Hanleyfrandsen9237

Oxidative stress is proven to be critical for the initiation and progression of vitiligo. Molecular hydrogen (H2) possesses potent antioxidant activity and has been shown to protect against various oxidative stress-related diseases. In this study, we first investigated the effects and mechanisms of H2 in human melanocytes damaged by hydrogen peroxide (H2O2). We initially found that H2 reduced intracellular reactive oxygen species (ROS) accumulation and malondialdehyde (MDA) levels in both vitiligo specimens and H2O2-treated melanocytes in vitro in a concentration- and time-dependent manner, concomitant with the enhancement of antioxidant enzyme activity. Correspondingly, H2 reversed H2O2-induced apoptosis and dysfunction in both normal and vitiligo melanocytes. H2 protected mitochondrial morphology and function in melanocytes under stress and promoted the activation of nuclear erythroid 2-related factor (Nrf2) signaling, while Nrf2 deficiency abolished the protective effect of H2 against H2O2-induced oxidative damage. Furthermore, H2 positively modulated β-catenin in H2O2-treated melanocytes, and the β-catenin pathway was implicated in H2-induced Nrf2 activation. Collectively, our results indicate that H2 could be a promising therapeutic agent for vitiligo treatment via attenuating oxidative damage, and its beneficial effect in human melanocytes might involve Wnt/β-catenin-mediated activation of Nrf2 signaling. Itch, initiated by the activation of sensory neurons, is frequently associated with dermatological diseases. MrgprA3+ sensory neurons have been identified as one of the major itch-sensing neuronal populations. Mounting evidence has demonstrated that peripheral pathological conditions induce physiological regulations of sensory neurons, which is critical for the maintenance of chronic itch sensation. However, the underlying molecular mechanisms are not clear. Here we performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis conditions. Our results revealed the unique molecular signature of itch-sensing neurons and the distinct transcriptional profile changes that result in response to dermatitis. We found enrichment of nine Mrgpr family members and two histamine receptors in MrgprA3+ neurons, suggesting that MrgprA3+ neurons are a direct neuronal target for histamine and Mrgprs agonists. In addition, Ptpn6 and Pcdh12 were identified as highly selective markers of MrgprA3+ neurons. We also discovered that MrgprA3+ neurons respond to skin dermatitis in a way that is unique from other sensory neurons by regulating a combination of transcriptional factors, ion channels, and key molecules involved in synaptic transmission. These results significantly increase our knowledge of itch transmission and uncover potential targets for combating itch. Hepatocellular carcinoma (HCC) remains a major clinical challenge. Although mitophagy is implicated in hepatocarcinogenesis, novel therapeutic options targeting mitophagy for HCC treatment still await further studies. Here, we demonstrate that sanguinarine induces cell death in HCC cell line MHCC-97H through the mitochondrial apoptosis pathway. Sanguinarine triggers mitochondrial dysfunction and PTEN-induced putative kinase 1 (PINK1)/Parkin upregulation and recruitment to mitochondria. Elevated levels of p62 and LC3-II/I ratios suggest that sanguinarine is both an inducer of autophagy and a blocker of autolysosome formation, which is further confirmed by LC3-II conversion levels in presence of autophagy and mitophagy inhibitors, as well as an autophagy activator. In addition, blocking autophagy promotes sanguinarine-induced cell death, indicating mitophagy plays a cytoprotective role in sanguinarine-treated cells. Our findings suggest that blocking mitophagy may contribute to sanguinarine-induced mitochondrial apoptosis through the prevention of damaged mitochondrial clearance. BACKGROUND PTEN is a tumour suppressor gene that has been proven to be related to breast cancer incidence and tumour progression. The aim of this study was to investigate the frequency of PTEN mutations in breast carcinomas in China and the relationships of PTEN mutations with clinicopathological parameters and clinical outcomes. MATERIAL AND METHODS Trimmomatic, Burrows-Wheeler Aligner (BWA), ANNOVAR, SAMtools, and Sanger sequencing were used to analyse PTEN mutations and identify variants in Chinese breast cancer. The frequency of PTEN mutations and the relationships of PTEN mutations with clinicopathological parameters and clinical outcomes were evaluated in breast carcinomas in China. RESULTS The rate of PTEN germline mutation was 0.23% (n = 9) among 3955 unselected primary breast cancer patients. Of these 9 patients, 2 carried pathogenic mutations, and both were identified as having infiltrative carcinoma. One patient had a family history. The other 7 patients carried only PTEN germline variants that were not identified as pathogenic mutations. CONCLUSIONS We studied the frequency of PTEN germline mutations in a sequential cohort of Chinese breast carcinoma patients. Based on these data, we hypothesize that the germline mutation of the PTEN gene is not closely related to the occurrence of breast cancer in the Chinese population. STA-4783 datasheet In the clinic, the PTEN germline mutation cannot be used as the basis for the detection of breast cancer. V.MiR-155 is an immune microRNA