Association between omentin-1 and heart failure with preserved ejection fraction in Chinese elderly patients.

BACKGROUND: Omentin-1 is a novel adipokine and is associated with chronic inflammation and cardiovascular diseases. However, it remains unclear whether omentin-1 levels are associated with diagnostic significance in elderly patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to investigate the correlation between omentin-1 and HFpEF in Chinese elderly patients. HYPOTHESIS: Omentin-1 may be invovled in HFpEF and there may be a difference of omentin-1 levels between HFpEF and control. METHODS: 217 subjects were selected, including 115 patients with HFpEF and 102 control subjects. Enzyme-linked immuno sorbent assay (ELISA) was used to detect plasma levels of omentin-1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The receiver operating characteristics (ROC) curve was used to examine the diagnostic performance of omentin-1 in HFpEF. RESULTS: The levels of omentin-1 decreased significantly in the HFpEF group (14.02 ± 8.35 vs. 19.74 ± 8.45 ng/mL, p < .001), while NT-proBNP, IL-6, and TNF-α levels were significantly increased in the HFpEF group compared with the control group. Spearman correlation analysis showed that omentin-1 levels were negatively correlated with E/e' (r = -.340, p < .001). The multivariate logistic regression analysis indicated that omentin-1 was an independent protective factor for HFpEF (odd ratio = 0.948, 95% confidence interval [CI] 0.905-0.993, p = .025). Omentin-1 levels were negatively correlated with NT-proBNP (r = -.273, p < .001) and TNF-α (r = -.221, p = .001). Diagnostic efficiency by ROC curve analysis in the patients with HFpEF showed that the area under the curve (AUC) for omentin-1 was equivalent to NT-proBNP (AUC: 0.734, 95%CI 0.667-0.802; AUC: 0.800, 95%CI 0.738-0.861). Subgroup analysis showed that in the patients between the age of 70 and 80, the predictive capability of omentin-1 was stronger than NT-proBNP (AUC: 0.809, 95%CI 0.680-0.937; AUC: 0.674, 95%CI 0.514-0.833). CONCLUSIONS: Omentin-1 levels which were associated with inflammation, were decreased in the HFpEF patients. It could be regarded as a valuable biomarker for the occurrence and development of HFpEF in elderly patients.

Integrative analysis reveals a four-gene signature for predicting survival and immunotherapy response in colon cancer patients using bulk and single-cell RNA-seq data.

Background: Colon cancer (CC) ranks as one of the leading causes of cancer-related mortality globally. Single-cell transcriptome sequencing (scRNA-seq) offers precise gene expression data for distinct cell types. This study aimed to utilize scRNA-seq and bulk transcriptome sequencing (bulk RNA-seq) data from CC samples to develop a novel prognostic model. Methods: scRNA-seq data was downloaded from the GSE161277 database. R packages including "Seurat", "Harmony", and "singleR" were employed to categorize eight major cell types within normal and tumor tissues. By comparing tumor and normal samples, differentially expressed genes (DEGs) across these major cell types were identified. Gene Ontology (GO) enrichment analyses of DEGs for each cell type were conducted using "Metascape". DEGs-based signature construction involved Cox regression and least absolute shrinkage operator (LASSO) analyses, performed on The Cancer Genome Atlas (TCGA) training cohort. Validation occurred in the GSE39582 and GSE33382 datasets. The expression pattern of prognostic genes was verified using spatial transcriptome sequencing (ST-seq) data. Ultimately, an established prognostic nomogram based on the gene signature and age was established and calibrated. Sensitivity to chemotherapeutic drugs was predicted with the "oncoPredict" R package. Results: Using scRNA-Seq data, we examined 33,213 cells, categorizing them into eight cell types within normal and tumor samples. GO enrichment analysis revealed various cancer-related pathways across DEGs in these cell types. Among the 55 DEGs identified via univariate Cox regression, four independent prognostic genes emerged: PTPN6, CXCL13, SPINK4, and NPDC1. Expression validation through ST-seq confirmed PTPN6 and CXCL13 predominance in immune cells, while SPINK4 and NPDC1 were relatively epithelial cell-specific. Creating a four-gene prognostic signature, Kaplan-Meier survival analyses emphasized higher risk scores correlating with unfavorable prognoses, confirmed across training and validation cohorts. The risk score emerged as an independent prognostic factor, supported by a reliable nomogram. Intriguingly, drug sensitivity analysis unveiled contrasting anti-cancer drug responses in the two risk groups, suggesting significant clinical implications. Conclusion: We developed a novel prognostic four-gene risk model, and these genes may act as potential therapeutic targets for CC.

Extracellular matrix-based gene signature for predicting prognosis in colon cancer and immune microenvironment.

