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Current Opinion in Pharmacology

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https://www.readbyqxmd.com/read/30223181/the-gut-liver-axis-in-hepatocarcinoma-a-focus-on-the-nuclear-receptor-fxr-and-the-enterokine-fgf19
#1
REVIEW
Marilidia Piglionica, Marica Cariello, Antonio Moschetta
Elevated bile acid (BA) concentrations in the liver is associated with severe disease, including cholestasis and hepatocellular carcinoma. The nuclear Farnesoid X Receptor (FXR) is the master regulator of BAs homeostasis. In the ileum, BA-dependent FXR activation induces the production of the fibroblast growth factor FGF19, a hormone that reaches the liver through the portal system where it represses the expression of CYP7A1, the rate limiting enzyme in the process of hepatic BAs synthesis. This gut-liver FXR-FGF19 dual action is the paradigm of physiological BA regulation and it is currently targeted in the clinical practice for liver disease such as primary cholangitis...
September 14, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30219638/pre-and-probiotic-overview
#2
REVIEW
Cesare Cremon, Maria Raffaella Barbaro, Marco Ventura, Giovanni Barbara
The dynamic relationship between gut microbiota and its human host is also known as a trophic association that might range from commensalism, where only the microbe enjoys a positive effect from the relationship, to intestinal symbiosis where both host and microbe benefit from their interaction. In the last years, we have started to understand how alterations of the gut microbiota composition leading to the disruption of host-microbial interactions are associated and/or predispose individuals to disease conditions ranging from inflammatory bowel diseases to allergy and functional gastrointestinal disorders, such as irritable bowel syndrome...
September 13, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30218940/endocannabinoids-in-the-treatment-of-gasytrointestinal-inflammation-and-symptoms
#3
REVIEW
Marcella Pesce, Giuseppe Esposito, Giovanni Sarnelli
The evolving policies regarding the use of therapeutic Cannabis have steadily increased the public interest in its use as a complementary and alternative medicine in several disorders, including inflammatory bowel disease. Endocannabinoids represent both an appealing therapeutic strategy and a captivating scientific dilemma. Results from clinical trials have to be carefully interpreted owing to possible reporting-biases related to cannabinoids psychotropic effects. Moreover, discriminating between symptomatic improvement and the real gain on the underlying inflammatory process is often challenging...
September 12, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30218939/fecal-microbiota-transfer-for-bowel-disorders-efficacy-or-hype
#4
REVIEW
Max Schmulson, Mohammad Bashashati
PURPOSE OF REVIEW: Dysbiosis has been related to the pathophysiology of disorders of - gut-brain interaction (DGBI) including irritable bowel syndrome (IBS) and functional constipation (FC). Accordingly, modulation of gut microbiota has been proposed as a potential treatment for these disorders. Gut microbiota modulation can be effected by probiotics, prebiotics, symbiotics, postbiotics, antibiotics and fecal transplantation (FMT) or bacteriotherapy. The latter is currently used for recurrent or severe Clostridium difficile colitis and has been the focus of recent research in IBS and FC...
September 12, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30216901/mucosal-permeability-and-mast-cells-as-targets-for-functional-gastrointestinal-disorders
#5
REVIEW
Åsa V Keita, Johan D Söderholm
The intestinal mucosa is constantly exposed to harmful luminal content, and uptake is closely controlled and regulated by neuro-immune factors. If control is broken, it might lead to ongoing enhanced mucosal permeability, potentially resulting in functional gastrointestinal disorders. The importance of mast cells in the regulation of the mucosal barrier has become obvious, and increased numbers and more activated mast cells have been observed in irritable bowel syndrome, functional dyspepsia and gastroesophageal reflux disease...
September 11, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30205360/in-silico-models-in-drug-development-where-we-are
#6
REVIEW
Janet Piñero, Laura I Furlong, Ferran Sanz
The use and utility of computational models in drug development has significantly grown in the last decades, fostered by the availability of high throughput datasets and new data analysis strategies. These in silico approaches are demonstrating their ability to generate reliable predictions as well as new knowledge on the mode of action of drugs and the mechanisms underlying their side effects, altogether helping to reduce the costs of drug development. The aim of this review is to provide a panorama of developments in the field in the last two years...
September 8, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30199758/placental-peptides-regulating-islet-adaptation-to-pregnancy-clinical-potential-in-gestational-diabetes-mellitus
#7
REVIEW
Sian Simpson, Lorna Smith, James Bowe
Pregnancy involves a progressive increase in insulin resistance and the β-cells must adapt to compensate and prevent gestational diabetes (GDM). In this review we discuss the evidence for placental peptides, including placental lactogen, hepatocyte growth factor, adiponectin and leptin, playing a role in the islet adaptation to pregnancy. The difficulties of translating data from rodent models into human pregnancy are covered and we summarise studies investigating associations between serum placental peptides and GDM risk...
