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Additionally, there was an increase in phosphorylated Smad1/5/9 (phospho-Smad1/5/9) -immunopositive astrocytes in the CA1 region 7 days after ischemia. Real-time PCR analysis showed an increase in the expression level of TGF-β1 mRNA in the hippocampus after ischemia. Intracerebroventricular injection of SB525334, an inhibitor of TGF-β/Smad signaling, reduced immunoreactivity for phospho-Smad1/5/9 in astrocytes. These results suggest that TGF-β1 may be a key molecule for ischemia-induced Smad1/5/9 phosphorylation in astrocytes, and TGF-β1-Smad1/5/9 signaling may play a role in post-ischemic events, including brain inflammation or tissue repair rather than neuroprotection of the hippocampus.Clostridioides difficile is an emerging One Health pathogen and a common etiologic agent of diarrhea, both in healthcare settings and the community. This bacterial species is highly diverse, and its global population has been classified in eight clades by multilocus sequence typing (MLST). The C. difficile MLST Clade 2 includes the NAP1/RT027/ST01 strain, which is highly recognized due to its epidemicity and association with severe disease presentation and mortality. By contrast, the remaining 83 sequence types (STs) that compose this clade have received much less attention. Selleck K-Ras(G12C) inhibitor 9 In response to this shortcoming, we reviewed articles published in English between 1999 and 2020 and collected information for 27 Clade 2 STs, with an emphasis on STs 01, 67, 41 and 188/231/365. Our analysis provides evidence of large phenotypic differences that preclude support of the rather widespread notion that ST01 and Clade 2 strains are "hypervirulent". Moreover, it revealed a profound lack of (meta)data for nearly 70% of the Clade 2 STs that have been identified in surveillance efforts. Targeted studies aiming to relate wet-lab and bioinformatics results to patient and clinical parameters should be performed to gain a more in-depth insight into the biology of this intriguing group of C. difficile isolates.Cocoa powder, derived Theobroma cacao, is a popular food ingredient that is commonly consumed in chocolate. Epidemiological and human intervention studies have reported that chocolate consumption is associated with reduced risk of cardiometabolic diseases. Laboratory studies have reported the dietary supplementation with cocoa or cocoa polyphenols can improve obesity and obesity-related comorbidities in preclinical models. Non-alcoholic fatty liver disease (NAFLD), one such comorbidity, is a risk factor for cirrhosis and hepatocellular carcinoma. Limited studies have examined the effect of cocoa/chocolate on NAFLD and underlying hepatoprotective mechanisms. Here, we examined the hepatoprotective effects of dietary supplementation with 80 mg/g cocoa powder for 10 wks in high fat (HF)-fed obese male C57BL/6J mice. We found that cocoa-supplemented mice had lower rate of body weight gain (22%), hepatic triacylglycerols (28%), lipid peroxides (57%), and mitochondrial DNA damage (75%) than HF-fed controls. These changes were associated with higher hepatic superoxide dismutase and glutathione peroxidase enzyme activity and increased expression of markers of hepatic mitochondrial biogenesis. We also found that the hepatic protein expression of sirtuin 3 (SIRT3), and mRNA expression of peroxisome proliferator activated receptor g coactivator (PGC) 1a, nuclear respiratory factor 1, and forkhead box O3 were higher in cocoa-treated mice compared to HF-fed controls. These factors play a role in coordinating mitochondrial biogenesis and expression of mitochondrial antioxidant response factors. Our results indicate that cocoa supplementation can mitigate the severity of NAFLD in obese mice and that these effects are related to SIRT3/PGC1a-mediated increases in antioxidant response and mitochondrial biogenesis.Gas plasma is a partially ionized gas increasingly recognized for targeting cancer. Several hypotheses attempt to explain the link between plasma treatment and cytotoxicity in cancer cells, all focusing on cellular membranes that are the first to be exposed to plasma-generated reactive oxygen species (ROS). One proposes high levels of aquaporins, membrane transporters of water and hydrogen peroxide, to mark tumor cell line sensitivity to plasma treatment. A second focuses on membrane-expression of redox-related enzymes such as NADPH oxidases (NOX) that may modify or amplify the effects of plasma-derived ROS, fueling plasma-induced cancer cell death. Another hypothesis is that the decreased cholesterol content of tumor cell membranes sensitizes these to plasma-mediated oxidation and subsequently, cytotoxicity. Screening 33 surface molecules in 36 tumor cell lines in correlation to their sensitivity to plasma treatment, the expression of aquaporins or NOX members could not explain the sensitivity but were rather associated with treatment resistance. Correlation with transporter or enzyme activity was not tested. Analysis of cholesterol content confirmed the proposed positive correlation with treatment resistance. Strikingly, the strongest correlation was found for baseline metabolic activity (Spearman r = 0.76). Altogether, these data suggest tumor cell metabolism as a novel testable hypothesis to explain cancer cell resistance to gas plasma treatment for further elucidating this innovative field's chances and limitations in oncology.The macrophage capping protein CAPG belongs to the gelsolin superfamily which modulates actin dynamics by capping the growing end of actin filaments in a Ca2+- and PIP2-dependent manner resulting in polymerization inhibition of actin filaments. In the last years, additional functions for CAPG in transcription regulation were described and higher CAPG amounts have been linked to increased invasiveness and migration behavior in different human tumor entities like e.g. glioblastoma. Nevertheless, there is a lack of knowledge how additional functions of CAPG are regulated. As CAPG contains several cysteine residues which may be accessible to oxidation we were especially interested to investigate how alterations in the cysteine oxidation state may influence the function, localization, and regulation of CAPG. In the present study, we provide strong evidence that CAPG is a redox-sensitive protein and identified two cysteines C282 and C290 as reversibly oxidized in glioblastoma cell lines. Whereas no evidence could be found that the canonical actin capping function of CAPG is redox-regulated, our results point to a novel role of the identified cysteines in the regulation of cell migration.