Prognostic value of triglyceride glucose index in population at high cardiovascular disease risk.

BACKGROUND: Early identification of populations at high cardiovascular disease (CVD) risk and improvement of risk factors can significantly decrease the probability of CVD development and improve outcomes. Insulin resistance (IR) is a CVD risk factor. The triglyceride glucose (TyG) index is a simple and reliable index for evaluating IR. However, no clinical studies on the prognostic value of the TyG index in a high risk CVD population have been conducted. This study evaluated the relationship between the TyG index and prognosis in a high risk CVD population. METHODS: This study enrolled 35,455 participants aged 35-75 years who were at high CVD risk and visited selected health centers and community service centers between 2017 and 2021. Their general clinical characteristics and baseline blood biochemical indicators were recorded. The TyG index was calculated as ln[fasting triglyceride (mg/dl)× fasting blood glucose (mg/dl)/2]. The endpoints were all-cause death and cardiovascular death during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the TyG index and endpoints. RESULTS: In the overall study population, the mean age of all participants was 57.9 ± 9.6 years, 40.7% were male, and the mean TyG index was 8.9 ± 0.6. All participants were divided into two groups based on the results of the RCS analysis, with a cut-off value of 9.83. There were 551 all-cause deaths and 180 cardiovascular deaths during a median follow-up time of 3.4 years. In the multivariate Cox proportional hazard model, participants with a TyG index ≥ 9.83 had a higher risk of all-cause death (Hazard ratio [HR] 1.86, 95% Confdence intervals [CI] 1.37-2.51, P<0.001) and cardiovascular death (HR 2.41, 95%CI 1.47-3.96, P = 0.001) than those with a TyG index < 9.83. Subgroup analysis revealed that there was no interaction between the TyG index and variables in all subgroup analyses. CONCLUSIONS: The high TyG index was associated with an increased risk of all-cause death and cardiovascular death in people at high risk of CVD. This finding demonstrates the value of the TyG index in the primary prevention of CVD. TRIAL REGISTRATION: retrospectively registered, the registration number is K2022-01-005 and the date is 2022.01.30.

The predictive value of the neutrophil/platelet ratio on in-hospital adverse events and long-term prognosis in patients with coronary artery disease after percutaneous coronary intervention and its possible internal mechanism.

The neutrophil-to-platelet ratio (NPR) is considered to be an indicator of inflammatory status. The value of the NPR in predicting in-hospital adverse events (AEs) and long-term prognosis after percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients has not yet been reported. Meanwhile, the mechanisms behind its predictive value for long-term prognosis remain unreported as well. The study retrospectively enrolled 7284 consecutive patients with CAD undergoing PCI from January 2012 to December 2018. Multivariable logistic regression analysis, multivariable Cox regression analysis, Kaplan‒Meier (KM) curve analysis, restricted cubic spline (RCS) curve analysis, and sensitivity analysis were used in the study. All-cause death was the endpoint of the study. According to the median value of the NPR, the patients were divided into two groups: the high group (NPR ≥ 0.02, n = 3736) and the low group (NPR < 0.02, n = 3548). Multivariate logistic regression analysis demonstrated that a high NPR was a risk factor for in-hospital AEs [odds ratio (OR) = 1.602, 95% CI 1.347-1.909, p = 0.001]. During a mean follow-up period of 3.01 ± 1.49 years, the multivariate Cox regression analysis showed that a high NPR affected the long-term prognosis of patients (HR 1.22, 95% CI 1.03-1.45, p = 0.025) and cardiac death (HR 1.49, 95% CI 1.14-1.95, p = 0.003). The subgroup analysis showed that the NPR was affected by age and sex. The mediation analysis identified that the effect of the NPR on long-term outcomes is partially mediated by serum creatinine (Scr) and triglycerides. The NPR may be a convenient indicator of in-hospital AEs and poor long-term and cardiac outcomes in CAD patients. It might have impacted prognosis through effects on kidney function and lipid metabolism.

A V-shaped association between high-density lipoprotein cholesterol levels and poor outcomes in patients after percutaneous coronary intervention.

