence, we conclude that ayahuasca shows promise as a therapeutic tool by enhancing self-acceptance and allowing safe exposure to emotional events. We postulate that ayahuasca could be of use in the treatment of impulse-related, personality and substance use disorders and also in the handling of trauma. More research is needed to assess the full potential of ayahuasca in the treatment of these disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Exosomes and Their Therapeutic Potentials of Stem Cells

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Chao Han

2016-01-01

Full Text Available Exosomes, a group of vesicles originating from the multivesicular bodies (MVBs, are released into the extracellular space when MVBs fuse with the plasma membrane. Numerous studies indicate that exosomes play important roles in cell-to-cell communication, and exosomes from specific cell types and conditions display multiple functions such as exerting positive effects on regeneration in many tissues. It is widely accepted that the therapeutic potential of stem cells may be mediated largely by the paracrine factors, so harnessing the paracrine effects of stem and progenitor cells without affecting these living, replicating, and potentially pluripotent cell populations is an advantage in terms of safety and complexity. Ascending evidence indicated that exosomes might be the main components of paracrine factors; thus, understanding the role of exosomes in each subtype of stem cells is far-reaching. In this review, we discuss the functions of exosomes from different types of stem cells and emphasize the therapeutic potentials of exosomes, providing an alternative way of developing strategies to cure diseases.

RBC micromotors carrying multiple cargos towards potential theranostic applications.

Science.gov (United States)

Wu, Zhiguang; Esteban-Fernández de Ávila, Berta; Martín, Aída; Christianson, Caleb; Gao, Weiwei; Thamphiwatana, Soracha Kun; Escarpa, Alberto; He, Qiang; Zhang, Liangfang; Wang, Joseph

2015-08-28

Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic resonance imaging. The simultaneous encapsulation of the imaging nanoparticles and therapeutic payloads within the same RBC micromotor has a minimal effect upon its propulsion behavior. The ability of the RBC micromotors to transport imaging and therapeutic agents at high speed and spatial precision through a complex microchannel network is also demonstrated. Such ability to load and transport diagnostic imaging agents and therapeutic drugs within a single cell-based motor, in addition to a lower toxicity observed once the drug is encapsulated within the multicargo RBC motor, opens the door to the development of theranostic micromotors that may simultaneously treat and monitor diseases.

Development and therapeutic application of internally emitting radiopharmaceuticals

International Nuclear Information System (INIS)

Adelstein, S.J.; Bloomer, W.D.

1980-01-01

This project is concerned with developing the potential of alpha-emitting radionuclides as agents for radiotherapy. Among the available α-emitters, astatine-211 appears most promising for testing the efficacy of α-emitters for therapeutic applications because: (1) it has some chemical similarities to iodine, an element that can readily be incorporated into numerous proteins and peptides; (2) it has a half life that is long enough to permit chemical manipulation yet short enough to minimize destruction of healthy cells; and (3) α-emission is associated with 100% of its decays. If appropriate biological carriers can be labeled with an alpha emitter such as 211 At, they could be of great utility in several areas of therapeutic medicine where elimination of specific cell populations is desired. While previous attempts to astatinate proteins using standard iodination techniques have been unsuccessful, effective labeling of proteins with astatine by first synthesizing an aryl astatide and then coupling this compound to the protein via an acylation has been achieved. Undergoing current investigation are several different aryl astatide-followed-by-acylation approaches including an astatinated Bolton-Hunter type reagent using concanavalin A (ConA) and melanocyte stimulating hormone (MSH) as model compounds

Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

Science.gov (United States)

Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

2014-01-01

Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation.

Science.gov (United States)

Faravelli, Irene; Riboldi, Giulietta; Nizzardo, Monica; Simone, Chiara; Zanetta, Chiara; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania

2014-09-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by degeneration of upper and lower motor neurons. There are currently no clinically impactful treatments for this disorder. Death occurs 3-5 years after diagnosis, usually due to respiratory failure. ALS pathogenesis seems to involve several pathological mechanisms (i.e., oxidative stress, inflammation, and loss of the glial neurotrophic support, glutamate toxicity) with different contributions from environmental and genetic factors. This multifaceted combination highlights the concept that an effective therapeutic approach should counteract simultaneously different aspects: stem cell therapies are able to maintain or rescue motor neuron function and modulate toxicity in the central nervous system (CNS) at the same time, eventually representing the most comprehensive therapeutic approach for ALS. To achieve an effective cell-mediated therapy suitable for clinical applications, several issues must be addressed, including the identification of the most performing cell source, a feasible administration protocol, and the definition of therapeutic mechanisms. The method of cell delivery represents a major issue in developing cell-mediated approaches since the cells, to be effective, need to be spread across the CNS, targeting both lower and upper motor neurons. On the other hand, there is the need to define a strategy that could provide a whole distribution without being too invasive or burdened by side effects. Here, we review the recent advances regarding the therapeutic potential of stem cells for ALS with a focus on the minimally invasive strategies that could facilitate an extensive translation to their clinical application.

Therapeutic application of lasers in ophthalmology

International Nuclear Information System (INIS)

Misiuk-Hojlo, M.; Krzyzanowska-Berkowska, P.; Hill-Bator, A.

2007-01-01

Lasers have found application in diverse branches of medicine. In ophthalmology, laser technology has various therapeutic and diagnostic applications. The purpose of this article is to review the major therapeutic applications of lasers in different eye disorders. The effects of lasers on biological tissues and different laser techniques as well as the indications for laser therapy in various parts of the eye are discussed. Lasers are used to treat glaucoma and many vascular disorders of the retina. Laser treatment may be useful in preventing the development of neovascularization in diabetic retinopathy, BRVO, or CRVO. Laser techniques are also available for the treatment of the exudative form of age-related macular degeneration (AMD) and some malignant and benign intraocular tumors and in retina abnormalities which predispose to rhegmatogenous retinal detachment. Corneal laser surgery is the most frequently applied laser procedure in ophthalmology. PRK, LASIK, and LASEK are used to correct errors in vision such as myopia, hyperopia, and astigmatism. Laser photocoagulation is also helpful in cataract surgery. Nowadays, lasers have become so universal that it is difficult to imagine ophthalmology without them. We are still witnessing rapid advances in the development of laser techniques, especially in plastic surgery, cataract extraction, and ocular imaging. (authors)

Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches

Science.gov (United States)

Zhang, Xi-Feng; Liu, Zhi-Guo; Shen, Wei; Gurunathan, Sangiliyandi

2016-01-01

Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs. PMID:27649147

Novel endogenous angiogenesis inhibitors and their therapeutic potential.

Science.gov (United States)

Rao, Nithya; Lee, Yu Fei; Ge, Ruowen

2015-10-01

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application.

Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases

Directory of Open Access Journals (Sweden)

Shaherin Basith

2016-07-01

Full Text Available Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions.

A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

Directory of Open Access Journals (Sweden)

Yuji Tada

2013-01-01

Full Text Available Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

Bioengineering natural product biosynthetic pathways for therapeutic applications.

Science.gov (United States)

Wu, Ming-Cheng; Law, Brian; Wilkinson, Barrie; Micklefield, Jason

2012-12-01

With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

Potential applications of biosurfactant rhamnolipids in agriculture and biomedicine.

Science.gov (United States)

Chen, Jianwei; Wu, Qihao; Hua, Yi; Chen, Jun; Zhang, Huawei; Wang, Hong

2017-12-01

Rhamnolipids have recently emerged as promising bioactive molecules due to their novel structures, diverse and versatile biological functions, lower toxicity, higher biodegradability, as well as production from renewable resources. The advantages of rhamnolipids make them attractive targets for research in a wide variety of applications. Especially rhamnolipids are likely to possess potential applications of the future in areas such as biomedicine, therapeutics, and agriculture. The purpose of this mini review is to provide a comprehensive prospective of biosurfactant rhamnolipids as potential antimicrobials, immune modulators, and virulence factors, and anticancer agents in the field of biomedicine and agriculture that may meet the ever-increasing future pharmacological treatment and food safety needs in human health.

The Role and Potential Therapeutic Application of Myeloid-Derived Suppressor Cells in Allo- and Autoimmunity

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Qi Zhang

2015-01-01

Full Text Available Myeloid-derived suppressor cells (MDSCs are a heterogeneous population of cells that consists of myeloid progenitor cells and immature myeloid cells. They have been identified as a cell population that may affect the activation of CD4+ and CD8+ T-cells to regulate the immune response negatively, which makes them attractive targets for the treatment of transplantation and autoimmune diseases. Several studies have suggested the potential suppressive effect of MDSCs on allo- and autoimmune responses. Conversely, MDSCs have also been found at various stages of differentiation, accumulating during pathological situations, not only during tumor development but also in a variety of inflammatory immune responses, bone marrow transplantation, and some autoimmune diseases. These findings appear to be contradictory. In this review, we summarize the roles of MDSCs in different transplantation and autoimmune diseases models as well as the potential to target these cells for therapeutic benefit.

The Potential for Emerging Microbiome-Mediated Therapeutics in Asthma.

Science.gov (United States)

Ozturk, Ayse Bilge; Turturice, Benjamin Arthur; Perkins, David L; Finn, Patricia W

2017-08-10

In terms of immune regulating functions, analysis of the microbiome has led the development of therapeutic strategies that may be applicable to asthma management. This review summarizes the current literature on the gut and lung microbiota in asthma pathogenesis with a focus on the roles of innate molecules and new microbiome-mediated therapeutics. Recent clinical and basic studies to date have identified several possible therapeutics that can target innate immunity and the microbiota in asthma. Some of these drugs have shown beneficial effects in the treatment of certain asthma phenotypes and for protection against asthma during early life. Current clinical evidence does not support the use of these therapies for effective treatment of asthma. The integration of the data regarding microbiota with technologic advances, such as next generation sequencing and omics offers promise. Combining comprehensive bioinformatics, new molecules and approaches may shape future asthma treatment.

An overview of leech and its therapeutic applications

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Parimannan Sivachandran

2015-05-01

Full Text Available Hirudotherapy has a broad spectrum of therapeutic application in the medical field ranging from cardiology, gynaecology, ophthalmology, plastic and reconstructive surgeries. In medieval and early modern medicine, leeches were used to remove blood from patients in an attempt to balance the biological humours. Leeches are widely used to treat venous congestion in microvascular replantation, free and conventional flap surgery and traumatology. Recently, Food and Drug Administration has approved the usage of live leeches as medical device for therapeutic applications. Presently, some of the leech species have declined dramatically in its population due to the over utilization of leech for medicinal purposes and also due to pollution in several parts of the world particularly in European and Asian countries. This review presents an overview of leech including the history, biology, classification, and its application as medical device. Further, it also covers the controversies and misconception related to leech species identification and complications of post hirudotherapy.

Quercetin: A wonder bioflvonoid with therapeutic potential in disease management

Directory of Open Access Journals (Sweden)

Alka Gupta

2016-03-01

Full Text Available In the last decade, considerable efforts have been made to develop health promising nutritional supplements. Quercetin is a plant-derived bioflavonoid which is recently gaining scientific interest for its antioxidant free radical scavenging effects and anti-inflammatory properties. This wonder flavanol exhibits therapeutic potential in various ailments like cancer, coronary artery, asthma and alzheimer (neurodegeneration diseases. Additional clinical uses include treatment of inflammatory conditions like gout, pancreatitis and prostatitis. It has been extensively studied for its gastroprotective effects, anti-obesity action, immune booster, reducing risk of cataract and reduction of diabetic complications. The present review briefly discusses about biological activity, mechanism of action and therapeutic potential of quercetin in prevention and mitigation of diseases.

Therapeutic potential of flurbiprofen against obesity in mice.

Science.gov (United States)

Hosoi, Toru; Baba, Sachiko; Ozawa, Koichiro

2014-06-20

Obesity is associated with several diseases including diabetes, nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease, and cancer. Therefore, anti-obesity drugs have the potential to prevent these diseases. In the present study, we demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited therapeutic potency against obesity. Mice were fed a high-fat diet (HFD) for 6 months, followed by a normal-chow diet (NCD). The flurbiprofen treatment simultaneously administered. Although body weight was significantly decreased in flurbiprofen-treated mice, growth was not affected. Flurbiprofen also reduced the HFD-induced accumulation of visceral fat. Leptin resistance, which is characterized by insensitivity to the anti-obesity hormone leptin, is known to be involved in the development of obesity. We found that one of the possible mechanisms underlying the anti-obesity effects of flurbiprofen may have been mediated through the attenuation of leptin resistance, because the high circulating levels of leptin in HFD-fed mice were decreased in flurbiprofen-treated mice. Therefore, flurbiprofen may exhibit therapeutic potential against obesity by reducing leptin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

Determination of the therapeutic potential of human umbilical cord ...

African Journals Online (AJOL)

This research was conducted to evaluate the therapeutic potential of human umbilical cord blood, by determining their effect on bacterial pathogens which included: Streptobacillus sp, Corynebacterium diphtheriae, Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli. Cord blood samples were obtained ...

Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

Science.gov (United States)

Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

2016-12-01

Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

Preparation, Surface Properties, and Therapeutic Applications of Gold Nanoparticles in Biomedicine.

Science.gov (United States)

Panahi, Yunes; Mohammadhosseini, Majid; Nejati-Koshki, Kazem; Abadi, Azam Jafari Najaf; Moafi, Hadi Fallah; Akbarzadeh, Abolfazl; Farshbaf, Masoud

2017-02-01

Gold nanoparticles (AuNPs) due to their unique properties and manifold surface functionalities have been applied in bio-nanotechnology. The application of GNPs in recent medical and biological research is very extensive. Especially it involves applications such as detection and photothermalysis of microorganisms and cancer stem cells, biosensors; optical bio-imaging and observing of cells and these nanostructures also serve as practical platforms for therapeutic agents. In this review we studied all therapeutic applications of gold nanoparticles in biomedicine, synthesis methods, and surface properties. © Georg Thieme Verlag KG Stuttgart · New York.

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Alana M. Horowitz

2017-08-01

Full Text Available Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

Therapeutic Applications of Monte Carlo Calculations in Nuclear Medicine

CERN Document Server

Sgouros, George

2003-01-01

This book examines the applications of Monte Carlo (MC) calculations in therapeutic nuclear medicine, from basic principles to computer implementations of software packages and their applications in radiation dosimetry and treatment planning. It is written for nuclear medicine physicists and physicians as well as radiation oncologists, and can serve as a supplementary text for medical imaging, radiation dosimetry and nuclear engineering graduate courses in science, medical and engineering faculties. With chapters is written by recognised authorities in that particular field, the book covers the entire range of MC applications in therapeutic medical and health physics, from its use in imaging prior to therapy to dose distribution modelling targeted radiotherapy. The contributions discuss the fundamental concepts of radiation dosimetry, radiobiological aspects of targeted radionuclide therapy and the various components and steps required for implementing a dose calculation and treatment planning methodology in ...

Therapeutic potential of regulatory macrophages generated from peritoneal dialysate in adriamycin nephropathy.

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Cao, Qi; Wang, Yiping; Wang, Changqi; Wang, Xin M; Lee, Vincent W S; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I; Harris, David C H

2018-04-01

Cell therapy using macrophages requires large amounts of cells, which are difficult to collect from patients. Patients undergoing peritoneal dialysis (PD) discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages can be modulated to become regulatory macrophages, which have shown great promise as a therapeutic strategy in experimental kidney disease and human kidney transplantation. This study aimed to examine the potential of using peritoneal macrophages (PMs) from peritoneal dialysate to treat kidney disease. Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both patients and mice undergoing PD. PMs from patients and mice undergoing PD were more mature than peripheral monocytes/macrophages, as shown by low expression of C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro culture. PMs from patients and mice undergoing PD displayed normal macrophage function and could be modulated into a regulatory (M2) phenotype. In vivo, adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively protected against kidney injury in mice with adriamycin nephropathy (AN). Importantly, the transfused peritoneal M2 macrophages maintained their M2 phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice undergoing PD exhibited conventional macrophage features. Peritoneal M2 macrophages derived from PD mice are able to reduce kidney injury in AN, suggesting that peritoneal macrophages from patients undergoing PD may have the potential for clinical therapeutic application.

ON POLISH FANTASTIC LITERATURE FOR YOUNG PEOPLE AND ITS THERAPEUTIC POTENTIAL

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Dominik Borowski

2017-04-01

Full Text Available The objective of this article is to provide an overview of the therapeutic potential of fantastic literature for young people on the example of the series of novels by Rafał Kosik. The paper consists of three parts. The first part presents the definition of fantastic literature with reference to the concepts introduced by Tzvetan Todorov, Roger Caillois, Eric Rabkin and dictionary entries. Then the therapeutic function of literature is discussed by citing psychological theses on the importance of narrative in human life, as well as Roman Ingarden’s theory of the aesthetic experience. This provides the basis for reflection on bibliotherapy and the use of fantastic literature within its framework. The third part of the article presents the concept of the series of novels about Felix, Net and Nika, referring to the opinions of critics and literary scholars. Subsequently the selected fragments of the novels are discussed, demonstrating their therapeutic potential.

The therapeutic potential of truffle fungi: a patent survey

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Małgorzata Gajos

2014-12-01

Full Text Available The purpose of this article is to research and retrieve patent information regarding the therapeutic use of truffles. Truffles have a unique value as a foodstuff and impact positively on human health and well-being. They are applied in such industries as the pharmaceutical industry and the cosmetic industry. Patent documentation available in the Espacenet network and the Patentscope service were analyzed by key word and patent specifications were examined to describe state of the art and to identify scientific research trends in therapeutic applications of truffles. Medicinal properties of truffles such as the anticancer or cardiovascular effect, a reduction in blood lipids, immunological resistance and increased energy were identified. Other therapeutic benefits include sedative action, prevention of hormonal imbalances in women, pre-menopause symptom relief, senile urethritis and prostate disorders, sleep disorders and increased absorption of calcium from milk. Truffles can also be used to alleviate symptoms of milk intolerance such as diarrhoea or bloating, to ease rheumatic pains and to treat and prevent further development or recurrence of senile cataract.

The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation

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Ahmet Ulugöl

2014-06-01

Full Text Available Although cannabis has been used for pain management for millennia, very few approved cannabinoids are indicated for the treatment of pain and other medical symptoms. Cannabinoid therapy re-gained attention only after the discovery of endocannabinoids and fatty acid amide hydrolase (FAAH and monoacylglycerol lipase (MAGL, the enzymes playing a role in endocannabinoid metabolism. Nowadays, research has focused on the inhibition of these degradative enzymes and the elevation of endocannabinoid tonus locally; special emphasis is given on multi-target analgesia compounds, where one of the targets is the endocannabinoid degrading enzyme. In this review, I provide an overview of the current understanding about the processes accounting for the biosynthesis, transport and metabolism of endocannabinoids, and pharmacological approaches and potential therapeutic applications in this area, regarding the use of drugs elevating endocannabinoid levels in pain conditions.

Potential non-oncological applications of histone deacetylase inhibitors.

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Ververis, Katherine; Karagiannis, Tom C

2011-01-01

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutic drugs. Their clinical utility in oncology stems from their intrinsic cytotoxic properties and combinatorial effects with other conventional cancer therapies. To date, the histone deacetylase inhibitors suberoylanilide hydroxamic acid (Vorinostat, Zolinza®) and depsipeptide (Romidepsin, Istodax®) have been approved by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Further, there are currently over 100 clinical trials involving the use of histone deacetylase inhibitors in a wide range of solid and hematological malignancies. The therapeutic potential of histone deacetylase inhibitors has also been investigated for numerous other diseases. For example, the cytotoxic properties of histone deacetylase inhibitors are currently being harnessed as a potential treatment for malaria, whereas the efficacy of these compounds for HIV relies on de-silencing latent virus. The anti-inflammatory properties of histone deacetylase inhibitors are the predominant mechanisms for other diseases, such as hepatitis, systemic lupus erythematosus and a wide range of neurodegenerative conditions. Additionally, histone deacetylase inhibitors have been shown to be efficacious in animal models of cardiac hypertrophy and asthma. Broad-spectrum histone deacetylase inhibitors are clinically available and have been used almost exclusively in preclinical systems to date. However, it is emerging that class- or isoform-specific compounds, which are becoming more readily available, may be more efficacious particularly for non-oncological applications. The aim of this review is to provide an overview of the effects and clinical potential of histone deacetylase inhibitors in various diseases. Apart from applications in oncology, the discussion is focused on the potential efficacy of histone deacetylase inhibitors for the treatment of neurodegenerative diseases, cardiac

Urinary Exosomes: The Potential for Biomarker Utility, Intercellular Signaling and Therapeutics in Urological Malignancy.

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Franzen, Carrie A; Blackwell, Robert H; Foreman, Kimberly E; Kuo, Paul C; Flanigan, Robert C; Gupta, Gopal N

2016-05-01

Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA with the potential to alter signaling pathways in recipient cells. While exosome research has flourished, few publications have specifically considered the role of genitourinary cancer shed exosomes in urine, their implication in disease progression and their usefulness as noninvasive biomarkers. In this review we examined the current literature on the role of exosomes in intercellular communication and as biomarkers, and their potential as delivery vehicles for therapeutic applications in bladder, prostate and renal cancer. We searched PubMed® and Google® with the key words prostate cancer, bladder cancer, kidney cancer, exosomes, microvesicles and urine. Relevant articles, including original research studies and reviews, were selected based on contents. A review of this literature was generated. Cancer exosomes can be isolated from urine using various techniques. Cancer cells have been found to secrete more exosomes than normal cells. These exosomes have a role in cellular communication by interacting with and depositing their cargo in target cells. Bladder, prostate and renal cancer exosomes have been shown to enhance migration, invasion and angiogenesis. These exosomes have also been shown to increase proliferation, confer drug resistance and promote immune evasion. Urinary exosomes can be isolated from bladder, kidney and prostate cancer. They serve as a potential reservoir for biomarker identification. Exosomes also have potential for therapeutics as siRNA or pharmacological agents can be loaded into exosomes. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

D-amino acid-containing supramolecular nanofibers for potential cancer therapeutics.

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Wang, Huaimin; Feng, Zhaoqianqi; Xu, Bing

2017-02-01

Nanostructures formed by peptides that self-assemble in water through non-covalent interactions have attracted considerable attention because peptides possess several unique advantages, such as modular design and easiness of synthesis, convenient modification with known functional motifs, good biocompatibility, low immunogenicity and toxicity, inherent biodegradability, and fast responses to a wide range of external stimuli. After about two decades of development, peptide-based supramolecular nanostructures have already shown great potentials in the fields of biomedicine. Among a range of biomedical applications, using such nanostructures for cancer therapy has attracted increased interests since cancer remains the major threat for human health. Comparing with L-peptides, nanostructures containing peptides made of D-amino acid (i.e., D-peptides) bear a unique advantage, biostability (i.e., resistance towards most of endogenous enzymes). The exploration of nanostructures containing D-amino acids, especially their biomedical applications, is still in its infancy. Herein we review the recent progress of D-amino acid-containing supramolecular nanofibers as an emerging class of biomaterials that exhibit unique features for the development of cancer therapeutics. In addition, we give a brief perspective about the challenges and promises in this research direction. Copyright © 2016 Elsevier B.V. All rights reserved.

Engineered Polymer-Based Nanomaterials for Diagnostic, Therapeutic and Theranostic Applications.

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Parisi, Ortensia Ilaria; Scrivano, Luca; Sinicropi, Maria Stefania; Picci, Nevio; Puoci, Francesco

2016-01-01

Nanomedicine can be defined as the medical application of molecular nanotechnology and it plays a key role and pharmaceutical research and development, especially related to cancer prevention, monitoring, diagnosis and treatment. In this context, nanomaterials are attracting significant research interest due to their abilities to stay in the blood for long time, accumulate in pathological sites including tumors or inflammatory areas via the enhanced permeability and retention (EPR) effect, and facilitate targeted delivery of specific therapeutic agents. In the last decades, considerable attention was attracted by the development of nano-sized carriers, based on natural or synthetic polymers, able to provide the controlled release of anticancer drugs in the aim to overcome the drawbacks associated to the conventional chemotherapy. Furthermore, when loaded with imaging agents, this kind of systems offers the opportunity to exploit optical or magnetic resonance imaging (MRI) in cancer diagnosis. Polymeric materials are characterized by several functionalities where both therapeutic and imaging components, and also targeting moieties, can be attached for simultaneous targeted therapy and imaging providing innovative platforms defined as theranostic agents with a great potential in monitoring and treatment of cancer.

Therapeutic ultrasound - Exciting applications and future challenges

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Saffari, Nader

2018-04-01

This paper presents an overview of the applications of ultrasound for the treatment of an ever-growing range of medical conditions. After presenting a brief history of the development of therapeutic ultrasound, the different mechanisms by which beneficial bio-effects are triggered will be discussed. This will be followed by a discussion of some of the more promising applications, some of which have already been licensed and introduced into the clinic. The case of liver tumour ablation will be discussed to demonstrate some of the engineering challenges that still need to be overcome before this technology finds wider uptake in the medical world.

Sugar-based amphiphilic polymers for biomedical applications: from nanocarriers to therapeutics.

Science.gov (United States)

Gu, Li; Faig, Allison; Abdelhamid, Dalia; Uhrich, Kathryn

2014-10-21

disease. The atherosclerotic cascade is usually triggered by the unregulated uptake of oxidized low-density lipoprotein, a cholesterol carrier, in macrophages of the blood vessel wall; SBAPs can significantly inhibit oxidized low-density lipoprotein uptake in macrophages and abrogate the atherosclerotic cascade. By modification of various functionalities (e.g., branching, stereochemistry, hydrophobicity, and charge) in the SBAP chemical structure, SBAP bioactivity was optimized, and influential structural components were identified. Despite the potential of SBAPs as atherosclerotic therapies, blood stability of the SBAP micelles was not ideal for in vivo applications, and means to stabilize them were pursued. Using kinetic entrapment via flash nanoprecipitation, SBAPs were formulated into nanoparticles with a hydrophobic solute core and SBAP shell. SBAP nanoparticles exhibited excellent physiological stability and enhanced bioactivity compared with SBAP micelles. Further, this method enables encapsulation of additional hydrophobic drugs (e.g., vitamin E) to yield a stable formulation that releases two bioactives. Both as nanoscale carriers and as polymer therapeutics, SBAPs are promising biomaterials for medical applications.

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

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Chui-Mian Zeng

2018-05-01

Full Text Available Frizzled receptors (FZDs are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs that serve as receptors for secreted Wingless-type (WNT ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

Psychiatric therapeutic applications of virtual reality technology (VRT): research prospectus and phenomenological critique.

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Bloom, R W

1997-01-01

There is theoretical and empirical research supporting the hypothesis that virtual reality technology (VRT) can be efficaciously applied to attenuate the symptoms of mental disorders (Baer, 1996; Rothbaum et al, 1995a, 1995b; Rothbaum et al, 1996.) Yet there is also research suggesting psychiatric therapeutic applications of VRT may induce noxious or unexpected psychological consequences (Kolasinski, 1996; Muscott & Gifford, 1994; Regan & Price, 1994; Regan & Ramsey, 1996; Strickland, 1995.) A prudent conclusion would be to advocate ever more sophisticated studies on psychiatric therapeutic applications of VRT concerning (1) increasing the overall socioadaptiveness of patients, (2) the robustness of moderating, modifying, or other intermediary variables effecting or affecting VRT therapeutic efficacy, and (3) variables, processes, and hypotheses generated from VRT applications in non-psychiatric fields.

Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications

NARCIS (Netherlands)

Rizzo, L.Y.; Theek, B.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria

2013-01-01

In recent years, the use of nanomedicine formulations for therapeutic and diagnostic applications has increased exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-)

Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery.

Science.gov (United States)

Segal, Scott; Narayanan, Ramesh; Dalton, James T

2006-04-01

Selective androgen receptor modulators (SARMS) bind to the androgen receptor and demonstrate anabolic activity in a variety of tissues; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents are able to induce bone and muscle growth, as well as shrinking the prostate. The potential of SARMS is to maximise the positive attributes of steroidal androgens as well as minimising negative effects, thus providing therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. This review summarises androgen physiology, the current status of the R&D of SARMS and potential therapeutic indications for this emerging class of drugs.

RNAi Therapeutics in Autoimmune Disease

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Seunghee Cha

2013-03-01

Full Text Available Since the discovery of RNA interference (RNAi, excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.

Design and surface modification of potential luminomagnetic nanocarriers for biomedical applications

International Nuclear Information System (INIS)

Dutta, Ranu K.; Sharma, Prashant K.; Pandey, Avinash C.

2010-01-01

Targeted delivery of therapeutics possesses the potential to localize therapeutic agents to a specific tissue as a mechanism to enhance treatment efficacy and mitigate side effects. Moeities that combine imaging and therapeutic modalities in a single macromolecular construct may confer advantages in the development and applications of nanomedicine. Here is an insight into the synthesis of luminomagnetic (luminescent and magnetic, simultaneously) nanocarriers of ZnO:Fe, synthesized by a simple co-precipitation method and surface modified by the ligand folate. This functionalized luminomagnetic nanocarrier system is a bioconjugation approach which combines the specificity of folate receptors on cancer cells with the excellent optical and magnetic properties of the nanoparticles so as to develop biocompatible molecular imaging agents, drug delivery systems, and hyperthermia agents. The vibrating sample magnetometer (VSM) studies showed clear hysteresis loops having coercivity 5.1 mT with corresponding magnetization of remanence 7.6 x 10 -3 emu/g, indicating strong magnetic character of the samples. X-ray diffraction (XRD) and transmission electron microscopy (TEM) measurements show that these nanoparticles are spherical with 6-9 nm size and hence are quite appropriate for in vivo applications as well. The immobilization of folic acid was confirmed by fourier transform infrared (FTIR) analysis. All these properties make these luminomagnetic nanocarriers one of the most feasible candidates for folate receptor-mediated biomedical applications.

Androgen-Forming Stem Leydig cells: Identification, Function and Therapeutic Potential

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Yunhui Zhang

2008-01-01

Full Text Available Leydig cells are the primary source of testosterone in the male, and differentiation of Leydig cells in the testes is one of the primary events in the development of the male body and fertility. Stem Leydig cells (SLCs exist in the testis throughout postnatal life, but a lack of cell surface markers previously hindered attempts to obtain purified SLC fractions. Once isolated, the properties of SLCs provide interesting clues for the ontogeny of these cells within the embryo. Moreover, the clinical potential of SLCs might be used to reverse age-related declines in testosterone levels in aging men, and stimulate reproductive function in hypogonadal males. This review focuses on the source, identification and outlook for therapeutic applications of SLCs. Separate pools of SLCs may give rise to fetal and adult generations of Leydig cell, which may account for their observed functional differences. These differences should in turn be taken into account when assessing the consequences of environmental pollutants such as the phthalate ester, diethylhexylphthalate (DEHP.

Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases.

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Harrell, C Randall; Simovic Markovic, Bojana; Fellabaum, Crissy; Arsenijevic, Aleksandar; Djonov, Valentin; Arsenijevic, Nebojsa; Volarevic, Vladislav

2018-05-18

Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases.MSC-derived exosomes were as efficient as transplanted MSCs in limiting the extent of eye injury and inflammation. Immediately after intravitreal injection, MSC-derived exosomes, due to nano-dimension, diffused rapidly throughout the retina and significantly attenuated retinal damage and inflammation. MSC-derived exosomes successfully delivered trophic and immunomodulatory factors to the inner retina and efficiently promoted survival and neuritogenesis of injured retinal ganglion cells. MSC-derived exosomes efficiently suppressed migration of inflammatory cells, attenuated detrimental Th1 and Th17 cell-driven immune response and ameliorated experimental autoimmune uveitis. MSC-derived exosomes were able to fuse with the lysosomes within corneal cells, enabling delivering of MSC-derived active β-glucuronidase and consequent catabolism of accumulated glycosaminoglycans, indicating their therapeutic potential in the treatment of Mucopolysaccharidosis VII (Sly Syndrome). Importantly, beneficent effects were noticed only in animals that received MSC-derived exosomes and were not seen after therapy with fibroblasts-derived exosomes confirming specific therapeutic potential of MSCs and their products in the treatment of eye diseases.In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

Life on the line: the therapeutic potentials of computer-mediated conversation.

Science.gov (United States)

Miller, J K; Gergen, K J

1998-04-01

In what ways are computer networking practices comparable to face-to-face therapy? With the exponential increase in computer-mediated communication and the increasing numbers of people joining topically based computer networks, the potential for grass-roots therapeutic (or antitherapeutic) interchange is greatly augmented. Here we report the results of research into exchanges on an electronic bulletin board devoted to the topic of suicide. Over an 11-month period participants offered each other valuable resources in terms of validation of experience, sympathy, acceptance, and encouragement. They also asked provocative questions and furnished broad-ranging advice. Hostile entries were rare. However, there were few communiques that parallel the change-inducing practices more frequent within many therapeutic settings. In effect, on-line dialogues seemed more sustaining than transforming. Further limits and potentials of on-line communication are explored.

Biosurfactants Produced by Marine Microorganisms with Therapeutic Applications.

Science.gov (United States)

Gudiña, Eduardo J; Teixeira, José A; Rodrigues, Lígia R

2016-02-18

Marine microorganisms possess unique metabolic and physiological features and are an important source of new biomolecules, such as biosurfactants. Some of these surface-active compounds synthesized by marine microorganisms exhibit antimicrobial, anti-adhesive and anti-biofilm activity against a broad spectrum of human pathogens (including multi-drug resistant pathogens), and could be used instead of existing drugs to treat infections caused by them. In other cases, these biosurfactants show anti-cancer activity, which could be envisaged as an alternative to conventional therapies. However, marine biosurfactants have not been widely explored, mainly due to the difficulties associated with the isolation and growth of their producing microorganisms. Culture-independent techniques (metagenomics) constitute a promising approach to study the genetic resources of otherwise inaccessible marine microorganisms without the requirement of culturing them, and can contribute to the discovery of novel biosurfactants with significant biological activities. This paper reviews the most relevant biosurfactants produced by marine microorganisms with potential therapeutic applications and discusses future perspectives and opportunities to discover novel molecules from marine environments.

Biosurfactants Produced by Marine Microorganisms with Therapeutic Applications

Directory of Open Access Journals (Sweden)

Eduardo J. Gudiña

2016-02-01

Full Text Available Marine microorganisms possess unique metabolic and physiological features and are an important source of new biomolecules, such as biosurfactants. Some of these surface-active compounds synthesized by marine microorganisms exhibit antimicrobial, anti-adhesive and anti-biofilm activity against a broad spectrum of human pathogens (including multi-drug resistant pathogens, and could be used instead of existing drugs to treat infections caused by them. In other cases, these biosurfactants show anti-cancer activity, which could be envisaged as an alternative to conventional therapies. However, marine biosurfactants have not been widely explored, mainly due to the difficulties associated with the isolation and growth of their producing microorganisms. Culture-independent techniques (metagenomics constitute a promising approach to study the genetic resources of otherwise inaccessible marine microorganisms without the requirement of culturing them, and can contribute to the discovery of novel biosurfactants with significant biological activities. This paper reviews the most relevant biosurfactants produced by marine microorganisms with potential therapeutic applications and discusses future perspectives and opportunities to discover novel molecules from marine environments.

Therapeutic potential of carbohydrates as regulators of macrophage activation.

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Lundahl, Mimmi L E; Scanlan, Eoin M; Lavelle, Ed C

2017-12-15

It is well established for a broad range of disease states, including cancer and Mycobacterium tuberculosis infection, that pathogenesis is bolstered by polarisation of macrophages towards an anti-inflammatory phenotype, known as M2. As these innate immune cells are relatively long-lived, their re-polarisation to pro-inflammatory, phagocytic and bactericidal "classically activated" M1 macrophages is an attractive therapeutic approach. On the other hand, there are scenarios where the resolving inflammation, wound healing and tissue remodelling properties of M2 macrophages are beneficial - for example the successful introduction of biomedical implants. Although there are numerous endogenous and exogenous factors that have an impact on the macrophage polarisation spectrum, this review will focus specifically on prominent macrophage-modulating carbohydrate motifs with a view towards highlighting structure-function relationships and therapeutic potential. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential Therapeutic Effects of Psilocybin.

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Johnson, Matthew W; Griffiths, Roland R

2017-07-01

Psilocybin and other 5-hydroxytryptamine 2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

Individual optimization of therapeutic applications and dosimetry of radiopharmaceuticals with the help of compartmental analysis

International Nuclear Information System (INIS)

Augusto Ciussani

2007-01-01

Complete test of publication follows. The successful application of radiopharmaceuticals requires a patient-specific optimization of the activity to be administered, in order to deliver the desired therapeutic dose to the target organ while saving the healthy tissues. For a therapy specifically tailored on the characteristics of the patient, the correct knowledge of the morphology of the regions of interest, of the fractional uptake and of the related kinetics is necessary. Compartmental modelling can represent a powerful and simple tool for deriving the information of interest. In this presentation, the potentiality of compartmental analysis will be illustrated and two applications presented. The first study was conducted in patients with the autonomous functioning thyroid nodule (AFTN) syndrome treated with 131 I at the Ospedale Maggiore Policlinico of Milano (Milano, Italy). In these patients, the great challenge is represented by the healthy lobe surrounding the malignant nodule. A model was developed, where nodule and lobe are considered as separate entities in order to provide distinct dose estimates for the two tissues. The model has been also used for the optimization of the sampling schedule and for interpretation of biokinetic discrepancies observed between the diagnostic tests and the therapeutic application. The second study, carried out at Ospedali Riuniti di Bergamo (Bergamo, Italy), dealt with the application of [ 186 Re]-HEDP (hydroxyethyliden-diphosphonate disodium salt) for palliation of pain due to bone metastases of primary carcinomas. On the basis of the biodistribution studies and of chromatographic measurements, a compartmental model was suggested, taking into account the possible dissociation of the compound after injection into the patient. Also in this case, the compartmental model represents a valuable tool for individual optimization of the therapeutic procedure and for a more precise evaluation of the radiation dose the organs.

Rhenium-188 - advantages and clinical potential for use of a readily available, cost effective therapeutic radioisotope for applications in nuclear medicine, oncology and interventional cardiology

International Nuclear Information System (INIS)

Knapp, F.F. jr.

2002-01-01

Full text: Carrier-free rhenium-188 (Re-188) is readily available from the alumina-based tungsten-188/rhenium-188 generator system and has many attractive properties for a wide variety of therapeutic applications. The 16.9 h half-life, emission of the 2.2 MeV beta particle and versatile chemistry make Re-188 an important candidate for applications where high radiation penetration is required. In addition, emission of a gamma photon (155 KeV, 15 %) permits evaluation of biodistribution, pharmacokinetics and dosimetry estimates. The long physical half-life of the tungsten-188 (W-188) parent (t 1/2 69 days) and consistent generator performance - with high Re-188 yields and low W-188 parent breakthrough - result in an indefinite shelf-life of several months, dependent on the levels of Re-188 required. Post generator elution in-growth of 62 % of Re-188 after 24 hours in combination with high elution yields (75-85 %) result in 50 % daily yields of the maximal Re-188 available. In addition to research being conducted for the development of a wide variety of new therapeutic radiopharmaceuticals and devices, Re-188 is also being evaluated in physician-sponsored clinical trials in over 15 countries, with applications in nuclear medicine, oncology and interventional cardiology. One major current clinical application involves post-angiographic treatment of arterial segments following PTCA using Re-188 perrhenate or MAG3 liquid-filled balloons as an effective and cost-effective approach for inhibition of the hyperplastic response to vessel damage, which delivers uniform dose to the vessel wall. Re-188-HEDP is being used for palliation of metastatic bone pain palliation. This agent is readily prepared from a simple 'kit' and provides pain palliation as effective as other commercially available agents. The use of the Re-188-labeled Anti-NCA-95 antibody (BW 50/183; CD66 a,b,c,e) in conjunction which external beam irradiation and chemotherapy is an effective method for

Dental implants modified with drug releasing titania nanotubes: therapeutic potential and developmental challenges.

Science.gov (United States)

Gulati, Karan; Ivanovski, Sašo

2017-08-01

The transmucosal nature of dental implants presents a unique therapeutic challenge, requiring not only rapid establishment and subsequent maintenance of osseointegration, but also the formation of resilient soft tissue integration. Key challenges in achieving long-term success are sub-optimal bone integration in compromised bone conditions and impaired trans-mucosal tissue integration in the presence of a persistent oral microbial biofilm. These challenges can be targeted by employing a drug-releasing implant modification such as TiO 2 nanotubes (TNTs), engineered on titanium surfaces via electrochemical anodization. Areas covered: This review focuses on applications of TNT-based dental implants towards achieving optimal therapeutic efficacy. Firstly, the functions of TNT implants will be explored in terms of their influence on osseointegration, soft tissue integration and immunomodulation. Secondly, the developmental challenges associated with such implants are reviewed including sterilization, stability and toxicity. Expert opinion: The potential of TNTs is yet to be fully explored in the context of the complex oral environment, including appropriate modulation of alveolar bone healing, immune-inflammatory processes, and soft tissue responses. Besides long-term in vivo assessment under masticatory loading conditions, investigating drug-release profiles in vivo and addressing various technical challenges are required to bridge the gap between research and clinical dentistry.

Therapeutic monoclonal antibody N-glycosylation - Structure, function and therapeutic potential.

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Cymer, Florian; Beck, Hermann; Rohde, Adelheid; Reusch, Dietmar

2018-03-01

Therapeutic antibodies (IgG-type) contain several post-translational modifications (PTMs) whereby introducing a large heterogeneity, both structural and functional, into this class of therapeutics. Of these modifications, glycosylation in the fragment crystallizable (Fc) region is the most heterogeneous PTM, which can affect the stability of the molecule and interactions with Fc-receptors in vivo. Hence, the glycoform distribution can affect the mode of action and have implications for bioactivity, safety and efficacy of the drug. Main topics of the manuscript include: What factors influence the (Fc) glycan pattern in therapeutic antibodies and how can these glycans be characterized? How does structure of the Fc-glycan relate to function and what methods are available to characterize those functions? Although heterogeneous in their scope, the different sections are intended to combine current knowledge on structure-function correlations of IgG glycan structures with regard to Fc (effector) functions, as well as basic aspects and methodologies for their assessment. Copyright © 2017. Published by Elsevier Ltd.

The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

DEFF Research Database (Denmark)

Hudson, Brian D; Ulven, Trond; Milligan, Graeme

2013-01-01

G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention...... safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge...

Synthesis of Biocompatible Nanoparticulate Coordination Polymers for Diagnostic and Therapeutic Applications

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Kandanapitiye, Murthi S.

