3,883 results match your criteria Drug Discoveries & Therapeutics [Journal]


Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis.

Int J Mol Sci 2018 Dec 14;19(12). Epub 2018 Dec 14.

Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.

Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic. Read More

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http://dx.doi.org/10.3390/ijms19124056DOI Listing
December 2018

Invasive and Non-invasive Stimulation of the Obese Human Brain.

Authors:
Burkhard Pleger

Front Neurosci 2018 29;12:884. Epub 2018 Nov 29.

Department of Neurology, BG University Clinic Bergmannsheil, Ruhr-University Bochum, Bochum, Germany.

Accumulating evidence suggests that non-invasive and invasive brain stimulation may reduce food craving and calorie consumption rendering these techniques potential treatment options for obesity. Non-invasive transcranial direct current stimulation (tDCS) or repetitive transcranial magnet stimulation (rTMS) are used to modulate activity in superficially located executive control regions, such as the dorsolateral prefrontal cortex (DLPFC). Modulation of the DLPFC's activity may alter executive functioning and food reward processing in interconnected dopamine-rich regions such as the striatum or orbitofrontal cortex. Read More

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http://dx.doi.org/10.3389/fnins.2018.00884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281888PMC
November 2018

From Discovery to Bedside: Targeting the Ubiquitin System.

Cell Chem Biol 2018 Nov 28. Epub 2018 Nov 28.

Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA 94008, USA.

The ubiquitin/proteasome system is a primary conduit for selective intracellular protein degradation. Since its discovery over 30 years ago, this highly regulated system continues to be an active research area for drug discovery that is exemplified by several approved drugs. Here we review compounds in preclinical testing, clinical trials, and approved drugs, with the aim of highlighting innovative discoveries and breakthrough therapies that target the ubiquitin system. Read More

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http://dx.doi.org/10.1016/j.chembiol.2018.10.022DOI Listing
November 2018

LncRNAs in ovarian cancer.

Clin Chim Acta 2018 Dec 13. Epub 2018 Dec 13.

Department of Obstetrics and Gynecology, Zhangjiagang First People's Hospital, Zhangjiagang 215600, Jiangsu, PR China. Electronic address:

Ovarian cancer is one of the most common gynecologic malignancies and has a poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators of cancer development. Studies have shown that the dysregulation of lncRNAs is frequently observed in ovarian cancer and greatly contributes to malignant phenotypical changes. Read More

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http://dx.doi.org/10.1016/j.cca.2018.12.013DOI Listing
December 2018
1 Read

β-Arrestin Based Receptor Signaling Paradigms: Potential Therapeutic Targets for Complex Age-Related Disorders.

Front Pharmacol 2018 28;9:1369. Epub 2018 Nov 28.

Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

G protein coupled receptors (GPCRs) were first characterized as signal transducers that elicit downstream effects through modulation of guanine (G) nucleotide-binding proteins. The pharmacotherapeutic exploitation of this signaling paradigm has created a drug-based field covering nearly 50% of the current pharmacopeia. Since the groundbreaking discoveries of the late 1990s to the present day, it is now clear however that GPCRs can also generate productive signaling cascades through the modulation of β-arrestin functionality. Read More

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http://dx.doi.org/10.3389/fphar.2018.01369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280185PMC
November 2018

Pathogenesis and therapeutic interventions for ANCA-associated vasculitis.

Nat Rev Rheumatol 2018 Dec 12. Epub 2018 Dec 12.

Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects systemic small vessels and is accompanied by the presence of ANCAs in the serum. This disease entity includes microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and drug-induced AAV. Similar to other autoimmune diseases, AAV develops in patients with a predisposing genetic background who have been exposed to causative environmental factors. Read More

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http://dx.doi.org/10.1038/s41584-018-0145-yDOI Listing
December 2018

Shotgun Proteomic Profiling of Bloodborne Nanoscale Extracellular Vesicles.

Methods Mol Biol 2019 ;1897:403-416

Drug Discovery Laboratory, Department of Neurology, Mary S. Easton Center for Alzheimer's Disease Research, University of California, Los Angeles, Los Angeles, CA, USA.

Analyses of bloodborne nanoscale extracellular vesicles (nsEVs) have shown tremendous promise in enabling the development of noninvasive blood-based clinical diagnostic tests, predicting and monitoring the efficacy of treatment programs, and identifying new drug targets in the context of health conditions such as cancer and Alzheimer's disease. In this chapter we present a protocol for generating global nsEV proteomic profiles that can further the utility of nsEV analysis for the above biomedical applications by enlightening us of differences in protein abundance across normal and disease state nsEVs. This protocol features the use of magnetic particle-based immunoprecipitation to enrich highly purified populations of nsEVs directly from plasma or serum samples. Read More

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http://dx.doi.org/10.1007/978-1-4939-8935-5_32DOI Listing
January 2019

Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials.

