Search results for " 2"
showing 10 items of 10825 documents
Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury
2017
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…
Plant polyphenols, chemoreception, taste receptors and taste management
2019
International audience; Purpose of review Polyphenols display beneficial health effects through chemopreventive actions on numerous chronic diseases including cancers, metabolic disorders, reproductive disorders and eating behaviour disorders. According to the principle of chemoreception, polyphenols bind cellular targets capable of accepting their stereochemistry, namely metabolizing enzymes and protein receptors, including taste receptors. The extraoral expression of taste receptors and their pharmacological interest in terms of novel drug therapies open up new perspectives on the potential use of these compounds and their interactions with other chemicals in cells. These new perspectives…
Overview of key molecular and pharmacological targets for diabetes and associated diseases
2021
Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by c…
A Physiology-Based Model of Human Bile Acid Metabolism for Predicting Bile Acid Tissue Levels After Drug Administration in Healthy Subjects and BRIC …
2019
Drug-induced liver injury (DILI) is a matter of concern in the course of drug development and patient safety, often leading to discontinuation of drug-development programs or early withdrawal of drugs from market. Hepatocellular toxicity or impairment of bile acid (BA) metabolism, known as cholestasis, are the two clinical forms of DILI. Whole-body physiology-based modelling allows a mechanistic investigation of the physiological processes leading to cholestasis in man. Objectives of the present study were: (1) the development of a physiology-based model of the human BA metabolism, (2) population-based model validation and characterisation, and (3) the prediction and quantification of alter…
SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective
2020
In less than five months, COVID-19 has spread from a small focus in Wuhan, China, to more than 5 million people in almost every country in the world, dominating the concern of most governments and public health systems. The social and political distresses caused by this epidemic will certainly impact our world for a long time to come. Here, we synthesize lessons from a range of scientific perspectives rooted in epidemiology, virology, genetics, ecology and evolutionary biology so as to provide perspective on how this pandemic started, how it is developing, and how best we can stop it.
Gatekeeper role of brain antigen‐presenting CD11c + cells in neuroinflammation
2015
Multiple sclerosis is the most frequent chronic inflammatory disease of the CNS. The entry and survival of pathogenic T cells in the CNS are crucial for the initiation and persistence of autoimmune neuroinflammation. In this respect, contradictory evidence exists on the role of the most potent type of antigen-presenting cells, dendritic cells. Applying intravital two-photon microscopy, we demonstrate the gatekeeper function of CNS professional antigen-presenting CD11c(+) cells, which preferentially interact with Th17 cells. IL-17 expression correlates with expression of GM-CSF by T cells and with accumulation of CNS CD11c(+) cells. These CD11c(+) cells are organized in perivascular clusters…
TGF-β inhibitor Smad7 regulates dendritic cell-induced autoimmunity
2017
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction. Mice devoid of Smad7 specifically in DCs are resistant to the development of experimental autoimmune ence…
Circadian Rhythm and Concentration of Melatonin in Breast Cancer Patients
2020
Background: Melatonin is a biomarker of the central circadian clock and its chronobiotic actions entraining circadian rhythms to the light-dark cycle are well known. Reduction in melatonin levels and altered circadian rhythms have been associated with a high risk of breast cancer. Melatonin has also shown to display anti-proliferative effects on breast cancer growth and proliferation. Evaluation of melatonin circadian rhythm alterations in patients bearing breast cancer may have interesting prognostic and therapeutic applications. Objective: To review studies evaluating the circadian rhythm of melatonin in breast cancer patients. The effects of surgery and chemotherapy on melatonin secreti…
Rapid degradation of ABCA1 protein following cAMP withdrawal and treatment with PKA inhibitor suggests ABCA1 is a short-lived protein primarily regul…
2020
Objectives: ATP-binding cassette transporter A1 (ABCA1) is a key player in the reverse cholesterol transport (RCT) and HDL biogenesis. Since RCT is compromised as a result of ABCA1 dysfunction in diabetic state, the objective of this study was to investigate the regulation of ABCA1 in a stably transfected 293 cells expressing ABCA1 under the control of cAMP response element. Methods: To delineate transcriptional and posttranscriptional regulation of ABCA1, 293 cells were stably transfected with the full length ABCA1 cDNA under the control of CMV promoter harboring cAMP response element. cAMP-mediated regulation of ABCA1 and cholesterol efflux were studied in the presence of 8-Br-cAMP and af…
Relative risk rather than absolute risk reduction should be preferred to sensitise the public to preventive actions.
2021
We thank Lawrence and colleagues1 for their interest in our work,2 about which they raised some comments as the need of expressing results in absolute rather than relative risks. As they appropriately mentioned in their correspondence, absolute risk is an important parameter for the estimation of the effect of an intervention and must sometimes be preferred to relative risk. However, when discussing with health professionals and policymakers, using absolute risk reductions, expressed as percentages, may incorrectly lead to an intervention being considered unnecessary. As example, what would be the point of reducing by 30% the occurrence of an event affecting 2% of the population? This is ex…