The combination of nanotechnology with medicinal chemistry has developed into a burgeoning research area. Nanomaterials (NMs) could be seamlessly interfaced with various facets in biology, biochemistry, medicinal chemistry and environmental chemistry that may not be available to the same material in the bulk scale. This dissertation research has focused on the development of nanoparticulate coordination polymers for diagnostic and therapeutic applications. Modern imaging techniques include X-ray computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET). We have successfully developed several types of nanoparticulate diagnostics and therapeutics that have some potential usefulness in biomedicine. Synthesis and characterization of nanoparticulate based PET (Positron emission tomography)/SPECT (Single photon emission computed tomography) are discussed in chapter 3. In chapter 4, preparation and potential utility of non-gadolinium based MRI contrast agent are reported for T1-weighted application. As far as the solely effectiveness of relaxation is concerned, Gd-based T 1-weighted MRI contrast agents have excellent enhancement of image contrast but they have risks of biological toxicity. Consequently, the search for T 1-weighted CAs with high efficacy and low toxicity has gained attention toward the Mn(II) and Fe(III). Fe(III) is considered to be more toxic to cells because free ferric or ferrous ions can catalyze the production of reactive oxygen species via the Fenton reactions. Paramagnetic chelates of Mn(II) could be employed as T1-weighted CAs. However, it is challenging to design and synthesize highly stable Mn(II) complexes that could maintain the integrity when administered to living system. Chapter 4 describes the synthesis and utility of nanoparticulate Mn analogue of Prussian blue (K2Mn 3[FeII(CN)6]2) as an effective T1 MRI contrast agent for cellular imaging X

Application of biomimetic HPLC to estimate lipophilicity, protein and phospholipid binding of potential peptide therapeutics

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Klara Livia Valko

2018-06-01

Full Text Available Peptide therapeutics are new modalities offering several challenges to drug discovery. They are generally less stable and permeable in vivo. The characterization of their lipophilicity cannot be carried out using the traditional in silico or wet octanol/water partition coefficients. The prediction of their in vivo distribution and permeability is also challenging. In this paper, it is demonstrated that the biomimetic properties such as lipophilicity, protein and phospholipid binding can be easily assessed by HPLC using chemically bonded protein and immobilized artificial membrane (IAM stationary phases. The obtained properties for a set of potential therapeutic peptides with 3 to 33 amino acids have been analysed and it was found that similar characteristics of the properties could be observed as for small molecule drugs. The albumin binding showed correlation with their measured lipophilicity on the C-18 stationary phase with acidic peptides showing stronger than expected albumin binding. The (IAM chromatography revealed peptide membrane affinity, which was stronger for positively charged peptides (containing arginine and showed correlation to the alpha-1-acid glycoprotein (AGP binding, which was also stronger for positively charged compounds. The in vivo volume of distribution and drug efficiency of the peptides have been estimated using the models developed for small molecules. One of the candidate linear peptides has been assessed in various cellular and in vivo assays and the results have confirmed the estimated cell partition and brain to plasma ratio. It can be demonstrated, that up to 21 amino acids, the peaks of the peptides obtained on the protein phase were symmetrical and narrow. The interaction of larger peptides with the protein stationary phases resulted in wide peaks showing multiple equilibrium processes with slow kinetics during chromatography. The larger peptides showed narrow and symmetrical peaks on the IAM column enabling

Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

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Sabrina Lusvarghi

2016-10-01

Full Text Available Griffithsin (GRFT, an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.

Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates?

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Gopalakrishnan, Ranganath; Frolov, Andrey I; Knerr, Laurent; Drury, William J; Valeur, Eric

2016-11-10

Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted.

Progranulin as a biomarker and potential therapeutic agent.

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Abella, Vanessa; Pino, Jesús; Scotece, Morena; Conde, Javier; Lago, Francisca; Gonzalez-Gay, Miguel Angel; Mera, Antonio; Gómez, Rodolfo; Mobasheri, Ali; Gualillo, Oreste

2017-10-01

Progranulin is a cysteine-rich secreted protein with diverse pleiotropic actions and participates in several processes, such as inflammation or tumorigenesis. Progranulin was first identified as a growth factor and, recently, it was characterised as an adipokine implicated in obesity, insulin resistance and rheumatic disease. At a central level, progranulin acts as a neurotropic and neuroprotective factor and protects from neural degeneration. In this review, we summarise the most recent research advances concerning the potential role of progranulin as a therapeutic target and biomarker in cancer, neurodegenerative and inflammatory diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Manufacturing of recombinant therapeutic proteins in microbial systems.

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Graumann, Klaus; Premstaller, Andreas

2006-02-01

Recombinant therapeutic proteins have gained enormous importance for clinical applications. The first recombinant products have been produced in E. coli more than 20 years ago. Although with the advent of antibody-based therapeutics mammalian expression systems have experienced a major boost, microbial expression systems continue to be widely used in industry. Their intrinsic advantages, such as rapid growth, high yields and ease of manipulation, make them the premier choice for expression of non-glycosylated peptides and proteins. Innovative product classes such as antibody fragments or alternative binding molecules will further expand the use of microbial systems. Even more, novel, engineered production hosts and integrated technology platforms hold enormous potential for future applications. This review summarizes current applications and trends for development, production and analytical characterization of recombinant therapeutic proteins in microbial systems.

Direct Fibrinolytic Snake Venom Metalloproteinases Affecting Hemostasis: Structural, Biochemical Features and Therapeutic Potential.

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Sanchez, Eladio F; Flores-Ortiz, Renzo J; Alvarenga, Valeria G; Eble, Johannes A

2017-12-05

Snake venom metalloproteinases (SVMPs) are predominant in viperid venoms, which provoke hemorrhage and affect hemostasis and thrombosis. P-I class enzymes consist only of a single metalloproteinase domain. Despite sharing high sequence homology, only some of them induce hemorrhage. They have direct fibrin(ogen)olytic activity. Their main biological substrate is fibrin(ogen), whose Aα-chain is degraded rapidly and independently of activation of plasminogen. It is important to understand their biochemical and physiological mechanisms, as well as their applications, to study the etiology of some human diseases and to identify sites of potential intervention. As compared to all current antiplatelet therapies to treat cardiovascular events, the SVMPs have outstanding biochemical attributes: (a) they are insensitive to plasma serine proteinase inhibitors; (b) they have the potential to avoid bleeding risk; (c) mechanistically, they are inactivated/cleared by α2-macroglobulin that limits their range of action in circulation; and (d) few of them also impair platelet aggregation that represent an important target for therapeutic intervention. This review will briefly highlight the structure-function relationships of these few direct-acting fibrinolytic agents, including, barnettlysin-I, isolated from Bothrops barnetti venom, that could be considered as potential agent to treat major thrombotic disorders. Some of their pharmacological advantages are compared with plasmin.

Direct Fibrinolytic Snake Venom Metalloproteinases Affecting Hemostasis: Structural, Biochemical Features and Therapeutic Potential

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Eladio F. Sanchez

2017-12-01

Full Text Available Snake venom metalloproteinases (SVMPs are predominant in viperid venoms, which provoke hemorrhage and affect hemostasis and thrombosis. P-I class enzymes consist only of a single metalloproteinase domain. Despite sharing high sequence homology, only some of them induce hemorrhage. They have direct fibrin(ogenolytic activity. Their main biological substrate is fibrin(ogen, whose Aα-chain is degraded rapidly and independently of activation of plasminogen. It is important to understand their biochemical and physiological mechanisms, as well as their applications, to study the etiology of some human diseases and to identify sites of potential intervention. As compared to all current antiplatelet therapies to treat cardiovascular events, the SVMPs have outstanding biochemical attributes: (a they are insensitive to plasma serine proteinase inhibitors; (b they have the potential to avoid bleeding risk; (c mechanistically, they are inactivated/cleared by α2-macroglobulin that limits their range of action in circulation; and (d few of them also impair platelet aggregation that represent an important target for therapeutic intervention. This review will briefly highlight the structure–function relationships of these few direct-acting fibrinolytic agents, including, barnettlysin-I, isolated from Bothrops barnetti venom, that could be considered as potential agent to treat major thrombotic disorders. Some of their pharmacological advantages are compared with plasmin.

Improving the Therapeutic Potential of Human Granzyme B for Targeted Cancer Therapy

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Georg Melmer

2013-01-01

Full Text Available Conventional cancer treatments lack specificity and often cause severe side effects. Targeted therapeutic approaches are therefore preferred, including the use of immunotoxins (ITs that comprise cell-binding and cell death-inducing components to allow the direct and specific delivery of pro-apoptotic agents into malignant cells. The first generation of ITs consisted of toxins derived from bacteria or plants, making them immunogenic in humans. The recent development of human cytolytic fusion proteins (hCFP consisting of human effector enzymes offers the prospect of highly-effective targeted therapies with minimal side effects. One of the most promising candidates is granzyme B (GrB and this enzyme has already demonstrated its potential for targeted cancer therapy. However, the clinical application of GrB may be limited because it is inactivated by the overexpression in tumors of its specific inhibitor serpin B9 (PI-9. It is also highly charged, which means it can bind non-specifically to the surface of non-target cells. Furthermore, human enzymes generally lack an endogenous translocation domain, thus the endosomal release of GrB following receptor-mediated endocytosis can be inefficient. In this review we provide a detailed overview of these challenges and introduce promising solutions to increase the cytotoxic potency of GrB for clinical applications.

Priming ammonia lyases and aminomutases for industrial and therapeutic applications

NARCIS (Netherlands)

Heberling, Matthew M.; Wu, Bian; Bartsch, Sebastian; Janssen, Dick B.

Ammonia lyases (AL) and aminomutases (AM) are emerging in green synthetic routes to chiral amines and an AL is being explored as an enzyme therapeutic for treating phenylketonuria and cancer. Although the restricted substrate range of the wild-type enzymes limits their widespread application, the

The Opioid System in Temporal Lobe Epilepsy: Functional Role and Therapeutic Potential

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Johannes Burtscher

2017-08-01

Full Text Available Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients often develop cognitive deficits and emotional blunting along the progression of the disease. The high incidence of resistance to antiepileptic drugs and a frequent lack of admissibility to surgery poses an unmet medical challenge. In the urgent quest of novel treatment strategies, neuropeptides are interesting candidates, however, their therapeutic potential has not yet been exploited. This review focuses on the functional role of the endogenous opioid system with respect to temporal lobe epilepsy, specifically in the hippocampus. The role of dynorphins and kappa opioid receptors (KOPr as modulators of neuronal excitability is well understood: both the reduced release of glutamate as well of postsynaptic hyperpolarization were shown in glutamatergic neurons. In line with this, low levels of dynorphin in humans and mice increase the risk of epilepsy development. The role of enkephalins is not understood so well. On one hand, some agonists of the delta opioid receptors (DOPr display pro-convulsant properties probably through inhibition of GABAergic interneurons. On the other hand, enkephalins play a neuro-protective role under hypoxic or anoxic conditions, most probably through positive effects on mitochondrial function. Despite the supposed absence of endorphins in the hippocampus, exogenous activation of the mu opioid receptors (MOPr induces pro-convulsant effects. Recently-expanded knowledge of the complex ways opioid receptors ligands elicit their effects (including biased agonism, mixed binding, and opioid receptor heteromers, opens up exciting new therapeutic potentials with regards to seizures and epilepsy. Potential adverse side effects of KOPr agonists may be minimized through functional selectivity. Preclinical data suggest a high potential of such compounds to control seizures, with a strong predictive validity toward human

CRISPR/Cas9 Genome Editing: A Promising Tool for Therapeutic Applications of Induced Pluripotent Stem Cells.

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Zhang, Yanli; Sastre, Danuta; Wang, Feng

2018-01-01

Induced pluripotent stem cells hold tremendous potential for biological and therapeutic applications. The development of efficient technologies for targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. The revolutionary technology for genome editing known as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) system is recently recognized as a powerful tool for editing DNA at specific loci. The ease of use of the CRISPR-Cas9 technology will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. More recently, this system was modified to repress (CRISPR interference, CRISPRi) or activate (CRISPR activation, CRISPRa) gene expression without alterations in the DNA, which amplified the scope of applications of CRISPR systems for stem cell biology. Here, we highlight latest advances of CRISPR-associated applications in human pluripotent stem cells. The challenges and future prospects of CRISPR-based systems for human research are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases

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Taiwo Betty Ayeleso

2017-11-01

Full Text Available The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA in the prevention and management of chronic diseases. Oleanolic acid is a pentacyclic triterpenoid widely found in plants, including fruits and vegetables with different techniques and chromatography platforms being employed in its extraction and isolation. Several studies have demonstrated the potential therapeutic effects of OA on different diseases and their symptoms. Furthermore, oleanolic acid also serves as a framework for the development of novel semi-synthetic triterpenoids that could prove vital in finding therapeutic modalities for various ailments. There are recent advances in the design and synthesis of chemical derivatives of OA to enhance its solubility, bioavailability and potency. Some of these derivatives have also been therapeutic candidates in a number of clinical trials. This review consolidates and expands on recent reports on the biological effects of oleanolic acid from different plant sources and its synthetic derivatives as well as their mechanisms of action in in vitro and in vivo study models. This review suggests that oleanolic acid and its derivatives are important candidates in the search for alternative therapy in the treatment and management of chronic diseases.

Some arachnidan peptides with potential medical application

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ME De Lima

2010-01-01

Full Text Available The search for new active drugs that can alleviate or cure different diseases is a constant challenge to researchers in the biological area and to the pharmaceutical industry. Historically, research has focused on the study of substances from plants. More recently, however, animal venoms have been attracting attention and studies have been successful in addressing treatment of accidents. Furthermore, venoms and their toxins have been considered good tools for prospecting for new active drugs or models for new therapeutic drugs. In this review, we discuss some possibilities of using different toxins, especially those from arachnid venoms, which have shown some potential application in diseases involving pain, hypertension, epilepsy and erectile dysfunction. A new generation of drugs is likely to emerge from peptides, including those found in animal venoms.

Small Scaffolds, Big Potential: Developing Miniature Proteins as Therapeutic Agents.

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Holub, Justin M

2017-09-01

Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs. This research overview discusses emerging developments involving the use of miniature proteins as scaffolds to design novel therapeutics for the treatment and study of human disease. Specifically, this review will explore strategies to: (i) stabilize miniature protein tertiary structure; (ii) optimize biomolecular recognition by grafting functional epitopes onto miniature protein scaffolds; and (iii) enhance cytosolic delivery of miniature proteins through the use of cationic motifs that facilitate endosomal escape. These objectives are discussed not only to address challenges in developing effective miniature protein-based drugs, but also to highlight the tremendous potential miniature proteins hold for combating and understanding human disease. Drug Dev Res 78 : 268-282, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Application of Long Noncoding RNAs in Osteosarcoma: Biomarkers and Therapeutic Targets

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Zhihong Li

2017-07-01

Full Text Available Osteosarcoma is the most common primary bone malignancy in children and adolescents. Although improvements in therapeutic strategies were achieved, the outcome remains poor for most patients with metastatic or recurrent osteosarcoma. Therefore, it is imperative to identify novel and effective prognostic biomarker and therapeutic targets for the disease. Long noncoding RNAs (lncRNAs are a novel class of RNA molecules defined as transcripts >200 nucleotides that lack protein coding potential. Many lncRNAs are deregulated in cancer and are important regulators for malignancies. Nine lncRNAs (91H, BCAR4, FGFR3-AS1, HIF2PUT, HOTTIP, HULC, MALAT-1, TUG1, UCA1 are upregulated and considered oncogenic for osteosarcoma. Loc285194 and MEG3 are two lncRNAs downregulated and as tumor suppressor for the disease. Moreover, the expressions of LINC00161 and ODRUL are associated with chemo-resistance of osteosarcoma. The mechanisms for these lncRNAs in regulating development of osteosarcoma are diverse, e.g. ceRNA, Wnt/β-catenin pathway, etc. The lncRNAs identified may serve as potential biomarkers or therapeutic targets for osteosarcoma.

The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization.

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Frecska, Ede; Bokor, Petra; Winkelman, Michael

2016-01-01

Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca is still a central element of many healing ceremonies in the Amazon Basin and its ritual consumption has become common among the mestizo populations of South America. Ayahuasca use amongst the indigenous people of the Amazon is a form of traditional medicine and cultural psychiatry. During the last two decades, the substance has become increasingly known among both scientists and laymen, and currently its use is spreading all over in the Western world. In the present paper we describe the chief characteristics of ayahuasca, discuss important questions raised about its use, and provide an overview of the scientific research supporting its potential therapeutic benefits. A growing number of studies indicate that the psychotherapeutic potential of ayahuasca is based mostly on the strong serotonergic effects, whereas the sigma-1 receptor (Sig-1R) agonist effect of its active ingredient dimethyltryptamine raises the possibility that the ethnomedical observations on the diversity of treated conditions can be scientifically verified. Moreover, in the right therapeutic or ritual setting with proper preparation and mindset of the user, followed by subsequent integration of the experience, ayahuasca has proven effective in the treatment of substance dependence. This article has two important take-home messages: (1) the therapeutic effects of ayahuasca are best understood from a bio-psycho-socio-spiritual model, and (2) on the biological level ayahuasca may act against chronic low grade inflammation and oxidative stress via the Sig-1R which can explain its widespread therapeutic indications.

The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization

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Ede eFrecska

2016-03-01

Full Text Available Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca is still a central element of many healing ceremonies in the Amazon Basin and its ritual consumption has become common among the mestizo populations of South America. Ayahuasca use amongst the indigenous people of the Amazon is a form of traditional medicine and cultural psychiatry. During the last two decades, the substance has become increasingly known among both scientists and laymen, and currently its use is spreading all over in the Western world. In the present paper we describe the chief characteristics of ayahuasca, discuss important questions raised about its use, and provide an overview of the scientific research supporting its potential therapeutic benefits. A growing number of studies indicate that the psychotherapeutic potential of ayahuasca is based mostly on the strong serotonergic effects, whereas the sigma-1 receptor agonist effect of its active ingredient dimethyltryptamine raises the possibility that the ethnomedical observations on the diversity of treated conditions can be scientifically verified. Moreover, in the right therapeutic or ritual setting with proper preparation and mindset of the user, followed by subsequent integration of the experience, ayahuasca has proven effective in the treatment of substance dependence. This article has two important take-home messages: 1 the therapeutic effects of ayahuasca are best understood from a bio-psycho-socio-spiritual model, and 2 on the biological level ayahuasca may act against chronic low grade inflammation and oxidative stress via the sigma-1 receptor which can explain its widespread therapeutic indications.

Host-guest supramolecular nanosystems for cancer diagnostics and therapeutics.

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Wang, Lei; Li, Li-li; Fan, Yun-shan; Wang, Hao

2013-07-26

Extensive efforts have been devoted to the construction of functional supramolecular nanosystems for applications in catalysis, energy conversion, sensing and biomedicine. The applications of supramolecular nanosystems such as liposomes, micelles, inorganic nanoparticles, carbon materials for cancer diagnostics and therapeutics have been reviewed by other groups. Here, we will focus on the recent momentous advances in the implementation of typical supramolecular hosts (i.e., cyclodextrins, calixarenes, cucurbiturils and metallo-hosts) and their nanosystems in cancer diagnostics and therapeutics. We discuss the evolutive process of supramolecular nanosystems from the structural control and characterization to their diagnostic and therapeutic function exploitation and even the future potentials for clinical translation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

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Asoka Banno

2018-01-01

Full Text Available Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients' symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects primarily by suppressing pro-inflammatory mediators and antagonizing the pro-inflammatory functions of various cell types relevant to asthma pathophysiology. Experimental findings strongly support the potential clinical benefits of PPAR agonists in the treatment of asthma. We review current literature, highlighting PPARs' key role in asthma pathogenesis and their agonists' therapeutic potential. With additional research and rigorous clinical studies, PPARs may become attractive therapeutic targets in this disease.

Nutraceuticals and their preventive or potential therapeutic value in Parkinson's disease.

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Chao, Jianfei; Leung, Yen; Wang, Mingfu; Chang, Raymond Chuen-Chung

2012-07-01

Parkinson's disease (PD) is the second most common aging-related disorder in the world, after Alzheimer's disease. It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and other parts of the brain, leading to motor impairment, cognitive impairment, and dementia. Current treatment methods, such as L-dopa therapy, are focused only on relieving symptoms and delaying progression of the disease. To date, there is no known cure for PD, making prevention of PD as important as ever. More than a decade of research has revealed a number of major risk factors, including oxidative stress and mitochondrial dysfunction. Moreover, numerous nutraceuticals have been found to target and attenuate these risk factors, thereby preventing or delaying the progression of PD. These nutraceuticals include vitamins C, D, E, coenzyme Q10, creatine, unsaturated fatty acids, sulfur-containing compounds, polyphenols, stilbenes, and phytoestrogens. This review examines the role of nutraceuticals in the prevention or delay of PD as well as the mechanisms of action of nutraceuticals and their potential applications as therapeutic agents, either alone or in combination with current treatment methods. © 2012 International Life Sciences Institute.

Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

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Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

2016-01-01

Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake. PMID:26973412

Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications

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Maria Giuseppina Cefalo

2016-01-01

Full Text Available Many central nervous system (CNS diseases including stroke, spinal cord injury (SCI, and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting.

Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

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Nien Yee Kow

2013-01-01

Full Text Available System lupus erythematosus (SLE is an immune-complex-mediated autoimmune condition with protean immunological and clinical manifestation. While SLE has classically been advocated as a B-cell or T-cell disease, it is unlikely that a particular cell type is more pathologically predominant than the others. Indeed, SLE is characterized by an orchestrated interplay amongst different types of immunopathologically important cells participating in both innate and adaptive immunity including the dendritic cells, macrophages, neutrophils and lymphocytes, as well as traditional nonimmune cells such as endothelial, epithelial, and renal tubular cells. Amongst the antigen-presenting cells and lymphocytes, and between lymphocytes, the costimulatory pathways which involve mutual exchange of information and signalling play an essential role in initiating, perpetuating, and, eventually, attenuating the proinflammatory immune response. In this review, advances in the knowledge of established costimulatory pathways such as CD28/CTLA-4-CD80/86, ICOS-B7RP1, CD70-CD27, OX40-OX40L, and CD137-CD137L as well as their potential roles involved in the pathophysiology of SLE will be discussed. Attempts to target these costimulatory pathways therapeutically will pave more potential treatment avenues for patients with SLE. Preliminary laboratory and clinical evidence of the potential therapeutic value of manipulating these costimulatory pathways in SLE will also be discussed in this review.

Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma.

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Liu, Tang; Shen, Jacson K; Li, Zhihong; Choy, Edwin; Hornicek, Francis J; Duan, Zhenfeng

2016-04-01

Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over-expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA-guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Triggering receptor expressed on myeloid cells 2 (TREM2): a potential therapeutic target for Alzheimer disease?

Science.gov (United States)

Deming, Yuetiva; Li, Zeran; Benitez, Bruno A; Cruchaga, Carlos

2018-06-20

There are currently no effective therapeutics for Alzheimer disease (AD). Clinical trials targeting amyloid beta thus far have shown very little benefit and only in the earliest stages of disease. These limitations have driven research to identify alternative therapeutic targets, one of the most promising is the triggering receptor expressed on myeloid cells 2 (TREM2). Areas covered: Here, we review the literature to-date and discuss the potentials and pitfalls for targeting TREM2 as a potential therapeutic for AD. We focus on research in animal and cell models for AD and central nervous system injury models which may help in understanding the role of TREM2 in disease. Expert opinion: Studies suggest TREM2 plays a key role in AD pathology; however, results have been conflicting about whether TREM2 is beneficial or harmful. More research is necessary before designing TREM2-targeting therapies. Successful therapeutics will most likely be administered early in disease.

Realizing the therapeutic potential of rare earth elements in designing nanoparticles to target and treat glioblastoma.

Science.gov (United States)

Lu, Victor M; McDonald, Kerrie L; Townley, Helen E

2017-10-01

The prognosis of brain cancer glioblastoma (GBM) is poor, and despite intense research, there have been no significant improvements within the last decade. This stasis implicates the need for more novel therapeutic investigation. One such option is the use of nanoparticles (NPs), which can be beneficial due to their ability to penetrate the brain, overcome the blood-brain barrier and take advantage of the enhanced permeation and retention effect of GBM to improve specificity. Rare earth elements possess a number of interesting natural properties due to their unique electronic configuration, which may prove therapeutically advantageous in an NP formulation. The underexplored exciting potential for rare earth elements to augment the therapeutic potential of NPs in GBM treatment is discussed in this review.

Potential Applications of Nanotechnology for the Diagnosis and Treatment of Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Joshua eMcCarroll

2014-01-01

Full Text Available Despite improvements in our understanding of pancreatic cancer and the emerging concept of personalized medicine for the treatment of this disease, it is still the fourth most common cause of cancer death in the western world. It is established that pancreatic cancer is a highly heterogeneous disease with a complex tumor microenvironment. Indeed the extensive stroma surrounding the cancer cells has been shown to be important in promoting tumor growth and metastases, as well as sequestering chemotherapeutic agents consequently decreasing delivery to the tumor cells. Nanotechnology has come to the forefront in the areas of medical diagnostics, imaging, and therapeutic drug delivery. This review will focus on the potential applications of nanotechnology for diagnosis, imaging, and delivery of therapeutic agents for the treatment of pancreatic cancer.

Pharmacokinetic properties of 2nd-generation fibroblast growth factor-1 mutants for therapeutic application.

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Xue Xia

Full Text Available Fibroblast growth factor-1 (FGF-1 is an angiogenic factor with therapeutic potential for the treatment of ischemic disease. FGF-1 has low intrinsic thermostability and is characteristically formulated with heparin as a stabilizing agent. Heparin, however, adds a number of undesirable properties that negatively impact safety and cost. Mutations that increase the thermostability of FGF-1 may obviate the need for heparin in formulation and may prove to be useful "2nd-generation" forms for therapeutic use. We report a pharmacokinetic (PK study in rabbits of human FGF-1 in the presence and absence of heparin, as well as three mutant forms having differential effects upon thermostability, buried reactive thiols, and heparin affinity. The results support the hypothesis that heparan sulfate proteoglycan (HSPG in the vasculature of liver, kidney and spleen serves as the principle peripheral compartment in the distribution kinetics. The addition of heparin to FGF-1 is shown to increase endocrine-like properties of distribution. Mutant forms of FGF-1 that enhance thermostability or eliminate buried reactive thiols demonstrate a shorter distribution half-life, a longer elimination half-life, and a longer mean residence time (MRT in comparison to wild-type FGF-1. The results show how such mutations can produce useful 2nd-generation forms with tailored PK profiles for specific therapeutic application.

Aspects of pericytes and their potential therapeutic use

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Justyna Różycka

2017-03-01

Full Text Available Pericytes, which are multi-potential stem cells, co-create the walls of the microvessels: capillaries, terminal arterioles and postcapillary venules. These cells are localized under the basement membrane, tightly encircling the endothelium. The most frequently mentioned molecular markers of pericytes include NG2 (neural-glial antigen 2, β-type platelet-derived growth factor receptor (PDGFRβ, smooth muscle α-actin (α-SMA, regulator of G protein signalling 5 (RGS5, the adhesion protein CD146 and nestin. Different functions in physiological processes are assigned to pericytes such as maintaining the integrity and senescence of endothelial cells, transregulation of vascular tone or the potential to differentiate into other cells. Probably they are also involved in pathological processes such as tissues fibrosis. In this review, we focus on the participation of pericytes in the process of blood vessel formation, the regeneration of skeletal muscle tissue and fibrosis. Strong evidence for pericytes’ participation in endothelial homeostasis, as well as in pathological conditions such as fibrosis, reveals a broad potential for the therapeutic use of these cells. Targeted pharmacological modulation of pericytes, leading to blocking signalling pathways responsible for the differentiation of pericytes into myofibroblasts, seems to be a promising strategy for the treatment of fibrosis in the early stages.

Aspects of pericytes and their potential therapeutic use.

Science.gov (United States)

Różycka, Justyna; Brzóska, Edyta; Skirecki, Tomasz

2017-03-13

Pericytes, which are multi-potential stem cells, co-create the walls of the microvessels: capillaries, terminal arterioles and postcapillary venules. These cells are localized under the basement membrane, tightly encircling the endothelium. The most frequently mentioned molecular markers of pericytes include NG2 (neural-glial antigen 2), β-type platelet-derived growth factor receptor (PDGFRβ), smooth muscle α-actin (α-SMA), regulator of G protein signalling 5 (RGS5), the adhesion protein CD146 and nestin. Different functions in physiological processes are assigned to pericytes such as maintaining the integrity and senescence of endothelial cells, transregulation of vascular tone or the potential to differentiate into other cells. Probably they are also involved in pathological processes such as tissues fibrosis. In this review, we focus on the participation of pericytes in the process of blood vessel formation, the regeneration of skeletal muscle tissue and fibrosis. Strong evidence for pericytes' participation in endothelial homeostasis, as well as in pathological conditions such as fibrosis, reveals a broad potential for the therapeutic use of these cells. Targeted pharmacological modulation of pericytes, leading to blocking signalling pathways responsible for the differentiation of pericytes into myofibroblasts, seems to be a promising strategy for the treatment of fibrosis in the early stages.

Microfluidic 3D cell culture: potential application for tissue-based bioassays

Science.gov (United States)

Li, XiuJun (James); Valadez, Alejandra V.; Zuo, Peng; Nie, Zhihong

2014-01-01

Current fundamental investigations of human biology and the development of therapeutic drugs, commonly rely on two-dimensional (2D) monolayer cell culture systems. However, 2D cell culture systems do not accurately recapitulate the structure, function, physiology of living tissues, as well as highly complex and dynamic three-dimensional (3D) environments in vivo. The microfluidic technology can provide micro-scale complex structures and well-controlled parameters to mimic the in vivo environment of cells. The combination of microfluidic technology with 3D cell culture offers great potential for in vivo-like tissue-based applications, such as the emerging organ-on-a-chip system. This article will review recent advances in microfluidic technology for 3D cell culture and their biological applications. PMID:22793034

Lectins, Interconnecting Proteins with Biotechnological/Pharmacological and Therapeutic Applications

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Luana Cassandra Breitenbach Barroso Coelho

2017-01-01

Full Text Available Lectins are proteins extensively used in biomedical applications with property to recognize carbohydrates through carbohydrate-binding sites, which identify glycans attached to cell surfaces, glycoconjugates, or free sugars, detecting abnormal cells and biomarkers related to diseases. These lectin abilities promoted interesting results in experimental treatments of immunological diseases, wounds, and cancer. Lectins obtained from virus, microorganisms, algae, animals, and plants were reported as modulators and tool markers in vivo and in vitro; these molecules also play a role in the induction of mitosis and immune responses, contributing for resolution of infections and inflammations. Lectins revealed healing effect through induction of reepithelialization and cicatrization of wounds. Some lectins have been efficient agents against virus, fungi, bacteria, and helminths at low concentrations. Lectin-mediated bioadhesion has been an interesting characteristic for development of drug delivery systems. Lectin histochemistry and lectin-based biosensors are useful to detect transformed tissues and biomarkers related to disease occurrence; antitumor lectins reported are promising for cancer therapy. Here, we address lectins from distinct sources with some biological effect and biotechnological potential in the diagnosis and therapeutic of diseases, highlighting many advances in this growing field.

International seminar on therapeutic applications of radiopharmaceuticals. Programme. Book of extended synopses

International Nuclear Information System (INIS)

1998-12-01

The document includes extended synopses of 64 presentations given at the International Seminar on Therapeutic Applications of Radiopharmaceuticals, held in Hyderabad, India, 18-22 January 1999. A separate indexing was prepared for each presentation

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

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Danbo Yang

2010-12-01

Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

International Nuclear Information System (INIS)

Yang, Danbo; Yu, Lei; Van, Sang

2010-01-01

The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

Energy Technology Data Exchange (ETDEWEB)

Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

2010-12-23

The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

Therapeutic potential of n-3 polyunsaturated fatty acids in disease.

Science.gov (United States)

Fetterman, James W; Zdanowicz, Martin M

2009-07-01

The potential therapeutic benefits of supplementation with n-3 polyunsaturated fatty acids (PUFAs) in various diseases are reviewed, and the antiinflammatory actions, activity, and potential drug interactions and adverse effects of n-3 PUFAs are discussed. Fish oils are an excellent source of long-chain n-3 PUFAs, such as eicosapentaenoic acid and docosahexaenoic acid. After consumption, n-3 PUFAs can be incorporated into cell membranes and reduce the amount of arachidonic acid available for the synthesis of proinflammatory eicosanoids (e.g., prostaglandins, leukotrienes). Likewise, n-3 PUFAs can also reduce the production of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1, and interleukin-6. Considerable research has been conducted to evaluate the potential therapeutic effects of fish oils in numerous conditions, including arthritis, coronary artery disease, inflammatory bowel disease, asthma, and sepsis, all of which have inflammation as a key component of their pathology. Additional investigations into the use of supplementation with fish oils in patients with neural injury, cancer, ocular diseases, and critical illness have recently been conducted. The most commonly reported adverse effects of fish oil supplements are a fishy aftertaste and gastrointestinal upset. When recommending an n-3 PUFA, clinicians should be aware of any possible adverse effect or drug interaction that, although not necessarily clinically significant, may occur, especially for patients who may be susceptible to increased bleeding (e.g., patients taking warfarin). The n-3 PUFAs have been shown to be efficacious in treating and preventing various diseases. The wide variation in dosages and formulations used in studies makes it difficult to recommend dosages for specific treatment goals.

Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

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Fabliha Ahmed Chowdhury

2018-01-01

Full Text Available Glioblastoma multiforme (GBM is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ, the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM.

Potential of Icariin Metabolites from Epimedium koreanum Nakai as Antidiabetic Therapeutic Agents

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Da Hye Kim

2017-06-01

Full Text Available The therapeutic properties of Epimedium koreanum are presumed to be due to the flavonoid component icariin, which has been reported to have broad pharmacological potential and has demonstrated anti-diabetic, anti-Alzheimer’s disease, anti-tumor, and hepatoprotective activities. Considering these therapeutic properties of icariin, its deglycosylated icaritin and glycosylated flavonoids (icaeriside II, epimedin A, epimedin B, and epimedin C were evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B and α-glucosidase. The results show that icaritin and icariside II exhibit potent inhibitory activities, with 50% inhibition concentration (IC50 values of 11.59 ± 1.39 μM and 9.94 ± 0.15 μM against PTP1B and 74.42 ± 0.01 and 106.59 ± 0.44 μM against α-glucosidase, respectively. With the exceptions of icaritin and icariside II, glycosylated flavonoids did not exhibit any inhibitory effects in the two assays. Enzyme kinetics analyses revealed that icaritin and icariside II demonstrated noncompetitive-type inhibition against PTP1B, with inhibition constant (Ki values of 11.41 and 11.66 μM, respectively. Moreover, molecular docking analysis confirmed that icaritin and icariside II both occupy the same site as allosteric ligand. Thus, the molecular docking simulation results were in close agreement with the experimental data with respect to inhibition activity. In conclusion, deglycosylated metabolites of icariin from E. koreanum might offer therapeutic potential for the treatment of type 2 diabetes mellitus.

RNAi therapeutics and applications of microRNAs in cancer treatment.

Science.gov (United States)

Uchino, Keita; Ochiya, Takahiro; Takeshita, Fumitaka

2013-06-01

RNA interference-based therapies are proving to be powerful tools for combating various diseases, including cancer. Scientists are researching the development of safe and efficient systems for the delivery of small RNA molecules, which are extremely fragile in serum, to target organs and cells in the human body. A dozen pre-clinical and clinical trials have been under way over the past few years involving biodegradable nanoparticles, lipids, chemical modification and conjugation. On the other hand, microRNAs, which control the balance of cellular biological processes, have been studied as attractive therapeutic targets in cancer treatment. In this review, we provide an overview of RNA interference-based therapeutics in clinical trials and discuss the latest technology for the systemic delivery of nucleic acid drugs. Furthermore, we focus on dysregulated microRNAs in human cancer, which have progressed in pre-clinical trials as therapeutic targets, and describe a wide range of strategies to control the expression levels of endogenous microRNAs. Further development of RNA interference technologies and progression of clinical trials will contribute to the achievement of practical applications of nucleic acid drugs.

The Role of the Endothelium in HPS Pathogenesis and Potential Therapeutic Approaches

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Irina Gavrilovskaya

2012-01-01

Full Text Available American hantaviruses cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS. Hantaviruses nonlytically infect endothelial cells and cause dramatic changes in barrier functions of the endothelium without disrupting the endothelium. Instead hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions of capillaries. The endothelium of arteries, veins, and lymphatic vessels is unique and central to the function of vast pulmonary capillary beds, which regulate pulmonary fluid accumulation. The endothelium maintains vascular barrier functions through a complex series of redundant receptors and signaling pathways that serve to both permit fluid and immune cell efflux into tissues and restrict tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to alter capillary permeability but also defines potential therapeutic targets for regulating acute pulmonary edema and HPS disease. Here we discuss interactions of HPS causing hantaviruses with the endothelium, potential endothelial cell-directed permeability mechanisms, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

Science.gov (United States)

Fischer, Benedikt; Kuganesan, Sharan; Gallassi, Andrea; Malcher-Lopes, Renato; van den Brink, Wim; Wood, Evan

2015-12-01

Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for

International seminar on therapeutic applications of radiopharmaceuticals. Programme. Book of extended synopses

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-12-01

The document includes extended synopses of 64 presentations given at the International Seminar on Therapeutic Applications of Radiopharmaceuticals, held in Hyderabad, India, 18-22 January 1999. A separate indexing was prepared for each presentation Refs, figs, tabs

Antimicrobial Peptides for Therapeutic Applications: A Review

Directory of Open Access Journals (Sweden)

Tsogbadrakh Mishig-Ochir

2012-10-01

Full Text Available Antimicrobial peptides (AMPs have been considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and different mechanisms of action compared to conventional antibiotics. Although AMPs possess considerable benefits as new generation antibiotics, their clinical and commercial development still have some limitations, such as potential toxicity, susceptibility to proteases, and high cost of peptide production. In order to overcome those obstacles, extensive efforts have been carried out. For instance, unusual amino acids or peptido-mimetics are introduced to avoid the proteolytic degradation and the design of short peptides retaining antimicrobial activities is proposed as a solution for the cost issue. In this review, we focus on small peptides, especially those with less than twelve amino acids, and provide an overview of the relationships between their three-dimensional structures and antimicrobial activities. The efforts to develop highly active AMPs with shorter sequences are also described.

Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles

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Bin Zhang

2016-02-01

Full Text Available The intense research focus on stem and progenitor cells could be attributed to their differentiation potential to generate new cells to replace diseased or lost cells in many highly intractable degenerative diseases, such as Alzheimer disease, multiple sclerosis, and heart diseases. However, experimental and clinical studies have increasingly attributed the therapeutic efficacy of these cells to their secretion. While stem and progenitor cells secreted many therapeutic molecules, none of these molecules singly or in combination could recapitulate the functional effects of stem cell transplantations. Recently, it was reported that extracellular vesicles (EVs could recapitulate the therapeutic effects of stem cell transplantation. Based on the observations reported thus far, the prevailing hypothesis is that stem cell EVs exert their therapeutic effects by transferring biologically active molecules such as proteins, lipids, mRNA, and microRNA from the stem cells to injured or diseased cells. In this respect, stem cell EVs are similar to EVs from other cell types. They are both primarily vehicles for intercellular communication. Therefore, the differentiating factor is likely due to the composition of their cargo. The cargo of EVs from different cell types are known to include a common set of proteins and also proteins that reflect the cell source of the EVs and the physiological or pathological state of the cell source. Hence, elucidation of the stem cell EV cargo would provide an insight into the multiple physiological or biochemical changes necessary to affect the many reported stem cell-based therapeutic outcomes in a variety of experimental models and clinical trials.

Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

Science.gov (United States)

Schepetkin, Igor A; Quinn, Mark T

2006-03-01

Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.

Therapeutic potential of Mediator complex subunits in metabolic diseases.

Science.gov (United States)

Ranjan, Amol; Ansari, Suraiya A

2018-01-01

The multisubunit Mediator is an evolutionary conserved transcriptional coregulatory complex in eukaryotes. It is needed for the transcriptional regulation of gene expression in general as well as in a gene specific manner. Mediator complex subunits interact with different transcription factors as well as components of RNA Pol II transcription initiation complex and in doing so act as a bridge between gene specific transcription factors and general Pol II transcription machinery. Specific interaction of various Mediator subunits with nuclear receptors (NRs) and other transcription factors involved in metabolism has been reported in different studies. Evidences indicate that ligand-activated NRs recruit Mediator complex for RNA Pol II-dependent gene transcription. These NRs have been explored as therapeutic targets in different metabolic diseases; however, they show side-effects as targets due to their overlapping involvement in different signaling pathways. Here we discuss the interaction of various Mediator subunits with transcription factors involved in metabolism and whether specific interaction of these transcription factors with Mediator subunits could be potentially utilized as therapeutic strategy in a variety of metabolic diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Serotonergic 5-HT6 Receptor Antagonists: Heterocyclic Chemistry and Potential Therapeutic Significance.

Science.gov (United States)

Bali, Alka; Singh, Shalu

2015-01-01

The serotonin 5-HT(6) receptor (5- HT(6)R) is amongst the recently discovered serotonergic receptors with almost exclusive localization in the brain. Hence, this receptor is fast emerging as a promising target for cognition enhancement in central nervous system (CNS) diseases such as Alzheimer's disease (cognitive function), obesity, schizophrenia and anxiety. The last decade has seen a surge of literature reports on the functional role of this receptor in learning and memory processes and investigations related to the chemistry and pharmacology of 5-HT(6) receptor ligands, especially 5- HT(6) receptor antagonists. Studies show the involvement of multiple neurotransmitter systems in cognitive enhancement by 5-HT(6)R antagonists including cholinergic, glutamatergic, and GABAergic systems. Several of the 5-HT(6)R ligands are indole based agents bearing structural similarity to the endogenous neurotransmitter serotonin. Based on the pharmacophoric models proposed for these agents, drug designing has been carried out incorporating various heterocyclic replacements for the indole nucleus. In this review, we have broadly summarized the medicinal chemistry and current status of this fairly recent class of drugs along with their potential therapeutic applications.

Therapeutic potential of CAR-T cell-derived exosomes: a cell-free modality for targeted cancer therapy.

Science.gov (United States)

Tang, Xiang-Jun; Sun, Xu-Yong; Huang, Kuan-Ming; Zhang, Li; Yang, Zhuo-Shun; Zou, Dan-Dan; Wang, Bin; Warnock, Garth L; Dai, Long-Jun; Luo, Jie

2015-12-29

Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events. As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable.

