Drug Discovery Research

05:09 EST 23rd January 2019 | BioPortfolio

Global proteomic and methylome analysis in human induced pluripotent stem cells reveals overexpression of a human TLR3 affecting proper innate immune response signaling.

When considering the clinical applications of autologous cell replacement therapy of human iPSC-derived cells there is a clear need to better understand what the immune response will be before we embark on extensive clinical trials to treat or model human disease. We performed a detailed assessment comparing human fibroblast cell lines (termed F1) reprogrammed into human iPSC and subsequently diff...

Tumor mutational burden (TMB) standardization initiatives: Recommendations for consistent TMB assessment in clinical samples to guide immunotherapy treatment decisions.

Characterization of tumors utilizing next-generation sequencing methods, including assessment of the number of somatic mutations (tumor mutational burden [TMB]), is currently at the forefront of the field of personalized medicine. Recent clinical studies have associated high TMB with improved patient response rates and survival benefit from immune checkpoint inhibitors; hence, TMB is emerging as a...

Discovery of sustainable drugs for neglected tropical diseases: cashew nut shell liquid (CNSL)-based hybrids target mitochondrial function and ATP production in Trypanosoma brucei.

In a search for effective and sustainable treatments for trypanosomiasis, we developed a library of hybrid compounds by merging the structural features of a previously synthesized quinone hit (4) with those of long-chain phenolic constituents from cashew nut shell liquid (CNSL). CNSL is an agro-waste product from cashew nut processing factories with great potential as a precursor for the productio...

Single-cell screening of tamoxifen abundance and effect using mass spectrometry and Raman-spectroscopy.

Monitoring drug uptake, its metabolism, and response on the single-cell level is invaluable for sustaining drug discovery efforts. In this study, we show the possibility of accessing the information about the aforementioned processes at the single-cell level by monitoring the anti-cancer drug, tamoxifen using live single-cell mass spectrometry (LSC-MS) and Raman spectroscopy. First, we explored wh...

Exosomes in Parkinson's disease: current perspectives and future challenges.

Exosomes, which are lipid bilayer membrane vesicles, have been implicated as carriers of biological macromolecules. In recent years, the functions of exosomes in the spreading of pathological conversion of proteins among neurons have drawn particular attention in Parkinson's disease research. Extracellular α-synuclein is proven to be associated with exosomes in vivo and in vitro. The contents of ...

DARK Classics in Chemical Neuroscience: Arecoline.

Arecoline is a naturally occurring psychoactive alkaloid from areca (betel) nuts of the areca palm (Areca catechu) endemic to South and Southeast Asia. A partial agonist of nicotinic and muscarinic acetylcholine receptors, arecoline evokes multiple effects on the central nervous system (CNS), including stimulation, alertness, elation and anxiolysis. Like nicotine, arecoline also evokes addiction a...

Mechanism-based pain management in chronic pancreatitis - is it time for a paradigm shift?

Introduction Pain is the most common symptom in chronic pancreatitis and treatment remains a challenge. Management of visceral pain in general, is only sparsely documented, and treatment in the clinic is typically based on empirical knowledge from somatic pain conditions. This may be problematic, as many aspects of the neurobiology differ significantly from somatic pain, and organs such as the gut...

An assessment of the translational relevance of Drosophila in drug discovery.

Drosophila melanogaster offers a powerful expedient and economical system with facile genetics. Because of the high sequence and functional conservation with human disease-associated genes, it has been cardinal in deciphering disease mechanisms at the genetic and molecular level. Drosophila are amenable to and respond well to pharmaceutical treatment which coupled to their genetic tractability has...

Response by McCord et al to Letter Regarding Article, "Designing a Better Mousetrap: Reflections on the November 28, 2017, US Food and Drug Administration Meeting on Next-Generation "High-Sensitivity" Cardiac Troponin Assays to Diagnose Myocardial Infarction".

Letter by Sandoval et al Regarding Article, "Designing a Better Mousetrap: Reflections on the November 28, 2017, US Food and Drug Administration Meeting on Next-Generation "High-Sensitivity" Cardiac Troponin Assays to Diagnose Myocardial Infarction".

Response by Thiene and Saffitz to Letter Regarding Article, "Autopsy as a Source of Discovery in Cardiovascular Medicine: Then and Now".

Letter by Atienza et al Regarding Article, "Autopsy as a Source of Discovery in Cardiovascular Medicine: Then and Now".

