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Current Pharmacology Reports

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https://www.readbyqxmd.com/read/29242771/sentinels-at-the-frontline-the-role-of-intraepithelial-lymphocytes-in-inflammatory-bowel-disease
#1
Madeleine D Hu, Karen L Edelblum
Purpose of review: Intestinal mucosal immunity is tightly regulated to ensure effective host defense against invasive microorganisms while limiting the potential for aberrant damage. In inflammatory bowel disease (IBD), an imbalance between effector and regulatory T cell populations results in an uncontrolled inflammatory response to commensal bacteria. Intraepithelial lymphocytes (IEL) are perfectly positioned within the intestinal epithelium to provide the first line of mucosal defense against luminal microbes or rapidly respond to epithelial injury...
December 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/29130028/sphingosine-kinases-sphingosine-1-phosphate-signaling-in-hepatic-lipid-metabolism
#2
Eric K Kwong, Xiaojiaoyang Li, Phillip B Hylemon, Huiping Zhou
The ever-increasing prevalence of metabolic diseases such as dyslipidemia and diabetes in the western world continues to be of great public health concern. Biologically active sphingolipids, such as sphingosine 1-phosphate (S1P) and ceramide, are important regulators of lipid metabolism. S1P not only directly functions as an active intracellular mediator, but also activates multiple signaling pathways via five transmembrane G-protein coupled receptors (GPCRs), S1PR1-5. S1P is exclusively formed by sphingosine kinases (SphKs)...
August 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28983453/remote-sensing-between-liver-and-intestine-importance-of-microbial-metabolites
#3
Zidong Donna Fu, Julia Yue Cui
Recent technological advancements including metagenomics sequencing and metabolomics have allowed the discovery of critical functions of gut microbiota in obesity, malnutrition, neurological disorders, asthma, and xenobiotic metabolism. Classification of the human gut microbiome into distinct "enterotypes" has been proposed to serve as a new paradigm for understanding the interplay between microbial variation and human disease phenotypes, as many organs are affected by gut microbiota modifications during the pathogenesis of diseases...
June 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28642837/environmental-influences-in-the-etiology-of-colorectal-cancer-the-premise-of-metabolomics
#4
Nicholas J W Rattray, Georgia Charkoftaki, Zahra Rattray, James E Hansen, Vasilis Vasiliou, Caroline H Johnson
PURPOSE OF REVIEW: In this review we discuss how environmental exposures predominate the etiology of colorectal cancer (CRC). With CRC being a personalized disease influenced by genes and environment, our goal was to explore the role metabolomics can play in identifying exposures, assessing the interplay between co-exposures, and the development of personalized therapeutic interventions. RECENT FINDINGS: Approximately 10 % of CRC cases can be explained by germ-line mutations, whereas the prevailing majority are caused by an initiating exposure event occurring decades prior to diagnosis...
June 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28993795/reactive-carbonyl-species-scavengers-novel-therapeutic-approaches-for-chronic-diseases
#5
Sean S Davies, Linda S Zhang
PURPOSE OF THE REVIEW: To summarize recent evidence supporting the use of reactive carbonyl species scavengers in the prevention and treatment of disease. RECENT FINDINGS: The newly developed 2-aminomethylphenol class of scavengers shows great promise in preclinical trials for a number of diverse conditions including neurodegenerative diseases and cardiovascular disease. In addition, new studies with the thiol-based and imidazole-based scavengers have found new applications outside of adjunctive therapy for chemotherapeutics...
April 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28983452/role-of-fxr-in-liver-inflammation-during-nonalcoholic-steatohepatitis
#6
Laura E Armstrong, Grace L Guo
PURPOSE OF REVIEW: About 15-25% of patients with simple steatosis of non-alcoholic fatty liver disease progresses to non-alcoholic steatohepatitis (NASH), and the underlying mechanism for this progression has not been elucidated. NASH ultimately could progress to cirrhosis, an irreversible condition. RECENT FINDINGS: Farnesoid X receptor (FXR) has been studied for its role in modulating inflammation, and the expression of FXR is down-regulated during NASH development...
April 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28758057/the-opportunities-of-metabolomics-in-drug-safety-evaluation
#7
Pengcheng Wang, Amina I Shehu, Xiaochao Ma
Although safety of drug candidates is carefully monitored in preclinical and clinical studies using a variety of approaches, drug toxicity may still occur in clinical practice. Therefore, novel approaches are needed to complement the current drug safety evaluation system. Metabolomics comprehensively analyzes the metabolites altered by drug exposure, which can therefore be used to profile drug metabolism, endobiotic metabolism, and drug-microbiota interactions. The information from metabolomic analysis can be used to determine the off-targets of a drug candidate, and thus provide a mechanistic understanding of drug toxicity...
