Kraruphove0801

Furthermore, betaine alleviated the changes of its downstream molecules P53, Bcl-2, Bax, phosphorylated MYPT1 (p-MYPT1), total MYPT1 (t-MYPT1), p27kip1, and Cleaved Caspase-3. According to what we observed, this study indicated that betaine treatment could protect RVF due to PAH, which may be achieved through an altered Rho A/ROCK signaling pathway.Pulmonary vascular remodeling (PVR) is the pathological basis of pulmonary hypertension (PH). Incomplete understanding of PVR etiology has hindered drug development for this devastating disease, which exhibits poor prognosis despite the currently available therapies. Endothelial-to-mesenchymal transition (EndMT), a process of cell transdifferentiation, has been recently implicated in cardiovascular diseases, including PH. But the questions of how EndMT occurs and how to pharmacologically target EndMT in vivo have yet to be further answered. Herein, by performing hematoxylin-eosin and immunofluorescence staining, transmission electron microscopy and Western blotting, we found that EndMT plays a key role in the pathogenesis of PH, and importantly that aspirin, a FDA-approved widely used drug, was capable of ameliorating PVR in a preclinical rat model of hypoxia-induced PH. Moreover, aspirin exerted its inhibitory effects on EndMT in vitro and in vivo by suppressing HIF-1α/TGF-β1/Smads/Snail signaling pathway. Our data suggest that EndMT represents an intriguing drug target for the prevention and treatment of hypoxic PH and that aspirin may be repurposed to meet the urgent therapeutic needs of hypoxic PH patients.Liposomes have been suggested as potential tools for cholesterol deposit mobilization from atherosclerotic lesions. Here, we explored the anti-atherosclerotic effects of phosphatidylserine (PS)-containing liposomes in vivo. High-fat diet-fed New Zealand white rabbits which were divided into groups receiving weekly intravenous injections of PS liposomes, atorvastatin-loaded PS (PSA) liposomes (100 μg phospholipid/kg), or control buffer for four weeks. The size and severity grade of atherosclerotic plaques as well as lipid profile were evaluated at the completion of study. In vitro, the expression and levels of anti/pro-inflammatory genes and proteins, respectively, and macrophage cholesterol efflux capacity (CEC) of nanoliposomes were evaluated. Both PS and PSA lowered serum LDL-C (P = 0.0034, P = 0.0041) and TC (P = 0.029, P = 0.0054) levels but did not alter TG and HDL-C levels. Plaque size and grade were reduced by PS (P = 0.0025, P = 0.0031) and PSA (P = 0.016, P = 0.027) versus control. Moreover, intima-media thickness was significantly reduced in the PS vs. control group (P = 0.01). In cultured cells, ICAM-1 expression in the PS (P = 0.022) and VCAM-1 expression in the PS and PSA groups (P = 0.037, P = 0.004) were suppressed while TGF-β expression was induced by both PS and PSA (P = 0.048, P = 0.046). Moreover, CEC from macrophages to nanoliposomes was enhanced by PSA (P = 0.003). Administration of anionic PS-containing liposomes could improve lipid profile and promote plaque regression through mechanisms that may involve cholesterol efflux and modulation of adhesion molecules.Gastric cancer is resistant to chemotherapy, especially in the later stages. The prevalence of gastric cancer increases after the age of 40, and its peak is in the 7th decade of life. The proteins tau (tubulin associated unit) and stathmin are overexpressed in gastric cancer and contribute to the progression of the disease by increasing cancer cell proliferation, invasion, and inducing drug resistance. This review summarizes the current knowledge on the expression of tau protein and stathmin in gastric cancer and their roles in drug resistance. Medline and PubMed databases were searched from 1990 till February 2021 for the terms "tau protein", "stathmin", and "gastric cancer." Two reviewers screened all articles and assessed prognostic studies on the role of tau and stathmin proteins in gastric cancer progression. selleck chemical Collectively, studies reported that both proteins are expressed at different concentrations in gastric cancer and could be significant molecular biomarkers for prognosis. Both proteins could be good candidates for targeted therapy of gastric cancer and are associated with resistance to taxanes.L-arginine supplementation increases nitric oxide (NO) formation and bioavailability in hypertension. We tested the possibility that many effects of L-arginine are mediated by increased formation of NO and enhanced nitrite, nitrate and nitrosylated species concentrations, thus stimulating the enterosalivary cycle of nitrate. Those effects could be prevented by antiseptic mouthwash. We examined how the derangement of the enterosalivary cycle of nitrate affects the improvement of endothelial dysfunction (assessed with isolated aortic ring preparation), the antihypertensive (assessed by tail-cuff blood pressure measurement) and the antioxidant effects (assessed with the fluorescent dye DHE) of L-arginine in two-kidney, one-clip hypertension model in rats by using chlorhexidine to decrease the number of oral bacteria and to decrease nitrate reductase activity assessed from the tongue (by ozone-based chemiluminiscence assay). Nitrite, nitrate and nitrosylated species concentrations were assessed (ozone-based chemiluminiscence). Chlorhexidine mouthwash reduced the number of oral bacteria and tended to decrease the nitrate reductase activity from the tongue. Antiseptic mouthwash blunted the improvement of the endothelial dysfunction and the antihypertensive effects of L-arginine, impaired L-arginine-induced increases in plasma nitrite and nitrosylated species concentrations, and blunted L-arginine-induced increases in aortic nitrate concentrations and vascular antioxidant effects. Our results show for the first time that the vascular and antihypertensive effects of L-arginine are prevented by antiseptic mouthwash. These findings