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[Social protection under the law: challenging to create, easy to destroy].
COP speed significantly increased (16 ± 20%) in YM only after vibration and was accompanied by increased activation of the lateral gastrocnemius. This is the first study to show that the effects of prolonged Achilles tendon vibration on strength and balance performances were apparent in young adults only. The differences between the age groups may be related to the attenuated gastrocnemius neuromuscular function in older adults.Many studies of vascular function limit the testing of premenopausal female participants to periods when female sex hormones, either endogenous or exogenous, are at their lowest concentration. This practice, when not part of the specific research question, may limit data surrounding the predominant physiological state of premenopausal females and pose a threat to external validity. In this Perspective, we briefly review the literature on the effect of female sex hormones on vascular function and discuss when limiting experimental testing to a certain phase of the menstrual cycle (MC) or oral contraceptive (OC) use may be appropriate. The goal of this Perspective is to open a dialog that may enhance data validity and the overall understanding of vascular function in premenopausal females.Mitochondria are both the primary provider of ATP and the pivotal regulator of cell death, which are essential for physiological muscle activities. Ca2+ plays a multifaceted role in mitochondrial function. During muscle contraction, Ca2+ influx into mitochondria activates multiple enzymes related to tricarboxylic acid (TCA) cycle and oxidative phosphorylation, resulting in increased ATP synthesis to meet the energy demand. Pathophysiological conditions such as skeletal muscle denervation or unloading also lead to elevated Ca2+ levels inside mitochondria. However, the outcomes of this steady-state elevation of mitochondrial Ca2+ level include exacerbated reactive oxygen species (ROS) generation, sensitized opening of mitochondrial permeability transition pore (mPTP), induction of programmed cell death, and ultimately muscle atrophy. Previously, both acute and long-term endurance exercises have been reported to activate certain signaling pathways to counteract ROS production. Meanwhile, electrical stimulation is known to help prevent apoptosis and alleviate muscle atrophy in denervated animal models and patients with motor impairment. There are various mechanistic studies that focus on the excitation-transcription coupling framework to understand the beneficial role of exercise and electrical stimulation. Interestingly, a recent study has revealed an unexpected role of rapid mitochondrial Ca2+ transients in keeping mPTP at a closed state with reduced mitochondrial ROS production. This discovery motivated us to contribute this review article to inspire further discussion about the potential mechanisms underlying differential outcomes of physiological mitochondrial Ca2+ transients and pathological mitochondrial Ca2+ elevation in skeletal muscle ROS production.During acute inflammation, the recruitment of leukocytes from the blood stream into the inflamed tissue is a well-described mechanism encompassing the interaction of endothelial cells with leukocytes allowing leukocytes to reach the site of tissue injury or infection where they can fulfill their function such as phagocytosis. read more This process requires a fine-tuned regulation of a plethora of signaling cascades, which are still incompletely understood. Here, connexin 43 (Cx43) and pannexin 1 (Panx1) are known to be pivotal for the correct communication of endothelial cells with leukocytes. Pharmacological as well as genetic approaches provide evidence that endothelial Cx43-hemichannels and Panx1-channels release signaling molecules including ATP and thereby regulate vessel function and permeability as well as the recruitment of leukocytes during acute inflammation. Furthermore, Cx43 hemichannels and Panx1-channels in leukocytes release signaling molecules and can mediate the activation and function of leukocytes in an autocrine manner. The focus of the present review is to summarize the current knowledge of the role of Cx43 and Panx1 in endothelial cells and leukocytes in the vasculature during acute inflammation and to discuss relevant molecular mechanisms regulating Cx43 and Panx1 function.As part of the ZOOMICS project, we set out to investigate common and diverging metabolic traits in the blood metabolome across various species by taking advantage of recent developments in high-throughput metabolomics. Here we provide the first comparative metabolomics analysis of fresh and stored human (n = 21, 10 males, 11 females), olive baboon (n = 20), and rhesus macaque (n = 20) red blood cells at baseline and upon 42 days of storage under blood bank conditions. The results indicated similarities and differences across species, which ultimately resulted in a differential propensity to undergo morphological alterations and lyse as a function of the duration of refrigerated storage. Focusing on purine oxidation, carboxylic acid, fatty acid, and arginine metabolism further highlighted species-specific metabolic wiring. For example, through a combination of steady state measurements and 13C615N4-arginine tracing experiments, we report an increase in arginine catabolism into ornithine in humans, suggestive of species-specific arginase 1 activity and nitric oxide synthesis-an observation that may impact the translatability of cardiovascular disease studies carried out in non-human primates (NHPs). Finally, we correlated metabolic measurements to storage-induced morphological alterations via scanning electron microscopy and hemolysis, which were