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Bladder cancer (BCa) is the most common cancer in the urinary system with high recurrence rate and poor prognosis. Circular RNA (circRNA) is a novel subclass of noncoding-RNA which participate in progression of BCa. Here, we identified a novel circRNA–circ3323 and aimed to investigate the role of circ3323 in progression of BCa. Public data of RNA sequencing was used to identify significant circRNA related to BCa. The role of circRNAs in progression of BCa was assessed in cytotoxicity assay, transwell assay and flow cytometry. Biotin-coupled RNA pull-down and fluorescence in situ hybridization were performed to evaluate the interaction between circRNAs and miRNAs. The expression of circ3323 was higher in BCa tissues and cells than in normal samples. Experiments in vitro showed that the knockdown of circ3323 inhibited cell proliferation and impeded the metastasis of BCa cells. Mechanistically, we demonstrated that circ3323 acts as a sponge for miR-186-5p and promotes host gene APP's expression. Clinically, circ3323 predicts worse overall survival of BCa patients, indicating its prognostic value. Our study identified that circ3323 modulates metastasis of BCa through miR-186-5p/APP axis and may serve as a promising prognostic biomarker for BCa, which provides novel insights into treatment of BCa. [ABSTRACT FROM AUTHOR]

DNA methylation is a widely researched epigenetic modification. It is associated with the occurrence and development of cancer and has helped evaluate patients' prognoses. However, most existing DNA methylation prognosis models have not simultaneously considered the changes of the downstream transcriptome. Methods. The RNA-Sequencing data and DNA methylation omics data of ovarian cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. The Consensus Cluster Plus algorithm was used to construct the methylated molecular subtypes of the ovary. Lasso regression was employed to build a multi-gene signature. An independent data set was applied to verify the prognostic value of the signature. The Gene Set Variation Analysis (GSVA) was used to carry out the enrichment analysis of the pathways linked to the gene signature. The IMvigor 210 cohort was used to explore the predictive efficacy of the gene signature for immunotherapy response. Results. We distinguished ovarian cancer samples into two subtypes with different prognosis, based on the omics data of DNA methylation. Differentially expressed genes and enrichment analysis among subtypes indicated that DNA methylation was related to fatty acid metabolism and the extracellular matrix (ECM)-receptor. Furthermore, we constructed an 8-gene signature, which proved to be efficient and stable in predicting prognostics in ovarian cancer patients with different data sets and distinctive pathological characteristics. Finally, the 8-gene signature could predict patients' responses to immunotherapy. The polymerase chain reaction experiment was further used to verify the expression of 8 genes. Conclusion. We analyzed the prognostic value of the related genes of methylation in ovarian cancer. The 8-gene signature predicted the prognosis and immunotherapy response of ovarian cancer patients well and is expected to be valuable in clinical application. [ABSTRACT FROM AUTHOR]

Platelet glycoprotein (GP) IIb/IIIa antagonists have been employed in selective patients after endovascular therapy (EVT) for acute ischemic stroke (AIS), yet application in patients without EVT is debated. This meta‐analysis of randomized controlled studies on AIS patients without EVT assessed the effectiveness and safety of platelet GP IIb/IIIa antagonists compared with traditional antiplatelet or thrombolysis therapy. Articles were retrieved from databases, including PubMed, Web of Science, EMBASE, and Cochrane. The risk of bias and certainty level of evidence were assessed. Fifteen studies were included. GP IIb/IIIa antagonists increased the proportion of patients with modified Rankin Scale (mRS) 0–1 (odd ratio [OR] 1.37, 95% confidence interval [CI] 1.04–1.81, p = 0.03), mRS 0–2 (OR 1.27, 95% CI 1.12–1.46, p = 0.0004), and Barthel Index (BI) 95–100 (OR 1.25, p = 0.005); decreased the proportion of stroke progression within 5 days (OR 0.66, p = 0.006); and lowered the mean mRS score at 90 days (mean difference [MD] −0.43, p = 0.002) and the National Institute of Health stroke scale score at 7 days (MD −1.64, p < 0.00001) compared with conventional treatment. Proportions of stroke recurrence within 90 days (OR 1.20, p = 0.60), any intracranial hemorrhage (aICH) (OR 1.20, p = 0.12), symptomatic intracranial hemorrhage (sICH) (OR 0.91, p = 0.88), and death (OR 0.87, p = 0.25) had no statistical difference between both groups. This meta‐analysis finds that compared with traditional antiplatelet or thrombolysis therapy, GP IIb/IIIa antagonists administered within 24–96 h of ischemic stroke onset significantly improve functional prognosis of patients with AIS not receiving EVT, as indicated by mRS and BI at 90 days, and do not increase the incidence of aICH, sICH, and death. [ABSTRACT FROM AUTHOR]

