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Previous studies revealed that direct contact with graphene oxide (GO) induced cytotoxic effects, but the importance of involvement of metabolic pathways, in particular lipid metabolism pathways, might be overlooked. In this study, human umbilical vein endothelial cells (HUVECs) were exposed to GO with large size (denoted as GO-L) or small size (denoted as GO-S), and transcriptomics were used to understand the mechanisms of cytotoxicity of GO at systemic levels. It was shown that GO-L more significantly induced cytotoxicity compared with GO-S. Transcriptomic analysis revealed that compared with GO-S, GO-L had larger impact on gene ontology terms related with mitochondrial function as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related with cell death and growth. But GO-S showed greater influence on KEGG pathways related with lipid metabolism. see more Both types of GO showed minimal impact on oxidative stress but increased de novo lipogenesis protein fatty acid synthase (FASN). However, only GO-S significantly promoted acyl-CoA synthetase 3 (ACSL3), a key enzyme responsible for esterification of free fatty acids and lipid droplet biogenesis. Not surprisingly, GO-L but not GO-S impaired lipid droplet biogenesis, and increasing lipid levels by oleic acid or α-linolenic acid reduced the cytotoxicity of GO-L to HUVECs. Combined, the results from this study suggested that impaired lipid droplet biogenesis was involved in GO-induced cytotoxicity in HUVECs, and inducing lipid droplet biogenesis could prevent the cytotoxicity of GO.Udenafil is a long-acting oral phosphodiesterase type 5 inhibitor used to treat erectile dysfunction which may also have beneficial effects on cardiovascular diseases. Udenafil is mainly biotransformed to the active metabolite N-dealkylated udenafil via cytochrome P450 3A. The aim of this study was to investigate the gender differences and dose proportionality of the toxicokinetics of udenafil and its metabolite N-dealkylated udenafil in rodents. Udenafil was administered orally by gavage to male and female B6C3F1/N mice (100, 240, 350, and 500 mg/kg) and F344 rats (60, 120, and 240 mg/kg). Plasma concentrations of udenafil and N-dealkylated udenafil were simultaneous measured via liquid chromatography-tandem mass spectrometry. Female mice showed higher systemic exposure to udenafil than male mice, whereas female rats showed lower systemic exposure to udenafil than male rats after repeated administration at high dose. Systemic exposure to the metabolite, N-dealkylated udenafil, was lower in female than male mice and rats. A dose proportionality assessment by power model revealed a lack of dose proportionality in systemic exposure (Cmax, AUC24h and AUCinf) after administration of 100-500 mg/kg of udenafil in mice and 60-240 mg/kg in rats. This study thus demonstrates gender and species differences with regard to the toxicokinetic profiles of udenafil and its active metabolite N-dealkylated udenafil after oral administration of udenafil to mice and rats of both sexes. Our findings suggest the possibility of gender differences in the toxicokinetics of udenafil in humans and suggests that further study is needed in this cohort.Since the discovery of the yellow fever virus in 1901, thus far, two hundred nineteen viral species are recognized as human pathogens. Each year, the number of viruses causing infections in humans increases, triggering epidemics and pandemics, such as the current COVID-19 pandemic. Pointing to bats as the natural host, in 2019, a genome highly identical to a bat coronavirus (COVID-19) spread all over the world, and the World Health Organization (WHO) officially confirmed it as a pandemic. The virus mainly spreads through the respiratory tract, uses angiotensin-converting enzyme 2 (ACE2) as a receptor, and is characterized by symptoms of fever, cough, and fatigue. Antivirals and vaccines have provided improvements in some cases, but the discovery of a new and diverse variety of viruses with outbreaks has posed a challenge in timely treatments for medical scientists. Currently, few specific antiviral strategies are being used, and many of the effective antiviral drugs and reported active molecules are under vital exploration. In this review, with the details of viral diseases, we summarize the current attempts in drug development, epidemiology, and the latest treatments and scientific advancements to combat the COVID-19 epidemic. Moreover, we discuss ways to reduce epidemics and pandemics in the near future.Posterior capsule opacification (PCO), resulting from residual lens epithelial cell (LEC) epithelial-mesenchymal transition (EMT), abnormal proliferation, and migration, is the most common complication of cataract surgery. A recent study determined that extracellular vesicles (EVs) and reactive oxygen species (ROS) regulate the EMT process during cutaneous wound healing and tumour metastasis. However, their underlying mechanism in PCO is unclear. In this study, we examined the secreted EVs from a scratch model in vitro. We found that the production of ROS was increased after mechanical injury, especially at the wound edge, and there was an increased viability of LECs, which can be blocked by diphenyleneiodonium, an NADPH oxidase inhibitor. Cell viability and migration were increased upon treatment with 1 μM H2O2, but significantly reduced when the concentration of H2O2 increased to 100 μM. Transwell assay showed that both post-surgery LECs and LECs treated with 1 μM H2O2 significantly induced the migration of normal LECs by EV secretion. Extraction and quantification of EVs derived from injured and H2O2-treated LECs showed a similar increase in production. Co-incubation of EVs from both injured and H2O2-treated LECs with normal LECs and organ-cultured mouse lenses activated EMT, which was attenuated by a ROS inhibitor. These results suggest that EVs participate in ROS-induced lens EMT, making EVs a potential target for treating PCO.Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis.