Hereditas最新文献

Background: Erectile dysfunction (ED) and Parkinson's disease (PD) are prevalent conditions that considerably impair patients' quality of life. Emerging evidence suggests a potential relationship between ED and PD, possibly mediated by shared biological mechanisms. This research seeks to examine shared transcriptomic alterations and the underlying biological pathways associated with ED and PD.

Methods: Gene expression profiles related to ED and PD were derived from the Gene Expression Omnibus database, specifically the GSE2457 and GSE7621 datasets. Differentially expressed genes (DEGs) between patients and controls were identified through differential expression analysis. Functional enrichment analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology analyses, were carried out to uncover the biological roles of the identified DEGs. To refine and validate potential key genes, machine learning algorithms, such as support vector machine-recursive feature elimination and LASSO regression, were employed. Immune infiltration analysis was carried out to examine potential immune responses related to the identified genes. Additionally, miRNA-gene and protein-protein interaction networks were established. Finally, the reliability of the selected genes was validated through external and experimental verification.

Results: In total, 25 overlapping DEGs were identified between ED and PD. Functional enrichment analysis demonstrated that these DEGs were involved in such biological processes as redox homeostasis and neuronal cell body function. KEGG pathway analysis indicated significant enrichment in pathways such as adrenergic signaling, cGMP-PKG signaling. Machine learning algorithms further refined the candidate genes, with SHOX2 and PIK3R6 demonstrating strong diagnostic potential. Immune infiltration analysis demonstrated correlations between the gene expression levels and various immune cell types. The constructed miRNA-gene regulatory networks revealed possible post-transcriptional regulatory mechanisms that modulated the expression of these genes. Finally, the diagnostic performance of these genes was verified in external datasets, with their performance further confirmed by ROC analysis and experimental verification.

Conclusion: This study identified the shared biological target between ED and PD through bioinformatics analyses. The key genes SHOX2 and PIK3R6 may serve as potential biomarkers. These results may offer new insights into the molecular mechanisms linking ED and PD.

Background: Coptisine (COP) is a natural compound extracted from Rhizoma Coptidis, and it represses the malignant biological behaviors of bladder cancer cells. However, the underlying molecular mechanism has not been fully elucidated. The aim of this study was to clarify the downstream mechanism by which COP treats bladder cancer.

Materials and methods: SwissTargetPrediction, STITCH, SymMap, ETCM, TCMSP, CTD databases were used to collect the related targets of COP. GeneCards, DisGeNET, TTD and OMIM databases were used to obtain the related targets of bladder cancer. A Venn diagram was used to identify the potential targets of COP in bladder cancer treatment. The protein-protein interaction network was constructed using STRING database, and Cytoscape 3.9.0 software was used to screen the hub targets. The binding relationship between COP and the hub targets was verified by molecular docking and molecular dynamics simulation. After the bladder cell lines T24 and BIU-87 were treated with different doses of COP, the regulatory effects of COP on PI3K/AKT pathway were investigated with western blotting. Additionally, the tumor-suppressive properties of COP on bladder cancer cells were validated with tumorigenesis model and metastasis model in nude mice.

Results: RAC-alpha serine/threonine-protein kinase 1 (AKT1), glycogen synthase kinase 3 beta (GSK3B), caspase-3 (CASP3), tumor necrosis factor (TNF) and cyclin D1 (CCND1) were identified as the main hub targets of COP in bladder cancer treatment. PI3K/AKT pathway was predicted to be a crucial pathway regulated by COP. The binding affinities between COP and AKT1, GSK3B, CASP3, TNF and CCND1 were high. COP treatment markedly repressed the phosphorylation level of ERK1/2, AKT1, PI3K p85 and mTOR in T24 and BIU-87 cells, and repressed the tumorigenesis and lung/liver metastasis of T24 cells in vivo.

Conclusion: COP may be a natural inhibitor for AKT1, GSK3B, CASP3, TNF and CCND1. COP represses PI3K/AKT pathway to suppress the progression of bladder cancer.

Coronary heart disease (CHD), is a complex cardiovascular disease driven by atherosclerosis, resulting from a dynamic interplay between dysregulated lipid metabolism and chronic inflammation. This study integrates bioinformatics analysis of GEO datasets with experimental validation to dissect molecular mechanisms underlying CHD pathogenesis. A total of 487 differentially expressed genes (DEGs) were identified (including 295 upregulated and 192 downregulated), with hub genes such as CD36, ALDH2, TNF-α, and IL1B highlighted in lipid handling, oxidative stress, and pro-inflammatory cascades. Weighted gene co-expression network analysis (WGCNA) revealed aberrant activation of lipid metabolism-related modules in CHD patients. KEGG enrichment highlighted their involvement in fatty acid transport, cholesterol homeostasis, NF-κB, and the IL-17 signaling. LASSO regression, applied to the combined datasets, identified SERPINA1, and GLUL as diagnostic biomarkers, with in vitro models supporting their pro-atherogenic roles in oxLDL-induced endothelial injury. Animal experiments further validated these findings: CHD rat models exhibited marked upregulation of SERPINA1, and GLUL in myocardial tissue, paralleled by increased M1 macrophage infiltration. Together, this study delineates the intricate lipid-immune axis in CHD and proposes novel candidate biomarkers and therapeutic targets, underscoring their potential for advancing precision medicine in CHD.