Exp Dermatol 2018 Dec 11. Epub 2018 Dec 11.

Integrative Stem Cell Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan.

Skin evolves essential appendages and indispensable types of cells that synergistically insulate the body from environmental insults. Residing in the specific regions in the skin such as epidermis, dermis and hair follicle, melanocytes perform an array of vital functions including defending the ultraviolet radiation and diversifying animal appearance. As one of the adult stem cells, melanocyte stem cells in the hair follicle bulge niche can proliferate, differentiate, and keep quiescence to control and coordinate tissue homeostasis, repair, and regeneration. Read More

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http://dx.doi.org/10.1111/exd.13856DOI Listing
December 2018
2 Reads

Synovial sarcoma: when epigenetic changes dictate tumour development.

Swiss Med Wkly 2018 11 2;148:w14667. Epub 2018 Dec 2.

Experimental Pathology Service, Institute of Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.

Synovial sarcoma is a highly aggressive soft tissue malignancy that often affects adolescents and young adults. It is associated with a unique chromosomal translocation that results in the formation and expression of the fusion gene SS18-SSX, which underlies its pathogenesis. Although SS18-SSX provides a potentially unique therapeutic target, all attempts to neutralise it have been unsuccessful thus far. Read More

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http://dx.doi.org/10.4414/smw.2018.14667DOI Listing
November 2018

EZH2, HIF-1, and Their Inhibitors: An Overview on Pediatric Cancers.

Front Pediatr 2018 19;6:328. Epub 2018 Nov 19.

Department of Experimental Medicine, Sapienza University, Rome, Italy.

During the past decades, several discoveries have established the role of epigenetic modifications and cellular microenvironment in tumor growth and progression. One of the main representatives concerning epigenetic modification is the polycomb group (PcG). It is composed of different highly conserved epigenetic effector proteins preserving, through several post-translational modifications of histones, the silenced state of the genes implicated in a wide range of central biological events such as development, stem cell formation, and tumor progression. Read More

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https://www.frontiersin.org/article/10.3389/fped.2018.00328/
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http://dx.doi.org/10.3389/fped.2018.00328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254013PMC
November 2018
2 Reads

Role of Academic Biobanks in Public-Private Partnerships in the European Biobanking and BioMolecular Resources Research Infrastructure Community.

Biopreserv Biobank 2018 Nov 30. Epub 2018 Nov 30.

5 Department of Human Genetics, Leiden University Medical Center , Leiden, the Netherlands .

Public-private partnerships (PPP) are an efficient means to advance scientific discoveries and boost the medical innovations needed to improve precision medicine. The increasing number and novel nature of such collaborations is keeping the biomedical field in a constant flux. Here we provide an update on PPP development involving academic biobanks in the BBMRI community (the European Biobanking and BioMolecular Resources Research Infrastructure) and report the views on PPP of 20 key players from this field. Read More

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http://dx.doi.org/10.1089/bio.2018.0024DOI Listing
November 2018

Copper-catalyzed arene amination in pure aqueous ammonia.

Org Biomol Chem 2018 Nov 29. Epub 2018 Nov 29.

One-stop Sharing Facility Center for Future Drug Discoveries, Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, Japan.

A simple protocol for copper-catalyzed arene amination using aqueous ammonia without any additional ligands and organic coordinating solvents has been developed. The reaction pathway via a Cu(i)/Cu(iii) mechanism is proposed based on the results of control experiments as well as DFT calculations. Read More

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http://dx.doi.org/10.1039/c8ob02708kDOI Listing
November 2018

Influence of PDLA nanoparticles size on drug release and interaction with cells.

J Biomed Mater Res A 2018 Nov 28. Epub 2018 Nov 28.

3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.

Polymeric nanoparticles (NPs) are strong candidates for the development of systemic and targeted drug delivery applications. Their size is a determinant property since it defines the NP-cell interactions, drug loading capacity, and release kinetics. Herein, poly(d,l-lactic acid) (PDLA) NPs were produced by the nanoprecipitation method, in which the influence of type and concentration of surfactant as well as PDLA concentration were assessed. Read More

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http://dx.doi.org/10.1002/jbm.a.36563DOI Listing
November 2018

Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial.

Neurosurgery 2018 Nov 26. Epub 2018 Nov 26.

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, Chicago, Illinois.

Background: More than a million Americans harbor a cerebral cavernous angioma (CA), and those who suffer a prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may confer a therapeutic benefit.

Objective: To evaluate whether atorvastatin produces a difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM) on magnetic resonance imaging in CAs that have demonstrated a symptomatic hemorrhage in the prior year. Read More

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http://dx.doi.org/10.1093/neuros/nyy539DOI Listing
November 2018
2 Reads

Report: Attenuation of apomorphine induced behavioral sensitization in rats pre-treated with tryptophan.