Therapeutic application of lasers in ophthalmology; Terapeutyczne zastosowanie laserow w okulistyce

Energy Technology Data Exchange (ETDEWEB)

Misiuk-Hojlo, M; Krzyzanowska-Berkowska, P; Hill-Bator, A [Department of Ophthalmology, Silesian Piasts University of Medicine in Wroclaw (Poland)

2007-07-01

Lasers have found application in diverse branches of medicine. In ophthalmology, laser technology has various therapeutic and diagnostic applications. The purpose of this article is to review the major therapeutic applications of lasers in different eye disorders. The effects of lasers on biological tissues and different laser techniques as well as the indications for laser therapy in various parts of the eye are discussed. Lasers are used to treat glaucoma and many vascular disorders of the retina. Laser treatment may be useful in preventing the development of neovascularization in diabetic retinopathy, BRVO, or CRVO. Laser techniques are also available for the treatment of the exudative form of age-related macular degeneration (AMD) and some malignant and benign intraocular tumors and in retina abnormalities which predispose to rhegmatogenous retinal detachment. Corneal laser surgery is the most frequently applied laser procedure in ophthalmology. PRK, LASIK, and LASEK are used to correct errors in vision such as myopia, hyperopia, and astigmatism. Laser photocoagulation is also helpful in cataract surgery. Nowadays, lasers have become so universal that it is difficult to imagine ophthalmology without them. We are still witnessing rapid advances in the development of laser techniques, especially in plastic surgery, cataract extraction, and ocular imaging. (authors)

Therapeutic benefits of Nanoparticles in Stroke

Directory of Open Access Journals (Sweden)

Stavros ePanagiotou

2015-05-01

Full Text Available Stroke represents one of the major causes of death and disability worldwide, for which no effective treatments are available. The thrombolytic drug alteplase (tissue plasminogen activator or tPA is the only treatment for acute ischemic stroke but its use is limited by several factors including short therapeutic window, selective efficacy and subsequent haemorrhagic complications. Numerous preclinical studies have reported very promising results using neuroprotective agents but they have failed at clinical trials because of either safety issues or lack of efficacy. The delivery of many potentially therapeutic neuroprotectants and diagnostic compounds to the brain is restricted by the blood-brain barrier (BBB. Nanoparticles (NPs, which can readily cross the BBB without compromising its integrity, have immense applications in the treatment of ischemic stroke. In this review, potential uses of NPs will be summarized for the treatment of ischemic stroke. Additionally, an overview of targeted NPs will be provided, which could be used in the diagnosis of stroke. Finally, the potential limitations of using NPs in medical applications will be mentioned. Since the use of NPs in stroke therapy is now emerging and is still in development, this review is far from comprehensive or conclusive. Instead, examples of NPs and their current use will be provided, as well as the potentials of NPs in an effort to meet the high demand of new therapies in stroke.

Delivery of Therapeutic Proteins Using Electrospun Fibers-Recent Developments and Current Challenges.

Science.gov (United States)

Seif, Salem; Planz, Viktoria; Windbergs, Maike

2017-10-01

Proteins play a vital role within the human body by regulating various functions and even serving as structural constituent of many body parts. In this context, protein-based therapeutics have attracted a lot of attention in the last few decades as potential treatment of different diseases. Due to the steadily increasing interest in protein-based therapeutics, different dosage forms were investigated for delivering such complex macromolecules to the human body. Here, electrospun fibers hold a great potential for embedding proteins without structural damage and for controlled release of the protein for therapeutic applications. This review provides a comprehensive overview of the current state of protein-based carrier systems using electrospun fibers, with special emphasis on discussing their potential and key challenges in developing such therapeutic strategies, along with a prospective view of anticipated future directions. © 2017 Deutsche Pharmazeutische Gesellschaft.

DNA molecules and human therapeutics | Danquah | African Journal ...

African Journals Online (AJOL)

Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display ...

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

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McKenna, Dennis J

2004-05-01

Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

Therapeutic and cosmetic applications of mangiferin: a patent review.

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Telang, Manasi; Dhulap, Sivakami; Mandhare, Anita; Hirwani, Rajkumar

2013-12-01

Mangiferin, a natural C-glucoside xanthone [2-C-β-D-glucopyranosyl-1, 3, 6, 7-tetrahydroxyxanthone], is abundantly present in young leaves and stem bark of the mango tree. The xanthonoid structure of mangiferin with C-glycosyl linkage and polyhydroxy components contributes to its free radical-scavenging ability, leading to a potent antioxidant effect as well as multiple biological activities. An extensive search was carried out to collect patent information on mangiferin and its derivatives using various patent databases spanning all priority years to date. The patents claiming therapeutic and cosmetic applications of mangiferin and its derivatives were analyzed in detail. The technology areas covered in this article include metabolic disorders, cosmeceuticals, multiple uses of the same compound, miscellaneous uses, infectious diseases, inflammation, cancer and autoimmune disorders, and neurological disorders. Mangiferin has the potential to modulate multiple molecular targets including nuclear factor-kappa B (NF-κB) signaling and cyclooxygenase-2 (COX-2) protein expression. Mangiferin exhibits antioxidant, antidiabetic, antihyperuricemic, antiviral, anticancer and antiinflammatory activities. The molecular structure of mangiferin fulfils the four Lipinski's requisites reported to favor high bioavailability by oral administration. There is no evidence of adverse side effects of mangiferin so far. Mangiferin could thus be a promising candidate for development of a multipotent drug.

Therapeutic applications of histone deacetylase inhibitors in sarcoma.

Science.gov (United States)

Tang, Fan; Choy, Edwin; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

2017-09-01

Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis. Importantly, preclinical studies have revealed that HDIs can not only sensitize sarcomas to chemotherapy and radiotherapy, but also increase treatment responses when combined with other chemotherapeutic drugs. Several phase I and II clinical trials have been conducted to assess the efficacy of HDIs either as monotherapy or in combination with standard chemotherapeutic agents or targeted therapeutic drugs for sarcomas. Combination regimen for sarcomas appear to be more promising than monotherapy when using HDIs. This review summarizes our current understanding and therapeutic applications of HDIs in sarcomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potential prospects of nanomedicine for targeted therapeutics in inflammatory bowel diseases.

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Pichai, Madharasi V A; Ferguson, Lynnette R

2012-06-21

Inflammatory bowel diseases (IBDs) such as Crohn's disease are highly debilitating. There are inconsistencies in response to and side effects in the current conventional medications, failures in adequate drug delivery, and the lack of therapeutics to offer complete remission in the presently available treatments of IBD. This suggests the need to explore beyond the horizons of conventional approaches in IBD therapeutics. This review examines the arena of the evolving IBD nanomedicine, studied so far in animal and in vitro models, before comprehensive clinical testing in humans. The investigations carried out so far in IBD models have provided substantial evidence of the nanotherapeutic approach as having the potential to overcome some of the current drawbacks to conventional IBD therapy. We analyze the pros and cons of nanotechnology in IBD therapies studied in different models, aimed at different targets and mechanisms of IBD pathogenesis, in an attempt to predict its possible impact in humans.

Emerging therapeutic potential of graviola and its constituents in cancers.

Science.gov (United States)

Qazi, Asif Khurshid; Siddiqui, Jawed A; Jahan, Rahat; Chaudhary, Sanjib; Walker, Larry A; Sayed, Zafar; Jones, Dwight T; Batra, Surinder K; Macha, Muzafar A

2018-04-05

Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.

DART MS based chemical profiling for therapeutic potential of Piper betle landraces.

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Bajpai, Vikas; Pandey, Renu; Negi, Mahendra Pal Singh; Kumar, Nikhil; Kumar, Brijesh

2012-12-01

Piper betle Linn. leaves are traditionally used as a folk medicine in India and other Asiatic countries. Twenty-one P. betle landraces were analyzed using a Direct Analysis in Real Time (DART) mass spectral technique and evaluated on the basis of molecules detected in the leaves. Clustering of landraces based on three well known biologically active phenols (m/z 151,165,193) showed two broad groups with high and low phenol contents suggesting differences in their therapeutic potential. Findings of this study could be useful in rapid screening of the landraces for determining their medicinal potential and optimum utilization of the bioresource.

Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.

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Brzóska, Malgorzata M; Borowska, Sylwia; Tomczyk, Michal

2016-01-01

Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heavy metal. Because numerous effects to Cd's toxic action result from its prooxidative properties, it seems reasonable that special attention should be directed to agents that can prevent or reduce this metal-induced oxidative stress and its consequences in tissues, organs and systems at risk of toxicity, including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous system as well as bone tissue. This review discusses a wide range of natural (plant and animal origin) and synthetic antioxidants together with many plant extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber officinale) that have been shown to prevent from Cd toxicity. Moreover, some attention has been focused on the fact that substances not possessing antioxidative potential may also prevent Cd-induced oxidative stress and its consequences. So far, most of the data on the protective effects of the natural and synthetic antioxidants and plant extracts come from studies in animals' models; however, numerous of them seem to be promising preventive/therapeutic strategies for Cd toxicity in humans. Further investigation of prophylactic and therapeutic use of antioxidants in populations exposed to Cd environmentally and occupationally is warranted, given that therapeutically effective chelation therapy for this toxic metal is currently lacking.

[The therapeutic and recreational potential of the «Goryachy Plyazh» physiotherapeutic facility on the Kunashir island].

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Veremchuk, L V; Chelnokova, B I; Barskova, L S; Gvozdenko, T A; Kukayev, I V; Savochkina, N L

2017-12-28

The ever increasing attention to the further development of the health resort business and touristic activities in this country implies the necessity of the proper scientifically sound substantiation for the more efficient exploitation of the available spa and health resort resources of the Russian Far East as well as the ample recreational potential of this region taking into consideration that they have not been completely utilized during the preceding period. The objective of the present study was to evaluate the of the «Goryachy Plyazh (Hot Beach)» physiotherapeutic facility on the Kunashir island. We have studies the chemical, bacteriological, and radiological properties of thermal waters from the natural sources located in the vicinity of the «Goryachy Plyazh» physiotherapeutic facility. The medical potential of the area was assessed in accordance with the methodological guidelines №96/226 on drawing up the bioclimatic passport approved by the Ministry of Public Health of the Russian Federation on the 7thFebruary of 1997. We have proposed the aggregate indicator of the therapeutic and recreational potential making it possible to evaluate the totality of health-improving properties in the combination with the landscape and climatic characteristics of the locality of interest. The neighbourhood of the «Goryachy Plyazh» physiotherapeutic facility on the Kunashir island was found to harbour the sources of mineral waters of various types. Specifically, siliceous thermal waters of varying ionic composition (e.g. containing chlorides, sodium, silicium, and boron) of the Omsk and Ursdon types are suitable for multipurpose therapeutic utilization including the protracted internal application for the treatment of chronic gastritis and other intestinal problems, diseases of liver and endocrine system, as well as metabolic disorders. Mineral water of the Kul'dursky type can be used for the external use in the form of bathing and other hydrotherapeutic procedures

Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

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José Manuel Calderón-Montaño

2014-01-01

Full Text Available Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na+/K+-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studies.

Regenerative medicine using adult neural stem cells: the potential for diabetes therapy and other pharmaceutical applications

Institute of Scientific and Technical Information of China (English)

Tomoko Kuwabara; Makoto Asashima

2012-01-01

Neural stem cells (NSCs),which are responsible for continuous neurogenesis during the adult stage,are present in human adults.The typical neurogenic regions are the hippocampus and the subventricular zone; recent studies have revealed that NSCs also exist in the olfactory bulb.Olfactory bulb-derived neural stem cells (OB NSCs) have the potential to be used in therapeutic applications and can be easily harvested without harm to the patient.Through the combined influence of extrinsic cues and innate programming,adult neurogenesis is a finely regulated process occurring in a specialized cellular environment,a niche.Understanding the regulatory mechanisms of adult NSCs and their cellular niche is not only important to understand the physiological roles of neurogenesis in adulthood,but also to provide the knowledge necessary for developing new therapeutic applications using adult NSCs in other organs with similar regulatory environments.Diabetes is a devastating disease affecting more than 200 million people worldwide.Numerous diabetic patients suffer increased symptom severity after the onset,involving complications such as retinopathy and nephropathy.Therefore,the development of treatments for fundamental diabetes is important.The utilization of autologous cells from patients with diabetes may address challenges regarding the compatibility of donor tissues as well as provide the means to naturally and safely restore function,reducing future risks while also providing a long-term cure.Here,we review recent findings regarding the use of adult OB NSCs as a potential diabetes cure,and discuss the potential of OB NSC-based pharmaceutical applications for neuronal diseases and mental disorders.

Therapeutic efficacy and toxicity of a single and double application of boron neutron capture therapy (BNCT) in a hamster cheek pouch oral precancer model

International Nuclear Information System (INIS)

Monti Hughes, A; Pozzi, E C C; Thorp, S; Garabalino, M A; Farias, R O; Gonzalez, S J; Heber, E M; Itoiz, M E; Aromando, R F; Molinari, A J; Miller, M; Nigg, D W; Curotto, P; Trivillin, V A; Schwint, A E

2012-01-01

Tumor development from tissue with potentially malignant disorders (PMD) gives rise to second primary tumors. We previously demonstrated the partial inhibitory effect on tumor development of Boron Neutron Capture Therapy (BNCT) mediated by the boron compounds BPA (boronophenylalanine) and decahydrodecaborate (GB-10) in a hamster pouch oral precancer model. Seeking to optimize BNCT, the aim of the present study was to contribute to the knowledge of BNCT radiobiology for oral precancer and assess new BNCT protocols in terms of inhibition of tumor development and radiotoxicity. Groups of cancerized hamsters were locally exposed to single or double applications (2 weeks apart) of BPA-BNCT or (GB-10 + BPA)-BNCT at a total dose of 8Gy to tissue with PMD; to a single application of BPA-BNCT at 6Gy and to a double application (4 weeks apart) of BPA-BNCT or (BPA + GB-10)-BNCT at a total dose of 10Gy. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumor development from tissue with PMD and mucositis were followed for 8 months. The marked therapeutic efficacy of single applications of BNCT at 6 and 8Gy were associated to severe radiotoxicity. Dose fractionation into 2 applications reduced mucositis but also reduced therapeutic efficacy, depending on dose and interval between applications. A double application (4 weeks apart) of (GB-10 + BPA)-BNCT at a total dose of 10Gy rendered the best therapeutic advantage, i.e. 63% - 100% inhibition of tumor development with only slight mucositis in 67% of cases. The data reported herein show that issues such as dose levels and dose fractionation, interval between applications, and choice of boron compounds are pivotal to therapeutic advantage and must be tailored for a particular pathology and anatomic site. The present study determined treatment conditions that would contribute to optimize BNCT for precancer and that would warrant cautious assessment in a clinical scenario (author)

Graphene- gold based nanocomposites applications in cancer diseases; Efficient detection and therapeutic tools.

Science.gov (United States)

Al-Ani, Lina A; AlSaadi, Mohammed A; Kadir, Farkaad A; Hashim, Najihah M; Julkapli, Nurhidayatullaili M; Yehye, Wageeh A

2017-10-20

Early detection and efficient treatment of cancer disease remains a drastic challenge in 21st century. Throughout the bulk of funds, studies, and current therapeutics, cancer seems to aggressively advance with drug resistance strains and recurrence rates. Nevertheless, nanotechnologies have indeed given hope to be the next generation for oncology applications. According to US National cancer institute, it is anticipated to revolutionize the perspectives of cancer diagnosis and therapy. With such success, nano-hybrid strategy creates a marvelous preference. Herein, graphene-gold based composites are being increasingly studied in the field of oncology, for their outstanding performance as robust vehicle of therapeutic agents, built-in optical diagnostic features, and functionality as theranostic system. Additional modes of treatments are also applicable including photothermal, photodynamic, as well as combined therapy. This review aims to demonstrate the various cancer-related applications of graphene-gold based hybrids in terms of detection and therapy, highlighting the major attributes that led to designate such system as a promising ally in the war against cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Is there a Biological Basis for Therapeutic Applications of Millimetre Waves and THz Waves?

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Mattsson, Mats-Olof; Zeni, Olga; Simkó, Myrtill

2018-03-01

Millimetre wave (MMW) and THz wave (THz) applications are already employed in certain industrial and medical environments for non-destructive quality control, and medical imaging, diagnosis, and therapy, respectively. The aim of the present study is to investigate if published experimental studies (in vivo and in vitro) provide evidence for "non-thermal" biological effects of MMW and THz. Such effects would occur in absence of tissue heating and associated damage and are the ones that can be exploited for therapeutic medical use. The investigated studies provide some evidence for both MMW and THz that can influence biological systems in a manner that is not obviously driven by tissue heating. However, the number of relevant studies is very limited which severely limits the drawing of any far-reaching conclusions. Furthermore, the studies have not addressed specific interaction mechanisms and do not provide hints for future mechanistic studies. Also, the studies do not indicate any specific importance regarding power density levels, frequencies, or exposure duration. It is also unclear if any specific biological endpoints are especially sensitive. Any therapeutic potential of MMW or THz has to be evaluated based on future high-quality studies dealing with physical, bio-physical, and biological aspects that have specific health-related perspectives in mind.

Combination therapy of potential gene to enhance oral cancer therapeutic effect

Science.gov (United States)

Yeh, Chia-Hsien; Hsu, Yih-Chih

2015-03-01

The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

Potential Applications of PET/MR Imaging in Cardiology.

Science.gov (United States)

Ratib, Osman; Nkoulou, René

2014-06-01

Recent advances in hybrid PET/MR imaging have opened new perspectives for cardiovascular applications. Although cardiac MR imaging has gained wider adoption for routine clinical applications, PET images remain the reference in many applications for which objective analysis of metabolic and physiologic parameters is needed. In particular, in cardiovascular diseases-more specifically, coronary artery disease-the use of quantitative and measurable parameters in a reproducible way is essential for the management of therapeutic decisions and patient follow-up. Functional MR images and dynamic assessment of myocardial perfusion from transit of intravascular contrast medium can provide useful criteria for identifying areas of decreased myocardial perfusion or for assessing tissue viability from late contrast enhancement of scar tissue. PET images, however, will provide more quantitative data on true tissue perfusion and metabolism. Quantitative myocardial flow can also lead to accurate assessment of coronary flow reserve. The combination of both modalities will therefore provide complementary data that can be expected to improve the accuracy and reproducibility of diagnostic procedures. But the true potential of hybrid PET/MR imaging may reside in applications beyond the domain of coronary artery disease. The combination of both modalities in assessment of other cardiac diseases such as inflammation and of other systemic diseases can also be envisioned. It is also predicted that the 2 modalities combined could help characterize atherosclerotic plaques and differentiate plaques with a high risk of rupture from stable plaques. In the future, the development of new tracers will also open new perspectives in evaluating myocardial remodeling and in assessing the kinetics of stem cell therapy in myocardial infarction. New tracers will also provide new means for evaluating alterations in cardiac innervation, angiogenesis, and even the assessment of reporter gene technologies

Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

Directory of Open Access Journals (Sweden)

Mostafa Wanees Ahmed El husseny

2017-01-01

Full Text Available Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM, insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

Therapeutic potential of umbilical cord blood cells for type 1 diabetes mellitus.

Science.gov (United States)

He, Binbin; Li, Xia; Yu, Haibo; Zhou, Zhiguang

2015-11-01

Type 1 diabetes mellitus (T1DM) is a chronic disorder that results from autoimmune-mediated destruction of pancreatic islet β-cells. However, to date, no conventional intervention has successfully treated the disease. The optimal therapeutic method for T1DM should effectively control the autoimmunity, restore immune homeostasis, preserve residual β-cells, reverse β-cell destruction, and protect the regenerated insulin-producing cells against re-attack. Umbilical cord blood is rich in regulatory T (T(reg)) cells and multiple types of stem cells that exhibit immunomodulating potential and hold promise in their ability to restore peripheral tolerance towards pancreatic islet β-cells through remodeling of immune responses and suppression of autoreactive T cells. Recently, reinfusion of autologous umbilical cord blood or immune cells from cord blood has been proposed as a novel therapy for T1DM, with the advantages of no risk to the donors, minimal ethical concerns, a low incidence of graft-versus-host disease and easy accessibility. In this review, we revisit the role of autologous umbilical cord blood or immune cells from cord blood-based applications for the treatment of T1DM. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

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Carolina Alves Nicolau

2018-02-01

Full Text Available Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7 followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic, and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1 antimicrobial activity; (2 treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy; (3 treatment of cardiovascular diseases, and (4 anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.

Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries.

Science.gov (United States)

Vieira, M H C; Oliveira, R J; Eça, L P M; Pereira, I S O; Hermeto, L C; Matuo, R; Fernandes, W S; Silva, R A; Antoniolli, A C M B

2014-12-12

Rupture of the Achilles tendon diminishes quality of life. The gold-standard therapy is a surgical suture, but this presents complications, including wound formation and inflammation. These complications spurred evaluation of the therapeutic potential of mesenchymal stem cells (MSCs) from adipose tissue. New Zealand rabbits were divided into 6 groups (three treatments with two time points each) evaluated at either 14 or 28 days after surgery: cross section of the Achilles tendon (CSAT); CSAT + Suture; and CSAT + MSC. A comparison between all groups at both time points showed a statistically significant increase in capillaries and in the structural organization of collagen in the healed tendon in the CSAT + Suture and CSAT + MSC groups at the 14-day assessment. Comparison between the two time points within the same group showed a statistically significant decrease in the inflammatory process and an increase in the structural organization of collagen in the CSAT and CSAT + MSC groups. A study of the genomic integrity of the cells suggested a linear correlation between an increase of injuries and culture time. Thus, MSC transplantation is a good alternative for treatment of Achilles tendon ruptures because it may be conducted without surgery and tendon suture and, therefore, has no risk of adverse effects resulting from the surgical wound or inflammation caused by nonabsorbable sutures. Furthermore, this alternative treatment exhibits a better capacity for wound healing and maintaining the original tendon architecture, depending on the arrangement of the collagen fibers, and has important therapeutic potential.

Therapeutic potential of paclitaxel-radiation treatment of a murine ovarian carcinoma

International Nuclear Information System (INIS)

Milas, Luka; Saito, Yoshihiro; Hunter, Nancy; Milross, Christopher G.; Mason, Kathryn A.

1996-01-01

Background. Paclitaxel has been shown to radiosensitize tumor cells in culture by arresting them in the most radiosensitive G 2 and M cell cycle phases. In vivo preclinical studies are now necessary to obtain full insight into the radiopotentiating potential of this drug and its ability to increase the therapeutic gain of radiotherapy. We tested its ability to enhance the tumor radioresponse of an ovarian carcinoma and to influence the normal tissue radioresponse of recipient mice. Methods. Mice bearing 8-mm isotransplants of a syngeneic ovarian carcinoma, designated OCA-I, in their legs were treated with 40 mg/kg paclitaxel i.v., 14-60 Gy single-dose local tumor irradiation, or both; radiation was given under ambient conditions 1-96 h after paclitaxel. Tumor growth delay, tumor cure rate (TCD 50 assay), and delay in tumor recurrences were measured. Normal tissue radioresponse was determined using jejunal crypt cell survival at 3.5 days after exposure of mice to 9-14 Gy single dose of total body irradiation; the mice were untreated or treated with 40 mg/kg i.v. paclitaxel 4-96 h before irradiation. Results. Paclitaxel alone was effective against OCA-I, but its combination with irradiation produced supra-additive tumor growth delay. It also reduced TCD 50 values and delayed tumor recurrences. The enhancement of tumor radioresponse ranged from 1.33 to 1.96; the value increased as the time between paclitaxel administration and tumor irradiation increased up to 48 h, but then decreased again at 96 h. In contrast, paclitaxel protected jejunum against radiation damage by factors of 1.03 to 1.07 when given 24-96 h before irradiation. It showed some potentiation of damage (by a factor of 1.07), but only when given 4 h before irradiation. Conclusions. Paclitaxel potentiated tumor radioresponse if given within 4 days before irradiation, whereas it caused radioprotection of normal tissue (jejunum) at that time. Therefore, paclitaxel significantly increased therapeutic gain

Effects of Neuropeptide Y on Stem Cells and Their Potential Applications in Disease Therapy

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Song Peng

2017-01-01

Full Text Available Neuropeptide Y (NPY, a 36-amino acid peptide, is widely distributed in the central and peripheral nervous systems and other peripheral tissues. It takes part in regulating various biological processes including food intake, circadian rhythm, energy metabolism, and neuroendocrine secretion. Increasing evidence indicates that NPY exerts multiple regulatory effects on stem cells. As a kind of primitive and undifferentiated cells, stem cells have the therapeutic potential to replace damaged cells, secret paracrine molecules, promote angiogenesis, and modulate immunity. Stem cell-based therapy has been demonstrated effective and considered as one of the most promising treatments for specific diseases. However, several limitations still hamper its application, such as poor survival and low differentiation and integration rates of transplanted stem cells. The regulatory effects of NPY on stem cell survival, proliferation, and differentiation may be helpful to overcome these limitations and facilitate the application of stem cell-based therapy. In this review, we summarized the regulatory effects of NPY on stem cells and discussed their potential applications in disease therapy.

Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

Directory of Open Access Journals (Sweden)

Neil V. Klinger

2016-01-01

Full Text Available Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin’s ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

Reactor-produced therapeutic radioisotopes

International Nuclear Information System (INIS)

Knapp, F.F. Jr.

2002-01-01

The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities.

Science.gov (United States)

Soler, Joaquim; Elices, Matilde; Franquesa, Alba; Barker, Steven; Friedlander, Pablo; Feilding, Amanda; Pascual, Juan C; Riba, Jordi

2016-03-01

Ayahuasca is a psychotropic plant tea used for ritual purposes by the indigenous populations of the Amazon. In the last two decades, its use has expanded worldwide. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested its therapeutic potential, reporting that its use has helped individuals abandon the consumption of addictive drugs. Furthermore, recent open-label studies in patients with treatment-resistant depression found that a single ayahuasca dose induced a rapid antidepressant effect that was maintained weeks after administration. Here, we conducted an exploratory study of the psychological mechanisms that could underlie the beneficial effects of ayahuasca. We assessed a group of 25 individuals before and 24 h after an ayahuasca session using two instruments designed to measure mindfulness capacities: The Five Facets Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ). Ayahuasca intake led to significant increases in two facets of the FFMQ indicating a reduction in judgmental processing of experiences and in inner reactivity. It also led to a significant increase in decentering ability as measured by the EQ. These changes are classic goals of conventional mindfulness training, and the scores obtained are in the range of those observed after extensive mindfulness practice. The present findings support the claim that ayahuasca has therapeutic potential and suggest that this potential is due to an increase in mindfulness capacities.

Psychedelics and hypnosis: Commonalities and therapeutic implications.

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Lemercier, Clément E; Terhune, Devin B

2018-06-01

Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby warrants empirical attention. Here we aim to elucidate the phenomenological and neurophysiological similarities and dissimilarities between psychedelic states and hypnosis in order to revisit how contemporary knowledge may inform their conjunct usage in psychotherapy. We review recent advances in phenomenological and neurophysiological research on psychedelics and hypnosis, and we summarize early investigations on the coupling of psychedelics and hypnosis in scientific and therapeutic contexts. Results/outcomes: We highlight commonalities and differences between psychedelics and hypnosis that point to the potential efficacy of combining the two in psychotherapy. We propose multiple research paths for coupling these two phenomena at different stages in the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy in order to prepare, guide and integrate the psychedelic experience with the aim of enhancing therapeutic outcomes. Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.

Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

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Laura Santangelo

2017-01-01

Full Text Available Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA from donor to recipient cells. Notably, tumor-derived exosomes (TDEs appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC, the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined.

Therapeutical evaluation of bevacizumab application in relapsed pterygium

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Mayara Martins Abrahão

Full Text Available Abstract Objective: Therapeutic evaluation of Bevacizumab application in relapsed pterygium concerning visual acuity, keratometry, refraction, symptomatology. Methods: Group 1 (4 patients received 0.1 ml of Bevacizumab (avastin, being evaluated posteriorly on the tenth and thirtieth days after the application, seeking to compare with the exam previously made, being it realized with the other two groups, in which Group 2 (4 patients received 0.2 ml of Bevacizumab and the Group 3 (3 patients received 1 ml of the placebo injection. Results: In this study, eleven eyes of eleven patients were evaluated. Among these patients, 7 were women (63.6% and 4 men (36.4%. There was a variation in the cylindrical diopter after the treatment with a dose of 0.1 ml of bevaciumab during the evaluation on the thirtieth day. Whereas the cylindrical shaft had a significantly larger modification after the application of 0.2 ml. Regarding the spherical diopter variation, there were modifications in the 3 groups. The keratometry varied in the 3 groups, mostly after the thirtieth day of evaluation. In relation to symptomatology, it was observed a reduction in the subjective evaluation of the eye burning sensation, the prurience mentioned by the patient and a reduction of the hyperemia biomicroscopy evaluation. Conclusion: In bevacizumab application in the recurrent pterygium treatment, there is modification of the spherical and cylindrical parameters of refraction, besides the changes in keratometry and the reduction of the symptomatology.

The multifaceted therapeutic potential of benfotiamine.

Science.gov (United States)

Balakumar, Pitchai; Rohilla, Ankur; Krishan, Pawan; Solairaj, Ponnu; Thangathirupathi, Arunachalam

2010-06-01

Thiamine, known as vitamin B(1), plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of benfotiamine. (c) 2010 Elsevier Ltd. All rights reserved.

Antibacterial Free Fatty Acids and Monoglycerides: Biological Activities, Experimental Testing, and Therapeutic Applications

Science.gov (United States)

Yoon, Bo Kyeong; Jackman, Joshua A.; Valle-González, Elba R.

2018-01-01

Antimicrobial lipids such as fatty acids and monoglycerides are promising antibacterial agents that destabilize bacterial cell membranes, causing a wide range of direct and indirect inhibitory effects. The goal of this review is to introduce the latest experimental approaches for characterizing how antimicrobial lipids destabilize phospholipid membranes within the broader scope of introducing current knowledge about the biological activities of antimicrobial lipids, testing strategies, and applications for treating bacterial infections. To this end, a general background on antimicrobial lipids, including structural classification, is provided along with a detailed description of their targeting spectrum and currently understood antibacterial mechanisms. Building on this knowledge, different experimental approaches to characterize antimicrobial lipids are presented, including cell-based biological and model membrane-based biophysical measurement techniques. Particular emphasis is placed on drawing out how biological and biophysical approaches complement one another and can yield mechanistic insights into how the physicochemical properties of antimicrobial lipids influence molecular self-assembly and concentration-dependent interactions with model phospholipid and bacterial cell membranes. Examples of possible therapeutic applications are briefly introduced to highlight the potential significance of antimicrobial lipids for human health and medicine, and to motivate the importance of employing orthogonal measurement strategies to characterize the activity profile of antimicrobial lipids. PMID:29642500

Radionuclides for therapeutic applications: Biological and medical aspects (present status, development and expectations)

International Nuclear Information System (INIS)

Wambersie, A.; Gahbauer, R.A.

2002-01-01

Different multidisciplinary therapeutic strategies and technical approaches are used today in cancer therapy. Among the techniques involving ionizing radiation, therapeutic applications of radioactive nuclides deserve a particular interest ; some clinical indications are well established, while several others are now being investigated, and some of them are promising. The efficacy of radionuclides in therapy often depends on technical factors such as specific activity, purity, chemical presentation, availability, etc. These factors are closely related, at least partly, to the production methods. This justifies the organization of the present Consultant's meeting by the IAEA. Brief information on cancer, its socio-economic aspects, and some data concerning cure rate are presented first

The Therapeutic Potential of Brown Adipocytes in Humans

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Craig ePorter

2015-10-01

Full Text Available Obesity and its metabolic consequences represent a significant clinical problem. From a thermodynamic standpoint, obesity results from a discord in energy intake and expenditure. To date, lifestyle interventions based on reducing energy intake and/or increasing energy expenditure have proved ineffective in the prevention and treatment of obesity, owing to poor long-term adherence to such interventions. Thus, an effective strategy to prevent or correct obesity is currently lacking.As the combustion engines of our cells, mitochondria play a critical role in energy expenditure. At a whole body level, approximately 80% of mitochondrial membrane potential generated by fuel oxidation is used to produce ATP, and the remaining 20% is lost through heat-producing uncoupling reactions. The coupling of mitochondrial respiration to ATP production represents an important component in whole body energy expenditure. Brown adipose tissue (BAT is densely populated with mitochondria containing the inner mitochondrial proton carrier uncoupling protein 1 (UCP. UCP1 uncouples oxidative phosphorylation, meaning that mitochondrial membrane potential is dissipated as heat. The recent re-discovery of BAT depots in adult humans has rekindled scientific interest in the manipulation of mitochondrial uncoupling reactions as a means to increase metabolic rate, thereby counteracting obesity and its associated metabolic phenotype. In this article, we discuss the evidence for the role BAT plays in metabolic rate and glucose and lipid metabolism in humans, and the potential for UCP1 recruitment in the white adipose tissue of humans. While the future holds much promise for a therapeutic role of UCP1 expressing adipocytes in human energy metabolism, particularly in the context of obesity, tissue specific strategies that activate or recruit UCP1 in human adipocytes represent an obligatory translation step for this early promise to be realized.

Therapeutic potential of mGluR5 targeting in Alzheimer's disease

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Anil eKumar

2015-06-01

Full Text Available Decades of research dedicated towards Alzheimer's disease (AD has culminated in much of the current understanding of the neurodegeneration associated with disease. However, delineating the pathophysiology and finding a possible cure for the disease is still wanting. This is in part due to the lack of knowledge pertaining to the connecting link between neurodegenerative and neuroinflammatory pathways. Consequently, the inefficacy and ill-effects of the drugs currently available for AD encourage the need for alternative and safe therapeutic intervention. In this review we highlight the potential of mGluR5, a metabotropic glutamatergic receptor, in understanding the mechanism underlying the neuronal death and neuroinflammation in AD. We also discuss the role of mGlu5 receptor in mediating the neuron-glia interaction in the disease. Finally, we discuss the potential of mGluR5 as target for treating AD.

Therapeutic Potential of Moringa oleifera Leaves in Chronic Hyperglycemia and Dyslipidemia: A Review

Science.gov (United States)

Mbikay, Majambu

2012-01-01

Moringa oleifera (M. oleifera) is an angiosperm plant, native of the Indian subcontinent, where its various parts have been utilized throughout history as food and medicine. It is now cultivated in all tropical and sub-tropical regions of the world. The nutritional, prophylactic, and therapeutic virtues of this plant are being extolled on the Internet. Dietary consumption of its part is therein promoted as a strategy of personal health preservation and self-medication in various diseases. The enthusiasm for the health benefits of M. oleifera is in dire contrast with the scarcity of strong experimental and clinical evidence supporting them. Fortunately, the chasm is slowly being filled. In this article, I review current scientific data on the corrective potential of M. oleifera leaves in chronic hyperglycemia and dyslipidemia, as symptoms of diabetes and cardiovascular disease (CVD) risk. Reported studies in experimental animals and humans, although limited in number and variable in design, seem concordant in their support for this potential. However, before M. oleifera leaf formulations can be recommended as medication in the prevention or treatment of diabetes and CVD, it is necessary that the scientific basis of their efficacy, the therapeutic modalities of their administration and their possible side effects be more rigorously determined. PMID:22403543

ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool.

Science.gov (United States)

Weissenberger, S; Klicperova-Baker, M; Zimbardo, P; Schonova, K; Akotia, D; Kostal, J; Goetz, M; Raboch, J; Ptacek, R

2016-01-01

The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations) and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD) symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo's time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201) are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods), deficits in social learning, and increased aggressiveness both in ADHD and in the population scoring high on Present Hedonism in the Zimbardo Time Perspective Inventory. We conclude that Zimbardo's time perspective offers both: 1) a potential diagnostic tool - the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2) a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder); however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD.

Therapeutic potential of Moringa oleifera leaves in chronic hyperglycemia and dyslipidemia: a review

Directory of Open Access Journals (Sweden)

Majambu eMbikay

2012-03-01

Full Text Available Moringa oleifera (M. oleifera is an angiosperm plant, native of the Indian subcontinent, where its various parts have been utilized throughout history as food and medicine. It is now cultivated in all tropical and subtropical regions of the world. The nutritional, prophylactic, and therapeutic virtues of this plant are being extolled on the Internet. Dietary consumption of its part is therein promoted as a strategy of personal health preservation and self-medication in various diseases. The enthusiasm for the health benefits of M. oleifera is in dire contrast with the scarcity of strong experimental and clinical evidence supporting them. Fortunately, the chasm is slowly being filled. In this article, I review current scientific data on the corrective potential of M. oleifera leaves in chronic hyperglycemia and dyslipidemia, as symptoms of diabetes and cardiovascular disease risk. Reported studies in experimental animals and humans, although limited in number and variable in design, seem concordant in their support for this potential. However, before M. oleifera leaf formulations can be recommended as medication in the prevention or treatment of diabetes and cardiovascular disease, it is necessary that the scientific basis of their efficacy, the therapeutic modalities of their administration and their possible side effects be more rigorously determined.

Microbial siderophore-based iron assimilation and therapeutic applications.

Science.gov (United States)

Li, Kunhua; Chen, Wei-Hung; Bruner, Steven D

2016-06-01

Siderophores are structurally diverse, complex natural products that bind metals with extraordinary specificity and affinity. The acquisition of iron is critical for the survival and virulence of many pathogenic microbes and diverse strategies have evolved to synthesize, import and utilize iron. There has been a substantial increase of known siderophore scaffolds isolated and characterized in the past decade and the corresponding biosynthetic gene clusters have provided insight into the varied pathways involved in siderophore biosynthesis, delivery and utilization. Additionally, therapeutic applications of siderophores and related compounds are actively being developed. The study of biosynthetic pathways to natural siderophores augments the understanding of the complex mechanisms of bacterial iron acquisition, and enables a complimentary approach to address virulence through the interruption of siderophore biosynthesis or utilization by targeting the key enzymes to the siderophore pathways.

Mass Spectrometry in Clinical Laboratory: Applications in Therapeutic Drug Monitoring and Toxicology.

Science.gov (United States)

Garg, Uttam; Zhang, Yan Victoria

2016-01-01

Mass spectrometry (MS) has been used in research and specialized clinical laboratories for decades as a very powerful technology to identify and quantify compounds. In recent years, application of MS in routine clinical laboratories has increased significantly. This is mainly due to the ability of MS to provide very specific identification, high sensitivity, and simultaneous analysis of multiple analytes (>100). The coupling of tandem mass spectrometry with gas chromatography (GC) or liquid chromatography (LC) has enabled the rapid expansion of this technology. While applications of MS are used in many clinical areas, therapeutic drug monitoring, drugs of abuse, and clinical toxicology are still the primary focuses of the field. It is not uncommon to see mass spectrometry being used in routine clinical practices for those applications.

Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine.

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Wang, Xijun

2014-04-01

Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.

The use of contact lenses in low vision rehabilitation: optical and therapeutic applications.

Science.gov (United States)

Vincent, Stephen J

2017-09-01

Ocular pathology that manifests at an early age has the potential to alter the vision-dependent emmetropisation mechanism, which co-ordinates ocular growth throughout childhood. The disruption of this feedback mechanism in children with congenital or early-onset visual impairment often results in the development of significant ametropia, including high levels of spherical refractive error, astigmatism and anisometropia. This review examines the use of contact lenses as a refractive correction, low vision aid and therapeutic intervention in the rehabilitation of patients with bilateral, irreversible visual loss due to congenital ocular disease. The advantages and disadvantages of the use of contact lenses for increased magnification (telescopes and microscopes) or field expansion (reverse telescopes) are discussed, along with the benefits and practical considerations for the correction of pathological high myopia. The historical and present use of therapeutic tinted contact lenses to reduce photosensitivity and nystagmus in achromatopsia, albinism and aniridia are also presented, including clinical considerations for the contact lens practitioner. In addition to the known optical benefits in comparison to spectacles for high levels of ametropia (an improved field of view for myopes and fewer inherent oblique aberrations), contact lenses may be of significant psycho-social benefit for patients with low vision, due to enhanced cosmesis and reduced conspicuity and potential related effects of improved self-esteem and peer acceptance. The contact lens correction of patients with congenital vision impairment can be challenging for both practitioner and patient but should be considered as a potential optical or therapeutic solution in modern low vision rehabilitation. © 2017 Optometry Australia.

Therapeutic potential of the original incretin hormone glucose-dependent insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's disease?

Science.gov (United States)

Irwin, Nigel; Gault, Victor; Flatt, Peter R

2010-09-01

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release. To date, the physiological importance of GIP has received much less attention than its younger sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to refocus on this important and somewhat neglected incretin hormone. The potential role of GIP as a treatment option for type 2 diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option for obesity, osteoporosis and cognitive impairment is also considered. Long-acting GIP receptor agonists offer a potential new class of antidiabetic drugs. Furthermore, recent observations suggest an as yet untapped potential for GIP agonists in the treatment of osteoporosis and cognitive impairment. In addition, GIP is known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or reverse, many of the obesity-associated metabolic disturbances. This review focuses on preclinical data generated to date. GIP-based therapeutics have potential for the treatment of type 2 diabetes and obesity, with the possibility of further beneficial actions in osteoporosis and cognitive decline.

Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent

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Der Jiun Ooi

2016-06-01

Full Text Available Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF isolated from M. latifolia rhizome methanolic extract (RME contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders.

Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy.

Science.gov (United States)

Witt-Enderby, Paula A; Radio, Nicholas M; Doctor, John S; Davis, Vicki L

2006-11-01

Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24-hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24-hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

Genome editing in pluripotent stem cells: research and therapeutic applications

Energy Technology Data Exchange (ETDEWEB)

Deleidi, Michela, E-mail: michela.deleidi@dzne.de [German Center for Neurodegenerative Diseases (DZNE) Tübingen within the Helmholtz Association, Tübingen (Germany); Hertie Institute for Clinical Brain Research, University of Tübingen (Germany); Yu, Cong [Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, University at Buffalo, New York (United States)

2016-05-06

Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases for ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications. - Highlights: • Programmable nucleases have proven efficient and specific for genome editing in human pluripotent stem cells (hPSCs). • Genome edited hPSCs can be employed to study gene function in health and disease as well as drug and chemical screens. • Genome edited hPSCs hold great promise for ex vivo gene therapy approaches. • Technical and safety issues should be first addressed to advance the clinical use of gene-edited hPSCs.

Genome editing in pluripotent stem cells: research and therapeutic applications

International Nuclear Information System (INIS)

Deleidi, Michela; Yu, Cong

2016-01-01

Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases for ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications. - Highlights: • Programmable nucleases have proven efficient and specific for genome editing in human pluripotent stem cells (hPSCs). • Genome edited hPSCs can be employed to study gene function in health and disease as well as drug and chemical screens. • Genome edited hPSCs hold great promise for ex vivo gene therapy approaches. • Technical and safety issues should be first addressed to advance the clinical use of gene-edited hPSCs.

[Nuclear transfer and therapeutic cloning].

Science.gov (United States)

Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

2005-03-01

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Potential therapeutic gain from using p(66)/Be neutrons

International Nuclear Information System (INIS)

Slabbert, J.P.; Jones, D.T.L.; Theron, C.; Serafin, A.; Bohm, L.; Schmitt, G.

1997-01-01

Neutron therapy will be beneficial to patients with tumor types which are resistant to photons but relatively sensitive to high-LET radiation. In this work 15 different cell types, mostly of human tumor decent, were exposed in vitro to 60 Co γ-rays and p(66)/Be neutrons. Micronuclei frequencies in bi-nucleated cells and surviving fractions were determined for each cell type. Following exposure to either 1 or 1.5 Gy neutrons, micronuclei frequencies were significantly correlated with that observed from 2 Gy photons. A strong correlation between mean inactivation doses determined for these radiation modalities from survival curve inactivation parameters, was also noted. In spite of this a significant correlation between the variation in neutron RBE values and photon resistance was established. It is concluded that although neutron and photo sensitivities are related in the group of cell types studies, the use of this high energy neutron source may constitute a potential therapeutic gain for some tumor types. (authors)

Manual on therapeutic uses of iodine-131. Incorporating: Applications guide, procedures guide, basics guide

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

This publication is part of practical radiation safety manual series for different fields of application aimed primarily at persons handling radiation sources on a daily routine basis, which could at same time be used by the competent authorities, supporting their efforts in the radiation protection training of workers or medical assistance personnel or helping on-site management to set up local radiation protection rules. It is dedicated to therapeutic uses of Iodine-131: its application and procedures guides.