show an important new mechanism that should be taken into consideration to explain how the use of antibacterial mouth rinse may affect arterial blood pressure and the risk of developing cardiovascular and other diseases.The novel coronavirus disease 2019 (COVID-19) has led to a serious global pandemic. Although an oxidative stress imbalance occurs in COVID-19 patients, the contributions of thiol/disulphide homeostasis and nitric oxide (NO) generation to the pathogenesis of COVID-19 have been poorly identified. Therefore, the aim of this study was to evaluate the effects of antiviral drug therapy on the serum dynamics of thiol/disulphide homeostasis and NO levels in COVID-19 patients. A total of 50 adult patients with COVID-19 and 43 sex-matched healthy control subjects were enrolled in this prospective study. Venous blood samples were collected immediately on admission to the hospital within 24 h after the diagnosis (pre-treatment) and at the 15th day of drug therapy (post-treatment). Serum native thiol and total thiol levels were measured, and the amounts of dynamic disulphide bonds and related ratios were calculated. The average pre-treatment total and native thiol levels were significantly lower than the post-treatment values (P less then 0.001 for all). We observed no significant changes in disulphide levels or disulphide/total thiol, disulphide/native thiol, or native thiol/total thiol ratios between pre- and post-treatments. There was also a significant increase in serum NO levels in the pre-treatment values when compared to control (P less then 0.001) and post-treatment measurements (P less then 0.01). Our results strongly suggest that thiol/disulphide homeostasis and nitrosative stress can contribute to the pathogenesis of COVID-19. This study was the first to show that antiviral drug therapy can prevent the depletion in serum thiol levels and decrease serum NO levels in COVID-19 patients.For patients in shock, decisions regarding administering or withholding IV fluids are both difficult and important. Although a strategy of relatively liberal fluid administration has traditionally been popular, recent trial results suggest that moving to a more fluid-restrictive approach may be prudent. The goal of this article was to outline how whole-body point-of-care ultrasound can help clarify both the possible benefits and the potential risks of fluid administration, aiding in the risk/benefit calculations that should always accompany fluid-related decisions.Although hypothermia has received substantial attention as an indicator of severity in anaphylaxis, it has been neglected from the perspective of whether it could act as a disease-modifying factor in this condition. Here, the impact of naturally occurring (spontaneous) hypothermia on anaphylaxis was evaluated in a murine model of ovalbumin (OVA)-induced allergy. Nonextreme changes in the ambient temperature (Ta) were used to modulate the magnitude of spontaneous hypothermia. At a Ta of 24°C, challenge with OVA intraperitoneally or intravenously resulted in a rapid, transient fall in body core temperature, which reached its nadir 4-6°C below baseline in 30 min. This hypothermic response was largely attenuated when the mice were kept at a Ta of 34°C. The Ta-dependent attenuation of hypothermia resulted in a survival rate of only 30%, as opposed to survival of 100% in the condition that favored the development of hypothermia. The protective effect of hypothermia did not involve changes in the rate of mast cell degranulation, as assessed by the concentration of mast cell protease-1 in bodily fluids. On the other hand, hypothermia improved oxygenation of the brain and kidneys, as indicated by higher NAD+/NADH ratios. Therefore, it is plausible to propose that naturally occurring hypothermia makes organs more resistant to the anaphylactic insult.Successful reproduction is very important for individuals and for society. Currently, the human health span and lifespan are the object of intense and productive investigation with great achievements, compared to the last century. However, reproduction span does not progress concomitantly with lifespan. Reproductive organs age, decreasing the levels of sexual hormones, which are protectors of health through their action on several organs of the body. Thus, this is the starting point of the organismal decay and infertility. This starting point is easily detected in women. In men, it goes under the surface, undetected, but it goes, nevertheless. Regarding fertility, aging alters the hormonal equilibrium, decreases the potential of reproductive organs, diminishes the quality of the gametes and worsen the reproductive outcomes. All these events happen at a different pace and affecting different organs in women and men. The question is what molecular pathways are involved in reproductive aging and if there is a possible halting or even reversion of the aging events. Answers to all these points will be explained in the present review.A moderately halophilic bacterium isolated from the water samples collected from a salt field, Salinivibrio sp. TGB10 was found capable of producing poly-3-hydroxybutytate (PHB) from various sugars. Cell dry weight (CDW) of 8.82 g/L and PHB titer of 6.84 g/L were obtained using glucose as the carbon source after 24 h of cultivation in shake flasks. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was synthesized when propionate was provided as secondary carbon source. Salinivibrio sp. TGB10 exhibited favorable tolerance to propionate. The use of 8 g/L propionate and 20 g/L glucose as combinational substrates yielded 1.45 g/L PHBV with a 3-hydroxyvalerate monomer content of 72.02 mol% in flask cultures. In bioreactor study, CDW of 33.45 g/L and PHBV titer of 27.36 g/L were obtained after 108 h of fed-batch cultivation. The results indicated that Salinivibrio sp. TGB10 is a promising halophilic bacterium for the production of PHBV with various polymer compositions.