encoded within the BIC gene. Dozens of researches have uncovered the importance of high expression of miR-155 in promoting the development of immune organs and strengthening immune response and inflammatory response. Some natural mutations located in the miR-155/BIC region were revealed to disturb the expression level of miR-155 in several mammalian species, and our previous study also identified several mutations occurring near the miR-155/BIC region in pigs. However, the consequences of BIC locus-harbored mutations in pig genome remain unclear. In this study, we used Chinese Meishan and British Large White pigs to identify mutations within the miR-155/BIC region, and explore whether there are effects on expressions of miR-155 and its target genes. Target sequencing identified six potential FOXP3 protein binding sites (AAACA) in the BIC gene, among which there were two A/C mutations (AAACC) at the -108 bp and -305 bp upstream of the miR-155 precursors in Meishan pigs, but not in Large White pigs. A series of experiments confirmed that the FOXP3 protein mainly binds to the -305 bp position, and the binding efficiency of the CC haplotype to FOXP3 protein was higher than that of the wild type, resulting in increased expression of miR-155, and consequentially decreased the expressions of its target genes. Our newly identified mutations are functional, which explain partial reasons for the difference in immunity between Meishan and Large White pigs, and provide potential molecular markers to genetically improve the disease resistance in the pig breeding practice. BACKGROUND The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries with cases reported worldwide. This novel Coronavirus Disease (COVID-19) is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which have not been completely understood to date. OBJECTIVES We provide a review of the differences in terms of pathogenesis, epidemiology and clinical features between COVID-19, SARS and MERS. SOURCES The most recent literature in English language regarding COVID-19 has been reviewed and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. CONTENT COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than SARS (9.5%) and much lower than MERS (34.4%). It cannot be excluded that because of the COVID-19 less severe clinical picture it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than MERS ( less then 1),. The gastrointestinal route of transmission of SARS-CoV-2, which has been also assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs to be further investigated. IMPLICATIONS There is still much more to know about COVID-19, especially as concerns mortality and capacity of spreading on a pandemic level. Nonetheless, all of the lessons we learned in the past from SARS and MERS epidemics are the best cultural weapons to face this new global threat. The extraction process of Glycyrrhiza soluble polysaccharide (GP) was optimized by RSM, a rat trauma model was established via longitudinal incision on the back skin. The effects of GP combined with microcapsule collagen on the repair of rat injury model were discussed at different levels, Based on the content of hydroxyproline at the whole animal level, the proliferation of granulation tissue stained by HE, the number of microvessels labeled by CD34, the production of collagen fibers stained by Masson, the level of phosphorylation of STAT3 protein and that of VEGF at protein level were investigated. The results showed that after the administration of GP combined with microcapsules, the content of hydroxyproline in granulation tissue increased, the proliferation of capillaries and fibroblasts in granulation tissue became active, and the number of microvessels in wound increased. The formation density of collagen fibers was uniform and orderly. GP combined with microcapsules could activate the expression of p-STAT3 and VEGF proteins and up-regulate the transcription level of VEGF mRNA and miRNA-21 genes. Furthermore, GP combined with microcapsules could accelerate wound healing and promote neovascularization. V.Different interpenetrating polymeric networks (IPN) based on sodium alginate, carrageenan and bentonite were developed to remove heavy metals and dyes from contaminated water. Four significant preparation factors; crosslinking time, calcium chloride concentration, alginate to carrageenan mass ratio,and bentonite to carrageenan mass ratio were studied and optimized via full factorial design and response surface methodology to determine the optimum composition with highest adsorption capacity. Different optimal conditions and combinations were found depending on the type of heavy metal or dye to be removed. Low calcium chloride concentration was a common factor in all cases of heavy metals and dyes removal which indicates the negative effect of excessive crosslinking on the removal percentage. The adsorption capacity of methylene blue, Fe3+, Ni2+, and Cr3+ ions is 1271, 1550, 1500 and 1540 mg/g adsorbent, respectively. Reusability tests confirmed that the optimized formulations can be reused five successive times without significant drop in their removal efficiency. Upon utilization of the optimized formulations on real contaminated waters from tannery plant and oasis groundwater, they demonstrated an excellent performance as they removed above 95% of the original heavy metals contaminants and 40% of the acidic dye content. V.