Manual on therapeutic uses of iodine-131. Incorporating: Applications guide, procedures guide, basics guide

International Nuclear Information System (INIS)

1996-01-01

This publication is part of practical radiation safety manual series for different fields of application aimed primarily at persons handling radiation sources on a daily routine basis, which could at same time be used by the competent authorities, supporting their efforts in the radiation protection training of workers or medical assistance personnel or helping on-site management to set up local radiation protection rules. It is dedicated to therapeutic uses of Iodine-131: its application and procedures guides

Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

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Manasi Das

Full Text Available Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined and single or dual drug loaded nanoparticles (unconjugated/folate conjugated. The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.

Amyloid-β peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease.

Science.gov (United States)

Hanenberg, Michael; McAfoose, Jordan; Kulic, Luka; Welt, Tobias; Wirth, Fabian; Parizek, Petra; Strobel, Lisa; Cattepoel, Susann; Späni, Claudia; Derungs, Rebecca; Maier, Marcel; Plückthun, Andreas; Nitsch, Roger M

2014-09-26

Passive immunization with anti-amyloid-β peptide (Aβ) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Aβ-specific DARPins. We further showed their ability to delay Aβ aggregation and prevent Aβ-mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Aβ-specific DARPins (D23 and 3×D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3×D23 treatments were shown to result in improved cognitive performance and reduced soluble Aβ levels. These findings demonstrate the therapeutic potential of Aβ-specific DARPins for the treatment of Alzheimer disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Therapeutic potential of bryophytes and derived compounds against cancer

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Abhijit Dey

2015-08-01

Full Text Available Bryophytes, taxonomically placed between the algae and the pteridophytes, are divided into three classes such as Liverworts, Hornworts and Mosses. Indigenous use involves this small group of plants to treat various diseases. Bryophytes have been investigated pharmacologically for active biomolecules. Several constituents with therapeutic potential have been isolated, characterized and investigated for antibacterial, antifungal, antiviral, antioxidative, antiinflamatory and anticancerous efficacy. The present review deals with the literature covering the anticancerous potential of bryophytes. Apart from the examples of the compounds and the containing bryophyte genera, the authors have tried to include the examples of cancer cell lines on which the efficacy have been tested and the mode of action of certain cytotoxic agents. Crude extracts and isolated compounds from bryophytes were found to possess potent cytotoxic properties. Different types of terpenoids and bibenzyls have been reported among the most potent cytotoxic compounds. Most of these compounds were found to induce apoptosis by activating a number of genes and enzymes. Biochemical markers such as DNA fragmentation, nuclear condensation, proteolysis of poly (ADP-ribose polymerase, activation of caspases, inhibition of antiapoptotic nuclear transcriptional factor-kappaB, activation of p38 mitogen-activated protein kinase etc. have been found to be associated with apoptotic and necrotic response. This review summarizes recent scientific findings and suggests further investigations to evaluate the cytotoxic efficacy of bryophytes.

Innovative Therapeutic Potential of Cannabinoid Receptors as Targets in Alzheimer's disease and Less Well-Known Diseases.

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Paez, Juan A; Campillo, Nuria E

2018-02-25

The discovery of cannabinoid receptors at the beginning of the 1990s, CB1 being cloned in 1990 and CB2 cloned in 1993, and the availability of selective and potent cannabimimetics could only be justified by the existence of endogenous ligands that are capable of binding to them. Thus, the characterisation and cloning of the first cannabinoid receptor (CB1) led to the isolation and characterisation of the first endocannabinoid, arachidonoylethanolamide (AEA), two years later and the subsequent identification of a family of lipid transmitters known as the fatty acid ester 2-arachidonoylglycerol (2-AG). The endogenous cannabinoid system is a complex signalling system that comprises transmembrane endocannabinoid receptors, their endogenous ligands (the endocannabinoids), the specific uptake mechanisms and the enzymatic systems related to their biosynthesis and degradation. The endocannabinoid system has been implicated in a wide diversity of biological processes, in both the central and peripheral nervous systems, including memory, learning, neuronal development, stress and emotions, food intake, energy regulation, peripheral metabolism, and the regulation of hormonal balance through the endocrine system. In this context, this article will review the current knowledge of the therapeutic potential of cannabinoid receptor as a target in Alzheimer's disease and other less well-known diseases that include, among others, multiple sclerosis, bone metabolism, and Fragile X syndrome. The therapeutic applications will be addressed through the study of cannabinoid agonists acting as single drugs and multi-target drugs highlighting the CB2 receptor agonist. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[The Functional Role of Exosomes in Cancer Biology and Their Potential as Biomarkers and Therapeutic Targets of Cancer].

Science.gov (United States)

Naito, Yutaka; Yoshioka, Yusuke; Ochiya, Takahiro

2015-06-01

Intercellular communication plays an important role in the regulation of various cellular events. In particular, cancer cells and the surrounding cells communicate with each other, and this intercellular communication triggers cancer initiation and progression through the secretion of molecules, including growth factors and cytokines. Recent advances in cancer biology have indicated that small membrane vesicles, termed exosomes, also serve as regulatory agents in intercellular communications. Exosomes contain functional cellular components, including proteins and microRNAs (miRNAs), and they transfer these components to recipient cells. This exosome-mediated intercellular communication leads to increased growth, invasion, and metastasis of cancer. Thus, researchers regard exosomes as important cues to understanding the molecular mechanisms of cancer biology. Indeed, several lines of evidence have demonstrated that exosomes can explain multiple aspects of cancer biology. In addition, increasing evidence suggests that exosomes and their specific molecules are also attractive for use as biomarkers and therapeutic targets in cancer. Recent reports showed the efficacy of a novel diagnosis by detecting component molecules of cancer-derived exosomes, including miRNAs and membrane proteins. Furthermore, clinical trials that test the application of exosomes for cancer therapy have already been reported. From these points of view, we will summarize experimental data that support the role of exosomes in cancer progression and the potential of exosomes for use in novel diagnostic and therapeutic approaches for cancer.

Survivin-T34A: molecular mechanism and therapeutic potential

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Jonathan R Aspe

2010-12-01

Full Text Available Jonathan R Aspe, Nathan R WallCenter for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Department of Basic Sciences, Loma Linda University, Loma Linda, CA, USAAbstract: The inhibitor of apoptosis protein survivin's threonine 34 to alanine (T34A mutation abolishes a phosphorylation site for p34(cdc2–cyclin B1, resulting in initiation of the mitochondrial apoptotic pathway in cancer cells; however, it has little known direct effects on normal cells. The possibility that targeting survivin in this way may provide a novel approach for selective cancer gene therapy has yet to be fully evaluated. Although a flurry of work was undertaken in the late 1990s and early 2000s, only minor advances on this mutant have recently taken place. We recently described that cells generated to express a stable form of the mutant protein released this survivin-T34A to the conditioned medium. When this conditioned medium was collected and deposited on naive tumor cells, conditioned medium T34A was as effective as some chemotherapeutics in the induction of tumor cell apoptosis, and when combined with other forms of genotoxic stressors potentiated their killing effects. We hope with this review to revitalize the T34A field, as there is still much that needs to be investigated. In addition to determining the therapeutic dose and the duration of drug therapy required at the disease site, a better understanding of other key factors is also important. These include knowledge of target cell populations, cell-surface receptors, changes that occur in the target tissue at the molecular and cellular level with progression of the disease, and the mechanism and site of therapeutic action.Keywords: survivin, T34A, apoptosis, proliferation, therapy

Sphingosine 1-phosphate (S1P) signalling: Role in bone biology and potential therapeutic target for bone repair.

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Sartawi, Ziad; Schipani, Ernestina; Ryan, Katie B; Waeber, Christian

2017-11-01

The lipid mediator sphingosine 1-phosphate (S1P) affects cellular functions in most systems. Interest in its therapeutic potential has increased following the discovery of its G protein-coupled receptors and the recent availability of agents that can be safely administered in humans. Although the role of S1P in bone biology has been the focus of much less research than its role in the nervous, cardiovascular and immune systems, it is becoming clear that this lipid influences many of the functions, pathways and cell types that play a key role in bone maintenance and repair. Indeed, S1P is implicated in many osteogenesis-related processes including stem cell recruitment and subsequent differentiation, differentiation and survival of osteoblasts, and coupling of the latter cell type with osteoclasts. In addition, S1P's role in promoting angiogenesis is well-established. The pleiotropic effects of S1P on bone and blood vessels have significant potential therapeutic implications, as current therapeutic approaches for critical bone defects show significant limitations. Because of the complex effects of S1P on bone, the pharmacology of S1P-like agents and their physico-chemical properties, it is likely that therapeutic delivery of S1P agents will offer significant advantages compared to larger molecular weight factors. Hence, it is important to explore novel methods of utilizing S1P agents therapeutically, and improve our understanding of how S1P and its receptors modulate bone physiology and repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diatomic interaction potential theory applications

CERN Document Server

Goodisman, Jerry

2013-01-01

Diatomic Interaction Potential Theory, Volume 2: Applications discusses the variety of applicable theoretical material and approaches in the calculations for diatomic systems in their ground states. The volume covers the descriptions and illustrations of modern calculations. Chapter I discusses the calculation of the interaction potential for large and small values of the internuclear distance R (separated and united atom limits). Chapter II covers the methods used for intermediate values of R, which in principle means any values of R. The Hartree-Fock and configuration interaction schemes des

Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

Energy Technology Data Exchange (ETDEWEB)

Thonel, Aurelie de [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); Mezger, Valerie, E-mail: valerie.mezger@univ-paris-diderot.fr [CNRS, UMR7216 Epigenetics and Cell Fate, Paris (France); University Paris Diderot, 75013 Paris (France); Garrido, Carmen, E-mail: valerie.mezger@univ-paris-diderot.fr [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); CHU, Dijon BP1542, Dijon (France)

2011-03-07

Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents.

Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

International Nuclear Information System (INIS)

Thonel, Aurelie de; Mezger, Valerie; Garrido, Carmen

2011-01-01

Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents

Convergence of anatomy, technology, and therapeutics: a review of laser-assisted drug delivers.

Science.gov (United States)

Brauer, Jeremy A; Krakowski, Andrew C; Bloom, Bradley S; Nguyen, Tuyet A; Geronemus, Roy G

2014-12-01

This is a very exciting time in cutaneous laser surgery with an ever-expanding therapeutic armamentarium and an increased sophistication of available technology. These recent trends have allowed for both a rapid development of interest and exploration of laser-assisted drug delivery and its potential applications. We review the current literature on anatomy, technology, and therapeutics as it relates to laser-assisted drug delivery. The focus of our review is on two areas of interest that have received much attention to date - photodynamic therapy in the treatment of actinic keratoses and nonmelanoma skin cancers as well as the treatment of scarring. We will also discuss potential complications of existing modalities used independently and in laser-assisted drug delivery and conclude with future indications for this burgeoning therapeutic methodology.

Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity

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Luc Van Kaer

2018-03-01

Full Text Available Tolerance against self-antigens is regulated by a variety of cell types with immunoregulatory properties, such as CD1d-restricted invariant natural killer T (iNKT cells. In many experimental models of autoimmunity, iNKT cells promote self-tolerance and protect against autoimmunity. These findings are supported by studies with patients suffering from autoimmune diseases. Based on these studies, the therapeutic potential of iNKT cells in autoimmunity has been explored. Many of these studies have been performed with the potent iNKT cell agonist KRN7000 or its structural variants. These findings have generated promising results in several autoimmune diseases, although mechanisms by which iNKT cells modulate autoimmunity remain incompletely understood. Here, we will review these preclinical studies and discuss the prospects for translating their findings to patients suffering from autoimmune diseases.

Emerging therapeutic potential for xenin and related peptides in obesity and diabetes.

Science.gov (United States)

Craig, Sarah L; Gault, Victor A; Irwin, Nigel

2018-04-06

Xenin-25 is a 25 amino acid peptide hormone co-secreted from the same enteroendocrine K-cell as the incretin peptide glucose-dependent insulinotropic polypeptide (GIP). There is no known specific receptor for xenin-25, but studies suggest that at least some biological actions may be mediated through interaction with the neurotensin receptor. Original investigation into the physiological significance of xenin-25 focussed on effects related to gastrointestinal transit and satiety. However, xenin-25 has been demonstrated in pancreatic islets and recently shown to possess actions in relation to the regulation of insulin and glucagon secretion, as well as promoting beta-cell survival. Accordingly, the beneficial impact of xenin-25, and related analogues, has been assessed in animal models of diabetes-obesity. In addition, studies have demonstrated that metabolically active fragment peptides of xenin-25, particularly xenin-8, possess independent therapeutic promise for diabetes, as well as serving as bioactive components for the generation of multi-acting hybrid peptides with antidiabetic potential. This review will focus on continuing developments with xenin compounds in relation to new therapeutic approaches for diabetes-obesity. This article is protected by copyright. All rights reserved.

Therapeutic antibodies as a treatment option for dengue fever.

Science.gov (United States)

Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

2013-11-01

Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

Allogenic banking of dental pulp stem cells for innovative therapeutics.

Science.gov (United States)

Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

2015-08-26

Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

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Teresa de Souza Fernandez

2013-01-01

Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

Recent novel tumor gatekeepers and potential therapeutic approaches

African Journals Online (AJOL)

Keywords: Cancer, Potent inhibitors, Gatekeepers, Therapeutic approaches, Oncogenic pathways. Tropical Journal ..... effects of the target suppression support change from a one gene .... Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017.

Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects

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Eva M Marco

2011-10-01

Full Text Available Public concern on mental health has noticeably increased given the high prevalence of neuropsychiatric disorders. Cognition and emotionality are the most affected functions in neuropsychiatric disorders, i.e. anxiety disorders, depression and schizophrenia. In this review, most relevant literature on the role of the endocannabinoid (eCB system in neuropsychiatric disorders will be presented. Evidence from clinical and animal studies is provided for the participation of CB1 and CB2 receptors (CB1R and CB2R in the above mentioned neuropsychiatric disorders. CBRs are crucial in some of the emotional and cognitive impairments reported, although more research is required to understand the specific role of the eCB system in neuropsychiatric disorders. Cannabidiol (CBD, the main non-psychotropic component of the Cannabis sativa plant, has shown therapeutic potential in several neuropsychiatric disorders. Although further studies are needed, recent studies indicate that CBD therapeutic effects may partially depend on facilitation of eCB-mediated neurotransmission. Last but not least, this review includes recent findings on the role of the eCB system in eating disorders. A deregulation of the eCB system has been proposed to be in the bases of several neuropsychiatric disorders, including eating disorders. Cannabis consumption has been related to the appearance of psychotic symptoms and schizophrenia. In contrast, the pharmacological manipulation of this eCB system has been proposed as a potential strategy for the treatment of anxiety disorders, depression, and anorexia nervosa. In conclusion, the eCB system plays a critical role in psychiatry; however, detrimental consequences of manipulating this endogenous system cannot be underestimated over the potential and promising perspectives of its therapeutic manipulation.

Chondroitin Sulfate (CS) Lyases: Structure, Function and Application in Therapeutics.

Science.gov (United States)

Rani, Aruna; Patel, Seema; Goyal, Arun

2018-01-01

Glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) are the chief natural polysaccharides which reside in biological tissues mainly in extracellular matrix. These CS along with adhesion molecules and growth factors are involved in central nervous system (CNS) development, cell progression and pathogenesis. The chondroitin lyases are the enzyme that degrade and alter the CS chains and hence modify various signalling pathways involving CS chains. These CS lyases are substrate specific, can precisely manipulate the CS polysaccharides and have various biotechnological, medical and therapeutic applications. These enzymes can be used to produce the unsaturated oligosaccharides, which have immune-modulatory, anti-inflammatory and neuroprotective properties. This review focuses on the major breakthrough of the chondroitin sulfate degrading enzymes, their structures and functioning mechanism. This also provides comprehensive information regarding production, purification, characterization of CS lyases and their major applications, both established as well as emerging ones such as neural development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

BONE TUMOR ENVIRONMENT AS POTENTIAL THERAPEUTIC TARGET IN EWING SARCOMA

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Françoise eREDINI

2015-12-01

Full Text Available Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, ES is an aggressive, rapidly fatal malignancy that mainly develops in osseous sites (85%, but also in extraskeletal soft tissue. It spreads naturally to the lungs, bones and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption is responsible for the clinical features of bone tumors including pain, vertebral collapse and spinal cord compression. Based on the vicious cycle concept of tumor cells and bone resorbing cells, drugs which target osteoclasts may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable niche for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing Sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates (BPs or drugs blocking the pro-resorbing cytokine Receptor Activator of NF-kappa B Ligand (RANKL. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

[Therapeutic use of hematopoietic growth factors. II. GM-CSF and G-CSF].

Science.gov (United States)

Royer, B; Arock, M

1998-01-01

The second part of this review on haematopoietic growth factors is focused on the therapeutic use of GM-CSF and G-CSF. Such therapeutic applications have raised very great hopes for clinical haematology. However, it should not be forgotten that these haematopoietic growth factors, which are very costly, are powerful two-edged weapons capable of triggering a cascade of reactions, and have a field of activity that often goes beyond the single highly specific property which it is hoped they possess. The risks and costs of their use are currently being evaluated. Waited developments concerning these molecules focus on three axes: a best use of factors already commercialized, especially concerning adaptation of posologies and new indications, the development of hybrid molecules from already known haematopoietic growth factors, possessing the advantages of respective factors, but not their disadvantages, the discovery of new haematopoietic growth factors with potential therapeutic application.

Diversity, nutritional composition and medicinal potential of Indian ...

African Journals Online (AJOL)

The present review aims to update the current status of mushrooms diversity in India with their nutritional and medicinal potential as well as ethnomedicinal uses for different future prospects in pharmaceutical application. Keywords: Mushroom diversity, nutritional value, therapeutic potential, bioactive compound

Therapeutic peptides for cancer therapy. Part I - peptide inhibitors of signal transduction cascades.

Science.gov (United States)

Bidwell, Gene L; Raucher, Drazen

2009-10-01

Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that inhibit signal transduction cascades are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Given our current knowledge of protein sequences, structures and interaction interfaces, therapeutic peptides that inhibit interactions of interest are easily designed. These peptides are advantageous because they are highly specific for the interaction of interest, and they are much more easily developed than small molecule inhibitors of the same interactions. The main hurdle to application of peptides for cancer therapy is their poor pharmacokinetic and biodistribution parameters. Therefore, successful development of peptide delivery vectors could potentially make possible the use of this new and very promising class of anticancer agents.

Clay minerals: Properties and applications to dermocosmetic products and perspectives of natural raw materials for therapeutic purposes-A review.

Science.gov (United States)

Moraes, Jemima Daniela Dias; Bertolino, Silvana Raquel Alina; Cuffini, Silvia Lucia; Ducart, Diego Fernando; Bretzke, Pedro Eriberto; Leonardi, Gislaine Ricci

2017-12-20

Clay minerals are layered materials with a number of peculiar properties, which find many relevant applications in various industries. Since they are easily found everywhere, they are particularly attractive due to their economic viability. In the cosmetic industry, clay minerals are often used as excipients to stabilize emulsions or suspensions and to modify the rheological behavior of these systems. They also play an important role as adsorbents or absorbents, not only in cosmetics but also in other industries, such as pharmaceuticals. This reviewer believes that since this manuscript is presented as covering topical applications that include pharmaceuticals, some types of clay minerals should be considered as a potential material to be used as drug delivery systems. We review several applications of clay minerals to dermocosmetic products, relating them to the underlying properties of these materials and exemplifying with a number of clay minerals available in the market. We also discuss the use of clay minerals in topically-applied products for therapeutic purposes, specially for skin treatment and protection. Copyright © 2017 Elsevier B.V. All rights reserved.

Oncogenic Human Papillomavirus: Application of CRISPR/Cas9 Therapeutic Strategies for Cervical Cancer

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Shuai Zhen

2017-12-01

Full Text Available Oncogenic human papillomaviruses (HPVs cause different types of cancer especially cervical cancer. HPV-associated carcinogenesis provides a classical model system for clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 based cancer therapies since the viral oncogenes E6 and E7 are exclusively expressed in cancerous cells. Sequence-specific gene knockdown/knockout using CRISPR/Cas9 shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, CRISPR/Cas9-based targeting therapy requires further validation of its efficacy in vitro and in vivo to eliminate the potential off-target effects, necessitates verification of the delivery vehicles and the combinatory use of conventional therapies with CRISPR/Cas9 to ensure the feasibility and safety. In this review we discuss the potential of combining CRISPR/Cas9 with other treatment options as therapies for oncogenic HPVs-associated carcinogenesis. and present our assessment of the promising path to the development of CRISPR/Cas9 therapeutic strategies for clinical settings.

Potential Applications of Manual Games,

Science.gov (United States)

1984-02-01

34 just because some electronic equipment is used to keep track of logistics, combat results, and force status. Even a highly computerized game like...D-A152 541 POTENTIAL APPLICATIONS OF MANUAL GAMES (U) RAND CORP ii SANTA MONICA CA T A BROW~N FEB 84 RAND/P-6957 UNCLASI7FIED F/G 12/2 N El..I 111 1...128 112.5 111 m; * _ 1.8 I1111 ’I’ll MICROCOPY RESOLUTION TEST CHART NATI NAl fii~ t1 RI 1A L4k, I POTENTIAL APPLICATIONS OF MANUJAL GAMES Lfl N Lfl

Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

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Shailendra Giri

Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

The potential therapeutic value for bereaved relatives participating in research: An exploratory study.

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Germain, Alison; Mayland, Catriona R; Jack, Barbara A

2016-10-01

Conducting research with the bereaved presents an immediate ethical challenge, as they are undoubtedly a vulnerable group, associated with high levels of distress and susceptible to both physical and mental health issues. A comprehensive understanding of the potential therapeutic benefits for bereaved relatives participating in palliative care research is limited, and therefore the ethics of engaging this group remain questionable. This paper describes a secondary analysis of qualitative data collected in the Care of the Dying Evaluation (CODE) project, examining the experiences of patients who died at home. It explores the motivations and potential benefits for bereaved relatives participating in research with reference to the recently developed concepts in bereavement theory. Cognitive interviews were conducted with 15 bereaved relatives and secondary analysis using a content analysis framework was employed to classify the data. The results center around six recurring concepts identified as adaptive in current bereavement theory: an opportunity to share the narrative accounts of the final hours of their relative's life; a search for sense and meaning in loss; an ongoing bond/attachment with the deceased; altruistic motivations; oscillation between loss and restorative orientations; and a sense of resilience. Overall, the participants found that taking part in the research was valuable and that it could be described as offering therapeutic benefits. The need for bereaved relatives to take part in research studies should be encouraged, as they provide an accurate proxy for the patient's experience of end-of-life care while also providing a valuable account of their own perspective as family member and carer. In addition, we highlight the need for ethics committees to be aware of the potential benefits for bereaved relatives participating in research of this kind.

Long-term delivery of protein therapeutics.

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Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

2015-03-01

Proteins are effective biotherapeutics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability, frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel-based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery-related issues. A large number of protein molecules are under clinical trials, and hence, there is an urgent need to develop new methods to deliver these highly potent biologics.

Genome-wide gene expression dataset used to identify potential therapeutic targets in androgenetic alopecia

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R. Dey-Rao

2017-08-01

Full Text Available The microarray dataset attached to this report is related to the research article with the title: “A genomic approach to susceptibility and pathogenesis leads to identifying potential novel therapeutic targets in androgenetic alopecia” (Dey-Rao and Sinha, 2017 [1]. Male-pattern hair loss that is induced by androgens (testosterone in genetically predisposed individuals is known as androgenetic alopecia (AGA. The raw dataset is being made publicly available to enable critical and/or extended analyses. Our related research paper utilizes the attached raw dataset, for genome-wide gene-expression associated investigations. Combined with several in silico bioinformatics-based analyses we were able to delineate five strategic molecular elements as potential novel targets towards future AGA-therapy.

Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

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Jinfan Tian

2017-01-01

Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

In vivo therapeutic potential of Dicer-hunting siRNAs targeting infectious hepatitis C virus.

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Watanabe, Tsunamasa; Hatakeyama, Hiroto; Matsuda-Yasui, Chiho; Sato, Yusuke; Sudoh, Masayuki; Takagi, Asako; Hirata, Yuichi; Ohtsuki, Takahiro; Arai, Masaaki; Inoue, Kazuaki; Harashima, Hideyoshi; Kohara, Michinori

2014-04-23

The development of RNA interference (RNAi)-based therapy faces two major obstacles: selecting small interfering RNA (siRNA) sequences with strong activity, and identifying a carrier that allows efficient delivery to target organs. Additionally, conservative region at nucleotide level must be targeted for RNAi in applying to virus because hepatitis C virus (HCV) could escape from therapeutic pressure with genome mutations. In vitro preparation of Dicer-generated siRNAs targeting a conserved, highly ordered HCV 5' untranslated region are capable of inducing strong RNAi activity. By dissecting the 5'-end of an RNAi-mediated cleavage site in the HCV genome, we identified potent siRNA sequences, which we designate as Dicer-hunting siRNAs (dh-siRNAs). Furthermore, formulation of the dh-siRNAs in an optimized multifunctional envelope-type nano device inhibited ongoing infectious HCV replication in human hepatocytes in vivo. Our efforts using both identification of optimal siRNA sequences and delivery to human hepatocytes suggest therapeutic potential of siRNA for a virus.

Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential.

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Vij, Neeraj

2011-09-01

The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

Therapeutic ultrasound

International Nuclear Information System (INIS)

Crum, Lawrence A

2004-01-01

The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications

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Arman Kilic

2012-01-01

Full Text Available Heat shock proteins (HSPs are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed.

The potential of prison-based democratic therapeutic communities.

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Bennett, Jamie; Shuker, Richard

2017-03-13

Purpose The purpose of this paper is to describe the work of HMP Grendon, the only prison in the UK to operate entirely as a series of democratic therapeutic communities and to summarise the research of its effectiveness. Design/methodology/approach The paper is both descriptive, providing an overview of the work of a prison-based therapeutic community, and offers a literature review regarding evidence of effectiveness. Findings The work of HMP Grendon has a wide range of positive benefits including reduced levels of disruption in prison, reduced self-harm, improved well-being, an environment that is experienced as more humane and reduced levels of reoffending. Originality/value The work of HMP Grendon offers a well established and evidenced approach to managing men who have committed serious violent and sexually violent offences. It also promotes and embodies a progressive approach to managing prisons rooted in the welfare tradition.

Behavioral Effects of a Novel Benzofuranyl-Piperazine Serotonin-2C Receptor Agonist Suggest a Potential Therapeutic Application in the Treatment of Obsessive–Compulsive Disorder

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Michelle M. Rodriguez

2017-05-01

suggests a potential therapeutic application in OCD.

Functional characterization of a competitive peptide antagonist of p65 in human macrophage-like cells suggests therapeutic potential for chronic inflammation

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Srinivasan M

2014-12-01

Full Text Available Mythily Srinivasan,1 Corinne Blackburn,1 Debomoy K Lahiri2,3 1Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, 2Institute of Psychiatry Research, Department of Psychiatry, 3Department of Medical and Molecular Genetics, School of Medicine, Indiana University-Purdue University, Indianapolis, IN, USA Abstract: Glucocorticoid-induced leucine zipper (GILZ is a glucocorticoid responsive protein that links the nuclear factor-kappa B (NFκB and the glucocorticoid signaling pathways. Functional and binding studies suggest that the proline-rich region at the carboxy terminus of GILZ binds the p65 subunit of NFκB and suppresses the immunoinflammatory response. A widely-used strategy in the discovery of peptide drugs involves exploitation of the complementary surfaces of naturally occurring binding partners. Previously, we observed that a synthetic peptide (GILZ-P derived from the proline-rich region of GILZ bound activated p65 and ameliorated experimental encephalomyelitis. Here we characterize the secondary structure of GILZ-P by circular dichroic analysis. GILZ-P adopts an extended polyproline type II helical conformation consistent with the structural conformation commonly observed in interfaces of transient intermolecular interactions. To determine the potential application of GILZ-P in humans, we evaluated the toxicity and efficacy of the peptide drug in mature human macrophage-like THP-1 cells. Treatment with GILZ-P at a wide range of concentrations commonly used for peptide drugs was nontoxic as determined by cell viability and apoptosis assays. Functionally, GILZ-P suppressed proliferation and glutamate secretion by activated macrophages by inhibiting nuclear translocation of p65. Collectively, our data suggest that the GILZ-P has therapeutic potential in chronic CNS diseases where persistent inflammation leads to neurodegeneration such as multiple sclerosis and Alzheimer’s disease. Keywords

Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

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Andrea eGras Navarro

2015-04-01

Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

RIG-I Like Receptors in Antiviral Immunity and Therapeutic Applications

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Michael Gale Jr.

2011-06-01

Full Text Available The RNA helicase family of RIG-I-like receptors (RLRs is a key component of host defense mechanisms responsible for detecting viruses and triggering innate immune signaling cascades to control viral replication and dissemination. As cytoplasm-based sensors, RLRs recognize foreign RNA in the cell and activate a cascade of antiviral responses including the induction of type I interferons, inflammasome activation, and expression of proinflammatory cytokines and chemokines. This review provides a brief overview of RLR function, ligand interactions, and downstream signaling events with an expanded discussion on the therapeutic potential of targeting RLRs for immune stimulation and treatment of virus infection.

Optimization of ultrasound parameters of myocardial cavitation microlesions for therapeutic application.

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Miller, Douglas L; Dou, Chunyan; Owens, Gabe E; Kripfgans, Oliver D

2014-06-01

Intermittent high intensity ultrasound scanning with contrast microbubbles can induce scattered cavitation microlesions in the myocardium, which may be of value for tissue reduction therapy. Anesthetized rats were treated in a heated water bath with 1.5 MHz focused ultrasound pulses, guided by an 8 MHz imaging transducer. The relative efficacy with 2 or 4 MPa pulses, 1:4 or 1:8 trigger intervals and 5 or 10 cycle pulses was explored in six groups. Electrocardiogram premature complexes (PCs) induced by the triggered pulse bursts were counted, and Evans blue stained cardiomyocyte scores (SCSs) were obtained. The increase from 2 to 4 MPa produced significant increases in PCs and SCSs and eliminated an anticipated decline in the rate of PC induction with time, which might hinder therapeutic efficacy. Increased intervals and pulse durations did not yield significant increases in the effects. The results suggest that cavitation microlesion production can be refined and potentially lead to a clinically robust therapeutic method. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

International Nuclear Information System (INIS)

Wairagu, Peninah M.; Park, Kwang Hwa; Kim, Jihye; Choi, Jong-Whan; Kim, Hyun-Won; Yeh, Byung-Il; Jung, Soon-Hee; Yong, Suk-Joong; Jeong, Yangsik

2014-01-01

Highlights: • The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. • Growth inhibition by NR ligands or TKIs is target receptor level-dependent. • T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs

Therapeutic Potential of Biologically Reduced Silver Nanoparticles from Actinomycete Cultures

International Nuclear Information System (INIS)

Sukanya, M.K.; Saju, K.A.; Praseetha, P.K.; Sakthivel, G.

2013-01-01

Silver nanoparticles are applied in nanomedicine from time immemorial and are still used as powerful antibiotic and anti-inflammatory agents. Antibiotics produced by actinomycetes are popular in almost all the therapeutic measures, and this study has proven that these microbes are also helpful in the biosynthesis of silver nanoparticles with good surface and size characteristics. Silver can be synthesized by various chemical methodologies, and most of them have turned to be toxic. This study has been successful in isolating the microbes from polluted environment, and subjecting them to the reduction of silver nanoparticles, characterizing the nanoparticles by UV spectrophotometry and transmission electron microscopy. The nanoparticles produced were tested for their antimicrobial property, and the zone of inhibition was greater than those produced by their chemically synthesized counterparts. Actinomycetes, helpful in bioremediating heavy metals, are useful for the production of metallic nanoparticles. The biosynthesized silver nanoparticles loaded with antibiotics prove to be better in killing the pathogens and have opened up new areas for developing nanobiotechnological research based on microbial applications.

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

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Knight, Jason S.; Meng, He; Coit, Patrick; Yalavarthi, Srilakshmi; Sule, Gautam; Gandhi, Alex A.; Grenn, Robert C.; Mazza, Levi F.; Ali, Ramadan A.; Renauer, Paul; Wren, Jonathan D.; Bockenstedt, Paula L.; Wang, Hui; Eitzman, Daniel T.; Sawalha, Amr H.

2017-01-01

Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils — neutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS. PMID:28931754

Woodland in Practical Skills Therapeutic Education

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Mata, Paula; Gibons, Kenneth; Mata, Fernando

2016-01-01

Modern urban life provides less opportunities to contact with nature, which is a potential cause of developmental deviances in children. We investigated the potential therapeutic effect of woodlands, within the context of Practical Skills Therapeutic Education at the Ruskin Mill College, UK. Data on physical and emotional perceptions were…

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

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Michihiro Fujiwara

2010-07-01

Full Text Available Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC, and the non-psychoactive components cannabidiol (CBD, cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

Zeta potential in colloid science principles and applications

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Hunter, Robert J; Rowell, R L

2013-01-01

Zeta Potential in Colloid Science: Principles and Applications covers the concept of the zeta potential in colloid chemical theory. The book discusses the charge and potential distribution at interfaces; the calculation of the zeta potential; and the experimental techniques used in the measurement of electrokinetic parameters. The text also describes the electroviscous and viscoelectric effects; applications of the zeta potential to areas of colloid science; and the influence of simple inorganic ions or more complex adsorbates on zeta potential. Physical chemists and people involved in the stu

Encapsulation Strategies of Bacteriophage (Felix O1) for Oral Therapeutic Application.

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Islam, Golam S; Wang, Qi; Sabour, Parviz M

2018-01-01

Due to emerging antibiotic-resistant strains among the pathogens, a variety of strategies, including therapeutic application of bacteriophages, have been suggested as a possible alternative to antibiotics in food animal production. As pathogen-specific biocontrol agents, bacteriophages are being studied intensively. Primarily their applications in the food industry and animal production have been recognized in the USA and Europe, for pathogens including Salmonella, Campylobacter, Escherichia coli, and Listeria. However, the viability of orally administered phage may rapidly reduce under the harsh acidic conditions of the stomach, presence of enzymes and bile. It is evident that bacteriophages, intended for phage therapy by oral administration, require efficient protection from the acidic environment of the stomach and should remain active in the animal's gastrointestinal tract where pathogen colonizes. Encapsulation of phages by spray drying or extrusion methods can protect phages from the simulated hostile gut conditions and help controlled release of phages to the digestive system when appropriate formulation strategy is implemented.

Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma.

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Redini, Françoise; Heymann, Dominique

2015-01-01

Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

Mass Spectrometry for Research and Application in Therapeutic Drug Monitoring or Clinical and Forensic Toxicology.

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Maurer, Hans H

2018-04-30

This paper reviews current applications of various hyphenated low- and high-resolution mass spectrometry techniques in the field of therapeutic drug monitoring and clinical/forensic toxicology in both research and practice. They cover gas chromatography, liquid chromatography, matrix-assisted laser desorption ionization, or paper spray ionization coupled to quadrupole, ion trap, time-of-flight, or Orbitrap mass analyzers.

Therapeutic potential of brain-derived neurotrophic factor (BDNF and a small molecular mimics of BDNF for traumatic brain injury

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Mary Wurzelmann

2017-01-01

Full Text Available Traumatic brain injury (TBI is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF, a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury.

Science.gov (United States)

Wurzelmann, Mary; Romeika, Jennifer; Sun, Dong

2017-01-01

Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

The Multidimensional Therapeutic Potential of Targeting the Brain Oxytocin System for the Treatment of Substance Use Disorders.

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Bowen, Michael T; Neumann, Inga D

2017-09-24

The neuropeptide oxytocin is released both into the blood and within the brain in response to reproductive stimuli, such as birth, suckling and sex, but also in response to social interaction and stressors. Substance use disorders, or addictions, are chronic, relapsing brain disorders and are one of the major causes of global burden of disease. Unfortunately, current treatment options for substance use disorders are extremely limited and a treatment breakthrough is sorely needed. There is mounting preclinical evidence that targeting the brain oxytocin system may provide that breakthrough. Substance use disorders are characterised by a viscous cycle of bingeing and intoxication, followed by withdrawal and negative affect, and finally preoccupation and anticipation that triggers relapse and further consumption. Administration of oxytocin has been shown to have a potential therapeutic benefit at each stage of this addiction cycle for numerous drugs of abuse. This multidimensional therapeutic utility is likely due to oxytocin's interactions with key biological systems that underlie the development and maintenance of addiction. Only a few human trials of oxytocin in addicted populations have been completed with the results thus far being mixed. There are numerous other trials underway, and the results are eagerly awaited. However, the ability to fully harness the potential therapeutic benefit of targeting the brain oxytocin system may depend on the development of molecules that selectively stimulate the oxytocin system, but that have superior pharmacokinetic properties to oxytocin itself.

Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications.

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Liu, Chang; Zhang, Li; Liu, Hao; Cheng, Kun

2017-11-28

The CRISPR-Cas9 genome-editing system is a part of the adaptive immune system in archaea and bacteria to defend against invasive nucleic acids from phages and plasmids. The single guide RNA (sgRNA) of the system recognizes its target sequence in the genome, and the Cas9 nuclease of the system acts as a pair of scissors to cleave the double strands of DNA. Since its discovery, CRISPR-Cas9 has become the most robust platform for genome engineering in eukaryotic cells. Recently, the CRISPR-Cas9 system has triggered enormous interest in therapeutic applications. CRISPR-Cas9 can be applied to correct disease-causing gene mutations or engineer T cells for cancer immunotherapy. The first clinical trial using the CRISPR-Cas9 technology was conducted in 2016. Despite the great promise of the CRISPR-Cas9 technology, several challenges remain to be tackled before its successful applications for human patients. The greatest challenge is the safe and efficient delivery of the CRISPR-Cas9 genome-editing system to target cells in human body. In this review, we will introduce the molecular mechanism and different strategies to edit genes using the CRISPR-Cas9 system. We will then highlight the current systems that have been developed to deliver CRISPR-Cas9 in vitro and in vivo for various therapeutic purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanotechnologies, technologies converging and potential biomedical applications

International Nuclear Information System (INIS)

Capuano, Vincenzo

2005-01-01

The applications of nanotechnology to biology and medicine appear really promising far diagnostics, for various therapeutic approaches and in medical instrumentations. The growing synergism among nanotechnology, biotechnology, information technology and cognitive sciences, their convergence (NBIC) from the nano scale, could involve on next decades great changes in medicine, from a reactive to a predictive and preventive approach. It is expected that NBIC converging technologies could achieve tremendous improvements in human abilities and enhance societal achievements. It appears therefore necessary a careful assessment of related social and ethical implications, in the framework of a constant dialogue between science and society [it

Potential applications of high temperature helium

International Nuclear Information System (INIS)

Schleicher, R.W. Jr.; Kennedy, A.J.

1992-09-01

This paper discusses the DOE MHTGR-SC program's recent activity to improve the economics of the MHTGR without sacrificing safety performance and two potential applications of high temperature helium, the MHTGR gas turbine plant and a process heat application for methanol production from coal

Alpha-1 antitrypsin: a potent anti-inflammatory and potential novel therapeutic agent.

LENUS (Irish Health Repository)

Bergin, David A

2012-04-01

Alpha-1 antitrypsin (AAT) has long been thought of as an important anti-protease in the lung where it is known to decrease the destructive effects of major proteases such as neutrophil elastase. In recent years, the perception of this protein in this simple one dimensional capacity as an anti-protease has evolved and it is now recognised that AAT has significant anti-inflammatory properties affecting a wide range of inflammatory cells, leading to its potential therapeutic use in a number of important diseases. This present review aims to discuss the described anti-inflammatory actions of AAT in modulating key immune cell functions, delineate known signalling pathways and specifically to identify the models of disease in which AAT has been shown to be effective as a therapy.

Comparison of manual and automated size measurements of lung metastases on MDCT images: Potential influence on therapeutic decisions

International Nuclear Information System (INIS)

Pauls, Sandra; Kuerschner, Christian; Dharaiya, Ekta; Muche, Rainer; Schmidt, Stefan A.; Krueger, Stefan; Brambs, Hans-Juergen; Aschoff, Andrik J.

2008-01-01

Purpose: The goal of this study was to evaluate the influence of automated measurement of diameter, area, and volume from chest CT scans on therapeutic decisions of lung nodules as compared to manual 2-D measurements. Patients and method: The retrospective study involved 25 patients with 75 lung metastases. Contrast enhanced CT scans (16 row) of the lung were performed three times during chemotherapy with a mean time interval of 67.9 days between scans. In each patient, three metastases were evaluated (n = 225). Automatic measurements were compared to manual assessment for the following parameters: diameter, area, and density. The influence on the therapeutic decisions was evaluated using the RECIST criteria. Results: The maximum diameter measured by the automatic application was on an average 27% (S.D. 39; CI: 0.22-0.32; p < 0.0001) higher than the maximum diameter with manual assessment, and the differences depended on metastases size. Based on diameter calculation, manual and automated assessment disagreed in up to 32% of therapeutic decisions. Volumetric assessment tended towards more changes in therapy as compared to diameter calculation. The calculation of mean transversal area of metastases was 36% (S.D. 0.305; CI: -0.40 to -0.32; p < 0.0001) less with automated measurement. Therapeutic strategy would be changed in up to 25.7% of nodules using automated area calculation. Automated assessment of nodules' area and volume could influence the therapeutic decisions in up to 51.4% of all nodules. Density of the nodules was not validated to determine the influence on therapeutic decisions. Conclusion: There is a discrepancy between the manual and automated size measurement of lung metastases which could be significant

Comparison of manual and automated size measurements of lung metastases on MDCT images: Potential influence on therapeutic decisions

Energy Technology Data Exchange (ETDEWEB)

Pauls, Sandra [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: sandra.pauls@uni-ulm.de; Kuerschner, Christian [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: chris.kuerschner@web.de; Dharaiya, Ekta [CT-Clinical Science, Philips Medical Systems, Highland Heights, OH 44143 (United States)], E-mail: ekta.shah@philips.com; Muche, Rainer [Institute of Biometrics, University of Ulm, Schwabstrasse 13, 89075 Ulm (Germany)], E-mail: rainer.muche@uni-ulm.de; Schmidt, Stefan A. [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: stefan-a.schmidt@gmx.de; Krueger, Stefan [Department of Internal Medicine II, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: s.krueger@uniklinik-ulm.de; Brambs, Hans-Juergen [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: hans-juergen.brambs@uniklinik-ulm.de; Aschoff, Andrik J. [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: andrik.aschoff@uni-ulm.de

2008-04-15

Purpose: The goal of this study was to evaluate the influence of automated measurement of diameter, area, and volume from chest CT scans on therapeutic decisions of lung nodules as compared to manual 2-D measurements. Patients and method: The retrospective study involved 25 patients with 75 lung metastases. Contrast enhanced CT scans (16 row) of the lung were performed three times during chemotherapy with a mean time interval of 67.9 days between scans. In each patient, three metastases were evaluated (n = 225). Automatic measurements were compared to manual assessment for the following parameters: diameter, area, and density. The influence on the therapeutic decisions was evaluated using the RECIST criteria. Results: The maximum diameter measured by the automatic application was on an average 27% (S.D. 39; CI: 0.22-0.32; p < 0.0001) higher than the maximum diameter with manual assessment, and the differences depended on metastases size. Based on diameter calculation, manual and automated assessment disagreed in up to 32% of therapeutic decisions. Volumetric assessment tended towards more changes in therapy as compared to diameter calculation. The calculation of mean transversal area of metastases was 36% (S.D. 0.305; CI: -0.40 to -0.32; p < 0.0001) less with automated measurement. Therapeutic strategy would be changed in up to 25.7% of nodules using automated area calculation. Automated assessment of nodules' area and volume could influence the therapeutic decisions in up to 51.4% of all nodules. Density of the nodules was not validated to determine the influence on therapeutic decisions. Conclusion: There is a discrepancy between the manual and automated size measurement of lung metastases which could be significant.

