Apmis最新文献

Ultrasonic examinations showed significant limitations in the early detection and prognostic prediction of sepsis-induced myocardial dysfunction (SIMD), needing assisting biomarkers. The diagnostic and prognostic potential of miR-324-3p in SIMD was evaluated in this study, aiming to explore a novel biomarker. The functional role of miR-324-3p in regulating myocardial cell injury was assessed in H9c2 cells. The study enrolled 210 sepsis patients, including 98 patients diagnosed with SIMD. The significance of miR-324-3p in SIMD risk prediction, screening, and prognosis prediction was evaluated. Moreover, ultrasonic parameters, involving LVEF, LVDd, LAD, and FS, were compared between sepsis and SIMD patients, and the diagnostic and prognostic values of these parameters were also assessed. Silencing miR-324-3p exerted significantly protective effects on myocardial cell injury. Increasing serum miR-324-3p was observed in SIMD patients and was positively correlated with Dallas grades. LVEF, LVDd, LAD, and FS also showed significance in discriminating SIMD patients, but a single parameter cannot possess both satisfactory sensitivity and specificity. Serum miR-324-3p could help improve the diagnostic accuracy, sensitivity, and specificity of ultrasonic parameters in screening SIMD, and miR-324-3p was also identified as an independent risk factor for the adverse prognosis of SIMD patients.

Ischemic stroke (IS), a life-threatening disease, carries a high risk of disability and death. Reverse transcription quantitative real-time polymerase chain reaction was utilized to measure the PART1 and miR-638 expression in patients with IS and oxygen–glucose deprivation/reoxygenation (OGD/R) model. Superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were determined by enzyme-linked immunosorbent assay kit. Cell viability was assessed using the cell counting kit-8 assay. Apoptotic cells were analyzed by flow cytometry. To explore the interaction between PART1 and miR-638, luciferase reporter and RNA immunoprecipitation (RIP) assays were carried out. In patients with IS and OGD/R-treated cells, PART1 exhibited upregulation, whereas miR-638 showed downregulation; there was a negative correlation between these two molecules. Knockdown of PART1 increased cell viability, decreased apoptosis, lowered MDA, LDH, IL-6 and TNF-α levels, and increased SOD activity. PART1 negatively regulated miR-638 expression, and inhibition of miR-638 reduced the protective effect of the knockdown of PART1 on OGD/R-treated cells. This study demonstrated that knockdown of PART1 inhibits IS-induced neurological injury by regulating miR-638 expression, which promotes the understanding of IS disease and provides new options for the treatment of the disease.

Osteoporotic fractures (OPF) impose a significant socioeconomic burden. Therefore, identifying reliable molecular biomarkers for early prediction and precise treatment of OPF is crucial. This study investigated the role of miR-143-3p in OPF. We analyzed serum from 188 OPF and 110 osteoporotic (OP) patients. qRT-PCR and ROC analyses showed that miR-143-3p was significantly downregulated in OPF versus OP controls (AUC = 0.893). More importantly, its expression level was markedly higher in patients with normal healing compared to delayed healing, positioning it primarily as a prognostic biomarker for healing outcomes rather than a diagnostic tool for fracture identification. Functionally, miR-143-3p inhibited apoptosis, promoted proliferation, and upregulated osteogenic markers (OCN, OPN, RUNX2). Mechanistically, it directly targeted and negatively regulated VASH1, as confirmed by luciferase assays and rescue experiments. In conclusion, miR-143-3p may serve as a promising prognostic biomarker for predicting fracture healing outcomes, potentially by targeting VASH1.