February 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28344923/impact-of-drug-treatment-at-neonatal-ages-on-variability-of-drug-metabolism-and-drug-drug-interactions-in-adult-life
#8
Stephanie Piekos, Chad Pope, Austin Ferrara, Xiao-Bo Zhong
PURPOSE OF REVIEW: As the number of patients taking more than one medication concurrently continues to increase, predicting and preventing drug-drug interactions (DDIs) is now more important than ever. Administration of one drug can cause changes in the expression and activity of drug metabolizing enzymes (DMEs) and alter the efficacy or toxicity of other medications that are substrates for these enzymes, resulting in a DDI. In today's medical practice, potential DDIs are evaluated based on the current medications a patient is taking with little regard to drugs the patient has been exposed to in the past...
February 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/29201631/infection-a-cause-of-and-cure-for-cancer
#9
REVIEW
Jenna H Newman, Andrew Zloza
Purpose of Review: This article provides a brief overview of the role that infections play in cancer emergence and cancer treatment. Recent Findings: A select number of pathogens have been reported to increase the incidence of specific cancers (directly through altering gene expression or indirectly through inducing chronic inflammation). These have been referred to as oncogenic pathogens. Conversely, a subset of pathogens has been demonstrated to preferentially cause lysis of tumor cells, leading to tumor regression and improved anti-tumor immunity...
2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28261547/progress-in-prediction-and-interpretation-of-clinically-relevant-metabolic-drug-drug-interactions-a-minireview-illustrating-recent-developments-and-current-opportunities
#10
REVIEW
Stephen Fowler, Peter N Morcos, Yumi Cleary, Meret Martin-Facklam, Neil Parrott, Michael Gertz, Li Yu
PURPOSE OF REVIEW: This review gives a perspective on the current "state of the art" in metabolic drug-drug interaction (DDI) prediction. We highlight areas of successful prediction and illustrate progress in areas where limits in scientific knowledge or technologies prevent us from having full confidence. RECENT FINDINGS: Several examples of success are highlighted. Work done for bitopertin shows how in vitro and clinical data can be integrated to give a model-based understanding of pharmacokinetics and drug interactions...
2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28966903/challenges-and-opportunities-with-predicting-in-vivo-phase-ii-metabolism-via-glucuronidation-from-in-vitro-data
#11
Shufan Ge, Yifan Tu, Ming Hu
Glucuronidation is the most important phase II metabolic pathway which is responsible for the clearance of many endogenous and exogenous compounds. To better understand the elimination process for compounds undergoing glucuronidation and identify compounds with desirable in vivo pharmacokinetic properties, many efforts have been made to predict in vivo glucuronidation using in vitro data. In this article, we reviewed typical approaches used in previous predictions. The problems and challenges in prediction of glucuronidation were discussed...
December 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28546917/challenges-in-the-delivery-of-therapies-to-melanoma-brain-metastases
#12
Gautham Gampa, Shruthi Vaidhyanathan, Brynna-Wilken Resman, Karen E Parrish, Svetomir N Markovic, Jann N Sarkaria, William F Elmquist
Brain metastases are a major cause of morbidity and mortality in patients with advanced melanoma. Recent approval of several molecularly-targeted agents and biologics has brought hope to patients with this previously untreatable disease. However, patients with symptomatic melanoma brain metastases have often been excluded from pivotal clinical trials. This may be in part attributed to the fact that several of the approved small molecule molecularly-targeted agents are substrates for active efflux at the blood-brain barrier, limiting their effective delivery to brain metastases...
December 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28534003/new-pharmacological-approaches-to-treating-non-motor-symptoms-of-parkinson-s-disease
#13
Michael A Kelberman, Elena M Vazey
PURPOSE OF REVIEW: Non-motor symptoms in patients with Parkinson's Disease (PD) are better predictors of quality of life changes, caregiver burden, and mortality than motor symptoms. Levodopa has limited, and sometimes detrimental, effects on these symptoms. In this review we discuss recent evidence on pharmacological treatments for non-motor symptoms. RECENT FINDINGS: Breakthroughs have been made in the treatment of psychosis and sleep dysfunction. Pimavanserin has become the first FDA approved drug for PD psychosis...