PRX1 knockdown potentiates vitamin K3 toxicity in cancer cells: a potential new therapeutic perspective for an old drug.

Science.gov (United States)

He, Tiantian; Hatem, Elie; Vernis, Laurence; Lei, Ming; Huang, Meng-Er

2015-12-21

Many promising anticancer molecules are abandoned during the course from bench to bedside due to lack of clear-cut efficiency and/or severe side effects. Vitamin K3 (vitK3) is a synthetic naphthoquinone exhibiting significant in vitro and in vivo anticancer activity against multiple human cancers, and has therapeutic potential when combined with other anticancer molecules. The major mechanism for the anticancer activity of vitK3 is the generation of cytotoxic reactive oxygen species (ROS). We thus reasoned that a rational redox modulation of cancer cells could enhance vitK3 anticancer efficiency. Cancer cell lines with peroxiredoxin 1 (PRX1) gene transiently or stably knocked-down and corresponding controls were exposed to vitK3 as well as a set of anticancer molecules, including vinblastine, taxol, doxorubicin, daunorubicin, actinomycin D and 5-fluorouracil. Cytotoxic effects and cell death events were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based assay, cell clonogenic assay, measurement of mitochondrial membrane potential and annexin V/propidium iodide double staining. Global ROS accumulation and compartment-specific H2O2 generation were determined respectively by a redox-sensitive chemical probe and H2O2-sensitive sensor HyPer. Oxidation of endogenous antioxidant proteins including TRX1, TRX2 and PRX3 was monitored by redox western blot. We observed that the PRX1 knockdown in HeLa and A549 cells conferred enhanced sensitivity to vitK3, reducing substantially the necessary doses to kill cancer cells. The same conditions (combination of vitK3 and PRX1 knockdown) caused little cytotoxicity in non-cancerous cells, suggesting a cancer-cell-selective property. Increased ROS accumulation had a crucial role in vitK3-induced cell death in PRX1 knockdown cells. The use of H2O2-specific sensors HyPer revealed that vitK3 lead to immediate accumulation of H2O2 in the cytosol, nucleus, and mitochondrial matrix. PRX1 silencing

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications

Directory of Open Access Journals (Sweden)

Jordi Bover

2016-11-01

Full Text Available Cardiovascular (CV calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD–MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc., we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions.

Boron Neutron Capture Therapty (BNCT) in an Oral Precancer Model: Therapeutic Benefits and Potential Toxicity of a Double Application of BNCT with a Six-Week Interval

Energy Technology Data Exchange (ETDEWEB)

Andrea Monti Hughes; Emiliano C.C. Pozzi; Elisa M. Heber; Silvia Thorp; Marcelo Miller; Maria E. Itoiz; Romina F. Aromando; Ana J. Molinari; Marcela A. Garabalino; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

2011-11-01

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10 + BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB- 10 + BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10 + BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.

Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms.

Science.gov (United States)

Marei, Hadir; Malliri, Angeliki

2017-07-03

Abnormal Rac1 signaling is linked to a number of debilitating human diseases, including cancer, cardiovascular diseases and neurodegenerative disorders. As such, Rac1 represents an attractive therapeutic target, yet the search for effective Rac1 inhibitors is still underway. Given the adverse effects associated with Rac1 signaling perturbation, cells have evolved several mechanisms to ensure the tight regulation of Rac1 signaling. Thus, characterizing these mechanisms can provide invaluable information regarding major cellular events that lead to aberrant Rac1 signaling. Importantly, this information can be utilized to further facilitate the development of effective pharmacological modulators that can restore normal Rac1 signaling. In this review, we focus on the pathological role of Rac1 signaling, highlighting the benefits and potential drawbacks of targeting Rac1 in a clinical setting. Additionally, we provide an overview of available compounds that target key Rac1 regulatory mechanisms and discuss future therapeutic avenues arising from our understanding of these mechanisms.

Synthetic biology in mammalian cells: Next generation research tools and therapeutics

Science.gov (United States)

Lienert, Florian; Lohmueller, Jason J; Garg, Abhishek; Silver, Pamela A

2014-01-01

Recent progress in DNA manipulation and gene circuit engineering has greatly improved our ability to programme and probe mammalian cell behaviour. These advances have led to a new generation of synthetic biology research tools and potential therapeutic applications. Programmable DNA-binding domains and RNA regulators are leading to unprecedented control of gene expression and elucidation of gene function. Rebuilding complex biological circuits such as T cell receptor signalling in isolation from their natural context has deepened our understanding of network motifs and signalling pathways. Synthetic biology is also leading to innovative therapeutic interventions based on cell-based therapies, protein drugs, vaccines and gene therapies. PMID:24434884

Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning.

Science.gov (United States)

Herbert, Julia; Thiermann, Horst; Worek, Franz; Wille, Timo

2017-08-15

Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning. Aim of this study was the development of an applicable and easy method to test the therapeutic efficiency of such substances. For this purpose, airway responsiveness in viable precision cut lung slices (PCLS) from rats was analysed. We showed that ACh-induced airway contractions were spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, contractions were irreversible. This effect could be antagonized by addition of the standard therapeutic atropine, thereby presenting a clear indication for treatment efficiency. Now, candidate therapeutic compounds can be evaluated, based on their ability to counteract the irreversible airway contraction in OP poisoned PCLS. Copyright © 2017 Elsevier B.V. All rights reserved.

VIP as a potential therapeutic agent in gram negative sepsis.

Science.gov (United States)

Ibrahim, Hiba; Barrow, Paul; Foster, Neil

2012-12-01

Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

Potential biomedical applications of marine algae.

Science.gov (United States)

Wang, Hui-Min David; Li, Xiao-Chun; Lee, Duu-Jong; Chang, Jo-Shu

2017-11-01

Functional components extracted from algal biomass are widely used as dietary and health supplements with a variety of applications in food science and technology. In contrast, the applications of algae in dermal-related products have received much less attention, despite that algae also possess high potential for the uses in anti-infection, anti-aging, skin-whitening, and skin tumor treatments. This review, therefore, focuses on integrating studies on algae pertinent to human skin care, health and therapy. The active compounds in algae related to human skin treatments are mentioned and the possible mechanisms involved are described. The main purpose of this review is to identify serviceable algae functions in skin treatments to facilitate practical applications in this high-potential area. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of Bridelia ferruginea benth for its therapeutic potential ...

African Journals Online (AJOL)

McRoy

Therapeutic effect of Bridelia ferruginea on pregnancy-induced impaired glucose tolerance. Int J Med Biomed ... A proportion of women with pregnancy-induced impaired glucose ... The long-term implications for ... The leaves were removed ...

The Therapeutic Potential of Monocyte/Macrophage Manipulation in the Treatment of Chemotherapy-Induced Painful Neuropathy

Directory of Open Access Journals (Sweden)

Karli Montague

2017-11-01

Full Text Available In cancer treatments a dose-limiting side-effect of chemotherapeutic agents is the development of neuropathic pain, which is poorly managed by clinically available drugs at present. Chemotherapy-induced painful neuropathy (CIPN is a major cause of premature cessation of treatment and so a greater understanding of the underlying mechanisms and the development of novel, more effective therapies, is greatly needed. In some cases, only a weak correlation between chemotherapy-induced pain and neuronal damage is observed both clinically and preclinically. As such, a critical role for non-neuronal cells, such as immune cells, and their communication with neurons in CIPN has recently been appreciated. In this mini-review, we will discuss preclinical evidence for the role of monocytes/macrophages in the periphery in CIPN, with a focus on that which is associated with the chemotherapeutic agents vincristine and paclitaxel. In addition we will discuss the potential mechanisms that regulate monocyte/macrophage–neuron crosstalk in this context. Informed by preclinical data, we will also consider the value of monocytes/macrophages as therapeutic targets for the treatment of CIPN clinically. Approaches that manipulate the signaling pathways discussed in this review show both promise and potential pitfalls. Nonetheless, they are emerging as innovative therapeutic targets with CX3CL1/R1-regulation of monocyte/macrophage–neuron communication currently emerging as a promising front-runner.

Ozone dosing alters the biological potential and therapeutic outcomes of plasma rich in growth factors.

Science.gov (United States)

Anitua, E; Zalduendo, M M; Troya, M; Orive, G

2015-04-01

Until now, ozone has been used in a rather empirical way. This in-vitro study investigates, for the first time, whether different ozone treatments of plasma rich in growth factors (PRGF) alter the biological properties and outcomes of this autologous platelet-rich plasma. Human plasma rich in growth factors was treated with ozone using one of the following protocols: a continuous-flow method; or a syringe method in which constant volumes of ozone and PRGF were mixed. In both cases, ozone was added before, during and after the addition of calcium chloride. Three ozone concentrations, of the therapeutic range 20, 40 and 80 μg/mL, were tested. Fibrin clot properties, growth factor content and the proliferative effect on primary osteoblasts and gingival fibroblasts were evaluated. Ozone treatment of PRGF using the continuous flow protocol impaired formation of the fibrin scaffold, drastically reduced the levels of growth factors and significantly decreased the proliferative potential of PRGF on primary osteoblasts and gingival fibroblasts. In contrast, treatment of PRGF with ozone using the syringe method, before, during and after the coagulation process, did not alter the biological outcomes of the autologous therapy. These findings suggest that ozone dose and the way that ozone combines with PRGF may alter the biological potential and therapeutic outcomes of PRGF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents

Directory of Open Access Journals (Sweden)

Verena Börger

2017-07-01

Full Text Available Extracellular vesicles (EVs, such as exosomes and microvesicles, have been identified as mediators of a newly-discovered intercellular communication system. They are essential signaling mediators in various physiological and pathophysiological processes. Depending on their origin, they fulfill different functions. EVs of mesenchymal stem/stromal cells (MSCs have been found to promote comparable therapeutic activities as MSCs themselves. In a variety of in vivo models, it has been observed that they suppress pro-inflammatory processes and reduce oxidative stress and fibrosis. By switching pro-inflammatory into tolerogenic immune responses, MSC-EVs very likely promote tissue regeneration by creating a pro-regenerative environment allowing endogenous stem and progenitor cells to successfully repair affected tissues. Accordingly, MSC-EVs provide a novel, very promising therapeutic agent, which has already been successfully applied to humans. However, the MSC-EV production process has not been standardized, yet. Indeed, a collection of different protocols has been used for the MSC-EV production, characterization and application. By focusing on kidney, heart, liver and brain injuries, we have reviewed the major outcomes of published MSC-EV in vivo studies.

Potential Diagnostic and Therapeutic Applications of Oligonucleotide Aptamers in Breast Cancer.

Science.gov (United States)

Wu, Xiaoqiu; Shaikh, Atik Badshah; Yu, Yuanyuan; Li, Yongshu; Ni, Shuaijian; Lu, Aiping; Zhang, Ge

2017-08-25

Breast cancer is one of the most common causes of cancer related deaths in women. Currently, with the development of early detection, increased social awareness and kinds of treatment options, survival rate has improved in nearly every type of breast cancer patients. However, about one third patients still have increased chances of recurrence within five years and the five-year relative survival rate in patients with metastasis is less than 30%. Breast cancer contains multiple subtypes. Each subtype could cause distinct clinical outcomes and systemic interventions. Thereby, new targeted therapies are of particular importance to solve this major clinical problem. Aptamers, often termed "chemical antibodies", are functionally similar to antibodies and have demonstrated their superiority of recognizing target with high selectivity, affinity and stability. With these intrinsic properties, aptamers have been widely studied in cancer biology and some are in clinical trials. In this review, we will firstly discuss about the global impacts and mechanisms of breast cancer, then briefly highlight applications of aptamers that have been developed for breast cancer and finally summarize various challenges in clinical translation of aptamers.

Ferulic acid and derivatives: molecules with potential application in the pharmaceutical field

Directory of Open Access Journals (Sweden)

Lívia Brenelli de Paiva

2013-09-01

Full Text Available Ferulic acid is a phenolic acid widely distributed in the plant kingdom. It presents a wide range of potential therapeutic effects useful in the treatments of cancer, diabetes, lung and cardiovascular diseases, as well as hepatic, neuro and photoprotective effects and antimicrobial and anti-inflammatory activities. Overall, the pharmaceutical potential of ferulic acid can be attributed to its ability to scavenge free radicals. However, recent studies have revealed that ferulic acid presents pharmacological properties beyond those related to its antioxidant activity, such as the ability to competitively inhibit HMG-CoA reductase and activate glucokinase, contributing to reduce hypercholesterolemia and hyperglycemia, respectively. The present review addresses ferulic acid dietary sources, the pharmacokinetic profile, antioxidant action mechanisms and therapeutic effects in the treatment and prevention of various diseases, in order to provide a basis for understanding its mechanisms of action as well as its pharmaceutical potential.

Synthesis and characterization of Cu/Ag nanoparticle loaded mullite nanocomposite system: A potential candidate for antimicrobial and therapeutic applications.

Science.gov (United States)

Kar, S; Bagchi, B; Kundu, B; Bhandary, S; Basu, R; Nandy, P; Das, S

2014-11-01

Microbial resistance to antibiotics has triggered the development of nanoscale materials as an alternative strategy. To stabilize these particles an inert support is needed. Porous nanomullite developed by sol-gel route is loaded with copper and silver nanoparticle by simple adsorption method. These nanocomposites are characterized using XRD, FTIR, TEM, SEM, EDAX and UV-visible spectrophotometer. Antibacterial activity of these nanocomposites against Gram positive and Gram negative bacteria are performed by bactericidal kinetics, flow cytometry and MTT assay. The underlying mechanisms behind the antimicrobial property and cell death are also investigated by EPR spectroscopy, intracellular ROS measurement and β-galactosidase assay. The cytocompatibility of the nanocomposites is investigated by cell viability (MTT), proliferation (Alamar blue) and wound healing assay of mammalian fibroblast cell line. Nanocomposites show a fairly uniform distribution of metal nanoparticle within mullite matrix. They show excellent antibacterial activity. Metal ions/nanoparticle is found to be released from the materials (CM and SM). Treated cells manifested high intracellular oxidative stress and β-galactosidase activity in the growth medium. The effect of nanocomposites on mammalian cell line depends on exposure time and concentration. The scratch assay shows normal cell migration with respect to control. The fabricated nanoparticles possess diverse antimicrobial mechanism and exhibit good cytocompatibility along with wound healing characteristics in mouse fibroblast cell line (L929). The newly synthesized materials are promising candidates for the development of antimicrobial ceramic coatings for biomedical devices and therapeutic applications. Copyright © 2014 Elsevier B.V. All rights reserved.

The dopamine hypothesis of drug addiction and its potential therapeutic value.

Directory of Open Access Journals (Sweden)

Marco eDiana

2011-11-01

Full Text Available Dopamine (DA transmission is deeply affected by drugs of abuse, and alterations in DA function are involved in various phases of drug addiction and potentially exploitable therapeutically. In particular, basic studies have documented a reduction in the electrophysiological activity of DA neurons in alcohol, opiate, cannabinoid and other drug-dependent rats. Further, DA release in the Nacc is decreased in virtually all drug-dependent rodents. In parallel, these studies are supported by increments in intracranial self stimulation (ICSS thresholds during withdrawal from alcohol, nicotine, opiates, and other drugs of abuse, thereby suggesting a hypofunction of the neural substrate of ICSS. Accordingly, morphological evaluations fed into realistic computational analysis of the Medium Spiny Neuron (MSN of the Nucleus accumbens (Nacc, post-synaptic counterpart of DA terminals, show profound changes in structure and function of the entire mesolimbic system. In line with these findings, human imaging studies have shown a reduction of dopamine receptors accompanied by a lesser release of endogenous DA in the ventral striatum of cocaine, heroin and alcohol-dependent subjects, thereby offering visual proof of the ‘dopamine-impoverished’ addicted human brain.The reduction in physiological activity of the DA system leads to the idea that an increment in its activity, to restore pre-drug levels, may yield significant clinical improvements (reduction of craving, relapse and drug-seeking/taking. In theory, it may be achieved pharmacologically and/or with novel interventions such as Transcranial Magnetic Stimulation (TMS. Its anatomo-physiological rationale as a possible therapeutic aid in alcoholics and other addicts will be described and proposed as a theoretical framework to be subjected to experimental testing in human addicts.

Report of the consultants' meeting on comparative laboratory evaluation of therapeutic radionuclides and radiopharmaceuticals

International Nuclear Information System (INIS)

1999-12-01

Therapeutic radiopharmaceuticals consist of two components - the radionuclide and the biological carrier. With regard to the radionuclide, an advantage of targeted radiotherapy is that there are a wide variety of radionuclides with different physical half-lives and radiation qualities that can be applied for this purpose. An important task is to select a radionuclide that is compatible with the needs of a particular clinical application. The identification of the ideal targeted radiotherapeutic for each potential clinical application is a difficult task because of the multitude of variables that must be considered, some relating to the radioisotope, and others to the biological carrier. Hence it is recommended that a Co-ordinated Research Programme be established by the Agency to enable participants to acquire and intercompare the methodological expertise to evaluate the relative merit of therapeutic radiopharmaceuticals. These studies will be performed using a model system selected either from those described in this report or a promising agent that has emerged in the time since this meeting. The molecular carrier will be labelled with 131 I, 125 I as well as other therapeutic radionuclides available to the participant (for example, 90 Y, 186 Re, 188 Re, 153 Sm, 166 Ho, 165 Dy). The potential radiopharmaceuticals will then be compared in a progression of studies evaluating biological integrity after labelling, internalisation and residualization of radioactivity in the tumour cell, in vitro cytotoxicity, tissue distribution, normal organ toxicity (determination of the maximum tolerated dose) and finally, therapeutic efficacy

Role of therapeutic drug monitoring in pulmonary infections : use and potential for expanded use of dried blood spot samples

NARCIS (Netherlands)

Hofman, Susan; Bolhuis, Mathieu S.; Koster, Remco A.; Akkerman, Onno W.; van Assen, Sander; Stove, Christophe; Alffenaar, Jan-Willem C.

Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample

Therapeutic potential of the metabolic modulator Metformin on osteosarcoma cancer stem-like cells.

Science.gov (United States)

Paiva-Oliveira, Daniela I; Martins-Neves, Sara R; Abrunhosa, Antero J; Fontes-Ribeiro, Carlos; Gomes, Célia M F

2018-01-01

Osteosarcoma is the most common primary bone tumour appearing in children and adolescents. Recent studies demonstrate that osteosarcoma possesses a stem-like cell subset, so-called cancer stem-like cells, refractory to conventional chemotherapeutics and pointed out as responsible for relapses frequently observed in osteosarcoma patients. Here, we explored the therapeutic potential of Metformin on osteosarcoma stem-like cells, alone and as a chemosensitizer of doxorubicin. Stem-like cells were isolated from human osteosarcoma cell lines, MNNG/HOS and MG-63, using the sphere-forming assay. Metformin cytotoxicity alone and combined with doxorubicin were evaluated using MTT/BrdU assays. Protein levels of AMPK and AKT were evaluated by Western Blot. Cellular metabolic status was assessed based on [ 18 F]-FDG uptake and lactate production measurements. Sphere-forming efficiency and expression of pluripotency transcription factors analysed by qRT-PCR were tested as readout of Metformin effects on stemness features. Metformin induced a concentration-dependent decrease in the metabolic activity and proliferation of sphere-forming cells and improved doxorubicin-induced cytotoxicity. This drug also down-regulated the expression of master regulators of pluripotency (OCT4, SOX2, NANOG), and decreased spheres' self-renewal ability. Metformin effects on mitochondria led to the activation and phosphorylation of the energetic sensor AMPK along with an upregulation of the pro-survival AKT pathway in both cell populations. Furthermore, Metformin-induced mitochondrial stress increased [ 18 F]-FDG uptake and lactate production in parental cells but not in the quiescent stem-like cells, suggesting the inability of the latter to cope with the energy crisis induced by metformin. This preclinical study suggests that Metformin may be a potentially useful therapeutic agent and chemosensitizer of osteosarcoma stem-like cells to doxorubicin.

Activated mammalian target of rapamycin is a potential therapeutic target in gastric cancer

International Nuclear Information System (INIS)

Xu, Da-zhi; Sun, Xiao-wei; Guan, Yuan-xiang; Li, Yuan-fang; Lin, Tong-yu; Geng, Qi-rong; Tian, Ying; Cai, Mu-yan; Fang, Xin-juan; Zhan, You-qing; Zhou, Zhi-wei; Li, Wei; Chen, Ying-bo

2010-01-01

The mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis. The purpose of our present study is to investigate the expression of activated mTOR (p-mTOR) in gastric cancer patients, their prognostic significance and the inhibition effect of RAD001 on tumor growth and to determine whether targeted inhibition of mTOR could be a potential therapeutic strategy for gastric cancer. The expression of p-mTOR was detected in specimens of 181 gastric cancers who underwent radical resection (R0) by immunohistochemistry. The correlation of p-mTOR expression to clinicopathologic features and survival of gastric cancer was studied. We also determined the inhibition effect of RAD001 on tumor growth using BGC823 and AGS human gastric cancer cell lines. Immunostaining for p-mTOR was positive in 93 of 181 (51.4%) gastric cancers, closely correlated with lymph node status and pTNM stage. Patients with p-mTOR positive showed significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those with p-mTOR-negative tumors in univariable analyses, and there was a trend toward a correlation between p-mTOR expression and survival in multivariable analyses. RAD001 markedly inhibited dose-dependently proliferation of human gastric carcinoma cells by down-regulating expression of p70s6k, p-p70s6k, C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53. In gastric cancer, p-mTOR is a potential therapeutic target and RAD001 was a promising treatment agent with inducing cell cycle arrest and apoptosis by down-regulating expression of C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53

ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool

Directory of Open Access Journals (Sweden)

Weissenberger S

2016-11-01

Full Text Available S Weissenberger,1 M Klicperova-Baker,2 P Zimbardo,3 K Schonova,1 D Akotia,1 J Kostal,2 M Goetz,4 J Raboch,1 R Ptacek1 1First Medical Faculty, Charles University, 2Institute of Psychology, Academy of Sciences of the Czech Republic, Praha, Czech Republic; 3Department of Psychology, Stanford University, Stanford, CA, USA; 4Second Faculty of Medicine, Department of Child Psychiatry, Charles University, Motol University Hospital, Praha, Czech RepublicAbstract: The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo’s time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201 are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods, deficits in social learning, and increased aggressiveness both in ADHD and in the population high on Present Hedonism. We conclude that Zimbardo’s time perspective offers both: 1 a potential diagnostic tool – the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2 a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder; however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD.Keywords: ADHD, time perspective, ZTPI, Zimbardo, addiction, alcoholism, delinquency

Potential Bedside Utility of the Clock-Drawing Test in Evaluating Rapid Therapeutic Response in the Natural Course of Schizophrenia: A Preliminary Study.

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Ransing, Ramdas Sarjerao; Khairkar, Praveen Homdeorao; Mishra, Kshirod; Sakekar, Gajanan

2017-01-01

The Clock-Drawing Test (CDT) is a brief, relatively time-efficient, easy to administer at bedside, and well-proven cognitive screening test that assesses a broad range of cognitive abilities in stroke, delirium, and dementia. However, challenges of comprehensive therapeutic outcome evaluations in schizophrenia can also be potentially overcome using CDT. The authors aimed to measure the therapeutic outcome using CDT in 101 schizophrenia patients, irrespective of their diagnostic subtypes. A repeated measures analysis of variance found that improvements on CDT and the Positive and Negative Syndrome Scale were closely correlated, reflecting critical information about therapeutic response measures in schizophrenia.

Nano technologies, technologies converging and potential biomedical applications

International Nuclear Information System (INIS)

Capuano, V.

2005-01-01

The applications of nano technology to biology and medicine appear really promising for diagnostics, for various therapeutic approaches and in medical instrumentations. The growing synergism among nano technology, biotechnology, information technology and cognitive sciences, their convergence (NBIC) from the nano scale, could involve on next decades great changes in medicine, from a reactive to a predictive and preventive approach. It is expected that NBIC converging technologies could achieve tremendous improvements in human abilities and enhance societal achievement of related social and ethical implications, in the framework of a constant dialogue between science and society [it

P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease.

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Ralevic, Vera

2015-01-01

This review considers the expression and roles of P2X receptors in the cardiovascular system in health and disease and their potential as therapeutic targets. P2X receptors are ligand gated ion channels which are activated by the endogenous ligand ATP. They are formed from the assembly of three P2X subunit proteins from the complement of seven (P2X1-7), which can associate to form homomeric or heteromeric P2X receptors. The P2X1 receptor is widely expressed in the cardiovascular system, being located in the heart, in the smooth muscle of the majority of blood vessels and in platelets. P2X1 receptors expressed in blood vessels can be activated by ATP coreleased with noradrenaline as a sympathetic neurotransmitter, leading to smooth muscle depolarisation and contraction. There is evidence that the purinergic component of sympathetic neurotransmission is increased in hypertension, identifying P2X1 receptors as a possible therapeutic target in this disorder. P2X3 and P2X2/3 receptors are expressed on cardiac sympathetic neurones and may, through positive feedback of neuronal ATP at this prejunctional site, amplify sympathetic neurotransmission. Activation of P2X receptors expressed in the heart increases cardiac myocyte contractility, and an important role of the P2X4 receptor in this has been identified. Deletion of P2X4 receptors in the heart depresses contractile performance in models of heart failure, while overexpression of P2X4 receptors has been shown to be cardioprotective, thus P2X4 receptors may be therapeutic targets in the treatment of heart disease. P2X receptors have been identified on endothelial cells. Although immunoreactivity for all P2X1-7 receptor proteins has been shown on the endothelium, relatively little is known about their function, with the exception of the endothelial P2X4 receptor, which has been shown to mediate endothelium-dependent vasodilatation to ATP released during shear stress. The potential of P2X receptors as therapeutic targets

Recent Trends in Nanotechnology-Based Drugs and Formulations for Targeted Therapeutic Delivery.

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Iqbal, Hafiz M N; Rodriguez, Angel M V; Khandia, Rekha; Munjal, Ashok; Dhama, Kuldeep

2017-01-01

In the recent past, a wider spectrum of nanotechnologybased drugs or drug-loaded devices and systems has been engineered and investigated with high interests. The key objective is to help for an enhanced/better quality of patient life in a secure way by avoiding/limiting drug abuse, or severe adverse effects of some in practice traditional therapies. Various methodological approaches including in vitro, in vivo, and ex vivo techniques have been exploited, so far. Among them, nanoparticles-based therapeutic agents are of supreme interests for an enhanced and efficient delivery in the current biomedical sector of the modern world. The development of new types of novel, effective and highly reliable therapeutic drug delivery system (DDS) for multipurpose applications is essential and a core demand to tackle many human health related diseases. In this context, nanotechnology-based several advanced DDS have been engineered with novel characteristics for biomedical, pharmaceutical and cosmeceutical applications that include but not limited to the enhanced/improved bioactivity, bioavailability, drug efficacy, targeted delivery, and therapeutically safer with an extra advantage of overcoming demerits of traditional drug formulations/designs. This review work is focused on recent trends/advances in nanotechnology-based drugs and formulations designed for targeted therapeutic delivery. Moreover, information is also reviewed and given from recent patents and summarized or illustrated diagrammatically to depict a better understanding. Recent patents covering various nanotechnology-based approaches for several applications have also been reviewed. The drug-loaded nanoparticles are among versatile candidates with multifunctional characteristics for potential applications in biomedical, and tissue engineering sector. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fifty Years of Research in ARDS. Cell-based Therapy for Acute Respiratory Distress Syndrome. Biology and Potential Therapeutic Value.

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Laffey, John G; Matthay, Michael A

2017-08-01

On the basis of several preclinical studies, cell-based therapy has emerged as a potential new therapeutic for acute respiratory distress syndrome (ARDS). Of the various cell-based therapy options, mesenchymal stem/stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord have the most experimental data to support their potential efficacy for lung injury from both infectious and noninfectious causes. Mechanistically, MSCs exert their beneficial effects by release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have antiinflammatory and pro-resolving effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by up-regulating sodium-dependent alveolar fluid clearance. MSCs also have antimicrobial effects mediated by release of antimicrobial factors and by up-regulating monocyte/macrophage phagocytosis. Phase 2a clinical trials to establish safety in ARDS are in progress, and two phase 1 trials did not report any serious adverse events. Several issues need further study, including: determining the optimal methods for large-scale production, reconstitution of cryopreserved cells for clinical use, defining cell potency assays, and determining the therapeutic potential of conditioned media derived from MSCs. Because ARDS is a heterogeneous syndrome, targeting MSCs to patients with ARDS with a more hyperinflammatory endotype may further enhance their potential for efficacy.

Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology.

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Gogineni, Vedanjali; Hamann, Mark T

2018-01-01

The oceans are a uniquely rich source of bioactive metabolites, of which sponges have been shown to be among the most prolific producers of diverse bioactive secondary metabolites with valuable therapeutic potential. Much attention has been focused on marine bioactive peptides due to their novel chemistry and diverse biological properties. As summarized in this review, marine peptides are known to exhibit various biological activities such as antiviral, anti-proliferative, antioxidant, anti-coagulant, anti-hypertensive, anti-cancer, antidiabetic, antiobesity, and calcium-binding activities. This review focuses on the chemistry and biology of peptides isolated from sponges, bacteria, cyanobacteria, fungi, ascidians, and other marine sources. The role of marine invertebrate microbiomes in natural products biosynthesis is discussed in this review along with the biosynthesis of modified peptides from different marine sources. The status of peptides in various phases of clinical trials is presented, as well as the development of modified peptides including optimization of PK and bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

Versican is a potential therapeutic target in docetaxel-resistant prostate cancer

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Arichi, Naoko; Mitsui, Yozo; Hiraki, Miho; Nakamura, Sigenobu; Hiraoka, Takeo; Sumura, Masahiro; Hirata, Hiroshi; Tanaka, Yuichiro; Dahiya, Rajvir; Yasumoto, Hiroaki; Shiina, Hiroaki

2015-01-01

In the current study, we investigated a combination of docetaxel and thalidomide (DT therapy) in castration-resistant prostate cancer (CRPC) patients. We identified marker genes that predict the effect of DT therapy. Using an androgen-insensitive PC3 cell line, we established a docetaxel-resistant PC-3 cell line (DR-PC3). In DR-PC3 cells, DT therapy stronger inhibited proliferation/viability than docetaxel alone. Based on gene ontology analysis, we found versican as a selective gene. This result with the findings of cDNA microarray and validated by quantitative RT-PCR. In addition, the effect of DT therapy on cell viability was the same as the effect of docetaxel plus versican siRNA. In other words, silencing of versican can substitute for thalidomide. In the clinical setting, versican expression in prostate biopsy samples (before DT therapy) correlated with PSA reduction after DT therapy (p<0.05). Thus targeting versican is a potential therapeutic strategy in docetaxel-resistant prostate cancer. PMID:25859560

Therapeutic Hypothermia in Stroke and Traumatic Brain Injury

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Alireza eFaridar

2011-12-01

Full Text Available Therapeutic hypothermia (TH is considered to improve survival with favorable neurological outcome in the case of global cerebral ischemia after cardiac arrest and perinatal asphyxia. The efficacy of hypothermia in acute ischemic stroke (AIS and traumatic brain injury (TBI, however, is not well studied. Induction of TH typically requires a multimodal approach, including the use of both pharmacological agents and physical techniques. To date, clinical outcomes for patients with either AIS or TBI who received TH have yielded conflicting results; thus, no adequate therapeutic consensus has been reached. Nevertheless, it seems that by determining optimal TH parameters and also appropriate applications, cooling therapy still has the potential to become a valuable neuroprotective intervention.Among the various methods for hypothermia induction, intravascular cooling (IVC may have the most promise in the awake patient in terms of clinical outcomes. Currently, the IVC method has the capability of more rapid target temperature attainment and more precise control of temperature. However, this technique requires expertise in endovascular surgery that can preclude its application in the field and/or in most emergency settings. It is very likely that combining neuroprotective strategies will yield better outcomes than utilizing a single approach.

Molecular hydrogen in sports medicine: new therapeutic perspectives.

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Ostojic, S M

2015-04-01

In the past 2 decades, molecular hydrogen emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. Beneficial effects of molecular hydrogen in clinical environment are observed especially in oxidative stress-mediated diseases, such as diabetes mellitus, brain stem infarction, rheumatoid arthritis, or neurodegenerative diseases. A number of more recent studies have reported that molecular hydrogen affects cell signal transduction and acts as an alkalizing agent, with these newly identified mechanisms of action having the potential to widen its application in clinical medicine even further. In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. This review will summarize recent research findings regarding the clinical aspects of molecular hydrogen use, emphasizing its application in the field of sports medicine. © Georg Thieme Verlag KG Stuttgart · New York.

Potential prospects of nanomedicine for targeted therapeutics in inflammatory bowel diseases

OpenAIRE

Pichai, Madharasi VA; Ferguson, Lynnette R

2012-01-01

Inflammatory bowel diseases (IBDs) such as Crohn’s disease are highly debilitating. There are inconsistencies in response to and side effects in the current conventional medications, failures in adequate drug delivery, and the lack of therapeutics to offer complete remission in the presently available treatments of IBD. This suggests the need to explore beyond the horizons of conventional approaches in IBD therapeutics. This review examines the arena of the evolving IBD nanomedicine, studied ...

Three Valuable Peptides from Bee and Wasp Venoms for Therapeutic and Biotechnological Use: Melittin, Apamin and Mastoparan

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Moreno, Miguel; Giralt, Ernest

2015-01-01

While knowledge of the composition and mode of action of bee and wasp venoms dates back 50 years, the therapeutic value of these toxins remains relatively unexploded. The properties of these venoms are now being studied with the aim to design and develop new therapeutic drugs. Far from evaluating the extensive number of monographs, journals and books related to bee and wasp venoms and the therapeutic effect of these toxins in numerous diseases, the following review focuses on the three most characterized peptides, namely melittin, apamin, and mastoparan. Here, we update information related to these compounds from the perspective of applied science and discuss their potential therapeutic and biotechnological applications in biomedicine. PMID:25835385

Silk constructs for delivery of muskuloskeletal therapeutics

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Meinel, Lorenz; Kaplan, David L.

2012-01-01

Silk fibroin (SF) is a biopolymer with distinguishing features from many other bio- as well as synthetic polymers. From a biomechanical and drug delivery perspective, SF combines remarkable versatility for scaffolding (solid implants, hydrogels, threads, solutions), with advanced mechanical properties and good stabilization and controlled delivery of entrapped protein and small molecule drugs, respectively. It is this combination of mechanical and pharmaceutical features which render SF so exciting for biomedical applications. his pattern along with the versatility of this biopolymer have been translated into progress for musculoskeletal applications. We review the use and potential of silk fibroin for systemic and localized delivery of therapeutics in diseases affecting the musculoskeletal system. We also present future directions for this biopolymer as well as the necessary research and development steps for their achievement. PMID:22522139

Nuclear data for production of therapeutic radionuclides. Summary report of second research coordination meeting

International Nuclear Information System (INIS)

Sublet, J.-Ch.; Capote Noy, R.

2004-11-01

A summary is given of the Second Research Coordination Meeting on Nuclear Data for Production of Therapeutic Radionuclides. The new library of evaluated cross section will cover the reactor and/or accelerator production of therapeutic radionuclides to appropriate specific activities and purity along with the relevant decay data. There are a significant number of radioisotopes in use or being proposed for therapeutic applications. As a consequence of the work undertaken during the course of this CRP, the resulting completeness and accuracy of the nuclear data for the production of these nuclides to appropriate specific activities and purity along with the re-definition of their decay data should be adequate for safe and efficient medical applications. The radioisotopes to be considered in the CRP were divided into two categories: Established Radioisotopes (therapeutic radioisotopes that have established clinical uses) and Emerging Radioisotopes (less-commonly used but potentially interesting radioisotopes for which medical applications have been demonstrated). Experimental data compilations and selection and preliminary evaluations for each of the reactions were extensively discussed during the meeting. The recommendations for both established and emerging radionuclides, and validation/testing of the cross section library are summarized. Technical discussions and the resulting work plan of the Coordinated Research Programme are summarized for every reaction path to be evaluated, along with actions and deadlines. Participants' contributions to the RCM are also attached. (author)

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

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Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Reactor production and processing of radioisotopes for therapeutic applications in nuclear medicine

International Nuclear Information System (INIS)

Knapp, F.F. Jr.; Mirzadeh, S.; Beets, A.L.

1995-01-01

Nuclear reactors continue to play an important role in providing radioisotopes for nuclear medicine. Many reactor-produced radioisotopes are ''neutron rich'' and decay by beta-emission and are thus of interest for therapeutic applications. This talk discusses the production and processing of a variety of reactor-produced radioisotopes of current interest, including those produced by the single neutron capture process, double neutron capture and those available from beta-decay of reactorproduced radioisotopes. Generators prepared from reactorproduced radioisotopes are of particular interest since repeated elution inexpensively provides many patient doses. The development of the alumina-based W-188/Re-188 generator system is discussed in detail

Current issues of RNAi therapeutics delivery and development.

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Haussecker, D

2014-12-10

the applications of RNAi therapeutics are rather limited. This is largely based on the observation that the biodistribution of RNAi formulations is typically more limited compared to small molecules and oral administration is not possible with current technologies. Similarly, the utility of a given RNAi formulation is limited to a few cell types and tissues at most and a universal delivery strategy should remain elusive for the foreseeable future. Therefore, to further expand on the therapeutic utility and patient convenience of RNAi, it is important to overcome a number of delivery-related technical and scientific challenges which will be discussed in this presentation. For systemic applications, these include the necessity for extended blood circulation times, vascular escape (probably the most rewarding inquiry currently), tissue penetration, cellular uptake, and escape into the cytoplasm. In terms of safety, it is important that these formulations do not accumulate in the body, do not cause excessive off-targeting due to 'chemical stickiness' (often useful for purposes of biodistribution), and overcome the physical/biological barriers in a controlled manner. The time for realizing the therapeutic potential of RNAi has come. At the same time, it is important to lay the foundations for the next leg of value creation by overcoming the challenges of delivering RNAi to new cell types. Based on results from exploratory research, the renewed interest in RNAi therapeutics and capital infusion, there is a reason to be optimistic that this can be achieved. Copyright © 2014 Elsevier B.V. All rights reserved.

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

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Mario Gimona

2017-06-01

Full Text Available Extracellular vesicles (EVs derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

Enlight: A Comprehensive Quality and Therapeutic Potential Evaluation Tool for Mobile and Web-Based eHealth Interventions.

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Baumel, Amit; Faber, Keren; Mathur, Nandita; Kane, John M; Muench, Fred

2017-03-21

concurrent validity analysis pointed to positive correlations of combined quality scores with selected variables. The combined score that did not include therapeutic persuasiveness and therapeutic alliance descriptively underperformed the other combined scores. This paper provides empirical evidence supporting the importance of persuasive design and therapeutic alliance within the context of a program's evaluation. Reliability metrics and preliminary concurrent validity analysis indicate the potential of Enlight in examining eHealth programs regardless of delivery mediums and clinical aims. ©Amit Baumel, Keren Faber, Nandita Mathur, John M Kane, Fred Muench. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.03.2017.

Development of Potential Small Molecule Therapeutics for Treatment of Ebola Virus.

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Schafer, Adam Michael; Cheng, Han; Lee, Charles; Du, Ruikun; Han, Julianna; Perez, Jasmine; Peet, Norton; Manicassamy, Balaji; Rong, Lijun

2017-10-10

Ebola virus has caused 26 outbreaks in 10 different countries since its identification in 1976, making it one of the deadliest emerging viral pathogens. The most recent outbreak in West Africa from 2014-16 was the deadliest yet and culminated in 11,310 deaths out of 28,616 confirmed cases. Currently there are no FDA-approved therapeutics or vaccines to treat Ebola virus infections. The slow development of effective vaccines combined with the severity of past outbreaks emphasizes the need to accelerate research into understanding the virus lifecycle and the development of therapeutics for post exposure treatment. Here we present a summary of the major findings on the Ebola virus replication cycle and the therapeutic approaches explored to treat this devastating disease. The major focus of this review is on small molecule inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

NLF20: an antimicrobial peptide with therapeutic potential against invasive Pseudomonas aeruginosa infection.

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Papareddy, Praveen; Kasetty, Gopinath; Kalle, Martina; Bhongir, Ravi K V; Mörgelin, Matthias; Schmidtchen, Artur; Malmsten, Martin

2016-01-01

Increasing resistance to antibiotics makes antimicrobial peptides interesting as novel therapeutics. Here, we report on studies of the peptide NLF20 (NLFRKLTHRLFRRNFGYTLR), corresponding to an epitope of the D helix of heparin cofactor II (HCII), a plasma protein mediating bacterial clearance. Peptide effects were evaluated by a combination of in vitro and in vivo methods, including antibacterial, anti-inflammatory and cytotoxicity assays, fluorescence and electron microscopy, and experimental models of endotoxin shock and Pseudomonas aeruginosa sepsis. The results showed that NLF20 displayed potent antimicrobial effects against the Gram-negative bacteria Escherichia coli and P. aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus and the fungi Candida albicans and Candida parapsilosis. Importantly, this antimicrobial effect was retained in human blood, particularly for P. aeruginosa. Fluorescence and electron microscopy studies showed that the peptide exerted membrane-breaking effects. In an animal model of P. aeruginosa sepsis, NLF20 reduced bacterial levels, resulting in improved survival. Reduced mortality was also observed in experimental animal models of endotoxin shock, which was paralleled with modulated IFN-γ, IL-10 and coagulation responses. Together, these results indicate that functional epitopes of HCII may have therapeutic potential against bacterial infection. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Upregulation of MARCKS in kidney cancer and its potential as a therapeutic target.