Pak J Pharm Sci 2018 Nov;31(6):2561-2567

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

Psychostimulants substances, some of which are abused by humans, are generally believed to produce sensitization effects when they are repeatedly administered to animals. Apomorphine, a non-narcotic derivative of morphine, having agonistic property for dopamine in order to produce psycho stimulant-like effects. Meanwhile, chronic administration leads to behavioral sensitization. Read More

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November 2018
4 Reads

The renaissance in psychedelic research: What do preclinical models have to offer.

Authors:
Kevin S Murnane

Prog Brain Res 2018 5;242:25-67. Epub 2018 Oct 5.

Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, Mercer University Health Sciences Center, Atlanta, GA, United States. Electronic address:

Human research with psychedelics is making groundbreaking discoveries. Psychedelics modify enduring elements of personality and seemingly reduce anxiety, depression, and substance dependence in small but well-designed clinical studies. Psychedelics are advancing through pharmaceutical regulatory systems, and neuroimaging studies have related their extraordinary effects to select brain networks. Read More

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http://dx.doi.org/10.1016/bs.pbr.2018.08.003DOI Listing
October 2018
7 Reads

Diverse roles of the E2/E3 hybrid enzyme UBE2O in the regulation of protein ubiquitination, cellular functions, and disease onset.

FEBS J 2018 Nov 23. Epub 2018 Nov 23.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, China.

The ubiquitin-proteasome system is an important regulatory machinery involved in proteostasis and cellular signaling. Proteins are ubiquitinated via the concerted action of E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes, and E3 ubiquitin ligases. Although most of the studies to date focus on the significance of E3 ubiquitin ligases in disease development and therapeutic treatment, recent discoveries suggest that E2 ubiquitin-conjugating enzymes might also be potential drug targets. Read More

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http://dx.doi.org/10.1111/febs.14708DOI Listing
November 2018
5 Reads

Protocol for a phase II, open-label exploratory study investigating the efficacy of fesoterodine for treatment of adult patients with spinal cord injury suffering from neurogenic detrusor overactivity for amelioration of autonomic dysreflexia.

BMJ Open 2018 Nov 21;8(11):e024084. Epub 2018 Nov 21.

International Collaboration on Repair Discoveries (ICORD), Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Introduction: Managing and preventing risk factors associated with cardiovascular and cerebrovascular impairment is well studied in able-bodied individuals. However, individuals with spinal cord injury (SCI) at or above the spinal segment T6 are prone to experience autonomic dysreflexia (AD) but also to suffer from neurogenic detrusor overactivity (NDO). Treatment of NDO would not only improve lower urinary tract function but could also reduce the severity and frequency of life-threatening episodes of AD. Read More

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http://dx.doi.org/10.1136/bmjopen-2018-024084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252748PMC
November 2018
2 Reads

Dual-ion delivery for synergistic angiogenesis and bactericidal capacity with silica-based microsphere.

Acta Biomater 2019 Jan 19;83:322-333. Epub 2018 Nov 19.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea. Electronic address:

Inhibition of bacterial growth with the simultaneous promotion of angiogenesis has been challenging in the repair and regeneration of infected tissues. Here, we aim to tackle this issue through the use of cobalt-doped silicate microspheres that can sustainably release dual ions (silicate and cobalt) at therapeutically-relevant doses. The cobalt was doped up to 2. Read More

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http://dx.doi.org/10.1016/j.actbio.2018.11.025DOI Listing
January 2019
4 Reads

Injectable hydrogel composite containing modified gold nanoparticles: implication in bone tissue regeneration.

Int J Nanomedicine 2018 1;13:7019-7031. Epub 2018 Nov 1.

Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea,

Background: For effective bone regeneration, it is necessary to implant a biocompatible scaffold that is capable of inducing cell growth and continuous osteogenic stimulation at the defected site. Here, we suggest an injectable hydrogel system using enzymatic cross-linkable gelatin (Gel) and functionalized gold nanoparticles (GNPs).

Methods: In this work, tyramine (Ty) was synthesized on the gelatin backbone (Gel-Ty) to enable a phenol crosslinking reaction with horseradish peroxidase (HRP). Read More

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http://dx.doi.org/10.2147/IJN.S185715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219106PMC
November 2018
1 Read

The interacting domains in cereblon differentially modulate the immunomodulatory drug-mediated ubiquitination and degradation of its binding partners.

