Int J Med Sci
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Objective: The pancreatic endocrinal system dominates the regulation of blood glucose levels in vivo, and the dysfunction of pancreatic endocrine β-cells is a major cause of the occurrence and development of Type 2 diabetes (T2D). Although microRNA (miRNA) have been found to be key regulators of pancreatic β-cells proliferation, differentiation and apoptosis, the underlying mechanism remains enigmatic. The aim of this study was to identify several novel miRNAs which might be involved in the etiopathogenesis of diabetic β-cells dysfunction. ⋯ At the same time, miR-452-5p was found to positively regulate the activity of the key rate-limiting enzyme branched-chain α-keto acid dehydrogenase-β (BCKDHB) in the catabolism of branched chain amino acids (BCAA), leading to mitochondrial dysfunction in pancreatic β-cells. Conclusions: miR-34a-5p and miR-452-5p were identified as the novel regulators of pancreatic endocrine dysfunction. These miRNAs might have the potential to be utilized as the new predictive biomarkers for the diagnosis of the occurrence and development of T2D, as well as the therapeutic targets for T2D treatment.
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Background: Asthenozoospermia, one of the most common causes of male infertility, is a complicate multifactorial pathological condition that genetic factors are involved in. However, the epigenetic signature and mechanism of asthenozoospermia still remain limited. Our study aimed to confirm the key microRNAs (miRNAs) and genes in asthenozoospermia and demonstrate the underlying epigenetic regulatory mechanisms. ⋯ Conclusion: This study firstly pooled several published studies and a GEO dataset to determine the significance of potential miRNAs and genes, such as miR-374b, miR-193a, miR-34b, BDNF, NTRK2, HNRNPD and EFTUD2 in regulating asthenozoospermia and underscore their interactions in the pathophysiological mechanism. Our results provided theoretical basis and new clues for potential therapeutic treatment in asthenozoospermia. Validations in vivo and in vitro are required in future studies.
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A functional p53 protein plays an important role in killing tumor cells. Previous studies showed that chemotherapeutic drug, paclitaxel (PTX), showed anti-tumor activity through inducing G2/M arrest and apoptosis by targeting microtubules in tumor cells. However, PTX was not sensitive to p53-inactivated papillary thyroid carcinoma (PTC) cells by inducing G2/M arrest only. ⋯ There was high level of p53 in rAd-p53-treated PTC cells. rAd-p53 + PTX increased the level of p21, p-ATM and γ-H2AX and decreased the level of Cyclin D1/E1, suggesting p53 activated p21 which negatively regulated cyclins to induce S arrest response to DNA damage in PTC cells. rAd-p53 + PTX increased the levels of cleaved-PARP-1, cleaved -Caspase 3, and BAX and decreased the level of BCL-XL, suggesting p53 regulates the expression of BAX/BCL-XL to mediate DNA damage-induced apoptosis in PTC cells. Furthermore, rAd-p53 + PTX showed significant tumor inhibition in TPC-1 xenograft model, with an inhibitory rate of 79.39%. TUNEL assay showed rAd-p53 + PTX induced notable apoptosis in tumor tissues. rAd-p53 showed good sensitization of PTX in vitro and in vivo through inducing DNA damage induced-apoptosis indicated p53-dependent apoptosis was essential for the antitumor effect of PTX in PTC.
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[This corrects the article DOI: 10.7150/ijms.29322.].
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Background: Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of complications such as autoimmune and vascular disorders. Aim: This study aimed to explore the relationship between NETs and vasculitis. ⋯ Conclusion: Neutrophil hyperactivity and its role in vasculitis are not yet fully understood. More studies aiming to determine the accurate function of NETs in vasculitis pathogenesis, particularly in humans, should be undertaken. Intensive research on NETs and vasculitis can increase the knowledge of medical practitioners and contribute to the development of new treatment methods to enhance patient outcomes in the future.