Background: Patients with severe trauma are at high risk of developing life-threatening complications, including acute respiratory failure and circulatory collapse. Extracorporeal membrane oxygenation (ECMO) offers critical support when conventional therapies fail. This narrative review aimed to analyze the clinical application of ECMO in patients with severe trauma, focusing on indications, complications, prognostic factors, and future directions.

Methods: A comprehensive literature search was conducted to identify studies published between January 2000 and April 2025. Sources included original research articles, systematic reviews, and meta-analyses, supplemented by relevant clinical guidelines and expert consensus statements pertaining to ECMO use in trauma care.

Results: Veno-venous ECMO has been primarily utilized in patients with trauma-associated acute respiratory distress syndrome, while veno-arterial ECMO has been employed in the management of cardiogenic shock and cardiac arrest. Reported survival rates were 72.3% for veno-venous ECMO and 39.0% for veno-arterial ECMO. ECMO has also been used in patients with traumatic brain injury and those undergoing extracorporeal cardiopulmonary resuscitation, although randomized controlled trial data remain limited Major complications include infection, hemorrhage, and thrombosis, which require coordinated prevention and management strategies. Prognostic tools such as the New Injury Severity Score, Simplified Acute Physiology Score III, and Sequential Organ Failure Assessment score are used in clinical evaluation, though trauma-specific models are still lacking.

Conclusion: ECMO offers a supportive treatment modality in the management of patients with severe trauma. To improve clinical outcomes, further development of trauma-specific decision tools, multicenter studies, and standardized protocols for anticoagulation and infection control is necessary to support individualized care.

Objective: To systematically review the latest evidence on risk factors and surgical treatment for gallbladder cancer (GBC), with a focus on current controversies and consensus in international guidelines, analyze the application prospects of minimally invasive surgery in advanced GBC, and provide direction for clinical practice and future research.

Methods: Literature on GBC risk factors, molecular mechanisms, and treatment strategies published from 2018 to 2024 was retrieved from databases including PubMed, Web of Science, and CNKI. The retrieved literature was summarized, compared, and critically analyzed.

Results: The pathogenesis of GBC involves a combination of genetic, environmental, and metabolic factors. Beyond gallstones and polyps, mutations in TP53 and ERBB2/ERBB3 genes, metabolic syndrome (obesity, hyperglycemia, hyperlipidemia), and chronic infections (Salmonella, Helicobacter) are significant risk factors. Surgical resection remains the primary curative approach, yet the optimal extent of surgery is debated: Is hepatic resection always necessary for T1b stage? What is the oncological safety of laparoscopic surgery for T2 stage? What is the value of extended resection for T4 stage? Recently, targeted therapies (e.g., against ERBB2, NTRK) and mmune checkpoint inhibitors (anti-PD-1/PD-L1)have shown promise in advanced GBC.

Conclusion: Combating GBC requires a comprehensive strategy encompassing health education, screening of high-risk populations, precise staging, and individualized multimodal treatment. Future research should focus on building molecular subtype-based prognostic models, conducting high-level clinical studies to resolve surgical controversies, and exploring the integration of novel adjuvant therapies with traditional surgery.

Background: N6-methyladenosine (m6A) methylation modification plays an essential role in the molecular pathogenesis of preeclampsia (PE). This study aimed to explore m6A modification in in vitro PE model, involving RNA binding motif protein 15 (RBM15) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB).

Methods: PE was induced by lipopolysaccharide (LPS) in HTR8/SVneo cells. Real-time quantification PCR was used for mRNA detection and Western blotting was used for protein detection. Cell cytokines were examined using enzyme-linked immunosorbent assay. Cell functions were evaluated using EdU assay, flow cytometry, and transwell assay. RNA immunoprecipitation assay and dual-luciferase reporter assay were utilized for validating molecular interaction.

Results: FOSB was highly expressed in placenta tissues from PE patients. Functionally, LPS-induced inflammation, proliferation inhibition, cell apoptosis and migration suppression were significantly abolished following FOSB knockdown. RBM15 upregulated FOSB expression via inducing m6A modification of FOSB mRNA. YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1) acted as an m6A reader protein, and RBM15 enhanced the binding between YTHDF1 and FOSB. RBM15 knockdown relieved LPS-caused trophoblast cell injury by inhibiting FOSB.