Biochem Biophys Res Commun 2018 Dec 17;507(1-4):443-449. Epub 2018 Nov 17.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China. Electronic address:

Cereblon (CRBN), a substrate receptor of the cullin-4 RING E3 ligase (CRL4), has been utilized for the targeted protein degradation via small molecular weight CRBN modulators. However, it is unclear whether and how proteins that interact with CRBN at different domains are affected by these modulators. Here, we use CRBN and its four binding partners, c-Jun, chloride channel protein CLC-1, transcription factor IKZF1, and MEIS2, as model proteins to investigate the effect of immunomodulatory drugs (IMiDs) including thalidomide, lenalidomide, and pomalidomide, on their stability, ubiquitination, and interaction with CRBN. Read More

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http://dx.doi.org/10.1016/j.bbrc.2018.11.058DOI Listing
December 2018
6 Reads

Topoisomerase 1B poisons: Over a half-century of drug leads, clinical candidates, and serendipitous discoveries.

Authors:
Maris A Cinelli

Med Res Rev 2018 Nov 19. Epub 2018 Nov 19.

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan.

Topoisomerases are DNA processing enzymes that relieve supercoiling (torsional strain) in DNA, are necessary for normal cellular division, and act by nicking (and then religating) DNA strands. Type 1B topoisomerase (Top1) is overexpressed in certain tumors, and the enzyme has been extensively investigated as a target for cancer chemotherapy. Various chemical agents can act as "poisons" of the enzyme's religation step, leading to Top1-DNA lesions, DNA breakage, and eventual cellular death. Read More

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http://dx.doi.org/10.1002/med.21546DOI Listing
November 2018
2 Reads

The use of proteomic technologies to study molecular mechanisms of multidrug resistance in cancer.

Eur J Med Chem 2018 Oct 11;162:423-434. Epub 2018 Oct 11.

Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Multidrug resistance (MDR), defined as the cross-resistance of cancer cells toward a broad range of chemotherapeutic agents, is a universal and intractable problem in chemotherapy. The understanding of MDR mechanisms is essential to discover the potential biomarkers for predicting multidrug resistance and more importantly, tackling and preventing multidrug resistance. Multiple technologies have been used to study MDR mechanisms including comparative genomic hybridization, DNA array, differential display RT-PCR and various immunoassays. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02235234183086
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http://dx.doi.org/10.1016/j.ejmech.2018.10.001DOI Listing
October 2018
5 Reads

Itaconate: an emerging determinant of inflammation in activated macrophages.

Immunol Cell Biol 2018 Nov 14. Epub 2018 Nov 14.

Key Laboratory for Arteriosclerology of Hunan Province, Medical Research Experiment Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Cardiovascular Disease, University of South China, Hengyang, Hunan, 421001, China.

Macrophages play a central role in innate immunity as the first line of defense against pathogen infection. Upon exposure to inflammatory stimuli, macrophages rapidly respond and subsequently undergo metabolic reprogramming to substantially produce cellular metabolites such as itaconate. As a derivate of the tricarboxylic acid cycle, itaconate is derived from the decarboxylation of cis-aconitate mediated by immunoresponsive gene 1 in the mitochondrial matrix. Read More

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http://dx.doi.org/10.1111/imcb.12218DOI Listing
November 2018
2 Reads

Impact of biobanks on research outcomes in rare diseases: a systematic review.

Orphanet J Rare Dis 2018 Nov 12;13(1):202. Epub 2018 Nov 12.

School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, Perth, WA, 6027, Australia.

Background: Alleviating the burden of rare diseases requires research into new diagnostic and therapeutic strategies. We undertook a systematic review to identify and compare the impact of stand-alone registries, registries with biobanks, and rare disease biobanks on research outcomes in rare diseases.

Methods: A systematic review and meta-aggregation was conducted using the preferred reporting items for systematic reviews and meta-analyses (the PRISMA statement). Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0
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http://dx.doi.org/10.1186/s13023-018-0942-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233271PMC
November 2018
5 Reads

Identification of a somatic mutation in the RHEB gene through high depth and ultra-high depth next generation sequencing in a patient with Hemimegalencephaly and drug resistant Epilepsy.

Eur J Med Genet 2018 Nov 8. Epub 2018 Nov 8.

Consultorio y Laboratorio de Neurogenética, Centro Universitario de Neurología y División Neurología, Hospital José María Ramos Mejía, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina; Programa de Medicina de Precisión y Genómica Clínica, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina. Electronic address:

Malformations of cortical development are a frequent cause of drug-resistant Epilepsy and developmental delay. Hemimegalencephaly is a Malformation of cortical development characterized by enlargement of all or a part of one cerebral hemisphere. Germline and somatic mutation in genes belonging to the Mammalian Target of Rapamycin (mTOR) pathway has been identified in patients suffering from epilepsy secondary to Hemimegalencephaly and focal cortical dysplasia. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17697212183057
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http://dx.doi.org/10.1016/j.ejmg.2018.11.005DOI Listing
November 2018
4 Reads

Bioactive Natural Spirolactone-Type 6,7---Kaurane Diterpenoids and Synthetic Derivatives.

