Int J Med Sci
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Background: Alterations in circulating CCL4 levels have been implicated in coronary artery disease (CAD), but the causal relationship and underlying mechanisms remain unclear. Objective: This study aims to analyse the role of CCL4 and its receptor (CCR5) in CAD using Mendelian randomisation (MR) analysis, bulk RNA and single cell RNA sequencing (scRNA-seq). Methods: The MR analysis was used to determine the causal relationship between 91 circulating inflammatory proteins and CAD. ⋯ Clinical specimens confirmed high levels of serum CCL4 expression in CAD patients by ELISA. Functional enrichment analysis revealed that CCL4 was primarily enriched in the cytokines and cytokine receptors, viral proteins with cytokines and cytokine receptors, and chemokine signaling pathways. Conclusion: Our study presented a genetic insight into the pathogenetic role of CCL4-CCR5 in CAD, which may provide new insights for further mechanistic and clinical investigations of inflammatory cytokine-mediated CAD.
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Background: Acute kidney injury (AKI) is a frequent complication in patients undergo-ing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to a combination of several factors: increased intra-abdominal pressure, heat stress and drug tox-icity. Methods: Patients admitted to Intensive Care Unit after CRS and HIPEC during 129 months. Data recorded were: demographic characteristics; severity of illness, haematology and basic chemistry panels (renal function and electrolytes), type of cancer and extension, HIPEC drug and temperature, fluid balance, ICU and hospital stay and mortality. ⋯ The presence of hydroelectrolytic alterations and polyuria was very frequent. The type of cancer, no mitomycin-based regimens and positive fluid balance during surgery were factors that suggest increased risk of AKI. However, although patients with AKI were clinically worse it was not associated with higher mortality.
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Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, whose complex etiology involves a genetic component. Growth arrest-specific 5 (GAS5), a long noncoding RNA (lncRNA) gene, has been recently shown to regulate renal fibrosis. Here, we aimed to explore the potential role of GAS5 gene polymorphisms in the predisposition to DKD. ⋯ Carriers of at least one minor allele (C) of rs55829688 (TC and CC; AOR, 1.317; 95% CI, 1.023-1.696; p=0.033) more frequently suffer from advanced DKD than do those homozygotes for the major allele (TT). Furthermore, in comparison to those who do not carry the minor allele of rs55829688 (TT), advanced DKD patients possessing at least one minor allele of rs55829688 (TC and CC) exhibited a lower glomerular filtration rate, revealing an impact of rs55829688 on renal co-morbidities of diabetes. In conclusion, our data indicate an association of GAS5 gene polymorphisms with the progression of DKD.
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Introduction: Lung cancer, characterized by uncontrolled cellular proliferation within the lung tissues, is the predominant cause of cancer-related fatalities worldwide. The traditional medicinal herb Piper longum has emerged as a significant contender in oncological research because of its documented anticancer attributes, suggesting its potential for novel therapeutic development. Methods: This study adopted network pharmacology and omics methodology to elucidate the anti-lung cancer potential of P. longum by identifying its bioactive constituents and their corresponding molecular targets. ⋯ Notably, our findings reaffirm the relevance of lung cancer genes, such as CTNNB1, STAT3, HIF1A, HSP90AA1, and ERBB2, integral to various cellular processes and pivotal in cancer genesis and advancement. Molecular docking assessments revealed pronounced affinity between 6-alpha-diol and HIF1A, underscoring their potential as therapeutic agents for lung cancer. Conclusion: This study not only highlights the bioactive compounds of P. longum but also reinforces the molecular underpinnings of its anticancer mechanism, paving the way for future lung cancer therapeutics.
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In the early stages of pregnancy, the maternal-fetal interface is enriched with natural killer (NK) cells that release growth factors to support fetal development and promote the remodeling of uterine spiral arteries. Previous studies have shown that the aberrant frequency and activity of decidual natural killer (dNK) cells are associated with recurrent pregnancy loss (RPL). Various factors regulate the roles of dNK cells and their interactions with trophoblasts to facilitate the colonization and maturation of semiallogeneic embryos. ⋯ Although there are few studies on the intervention of malfunctioning dNK cells, this strategy shows promise in regulating abnormal miRNA production in NK cells. This study confirmed miR-122-5p downregulation in dNK cells from patients experiencing unexplained RPL. miR-122-5p regulates apoptosis, inflammatory factor secretion, and cytotoxicity of NK cells. miR-122-5p may contribute to immune tolerance at the maternal-fetal interface by targeting transcription factor T-bet. This study provides a deeper understanding of the mechanisms by which miR-122-5p regulates the function of dNK cells and trophoblasts at the maternal-fetal interface to ensure successful pregnancy.