Cell cycle progression and cell proliferation are tightly controlled processes physiologically; however, in cancerous cells, uncontrolled cell proliferation may be attributed to abnormal expression of the cyclin genes. Therefore, analysis of the expression of the cyclin genes may result in the discovery of biomarkers that can be used to predict a prognosis and help to evaluate the therapeutic efficacy more accurately in several types of cancer, including breast cancer. In this study, 15 subtypes of the cyclin genes in breast cancer from public databases were selected using bioinformatics analysis, the correlation between their transcriptional expression levels and survival rates were analyzed, and the results were further confirmed using reverse transcription-quantitative PCR in vitro in various breast cancer cell lines. The expression of the majority of the cyclin genes in SK-BR-3, a HER2 overexpressing breast cancer cell line, was lower than that in MCF-10A cells. CCNC mRNA expression was higher and CCNH mRNA expression was lower in tumor and tumor-adjacent tissues compared with that in normal tissues; however, CCNC expression was lower and CCNH expression was higher in breast cancer cell lines compared with that in MCF-10A cells. The expression of the 13 other cyclin genes in breast cancer cell lines was generally consistent with the data from the bioinformatics analyses of breast cancer tissue samples, tumor-adjacent tissues, and normal tissues. Low expression of CCNA2, CCNB1/2, CCNC, CCND1, CCNE1/2 and CCNF, and high expression of CCNA1, CCNB3, CCND2/3, CCNG1/2 and CCNH genes was correlated with a higher survival rate for breast cancer patients (P<0.05). In conclusion, CCNA2, CCNB1/2, CCND1/2 and CCNE1/2 may serve as relatively mature and accurate biomarkers, and CCNG1/2 may be used to evaluate the prognosis and therapeutic efficacy of hormone receptor-positive breast cancer. Furthermore, CCNA1, CCNB3, CCNC, CCND3, CCNF and CCNH may serve as promising targets for the management of breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To identify new trends and potential hotspots in research on rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD). Materials and Methods: The Web of Science (WOS) database was used to search for RA‐ILD‐related literature published between August 31, 2002 and August 31, 2022. CiteSpace 6.1.R3, VOSviewer version 1.6.17, Scimago Graphica, and Pajek V2.0 visualization software were used to conduct a comprehensive analysis and network visualization mapping of the authors, countries, institutions, journals, cited references, and keywords. Results: A total of 2412 articles were retrieved, and the number of articles published has grown annually since 2002. Eric L. Matteson was the most prolific author, and the Mayo Clinic and UNITED STATES have the highest publishing volume and influence. Clinical Rheumatology is the journal with the most papers published. Rheumatology was the most cited journal. The citation clusters and keywords concentrated on the mechanism, treatment, and predictive and prognostic factors. Conclusion: Pathogenesis, treatment, and predictive and prognostic factors were among the RA‐ILD research directions and hotspots. Antirheumatoid drugs, especially biologics and small molecule inhibitors, were among the most actively researched treatment options. The results of this study provides an in‐depth understanding of the development of RA‐ILD publications, aids researchers in understanding hotspots and trends and provides a new perspective for future RA‐ILD research. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is a chronic immune-mediated disease with heterogeneity. In this study, we used machine-learning approaches to characterize the immune cell profiles and to identify the heterogeneity of IgG4-RD. The XGBoost model discriminated IgG4-RD from HCs with an area under the receiver operating characteristic curve of 0.963 in the testing set. There were two clusters of IgG4-RD by k-means clustering of immunological profiles. Cluster 1 featured higher proportions of memory CD4+T cell and were at higher risk of unfavorable prognosis in the follow-up, while cluster 2 featured higher proportions of naïve CD4+T cell. In the multivariate logistic regression, cluster 2 was shown to be a protective factor (OR 0.30, 95% CI 0.10–0.91, P = 0.011). Therefore, peripheral immunophenotyping might potentially stratify patients with IgG4-RD and predict those patients with a higher risk of relapse at early time. • IgG4-RD patients had altered immunological subsets, by which can be distinguished from healthy people. • Machine-learning approach was effective to detect the features of immunophenotype of IgG4-RD and to identify the heterogeneity of IgG4-RD. • IgG4-RD patients with elevated of CD4+ memory T cells were at higher risk for relapse, calling for more attention during follow-up. [ABSTRACT FROM AUTHOR]

