Search results for "MAI"

The potassium channels TASK2 and TREK1 regulate functional differentiation of murine skeletal muscle cells.

2015

Two-pore domain potassium (K2P) channels influence basic cellular parameters such as resting membrane potential, cellular excitability, or intracellular Ca2+-concentration [Ca2+]i. While the physiological importance of K2P channels in different organ systems (e.g., heart, central nervous system, or immune system) has become increasingly clear over the last decade, their expression profile and functional role in skeletal muscle cells (SkMC) remain largely unknown. The mouse SkMC cell line C2C12, wild-type mouse muscle tissue, and primary mouse muscle cells (PMMs) were analyzed using quantitative PCR, Western blotting, and immunohistochemical stainings as well as functional analysis includin…

Evaluation of an Antioxidant and Anti-inflammatory Cocktail Against Human Hypoactivity-Induced Skeletal Muscle Deconditioning

2020

International audience; Understanding the molecular pathways involved in the loss of skeletal muscle mass and function induced by muscle disuse is a crucial issue in the context of spaceflight as well as in the clinical field, and development of efficient countermeasures is needed. Recent studies have reported the importance of redox balance dysregulation as a major mechanism leading to muscle wasting. Our study aimed to evaluate the effects of an antioxidant/anti-inflammatory cocktail (741 mg of polyphenols, 138 mg of vitamin E, 80 mu g of selenium, and 2.1 g of omega-3) in the prevention of muscle deconditioning induced by long-term inactivity. The study consisted of 60 days of hypoactivi…

2018

There are two important gaps of knowledge in depression treatment, namely the lack of biomarkers predicting response to antidepressants and the limited knowledge of the molecular mechanisms underlying clinical improvement. However, individually tailored treatment strategies and individualized prescription are greatly needed given the huge socio-economic burden of depression, the latency until clinical improvement can be observed and the response variability to a particular compound. Still, individual patient-level antidepressant treatment outcomes are highly unpredictable. In contrast to other therapeutic areas and despite tremendous efforts during the past years, the genomics era so far ha…

Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin β and promotes transendothelial cell migration.

2016

The adhesion molecule CD99 is essential for the transendothelial migration of leukocytes. In this study, we used biochemical and cellular assays to show that CD99 undergoes ectodomain shedding by the metalloprotease meprin β and subsequent intramembrane proteolysis by γ-secretase. The cleavage site in CD99 was identified by mass spectrometry within an acidic region highly conserved through different vertebrate species. This finding fits perfectly to the unique cleavage specificity of meprin β with a strong preference for aspartate residues and suggests coevolution of protease and substrate. We hypothesized that limited CD99 cleavage by meprin β would alter cellular transendothelial migratio…

Diagnostic and Therapeutic Approach to Sleep Disorders, High Blood Pressure and Cardiovascular Diseases. A Consensus Document by the Italian Society …

2021

Hypertension is a major contributor to fatal/nonfatal cardiovascular diseases, and timely identification and appropriate management of factors affecting hypertension and its control are mandatory public health issues. By inducing neurohormonal alterations and metabolic impairment, sleep disorders have an impact on a variety of cardiovascular risk factors, including hypertension, and ultimately increase the risk of cardiovascular events. There is evidence that qualitative and quantitative sleep disorders are associated with resistant hypertension and with impaired circadian blood pressure variations. However, sleep disturbances are often unrecognized, or heterogeneity exists in their managem…

Efficient and reproducible experimental infections of rats with Blastocystis spp.

2018

Although Blastocystis spp. infect probably more than 1 billion people worldwide, their clinical significance is still controversial and their pathophysiology remains poorly understood. In this study, we describe a protocol for an efficient and reproducible model of chronic infection in rats, laying the groundwork for future work to evaluate the pathogenic potential of this parasite. In our experimental conditions, we were unable to infect rats using vacuolar forms of an axenically cultivated ST4 isolate, but we successfully established chronic infections of 4 week-old rats after oral administration of both ST3 and ST4 purified cysts isolated from human stool samples. The infection protocol …

Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2

2016

We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728–1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nM). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this …

Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors

2021

The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirabl…

A comprehensive approach to assigning periodontal prognosis

2018

Abstract Aim The purpose of this retrospective case series study was to evaluate the usefulness and performance of a comprehensive approach to assigning periodontal prognosis by assessing the risk of tooth loss due to periodontal disease (TLPD) and estimate the survival time (ST) of periodontally compromised teeth (PCT). Material and Methods The Long‐Term Outcome (LTO) index was utilized to assess the risk of TLPD, at baseline, in 100 patients following periodontal maintenance for a mean 24.7 year (±2.4). A TLPD prediction model was utilized to assign ST to PCT. The performance of the TLPD prediction based on both parameters was assessed. Results The mean TLPD rate increased as the LTO inde…

The Metalloprotease Meprin β Is an Alternative β-Secretase of APP

2017

The membrane bound metalloprotease meprin β is important for collagen fibril assembly in connective tissue formation and for the detachment of the intestinal mucus layer for proper barrier function. Recent proteomic studies revealed dozens of putative new substrates of meprin β, including the amyloid precursor protein (APP). It was shown that APP is cleaved by meprin β in distinct ways, either at the β-secretase site resulting in increased levels of Aβ peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments. The latter event was discussed to be rather neuroprotective, whereas the ectodomain shedding of APP by meprin β reminiscent to BACE-1 is in line with the amyloid h…