Background: The extracellular matrix (ECM) plays a vital role in progression, expansion, and prognosis of malignancies. In this study, we aimed to explore a novel ECM-based prognostic model for patients with colon cancer (CC). Methods: ECM-related genes were obtained from Molecular Signatures database. Differential expression analysis was performed using the CC dataset from The Cancer Genome Atlas (TCGA) database. Four ECM-related genes related to overall survival were identified using the Cox regression and LASSO analysis. Then an ECM-related signature was developed and verified in three independent CC cohorts (GSE33882, GSE39582 and GSE29621) from the Gene Expression Omnibus (GEO). A prognostic nomogram was developed incorporating the ECM-related gene signature with clinical risk factors. CIBERSORT was used to explore the immune cell infiltration level. Human Protein Atlas (HPA) database was utilized to validate the expression levels of identified prognostic ECM genes. Results: Four ECM-related genes (CXCL13, CXCL14, SFRP5 and THBS4) were identified to develop an ECM-based gene signature and demarcated CC patients into the high- and low-risk groups. In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001). In addition, ECM-related signature was significantly associated with consensus molecular subtype 4 (CMS4) as well as other known clinical risk factors such as a higher Tumor, Nodal Involvement, Metastasis (TNM) stage. Moreover, the risk score derived from the ECM-based gene signature could be utilized as an independent prognostic factor for CC patients. A nomogram including the ECM-related gene signature, age and stage was developed to serve clinical practice. CIBERSORT analysis showed immune cell infiltration was different between high- and low-risk groups. The immunohistochemical results derived from HPA indicated differential expression of prognosis-related ECM genes in CC and normal tissues. Conclusions: In the present study, a novel risk model based on ECM-signature could effectively reflect individual risk classification and provide potential therapeutic targets for CC patients. Moreover, the prognostic nomogram may help predict individualized survival.

Inflammatory Factors Induce Thrombosis through the miR-146b-3p/p38MAPK/COX-2 Pathway.

OBJECTIVE: Inflammatory responses play important roles in the pathogenesis of atherosclerosis. The purpose of this study was to investigate the relationship between microRNA-146b-3p (miR-146b-3p) and inflammatory factors in thrombosis. METHOD: THP-1 cells were cultured in vitro, Western blot was used to determine the protein levels of COX-2 and p38MAPK in the cells, and real-time PCR was used to detect the mRNA expression of miRNA-146b-3p and COX-2. A lentiviral expression vector of miRNA-146b-3p and its inhibitor were constructed to transfect THP-1 cells. COX-2 and p38MAPK expression in transfected cells was detected by Western blot and real-time PCR, respectively. RESULTS: Ang II and TNF-α could elevate the expression of COX-2 in monocytes. The expression of COX-2 was upregulated by p38MAPK, which could be phosphorylated by Ang II, while there was an increasing tendency of p38MAPK phosphorylation after TNF-α stimulation. In addition, COX-2 expression and P38MAPK phosphorylation could be downregulated by miRNA-146b-3p and upregulated by the miRNA-146b-3p inhibitor. Ang II could increase miR-146b-3p expression, although there was no significant difference; however, the expression of miR-146b-3p was enhanced significantly by TNF-α. CONCLUSION: Our data implied that altered expression of miR-146b-3p was closely related to the progression of inflammation mediating the P38MAPK/COX-2 pathway. We suggest that the miR-146b-3p/p38MAPK/COX-2 pathway plays a key role in inflammation and arterial thrombosis.

Circulating CTRP1 Levels Are Increased and Associated with the STOD in Essential Hypertension in Chinese Patients.

This study aimed to investigate the correlation between complement C1q tumor necrosis factor-related protein 1 (CTRP1) and subclinical target organ damage (STOD) in essential hypertension (EH). 720 patients were enrolled in this study, including 360 healthy subjects and 360 patients with EH. The EH group included 183 patients complicated with STOD and 177 patients without STOD. In the STOD group, there were 87 patients with left ventricular hypertrophy (LVH), 32 patients with microalbuminuria (MAU), and 58 patients with complication of LVH and MAU. Enzyme-linked immunosorbent assay (ELISA) was used to detect the CTRP1, adiponectin (APN), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). We found that CTRP1 levels were higher in patients with EH than those in healthy subjects; moreover, the level of CTRP1 of patients in the group complicated with EH and STOD was increased compared with EH patients without STOD. CTRP1 levels in the group complicated with LVH and MAU were significantly higher than those in the LVH group and the MAU group. Furthermore, APN, CTRP1, and IL-6 were three factors that influenced the STOD of EH patients, among which CTRP1 and IL6 were positively related with the complication of hypertension and STOD. In conclusion, CTRP1 levels are increased and associated with the STOD (heart and kidney) in essential hypertension, which can be regarded as a novel biomarker in the prediction of prognosis for patients with essential hypertension.