Aims: Effective and applicable predictors of end-stage kidney disease (ESKD) are needed for patients with myeloperoxidase–antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV) and kidney involvement. We investigated whether urinary matrix metalloproteinase-7 (uMMP7) was associated with kidney injury severity and incident ESKD in MPO-AAV. Results: A prospective two-stage study was conducted in 150 patients with newly diagnosed MPO-AAV in two independent cohorts. uMMP7 was measured on the days of initial and repeat kidney biopsies. In stage I, a higher initial uMMP7 level was associated with a lower estimated glomerular filtration rate (eGFR), higher level of proteinuria, and greater extent of kidney pathologic lesions. This elevated uMMP7 protein level is activated and potentially derived from the enhanced kidney production induced by oxidative stress. In stage II, uMMP7 at initial biopsy was independently associated with the incidence of ESKD over 6 years. The higher uMMP7 group (vs. lower) had an adjusted hazard ratio of 3.79 (95% confidence interval [CI], 1.49–6.09) for ESKD in the test cohort. Findings were similar in the validation cohort. A combination of data from the two cohorts revealed that adding uMMP7 into clinical or clinicopathologic models significantly improved risk discrimination for future ESKD. Innovation: An elevated uMMP7 level in MPO-AAV was independently associated with severe kidney injury and incident ESKD. Conclusions: uMMP7 in MPO-AAV improves identification of patients at risk of ESKD and may enable early and optimized therapy to improve outcomes. Antioxid. Redox Signal. 37, 246–256. [ABSTRACT FROM AUTHOR]

Member of the V-type ATPase family have attracted vast attention in tumor progression. Nevertheless, the specific member of V-ATPase, ATP6V1C2, its regulatory function in colorectal cancer (CRC) progression was poorly understood. In this study, comprehensive analyses demonstrated the role of ATP6V1C2 in CRC progression and drug screening based on ATP6V1C2 was carried out. As a result, among the ATPV1s family, ATP6V1C2 was significantly highly expressed in CRC. Immuno-infiltration analysis suggests that, the interaction between CRC cells and immune cells resulting in reduced immune and estimate scores. GSEA analysis found that, ATP6V1C2 negatively correlates with immune cells，especially CD8T cells. Next, Ecotyper database queries indicated that ATP6V1C2 was negatively correlates with characteristic gene expression in CD8T cells. Then, COX regression analysis and survival curves made it clear that ATP6V1C2 is positively correlates with clinicopathological progression leading to poor CRC prognosis. CellMiner explore told us LOR-253 and Sonidegib may be effective in CRC cancer treatment. Molecular Docking between ATP6V1C2 and 9 first-line and 9 natural drugs showed that ATP6V1C2 was recognized by the best geometrical and energetic matching pattern of 2 First-line and 4 natural drugs. RT-PCR and immunoblotting confirmed that ATP6V1C2 was significantly overexpressed in CRC. Four natural drugs screened by molecular docking were effective in cell proliferation inhibition by CCK8 test. In summary, ATP6V1C2 may be a new therapeutic target for CRC. The illustration is shown in Figure 9. [ABSTRACT FROM AUTHOR]

Background: The risk factors for the survival of elderly patients with oral squamous cell carcinoma (OSCC) are multifarious. Here, we developed a novel clinical signature to serve as an indicator of prognosis in these patients. Materials and methods: Clinicopathological data were collected for 554 patients aged ≥ 60 years who were treated for primary OSCC. Overall survival (OS), disease-specific survival, and disease-free survival were the primary outcomes. Results: Multivariate cox regression analysis showed that high N stage, low hemoglobin level, low body mass index (BMI), and high neutrophil-to-lymphocyte ratio (NLR) showed a poor survival (P < 0.05). A nomogram was constructed with a c-index of 0.702. Conclusion: A novel clinical signature including hemoglobin level, BMI, and NLR, which are obtained through noninvasive examinations can be used as prognostic indicators in clinical practice for elderly patients with OSCC. [ABSTRACT FROM AUTHOR]

Objective: Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear.Materials and Methods: Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I-II) and advanced-stage (clinical stage III-IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan-Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations.Results: In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC.Conclusion: In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation. [ABSTRACT FROM AUTHOR]