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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Review Case Reports
Investigating the Process of Autoimmune Inner Ear Disease: Unveiling the Intricacies of Pathogenesis and Therapeutic Strategies.
Autoimmune inner ear disease (AIED) is a rare condition characterized by immune-mediated damage to the inner ear, leading to progressive sensorineural hearing loss (SNHL) and vestibular symptoms such as vertigo and tinnitus. This study investigates the pathogenesis and therapeutic strategies for AIED through the analysis of three cases with different underlying autoimmune disorders: rheumatoid arthritis, relapsing polychondritis, and IgG4-related disease. The etiology of AIED involves complex immunopathological mechanisms, including molecular mimicry and the "bystander effect," with specific autoantibodies, such as those against heat shock protein 70 (HSP70), playing a potential role in cochlear damage. ⋯ Early intervention is crucial for favorable outcomes, as demonstrated in the studied cases, where timely corticosteroid and immunosuppressive treatments led to significant hearing improvement. The study underscores the importance of personalized treatment strategies based on individual immunologic profiles and comorbidities. Our findings highlight the heterogeneity of AIED and the potential for biologic therapies in refractory cases.