Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Spinal cord ischemia-reperfusion injury (SCIRI) is a major contributor to neurological damage and mortality associated with spinal cord dysfunction. This study aims to explore the possible mechanism of Propofol and G-protein-coupled receptor-interacting protein 1 (GIT1) in regulating SCIRI in rat models. SCIRI rat models were established and injected with Propofol, over expression of GIT1 (OE-GIT1), or PI3K inhibitor (LY294002). ⋯ LY294002 can also decrease GIT1 expression levels in SCIRI rats. Propofol can attenuate neurological dysfunction induced by SCIRI, decrease spinal cord tissue injury and BSCB permeability in addition to suppressing cell apoptosis and inflammatory cytokines, whereas further treatment by LY294002 can partially reverse the protective effect of Propofol on SCIRI. Propofol can activate PI3K/AKT signal pathway to increase GIT1 expression level, thus attenuating SCIRI in rat models.
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Peripheral T-cell lymphoma (PTCL) is an extensive class of heterogeneous diseases with dismal outcomes. Brentuximab vedotin (BV) is an antibody‒drug conjugate (ADC) comprising CD30-directed antibody. This review aimed to evaluate the efficacy and safety of BV for treating PTCL. ⋯ For survival outcomes, the longest median PFS was 8.3 months, and the longest median OS was 26.3 months. The most common adverse event was peripheral neuropathy and neutropenia. The analysis suggested that BV alone or in combination with other drugs improved the response and survival rates in PTCL patients and was associated with tolerable adverse effects.
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Kidney transplantation is a pivotal treatment for end-stage renal disease (ESKD). However, renal ischemia-reperfusion injury (IRI) during surgery significantly impacts graft function. Despite unclear molecular mechanisms, no specific therapies or preventative measures are available. ⋯ PPI network analysis revealed IL6 as the gene with the highest connectivity, and the gene-miRNA network indicated IL6 might be regulated by miR-let-7a. Animal experiments revealed decreased miR-let-7a and increased IL6 levels in the model group, identifying potential therapeutic targets. MiR-let-7a regulates ferroptosis in renal IRI by targeting IL6, highlighting IL6 as a crucial gene in the ferroptosis process of renal IRI.
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Cisplatin (DDP) resistance represents a pivotal contributing factor to chemotherapy failure and adverse patient outcomes in gastric cancer (GC). The objective of present study was to investigate the roles and underlying mechanisms of myocyte enhancer factor 2A (MEF2A) in DDP resistance in GC. AGS and MKN-45 cells was applied to construct DDP-resistant cells. ⋯ Mechanistically, MEF2A play as a transcriptional activator of NFKBIA, which led to the reduction of phosphorylation of p65 and cytoplasmic retention. Moreover, MEF2A overexpression promoted the sensitivity of GC cells to DDP and tumor growth, whereas these effects were reversed by NFKBIA silence. Collectively, MEF2A mitigated the DDP resistance in GC cells by modulatory actions on the NFKBIA/NF-κB signaling, shedding light on MEF2A/NFKBIA might be promising intervention target for improving DDP resistance in GC.
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Atherosclerosis, a major cause of cardiovascular diseases, is characterized by the accumulation of oxidized lipoproteins (ox-LDL) within arterial walls, leading to inflammation and plaque formation. Hydrogen sulfide (H2S) has demonstrated anti-inflammatory and vascular protective properties, but its role in modulating macrophage endocytosis of ox-LDL and its impact on early atherosclerosis development remains unclear. Macrophage cultures were utilized for ox-LDL uptake experiments. ⋯ Furthermore, H2S down-regulated ox-LDL receptors CD36 and SR-A through the NF-κB signal pathway. H2S inhibits early atherosclerosis development by modulating macrophage uptake of ox-LDL through the down-regulation of CD36 and SR-A receptors via the NF-κB signaling pathway. These findings provide new evidence for the role of H2S in atherosclerosis and its potential therapeutic value.