Molecules 2018 Nov 8;23(11). Epub 2018 Nov 8.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

Diterpenoids are widely distributed natural products and have caused considerable interest because of their unique skeletons and antibacterial and antitumor activities and so on. In light of recent discoveries, -kaurane diterpenoids, which exhibit a wide variety of biological activities, such as anticancer and anti-inflammatory activities, pose enormous potential to serve as a promising candidate for drug development. Among them, spirolactone-type 6,7---kaurane diterpenoids, with interesting molecular skeleton, complex oxidation patterns, and bond formation, exhibit attractive activities. Read More

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http://www.mdpi.com/1420-3049/23/11/2914
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http://dx.doi.org/10.3390/molecules23112914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278314PMC
November 2018
2 Reads

Silk-Based Antimicrobial Polymers as a New Platform to Design Drug-Free Materials to Impede Microbial Infections.

Macromol Biosci 2018 Dec 8;18(12):e1800262. Epub 2018 Nov 8.

Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.

Surgical site infections (SSI) represent a serious health problem that occur after invasive surgery, thus new antimicrobial biomaterials able to prevent SSI are needed. Silks are natural biopolymers with excellent biocompatibility, low immunogenicity and controllable biodegradability. Spider silk-based materials can be bioengineered and functionalized with specific peptides, such as antimicrobial peptides, creating innovative polymers. Read More

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http://doi.wiley.com/10.1002/mabi.201800262
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http://dx.doi.org/10.1002/mabi.201800262DOI Listing
December 2018
8 Reads

Bacteriophage Therapy: Clinical Trials and Regulatory Hurdles.

Front Cell Infect Microbiol 2018 23;8:376. Epub 2018 Oct 23.

The Marshall Centre for Infectious Diseases Research and Training, School of Biomedical Sciences, The University of Western Australia, Crawley, WA, Australia.

Increasing reports of antimicrobial resistance and limited new antibiotic discoveries and development have fuelled innovation in other research fields and led to a revitalization of bacteriophage (phage) studies in the Western world. Phage therapy mainly utilizes obligately lytic phages to kill their respective bacterial hosts, while leaving human cells intact and reducing the broader impact on commensal bacteria that often results from antibiotic use. Phage therapy is rapidly evolving and has resulted in cases of life-saving therapeutic use and multiple clinical trials. Read More

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https://www.frontiersin.org/article/10.3389/fcimb.2018.00376
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http://dx.doi.org/10.3389/fcimb.2018.00376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205996PMC
October 2018
18 Reads

Stress-driven discovery in the natural products: A gateway towards new drugs.

Biomed Pharmacother 2019 Jan 3;109:459-467. Epub 2018 Nov 3.

UQ Diamantina Institute, Translational Research Institute, Faculty of Medicine, The University of Queensland, 37 Kent Street Woolloongabba, Brisbane, QLD 4102, Australia; Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Pigdons Road, Waurn Ponds, Victoria 3216, Australia; School of Agriculture and Food, The University of Melbourne, Parkville, VIC 3010, Australia.

Elicitation by chemical means including heavy metals is one of a novel technique for drug discoveries. In this review, the effect of heavy metals on animal, plants and microorganisms for the production of novel compounds with the unique structures has been discussed. The number of parameters such as metal concentration, type, dose, treatment schedule, duration of metal exposure, and nutrient composition are significant factors altering the secondary metabolites production. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07533322183719
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http://dx.doi.org/10.1016/j.biopha.2018.10.173DOI Listing
January 2019
14 Reads
2.023 Impact Factor

The biological and pharmacological roles of polyphenol flavonoid tilianin.

Eur J Pharmacol 2019 Jan 31;842:291-297. Epub 2018 Oct 31.

College of Veterinary Medicine and Biosafety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea. Electronic address:

Archaeological evidence for phytomedicine has established the importance of plants as a source of biologically active molecules with beneficial effects. Related studies constitute significant tools for novel drug discovery. A major benefit of phytomedicine is that standard ethnopharmacological evidence regarding traditional uses can give indications for molecules that may be therapeutically significant. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00142999183062
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http://dx.doi.org/10.1016/j.ejphar.2018.10.044DOI Listing
January 2019
4 Reads
2.530 Impact Factor

Genomic and Transcriptomic Characterization Links Cell Lines with Aggressive Head and Neck Cancers.