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Chen, C-H; Fong, L W R; Yu, E; Wu, R; Trott, J F; Weiss, R H

2017-06-22

Targeted therapeutics, such as those abrogating hypoxia inducible factor (HIF)/vascular endothelial growth factor signaling, are initially effective against kidney cancer (or renal cell carcinoma, RCC); however, drug resistance frequently occurs via subsequent activation of alternative pathways. Through genome-scale integrated analysis of the HIF-α network, we identified the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) as a potential target molecule for kidney cancer. In a screen of nephrectomy samples from 56 patients with RCC, we found that MARCKS expression and its phosphorylation are increased and positively correlate with tumor grade. Genetic and pharmacologic suppression of MARCKS in high-grade RCC cell lines in vitro led to a decrease in cell proliferation and migration. We further demonstrated that higher MARCKS expression promotes growth and angiogenesis in vivo in an RCC xenograft tumor. MARCKS acted upstream of the AKT/mTOR pathway, activating HIF-target genes, notably vascular endothelial growth factor-A. Following knockdown of MARCKS in RCC cells, the IC50 of the multikinase inhibitor regorafenib was reduced. Surprisingly, attenuation of MARCKS using the MPS (MARCKS phosphorylation site domain) peptide synergistically interacted with regorafenib treatment and decreased survival of kidney cancer cells through inactivation of AKT and mTOR. Our data suggest a major contribution of MARCKS to kidney cancer growth and provide an alternative therapeutic strategy of improving the efficacy of multikinase inhibitors.

The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

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Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

2013-09-01

Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. © 2013 FEBS.

Survey of potential electronic applications of high temperature superconductors

International Nuclear Information System (INIS)

Hammond, R.B.; Bourne, L.C.

1991-01-01

In this paper the authors present a survey of the potential electronic applications of high temperature superconductor (HTSC) thin films. During the past four years there has been substantial speculation on this topic. The authors will cover only a small fraction of the potential electronic applications that have been identified. Their treatment is influenced by the developments over the past few years in materials and device development and in market analysis. They present their view of the most promising potential applications. Superconductors have two important properties that make them attractive for electronic applications. These are (a) low surface resistance at high frequencies, and (b) the Josephson effect

Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

Science.gov (United States)

Putcha, Lakshmi

2011-01-01

An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

Science.gov (United States)

Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

2017-12-01

To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS

Directory of Open Access Journals (Sweden)

Jeong Eun Kim

2018-04-01

Full Text Available Pemetrexed and platinum (PP combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM. However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions. We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found.

Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS.

Science.gov (United States)

Kim, Jeong Eun; Kim, Deokhoon; Hong, Yong Sang; Kim, Kyu-Pyo; Yoon, Young Kwang; Lee, Dae Ho; Kim, Sang-We; Chun, Sung-Min; Jang, Se Jin; Kim, Tae Won

2018-04-01

Pemetrexed and platinum (PP) combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM). However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions). We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Therapeutic Effect of External Application of Ligustrazine Combined with Holistic Nursing on Pressure Sores.

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Niu, Junzhi; Han, Lin; Gong, Fen

2016-08-15

BACKGROUND This study aimed to explore the therapeutic effect of external application of ligustrazine combined with holistic nursing on pressure sores, as well as the underlying mechanism. MATERIAL AND METHODS From February 2014 to March 2015, a total of 32 patients with Phase II and Phase III pressure sores were enrolled and randomly assigned to an experimental group or a control group. The clinical data were comparable between the 2 groups. In addition to holistic nursing, the patients in the experimental group received 4 weeks of continuous external application of ligustrazine, whereas patients in the control group received compound clotrimazole cream. Therapeutic effect and healing time were recorded. HaCaT cells were used as an in vitro model for mechanism analysis of the effect of ligustrazine in treating pressure sores. After culturing with different concentrations of ligustrazine or the inhibitor of AKT (LY294002) for 72 h, cell viability, clone formation numbers, and levels of phosphatidyl inositol 3-kinase (PI3K), p-AKT, and p-mammalian target of rapamycin (mTOR) were determined. RESULTS Compared to the control group, the total effective rate in the experimental group was significantly higher, and the healing time was significantly reduced. Cell viability and clone formation numbers were significantly upregulated by ligustrazine in a dose-dependent manner. Both the cell viability and clone formation numbers were significantly inhibited by application of LY294002. CONCLUSIONS Our results suggest that ligustrazine combined with holistic nursing is an effective treatment of pressure sores. The protective effect may be associated with the promotion of cell growth by activation of the PI3K/AKT pathway.

Stem cells in degenerative orthopaedic pathologies: effects of aging on therapeutic potential.

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Atesok, Kivanc; Fu, Freddie H; Sekiya, Ichiro; Stolzing, Alexandra; Ochi, Mitsuo; Rodeo, Scott A

2017-02-01

The purpose of this study was to summarize the current evidence on the use of stem cells in the elderly population with degenerative orthopaedic pathologies and to highlight the pathophysiologic mechanisms behind today's therapeutic challenges in stem cell-based regeneration of destructed tissues in the elderly patients with osteoarthritis (OA), degenerative disc disease (DDD), and tendinopathies. Clinical and basic science studies that report the use of stem cells in the elderly patients with OA, DDD, and tendinopathies were identified using a PubMed search. The studies published in English have been assessed, and the best and most recent evidence was included in the current study. Evidence suggests that, although short-term results regarding the effects of stem cell therapy in degenerative orthopaedic pathologies can be promising, stem cell therapies do not appear to reverse age-related tissue degeneration. Causes of suboptimal outcomes can be attributed to the decrease in the therapeutic potential of aged stem cell populations and the regenerative capacity of these cells, which might be negatively influenced in an aged microenvironment within the degenerated tissues of elderly patients with OA, DDD, and tendinopathies. Clinical protocols guiding the use of stem cells in the elderly patient population are still under development, and high-level randomized controlled trials with long-term outcomes are lacking. Understanding the consequences of age-related changes in stem cell function and responsiveness of the in vivo microenvironment to stem cells is critical when designing cell-based therapies for elderly patients with degenerative orthopaedic pathologies.

Therapeutic applications of resveratrol and its derivatives on periodontitis.

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Chin, Yu-Tang; Cheng, Guei-Yun; Shih, Ya-Jung; Lin, Chi-Yu; Lin, Shan-Jen; Lai, Hsuan-Yu; Whang-Peng, Jacqueline; Chiu, Hsien-Chung; Lee, Sheng-Yang; Fu, Earl; Tang, Heng-Yuan; Lin, Hung-Yun; Liu, Leroy F

2017-09-01

Periodontitis is an inflammatory disease of the supporting tissues of the teeth induced by periodontopathic bacteria that results in the progressive destruction of periodontal tissues. Treatment of periodontitis is painful and time-consuming. Recently, herbal medicines have been considered for use in treating inflammation-related diseases, including periodontitis. Resveratrol and its derivative 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside (THSG), a polyphenol extracted from Polygonum multiflorum, have anti-inflammatory properties and other medical benefits. Here, we highlight the importance of resveratrol and its glycosylated derivative as possible complementary treatments for periodontitis and their potential for development as innovative therapeutic strategies. In addition, we present evidence and discuss the mechanisms of action of resveratrol and THSG on periodontitis, focusing on Porphyromonas gingivalis-induced inflammatory responses in human gingival fibroblasts and animal modeling of ligature-induced periodontitis. We also illuminate the signal transduction pathways and the cytokines involved. © 2017 New York Academy of Sciences.

Biomaterials and therapeutic applications

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Ferraro, Angelo

2016-03-01

A number of organic and inorganic, synthetic or natural derived materials have been classified as not harmful for the human body and are appropriate for medical applications. These materials are usually named biomaterials since they are suitable for introduction into living human tissues of prosthesis, as well as for drug delivery, diagnosis, therapies, tissue regeneration and many other clinical applications. Recently, nanomaterials and bioabsorbable polymers have greatly enlarged the fields of application of biomaterials attracting much more the attention of the biomedical community. In this review paper I am going to discuss the most recent advances in the use of magnetic nanoparticles and biodegradable materials as new biomedical tools.

Potential therapeutic agents for circulatory diseases from Bauhinia glauca Benth.subsp. pernervosa. (Da Ye Guan Men).

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Tang, Yingzhan; Ling, Junhong; Zhang, Peng; Zhang, Xiangrong; Zhang, Na; Wang, Wenli; Li, Jiayuan; Li, Ning

2015-08-15

Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1-29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly. Copyright © 2015. Published by Elsevier Ltd.

Potential application of lithium in Parkinson’s and other neurodegenerative diseases

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Carol A Lazzara

2015-10-01

Full Text Available Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson’s disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of Calpain-1. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.

Quality Assurance Issues for Therapeutic Application of Radioactive Microspheres

International Nuclear Information System (INIS)

Dezarn, William A.

2008-01-01

The use of radioactive microspheres for the treatment of hepatic cancer is a procedure that raises unique quality assurance (QA) concerns. The greatest of these concerns is the coordination of the responsibilities among the medical team members from interventional radiology, radiation oncology, nuclear medicine, and medical physics. A single QA practice and procedure guidance document does not currently exist that addresses the range of issues of concern for radioactive microspheres. A small sampling of QA issues of concern include imaging QA, procedure-specific imaging protocols, detector calibration, activity measurement, radiation safety, patient dose calculations, and patient-specific QA. Some of the items listed have historically been the responsibility of a single team member, and other items have been concerns for all. A procedural overview of the therapeutic application of radioactive microspheres is presented to illustrate the broad, team-based QA approach necessary to safely and effectively deliver this type of treatment. From this overview, the reader will be able to customize the local QA protocol to meet the local division of responsibilities

Therapeutic cloning: The ethical limits

International Nuclear Information System (INIS)

Whittaker, Peter A.

2005-01-01

A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

A reduced-order, single-bubble cavitation model with applications to therapeutic ultrasound.

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Kreider, Wayne; Crum, Lawrence A; Bailey, Michael R; Sapozhnikov, Oleg A

2011-11-01

Cavitation often occurs in therapeutic applications of medical ultrasound such as shock-wave lithotripsy (SWL) and high-intensity focused ultrasound (HIFU). Because cavitation bubbles can affect an intended treatment, it is important to understand the dynamics of bubbles in this context. The relevant context includes very high acoustic pressures and frequencies as well as elevated temperatures. Relative to much of the prior research on cavitation and bubble dynamics, such conditions are unique. To address the relevant physics, a reduced-order model of a single, spherical bubble is proposed that incorporates phase change at the liquid-gas interface as well as heat and mass transport in both phases. Based on the energy lost during the inertial collapse and rebound of a millimeter-sized bubble, experimental observations were used to tune and test model predictions. In addition, benchmarks from the published literature were used to assess various aspects of model performance. Benchmark comparisons demonstrate that the model captures the basic physics of phase change and diffusive transport, while it is quantitatively sensitive to specific model assumptions and implementation details. Given its performance and numerical stability, the model can be used to explore bubble behaviors across a broad parameter space relevant to therapeutic ultrasound.

Augmentation of therapeutic potential of curcumin using nanotechnology: current perspectives.

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Sivasami, Pulavendran; Hemalatha, Thiagarajan

2018-02-28

Curcumin, an active principle of Curcuma longa, is extracted from the rhizome. Its therapeutic efficiency has been proved using various in vitro and in vivo models. Inflammatory, neoplastic and preneoplastic diseases are the major targets using curcumin as therapeutic agent. Feasible clinical formulations could not be obtained because of its lack of solubility, stability and higher degradation rate. Recently, many techniques have been evolved to improve the physicochemical properties of pharmacological compounds, thereby increasing their biological activity. Curcumin has been developed using various techniques, particularly micro and nanotechnology to improve its stability and bioavailability. This review focuses on the studies pertaining to the delivery of curcumin in the form of micro and nanosize formulations for the treatment of a variety of diseases.

Generation of “LYmph Node Derived Antibody Libraries” (LYNDAL) for selecting fully human antibody fragments with therapeutic potential.

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Diebolder, Philipp; Keller, Armin; Haase, Stephanie; Schlegelmilch, Anne; Kiefer, Jonathan D; Karimi, Tamana; Weber, Tobias; Moldenhauer, Gerhard; Kehm, Roland; Eis-Hübinger, Anna M; Jäger, Dirk; Federspil, Philippe A; Herold-Mende, Christel; Dyckhoff, Gerhard; Kontermann, Roland E; Arndt, Michaela A E; Krauss, Jürgen

2014-01-01

The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro,the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential.

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions.

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Sofia, M Anthony; Rubin, David T

2017-04-01

The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

Therapeutic applications of radiopharmaceuticals. Proceedings of an international seminar

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-06-01

The potential of radionuclides in therapy has been recognised for many decades. A number of radionuclides such as iodine-131, phosphorous-32, yttrium-90 and 1-131 MIBG have been in use for the treatment of many benign and malignant disorders. Recently, however, there has been a significant growth of this branch of nuclear medicine with the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain, neuroendocrine and other tumours. The prospect of localising or treating neoplastic diseases using specific antibodies labelled with radioactive isotopes capable of delivering large amounts of internally administered radiation may have the potential to fulfil the promise of EhrIich's 'magic bullet', which has tantalised investigators worldwide for the past sixty years. Recent success in this area has been largely due to genetic and molecular techniques that now permit production of a large number of suitable peptides and monoclonal antibodies directed against specific epitopes individually characteristic of specific tumours. The input of the radiochemist and the development of labelling techniques that do not destroy the immunological integrity of the monoclonal antibodies have also been essential ingredients of the success story. Recent significant advances in monoclonal antibody techniques for pretargeting make it very likely that radiopharmaceuticals will become an important part of therapy for various cancers. It may also be possible that in addition to the use of beta particles, alpha particles may soon become a mainstay of therapeutic nuclear medicine. Cancer researchers, looking for an extremely potent and highly specific way to target cancer cells, are investigating the use of monoclonal antibodies and peptides attached to alpha emitting radionuclides in early clinical trials. Today the field of radionuclide therapy is going through an extremely interesting and exciting phase and is poised for greater growth

Therapeutic applications of radiopharmaceuticals. Proceedings of an international seminar

International Nuclear Information System (INIS)

2001-06-01

The potential of radionuclides in therapy has been recognised for many decades. A number of radionuclides such as iodine-131, phosphorous-32, yttrium-90 and 1-131 MIBG have been in use for the treatment of many benign and malignant disorders. Recently, however, there has been a significant growth of this branch of nuclear medicine with the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain, neuroendocrine and other tumours. The prospect of localising or treating neoplastic diseases using specific antibodies labelled with radioactive isotopes capable of delivering large amounts of internally administered radiation may have the potential to fulfil the promise of EhrIich's 'magic bullet', which has tantalised investigators worldwide for the past sixty years. Recent success in this area has been largely due to genetic and molecular techniques that now permit production of a large number of suitable peptides and monoclonal antibodies directed against specific epitopes individually characteristic of specific tumours. The input of the radiochemist and the development of labelling techniques that do not destroy the immunological integrity of the monoclonal antibodies have also been essential ingredients of the success story. Recent significant advances in monoclonal antibody techniques for pretargeting make it very likely that radiopharmaceuticals will become an important part of therapy for various cancers. It may also be possible that in addition to the use of beta particles, alpha particles may soon become a mainstay of therapeutic nuclear medicine. Cancer researchers, looking for an extremely potent and highly specific way to target cancer cells, are investigating the use of monoclonal antibodies and peptides attached to alpha emitting radionuclides in early clinical trials. Today the field of radionuclide therapy is going through an extremely interesting and exciting phase and is poised for greater growth

Bacterial inclusion bodies as potential synthetic devices for pathogen recognition and a therapeutic substance release.

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Talafová, Klaudia; Hrabárová, Eva; Chorvát, Dušan; Nahálka, Jozef

2013-02-07

Adhesins of pathogens recognise the glycans on the host cell and mediate adherence. They are also crucial for determining the tissue preferences of pathogens. Currently, glyco-nanomaterials provide potential tool for antimicrobial therapy. We demonstrate that properly glyco-tailored inclusion bodies can specifically bind pathogen adhesins and release therapeutic substances. In this paper, we describe the preparation of tailored inclusion bodies via the conjugation of indicator protein aggregated to form inclusion bodies with soluble proteins. Whereas the indicator protein represents a remedy, the soluble proteins play a role in pathogen recognition. For conjugation, glutaraldehyde was used as linker. The treatment of conjugates with polar lysine, which was used to inactivate the residual glutaraldehyde, inhibited unwanted hydrophobic interactions between inclusion bodies. The tailored inclusion bodies specifically interacted with the SabA adhesin from Helicobacter pylori aggregated to form inclusion bodies that were bound to the sialic acids decorating the surface of human erythrocytes. We also tested the release of indicator proteins from the inclusion bodies using sortase A and Ssp DNAB intein self-cleaving modules, respectively. Sortase A released proteins in a relatively short period of time, whereas the intein cleavage took several weeks. The tailored inclusion bodies are promising "nanopills" for biomedical applications. They are able to specifically target the pathogen, while a self-cleaving module releases a soluble remedy. Various self-cleaving modules can be enabled to achieve the diverse pace of remedy release.

Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

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Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

2014-12-01

This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats.

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Zhang, Yuanyuan; Yan, Yi; Cao, Yi; Yang, Yongtao; Zhao, Qing; Jing, Rui; Hu, Jiayi; Bao, Juan

2017-08-15

The present study was carried out to understand the therapeutic effect of curcumin (CUR) against stroke in the experimental animal model. The study investigates the healing effect of CUR on mitochondrial dysfunction and inflammation. Male albino, Wistar strain rats were used for the induction of middle cerebral artery occlusion (MCAO), and reperfusion. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the brain region. Western blot analysis was used to determine the protein expression levels of Bax, Bcl-2, p53, and Sirt1. The water level was determined in brain region by using standard method. Experimental results indicated that the use of CUR significantly reduced brain edema and water content. IL-6 and TNF-α were significantly reduced in the brain region following use of CUR. Mitochondrial membrane potential (MMP) also reduced significantly after CUR treatment. Protein expression of p53 and Bax were significantly reduced, whereas Bcl-2 and Sirt1 were increased following CUR treatment. Taking all these data together, it is suggested that the use of CUR may be a potential therapeutic agent for the treatment of stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacological effects and potential therapeutic targets of DT-13.

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Khan, Ghulam Jilany; Rizwan, Mohsin; Abbas, Muhammad; Naveed, Muhammad; Boyang, Yu; Naeem, Muhammad Ahsan; Khan, Sara; Yuan, Shengtao; Baig, Mirza Muhammad Faran Ashraf; Sun, Li

2018-01-01

DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies. In vivo and in vitro studies show that the drug regulates multiple cellular functions for its several pharmacological effects including, anti-adhesive effects via regulation of tissue factor and transforming growth factor; anti-migratory effects through indirect regulation of NM-IIA in the tumor microenvironment, Tissue factor, down-regulation of CCR5-CCL5 axis and MMP-2/9 inhibition; anti-metastatic effects via regulation of MMPs and tissue factor; pro-apoptotic effects by modulation of endocytosis of EGF receptor; anti-angiogenic effects via regulation of HIF-1α,ERK, Akt signalling and autophagy inducing characteristics by regulating PI3K/Akt/mTOR signalling pathway. In addition to anti-tumor activities, DT-13 has significant anti-inflammatory, cardioprotective, hepatoprotective and immunomodulating effects. Pharmaceutical dosage form and targeted drug delivery system for DT-13 has not been established yet. Moreover, DT-13, has not been studied for its action on brain, colorectal, hepatic, pancreatic, prostate and blood cancers. Similarly the effects of drug on carbohydrate and glucose metabolism is another niche yet to be explored. In some traditional therapies, crude drug from the plant is used against diabetic and neurological disorders that are not reported in scientific literature, however due to profound effects of

The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control.

Science.gov (United States)

Decker, M W; Meyer, M D; Sullivan, J P

2001-10-01

Due to the limitations of currently available analgesics, a number of novel alternatives are currently under investigation, including neuronal nicotinic acetylcholine receptor (nAChR) agonists. During the 1990s, the discovery of the antinociceptive properties of the potent nAChR agonist epibatidine in rodents sparked interest in the analgesic potential of this class of compounds. Although epibatidine also has several mechanism-related toxicities, the identification of considerable nAChR diversity suggested that the toxicities and therapeutic actions of the compound might be mediated by distinct receptor subtypes. Consistent with this view, a number of novel nAChR agonists with antinociceptive activity and improved safety profiles in preclinical models have now been identified, including A-85380, ABT-594, DBO-83, SIB-1663 and RJR-2403. Of these, ABT-594 is the most advanced and is currently in Phase II clinical evaluation. Nicotinically-mediated antinociception has been demonstrated in a variety of rodent pain models and is likely mediated by the activation of descending inhibitory pathways originating in the brainstem with the predominant high-affinity nicotine site in brain, the alpha4beta2 subtype, playing a critical role. Thus, preclinical findings suggest that nAChR agonists have the potential to be highly efficacious treatments in a variety of pain states. However, clinical proof-of-principle studies will be required to determine if nAChR agonists are active in pathological pain.

8. Therapeutic and Educational Potential of Combining Cognitive Behavioural Therapy and Art – Qualitative Analysis of a Case Study

Directory of Open Access Journals (Sweden)

Růžička Michal

2016-03-01

Full Text Available Cognitive behavioural psychotherapy is, just like other psychotherapeutic systems, of an eclectic nature. Should a therapist be successful across a wide range of issues, he/she needs to be adaptable, flexible and eclectic in terms of the techniques applied. Eclectically oriented therapists use a wide range of interventions; however, they adhere to individual theoretical structures. The aim of the paper is to point out the application of a combination of artistic activities within the system of the Cognitive behavioural therapy. For this purpose the paper presents a qualitative analysis of two case studies. We formulated the following research questions. Can the methods of combining the cognitive behavioural therapy and art accelerate the course of therapy? Can the methods of combining the cognitive behavioural therapy and art be perceived by the client as effective? The phenomenon investigated in the case study is a functional analysis of a client’s case and subsequent application of therapeutic and educational techniques of the Cognitive behavioural therapy and art. In both case studies it was demonstrated that the involvement of therapeutic elements accelerated the course of therapy. The clients in the research sample assessed the therapy as beneficial.

c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

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Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

2015-06-03

c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

Resveratrol, Potential Therapeutic Interest in Joint Disorders: A Critical Narrative Review

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Christelle Nguyen

2017-01-01

Full Text Available Trans-resveratrol (t-Res is a natural compound of a family of hydroxystilbenes found in a variety of spermatophyte plants. Because of its effects on lipids and arachidonic acid metabolisms, and its antioxidant activity, t-Res is considered as the major cardioprotective component of red wine, leading to the “French Paradox” health concept. In the past decade, research on the effects of resveratrol on human health has developed considerably in diverse fields such as cancer, neurodegenerative and cardiovascular diseases, and metabolic disorders. In the field of rheumatic disorders, in vitro evidence suggest anti-inflammatory, anti-catabolic, anti-apoptotic and anti-oxidative properties of t-Res in various articular cell types, including chondrocytes and synoviocytes, along with immunomodulation properties on T and B lymphocytes. In preclinical models of osteoarthritis and rheumatoid arthritis, resveratrol has shown joint protective effects, mainly mediated by decreased production of pro-inflammatory and pro-degradative soluble factors, and modulation of cellular and humoral responses. Herein, we comprehensively reviewed evidence supporting a potential therapeutic interest of t-Res in treating symptoms related to rheumatic disorders.

Potencial terapéutico de los canabinoides como neuroprotectores Therapeutical potential of cannabinoids as neuroprotective agents

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Laymi Martínez García

2007-12-01

Full Text Available La planta Cannabis sativa L. o cáñamo ha captado desde tiempos antiquísimos la atención del hombre en el campo de la salud y terapéutica humanas y todavía, a inicios del siglo XXI, continúa despertando polémicas en la comunidad científica como fuente natural y en el estudio y aplicación de sus derivados. Desde el punto de vista fitoquímico se han descrito más de 70 derivados de tipo canabinoide farmacológicamente activos sobre el sistema nervioso central. En la actualidad se han generado valiosísimas fuentes de información que relacionan la especie botánica Cannabis sativa L. y sus metabolitos secundarios con la medicina (tratamiento terapéutico, farmacología (modelos experimentales y química sintética (diseño y generación de nuevas estructuras, las cuales avalan la importancia del estudio de esta planta, sus extractos, metabolitos y precursores como fuente de agentes terapéuticos. Por tal motivo se presenta una revisión de la información existente sobre las potenciales implicaciones terapéuticas de sistemas moleculares canabinoidales (endógenos, naturales y sintéticos en el tratamiento de enfermedades neurodegenerativas del sistema nervioso central, que incluye: conceptos de tipos de canabinoides, sistemas de receptores canabinoides CB1 y CB2 y evidencias preclínicas de los efectos neuroprotectores de canabinoides desde 1970 hasta el 2005Cannabis sativa L. or cáñamo has focused man's attention for its therapeutical and medical application since ancient times, and yet, at the beginning of XXI century, this plant continues being polemic for the scientific community as a natural source and in the study and application of its derivatives. More than 70 cannabinoid compounds with pharmacological action on the central nervous system have been phytochemically described. At present, a great amount of valuable information and experimental data have been generated that correlate Cannabis sativa and its secondary metabolites

Therapeutic relationship on the web: to face or not to face?

Directory of Open Access Journals (Sweden)

Ana Sfoggia

2014-03-01

Full Text Available In this age of unprecedented expansion of media and information dissemination and sharing, the use of electronic means should be reconsidered. The use of new technologies should be studied to understand how it may affect the relationship between patient and therapist during psychotherapy or psychoanalytic treatments. This study offers a critical discussion of the effect of technologies on clinical practice, and vignettes are used to describe their impact on frame, anonymity, abstinence and therapeutic neutrality. Transfer and countertransference issues resulting from these changes are also discussed. The potential benefits of new technologies in psychotherapy are appreciated, but the authors draw attention to the need to reflect about the presence of the therapist in those technologies and the preservation of the therapeutic setting, so that a satisfactory progression of the work of the dyad is ensured. This study also discusses the use of technologies in the expansion of learning and application of the therapeutic technique to overcome geographic and time barriers, among others.

Myofibrillogenesis regulator 1 (MR-1 is a novel biomarker and potential therapeutic target for human ovarian cancer

Directory of Open Access Journals (Sweden)

Feng Jingjing

2011-06-01

Full Text Available Abstract Background Myofibrillogenesis regulator 1 (MR-1 is overexpressed in human cancer cells and plays an essential role in cancer cell growth. However, the significance of MR-1 in human ovarian cancer has not yet been explored. The aim of this study was to examine whether MR-1 is a predictor of ovarian cancer and its value as a therapeutic target in ovarian cancer patients. Methods Reverse-transcription polymerase chain reaction (PCR and quantitative real-time PCR were used to detect MR-1 mRNA levels in tissue samples from 26 ovarian cancer patients and 25 controls with benign ovarian disease. Anti-MR-1 polyclonal antibodies were prepared, tested by ELISA and western blotting, and then used for immunohistochemical analysis of the tissue samples. Adhesion and invasion of 292T cells was also examined after transfection of a pMX-MR-1 plasmid. Knockdown of MR-1 expression was achieved after stable transfection of SKOV3 cells with a short hairpin DNA pGPU6/GFP/Neo plasmid against the MR-1 gene. In addition, SKOV3 cells were treated with paclitaxel and carboplatin, and a potential role for MR-1 as a therapeutic target was evaluated. Results MR-1 was overexpressed in ovarian cancer tissues and SKOV3 cells. 293T cells overexpressed MR-1, and cellular spread and invasion were enhanced after transfection of the pMX-MR-1 plasmid, suggesting that MR-1 is critical for ovarian cancer cell growth. Knockdown of MR-1 expression inhibited cell adhesion and invasion, and treatment with anti-cancer drugs decreased its expression in cancer cells. Taken together, these results provide the first evidence of the cellular and molecular mechanisms by which MR-1 might serve as a novel biological marker and potential therapeutic target for ovarian cancer. Conclusions MR-1 may be a biomarker for diagnosis of ovarian cancer. It may also be useful for monitoring of the effects of anti-cancer therapies. Further studies are needed to clarify whether MR-1 is an early

TU-EF-210-00: Therapeutic Strategies and Image Guidance

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-06-15

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

TU-EF-210-00: Therapeutic Strategies and Image Guidance

International Nuclear Information System (INIS)

2015-01-01

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare

Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer Treatment.

Science.gov (United States)

Atkinson, Stuart P; Andreu, Zoraida; Vicent, María J

2018-01-23

Polymer therapeutics (PTs) provides a potentially exciting approach for the treatment of many diseases by enhancing aqueous solubility and altering drug pharmacokinetics at both the whole organism and subcellular level leading to improved therapeutic outcomes. However, the failure of many polymer-drug conjugates in clinical trials suggests that we may need to stratify patients in order to match each patient to the right PT. In this concise review, we hope to assess potential PT-specific biomarkers for cancer treatment, with a focus on new studies, detection methods, new models and the opportunities this knowledge will bring for the development of novel PT-based anti-cancer strategies. We discuss the various "hurdles" that a given PT faces on its passage from the syringe to the tumor (and beyond), including the passage through the bloodstream, tumor targeting, tumor uptake and the intracellular release of the active agent. However, we also discuss other relevant concepts and new considerations in the field, which we hope will provide new insight into the possible applications of PT-related biomarkers.

Therapeutic hypothermia for acute stroke

DEFF Research Database (Denmark)

Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

2003-01-01

Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

Mechanism of oral tolerance induction to therapeutic proteins.

Science.gov (United States)

Wang, Xiaomei; Sherman, Alexandra; Liao, Gongxian; Leong, Kam W; Daniell, Henry; Terhorst, Cox; Herzog, Roland W

2013-06-15

Oral tolerance is defined as the specific suppression of humoral and/or cellular immune responses to an antigen by administration of the same antigen through the oral route. Due to its absence of toxicity, easy administration, and antigen specificity, oral tolerance is a very attractive approach to prevent unwanted immune responses that cause a variety of diseases or that complicate treatment of a disease. Many researchers have induced oral tolerance to efficiently treat autoimmune and inflammatory diseases in different animal models. However, clinical trials yielded limited success. Thus, understanding the mechanisms of oral tolerance induction to therapeutic proteins is critical for paving the way for clinical development of oral tolerance protocols. This review will summarize progress on understanding the major underlying tolerance mechanisms and contributors, including antigen presenting cells, regulatory T cells, cytokines, and signaling pathways. Potential applications, examples for therapeutic proteins and disease targets, and recent developments in delivery methods are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Therapeutic potential of eccentric exercises for age-related muscle atrophy

Directory of Open Access Journals (Sweden)

Jae-Young Lim

2016-09-01

Full Text Available Recent studies have focused on evidence-based interventions to prevent mobility decline and enhance physical performance in older adults. Several modalities, in addition to traditional strengthening programs, have been designed to manage age-related functional decline more effectively. In this study, we reviewed the current relevant literatures to assess the therapeutic potential of eccentric exercises for age-related muscle atrophy (sarcopenia. Age-related changes in human skeletal muscle, and their relationship with physical performance, are discussed with reference to in vitro physiologic and human biomechanics studies. An overview of issues relevant to sarcopenia is provided in the context of the recent consensus on the diagnosis and management of the condition. A decline in mobility among the aging population is closely linked with changes in the muscle force–velocity relationship. Interventions based specifically on increasing velocity and eccentric strength can improve function more effectively compared with traditional strengthening programs. Eccentric strengthening programs are introduced as a specific method for improving both muscle force and velocity. To be more effective, exercise interventions for older adults should focus on enhancing the muscle force–velocity relationship. Exercises that can be performed easily, and that utilize eccentric strength (which is relatively spared during the aging process, are needed to improve both muscle force and velocity.

Investigation of Stilbenoids as Potential Therapeutic Agents for Rotavirus Gastroenteritis

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Judith M. Ball

2015-01-01

Full Text Available Rotavirus (RV infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea hairy root cultures were induced to produce stilbenoids, which were purified by high performance countercurrent chromatography (HPCCC and analyzed by HPLC. HT29.f8 cells were infected with RV in the presence stilbenoids. Cell viability counts showed no cytotoxic effects on HT29.f8 cells. Viral infectivity titers were calculated and comparatively assessed to determine the effects of stilbenoid treatments. Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers. Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication. These studies show the therapeutic potential of the stilbenoids against RV replication.

Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer's disease.

Science.gov (United States)

Kobayashi, Yodai; Sugahara, Hirosuke; Shimada, Kousuke; Mitsuyama, Eri; Kuhara, Tetsuya; Yasuoka, Akihito; Kondo, Takashi; Abe, Keiko; Xiao, Jin-Zhong

2017-10-18

It has previously been shown that the consumption of probiotics may have beneficial effects not only on peripheral tissues but also on the central nervous system and behavior via the microbiota-gut-brain axis, raising the possibility that treatment with probiotics could be an effective therapeutic strategy for managing neurodegenerative disorders. In this study, we investigated the effects of oral administration of Bifidobacterium breve strain A1 (B. breve A1) on behavior and physiological processes in Alzheimer's disease (AD) model mice. We found that administration of B. breve A1 to AD mice reversed the impairment of alternation behavior in a Y maze test and the reduced latency time in a passive avoidance test, indicating that it prevented cognitive dysfunction. We also demonstrated that non-viable components of the bacterium or its metabolite acetate partially ameliorated the cognitive decline observed in AD mice. Gene profiling analysis revealed that the consumption of B. breve A1 suppressed the hippocampal expressions of inflammation and immune-reactive genes that are induced by amyloid-β. Together, these findings suggest that B. breve A1 has therapeutic potential for preventing cognitive impairment in AD.

Conotoxins that confer therapeutic possibilities

KAUST Repository

Essack, Magbubah

2012-06-04

Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 2012 by the authors; licensee MDPI.

Conotoxins that confer therapeutic possibilities

KAUST Repository

Essack, Magbubah; Bajic, Vladimir B.; Archer, John A.C.

2012-01-01

Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 2012 by the authors; licensee MDPI.

Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

Science.gov (United States)

Bai, Litao; Gao, Jialiang; Wei, Fan; Zhao, Jing; Wang, Danwei; Wei, Junping

2018-01-01

Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction. Many effects are attributed to ginsenosides, including gluconeogenesis reduction, improvement of insulin resistance, glucose transport, insulinotropic action, islet cell protection, hepatoprotective activity, anti-inflammatory effect, myocardial protection, lipid regulation, improvement of glucose tolerance, antioxidation, improvement of erectile dysfunction, regulation of gut flora metabolism, neuroprotection, anti-angiopathy, anti-neurotoxic effects, immunosuppression, and renoprotection effect. The molecular targets of these effects mainly contains GLUTs, SGLT1, GLP-1, FoxO1, TNF-α, IL-6, caspase-3, bcl-2, MDA, SOD, STAT5-PPAR gamma pathway, PI3K/Akt pathway, AMPK-JNK pathway, NF-κB pathway, and endoplasmic reticulum stress. Rg1, Rg3, Rb1, and compound K demonstrated the most promising therapeutic prospects as potential adjuvant medicines for the treatment of diabetes. This paper highlights the underlying pharmacological mechanisms of the

Lichen-derived compounds show potential for central nervous system therapeutics.

Science.gov (United States)

Reddy, R Gajendra; Veeraval, Lenin; Maitra, Swati; Chollet-Krugler, Marylène; Tomasi, Sophie; Dévéhat, Françoise Lohézic-Le; Boustie, Joël; Chakravarty, Sumana

2016-11-15

Natural products from lichens are widely investigated for their biological properties, yet their potential as central nervous system (CNS) therapeutic agents is less explored. The present study investigated the neuroactive properties of selected lichen compounds (atranorin, perlatolic acid, physodic acid and usnic acid), for their neurotrophic, neurogenic and acetylcholine esterase (AChE) activities. Neurotrophic activity (neurite outgrowth) was determined using murine neuroblastoma Neuro2A cells. A MTT assay was performed to assess the cytotoxicity of compounds at optimum neurotrophic activity. Neuro2A cells treated with neurotrophic lichen compounds were used for RT-PCR to evaluate the induction of genes that code for the neurotrophic markers BDNF and NGF. Immunoblotting was used to assess acetyl H3 and H4 levels, the epigenetic markers associated with neurotrophic and/or neurogenic activity. The neurogenic property of the compounds was determined using murine hippocampal primary cultures. AChE inhibition activity was performed using a modified Ellman's esterase method. Lichen compounds atranorin, perlatolic acid, physodic acid and (+)-usnic acid showed neurotrophic activity in a preliminary cell-based screening based on Neuro2A neurite outgrowth. Except for usnic acid, no cytotoxic effects were observed for the two depsides (atranorin and perlatolic acid) and the alkyl depsidone (physodic acid). Perlatolic acid appears to be promising, as it also exhibited AChE inhibition activity and potent proneurogenic activity. The neurotrophic lichen compounds (atranorin, perlatolic acid, physodic acid) modulated the gene expression of BDNF and NGF. In addition, perlatolic acid showed increased protein levels of acetyl H3 and H4 in Neuro2A cells. These lichen depsides and depsidones showed neuroactive properties in vitro (Neuro2A cells) and ex vivo (primary neural stem or progenitor cells), suggesting their potential to treat CNS disorders. Copyright © 2016 Elsevier Gmb

Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading.

Science.gov (United States)

Sutaria, Dhruvitkumar S; Badawi, Mohamed; Phelps, Mitch A; Schmittgen, Thomas D

2017-05-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.

CK1δ in lymphoma: gene expression and mutation analyses and validation of CK1δ kinase activity for therapeutic application

Directory of Open Access Journals (Sweden)

Brigitte Sophia Winkler

2015-02-01

Full Text Available The prognosis of lymphoid neoplasms has improved considerably during the last decades. However, treatment response for some lymphoid neoplasms is still poor, indicating the need for new therapeutic approaches. One promising new strategy is the inhibition of kinases regulating key signal transduction pathways, which are of central importance in tumorigenesis. Kinases of the CK1 family may represent an attractive drug target since CK1 expression and/or activity are associated with the pathogenesis of malignant diseases. Over the last years efforts were taken to develop highly potent and selective CK1-specific inhibitor compounds and their therapeutic potential has now to be proved in pre-clinical trials. Therefore, we analyzed expression and mutational status of CK1δ in several cell lines representing established lymphoma entities, and also measured the mRNA expression level in primary lymphoma tissue as well as non-neoplastic blood cells. For a selection of lymphoma cell lines we furthermore determined CK1δ kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors as a putative therapeutic option in the treatment of lymphoid neoplasms.

The endocrine system and sarcopenia: potential therapeutic benefits.

Science.gov (United States)

McIntire, Kevin L; Hoffman, Andrew R

2011-12-01

Age related muscle loss, known as sarcopenia, is a major factor in disability, loss of mobility and quality of life in the elderly. There are many proposed mechanisms of age-related muscle loss that include the endocrine system. A variety of hormones regulate growth, development and metabolism throughout the lifespan. Hormone activity may change with age as a result of reduced hormone secretion or decreased tissue responsiveness. This review will focus on the complex interplay between the endocrine system, aging and skeletal muscle and will present possible benefits of therapeutic interventions for sarcopenia.

Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

Directory of Open Access Journals (Sweden)

Tom J. Burdon

2011-01-01

Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment.

Science.gov (United States)

Kojima, Ryosuke; Bojar, Daniel; Rizzi, Giorgio; Hamri, Ghislaine Charpin-El; El-Baba, Marie Daoud; Saxena, Pratik; Ausländer, Simon; Tan, Kelly R; Fussenegger, Martin

2018-04-03

Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson's disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.

Potential game theory applications in radio resource allocation

CERN Document Server

Lã, Quang Duy; Soong, Boon-Hee

2016-01-01

This book offers a thorough examination of potential game theory and its applications in radio resource management for wireless communications systems and networking. The book addresses two major research goals: how to identify a given game as a potential game, and how to design the utility functions and the potential functions with certain special properties in order to formulate a potential game. After proposing a unifying mathematical framework for the identification of potential games, the text surveys existing applications of this technique within wireless communications and networking problems found in OFDMA 3G/4G/WiFi networks, as well as next-generation systems such as cognitive radios and dynamic spectrum access networks. Professionals interested in understanding the theoretical aspect of this specialized field will find Potential Game Theory a valuable resource, as will advanced-level engineering students. It paves the way for extensive and rigorous research exploration on a topic whose capacity for...

Therapeutic Potential of Human Adipose-Derived Stem/Stromal Cell Microspheroids Prepared by Three-Dimensional Culture in Non-Cross-Linked Hyaluronic Acid Gel.

Science.gov (United States)

Mineda, Kazuhide; Feng, Jingwei; Ishimine, Hisako; Takada, Hitomi; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Kanayama, Koji; Kato, Harunosuke; Mashiko, Takanobu; Hashimoto, Ichiro; Nakanishi, Hideki; Kurisaki, Akira; Yoshimura, Kotaro

2015-12-01

Three-dimensional culture of mesenchymal stem/stromal cells for spheroid formation is known to enhance their therapeutic potential for regenerative medicine. Spheroids were prepared by culturing human adipose-derived stem/stromal cells (hASCs) in a non-cross-linked hyaluronic acid (HA) gel and compared with dissociated hASCs and hASC spheroids prepared using a nonadherent dish. Preliminary experiments indicated that a 4% HA gel was the most appropriate for forming hASC spheroids with a relatively consistent size (20-50 µm) within 48 hours. Prepared spheroids were positive for pluripotency markers (NANOG, OCT3/4, and SOX-2), and 40% of the cells were SSEA-3-positive, a marker of the multilineage differentiating stress enduring or Muse cell. In contrast with dissociated ASCs, increased secretion of cytokines such as hepatocyte growth factor was detected in ASC spheroids cultured under hypoxia. On microarray ASC spheroids showed upregulation of some pluripotency markers and downregulation of genes related to the mitotic cell cycle. After ischemia-reperfusion injury to the fat pad in SCID mice, local injection of hASC spheroids promoted tissue repair and reduced the final atrophy (1.6%) compared with that of dissociated hASCs (14.3%) or phosphate-buffered saline (20.3%). Part of the administered hASCs differentiated into vascular endothelial cells. ASC spheroids prepared in a HA gel contain undifferentiated cells with therapeutic potential to promote angiogenesis and tissue regeneration after damage. This study shows the therapeutic value of human adipose-derived stem cell spheroids prepared in hyarulonic acid gel. The spheroids have various benefits as an injectable cellular product and show therapeutic potential to the stem cell-depleted conditions such as diabetic chronic skin ulcer. ©AlphaMed Press.

c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

International Nuclear Information System (INIS)

Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

2015-01-01

c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

Therapeutic potential of alpha-ketoglutarate against acetaminophen-induced hepatotoxicity in rats

Directory of Open Access Journals (Sweden)

Lalita Mehra

2016-01-01

Full Text Available Objective: Alpha-ketoglutarate (α-KG is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP induced toxicity in rats. Materials and Methods: Animals were divided into three groups of six animals each. Group I (Vehicle control: Normal Saline, Group II (APAP: A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + α-KG: APAP as in Group II with α-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP with oxidative stress markers including malondialdehyde (MDA, reduced glutathione (GSH, superoxide dismutase (SOD, catalase (CAT, and histopathology were analyzed. Results: The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of α-KG showed a significant (P < 0.05 reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of α-KG. Conclusion: These results indicate the possible therapeutic potential of α-KG in protecting liver damage by APAP in rats.