Conclusion: These results collectively suggested that RBM15 accelerated trophoblast cell dysfunction via mediating m6A modification of FOSB mRNA through the identification by YTHDF1.

Parkinson's disease (PD) is closely linked to mitochondrial dysfunction and mitophagy, a key mechanism in PD pathogenesis. However, no dedicated bibliometric analysis of mitophagy in PD exists. This study used data from the Web of Science Core Collection to map the global research landscape of mitophagy in PD. The analysis of 1,578 publications (2007-2024) identifies the United States as the most productive country. McGill University ranks as the top institution, and Nobutaka Hattori is the most prolific author. The journal Autophagy is the journal with the highest number of publications in this field. Core research themes included PINK1/Parkin, mitochondrial quality control, α-synuclein, neuroinflammation, and ferroptosis. The study provides insights into the current status of global collaboration and translational progress in this field. Future efforts should aim to further explore new pathways, enhance clinical translation, and promote collaborative partnerships to advance research and address challenges in the field.

Background: The incidence of pediatric ulcerative colitis (UC) is increasing yearly, and it is urgent to explore precise diagnostic biomarkers and molecular mechanisms. This study aims to investigate the diagnostic value of miR-340-5p in pediatric UC and its molecular mechanism mediated through targeting MAP3K2.

Methods: Eighty-five pediatric UC patients and 50 healthy controls were enrolled. The expression levels of miR-340-5p and MAP3K2 were detected by qRT-PCR, and Pearson's correlation analysis was conducted. An in vitro model was established by inducing HT-29 cells with dextran sulfate sodium. The target was verified by dual-luciferase assay. Flow cytometry, ELISA, and oxidative stress detection were used to verify the cellular functions regulated by the miR-340-5p/MAP3K2 axis.

Results: In pediatric patients with UC, miR-340-5p was significantly downregulated and negatively correlated with PUCAI, CRP, and ESR (P < 0.0001). Additionally, the diagnostic area of miR-340-5p under the ROC curve was 0.908. Mechanistically, miR-340-5p directly interacts with MAP3K2, leading to suppressed expression of its mRNA and protein. Functional experiments revealed that miR-340-5p overexpression reversed DSS-induced exacerbated cell apoptosis, reduced levels of TNF-α, IL-6, IL-17, IL-1β, and MDA, and increased GSH. Conversely, the beneficial effects of miR-340-5p were attenuated by oe-MAP3K2 overexpression.

Conclusions: miR-340-5p may serve as a diagnostic biomarker for pediatric UC and exerts its effects by targeting MAP3K2 to regulate cell apoptosis, inflammatory responses, and oxidative stress.

Objective: To investigate the effects of "Shengjiang Powder", a representative formula for "simultaneous treatment of liver and heart," on liver tissue inflammation and fibrosis in mice with atherosclerosis(AS) concurrent with non-alcoholic fatty liver disease (NAFLD).

Methods: Ten wild-type male C57/B6J mice were assigned to the control group, and 40 ApoE -/- mouse were randomly divided into the model group, atorvastatin group, and traditional Chinese medicine (TCM) treatment groups. The model group, atorvastatin group, and TCM treatment groups were fed a high-fat Western diet for 12 weeks. Atorvastatin and TCM groups were administered via gavage, while the control group and model group received sterile purified water via gavage for 12 weeks. Serum levels of ALT, AST, TRIG, TC, LDL, as well as liver tissue levels of SOD, MDA, and GSH were measured. HE staining was used to evaluate liver tissue morphology and inflammatory infiltration. Western blot was used to detect the effect of Shengjiang Powder on the activation of AMPK/mTOR signaling pathway. Network pharmacology analysis was performed beforehand to identify potential targets of Shengjiang Powder in regulating fatty liver and atherosclerosis, with AMPK identified as a key target.

Results: Compared with the model group, the Shengjiang Powder treatment reduced serum levels of TRIG, TC, and LDL (P < 0.05), increased liver SOD and GSH activity (P < 0.01), decreased MDA (P < 0.01), alleviated liver steatosis, reduces the area of aortic sinus plaques, improved hepatic steatosis and inflammation, inhibited the expression of inflammatory factors and activated the AMPK/mTOR signaling pathway, consistent with the network pharmacology prediction that AMPK is a critical regulatory target.

Conclusion: Treatment with "Shengjiang Powder," a representative formula for "simultaneous treatment of liver and heart," can slow the progression of atherosclerosis and concurrent NAFLD. The dosage shows a positive correlation with efficacy, and this effect is related to the regulation of liver oxidative stress and inflammation-induced fibrosis pathways.