Search results for "induced"
showing 10 items of 1287 documents
Dysfunctional mitochondrial fission impairs cell reprogramming
2016
We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered…
The purine analogues abacavir and didanosine increase acetaminophen-induced hepatotoxicity by enhancing mitochondrial dysfunction
2016
Background NRTIs are essential components of HIV therapy with well-documented, long-term mitochondrial toxicity in hepatic cells, but whose acute effects on mitochondria are unclear. As acetaminophen-induced hepatotoxicity also involves mitochondrial interference, we hypothesized that it would be exacerbated in the context of ART. Methods We evaluated the acute effects of clinically relevant concentrations of the most widely used NRTIs, alone or combined with acetaminophen, on mitochondrial function and cellular viability. Results The purine analogues abacavir and didanosine produced an immediate and concentration-dependent inhibition of oxygen consumption and complex I and III activity. Th…
Extracellular Vesicles From the Helminth Fasciola hepatica Prevent DSS-Induced Acute Ulcerative Colitis in a T-Lymphocyte Independent Mode
2018
The complexity of the pathogenesis of inflammatory bowel disease (ulcerative colitis and Crohn's disease) has led to the quest of empirically drug therapies, combining immunosuppressant agents, biological therapy and modulators of the microbiota. Helminth parasites have been proposed as an alternative treatment of these diseases based on the hygiene hypothesis, but ethical and medical problems arise. Recent reports have proved the utility of parasite materials, mainly excretory/secretory products as therapeutic agents. The identification of extracellular vesicles on those secreted products opens a new field of investigation, since they exert potent immunomodulating effects. To assess the ef…
Depleted uranium induces human carcinogenesis involving the immune and chaperoning systems: Realities and working hypotheses
2019
Abstract Cancer is caused by a combination of factors, genetic, epigenetics and environmental. Among the latter, environmental pollutants absorbed by contact, inhalation, or ingestion are major proven or suspected culprits. Depleted uranium (DU) is one of them directly pertinent to the military and civilians working in militarized areas. It is considered a weak carcinogen but its implication in cancer development in exposed individuals is supported by various data. Since not all subjects exposed to DU develop cancer, it is likely that DU-dependent carcinogenesis requires cofactors, such as genetic predisposition and deficiencies of the chaperoning and immune systems. It is of the essence to…
A New Method for Studying Licking Behavior Determinants in Rodents: Application to Diet-Induced Obese Mice
2018
OBJECTIVE An original device for exploring taste-guided reward behavior in rodents using a newly designed computer-controlled liquid delivery system equipped with "lickometers" is described. METHODS This octagonal shaped "gustometer" is composed of eight shutters that give random access during a few seconds to eight bottles delivering different liquid stimuli. This original design, which forces the animal to move for access to the drinking source, allows a simultaneous analysis of the licking behavior and motivation to drink. Determination of the sucrose licking behavior in diet-induced obese mice was used to validate this method because nutritional obesity disturbs the sweet taste percepti…
Non-Radiation Based Early Pain Relief Treatment Options for Patients With Non-Small Cell Lung Cancer and Cancer Induced Bone Pain: A Systematic Review
2020
Introduction: Cancer induced bone pain (CIBP) is frequent in patients with non-small cell lung cancer (NSCLC). Radiation therapy continues to be the gold standard for treatment of painful bone metastases, however only a limited number of metastases can be irradiated. We evaluated non-radiation based early CIBP relief options in NSCLC through a systematic review. Methods: Systematic review including all prospective articles published between 01-1994 and 06-2020 on Pubmed, Cochrane Library and ClinicalTrials.gov database. Inclusion: nonradiation based trials evaluating CIBP early pain relief options (initially defined as pain score evaluated within two weeks, because of no randomized trials, …
Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the Europe…
2020
Background Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in the FDA drug label and a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic…
NEPA as antiemetic prophylaxis after failure of 5HT3-RA plus dexamethasone in patients receiving carboplatin and gemcitabine chemotherapy: A monocent…
2020
Introduction Chemotherapy-induced nausea and vomiting (CINV) may affect adherence to planned chemotherapy treatments and compromise patients’ quality of life during the therapy. NEPA is an oral fixed combination of netupitant, a highly-selective NK1-RA and palonosetron, a 5HT3-RA, approved for the prevention of acute and delayed CINV. The aim of this study was to evaluate the efficacy and safety of NEPA with dexamethasone for CINV prophylaxis in the challenging setting of carboplatin and gemcitabine combination chemotherapy, after failure of prophylaxis with 5HT3 receptor antagonist. Methods Eligible patients were undergoing carboplatin and gemcitabine combination chemotherapy for metastati…
A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function
2017
Obesity and type 2 diabetes are associated with metabolic defects and adipose tissue inflammation. Foxp3(+) regulatory T cells (Tregs) control tissue homeostasis by counteracting local inflammation. However, if and how T cells interlink environmental influences with adipocyte function remains unknown. Here, we report that enhancing sympathetic tone by cold exposure, beta3-adrenergic receptor (ADRB3) stimulation or a short-term high-calorie diet enhances Treg induction in vitro and in vivo. CD4(+) T cell proteomes revealed higher expression of Foxp3 regulatory networks in response to cold or ADRB3 stimulation in vivo reflecting Treg induction. Specifically, Ragulator-interacting protein C17o…
Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Drug-Induced Inotropic Effects in Early Drug Development. Part 2: Design…
2019
Contractility of the myocardium engines the pumping function of the heart and is enabled by the collective contractile activity of its muscle cells: cardiomyocytes. The effects of drugs on the contractility of human cardiomyocytes in vitro can provide mechanistic insight that can support the prediction of clinical cardiac drug effects early in drug development. Cardiomyocytes differentiated from human-induced pluripotent stem cells have high potential for overcoming the current limitations of contractility assays because they attach easily to extracellular materials and last long in culture, while having human- and patient-specific properties. Under these conditions, contractility measureme…