EFFICACY OF SOFT TISSUE APPLICATION, MANUALLY-THERAPEUTICAL TECHNIQUES FOR KNEE ARTHROKINEMATICS RECOVERY COMPLEX IN PATIENTS AFTER ARTHROSCOPIC MENISCECTOMY

Directory of Open Access Journals (Sweden)

Kostov Rostislav V

2015-07-01

Full Text Available Introduction: In this article we present the final effect of the application of complex soft tissue manually-treatment system for recovery of joint kinematics in patients with moderate and minimal protective period of rehabilitation after arthroscopic meniscectomy. Material and Methods: The study was conducted in 2005-2012 into three medical centers in Bulgaria: Blagoevgrad, Sofia and Pleven. The study included a total of 110 patients divided into three groups (Control and Experimental I and Experimental Group II who studied the effect of topical application of the manual therapeutic techniques compared to traditional rehabilitation methods applied. For testing the efficacy of a treatment approach in the three groups of patients, the results have processed by the method of variational analysis. Results: After analysis of results we find significantly more fully and without residual short violations recovery for all controlled parameters in patients who have implemented comprehensive manually-therapeutic treatment compared with control group patients. Conclusion: Application of adequate physiological and pedagogically grounded complex rehabilitation is required in patients after arthroscopic meniscectomy model with motor deficits in tractable routine rehabilitation. Observations allow us to offer a methodology for implementation in general practice rehabilitation in patients after meniscal ruptures treated by arthroscopic meniscectomy and motor deficits, intractable routine rehabilitation.

Multifunctional, chitosan-based nano therapeutics: design and application for two- and three-dimensional cell culture systems

Science.gov (United States)

Suarato, Giulia

There is a constant demand for sensitive and effective anti-cancer drug delivery systems, capable of detecting early-stage pathological conditions and increasing patient survival. Recently, chitosan-based drug delivery nanocomplexes have shown to smartly respond to the distinctive features of the tumor microenvironment, a complex network of extracellular molecules, stromal and endothelial cells, which supports the tumor formation and its metastatic invasion. Due to biocompatibility, easy chemical tailorability, and pH-responsiveness, chitosan has emerged as a promising candidate for the formulation of supramolecular multifunctional materials. The present study focuses on the design, fabrication and characterization of fluorescently labelled, hydrophobically modified glycol chitosan nano-micelles (HGC NPs), suitably tailored for the delivery of anti-neoplastic compounds to various tumor models. Doxorubicin-loaded HGC NPs have been delivered to a bone cancer model, both in monolayer and in 3D spheroid configuration, to assess for differences in the delivery profiles and in the therapeutic efficacy. Compared to the free drug, nanocomplexes showed rapid uptake and a more homogeneous distribution in 3D spheroids, a powerful cellular tool which recapitulates some of the in vivo tumor microenvironment features. In a second part of this thesis work, with the purpose of designing an active targeting tumor-homing nano-therapeutic system, HGC NPs have been linked, via avidin-biotin interaction, with a IVS4 peptide, a small molecule with inhibitory activity on MMP-14-mediated functions. An extensive study conducted on triple negative breast cancer cells in monolayer revealed the MMP-14-IVS4-HGC association at the cancer cell membrane, the preferential uptake, and the consequent impairment of protease-associated migratory ability. As an additional application of our engineered construct, HGC micelles have been decorated with a liver kinase B1 (LKB1), a critical kinase involved

Insights into cell-free therapeutic approach: Role of stem cell "soup-ernatant".

Science.gov (United States)

Raik, Shalini; Kumar, Ajay; Bhattacharyya, Shalmoli

2018-03-01

Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

When Medicine Meets Engineering—Paradigm Shifts in Diagnostics and Therapeutics

Directory of Open Access Journals (Sweden)

Aleidy Silva

2013-02-01

Full Text Available During the last two decades, the manufacturing techniques of microfluidics-based devices have been phenomenally advanced, offering unlimited potential for bio-medical technologies. However, the direct applications of these technologies toward diagnostics and therapeutics are still far from maturity. The present challenges lay at the interfaces between the engineering systems and the biocomplex systems. A precisely designed engineering system with narrow dynamic range is hard to seamlessly integrate with the adaptive biological system in order to achieve the design goals. These differences remain as the roadblock between two fundamentally non-compatible systems. This paper will not extensively review the existing microfluidic sensors and actuators; rather, we will discuss the sources of the gaps for integration. We will also introduce system interface technologies for bridging the differences to lead toward paradigm shifts in diagnostics and therapeutics.

Investigation of therapeutic potentials of some selected medicinal plants using neutron activation analysis

International Nuclear Information System (INIS)

Abubakar, Sani; Isa, Nasiru Fage; Usman, Ahmed Rufa’i; Khandaker, Mayeen Uddin; Abubakar, Nuraddeen

2015-01-01

Series of attempts were made to investigate concentrations of trace elements and their therapeutic properties in various medicinal plants. In this study, samples of some commonly used plants were collected from Bauchi State, Nigeria. They includes leaves of azadirachta indica (neem), Moringa Oleifera (moringa), jatropha curcas (purgin Nut), guiera senegalensis (custard apple) and anogeissus leiocarpus (African birch). These samples were analyzed for their trace elements contents with both short and long irradiation protocols of Instrumental Neutron Activation Analysis (INAA) at Nigerian Research Reactor-1 (NIRR-1) of Ahmadu Bello University, Zaria, Nigeria. The level of trace elements found varies from one sample to another, with some reported at hundreds of mg/Kg dry weight. The results have been compared with the available literature data. The presence of these trace elements indicates promising potentials of these plants for relief of certain ailments

Investigation of therapeutic potentials of some selected medicinal plants using neutron activation analysis

Energy Technology Data Exchange (ETDEWEB)

Abubakar, Sani; Isa, Nasiru Fage [Bayero University, Kano Nigeria (Nigeria); Usman, Ahmed Rufa’i [University of Malaya, Kuala Lumpur (Malaysia); Umaru Musa Yar’adua University, Katsina Nigeria (Nigeria); Khandaker, Mayeen Uddin [University of Malaya, Kuala Lumpur (Malaysia); Abubakar, Nuraddeen [Center for Energy Research and Training, Ahmadu Bello University, Zaria Nigeria (Nigeria)

2015-04-24

Series of attempts were made to investigate concentrations of trace elements and their therapeutic properties in various medicinal plants. In this study, samples of some commonly used plants were collected from Bauchi State, Nigeria. They includes leaves of azadirachta indica (neem), Moringa Oleifera (moringa), jatropha curcas (purgin Nut), guiera senegalensis (custard apple) and anogeissus leiocarpus (African birch). These samples were analyzed for their trace elements contents with both short and long irradiation protocols of Instrumental Neutron Activation Analysis (INAA) at Nigerian Research Reactor-1 (NIRR-1) of Ahmadu Bello University, Zaria, Nigeria. The level of trace elements found varies from one sample to another, with some reported at hundreds of mg/Kg dry weight. The results have been compared with the available literature data. The presence of these trace elements indicates promising potentials of these plants for relief of certain ailments.

Investigation of therapeutic potentials of some selected medicinal plants using neutron activation analysis

Science.gov (United States)

Abubakar, Sani; Usman, Ahmed Rufa'i.; Isa, Nasiru Fage; Khandaker, Mayeen Uddin; Abubakar, Nuraddeen

2015-04-01

Series of attempts were made to investigate concentrations of trace elements and their therapeutic properties in various medicinal plants. In this study, samples of some commonly used plants were collected from Bauchi State, Nigeria. They includes leaves of azadirachta indica (neem), Moringa Oleifera (moringa), jatropha curcas (purgin Nut), guiera senegalensis (custard apple) and anogeissus leiocarpus (African birch). These samples were analyzed for their trace elements contents with both short and long irradiation protocols of Instrumental Neutron Activation Analysis (INAA) at Nigerian Research Reactor-1 (NIRR-1) of Ahmadu Bello University, Zaria, Nigeria. The level of trace elements found varies from one sample to another, with some reported at hundreds of mg/Kg dry weight. The results have been compared with the available literature data. The presence of these trace elements indicates promising potentials of these plants for relief of certain ailments.

Concentration of 188Re-Perrhenate for Therapeutic Radiopharmaceuticals

International Nuclear Information System (INIS)

Bokhari, T.H.; Hina, S.; Ahmad, M.; Iqbal, M.

2013-01-01

Summary: Rhenium-188 (T1/2=16.9h) has great potential for a variety of therapeutic applications, including radionuclide synovectomy, oncology and bone pain palliation. The radioactive concentration of 188Re is dependent upon the specific activity of 188W, which dictates the bed size of the alumina/gel column. Due to the high content of inactive tungsten in neutron irradiated WO3, large columns containing aluminum oxide or gel are needed to prepare to double neutron capture based 188W/188Re generators that results in large elution volumes containing relatively high188W contents and low concentrations of /sup 188/ ReO/sub 4/ This decrease in specific volume of 188ReO/sub 4/ places a limitation because a high radioactive concentration of 188ReO4 - is always needed for filling angioplasty balloons or other therapeutic radiopharmaceuticals like188Re -EHDP 188Re -EDTMP, 188Re - MAG3 and 188Re -DTPA. We report post elution concentration of 188ReO4 - using in- house prepared lead cation exchange and alumina columns. Using these columns high bolus volume (10 mL saline) of 188ReO4 - can conveniently be concentrated in 1 mL of physiological saline for therapeutic use. (author)

Synthesis and optimization of chitosan nanoparticles: Potential applications in nanomedicine and biomedical engineering.

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Ghadi, Arezou; Mahjoub, Soleiman; Tabandeh, Fatemeh; Talebnia, Farid

2014-01-01

Chitosan nanoparticles have become of great interest for nanomedicine, biomedical engineering and development of new therapeutic drug release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity. The aim of the present study was to synthesis and optimize of the chitosan nanoparticles for industrial and biomedical applications. Fe3O4 was synthesized and optimized as magnetic core nanoparticles and then chitosan covered this magnetic core. The size and morphology of the nano-magnetic chitosan was analyzed by scanning electron microscope (SEM). Topography and size distribution of the nanoparticles were shown with two-dimensional and three-dimensional images of atomic force microscopy (AFM). The nanoparticles were analyzed using transmission electron microscopy (TEM). The chitosan nanoparticles prepared in the experiment exhibited white powder shape. The SEM micrographs of the nano-magnetic chitosan showed that they were approximately uniform spheres. The unmodified chitosan nanoparticles composed of clusters of nanoparticles with sizes ranging from 10 nm to 80 nm. AFM provides a three-dimensional surface profile. The TEM image showed physical aggregation of the chitosan nanoparticles. The results show that a novel chitosan nanoparticle was successfully synthesized and characterized. It seems that this nanoparticle like the other chitosan nano particles has potential applications for nanomedicine, biomedical engineering, industrial and pharmaceutical fields.

Therapeutic Nanodevices

Science.gov (United States)

Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

From POEM to POET: Applications and perspectives for submucosal tunnel endoscopy.

Science.gov (United States)

Chiu, Philip W Y; Inoue, Haruhiro; Rösch, Thomas

2016-12-01

Recent advances in submucosal endoscopy have unlocked a new horizon for potential development in diagnostic and therapeutic endoscopy. Increasing evidence has demonstrated that peroral endoscopic myotomy (POEM) is not only clinically feasible and safe, but also has excellent results in symptomatic relief of achalasia. The success of submucosal endoscopy in performance of tumor resection has confirmed the potential of this new area in diagnostic and therapeutic endoscopy. This article reviews the current applications and evidence, from POEM to peroral endoscopic tunnel resection (POET), while exploring the possible future clinical applications in this field. © Georg Thieme Verlag KG Stuttgart · New York.

Neutrophils: potential therapeutic targets in tularemia?

Directory of Open Access Journals (Sweden)

Lee-Ann H Allen

2013-12-01

Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

Bacteriophages-potential for application in wastewater treatment processes

International Nuclear Information System (INIS)

Withey, S.; Cartmell, E.; Avery, L.M.; Stephenson, T.

2005-01-01

Bacteriophages are viruses that infect and lyse bacteria. Interest in the ability of phages to control bacterial populations has extended from medical applications into the fields of agriculture, aquaculture and the food industry. Here, the potential application of phage techniques in wastewater treatment systems to improve effluent and sludge emissions into the environment is discussed. Phage-mediated bacterial mortality has the potential to influence treatment performance by controlling the abundance of key functional groups. Phage treatments have the potential to control environmental wastewater process problems such as: foaming in activated sludge plants; sludge dewaterability and digestibility; pathogenic bacteria; and to reduce competition between nuisance bacteria and functionally important microbial populations. Successful application of phage therapy to wastewater treatment does though require a fuller understanding of wastewater microbial community dynamics and interactions. Strategies to counter host specificity and host cell resistance must also be developed, as should safety considerations regarding pathogen emergence through transduction

Nucleotide excision repair is a potential therapeutic target in multiple myeloma

Science.gov (United States)

Szalat, R; Samur, M K; Fulciniti, M; Lopez, M; Nanjappa, P; Cleynen, A; Wen, K; Kumar, S; Perini, T; Calkins, A S; Reznichenko, E; Chauhan, D; Tai, Y-T; Shammas, M A; Anderson, K C; Fermand, J-P; Arnulf, B; Avet-Loiseau, H; Lazaro, J-B; Munshi, N C

2018-01-01

Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM. PMID:28588253

Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

Directory of Open Access Journals (Sweden)

Anja Geiselhart

2012-01-01

Full Text Available Fanconi anemia (FA is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC. This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients.

Development of therapeutic antibodies to G protein-coupled receptors and ion channels: Opportunities, challenges and their therapeutic potential in respiratory diseases.

Science.gov (United States)

Douthwaite, Julie A; Finch, Donna K; Mustelin, Tomas; Wilkinson, Trevor C I

2017-01-01

The development of recombinant antibody therapeutics continues to be a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Therapeutic drug targets such as soluble cytokines, growth factors and single transmembrane spanning receptors have been successfully targeted by recombinant monoclonal antibodies and the development of new product candidates continues. Despite this growth, however, certain classes of important disease targets have remained intractable to therapeutic antibodies due to the complexity of the target molecules. These complex target molecules include G protein-coupled receptors and ion channels which represent a large target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these important regulators of cell function. Given this opportunity, a significant effort has been applied to address the challenges of targeting these complex molecules and a number of targets are linked to the pathophysiology of respiratory diseases. In this review, we provide a summary of the importance of GPCRs and ion channels involved in respiratory disease and discuss advantages offered by antibodies as therapeutics at these targets. We highlight some recent GPCRs and ion channels linked to respiratory disease mechanisms and describe in detail recent progress made in the strategies for discovery of functional antibodies against challenging membrane protein targets such as GPCRs and ion channels. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiolabelled multifunctional nanoparticles for targeted diagnostic and therapeutic applications in oncology

International Nuclear Information System (INIS)

Rangger, C.

2013-01-01

Nanoparticles, liposomes in particular, have gained great attention as easily engineerable nanoscale systems with distinct properties, offering an ideal platform for a variety of diagnostic and therapeutic applications. The aim of this PhD thesis was the design, synthesis as well as the in vitro and in vivo evaluation of several radiolabelled multifunctional liposomal nanoparticles for the targeted imaging of tumour cells and tumour-induced angiogenesis. Radiolabelling methods for different radionuclides were developed and the liposomes were functionalised with polyethylene glycol (PEG) to improve the pharmacokinetic profile. Targeting sequences such as the tripeptide Arg-Gly-Asp (RGD), the neuropeptide substance P (SP), the somatostatin analogue tyrosine-3-octreotide (TOC), and the vasoactive intestinal peptide (VIP) were tested for their applicability as tools for the targeted delivery of imaging agents. Finally, by the combination of two targeting sequences, namely RGD and SP, on one liposome multireceptor-targeting (hybrid-targeting) was investigated. These multifunctional vehicles were also functionalized with imaging labels for the detection and imaging of tumours by single photon emission computed tomography (SPECT), fluorescence microscopy as well as magnetic resonance (MR) imaging. The liposomes developed in this thesis showed multifunctional properties combining several imaging approaches with specific targeting for oncological applications. In vitro behaviour, e.g., receptor binding could be improved, resulting in optimised targeting shown both by the radiolabel and fluorescent label. However, the in vivo properties, especially the tumour targeting characteristics remained suboptimal, revealing the challenges of targeting approaches in nanoscience. Nonetheless, these results brought important insights for the development and optimisation of multifunctional nanocarriers. (author) [de

Therapeutic potential of agmatine for CNS disorders.

Science.gov (United States)

Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S

2017-09-01

Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Applying a soft-robotic glove as assistive device and training tool with games to support hand function after stroke: Preliminary results on feasibility and potential clinical impact.

Science.gov (United States)

Prange-Lasonder, Gerdienke B; Radder, Bob; Kottink, Anke I R; Melendez-Calderon, Alejandro; Buurke, Jaap H; Rietman, Johan S

2017-07-01

Recent technological developments regarding wearable soft-robotic devices extend beyond the current application of rehabilitation robotics and enable unobtrusive support of the arms and hands during daily activities. In this light, the HandinMind (HiM) system was developed, comprising a soft-robotic, grip supporting glove with an added computer gaming environment. The present study aims to gain first insight into the feasibility of clinical application of the HiM system and its potential impact. In order to do so, both the direct influence of the HiM system on hand function as assistive device and its therapeutic potential, of either assistive or therapeutic use, were explored. A pilot randomized clinical trial was combined with a cross-sectional measurement (comparing performance with and without glove) at baseline in 5 chronic stroke patients, to investigate both the direct assistive and potential therapeutic effects of the HiM system. Extended use of the soft-robotic glove as assistive device at home or with dedicated gaming exercises in a clinical setting was applicable and feasible. A positive assistive effect of the soft-robotic glove was proposed for pinch strength and functional task performance 'lifting full cans' in most of the five participants. A potential therapeutic impact was suggested with predominantly improved hand strength in both participants with assistive use, and faster functional task performance in both participants with therapeutic application.

Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology".

Science.gov (United States)

Insel, Paul A; Amara, Susan G; Blaschke, Terrence F; Meyer, Urs A

2017-01-06

Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.

RNA Interference and its therapeutic applications

Directory of Open Access Journals (Sweden)

Srinivasa Rao T

2011-10-01

Full Text Available RNAi is a potent method, requiring only a few molecules of dsRNA per cell to silence the expression. Long molecules of double stranded RNA (dsRNA trigger the process. The dsRNA comes from virus and transposon activity in natural RNAi process, while it can be injected in the cells in experimental processes. The strand of the dsRNA that is identical in sequence to a region in target mRNA molecule is called the sense strand, and the other strand which is complimentary is termed the antisense strand. An enzyme complex called DICER thought to be similar to RNAase III then recognizes dsRNA, and cuts it into roughly 22- nucleotide long fragments. These fragments termed siRNAs for “small interfering RNAs” remain in double stranded duplexes with very short 3' overhangs. However, only one of the two strands, known as the guide strand or antisense strand binds the argonaute protein of RNA-induced silencing complex (RISC and target the complementary mRNA resulting gene silencing. The other anti-guide strand or passenger strand is degraded as a RISC substrate during the process of RISC activation. This form of RNAi is termed as post transcriptional gene silencing (PTGS; other forms are also thought to operate at the genomic or transcriptional level in some organisms. In mammals dsRNA longer than 30 base pairs induces a nonspecific antiviral response. This so-called interferon response results in a nonspecific arrest in translation and induction of apoptosis. This cascade induces a global non-specific suppression of translation, which in turn triggers apoptosis. Interestingly, dsRNAs less than 30 nt in length do not activate the antiviral response and specifically switched off genes in human cells without initiating the acute phase response. Thus these siRNAs are suitable for gene target validation and therapeutic applications in many species, including humans. [Vet. World 2011; 4(5.000: 225-229

Punica granatum fabricated platinum nanoparticles: A therapeutic pill for breast cancer

Science.gov (United States)

Jha, Babita; Rao, Mugdha; Chattopadhyay, A.; Bandyopadhyay, A.; Prasad, K.; Jha, Anal K.

2018-05-01

The current research highlights the fabrication of biocompatible platinum nanoparticles (Pt NPs) in first hand from arils of Punica granatum by using green chemistry approach. Formation of Pt NPs was determined by UV-visible, X-ray diffraction, and FTIR techniques. The anti-cancer potential of fabricated Pt NPs was evaluated by MTT assay on MCF7 and MDA-MB-231 breast cancer cell lines. This work is foreshadowing the prospect of Pt NPs application as a therapeutic drug for cancer treatment.

The potential of AR-V7 as a therapeutic target.

Science.gov (United States)

Uo, Takuma; Plymate, Stephen R; Sprenger, Cynthia C

2018-03-01

The androgen receptor variant AR-V7 is gaining attention as a potential predictive marker for as well as one of the resistance mechanisms to the most current anti-androgen receptor (AR) therapies in castration-resistant prostate cancer (CRPC). Accordingly, development of next-generation drugs that directly or indirectly target AR-V7 signaling is urgently needed. Areas covered: We review proposed mechanisms of drug resistance in relation to AR-V7 status, the mechanisms of generation of AR-V7, and its transcriptome, cistrome, and interactome. Pharmacological agents that interfere with these processes are being developed to counteract pan AR and AR-V7-specific signaling. Also, we address the current status of the preclinical and clinical studies targeting AR-V7 signaling. Expert opinion: AR-V7 is considered a true therapeutic target, however, it remains to be determined if AR-V7 is a principal driver or merely a bystander requiring heterodimerization with co-expressed full-length AR or other variants to drive CRPC progression. While untangling AR-V7 biology, multiple strategies are being developed to counteract drug resistance, including selective blockade of AR-V7 signaling as well as inhibition of pan-AR signaling. Ideally anti-AR therapies will be combined with agents preventing activation and enrichment of AR negative tumor cells that are otherwise depressed by AR activity axis.

Therapeutic potential of gel-based injectables for vocal fold regeneration

Science.gov (United States)

Bartlett, Rebecca S.; Thibeault, Susan L.; Prestwich, Glenn D.

2012-01-01

Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. PMID:22456756

Function and Therapeutic Potential of Mesenchymal Stem Cells in Atherosclerosis

Directory of Open Access Journals (Sweden)

Feifei Li

2017-05-01

Full Text Available Atherosclerosis is a complicated disorder and largely attributable to dyslipidaemia and chronic inflammation. Despite therapeutic advances over past decades, atherosclerosis remains the leading cause of mortality worldwide. Due to their capability of immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs have evolved as an attractive therapeutic agent in various diseases including atherosclerosis. Accumulating evidences support the protective role of MSCs in all stages of atherosclerosis. In this review, we highlight the current understanding of MSCs including their characteristics such as molecular markers, tissue distribution, migratory property, immune-modulatory competence, etc. We also summarize MSC functions in animal models of atherosclerosis. MSC transplantation is able to modulate cytokine and chemokine secretion, reduce endothelial dysfunction, promote regulatory T cell function, decrease dyslipidemia, and stabilize vulnerable plaques during atherosclerosis development. In addition, MSCs may migrate to lesions where they develop into functional cells during atherosclerosis formation. Finally, the perspectives of MSCs in clinical atherosclerosis therapy are discussed.

Therapeutic potential of gel-based injectables for vocal fold regeneration

International Nuclear Information System (INIS)

Bartlett, Rebecca S; Thibeault, Susan L; Prestwich, Glenn D

2012-01-01

Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. (paper)

DEPDC5 as a potential therapeutic target for epilepsy.

Science.gov (United States)

Myers, Kenneth A; Scheffer, Ingrid E

2017-06-01

Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy. Areas covered: This review summarizes the mTOR pathway, including regulators and downstream effectors, emphasizing recent developments in the understanding of the complex role of the GATOR1 complex. We review the epilepsy types associated with mTOR overactivity, including tuberous sclerosis, polyhydramnios megalencephaly symptomatic epilepsy, cortical dysplasia, non-lesional focal epilepsy and post-traumatic epilepsy. Currently available mTOR inhibitors are discussed, primarily rapamycin analogs and ATP competitive mTOR inhibitors. Expert opinion: DEPDC5 is an attractive therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely be anti-epileptogenic and more selective than currently available mTOR inhibitors. Therapeutic effects might be synergistic with certain existing dietary therapies, including the ketogenic diet.

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

International Nuclear Information System (INIS)

Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

2012-01-01

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

Energy Technology Data Exchange (ETDEWEB)

Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: David.Ammar@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: Chapla.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: Puneet.Tyagi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: Uday.Kompella@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: Robert.Enzenauer@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: Mark.Petrash@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)

2012-10-01

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

Terapeutický potenciál vzťahov z hľadiska dvoch rovín komunikácie (Therapeutic Potential of Relationships

Directory of Open Access Journals (Sweden)

Reginald A. Slavkovský

2013-06-01

Full Text Available In my paper I deal with connections between relationships, their philosophical reflection and therapy. As a relationship I think here particularly a (therapeutic relationship between two or more people, but also man's relationship to other realities and to himself. It turns out that the basic dynamics of the therapeutic relationship of somebody to himself or herself is determined by entering into specific relationships to others, especially to other people. Different methodological approaches can in different ways contribute to the understanding of the therapeutic dimension of relationships. A look at interpersonal relations from the perspective of communication presents significant contribution to the understanding of these interpersonal relations. Therapeutic approach through relationship is a good option anywhere the pathology of living out and of behaviour probably has its roots in the relationships. In order to understand various types of pathology in communication, and based on that then to search for an appropriate therapeutic approach, it is useful to distinguish two levels of communication, which different authors label in different ways, because they come to them through diverse paths, often as a result of analogy with other area of life. I introduce some concepts of analysis of communication in terms of their therapeutic potential.

Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma

DEFF Research Database (Denmark)

Serakinci, Nedime; Christensen, Rikke; Sørensen, Flemming Brandt

2011-01-01

The field of stem cell biology continues to evolve by characterization of further types of stem cells and by exploring their therapeutic potential for experimental and clinical applications. Human mesenchymal stem cells (hMSCs) are one of the most promising candidates simply because...... better understanding and in vivo supporting data. The homing ability of hMSCs was investigated by creating a human xenograft model by transplanting an ovarian cancer cell line into immunocompromised mice. Then, genetically engineered hMSC-telo1 cells were injected through the tail vein...

Nanomedicine applications in women's health: state of the art.

Science.gov (United States)

Lloyd-Parry, Oliver; Downing, Charlotte; Aleisaei, Eisa; Jones, Celine; Coward, Kevin

2018-01-01

State-of-the-art applications of nanomedicine have the potential to revolutionize the diagnosis, prevention, and treatment of a range of conditions and diseases affecting women's health. In this review, we provide a synopsis of potential applications of nanomedicine in some of the most dominant fields of women's health: mental health, sexual health, reproductive medicine, oncology, menopause-related conditions and dementia. We explore published studies arising from in vitro and in vivo experiments, and clinical trials where available, to reveal novel and highly promising therapeutic applications of nanomedicine in these fields. For the first time, we summarize the growing body of evidence relating to the use of nanomaterials as experimental tools for the detection, prevention, and treatment of significant diseases and conditions across the life course of a cisgender woman, from puberty to menopause; revealing the far-reaching and desirable theoretical impact of nanomedicine across different medical disciplines. We also present an overview of potential concerns regarding the therapeutic applications of nanomedicine and the factors currently restricting the growth of applied nanomedicine.

Kinase inhibitors of the IGF-1R as a potential therapeutic agent for rheumatoid arthritis.

Science.gov (United States)

Tsushima, Hiroshi; Morimoto, Shinji; Fujishiro, Maki; Yoshida, Yuko; Hayakawa, Kunihiro; Hirai, Takuya; Miyashita, Tomoko; Ikeda, Keigo; Yamaji, Ken; Takamori, Kenji; Takasaki, Yoshinari; Sekigawa, Iwao; Tamura, Naoto

2017-08-01

We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro. Cell proliferation was evaluated by cell count and immunoblotting. The expression of IGF-1 and IGF-1 R was evaluated by RT-PCR. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay, and osteoclast-specific enzyme production. Angiogenesis was evaluated by a tube formation assay using human umbilical vein endothelial cells (HUVECs). The proliferation of MH7A cells was found to be inhibited in the presence of NVP-AEW541, and the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was downregulated in MH7A cells. IGF-1 and IGF-1 R mRNA expression levels were upregulated during formation of M-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)-mediated osteoclast formation. Moreover, osteoclastogenesis was suppressed in the presence of NVP-AEW541. The formation of the tubular network was enhanced by IGF-1, and this effect was neutralized by NVP-ARE541. Our findings suggest that NVP-AEW541 may be utilized as a potential therapeutic agent in the treatment of RA.

CXCR4-specific Nanobodies as potential therapeutics for WHIM syndrome

DEFF Research Database (Denmark)

de Wit, Raymond H; Heukers, Raimond; Brink, Hendrik

2017-01-01

WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: Warts, Hypogammaglobulinemia, Infections and Myelokathexis. The disease is primarily caused by C-terminal truncation mutations of the chemokine receptor CXCR4. Consequently, these CXCR4-WHIM...... as alternative therapeutics for CXCR4-associated diseases like WHIM syndrome....

Differences in abuse potential of ADHD drugs measured by contrasting poison centre and therapeutic use data.

Science.gov (United States)

Jensen, Louise Schow; Pagsberg, Anne Katrine; Dalhoff, Kim Peder

2015-05-01

Atomoxetine (ATX) is the treatment of choice for attention deficit hyperactivity disorders with co-morbid risk of drug abuse, although its abuse potential needs to be qualified. The purpose of this study is to analyse ATX misuse in relation to therapeutic use and compare our results with that of methylphenidate (MPH). Data on enquiries were extracted from the Danish Poison Information Centre database (January 2006 to June 2012), while data on therapeutic use were provided by the Danish State Serum Institute (2007-2011). The study included 28 ATX and 394 MPH enquiries. Frequency of ATX enquiries did not show a significant correlation to either sale or number of treated patients but for MPH, both correlations were significant (p = 0.001 and p = 0.0008, respectively). The enquiries/number of treated patients relationship differed significantly between ATX and MPH (p = 0.018), but not the enquiries/sale relationship. The proportion of exposures motivated by recreational drug use was significantly lower for ATX (19%) than that for MPH (40%) (p = 0.038). These results suggest that ATX is used by adults for non-medical purposes including recreational use, but to a lesser extent than MPH.

Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.

Science.gov (United States)

Daige, Christopher L; Wiggins, Jason F; Priddy, Leslie; Nelligan-Davis, Terri; Zhao, Jane; Brown, David

2014-10-01

miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR34a targets. The administration of the formulated miR34a mimic caused significant tumor growth inhibition in both models of liver cancer, and tumor regression was observed in more than one third of the animals. The antitumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers. ©2014 American Association for Cancer Research.

Application of Disposable Bag Bioreactors in Tissue Engineering and for the Production of Therapeutic Agents

Science.gov (United States)

Eibl, R.; Eibl, D.

In order to increase process efficiency, many pharmaceutical and biotechnology companies have introduced disposable bag technology over the last 10 years. Because this technology also greatly reduces the risk of cross-contamination, disposable bags are preferred in applications in which an absolute or improved process safety is a necessity, namely the production of functional tissue for implantation (tissue engineering), the production of human cells for the treatment of cancer and immune system diseases (cellular therapy), the production of viruses for gene therapies, the production of therapeutic proteins, and veterinary as well as human vaccines.

Therapeutic ultrasound - The healing sound and its applications in oral diseases: The review of literature

Directory of Open Access Journals (Sweden)

Jyothirmai Koneru

2012-01-01

Full Text Available The application of medical ultrasound was mainly centered on the soft tissue diagnostic imaging until now. Recently, its use has been widened and adopted for various therapeutic purposes. It has been reported to facilitate the healing of bone fractures, wounds, apthous ulcers and temporomandibular disorders. In addition, ultrasound has also been shown to facilitate delivery of chemotherapeutic drugs into tumors, promote gene therapy to targeted tissues, and deliver thrombolytic drugs into blood clots. This article reviews the principles and current status of ultrasound-based treatments.

Potential Therapeutic Uses of p19ARF Mimics in Mammary Tumorigenesis

National Research Council Canada - National Science Library

Hann, Stephen R

2005-01-01

Since many breast tumors have deregulated c-Myc we hypothesize that an ARF mimic would be a valuable therapeutic agent for breast cancer to inhibit c-Myc-induced transformation/tumorigenesis without...

Differential solubility of curcuminoids in serum and albumin solutions: implications for analytical and therapeutic applications

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Quitschke Wolfgang W

2008-11-01

Full Text Available Abstract Background Commercially available curcumin preparations contain a mixture of related polyphenols, collectively referred to as curcuminoids. These encompass the primary component curcumin along with its co-purified derivatives demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids have numerous biological activities, including inhibition of cancer related cell proliferation and reduction of amyloid plaque formation associated with Alzheimer disease. Unfortunately, the solubility of curcuminoids in aqueous solutions is exceedingly low. This restricts their systemic availability in orally administered formulations and limits their therapeutic potential. Results Methods are described that achieve high concentrations of soluble curcuminoids in serum. Solid curcuminoids were either mixed directly with serum, or they were predissolved in dimethyl sulfoxide and added as aliquots to serum. Both methods resulted in high levels of curcuminoid-solubility in mammalian sera from different species. However, adding aliquots of dimethyl sulfoxide-dissolved curcuminoids to serum proved to be more efficient, producing soluble curcuminoid concentrations of at least 3 mM in human serum. The methods also resulted in the differential solubility of individual curcuminoids in serum. The addition of dimethyl sulfoxide-dissolved curcuminoids to serum preferentially solubilized curcumin, whereas adding solid curcuminoids predominantly solubilized bisdemethoxycurcumin. Either method of solubilization was equally effective in inhibiting dose-dependent HeLa cell proliferation in culture. The maximum concentration of curcuminoids achieved in serum was at least 100-fold higher than that required for inhibiting cell proliferation in culture and 1000-fold higher than the concentration that has been reported to prevent amyloid plaque formation associated with Alzheimer disease. Curcuminoids were also highly soluble in solutions of purified albumin, a major component of

Role of MicroRNA-1 in Human Cancer and Its Therapeutic Potentials

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Chao Han

2014-01-01

Full Text Available While the mechanisms of human cancer development are not fully understood, evidence of microRNA (miRNA, miR dysregulation has been reported in many human diseases, including cancer. miRs are small noncoding RNA molecules that regulate posttranscriptional gene expression by binding to complementary sequences in the specific region of gene mRNAs, resulting in downregulation of gene expression. Not only are certain miRs consistently dysregulated across many cancers, but they also play critical roles in many aspects of cell growth, proliferation, metastasis, apoptosis, and drug resistance. Recent studies from our group and others revealed that miR-1 is frequently downregulated in various types of cancer. Through targeting multiple oncogenes and oncogenic pathways, miR-1 has been demonstrated to be a tumor suppressor gene that represses cancer cell proliferation and metastasis and promotes apoptosis by ectopic expression. In this review, we highlight recent findings on the aberrant expression and functional significance of miR-1 in human cancers and emphasize its significant values for therapeutic potentials.

[Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism].

Science.gov (United States)

Valdespino-Gómez, Víctor Manuel; Valdespino-Castillo, Patricia Margarita; Valdespino-Castillo, Víctor Edmundo

2015-01-01

Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Therapeutic Process and Outcome: The Interplay of Research

Science.gov (United States)

Campbel, Holly

2008-01-01

From Freud through to modern times researchers have aimed to develop a clearer understanding of therapeutic processes and outcomes. Despite this continued interest in the field, the representation of psychotherapy processes and the applicability of research findings and recommendations to the therapeutic field continue to prove difficult.…

Therapeutic intervention scoring system-28 (TISS-28: diretrizes para aplicação Therapeutic intervention scoring system-28 (tiss-28: directrices para su aplicación Therapeutic intervention scoring system-28 (tiss-28: directions for application

Directory of Open Access Journals (Sweden)

Katia Grillo Padilha

2005-06-01

Full Text Available O Therapeutic Intervention Scoring System-28 (TISS-28 é um instrumento que permite dimensionar carga de trabalho de enfermagem em Unidade de Terapia Intensiva e estimar gravidade da doença. Apresenta-se nesta publicação as definições operacionais para sua aplicação, proposta por um grupo de especialistas na área, com vistas a uniformizar o significado de cada um dos itens e evitar vieses de interpretação.El Therapeutic Intervention Scoring System-28 (TISS-28 es un instrumento que permite dimensionar carga de trabajo de enfermería en una Unidad de Terapia Intensiva y estimar la gravedad de la enfermedad. Se presenta en esta publicación las definiciones operacionales para su aplicación, propuesta por un grupo de especialistas en el área, con vistas a uniformizar el significado de cada uno de los items y evitar sesgos de interpretación.Therapeutic Intervention Scoring System-28 (TISS-28 is a tool that enables the measurement of the nursing work load in Intensive Care Units and the estimate of how grave the disease is. In this study are presented the operational definitions for its application, proposed by a group of specialists in the area, with the aim of rendering uniform the meaning of each of the items and preventing interpretation biases.

Llama nanoantibodies with therapeutic potential against human norovirus diarrhea.

Science.gov (United States)

Garaicoechea, Lorena; Aguilar, Andrea; Parra, Gabriel I; Bok, Marina; Sosnovtsev, Stanislav V; Canziani, Gabriela; Green, Kim Y; Bok, Karin; Parreño, Viviana

2015-01-01

Noroviruses are a major cause of acute gastroenteritis, but no vaccines or therapeutic drugs are available. Llama-derived single chain antibody fragments (also called VHH) are small, recombinant monoclonal antibodies of 15 kDa with several advantages over conventional antibodies. The aim of this study was to generate recombinant monoclonal VHH specific for the two major norovirus (NoV) genogroups (GI and GII) in order to investigate their potential as immunotherapy for the treatment of NoV diarrhea. To accomplish this objective, two llamas were immunized with either GI.1 (Norwalk-1968) or GII.4 (MD2004) VLPs. After immunization, peripheral blood lymphocytes were collected and used to generate two VHH libraries. Using phage display technology, 10 VHH clones specific for GI.1, and 8 specific for GII.4 were selected for further characterization. All VHH recognized conformational epitopes in the P domain of the immunizing VP1 capsid protein, with the exception of one GII.4 VHH that recognized a linear P domain epitope. The GI.1 VHHs were highly specific for the immunizing GI.1 genotype, with only one VHH cross-reacting with GI.3 genotype. The GII.4 VHHs reacted with the immunizing GII.4 strain and showed a varying reactivity profile among different GII genotypes. One VHH specific for GI.1 and three specific for GII.4 could block the binding of homologous VLPs to synthetic HBGA carbohydrates, saliva, and pig gastric mucin, and in addition, could inhibit the hemagglutination of red blood cells by homologous VLPs. The ability of Nov-specific VHHs to perform well in these surrogate neutralization assays supports their further development as immunotherapy for NoV treatment and immunoprophylaxis.

Emerging nanotechnology based strategies for diagnosis and therapeutics of urinary tract infections: A review.

Science.gov (United States)

Kumar, M S; Das, A P

2017-11-01

At present, various diagnostic and therapeutic approaches are available for urinary tract infections. But, still the quest for development of more rapid, accurate and reliable approach is an unending process. The pathogens, especially uropathogens are adapting to new environments and antibiotics day by day rapidly. Therefore, urinary tract infections are evolving as hectic and difficult to eradicate, increasing the economic burden to the society. The technological advances should be able to compete the adaptability characteristics of microorganisms to combat their growth in new environments and thereby preventing their infections. Nanotechnology is at present an extensively developing area of immense scientific interest since it has diverse potential applications in biomedical field. Nanotechnology may be combined with cellular therapy approaches to overcome the limitations caused by conventional therapeutics. Nanoantibiotics and drug delivery using nanotechnology are currently growing areas of research in biomedical field. Recently, various categories of antibacterial nanoparticles and nanocarriers for drug delivery have shown their potential in the treatment of infectious diseases. Nanoparticles, compared to conventional antibiotics, are more beneficial in terms of decreasing toxicity, prevailing over resistance and lessening costs. Nanoparticles present long term therapeutic effects since they are retained in body for relatively longer periods. This review focuses on recent advances in the field of nanotechnology, principally emphasizing diagnostics and therapeutics of urinary tract infections. Copyright © 2017 Elsevier B.V. All rights reserved.

A derating method for therapeutic applications of high intensity focused ultrasound

Science.gov (United States)

Bessonova, O. V.; Khokhlova, V. A.; Canney, M. S.; Bailey, M. R.; Crum, L. A.

2010-05-01

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. A new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal wave-forms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue.

Therapeutic Perspectives of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops

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Kateřina Štulíková

2018-03-01

Full Text Available Hop (Humulus lupulus L., as a key ingredient for beer brewing, is also a source of many biologically active molecules. A notable compound, 8-prenylnaringenin (8-PN, structurally belonging to the group of prenylated flavonoids, was shown to be a potent phytoestrogen, and thus, became the topic of active research. Here, we overview the pharmacological properties of 8-PN and its therapeutic opportunities. Due to its estrogenic effects, administration of 8-PN represents a novel therapeutic approach to the treatment of menopausal and post-menopausal symptoms that occur as a consequence of a progressive decline in hormone levels in women. Application of 8-PN in the treatment of menopause has been clinically examined with promising results. Other activities that have already been assessed include the potential to prevent bone-resorption or inhibition of tumor growth. On the other hand, the use of phytoestrogens is frequently questioned regarding possible adverse effects associated with long-term consumption. In conclusion, we emphasize the implications of using 8-PN in future treatments of menopausal and post-menopausal symptoms, including the need for precise evidence and further investigations to define the safety risks related to its therapeutic use.

Opposite Interplay Between the Canonical WNT/β-Catenin Pathway and PPAR Gamma: A Potential Therapeutic Target in Gliomas.

Science.gov (United States)

Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

2018-06-01

In gliomas, the canonical Wingless/Int (WNT)/β-catenin pathway is increased while peroxisome proliferator-activated receptor gamma (PPAR-γ) is downregulated. The two systems act in an opposite manner. This review focuses on the interplay between WNT/β-catenin signaling and PPAR-γ and their metabolic implications as potential therapeutic target in gliomas. Activation of the WNT/β-catenin pathway stimulates the transcription of genes involved in proliferation, invasion, nucleotide synthesis, tumor growth, and angiogenesis. Activation of PPAR-γ agonists inhibits various signaling pathways such as the JAK/STAT, WNT/β-catenin, and PI3K/Akt pathways, which reduces tumor growth, cell proliferation, cell invasiveness, and angiogenesis. Nonsteroidal anti-inflammatory drugs, curcumin, antipsychotic drugs, adiponectin, and sulforaphane downregulate the WNT/β-catenin pathway through the upregulation of PPAR-γ and thus appear to provide an interesting therapeutic approach for gliomas. Temozolomide (TMZ) is an antiangiogenic agent. The downstream action of this opposite interplay may explain the TMZ-resistance often reported in gliomas.

Avian Diagnostic and Therapeutic Antibodies

Energy Technology Data Exchange (ETDEWEB)

Bradley, David Sherman [UND SMHS

2012-12-31

A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

Design Considerations in Therapeutic Exergaming

OpenAIRE

Doyle, Julie; Kelly, Daniel; Caulfield, B.

2011-01-01

In this paper we discuss the importance of feedback in therapeutic exergaming. It is widely believed that exergaming benefits the patient in terms of encouraging adherence and boosting the patient’s confidence of correct execution and feedback is essential in achieving these. However, feedback and in particular visual feedback, may also have potential negative effects on the quality of the exercise. We describe in this paper a prototype single-sensor therapeutic exergame that we have develope...

Japan's patent issues relating to life science therapeutic inventions.

