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  • Ortiz posted an update 9 months ago

    Interestingly, κ-CGN treatment did not cause typical diabetic symptoms in mice, as indicated by low levels of fasting and postprandial blood glucose, in addition to normal pancreatic tissue and insulin secretion. The binding studies revealed that κ-CGN could competitively bind to the insulin receptor with FITC-insulin and thereby disrupt PI3K and Akt activation, thus suppressing expression of glucose transporters and glycogen synthase. In summary, this study revealed that κ-CGN reduced weight gain without affecting food intake, but impaired glucose metabolism in mice by interfering with insulin binding to receptors, thereby affecting the sensitivity of insulin and inhibiting the insulin PI3K/AKT signaling pathway, causing non-diabetic weight gain reduction.The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.Non-coding RNAs (ncRNAs) contribute to the regulation of gene expression. By acting as competing endogenous RNA (ceRNA), long non-coding RNAs (lncRNAs) hijack microRNAs (miRNAs) and inhibit their ability to bind their coding targets. Viral miRNAs can compete with and target the same transcripts as human miRNAs, shifting the balance in networks associated with multiple cellular processes and diseases. Epstein-Barr virus (EBV) is an example of how a subset of viral coding RNA and non-coding RNAs can cause deregulation of human transcripts and contribute to the development of EBV-associated malignancies. EBV non-coding transforming genes include lncRNAs (i.e circular RNAs), and small ncRNAs (i.e. GSK2643943A in vivo miRNAs). Among the latter, most ongoing research has focused on miR-BARTs whereas target many genes associated with apoptosis and epithelial-mesenchymal transition, in EBV-associated gastric cancer (GC). In this review, we propose to include the interactions between EBV ncRNAs human transcripts in the hypothesis known as “competitive viral and host RNAs”. These interactions may shift the balance in biological pathways such as apoptosis and epithelial-mesenchymal transition in EBV-associated gastric cancer.In this study, we performed an integrated physiological and chloroplast proteome analysis of wheat seedling leaves under salt and osmotic stresses by label-free based quantitative proteomic approach. Both salt and osmotic stresses significantly increased the levels of abscisic acid and methyl jasmonate and led to damages of chloroplast ultrastructure. Main parameters of chlorophyll fluorescence and gas exchange showed a significant decline under both stresses. Quantitative proteomic analysis identified 194 and 169 chloroplast-localized differentially accumulated proteins (DAPs) responsive to salt and osmotic stresses, respectively. The abundance of main DAPs involved in light-dependent reaction were increased under salt stress, but decreased in response to osmotic stress. On the contrary, salt stress induced a significant upregulation of the DAPs associated with Calvin cycle, transcription and translation, amino acid metabolism, carbon and nitrogen metabolism, and some of them exhibited a downregulation underIn this study, we employed label-free based quantitative proteomic approach to perform an integrated physiological and large-scale chloroplast proteome analysis of wheat seedling leaves under salt and osmotic stresses, which laid a solid foundation for future studies into the response and defense mechanisms of wheat chloroplast in response to abiotic stresses.Our prior studies identified a high-risk phenotype (ie, high pain sensitivity variant of the catechol-O-methyltransferase gene (Single Nucleotide Polymorphism [SNP] rs6269) and pain catastrophizing scores) for shoulder pain. The current study identified sensory and psychological predictors of heightened pain responses following exercise-induced shoulder injury. Healthy participants (N = 131) with the SNP rs6269 catechol-O-methyltransferase gene and Pain Catastrophizing Scale scores ≥5 underwent baseline sensory and psychological testing followed by an established shoulder fatigue protocol, to induce muscle injury. Movement-evoked pain, pain intensity, disability, and strength were assessed 24 hours postinjury. Demographic, sensory, and psychological variables were included as predictors in full and parsimonious models for each outcome. The highest variance explained was for the shoulder disability outcome (full model R2 = .20, parsimonious R2 = .13). In parsimonious models, the individual predictors identified were 1) 1st pulse heat pain sensitivity for isometric shoulder movement-evoked pain and pain intensity; 2) pressure pain threshold for shoulder disability; 3) fear of pain for active shoulder movement-evoked pain and shoulder disability; and 4) depressive symptoms for shoulder strength. Findings indicate specific pain sensitivity and psychological measures may have additional prognostic value for self-reported disability within a high-risk phenotype. These findings should be tested in a clinical cohort for validation. PERSPECTIVE The current study extends previous work by providing insight regarding how poor shoulder outcomes may develop within a high-risk phenotype. Specifically, 1st pulse heat pain sensitivity and pressure pain threshold were sensory measures, and fear of pain and depressive symptoms were psychological measures, that improved prediction of different shoulder outcomes.

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