December 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28042530/enzyme-prodrug-systems-for-cancer-gene-therapy
#14
Obeid M Malekshah, Xuguang Chen, Alireza Nomani, Siddik Sarkar, Arash Hatefi
The use of enzyme/prodrug system has gained attention because it could help improve the efficacy and safety of conventional cancer chemotherapies. In this approach, cancer cells are first transfected with a gene that can express an enzyme with ability to convert a non-toxic prodrug into its active cytotoxic form. As a result, the activated prodrug could kill the transfected cancer cells. Despite the significant progress of different suicide gene therapy protocols in preclinical studies and early clinical trials, none has reached the clinic due to several shortcomings...
December 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28936389/disease-progression-modeling-key-concepts-and-recent-developments
#15
Sarah F Cook, Robert R Bies
Disease modeling involves the use of mathematical functions to describe quantitatively the time course of disease progression. In order to characterize the natural progression of disease, these models generally incorporate longitudinal data for some biomarker(s) of disease severity or can incorporate more direct measures of disease severity. Disease models are also often linked to pharmacokinetic-pharmacodynamic models so that the influence of drug treatment on disease progression can be quantified and evaluated...
October 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28758056/single-cell-transcriptome-analysis-of-developing-and-regenerating-spiral-ganglion-neurons
#16
Kelvin Y Kwan
The spiral ganglion neurons (SGNs) of the cochlea are essential for our ability to hear. SGN loss after exposure to ototoxic drugs or loud noise results in hearing loss. Pluripotent stem cell-derived and endogenous progenitor cell types have the potential to become SGNs and are cellular foundations for replacement therapies. Repurposing transcriptional regulatory networks to promote SGN differentiation from progenitor cells is a strategy for regeneration. Advances in the Fludigm C1 workflow or Drop-seq allow sequencing of single cell transcriptomes to reveal variability between cells...
October 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/27774408/bioinformatic-analysis-of-dna-methylation-in-neural-progenitor-cell-models-of-alcohol-abuse
#17
Eileen N Oni, Ronald P Hart
Several recent publications sought to investigate the effects of ethanol treatment on models of central nervous system development, specifically through changes in DNA methylation. Regulation of DNA methylation causes a long-lasting, epigenetic change in the capacity of the genome to respond to developmental or metabolic stimuli. Changes in technologies for quantifying DNA methylation have increased the ability to identify and interpret potential effects of ethanol. Here, we review these recent studies in order to evaluate the detection technologies and bioinformatic analyses...
October 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/27795941/a-molecular-aspect-in-the-regulation-of-drug-metabolism-does-pxr-induced-enzyme-expression-always-lead-to-functional-changes-in-drug-metabolism
#18
Yuan Wei, Chenxiao Tang, Vinayak Sant, Song Li, Samuel M Poloyac, Wen Xie
Pregnane X receptor (PXR, NR112) is a xenobiotic receptor whose primary function is to regulate the expression of drug-metabolizing enzymes (DMEs) and drug transporters. Drug-induced PXR activation and subsequent enzyme and transporter induction has been proposed to be an important mechanism for the drug-drug interactions. In addition to activating PXR, many pharmaceutical chemicals can also function as reversible or irreversible inhibitors of DMEs, which may also impact the pharmacokinetics and pharmacodynamics (PK/PD) of drugs...
August 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/27774407/a-critical-review-of-methodologies-to-detect-reactive-oxygen-and-nitrogen-species-stimulated-by-nadph-oxidase-enzymes-implications-in-pesticide-toxicity
#19
Balaraman Kalyanaraman, Micael Hardy, Jacek Zielonka
In this review, potential fluorescent probe applications for detecting reactive oxygen and nitrogen species (ROS/RNS) generated from NADPH oxidases (e.g., Nox2) and nitric oxide synthase enzymes are discussed in the context of pesticide toxicology. Identification of the specific marker products derived from the interaction between ROS/RNS and the fluorescent probes (e.g., hydroethidine and coumarin boronate) is critical. Due to the complex nature of reactions between the probes and ROS/RNS, we suggest avoiding the use of fluorescence microscopy for detecting oxidizing/nitrating species...
August 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/27617186/progress-and-prospects-of-reactive-oxygen-species-in-metal-carcinogenesis
#20
Lei Wang, James T F Wise, Zhuo Zhang, Xianglin Shi
Carcinogenesis induced by environmental metal exposure is a major public health concern. The exact mechanisms underlying metal carcinogenesis remain elusive. In the past few decades, the relationship between metal induced generation of reactive oxygen species (ROS) and the mechanism of metal carcinogenesis has been established. The carcinogenic process is a very complex one. In the early stage of metal carcinogenesis or cell transformation high levels of ROS are oncogenic by causing DNA damage, genetic instability, epigenetic alteration, and metabolic reprogramming, leading to malignant transformation...
August 2016: Current Pharmacology Reports
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