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High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson's disease, Alzheimer's disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment. [ABSTRACT FROM AUTHOR]

Aims: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. Methods: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment‐emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. Results: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment‐emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre‐specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug‐related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post‐treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90‐day assessment. Conclusion: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real‐world large population. [ABSTRACT FROM AUTHOR]

miRNAs are a class of small non‐coding RNAs that are involved in various biological processes. In the preliminary work of the laboratory, found that miR‐383‐5p was down‐regulated in the liver tissue of acute cold stress rats and has been shown to be an important regulatory factor in tumour proliferation, but there are very few studies involving the mediation of cold stress in rat liver tissues. Therefore, the purpose of this study was to determine the effect of miR‐383‐5p on the livers of cold stress rats by simulating the cold stress state of rat liver tissues in vitro using H2O2 to induce rat hepatocyte oxidative stress. The results showed that MDA content, Caspase 3 and Cyto C protein levels increased significantly; GPx activity and SOD1 protein levels decreased significantly and miR‐383‐5p expression was significantly down‐regulated in rat liver tissues after cold stress. Different concentrations of H2O2 was added to rat hepatocytes, and the results showed that the expression of miR‐383‐5p, the ROS level, and the apoptosis rate in rat hepatocytes was increased significantly in a concentration‐dependent fashion. Transfection of miR‐383‐5p inhibitor revealed that the apoptosis rate of rat hepatocytes, and the protein level of apoptosis‐related protein Caspase 3 were reduced; the results of the dual‐luciferase reporter gene assay showed that miR‐383‐5p targeted regulation of Bcl2. The results suggested that the expression of miR‐383‐5p was up‐regulated in oxidative stress rat hepatocytes and may aggravate the apoptosis of rat hepatocytes induced by targeting inhibition of Bcl2 translation. [ABSTRACT FROM AUTHOR]

Quinalizarin, a bioactive and highly selective compound, is known to promote apoptosis in colon and lung cancer cells. However, studies evaluating quinalizarin‐induced apoptosis in melanoma cells have not been conducted. In the present study, we investigated the underlying mechanisms of antimelanoma activity of quinalizarin in human melanoma A375 cells. The MTT assay and Trypan blue staining were used to evaluate the cell viability. The flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Western blot was used to detect the expression of cell cycle and apoptosis‐related proteins, MAPK, and STAT3. The results revealed a significant dose and time dependent effect of quinalizarin on inhibiting proliferation in three kinds of human melanoma cells, and had no significant toxic effects on normal cells. Moreover, quinalizarin triggered G2/M phase cell arrest by modulating the protein expression levels of CDK 1/2, cyclin A, cyclin B, p21 and p27, and induced apoptosis by down‐regulating the antiapoptotic protein Bcl‐2 and upregulating the proapoptotic protein BAD, leading to the activation of caspase‐3 and PARP in the caspase cascade in A375 cells. Quinalizarin treatment led to apoptosis of A375 cells via activation of MAPK and inhibition of STAT3 signaling pathways. In addition, quinalizarin increased the level of ROS, but ROS scavenger NAC inhibited quinalizarin‐induced apoptosis by regulating MAPK and STAT3 signaling pathways. In summary, quinalizarin induces cell cycle arrest and apoptosis via ROS‐mediated MAPK and STAT3 signaling pathways in human melanoma A375 cells, and quinalizarin may be used as a novel and effective antimelanoma therapeutic. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of single‐stranded non‐coding small RNA molecules, which participate in the regulation of many physiological processes, and play a crucial role in cancer, metabolism and other processes. Rno‐miR‐425‐5p has been shown to play a role in the response to cold stress. To explore the mechanism by which rno‐miR‐425‐5p regulates the response to cold stress, we analysed the candidate target genes of rno‐miR‐425‐5p. After verification in rat hepatocyte BRL cells and in rat liver tissue, we identified several target genes that were altered in expression in response to cold stress. In rat liver tissue, the expression of rno‐miR‐425‐5p was significantly increased and the expression levels of target genes DLST and SLC16A1 were decreased under cold stress. The miRNA and mRNA levels were analysed by quantitative real‐time PCR and the protein levels were detected by Western blot analysis. Combined with the results of bioinformatic analysis, we concluded that rno‐miR‐425‐5p reduced the expression of DLST and SLC16A1, inhibiting energy release from the tricarboxylic acid cycle and preventing the liver from being injured by excessive energy mobilization. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article I Quinalizarin induces cycle arrest and apoptosis via reactive oxygen species-mediated signaling pathways in human melanoma A375 cells i by Ying-Hua Luo et al., https://doi.org/10.1002/ddr.21582. [Extracted from the article]

O-GlcNAcylation is a dynamic, reversible and atypical O-glycosylation that regulates various cellular physiological processes via conformation, stabilisation, localisation, chaperone interaction or activity of target proteins. The O-GlcNAcylation cycle is precisely controlled by collaboration between O-GlcNAc transferase and O-GlcNAcase. Uridine-diphosphate-N-acetylglucosamine, the sole donor of O-GlcNAcylation produced by the hexosamine biosynthesis pathway, is controlled by the input of glucose, glutamine, acetyl coenzyme A and uridine triphosphate, making it a sensor of the fluctuation of molecules, making O-GlcNAcylation a pivotal nutrient sensor for the metabolism of carbohydrates, amino acids, lipids and nucleotides. O-GlcNAcylation, particularly prevalent in liver, is the core hub for controlling systemic glucose homeostasis due to its nutritional sensitivity and precise spatiotemporal regulation of insulin signal transduction. The pathology of various liver diseases has highlighted hepatic metabolic disorder and dysfunction, and abnormal O-GlcNAcylation also plays a specific pathological role in these processes. Therefore, this review describes the unique features of O-GlcNAcylation and its dynamic homeostasis maintenance. Additionally, it explains the underlying nutritional sensitivity of O-GlcNAcylation and discusses its mechanism of spatiotemporal modulation of insulin signal transduction and liver metabolic homeostasis during the fasting and feeding cycle. This review emphasises the pathophysiological implications of O-GlcNAcylation in nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and hepatic fibrosis, and focuses on the adverse effects of hyper O-GlcNAcylation on liver cancer progression and metabolic reprogramming., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)