Cell Rep 2018 Oct;25(5):1332-1345.e5

Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. Electronic address:

Cell lines are important tools for biological and preclinical investigation, and establishing their relationship to genomic alterations in tumors could accelerate functional and therapeutic discoveries. We conducted integrated analyses of genomic and transcriptomic profiles of 15 human papillomavirus (HPV)-negative and 11 HPV-positive head and neck squamous cell carcinoma (HNSCC) lines to compare with 279 tumors from The Cancer Genome Atlas (TCGA). We identified recurrent amplifications on chromosomes 3q22-29, 5p15, 11q13/22, and 8p11 that drive increased expression of more than 100 genes in cell lines and tumors. Read More

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http://dx.doi.org/10.1016/j.celrep.2018.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280671PMC
October 2018
4 Reads

Tumor suppressor miR-145-5p sensitizes prolactinoma to bromocriptine by downregulating TPT1.

J Endocrinol Invest 2018 Oct 28. Epub 2018 Oct 28.

Department of Histology and Embryology, Medical School of Sun Yat-sen University, No. 74, Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.

Purpose: Prolactinoma is the most commonly seen secretory tumor of pituitary glands, which accounts for approximately up to 40% of total pituitary adenomas. Due to its high drug resistance, dopamine agonist, such as bromocriptine, has limited effect on the treatment of patients with prolactinoma. Recent discoveries have revealed that multiple miRNAs were involved in regulating drug resistance. Read More

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http://link.springer.com/10.1007/s40618-018-0963-4
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http://dx.doi.org/10.1007/s40618-018-0963-4DOI Listing
October 2018
7 Reads

Microbial Sterolomics as a Chemical Biology Tool.

Authors:
Brad A Haubrich

Molecules 2018 Oct 25;23(11). Epub 2018 Oct 25.

Department of Chemistry, University of Nevada, Reno, Reno, NV 89557, USA.

Metabolomics has become a powerful tool in chemical biology. Profiling the human sterolome has resulted in the discovery of noncanonical sterols, including oxysterols and meiosis-activating sterols. They are important to immune responses and development, and have been reviewed extensively. Read More

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http://www.mdpi.com/1420-3049/23/11/2768
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http://dx.doi.org/10.3390/molecules23112768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278499PMC
October 2018
3 Reads

Inflammation and Gut-Brain Axis During Type 2 Diabetes: Focus on the Crosstalk Between Intestinal Immune Cells and Enteric Nervous System.

Front Neurosci 2018 10;12:725. Epub 2018 Oct 10.

NeuroMicrobiota, European Associated Laboratory INSERM/UCLouvain, Brussels, Belgium.

The gut-brain axis is now considered as a major actor in the control of glycemia. Recent discoveries show that the enteric nervous system (ENS) informs the hypothalamus of the nutritional state in order to control glucose entry in tissues. During type 2 diabetes (T2D), this way of communication is completely disturbed leading to the establishment of hyperglycemia and insulin-resistance. Read More

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https://www.frontiersin.org/articles/10.3389/fnins.2018.0072
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https://www.frontiersin.org/article/10.3389/fnins.2018.00725
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http://dx.doi.org/10.3389/fnins.2018.00725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191495PMC
October 2018
5 Reads

Modernized Classification of Cardiac Antiarrhythmic Drugs.

Circulation 2018 Oct;138(17):1879-1896

Physiological Laboratory (C.L.-H.H.), University of Cambridge, United Kingdom.

Background: Among his major cardiac electrophysiological contributions, Miles Vaughan Williams (1918-2016) provided a classification of antiarrhythmic drugs that remains central to their clinical use.

Methods: We survey implications of subsequent discoveries concerning sarcolemmal, sarcoplasmic reticular, and cytosolic biomolecules, developing an expanded but pragmatic classification that encompasses approved and potential antiarrhythmic drugs on this centenary of his birth.

Results: We first consider the range of pharmacological targets, tracking these through to cellular electrophysiological effects. Read More

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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035455DOI Listing
October 2018

Design, Synthesis and Antifibrosis Activity in Liver of Nonsecosteroidal Vitamin D Receptor Agonists with Phenyl-pyrrolyl Pentane Skeleton.

J Med Chem 2018 Oct 10. Epub 2018 Oct 10.

Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components and results to impairment of liver function. Vitamin D plays a critical role in the development of liver fibrosis as it inhibits transforming growth factor β1 (TGFβ1)-induced excessive deposition of ECM in activated hepatic stellate cells (HSCs). Here, a series of novel nonsecosteroidal Vitamin D receptor (VDR) agonists with phenyl-pyrrolyl pentane skeleton was designed and synthesized. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.8b01165DOI Listing
October 2018
9 Reads
5.450 Impact Factor

Antifungal drugs: New insights in research & development.

Pharmacol Ther 2018 Oct 19. Epub 2018 Oct 19.