September 7, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30193150/recent-advances-in-combinatorial-drug-screening-and-synergy-scoring
#8
REVIEW
Tea Pemovska, Johannes W Bigenzahn, Giulio Superti-Furga
Treatment of complex diseases such as cancer, cardiovascular disease, diabetes or neurological disorders frequently warrants the utilization of drug combinations for therapeutic intervention. In fact, the most successful example is the current standard of care for HIV patients. However, identification of successful drug cocktails is not a simple task and is hampered by lack of standardization in terminology, experimental protocols and models as well as data analysis. Here we discuss the most recent developments in combinatorial drug screening by covering technological advancements in screening strategies, cellular model systems as well as novel drug classes...
September 4, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30189347/opioid-receptors-in-the-gi-tract-targets-for-treatment-of-both-diarrhea-and-constipation-in-functional-bowel-disorders
#9
REVIEW
J Pannemans, M Corsetti
Opioids have been used for centuries, mostly as a sedative and to treat pain. Currently, they are used on a global scale for the treatment of acute and chronic pain in diseases as osteoarthritis, fibromyalgia, and low back pain. Binding of opioids on opioid receptors can cause a range of different effects such as changes in stress response, analgesia, motor activity and autonomic functions. This review provide a synthetic summary of the most recent literature on the use of drugs acting on mu-receptors to treat two prevalent functional bowel disorders, presenting with opposite bowel habit...
September 3, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30149217/turning-omics-data-into-therapeutic-insights
#10
REVIEW
Amanda Kedaigle, Ernest Fraenkel
Omics technologies have made it easier and cheaper to evaluate thousands of biological molecules at once. These advances have led to novel therapies approved for use in the clinic, elucidated the mechanisms behind disease-associated mutations, led to increased accuracy in disease subtyping and personalized medicine, and revealed novel uses and treatment regimes for existing drugs through drug repurposing and pharmacology studies. In this review, we summarize some of these milestones and discuss the potential of integrative analyses that combine multiple data types for further advances...
August 24, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30144686/islet-micrornas-in-health-and-type-2-diabetes
#11
REVIEW
Anna Wendt, Jonathan Ls Esguerra, Lena Eliasson
Failure of the β-cell to secrete enough insulin is a major contributing factor in the pathogenesis of type-2 diabetes (T2D). MicroRNAs provide an extra layer in the regulation of protein expression, and are thus involved in β-cell compensation during development of the disease. In this review, we discuss how microRNAs can regulate their target protein expression and phenotypic output, present the status of nutritional regulation of microRNA expression, and summarize work on microRNA expression in human islets...
August 22, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30144650/the-present-state-of-the-tuberculosis-drug-development-pipeline
#12
REVIEW
M Daben J Libardo, Helena Im Boshoff, Clifton E Barry
Tuberculosis now ranks as the leading cause of death in the world due to a single infectious agent. Current standard of care treatment can achieve very high cure rates for drug-sensitive disease but requires a 6-month duration of chemotherapy. Drug-resistant disease requires significantly longer treatment durations with drugs associated with a higher risk of adverse events. Thus, there is a pressing need for a drug regimen that is safer, shorter in duration and superior to current front-line chemotherapy in terms of efficacy...
August 22, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30142486/inflammatory-stress-in-islet-%C3%AE-cells-therapeutic-implications-for-type-2-diabetes
#13
REVIEW
Maria Lytrivi, Mariana Igoillo-Esteve, Miriam Cnop
Type 2 diabetes is a common complex disease. Relatively little is known about the underlying pathophysiology. Mild islet inflammation has been suggested to play a pathogenic role; here we review the available evidence. Mild islet inflammation is histologically detected in pancreas sections of type 2 diabetic patients. In experimental models, it can be triggered by excess nutrients, amyloid, lipopolysaccharide, and endoplasmic reticulum and oxidative stress. Transcriptome studies do not consistently identify pro-inflammatory gene expression signatures in type 2 diabetic islets, and genetic evidence calls into question the causality of inflammation...
August 21, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30142480/mechanisms-of-resistance-to-the-partner-drugs-of-artemisinin-in-the-malaria-parasite
#14
REVIEW
Rowena E Martin, Sarah H Shafik, Sashika N Richards
The deployment of artemisinin-based combination therapies (ACTs) has been, and continues to be, integral to reducing the number of malaria cases and deaths. However, their efficacy is being increasingly jeopardized by the emergence and spread of parasites that are resistant (or partially resistant) to the artemisinin derivatives and to their partner drugs, with the efficacy of the latter being especially crucial for treatment success. A detailed understanding of the genetic determinants of resistance to the ACT partner drugs, and the mechanisms by which they mediate resistance, is required for the surveillance of molecular markers and to optimize the efficacy and lifespan of the partner drugs through resistance management strategies...