significantly lower in human red cells compared to both NHPs.We conducted this study to examine whether acid-sensing ion channels (ASICs) are involved in the modulation of urinary bladder activity with or without intravesical irritation induced by acetic acid. All in vivo evaluations were conducted during continuous infusion cystometry in decerebrated unanesthetized female mice. During cystometry with a pH 6.3 saline infusion, an i.p. injection of 30 μmol/kg A-317567 (a potent, non-amiloride ASIC blocker) increased the intercontraction interval (ICI) by 30% (P less then 0.001), whereas vehicle injection had no effect. An intravesical acetic acid (pH 3.0) infusion induced bladder hyperactivity, with reductions in ICI and maximal voiding pressure (MVP) by 79% (P less then 0.0001) and 29% (P less then 0.001), respectively. A-317567 (30 μmol/kg i.p.) alleviated hyperreflexia by increasing the acid-shortened ICI by 76% (P less then 0.001). This dose produced no effect on MVP under either intravesical pH condition. Further analysis in comparison with vehicle showed that the increase in ICI (or bladder capacity) by the drug was not dependent on bladder compliance. Meanwhile, intravesical perfusion of A-317567 (100 μM) had no effect on bladder activity during pH 6.0 saline infusion cystometry, and drug perfusion at neither 100 μM nor 1 mM produced any effects on bladder hyperreflexia during pH 3.0 acetic acid infusion cystometry. A-317567 has been suggested to display extremely poor penetrability into the central nervous system and thus to be a peripherally active blocker. Taken together, our results suggest that blockade of ASIC signal transduction increases bladder capacity under normal intravesical pH conditions and alleviates bladder hyperreflexia induced by intravesical acidification and that the site responsible for this action is likely to be the dorsal root ganglia.Introduction Although electronic cigarettes (e-cigarettes) were originally developed to deliver aerosolized nicotine to lungs, recent data have shown that consumers also use them for inhalation of other drugs, including cannabidiol (CBD). The aim of this study was to test the acute inhalation toxicity of flavored CBD-containing aerosols emitted from e-cigarettes. Methods Bronchial epithelial cells (H292) cells were exposed to aerosol generated from e-cigarettes refilled either with (1) propylene glycol solvent only (PG, control), (2) commercially purchased unflavored solution with CBD, or (3) commercially purchased solutions with and without CBD and with different flavors. The in vitro toxicological effects were assessed using the following methods (1) trypan blue exclusion assay (cell viability), (2) neutral red uptake assay (metabolic activity), and (3) ELISA (concentrations of inflammatory mediators). Results Most flavored products with or without CBD were cytotoxic as compared to the air control. Overall, aerosols with CBD were more cytotoxic than aerosols without CBD irrelevant of the flavoring used in the product. Although, unflavored aerosols containing CBD in PG were significantly more cytotoxic than aerosols containing only PG, not all flavored products containing CBD were significantly more toxic than the same flavored products without CBD. Most CBD containing products significantly increase the concentration of cytokines released as compared to the same flavored products without CBD. Conclusion Different flavors show different cytotoxic effects in CBD-containing e-cigarettes. Aerosols emitted from CBD containing e-cigarettes were more cytotoxic than those emitted from CBD-free e-cigarettes.Water is critical for the survival of most cells and organisms. Remarkably, a small number of multicellular animals are able to survive nearly complete drying. The phenomenon of anhydrobiosis, or life without water, has been of interest to researchers for over 300 years. In this review we discuss advances in our understanding of protectants and mechanisms of desiccation tolerance that have emerged from research in three anhydrobiotic invertebrates brine shrimp (Artemia), roundworms (nematodes), and tardigrades (water bears). Discovery of molecular protectants that allow each of these three animals to survive drying diversifies our understanding of desiccation tolerance, and convergent themes suggest mechanisms that may offer a general model for engineering desiccation tolerance in other contexts.Acute kidney injury (AKI) is one of the most common complications affecting hospitalized patients associated with an extremely high mortality rate. However, the underlying pathogenesis of AKI remains unclear that largely limits its effective management in clinic. Increasing evidence demonstrated the importance of long non-coding RNAs (lncRNAs) in the pathogenesis of AKI, because of their regulatory roles in transcription, translation, chromatin modification, and cellular organization. Here, we reported a new role of LRNA9884 in AKI. Using experimental cisplatin-induced AKI model, we found that LRNA9884 was markedly up-regulated in the nucleus of renal tubular epithelium in mice with AKI. We found that silencing of LRNA9884 effectively inhibited the production of inflammatory cytokines MCP-1, IL-6, and TNF-α in the mouse renal tubular epithelial cells (mTECs) under IL-1β stimulation in vitro. Mechanistically, LRNA9884 was involved into NF-κB-mediated inflammatory cytokines production especially on macrophage migration inhibitory factor (MIF). Collectedly, our study suggested LRNA9884 promoted MIF-triggered the production of inflammatory cytokines via NF-κB pathway after AKI injury. This study uncovered LRNA9884 has an adverse impact in AKI, and targeting LRNA9884 might represent a potential therapeutic target for AKI.
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