Graduate Programme in Genomic Science and Biotechnology, Catholic University of Brasília, Brazil; Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brazil. Electronic address:

The need for better antifungal therapy is commonly accepted in view of the high mortality rates associated with systemic infections, the low number of available antifungal classes, their associated toxicity and the increasing number of infections caused by strains with natural or acquired resistance. The urgency to expand the range of therapeutic options for the treatment of fungal infections has led researchers in recent decades to seek alternative antifungal targets when compared to the conventional ones currently used. Although new potential targets are reported, translating the discoveries from bench to bedside is a long process and most of these drugs fail to reach the patients. Read More

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http://dx.doi.org/10.1016/j.pharmthera.2018.10.008DOI Listing
October 2018

HSF1 as a Cancer Biomarker and Therapeutic Target.

Curr Cancer Drug Targets 2018 Oct 18. Epub 2018 Oct 18.

Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Bloomington, IN 47405. United States.

Heat shock factor 1 (HSF1) was discovered in 1984 as the master regulator of the heat shock response. In this classical role, HSF1 is activated following cellular stresses such as heat shock that ultimately lead to HSF1-mediated expression of heat shock proteins to protect the proteome and survive these acute stresses. However, it is now becoming clear that HSF1 also plays a significant role in several diseases, perhaps none more prominent than cancer. Read More

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http://dx.doi.org/10.2174/1568009618666181018162117DOI Listing
October 2018
4 Reads

Progress in Inherited Retinal Disease Drug Discovery and Development: A Foundation's Perspective.

Authors:
Benjamin Yerxa

Pharm Res 2018 Oct 18;35(11):239. Epub 2018 Oct 18.

Foundation Fighting Blindness, 7168 Columbia Gateway Drive, Suite 100, Columbia, Maryland, 21046, USA.

Ophthalmic drug discovery and development has enjoyed a recent renaissance, with a major shift away from reformulating old systemic drugs for ocular use to de novo discovery of drugs for specific ocular disease targets. This shift, coupled with a revolution in molecular biology and genetic sequencing, has uncovered an unprecedented number and variety of novel targets for therapeutic intervention in eye disease. With such a treasure chest of new science to pursue, it also creates a new challenge for translating the lab-based discoveries through the translational "valley of death" into full scale industry-led development of new, approved therapeutics to treat eye disease. Read More

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http://dx.doi.org/10.1007/s11095-018-2514-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208581PMC
October 2018
3 Reads

Translational potential of allosteric modulators targeting the cannabinoid CB receptor.

Acta Pharmacol Sin 2018 Oct 17. Epub 2018 Oct 17.

Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.

The cannabinoid type-1 (CB) receptor, a G-protein-coupled receptor, is an attractive target for drug discovery due to its involvement in many physiological processes. Historically, drug discovery efforts targeting the CB receptor have focused on the development of orthosteric ligands that interact with the active site to which endogenous cannabinoids bind. Research performed over the last several decades has revealed substantial difficulties in translating CB orthosteric ligands into druggable candidates. Read More

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http://www.nature.com/articles/s41401-018-0164-x
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http://dx.doi.org/10.1038/s41401-018-0164-xDOI Listing
October 2018
9 Reads

Molecularly Targeted Therapy for Neuroblastoma.

Children (Basel) 2018 Oct 15;5(10). Epub 2018 Oct 15.

The University of Minnesota Masonic Children's Hospital/Masonic Cancer Center, Riverside Avenue, Minneapolis, MN 55454, USA.

Neuroblastoma is the most common extra-cranial solid tumor encountered in childhood and accounts for 15% of pediatric cancer-related deaths. Although there has been significant improvement in the outcomes for patients with high-risk disease, the therapy needed to achieve a cure is quite toxic and for those that do experience a disease recurrence, the prognosis is very dismal. Given this, there is a tremendous need for novel therapies for children with high-risk neuroblastoma and the molecular discoveries over recent years provide hope for developing new, less toxic, and potentially more efficacious treatments. Read More

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http://www.mdpi.com/2227-9067/5/10/142
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http://dx.doi.org/10.3390/children5100142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210520PMC
October 2018
1 Read

Impact of Variable RNA-Sequencing Depth on Gene Expression Signatures and Target Compound Robustness: Case Study Examining Brain Tumor (Glioma) Disease Progression.

JCO Precis Oncol 2018 Sep;2

Queen's University Belfast.

Purpose: Gene expression profiling can uncover biologic mechanisms underlying disease and is important in drug development. RNA sequencing (RNA-seq) is routinely used to assess gene expression, but costs remain high. Sample multiplexing reduces RNAseq costs; however, multiplexed samples have lower cDNA sequencing depth, which can hinder accurate differential gene expression detection. Read More

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http://ascopubs.org/doi/10.1200/PO.18.00014
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http://dx.doi.org/10.1200/PO.18.00014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186166PMC
September 2018
5 Reads

p53 modeling as a route to mesothelioma patients stratification and novel therapeutic identification.

J Transl Med 2018 Oct 13;16(1):282. Epub 2018 Oct 13.