August 21, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30103073/potential-of-mesenchymal-stromal-cells-for-improving-islet-transplantation-outcomes
#15
REVIEW
Chloe L Rackham, Peter M Jones
Allogeneic islet transplantation as a therapy for Type 1 Diabetes (T1D) is restricted by the limited availability of donor islets, loss of functional islets during pre-transplantation culture in vitro and further extensive loss during the immediate post-transplantation period when islet function and survival is compromised by the hypoxic, inflammatory host environment. In the longer term pathogenic T cell responses drive autoimmunity and chronic allograft rejection. Experimental studies have demonstrated that mesenchymal stromal cells (MSCs) have significant potential to improve the outcomes of clinical islet transplantation...
August 10, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30092386/how-scientific-literature-analysis-yields-innovative-therapeutic-hypothesis-through-integrative-iterations
#16
REVIEW
Francois Iris, Athanasios Beopoulos, Manuel Gea
It is becoming generally accepted that the current diagnostic system often guarantees, rather than diminishes, disease heterogeneity. In effects, syndrome-dominated conceptual thinking has become a barrier to understanding the biological causes of complex, multifactorial diseases characterized by clinical and therapeutic heterogeneity. Furthermore, not only is the flood of currently available medical and biological information highly heterogeneous, it is also often conflicting. Together with the entire absence of functional models of pathogenesis and pathological evolution of complex diseases, this leads to a situation where illness activity cannot be coherently approached and where therapeutic developments become highly problematic...
August 6, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30086433/identifying-novel-therapeutic-targets-for-diabetes-through-improved-understanding-of-islet-adhesion-receptors
#17
REVIEW
Oladapo E Olaniru, Shanta J Persaud
Adhesion receptors are transmembrane proteins that mediate cell-cell and cell-matrix communications. In addition to their adhesive role in maintaining islet architecture, they are also important for promoting islet cell survival, proliferation and secretory function. Their capacity for improving β-cell mass and insulin secretion suggest that they may be suitable targets for pharmacological intervention, and their interactions with extracellular matrix proteins hold promise in improving islet transplantation outcomes...
August 4, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30081259/will-ipsc-cardiomyocytes-revolutionize-the-discovery-of-drugs-for-heart-disease
#18
REVIEW
Arne An Bruyneel, Wesley L McKeithan, Dries Am Feyen, Mark Mercola
Cardiovascular disease remains the largest single cause of mortality in the Western world, despite significant advances in clinical management over the years. Unfortunately, the development of new cardiovascular medicines is stagnating and can in part be attributed to the difficulty of screening for novel therapeutic strategies due to a lack of suitable models. The advent of human induced pluripotent stem cells and the ability to make limitless numbers of cardiomyocytes could revolutionize heart disease modeling and drug discovery...
August 3, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30077118/mechanisms-of-artemisinin-resistance-in-plasmodium-falciparum-malaria
#19
REVIEW
Niraja Suresh, Kasturi Haldar
Artemisinin-based combination therapies (ACTs) have substantially reduced worldwide malaria burden and deaths. But malaria parasites have become resistant to artemisinins. Prior studies suggested two different molecular pathways of artemisinin-resistance. Here we unify recent findings into a single model, where elevation of a lipid, phosphatidylinositol-3-phosphate (PI3P) results in vesicle expansion that increases the engagement with the unfolded protein response (UPR). Vesicle expansion (rather than increasing individual genetic determinants of the UPR) efficiently induces artemisinin resistance likely by promoting 'proteostasis' (protein translation coupled to proper protein folding and vesicular remodeling) to mitigate artemisinin-induced proteopathy (death from global abnormal protein-toxicity)...
August 1, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/30077117/acting-beyond-2020-better-characterization-of-praziquantel-and-promising-antischistosomal-leads
#20
REVIEW
Gordana Panic, Jennifer Keiser
The commitment to eliminate schistosomiasis as a public health problem has mobilized the expansion of praziquantel treatment to meet the London Declaration targets. New research has thus sought to elucidate praziquantel's safety and efficacy in key demographics such as preschoolers and pregnant women, as well as novel elements of its pharmacokinetics and pharmacodynamics. At the same time, reliance on praziquantel ad infinitum would place schistosomiasis control at risk, should resistance occur. In response, the academic community has been filling the pre-clinical drug discovery pipeline with novel or resurrected drug candidates against schistosomiasis...
August 1, 2018: Current Opinion in Pharmacology
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