Int J Med Sci
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Receptor-interacting protein 3 (Ripk3) plays a crucial part in acute lung injury (ALI) by regulating inflammation-induced endothelial damage in the lung tissue. The precise mechanisms through which Ripk3 contributes to the endothelial injury in ALI still remain uncertain. In the current research, we employed Ripk3-deficient (Ripk3-/-) mice to examine the role of Ripk3 in ALI progression, focusing on its effects on endothelial cells (ECs), mitochondrial damage and necroptosis. ⋯ Ripk3 upregulation suppressed the AMP-activated protein kinase (AMPK) pathway and activated Drp1-mediated mitochondrial fission, increasing mitochondrial permeability transition pore (mPTP) opening and PMVEC necroptosis. Conversely, Ripk3 deletion activated the AMPK/Drp1-mitochondrial fission pathway, preventing mPTP opening and PMVEC necroptosis in ALI. These findings demonstrated that Ripk3 promotes necroptosis through the AMPK/Drp1/mPTP opening pathway, identifying a potential therapeutic target for ALI treatment.
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Nephrotoxicity remains a significant concern associated with tyrosine kinase inhibitors, such as dasatinib (DASA). Previous studies have shown that DASA can induce renal tubular cell death, contributing to its nephrotoxic effects. In contrast, naringenin (NGN) is known for its antioxidant and anti-inflammatory properties. ⋯ Notably, DASA treatment upregulated the gene expression of the pro-apoptotic gene BAX while downregulating the expression of BCL-2 and Caspase-3 in kidney tissues. These findings suggest that NGN exerts nephroprotective effects against DASA-induced nephrotoxicity through its antioxidant, anti-inflammatory, and anti-apoptotic properties. Further investigations are warranted to elucidate the underlying mechanisms involved.
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Pancreatic ductal adenocarcinoma (PDAC) is a major global health challenge owing to late diagnosis and inherently metastatic nature. Although surgical intervention offers a potential remedy, only few patients are eligible, and drug resistance further complicates treatment. The therapeutic limitations have catalyzed a search for alternative treatments, particularly natural products. ⋯ Molecular docking analysis revealed that HMTA potentially could interact with tubulin, and in vitro assay confirmed it suppresses tubulin polymerization. HMTA significantly inhibited BxPC-3 xenograft tumor growth in mice. Overall, these findings suggested that HMTA is a promising candidate for PDAC therapy.
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Review Meta Analysis
Differences of the Chest Images Between Coronavirus Disease 2019 (COVID-19) Patients and Influenza Patients: A Systematic Review and Meta-analysis.
Background: Coronavirus disease 2019 (COVID-19) and influenza are two infectious diseases that can pose a great threat to human health. We aimed to compare the differences in chest images between patients with COVID-19 and influenza to deepen the understanding of these two diseases. Methods: We searched PubMed, Embase and Web of Science for articles published before December 25, 2023, and performed a meta-analysis using Stata 14.0 with a random-effects model. ⋯ Patients with COVID-19 showed more ground-glass opacities (OR=2.83, 95% CI: 1.85-4.32), reverse halo signs (OR=3.47, 95% CI: 2.37-5.08), interlobular septal thickening (OR=2.16, 95% CI: 1.55-3.01), vascular enlargement (OR=5.00, 95% CI: 1.80-13.85) and crazy-paving patterns (OR=2.63, 95% CI: 1.57-4.41) on chest images than patients with influenza. We also found that compared with influenza patients, pleural effusion was rare in COVID-19 patients (OR=0.15, 95% CI: 0.07-0.31). Conclusions: There are some differences in the manifestations and distributions of lesions between patients with COVID-19 and influenza on chest images, which is helpful to distinguish these two infectious diseases.
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Meta Analysis
Immunological Insights into the Causal Link Between Arthritis, Osteoarthritis, and Frailty: An Integrated Analytical Study.
Background: Previous observational studies have observed associations between rheumatoid arthritis (RA), knee osteoarthritis (KOA), hip osteoarthritis (HOA), and frailty, but the causal relationships remain unestablished. Objective: This study aimed to evaluate the causal relationships between RA, KOA, HOA, KneeHipOA, and frailty using Mendelian randomization (MR) and bioinformatics analysis. Methods: We performed two-sample MR to test for causality between RA, KOA, HOA, KneeHipOA, and frailty. ⋯ Our findings suggested that increases in monocyte cell AC, eosinophil cell AC, and neutrophil cell AC were associated with a higher risk of frailty. Conclusion: This research provides evidence supporting the associations between RA, KOA, HOA, KneeHipOA, and frailty. It also highlights the significant role of circulating immune cells in the development of frailty, indicating the importance of frailty management from an immunological perspective.