Patients' views on a new treatment for Bulimia nervosa and binge eating disorder combining physical exercise and dietary therapy (the PED-t). A qualitative study.

A new group based treatment for patients with bulimia nervosa (BN) and binge eating disorder (BED), combining guided Physical Exercise and Dietary therapy (PED-t), has shown the capacity to alleviate BN and BED symptoms. The PED-t is run by therapists with a professional background in sport sciences and nutrition, which in many clinical settings is an uncommon group of professionals. The symptom r...

Exploring the assessment of Adjustment Disorders: Differences between a general and a clinical sample.

Adjustment Disorders (AjD) are one of the most prevalent psychological problems in primary and hospital care. It is necessary to have evidence-based instruments to help professionals diagnose and better understand this problem, which has been little studied. This study presents an adaptation of the Inventory of Complicated Grief for the assessment of AjD symptoms, referred to as the Inventory of S...

The Effect of Pulmonary Rehabilitation on the Physical Activity Level and General Clinical Status of Patients with Bronchiectasis.

We aimed to investigate the effects of pulmonary rehabilitation (PR) on the level of physical activity (PA) and the general clinical status in adult patients with non-cystic fibrosis bronchiectasis.

Angiotensin-Converting Enzyme Inhibitors Induce Cough.

Angiotensin-converting enzyme inhibitors (ACE-I) are widely used in diseases, such as hypertension, congestive heart failure, and myocardial infarction. Although these drugs are well tolerated, one out of five patients discontinues ACE-I due to drug side effects, mainly chronic cough. However, the pathogenesis of ACE-I-induced cough remains controversial and requires further study. In this review,...

Epidemiological Profile and Antimicrobial Resistance Pattern of Enteric Fever in a Tertiary Care Hospital of North India - a Seven Year Ambispective Study.

Enteric-fever is a major public-health problem in developing countries emerging as multidrug-resistant, Nalidixic-acid resistant and extremely drug-resistant Salmonella (Pakistan, 2016), has intensified the use of WHO watch/reserve group antimicrobials such as azithromycin and meropenem.

Pharyngeal Papilloma: a Rare Non-Pulmonary Cause of Hemoptysis.

The most common benign neoplasm of the pharynx is papilloma. It is characterized by bulging brittle lesions, which are pedicled or sessile, whitish-grey or pinkish colour. Progressive hoarseness is the main clinical feature. When the papillomata spread throughout the tracheobronchial tree symptoms such as chronic cough, stridor, dyspnea or acute respiratory distress are mostly present. Hemoptysis ...

SNOMED CT Concept Hierarchies for Computable Clinical Phenotypes From Electronic Health Record Data: Comparison of Intensional Versus Extensional Value Sets.

Defining clinical phenotypes from electronic health record (EHR)-derived data proves crucial for clinical decision support, population health endeavors, and translational research. EHR diagnoses now commonly draw from a finely grained clinical terminology-either native SNOMED CT or a vendor-supplied terminology mapped to SNOMED CT concepts as the standard for EHR interoperability. Accordingly, ele...

Perspectives of Nonphysician Clinical Students and Medical Lecturers on Tablet-Based Health Care Practice Support for Medical Education in Zambia, Africa: Qualitative Study.

Zambia is faced with a severe shortage of health workers and challenges in national health financing. This burdens the medical licentiate practitioner (MLP) program for training nonphysician clinical students in Zambia because of the shortage of qualified medical lecturers and learning resources at training sites. To address this shortage and strengthen the MLP program, a self-directed electronic ...

TheraSphere Yttrium-90 Glass Microspheres Combined With Chemotherapy Versus Chemotherapy Alone in Second-Line Treatment of Patients With Metastatic Colorectal Carcinoma of the Liver: Protocol for the EPOCH Phase 3 Randomized Clinical Trial.

Colorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line ...

Effectiveness of mid-thoracic spine mobilization versus therapeutic exercise in patients with subacute stroke: A randomized clinical trial.

Although commonly used in clinical settings, evidence regarding the beneficial effectiveness of joint mobilization and therapeutic exercise in patients with stroke is still lacking.

Fetal edema, not overgrowth, is associated with neonatal lethal Costello syndrome due to the HRAS p.Gly12Val mutation.

Superior Mesenteric Artery Syndrome in a Case of Juvenile Dermatomyositis: A Unique Complication.

Atypical Cardiac Manifestations of Systemic Myositis.

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