CYLD Cutaneous syndrome (CCS) is a rare autosomal dominantly inherited disease associated with multiple nodular adnexal skin tumors, most commonly trichoepitheliomas and cylindromas. There is no evidence-based treatment for this disease. This study aimed to present the histological response and to investigate whether molecular and immunohistochemical analyses (exome sequencing) may provide insight into the rapid disease development and lack of response to treatment with Vismodegib. A patient treated with the Hedgehog Pathway Inhibitor Vismodegib. The CYLD (c.1437_1438del, p.Pro480PhefsTer16) frameshift deletion was identified in the family of our patient. In addition, our patient also lost the unaffected allele and was consequently homozygous for the deletion. Treatment with Vimodegib was unfortunately not effective. Furthermore, we observed no possible biomarkers of progression and/or treatment response. Hopefully, further studies will contribute to the genetic understanding of BSS and identify patients at high risk of developing severe disease, thereby supporting the stratification of patients who will benefit from early surgical treatment or treatment with Vismodegib.

Dysbiosis, an imbalance in the gut microbiota, has emerged as a critical factor in the development of various metabolic diseases, including dyslipidemia. Dyslipidemia, a multifactorial disorder influenced by both genetic and environmental factors, is a significant risk factor for cardiovascular diseases (CVD), such as coronary artery disease (CAD) and stroke. The gut microbiota plays a pivotal role in maintaining lipid homeostasis, interacting with the host's immune, metabolic, and endocrine systems. Recent studies have highlighted the involvement of microbiota-derived metabolites, such as bile acids, lipopolysaccharides, and short-chain fatty acids (SCFAs), in modulating lipid levels and regulating hyperlipidemia. Understanding these complex microbiome-host interactions opens new avenues for therapeutic interventions aimed at correcting lipid imbalances and restoring microbial balance. Approaches such as probiotics, prebiotics, synbiotics, and dietary modifications hold promise in managing dyslipidemia and preventing associated cardiovascular diseases. As research continues to unravel these connections, the microbiome is increasingly recognized as a promising target for therapeutic strategies in dyslipidemia.

The gut microbiota (GM) has emerged as an important element in the management of host metabolism, immune functions, and overall metabolic well-being. This review consolidates contemporary research regarding the intricate relationship between GM and diabetes mellitus, focusing on the mechanisms by which microbial composition and activity affect the development of both Type 1 (T1D) and Type 2 diabetes (T2D). Dysbiosis—characterized by diminished microbial diversity, a modified Firmicutes/Bacteroidetes ratio, and a reduction in advantageous SCFA-producing bacteria—has been significantly associated with disrupted glucose metabolism, insulin resistance, and persistent inflammation. Additionally, the review discusses the potential for microbial signatures and metabolites, such as SCFAs, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), to serve as novel biomarkers for early detection and risk evaluation. Moreover, it investigates therapeutic approaches designed to reestablish microbial balance through the use of probiotics, prebiotics, dietary changes, fecal microbiota transplantation (FMT), and microbiome engineering. By integrating findings from recent research, this paper emphasizes the groundbreaking possibilities of microbiome-centric diagnostics and treatments in individualized diabetes care.

Transcription factor TCF21 is downregulated in lung adenocarcinoma (LUAD), contributing to poor treatment outcomes. This study explores its role in regulating CD8⁺ T cell-mediated antitumor immunity and metastasis. TCF21 expression was analyzed via TCGA. Downstream target ERO1A was identified using JASPAR prediction, validated by dual-luciferase/ChIP assays. LUAD mouse models and cell experiments (Transwell, flow cytometry, LDH/ELISA) assessed impacts on metastasis and CD8⁺ T cell function. The results showed that TCF21 overexpression inhibited LUAD migration/invasion and enhanced CD8⁺ T cell cytotoxicity. Mechanistically, TCF21 repressed ERO1A transcription, reducing IDO1 expression. Conversely, ERO1A overexpression promoted metastasis and suppressed CD8⁺ T cell activity via IDO1 upregulation. Knockdown of ERO1A or IDO1 blockade reversed the pro-tumor effects of TCF21 loss. In conclusion, TCF21 downregulation in LUAD activates the ERO1A-IDO1 axis, enabling immune escape from CD8⁺ T cell killing and accelerating malignancy.