School of Environment and Life Sciences, University of Salford, Salford, UK.

Background: Malignant pleural mesothelioma (MPM) is an orphan disease that is difficult to treat using traditional chemotherapy, an approach which has been effective in other types of cancer. Most chemotherapeutics cause DNA damage leading to cell death. Recent discoveries have highlighted a potential role for the p53 tumor suppressor in this disease. Read More

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http://dx.doi.org/10.1186/s12967-018-1650-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186085PMC
October 2018
1 Read

Advances in the available non-biological pharmacotherapy prevention and treatment of acute mountain sickness and high altitude cerebral and pulmonary oedema.

Expert Opin Pharmacother 2018 Dec 11;19(17):1891-1902. Epub 2018 Oct 11.

c Department of Medicine , University of Birmingham , Edgbaston , UK.

Introduction: The physiological responses on exposure to high altitude are relatively well known, but new discoveries are still being made, and novel prevention and treatment strategies may arise. Basic information has changed little since our previous review in this journal 10 years ago, but considerable more detail on standard therapies, and promising new approaches are now available. Areas covered: Herein, the authors review the role of pharmacological agents in preventing and treating high-altitude illnesses. Read More

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https://www.tandfonline.com/doi/full/10.1080/14656566.2018.1
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http://dx.doi.org/10.1080/14656566.2018.1528228DOI Listing
December 2018
6 Reads

Crystal structure prediction: reflections on present status and challenges.

Authors:
Artem R Oganov

Faraday Discuss 2018 Oct;211(0):643-660

Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, 3 Nobel St., Moscow 143026, Russia.

Long thought to be impossible, crystal structure prediction (CSP) is a thriving field today, with many important discoveries in fields as diverse as computational materials discovery, drug design, high-pressure chemistry and mineralogy of the Earth's and planetary interiors. However, major challenges remain, warranting more research. In these Concluding Remarks, I try to summarize my personal view of the enormous progress made in the field of CSP and the open questions and challenges that keep this field more exciting than ever. Read More

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http://dx.doi.org/10.1039/c8fd90033gDOI Listing
October 2018

Exploring inhalable polymeric dry powders for anti-tuberculosis drug delivery.

Mater Sci Eng C Mater Biol Appl 2018 Dec 11;93:1090-1103. Epub 2018 Sep 11.

3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal. Electronic address:

The growing interest on polymeric delivery systems for pulmonary administration of drugs anticipates a more direct and efficient treatment of diseases such as tuberculosis (TB) that uses the pulmonary route as the natural route of infection. Polymeric microparticles or nano-in-microparticles offer target delivery of drugs to the lungs and the potential to control and sustain drug release within TB infected macrophages improving the efficiency of the anti-TB treatment and reducing side effects. In a dry powder form these inhalable delivery systems have increased stability and prolonged storage time without requiring refrigeration, besides being cost-effective and patient convenient. Read More

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http://dx.doi.org/10.1016/j.msec.2018.09.004DOI Listing
December 2018
8 Reads

Pharmacogenetic content of commercial genome-wide genotyping arrays.

Pharmacogenomics 2018 Oct 1;19(15):1159-1167. Epub 2018 Oct 1.

Beaulieu-Saucier Université de Montréal Pharmacogenomics Centre, 5000 Belanger Street, Montreal, H1T 1C8, Canada.

Aim: We have evaluated the pharmacogenetic content of commercial human genome-wide genotyping arrays, as it is a critical determinant to enabling pharmacogenomic discoveries.

Methods: Using bioinformatics approaches, we assessed 27,811 genetic variants in 3146 genes for their presence in 18 Illumina and 15 Affymetrix genome-wide arrays.

Results: The pharmacogenetic content of the arrays varied greatly. Read More

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https://www.futuremedicine.com/doi/10.2217/pgs-2017-0129
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http://dx.doi.org/10.2217/pgs-2017-0129DOI Listing
October 2018
2 Reads

Atypical leishmaniasis: A global perspective with emphasis on the Indian subcontinent.

PLoS Negl Trop Dis 2018 09 27;12(9):e0006659. Epub 2018 Sep 27.

Department of Biochemistry and Microbial Sciences, Central University of Punjab, Bathinda, Punjab, India.

Background: Among the neglected tropical diseases, leishmaniasis continues to be prevalent in many tropical and subtropical countries despite international, national, and local efforts towards its control and elimination over the last decade. This warrants a critical evaluation of such factors as under-reporting, asymptomatic infections, post kala azar dermal leishmaniasis (PKDL) cases, and drug resistance. In this review, we highlight lesser-understood atypical presentations of the disease involving atypical parasite strains against a background of classical leishmaniasis with a focus on the Indian subcontinent. Read More

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http://dx.doi.org/10.1371/journal.pntd.0006659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159859PMC
September 2018