COMMD10 inhibited DNA damage to promote the progression of gastric cancer.

PURPOSE: The copper metabolism MURR1 domain 10 (COMMD10) plays a role in a variety of tumors. Here, we investigated its role in gastric cancer (GC). METHODS: Online prediction tools, quantitative real-time PCR, western blotting and immunohistochemistry were used to evaluate the expression of COMMD10 in GC. The effect of COMMD10 knockdown was investigated in the GC cell lines and in in vivo xenograft tumor experiments. Western blotting and immunofluorescence were used to explore the relationships between COMMD10 and DNA damage. RESULTS: The expression of COMMD10 was upregulated in GC compared to that in para-cancerous tissue and correlated with a higher clinical TNM stage (P = 0.044) and tumor size (P = 0.0366). High COMMD10 expression predicted poor prognosis in GC. Knockdown of COMMD10 resulted in the suppression of cell proliferation, migration, and invasion, accompanied by cell cycle arrest and an elevation in apoptosis rate. Moreover, the protein expression of COMMD10 was decreased in cisplatin-induced DNA-damaged GC cells. Suppression of COMMD10 impeded DNA damage repair, intensified DNA damage, and activated ATM-p53 signaling pathway in GC. Conversely, restoration of COMMD10 levels suppressed DNA damage and activation of the ATM-p53 signaling cascade. Additionally, knockdown of COMMD10 significantly restrained the growth of GC xenograft tumors while inhibiting DNA repair, augmenting DNA damage, and activating the ATM-p53 signaling pathway in xenograft tumor tissue. CONCLUSION: COMMD10 is involved in DNA damage repair and maintains genomic stability in GC; knockdown of COMMD10 impedes the development of GC by exacerbating DNA damage, suggesting that COMMD10 may be new target for GC therapy.

Integrative single-cell analysis: dissecting CD8 + memory cell roles in LUAD and COVID-19 via eQTLs and Mendelian Randomization.

Lung adenocarcinoma exhibits high incidence and mortality rates, presenting a significant health concern. Concurrently, the COVID-19 pandemic has emerged as a grave global public health challenge. Existing literature suggests that T cells, pivotal components of cellular immunity, are integral to both antiviral and antitumor responses. Yet, the nuanced alterations and consequent functions of T cells across diverse disease states have not been comprehensively elucidated. We gathered transcriptomic data of peripheral blood mononuclear cells from lung adenocarcinoma patients, COVID-19 patients, and healthy controls. We followed a standardized analytical approach for quality assurance, batch effect adjustments, and preliminary data processing. We discerned distinct T cell subsets and conducted differential gene expression analysis. Potential key genes and pathways were inferred from GO and Pathway enrichment analyses. Additionally, we implemented Mendelian randomization to probe the potential links between pivotal genes and lung adenocarcinoma susceptibility. Our findings underscored a notable reduction in mature CD8 + central memory T cells in both lung adenocarcinoma and COVID-19 cohorts relative to the control group. Notably, the downregulation of specific genes, such as TRGV9, could impede the immunological efficacy of CD8 + T cells. Comprehensive multi-omics assessment highlighted genetic aberrations in genes, including TRGV9, correlating with heightened lung adenocarcinoma risk. Through rigorous single-cell transcriptomic analyses, this investigation meticulously delineated variations in T cell subsets across different pathological states and extrapolated key regulatory genes via an integrated multi-omics approach, establishing a robust groundwork for future functional inquiries. This study furnishes valuable perspectives into the etiology of multifaceted diseases and augments the progression of precision medicine.

Knockout of Rnf213 Ameliorates Cerebral Ischemic-reperfusion Injury by Inhibiting Neuronal Apoptosis Through the Akt/GSK-3ß/ß-catenin/Bcl-2 Pathway.

Previous studies by us and others have shown that RING finger protein 213 (RNF213) is associated with cerebrovascular disease and systemic vasculopathy. Indeed, Rnf213 mRNA expression is increased in cerebral ischemia reperfusion injury (CIRI). The purpose of the present study was to investigate the role of Rnf213 in CIRI. Using the middle cerebral artery occlusion (MCAO) model, we confirmed that the expression of RNF213 protein was significantly upregulated in neurons in the ischemic penumbra. Rnf213 knockout mice were successfully generated using CRISPR/Cas9 technology. According to TTC staining and Bederson neurological scale, removal of Rnf213 decreased brain infarct volume and improved neurological deficit score, although the restoration of cerebral blood flow after MCAO was similar in WT and Rnf213-/- mice. In addition, the levels of p-Akt, p-GSK-3ß, ß-catenin and Bcl-2 were significantly increased 24 h after MCAO in the ischemic penumbra of the Rnf213-/- mice compared to WT mice, indicating that Rnf213 removal may ameliorate neuronal apoptosis by regulating the Akt/GSK-3ß/ß-catenin/Bcl-2 signaling pathway. Taken together, our study reveals that Rnf213 regulates neuronal apoptosis in CIRI, therefore impacting on brain infarct volume in brain ischemia.

Research on Influencing Factors of Clinical Efficacy of Meniscus Resection Based on Logistic Regression Analysis.

In order to solve the factors affecting the clinical efficacy of meniscus resection, a method based on logistic regression analysis is proposed. From May 2019 to May 2020, 60 patients with discoid meniscus who underwent arthroscopic surgery in the Joint Department of the Second Hospital of a certain city were selected as the research objects; the surgical methods are divided into partial meniscus excision and plasty and total meniscus resection. The Lysholm function score was used to evaluate the clinical efficacy of arthroscopic surgery for discoid meniscus injuries before and 3, 6, and 12 months after surgery and postoperative application of Ikeuchi score and Tegner exercise ability score to assess age, gender, body mass index (BMI), duration of symptoms, and the influence of meniscus injury types and surgical methods on the efficacy of arthroscopic surgery for discoid meniscus injuries. Experimental results show that Ikeuchi's assessment of the excellent and good rate of arthroscopic knee joints was significantly higher than that of the control group, the incidence of postoperative pain was significantly lower than that of the control group, and the difference was statistically significant (P < 0.05). Postoperative pain and premature weight-bearing of discoid meniscus injury of knee joint, factors such as noncold compress after operation, articular cartilage damage, age, and time from onset to operation are closely related; the difference was statistically significant (P < 0.05). Postoperative evaluation according to Ikeuchi score: excellent in 38 cases, good in 14 cases, 8 cases were poor, and the excellent and good rate was 86.7%. The patient's age, type of meniscus tear, and duration of symptoms have a certain impact on the postoperative clinical efficacy of discoid meniscus injury; BMI and surgical methods have no significant impact. Logistic regression analysis results show that postoperative pain and premature weight-bearing of discoid meniscus injury of the knee joint, no cold compress after operation, accompanied by articular cartilage damage, age, and factors such as onset to operation time are closely related; the difference was statistically significant (P < 0.05). It proves that arthroscopic surgery for discoid meniscus injury has the advantages of less damage and faster recovery, it is the first choice for the treatment of discoid meniscus injury, and the postoperative effect is significant in young patients and those with short duration of symptoms; mixed tears have a greater impact on the postoperative recovery of patients with discoid meniscus injury; therefore, patients with discoid meniscus injury should undergo surgery as soon as possible and perform active rehabilitation exercises after the operation.