Science.gov (United States)

Tessensohn, John A

2014-09-01

Japan has made 'innovation in science and technology' as one of its central pillars to ensure high growth in its next stage of economic development and its life sciences market which hosts regenerative medicine was proclaimed to be 'the best market in the world right now.' Although life science therapeutic inventions are patentable subject matter under Japanese patent law, there are nuanced obviousness and enablement challenges under Japanese patent law that can be surmounted in view of some encouraging Japanese court developments in fostering a pro-patent applicant environment in the life sciences therapeutic patent field. Nevertheless, great care must be taken when drafting and prosecuting such patent applications in the world's second most important life sciences therapeutic market.

Targeting methionine cycle as a potential therapeutic strategy for immune disorders.

Science.gov (United States)

Li, Heng; Lu, Huimin; Tang, Wei; Zuo, Jianping

2017-08-23

Methionine cycle plays an essential role in regulating many cellular events, especially transmethylation reactions, incorporating the methyl donor S-adenosylmethionine (SAM). The transmethylations and substances involved in the cycle have shown complicated effects and mechanisms on immunocytes developments and activations, and exert crucial impacts on the pathological processes in immune disorders. Areas covered: Methionine cycle has been considered as an effective means of drug developments. This review discussed the role of methionine cycle in immune responses and summarized the potential therapeutic strategies based on the cycle, including SAM analogs, methyltransferase inhibitors, S-adenosylhomocysteine hydrolase (SAHH) inhibitors, adenosine receptors specific agonists or antagonists and homocysteine (Hcy)-lowering reagents, in treating human immunodeficiency virus (HIV) infections, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis (SSc) and other immune disorders. Expert opinion: New targets and biomarkers grown out of methionine cycle have developed rapidly in the past decades. However, impacts of epigenetic regulations on immune disorders are unclear and whether the substances in methionine cycle can be clarified as biomarkers remains controversial. Therefore, further elucidation on the role of epigenetic regulations and substances in methionine cycle may contribute to exploring the cycle-derived biomarkers and drugs in immune disorders.

Recent developments in therapeutic applications of Cyanobacteria.

Science.gov (United States)

Raja, Rathinam; Hemaiswarya, Shanmugam; Ganesan, Venkatesan; Carvalho, Isabel S

2016-05-01

The cyanobacteria (blue-green algae) are photosynthetic prokaryotes having applications in human health with numerous biological activities and as a dietary supplement. It is used as a food supplement because of its richness in nutrients and digestibility. Many cyanobacteria (Microcystis sp, Anabaena sp, Nostoc sp, Oscillatoria sp., etc.) produce a great variety of secondary metabolites with potent biological activities. Cyanobacteria produce biologically active and chemically diverse compounds belonging to cyclic peptides, lipopeptides, fatty acid amides, alkaloids and saccharides. More than 50% of the marine cyanobacteria are potentially exploitable for extracting bioactive substances which are effective in killing cancer cells by inducing apoptotic death. Their role as anti-viral, anti-tumor, antimicrobial, anti-HIV and a food additive have also been well established. However, such products are at different stages of clinical trials and only a few compounds have reached to the market.

Drawing trauma: the therapeutic potential of witnessing the child's visual testimony of war.

Science.gov (United States)

Farley, Lisa; Mishra Tarc, Aparna

2014-10-01

Countertransference plays an often neglected role in witnessing children's testimony of war and trauma. A dual notion of countertransference, based on the work of Winnicott and Klein, is offered that involves both internal conflict related to early life experience and socially mediated notions of childhood, war, and trauma circulating in a given time and place. A drawing by a thirteen-year-old boy living in the refugee camps in Darfur is used to show how countertransference affects our interpretation of the image, even while its symbolization in language establishes the conditions for a potentially therapeutic response. It is argued that a psychoanalytic reading can supplement the "legal-conscious terminology" in which the Darfur archive has been predominantly framed (Felman 2002, p. 5). This expanded view of witnessing involves reading the child's testimony both for the history of violence it conveys and for the social and emotional histories it calls up in the witness as the ground and possibility of justice. © 2014 by the American Psychoanalytic Association.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications.

Science.gov (United States)

Kraehenmann, Rainer

2017-01-01

A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or 'classical' psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca - a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelicassisted therapy will be provided. Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

Science.gov (United States)

Kraehenmann, Rainer

2017-01-01

Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics such as the prototypical psychedelic drug lysergic acid diethylamide (LSD) psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception mental imagery emotion activation fear memory extinction and sense of self and body. Differences between these two states are related to differential perceptual input from the environment clarity of consciousness and meta-cognitive abilities. Therefore psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. PMID:28625125

Biomimetically grown apatite spheres from aggregated bioglass nanoparticles with ultrahigh porosity and surface area imply potential drug delivery and cell engineering applications.

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El-Fiqi, Ahmed; Buitrago, Jennifer O; Yang, Sung Hee; Kim, Hae-Won

2017-09-15

Here we communicate the generation of biomimetically grown apatite spheres from aggregated bioglass nanoparticles and the potential properties applicable for drug delivery and cell/tissue engineering. Ion releasing nanoparticulates of bioglass (85%SiO 2 -15%CaO) in a mineralizing medium show an intriguing dynamic phenomenon - aggregation, mineralization to apatite, integration and growth into micron-sized (1.5-3μm) spheres. During the progressive ionic dissolution/precipitation reactions, nano-to-micro-morphology, glass-to-crystal composition, and the physico-chemical properties (porosity, surface area, and charge) change dynamically. With increasing reaction period, the apatite becomes more crystallized with increased crystallinity and crystal size, and gets a composition closer to the stoichiometry. The developed microspheres exhibit hierarchical surface nanostructure, negative charge (ς-potential of -20mV), and ultrahigh mesoporosity (mesopore size of 6.1nm, and the resultant surface area of 63.7m 2 /g and pore volume of 0.153cm 3 /g) at 14days of mineralization, which are even higher than those of its precursor bioglass nanoparticles. Thanks to these properties, the biomimetic mineral microspheres take up biological molecules effectively, i.e., loading capacity of positive-charged protein is over 10%. Of note, the release is highly sustainable at a constant rate, i.e., profiling almost 'zero-order' kinetics for 4weeks, suggesting the potential usefulness as protein delivery systems. The biomimetic mineral microspheres hold some remnant Si in the core region, and release calcium, phosphate, and silicate ions over the test period, implying the long-term ionic-related therapeutic functions. The mesenchymal stem cells favour the biomimetic spheres with an excellent viability. Due to the merit of sizes (a few micrometers), the spheres can be intercalated into cells, mediating cellular interactions in 3D cell-spheroid engineering, and also can stimulate osteogenic

HAMLET: functional properties and therapeutic potential.

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Ho C S, James; Rydström, Anna; Trulsson, Maria; Bålfors, Johannes; Storm, Petter; Puthia, Manoj; Nadeem, Aftab; Svanborg, Catharina

2012-10-01

Human α-lactalbumin made lethal to tumor cells (HAMLET) is the first member in a new family of protein-lipid complexes that kills tumor cells with high selectivity. The protein component of HAMLET is α-lactalbumin, which in its native state acts as a substrate specifier in the lactose synthase complex, thereby defining a function essential for the survival of lactating mammals. In addition, α-lactalbumin acquires tumoricidal activity after partial unfolding and binding to oleic acid. The lipid cofactor serves the dual role as a stabilizer of the altered fold of the protein and a coactivator of specific steps in tumor cell death. HAMLET is broadly tumoricidal, suggesting that the complex identifies conserved death pathways suitable for targeting by novel therapies. Sensitivity to HAMLET is defined by oncogene expression including Ras and c-Myc and by glycolytic enzymes. Cellular targets are located in the cytoplasmic membrane, cytoskeleton, mitochondria, proteasomes, lysosomes and nuclei, and specific signaling pathways are rapidly activated, first by interactions of HAMLET with the cell membrane and subsequently after HAMLET internalization. Therapeutic effects of HAMLET have been demonstrated in human skin papillomas and bladder cancers, and HAMLET limits the progression of human glioblastomas, with no evidence of toxicity for normal brain or bladder tissue. These findings open up new avenues for cancer therapy and the understanding of conserved death responses in tumor cells.

Radiotherapy in conjunction with 7-hydroxystaurosporine: a multimodal approach with tumor pO2 as a potential marker of therapeutic response.

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Khan, Nadeem; Mupparaju, Sriram P; Hou, Huagang; Lariviere, Jean P; Demidenko, Eugene; Swartz, Harold M; Eastman, Alan

2009-11-01

Checkpoint inhibitors potentially could be used to enhance cell killing by DNA-targeted therapeutic modalities such as radiotherapy. UCN-01 (7-hydroxystaurosporine) inhibits S and G2 checkpoint arrest in the cells of various malignant cell lines and has been investigated in combination with chemotherapy. However, little is known about its potential use in combination with radiotherapy. We report the effect of 20 Gy radiation given in conjunction with UCN-01 on the pO2 and growth of subcutaneous RIF-1 tumors. Multisite EPR oximetry was used for repeated, non-invasive tumor pO2 measurements. The effect of UCN-01 and/or 20 Gy on tumor pO2 and tumor volume was investigated to determine therapeutic outcomes. Untreated RIF-1 tumors were hypoxic with a tissue pO2 of 5-7 mmHg. Treatment with 20 Gy or UCN-01 significantly reduced tumor growth, and a modest increase in tumor pO2 was observed in tumors treated with 20 Gy. However, irradiation with 20 Gy 12 h after UCN-01 treatment resulted in a significant inhibition of tumor growth and a significant increase in tumor pO2 to 16-28 mmHg from day 1 onward compared to the control, UCN-01 or 20-Gy groups. Treatment with UCN-01 12 h after 20 Gy also led to a similar growth inhibition of the tumors and a similar increase in tumor pO2. The changes in tumor pO2 observed after the treatment correlated inversely with the tumor volume in the groups receiving UCN-01 with 20 Gy. This multimodal approach could be used to enhance the outcome of radiotherapy. Furthermore, tumor pO2 could be a potential marker of therapeutic response.

Antioxidant Potential of a Polyherbal Antimalarial as an Indicator of Its Therapeutic Value

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Protus Arrey Tarkang

2013-01-01

Full Text Available Nefang is a polyherbal product composed of Mangifera indica (bark and leaf, Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum (leaves, used for the treatment of malaria. Compounds with antioxidant activity are believed to modulate plasmodial infection. Antioxidant activity of the constituent aqueous plants extracts, in vitro, was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH, total phenolic content (TPC, and ferric reducing antioxidant power (FRAP methods and, in vivo, Nefang (100 and 500 mg kg−1 activity was evaluated in carbon tetrachloride-induced oxidative stressed Wistar rats. Superoxide dismutase, catalase activities, and lipid peroxidation by the malondialdehyde and total proteins assays were carried out. P. guajava, M. indica leaf, and bark extracts had the highest antioxidant properties in all three assays, with no statistically significant difference. Rats treated with the carbon tetrachloride had a statistically significant decrease in levels of triglycerides, superoxide dismutase, and catalase (P<0.05 and increase in malondialdehyde activity, total protein levels, and liver and renal function markers, whereas rats treated with Nefang showed increased levels in the former and dose-dependent decrease towards normal levels in the later. These results reveal the constituent plants of Nefang that contribute to its in vivo antioxidant potential. This activity is a good indication of the therapeutic potential of Nefang.

Geothermal Direct Heat Application Potential

Energy Technology Data Exchange (ETDEWEB)

Lienau, Paul J

1989-01-01

The geothermal direct-use industry growth trends, potential, needs, and how they can be met, are addressed. Recent investigations about the current status of the industry and the identification of institutional and technical needs provide the basis on which this paper is presented. Initial drilling risk is the major obstacle to direct-use development. The applications presented include space and district heating projects, heat pumps (heating and cooling), industrial processes, resorts and pools, aquaculture and agriculture.

The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

Science.gov (United States)

Marshall, Jamie L.; Kwok, Yukwah; McMorran, Brian; Baum, Linda G.; Crosbie-Watson, Rachelle H.

2013-01-01

Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important therapeutic target. Here, we review current protein replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. PMID:23601082

MRI-guided therapeutic ultrasound: Temperature feedback control for extracorporeal and endoluminal applicators

Science.gov (United States)

Salomir, Rares

2005-09-01

Therapeutic ultrasound is a mini-invasive and promising tool for in situ ablation of non-resectable tumors in uterus, breast, esophagus, kidney, liver, etc. Extracorporeal, endoluminal, and interstitial applicators have been successfully tested to date. Magnetic resonance imaging (MRI) is the only available technique providing non-invasive temperature mapping, together with excellent contrast of soft tissue. Coupling of these two technologies offers the advantage of both: (1) on line spatial guidance to the target region, and (2) thermal dose control during the treatment. This talk will provide an overview of the author's experience with automatic, active feedback control of the temperature evolution in tissues, which has been demonstrated with MRI compatible extracorporeal transducers (focused beam) or endoluminal applicators (plane waves). The feedback loop is based on fast switching capabilities of the driving electronics and real time data transfer out of the MR scanner. Precision of temperature control was typically better than 1°C. This approach is expected to improve the efficacy of the treatment (complete tumor ablation) and the thermal security of the critical regions crossed by the acoustic beam. It also permits one to reach an under-lethal heating regime for local drug delivery using thermosensitive liposomes or gene expression control based on hsp promoters.

Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

Science.gov (United States)

Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

2017-01-01

Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Metabolic analysis of radioresistant medulloblastoma stem-like clones and potential therapeutic targets.

Directory of Open Access Journals (Sweden)

Lue Sun

Full Text Available Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs by irradiation of the human medulloblastoma cell line ONS-76. Here, we assessed reactive oxygen species (ROS production, mitochondria function, oxygen consumption rate (OCR, energy state, and metabolites of glycolysis and tricarboxylic acid cycle in rMSLCs and parental cells. rMSLCs showed higher lactate production and lower oxygen consumption rate than parental cells. Additionally, rMSLCs had low mitochondria mass, low endogenous ROS production, and existed in a low-energy state. Treatment with the metabolic modifier dichloroacetate (DCA resulted in mitochondria dysfunction, glycolysis inhibition, elongated mitochondria morphology, and increased ROS production. DCA also increased radiosensitivity by suppression of the DNA repair capacity through nuclear oxidization and accelerated the generation of acetyl CoA to compensate for the lack of ATP. Moreover, treatment with DCA decreased cancer stem cell-like characters (e.g., CD133 positivity and sphere-forming ability in rMSLCs. Together, our findings provide insights into the specific metabolism of rMSLCs and illuminate potential metabolic targets that might be exploited for therapeutic benefit in medulloblastoma.

Type I IL-1 Receptor (IL-1RI as Potential New Therapeutic Target for Bronchial Asthma

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Jyh-Hong Lee

2010-01-01

Full Text Available The IL-1R/TLR family has been receiving considerable attention as potential regulators of inflammation through their ability to act as either activators or suppressors of inflammation. Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, allergic inflammation, elevated serum total, allergen-specific IgE levels, and increased Th2 cytokine production. The discovery that the IL-1RI–IL-1 and ST2–IL-33 pathways are crucial for allergic inflammation has raised interest in these receptors as potential targets for developing new therapeutic strategies for bronchial asthma. This paper discusses the current use of neutralizing mAb or soluble receptor constructs to deplete cytokines, the use of neutralizing mAb or recombinant receptor antagonists to block cytokine receptors, and gene therapy from experimental studies in asthma. Targeting IL-1RI–IL-1 as well as ST2–IL-33 pathways may promise a disease-modifying approach in the future.

The therapeutic collaboration in life design counselling: The case of ...

African Journals Online (AJOL)

The collaboration coding system enables the assessment of each therapeutic exchange within and outside of the client's therapeutic zone of proximal development, defined as the space between the client's actual therapeutic developmental level and his/her potential developmental level fomented by a collaborative ...

Pharmacokinetics of cotinine in rats: a potential therapeutic agent for disorders of cognitive function.

Science.gov (United States)

Li, Pei; Beck, Wayne D; Callahan, Patrick M; Terry, Alvin V; Bartlett, Michael G

2015-06-01

Attention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (iv) PK information. In this study, plasma samples were obtained up to 48 h after COT was dosed to rats orally and iv at a dose of 3mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and iv administrations. The data were fitted into a one-compartment model and a two-compartment model for the oral and iv groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. Several important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogs as agents for improving cognition. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Stem Cell Therapy and Breast Cancer Treatment: review of stem cell research and potential therapeutic impact against cardiotoxicities due to breast cancer treatment

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Thomas E. Sharp

2014-11-01

Full Text Available A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually lead to heart failure (HF. This cardiomyocyte toxicity can leave the breast cancer survivor with a probable diagnosis of dilated or restrictive cardiomyopathy (DCM or RCM. While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies. There is a need to develop novel therapeutics that can either prevent or reverse the cardiac injury caused by cancer therapeutics. These new therapeutics should promote the regeneration of lost or deteriorating myocardium. Over the last several decades the therapeutic potential of cell-based therapy has been investigated for HF patients. In this review we discuss the progress of preclinical and clinical stem cell research for the diseased heart and discuss the possibility of utilizing these novel therapies to combat cardiotoxicity observed in breast cancer survivors.

MCM-41 mesoporous silica nanoparticles functionalized with aptamer and radiolabelled with 90Y and 159Gd as a potential therapeutic agent against colorectal cancer

International Nuclear Information System (INIS)

Ferreira, Carolina de Aguiar

2014-01-01

Colorectal cancer (CRC) is a malignancy that affects large intestine and rectum, and it is the most common malignancy of the gastrointestinal tract, the third most commonly diagnosed type of cancer in the world and the second leading cause of cancer-related death in the United States. Nowadays, available therapeutic procedures for this type of cancer are limited and ineffective. Conventional radiotherapy is not an often used approach in the treatment of CRC due to the fact that peristaltic movements hamper the targeting of ionizing radiation and this type of treatment is used as adjuvant and palliative to control symptoms. Therefore, surgical intervention is the primary therapeutic choice against this disease. Researches based on the combination of radioisotopes and nanostructured carriers systems have demonstrated significant results in improving the selectivity action as well as reducing the radiation dose into healthy tissues. MCM-41 mesoporous silica nanoparticles have unique characteristics such as high surface area and well-defined pore diameters making these nanoparticles an ideal candidate of therapeutic agent carrier. Thus, the objective of this work is to synthesize and characterize MCM-41 mesoporous silica nanoparticles conjugated with yttrium-90 and gadolinium-159 and evaluate this system as a potential therapeutic agent. The nanoparticles were synthesized via sol-gel method. The sample was characterized using FTIR, SAXS, PCS, Zeta Potential analysis, Thermal analysis, CHN elemental analysis, nitrogen adsorption, scanning and transmission electron microscopy. The ability to incorporate Y +3 and Gd +3 ion was determined in vitro using different ratios (1:1, 1:3, 1:5 v/v) of YCL 3 and Gd 2 O 3 and silica nanoparticles dispersed in saline, pH 7.4. The non-incorporated Y +3 and Gd +3 ions were removed by ultracentrifugation procedure and the concentration of ions in the supernatant was determined by ICP-AES. Cell viability was assessed by colorimetric MTT

About the use of nano-therapeutic means in medicine (ro.

Directory of Open Access Journals (Sweden)

Romeo T. Cristina

2013-11-01

Full Text Available Nanobiotehnology is a relatively new field of research, being the interface between the life sciences and nanotechnology. In this area where the work dimensions are between 1 nm and 100 nm the recovery of biomolecules’ quality and the processes involved it is proposed, in the development of materials or devices with certain medical activity. This bibliographic approach proposes a first foray into nano-therapeutic resources use in the medical field. Are presented sintheticaly the main nanomaterials, their properties and potential applications in nanomedicine, magnetic fluids, their synthezis and stabilization as well as recent advances in this topic.

Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine application

Science.gov (United States)

Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Kim, Hye Hyun; Seo, Hansu; Lee, Kang Dae; Oh, Junghwan

2017-01-01

In this review, specific attention is paid to the development of nanostructured magnetic hydroxyapatite (MHAp) and its potential application in controlled drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the development of contrast agents for magnetic resonance imaging. Both magnetite and hydroxyapatite materials have excellent prospects in nanomedicine with multifunctional therapeutic approaches. To date, many research articles have focused on biomedical applications of nanomaterials because of which it is very difficult to focus on any particular type of nanomaterial. This study is possibly the first effort to emphasize on the comprehensive assessment of MHAp nanostructures for biomedical applications supported with very recent experimental studies. From basic concepts to the real-life applications, the relevant characteristics of magnetic biomaterials are patented which are briefly discussed. The potential therapeutic and diagnostic ability of MHAp-nanostructured materials make them an ideal platform for future nanomedicine. We hope that this advanced review will provide a better understanding of MHAp and its important features to utilize it as a promising material for multifunctional biomedical applications. PMID:29200851

Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine application.

Science.gov (United States)

Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Kim, Hye Hyun; Seo, Hansu; Lee, Kang Dae; Oh, Junghwan

2017-01-01

In this review, specific attention is paid to the development of nanostructured magnetic hydroxyapatite (MHAp) and its potential application in controlled drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the development of contrast agents for magnetic resonance imaging. Both magnetite and hydroxyapatite materials have excellent prospects in nanomedicine with multifunctional therapeutic approaches. To date, many research articles have focused on biomedical applications of nanomaterials because of which it is very difficult to focus on any particular type of nanomaterial. This study is possibly the first effort to emphasize on the comprehensive assessment of MHAp nanostructures for biomedical applications supported with very recent experimental studies. From basic concepts to the real-life applications, the relevant characteristics of magnetic biomaterials are patented which are briefly discussed. The potential therapeutic and diagnostic ability of MHAp-nanostructured materials make them an ideal platform for future nanomedicine. We hope that this advanced review will provide a better understanding of MHAp and its important features to utilize it as a promising material for multifunctional biomedical applications.

An exploration of the potential mechanisms and translational potential of five medicinal plants for applications in Alzheimer's disease.

Science.gov (United States)

Shakir, Taner; Coulibaly, Ahmed Y; Kehoe, Patrick G

2013-01-01

Alzheimer's disease (AD) is the most common type of dementia, and represents a vast worldwide socio-economic burden, and in the absence of a current cure, effective therapeutic strategies are still needed. Cholinergic and cerebral blood flow deficits, excessive levels of oxidative stress, neuroinflammation and glutamate excitatory mechanisms are all believed to contribute to the development and progression of the disease. Scoparia dulcis, Catharanthus roseus, Sesamum indicum, Erythrina senegalensis and Vigna unguiculata represent five plants that have been used as traditional medicines for the treatment of AD in certain cultures. Review of the scientific literature was conducted to explore the properties of these plants that might be beneficial and explain what would be perceived by many to be largely anecdotal evidence of their benefit. All plants were found to possess varying levels of anti-oxidant capability. Scoparia dulcis was also found to potentiate nerve growth factor-like effects upon cell lines. Catharanthus roseus appears to inhibit acetylcholinesterase with relatively high potency, while Sesamum indicum demonstrated the strongest antioxidant ability. Comparisons with currently used plant derived therapeutics illustrate how these plants may be likely to have some therapeutic benefits in AD. The evidence presented also highlights how appropriate dietary supplementation with some of these plants in various cultural settings might have effects analogous or complementary to the so-called protective Mediterranean diet. However, prior to embarking on making any formal recommendations to this end, further rigorous evaluation is needed to better elucidate the breadth and potential toxicological aspects of medicinal properties harboured by these plants. This would be vital to ensuring a more informed and safe delivery of preparations of these plants if they were to be considered as a form of dietary supplementation and where appropriate, how these might interact

Potential of Starch Nanocomposites for Biomedical Applications

Science.gov (United States)

Zakaria, N. H.; Muhammad, N.; Abdullah, M. M. A. B.

2017-06-01

In recent years, the development of biodegradable materials from renewable sources based on polymeric biomaterials have grown rapidly due to increase environmental concerns and the shortage of petroleum sources. In this regard, naturally renewable polymers such as starch has shown great potential as environmental friendly materials. Besides, the unique properties of starch such as biodegradable and non-toxic, biocompatible and solubility make them useful for a various biomedical applications. Regardless of their unique properties, starch materials are known to have limitations in term of poor processability, low mechanical properties, poor long term stability and high water sensitivity. In order to overcome these limitations, the incorporation of nano size fillers into starch materials (nanocomposites) has been introduced. This review aims to give an overview about structure and characteristics of starch, modification of starch by nanocomposites and their potential for biomedical applications.

Exploring the Hybridization Thermodynamics of Spherical Nucleic Acids to Tailor Probes for Diagnostic and Therapeutic Applications

Science.gov (United States)

Randeria, Pratik Shailesh

Spherical nucleic acids (SNAs), three-dimensional nanoparticle conjugates composed of densely packed and highly oriented oligonucleotides around organic or inorganic nanoparticles, are an emergent class of nanostructures that show promise as single-entity agents for intracellular messenger RNA (mRNA) detection and gene regulation. SNAs exhibit superior biocompatibility and biological properties compared to linear oligonucleotides, enabling them to overcome many of the limitations of linear oligonucleotides for use in biomedical applications. However, the origins of these biologically attractive properties are not well understood. In this dissertation, the chemistry underlying one such property is studied in detail, and the findings are applied towards the rational design of more effective SNAs for diagnostic and therapeutic applications. Chapter 1 introduces the synthesis of SNAs, the unique properties that make them superior to linear nucleic acids for biomedicine, and previously studied applications of these structures. Chapter 2 focuses on quantitatively studying the impact of the chemical structure of the SNA on its ability to hybridize multiple complementary nucleic acids. This chapter lays the groundwork for understanding the factors that govern SNA hybridization thermodynamics and how to tailor SNAs to increase their binding affinity to target mRNA strands. Chapters 3 and 4 capitalize on this knowledge to engineer probes for intracellular mRNA detection and gene regulation applications. Chapter 3 reports the development of an SNA-based probe that can simultaneously report the expression level of two different mRNA transcripts in live cells and differentiate diseased cells from non-diseased cells. Chapter 4 investigates the use of topically-applied SNAs to down-regulate a critical mediator of impaired wound healing in diabetic mice to accelerate wound closure. This study represents the first topical therapeutic application of SNA nanotechnology to treat open

QUADrATiC: scalable gene expression connectivity mapping for repurposing FDA-approved therapeutics.

Science.gov (United States)

O'Reilly, Paul G; Wen, Qing; Bankhead, Peter; Dunne, Philip D; McArt, Darragh G; McPherson, Suzanne; Hamilton, Peter W; Mills, Ken I; Zhang, Shu-Dong

2016-05-04

Gene expression connectivity mapping has proven to be a powerful and flexible tool for research. Its application has been shown in a broad range of research topics, most commonly as a means of identifying potential small molecule compounds, which may be further investigated as candidates for repurposing to treat diseases. The public release of voluminous data from the Library of Integrated Cellular Signatures (LINCS) programme further enhanced the utilities and potentials of gene expression connectivity mapping in biomedicine. We describe QUADrATiC ( http://go.qub.ac.uk/QUADrATiC ), a user-friendly tool for the exploration of gene expression connectivity on the subset of the LINCS data set corresponding to FDA-approved small molecule compounds. It enables the identification of compounds for repurposing therapeutic potentials. The software is designed to cope with the increased volume of data over existing tools, by taking advantage of multicore computing architectures to provide a scalable solution, which may be installed and operated on a range of computers, from laptops to servers. This scalability is provided by the use of the modern concurrent programming paradigm provided by the Akka framework. The QUADrATiC Graphical User Interface (GUI) has been developed using advanced Javascript frameworks, providing novel visualization capabilities for further analysis of connections. There is also a web services interface, allowing integration with other programs or scripts. QUADrATiC has been shown to provide an improvement over existing connectivity map software, in terms of scope (based on the LINCS data set), applicability (using FDA-approved compounds), usability and speed. It offers potential to biological researchers to analyze transcriptional data and generate potential therapeutics for focussed study in the lab. QUADrATiC represents a step change in the process of investigating gene expression connectivity and provides more biologically-relevant results than

Therapeutic radionuclides: Making the right choice

International Nuclear Information System (INIS)

Srivastava, S.C.

1996-01-01

Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article

Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases

Directory of Open Access Journals (Sweden)

Hideyuki eTakeuchi

2014-09-01

Full Text Available Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS. Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g. minocycline have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases.

The potential usefulness of the Response Index in positron emission tomography assessing the therapeutic effect of pre-operative chemotherapy for advanced colorectal cancer.

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Nomura, Masatoshi; Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Matsuda, Chu; Ikenaga, Masakazu; Yamamoto, Hirofumi; Murata, Kohei; Doki, Yuichiro; Mori, Masaki; Mizushima, Tsunekazu

2017-12-01

Pre-operative chemotherapy is an option for patients with local advanced rectal cancer, but the response rate to pre-operative chemotherapy with oxaliplatin is still low. If the therapeutic effect of pre-operative chemotherapy could be assessed, we may be able to convert to surgery early. The purpose of the present study was to validate the correlation between the maximum standardized uptake value (SUV max ) in 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) of the primary tumor and the therapeutic effect of pre-operative chemotherapy in advanced colorectal cancer. Retrospective cohort study from January 2011 to October 2015. We examined 28 patients with pathologically confirmed sigmoid or rectal cancer that underwent pre-operative chemotherapy and surgery. The correlation between Response Index (RI), calculated as (SUV max after chemotherapy)/(SUV max before chemotherapy), and the therapeutic effect on the primary tumor in advanced colorectal cancer. The degree of differentiation (p = 0.04), SUV max in the primary tumor after chemotherapy (p = 0.02), and RI (p = 0.008) were significant predictors of the therapeutic effect in univariate analysis. The areas under the ROC curve constructed with RI and therapeutic effect was 0.77. The optimal cut-off values for the RI in the responder group was effect of chemotherapy on advanced colorectal cancer. Thus, RI is potentially useful for predicting the therapeutic effect in advanced colorectal cancer.

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

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Nijhof, I. S.; Groen, R. W. J.; Noort, W. A.

2015-01-01

lenalidomide- and/or bortezomib-refractory patients. In these assays, lenalidomide but not bortezomib, synergistically enhanced daratumumab-mediated multiple myeloma lysis through activation of natural killer cells. Finally, in an in vivo xenograft model, only the combination of daratumumab with lenalidomide......Purpose: Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, the prognosis of patients with multiple myeloma who become refractory to the novel agents lenalidomide and bortezomib is very poor, indicating the urgent need for new...... therapeutic options for these patients. The human CD38 monoclonal antibody daratumumab is being evaluated as a novel therapy for multiple myeloma. Prompted with the encouraging results of ongoing clinical phase I/II trials, we now addressed the potential value of daratumumab alone or in combination...

A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome.

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Lu, Simin; Kanekura, Kohsuke; Hara, Takashi; Mahadevan, Jana; Spears, Larry D; Oslowski, Christine M; Martinez, Rita; Yamazaki-Inoue, Mayu; Toyoda, Masashi; Neilson, Amber; Blanner, Patrick; Brown, Cris M; Semenkovich, Clay F; Marshall, Bess A; Hershey, Tamara; Umezawa, Akihiro; Greer, Peter A; Urano, Fumihiko

2014-12-09

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced by high cytosolic calcium mediated by the loss of function of WFS1. Calpain hyperactivation is observed in the WFS1 knockout mouse as well as in neural progenitor cells derived from induced pluripotent stem (iPS) cells of Wolfram syndrome patients. A small-scale small-molecule screen targeting ER calcium homeostasis reveals that dantrolene can prevent cell death in neural progenitor cells derived from Wolfram syndrome iPS cells. Our results demonstrate that calpain and the pathway leading its activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases.

Nucleic acid aptamer-guided cancer therapeutics and diagnostics: the next generation of cancer medicine.

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Xiang, Dongxi; Shigdar, Sarah; Qiao, Greg; Wang, Tao; Kouzani, Abbas Z; Zhou, Shu-Feng; Kong, Lingxue; Li, Yong; Pu, Chunwen; Duan, Wei

2015-01-01

Conventional anticancer therapies, such as chemo- and/or radio-therapy are often unable to completely eradicate cancers due to abnormal tumor microenvironment, as well as increased drug/radiation resistance. More effective therapeutic strategies for overcoming these obstacles are urgently in demand. Aptamers, as chemical antibodies that bind to targets with high affinity and specificity, are a promising new and novel agent for both cancer diagnostic and therapeutic applications. Aptamer-based cancer cell targeting facilitates the development of active targeting in which aptamer-mediated drug delivery could provide promising anticancer outcomes. This review is to update the current progress of aptamer-based cancer diagnosis and aptamer-mediated active targeting for cancer therapy in vivo, exploring the potential of this novel form of targeted cancer therapy.

Advances in the delivery of RNA therapeutics: from concept to clinical reality.

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Kaczmarek, James C; Kowalski, Piotr S; Anderson, Daniel G

2017-06-27

The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

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Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

2017-01-01

Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer

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Lin, Chaoyang [Shandong Univ., Jinan (China); Zhang, Pengju [Shandong Univ., Jinan (China); Jiang, Anli [Shandong Univ., Jinan (China); Mao, Jian-Hua [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wei, Guangwei [Shandong Univ. School of Medicine, Jinan (China)

2017-03-30

C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.

Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

DEFF Research Database (Denmark)

Fosgerau, Keld; Weber, Uno J; Gotfredsen, Jacob W

2010-01-01

Background  The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feas......Background  The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated...... the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies...... was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Conclusions Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining...

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 ...

Curcumin, a potential therapeutic candidate for retinal diseases.

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Wang, Lei-Lei; Sun, Yue; Huang, Kun; Zheng, Ling

2013-09-01

Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Medicinal Chemistry of Therapeutic Oligonucleotides.

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Wan, W Brad; Seth, Punit P

2016-11-10

Oligonucleotide-based therapeutics have made rapid progress in the clinic for treatment of a variety of disease indications. Unmodified oligonucleotides are polyanionic macromolecules with poor drug-like properties. Over the past two decades, medicinal chemists have identified a number of chemical modification and conjugation strategies which can improve the nuclease stability, RNA-binding affinity, and pharmacokinetic properties of oligonucleotides for therapeutic applications. In this perspective, we present a summary of the most commonly used nucleobase, sugar and backbone modification, and conjugation strategies used in oligonucleotide medicinal chemistry.

Vitamin D: new roles and therapeutic potential in inflammatory bowel disease.

LENUS (Irish Health Repository)

Raftery, Tara

2012-11-01

Inflammatory bowel disease (IBD) encompasses 2 independent but related entities: ulcerative colitis (UC) and Crohn\\'s disease. Crohn\\'s disease is characterised by transmural patchy inflammation which can involve any portion of the gastrointestinal tract. UC is characterised by superficial inflammation that begins in the rectum and extends proximally along the colon. In Europe, approximately 2.2 million people have a diagnosis of IBD. The aetiology of IBD is unknown, however, immune, environmental and genetic factors are thought to be involved. Individuals with IBD are at risk of developing osteoporosis. In line with this, there are clear guidelines that recommend vitamin D supplementation for IBD patients to prevent bone disease, especially when undergoing steroid treatment. Despite an established role for vitamin D in IBD, deficiency is common. More novel effects of vitamin D beyond bone are emerging. It is now well established that vitamin D is an important regulator of the immune system which may have implications for the development, severity and management of immune related disorders such as IBD. The efficacy of vitamin D as an immune modulator in IBD remains to be proven. This review aims to evaluate the evidence implicating vitamin D deficiency in IBD pathogenesis, to examine vitamin D\\'s anti-inflammatory mechanisms and to explore its therapeutic potential, optimal serum levels and dietary intakes which may support immune function in this disease.

Identification of thioaptamer ligand against E-selectin: potential application for inflamed vasculature targeting.

Directory of Open Access Journals (Sweden)

Aman P Mann

Full Text Available Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA against E-selectin (ESTA-1 by employing a two-step selection strategy: a recombinant protein-based TA binding selection from a combinatorial library followed by a cell-based TA binding selection using E-selectin expressing human microvascular endothelial cells. ESTA-1 selectively bound to E-selectin with nanomolar binding affinity (K(D = 47 nM while exhibiting minimal cross reactivity to P- and L-selectin. Furthermore, ESTA-1 binding to E-selectin on the endothelial cells markedly antagonized the adhesion (over 75% inhibition of sLe(x positive HL-60 cells at nanomolar concentration. ESTA-1 also bound specifically to the inflamed tumor-associated vasculature of human carcinomas derived from breast, ovarian, and skin but not to normal organs, and this binding was highly associated with the E-selectin expression level. Similarly, intravenously injected ESTA-1 demonstrated distinct binding to the tumor vasculature in a breast cancer xenograft model. Together, our data substantiates the discovery of a thioaptamer (ESTA-1 that binds to E-selectin with high affinity and specificity, thereby highlighting the potential application of ESTA-1 for E-selectin targeted delivery.

Multi-targeting Andrographolide and its Natural Analogs as Potential Therapeutic Agents.

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Kishore, V; Yarla, Nagendra Sastry; Bishayee, Anupam; Putta, Swathi; Malla, Ramarao; Neelapu, Nageswara Rao Reddy; Challa, Surekha; Das, Subhasish; Shiralgi, Yallappa; Hegde, Gurumurthy; Dhananjaya, Bhadrapura Lakkappa

2017-01-01

Andrographis paniculata (A. paniculata) is a medicinal plant used in the Indian and Chinese traditional medicinal systems for its various beneficial properties of therapeutics. This is due to the presence of a diterpene lactone called 'andrographolide'. Several biological activities like antiinflammatory, antitumour, anti-hyperglycaemic, anti-fertility, antiviral, cardio protective and hepatoprotective properties are attributed to andrographolide and its natural analogs. The studies have shown that not only this diterpene lactone (andrographolide), but also other related terpenoid analogs from A. paniculata could be exploited for disease prevention due to their structural similarity with diverse pharmacological activities. Several scientific groups are trying to unveil the underlying mechanisms involved in these biological actions brough aout by andrographolide and its analogs. This review aims at giving an overview on the therapeutical and/or pharmacological activities of andrographolide and its derivatives and also exemplify the underlying mechanisms involved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Melatonin and Nitrones As Potential Therapeutic Agents for Stroke

Directory of Open Access Journals (Sweden)

Alejandro Romero

2016-11-01

Full Text Available Stroke is a disease of aging affecting millions of people worldwide, and recombinant tissue-type plasminogen activator (r-tPA is the only treatment approved. However, r-tPA has a low therapeutic window and secondary effects which limit its beneficial outcome, urging thus the search for new more efficient therapies. Among them, neuroprotection based on melatonin or nitrones, as free radical traps, have arisen as drug candidates due to their strong antioxidant power. In this Perspective article, an update on the specific results of the melatonin and several new nitrones are presented.

NAD+ : A key metabolic regulator with great therapeutic potential.

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Sultani, G; Samsudeen, A F; Osborne, B; Turner, N

2017-10-01

Nicotinamide adenine dinucleotide (NAD + ) is a ubiquitous metabolite that serves an essential role in the catabolism of nutrients. Recently, there has been a surge of interest in NAD + biology, with the recognition that NAD + influences many biological processes beyond metabolism, including transcription, signalling and cell survival. There are a multitude of pathways involved in the synthesis and breakdown of NAD + , and alterations in NAD + homeostasis have emerged as a common feature of a range of disease states. Here, we provide an overview of NAD + metabolism and summarise progress on the development of NAD + -related therapeutics. © 2017 British Society for Neuroendocrinology.

Insights on the neuromodulatory propensity of Selaginella (Sanjeevani) and its potential pharmacological applications.

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Chandran, Girish; Muralidhara

2014-02-01

Exploiting the potential of natural compounds to attenuate endogenous redox status to achieve neuroprotection is a novel concept in human disease therapy. This has necessitated a need to identify newer efficient phytochemicals possessing propensity to act on various biochemical therapeutic targets with low or no toxicity. Selaginella is a lithophytic pteridophyte which grows on constantly irrigated rocks in high altitude zones in different parts of the world. It is appraised to be "Sanjeevani" (the resurrection herb) based on its mythological reference in the Indian epic "Ramayana". Due to the presence of a unique disaccharide, trehalose, most species of Selaginella can survive severe drought conditions, maintaining the plant's structural stability and resurrect during rains. Several species of the genus are used in ethnic medicine for the therapy of jaundice, chronic trachitis, lung cancer, labor pain and wound healing. The major natural compounds in the genus Selaginella are characteristic flavonoid-dimers, called 'biflavonoids'. Although various biological effects of Selaginella have been documented in vitro, studies on its neuromodulatory properties are nonexisting despite the presence of potentially therapeutic biflavonoids. We have reviewed the existing literature on the possible pharmacological properties of Selaginella. Further, recent evidence gathered from our laboratory on the neuromodulatory propensity of S. delicatula employing in vivo models of chemically induced neurodegenerative diseases in rodents and Drosophila are discussed. Our findings point to a mechanism which modulates redox status and mitochondrial dysfunction suggesting their possible therapeutic use in oxidative stress-mediated neurodegenerative diseases including Parkinson's disease.

American Society for Therapeutic Radiology and Oncology (ASTRO) Emerging Technology Committee Report on Electronic Brachytherapy

International Nuclear Information System (INIS)

Park, Catherine C.; Yom, Sue S.; Podgorsak, Matthew B.; Harris, Eleanor; Price, Robert A.; Bevan, Alison; Pouliot, Jean; Konski, Andre A.; Wallner, Paul E.

2010-01-01

The development of novel technologies for the safe and effective delivery of radiation is critical to advancing the field of radiation oncology. The Emerging Technology Committee of the American Society for Therapeutic Radiology and Oncology appointed a Task Group within its Evaluation Subcommittee to evaluate new electronic brachytherapy methods that are being developed for, or are already in, clinical use. The Task Group evaluated two devices, the Axxent Electronic Brachytherapy System by Xoft, Inc. (Fremont, CA), and the Intrabeam Photon Radiosurgery Device by Carl Zeiss Surgical (Oberkochen, Germany). These devices are designed to deliver electronically generated radiation, and because of their relatively low energy output, they do not fall under existing regulatory scrutiny of radioactive sources that are used for conventional radioisotope brachytherapy. This report provides a descriptive overview of the technologies, current and future projected applications, comparison of competing technologies, potential impact, and potential safety issues. The full Emerging Technology Committee report is available on the American Society for Therapeutic Radiology and Oncology Web site.

Will Synergizing Vaccination with Therapeutics Boost Measles Virus Eradication?

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Plemper, Richard K; Hammond, Anthea L

2014-01-01

Introduction Measles virus is a major human pathogen responsible for approximately 150,000 measles deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence combined with public anxieties about vaccination safety has increased vaccine refusal especially in the European region, which has resulted in measles resurgence in some areas. Areas covered Here, we discuss whether synergizing effective measles therapeutics with vaccination could contribute to solving an endgame conundrum of measles elimination by accelerating the eradication effort. Based on an anticipated use for protection of high-risk contacts of confirmed measles cases through post-exposure prophylaxis, we identify key elements of the desirable drug profile, review current disease management strategies and the state of experimental inhibitor candidates, evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics for the management of persistent viral infection of the CNS. Assuming a post-measles world with waning measles immunity, we contemplate the possible impact of therapeutics on controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles virus. Expert opinion Efficacious therapeutics given for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent patient population dictates the drug profile; the article must be safe and efficacious, orally available, shelf-stable at ambient temperature, and amenable to cost-effective manufacture

Therapeutic Potential of Plants as Anti-Microbials for Drug Discovery