BACKGROUND: High density lipoprotein cholesterol (HDL-C) is considered as "good cholesterol". Recent evidence suggests that a high HDL-C level may increase the risk of poor outcomes in some populations. PURPOSE: To investigate the association between HDL-C levels and poor outcomes in patients after percutaneous coronary intervention (PCI). METHODS: Patients undergoing PCI during January 2012 and December 2018 were consecutively recruited and divided into three groups with different HDL-C levels: HDL-C ≤ 25 mg/dL, 25 < HDL-C ≤ 60 mg/dL, HDL-C > 60 mg/dL by the restricted cubic spline (RCS) analysis and assessed for all-cause mortality (ACM). The association between HDL-C levels and poor outcomes was assessed by multivariable cox regression analysis. RESULTS: The patients were followed with a median duration of 4 years. Of the 7284 participants, 727 all-cause deaths and 334 cardiovascular deaths occurred. A V-shaped association of HDL-C with the prognosis was observed, patients with either excessively low or high HDL-C levels reporting a higher risk than those with midrange values. After adjustment for confounding factors, the former exhibited a higher cumulative rate of ACM and cardiovascular mortality (CM) than the latter [low HDL-C: for ACM, hazard ratio (HR), 1.96; 95%CI, 1.41, 2.73, P < 0.001; for CM, HR, 1.66; 95%CI, 1.03, 2.67; P = 0.037; high HDL-C: for ACM, HR, 1.73; 95%CI, 1.29, 2.32, P < 0.001; for CM, HR, 1.73; 95%CI, 1.16, 2.58; P = 0.007]. CONCLUSION: HDL-C levels display a V-shaped association with poor outcomes in patients after PCI, with excessively high or low HDL-C suggesting a higher mortality risk. An optimal HDL-C level may fall in the range of 25-60 mg/dL.

Hydrogen-bonding network of N,N'-bis[2-(tert-butyldimethylsiloxy)ethyl]ethylenediammonium dichloride.

The title salt, C18H46N2O2Si2(2+)·2Cl(-), has been synthesized by reaction of N,N'-bis(2-hydroxyethyl)ethylenediamine with tert-butyldimethylsilyl chloride. The zigzag backbone dication is located across an inversion centre and the two chloride anions are related by inversion symmetry. The ionic components form a supramolecular two-dimensional network via N-H···Cl hydrogen bonding, which is responsible for the high melting point compared with the oily compound N,N'-bis[2-(tert-butyldimethylsiloxy)ethyl]ethylenediamine.

A Pilot Study About the Role of PANoptosis-Based Genes in Atherosclerosis Development.

Background: As a chronic inflammatory disease, atherosclerosis (AS) and ischemia events are primarily affected by inflammation in AS. PANoptosis has been implicated in many human systemic disorders, including infection, cancer, neurodegeneration, and inflammation. On the other hand, little is understood about PANoptosis's function in AS. Methods: We used consensus clustering to divide the GSE100927 dataset into two panoptosis-related subgroups. PANoptosis-associated genes were screened by differential analysis and weighted gene co-expression network analysis (WGCNA) and enriched by ClueGO software. Investigating LASSO regression and MCODE to identify AS Diagnostic Markers. Immunoinfiltration analysis and single-cell analysis were used to search for cell types associated with the diagnostic genes. Final validation was performed by polymerase chain reaction (PCR). Results: We classified the GSE100927 dataset into two PANoptosis-related subtypes based on the expression of PANoptosis-related genes (PRGs) using consensus clustering. A total of 36 PANoptosis-associated genes were screened in the differentially expressed genes and WGCNA-related module. 4 hub genes were identified by MCODE and LASSO regression, and 3 AS diagnostic markers (ACP5, CCL3, HMOX1) were screened by external validation set. Immunoinfiltration analysis and single-cell analysis showed that the three diagnostic markers were associated with macrophages, and PCR results demonstrated that ACP5 and HMOX1 could be used as AS diagnostic markers. Conclusion: Our study identified ACP5 and HMOX1 as diagnostic genes for AS that may be associated with PANoptosis. ACP5 and HMOX1 may be involved in the pathogenesis of AS by regulating macrophage PANoptosis.

Genetic screening of MMP1 as a potential pathogenic gene in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome. Airway inflammation and remodeling are the two key processes involved in COPD pathogenesis. However, the key pathogenic genes driving COPD development have not been revealed. This study aims to identify and validate hub gene(s) underlying COPD development through bioinformatics analysis and experimental validation. METHODS: Three lung tissue sequencing datasets of the COPD (including GSE38974, GSE103174, and GSE106986) were analyzed. Further, differentially expressed genes (DEGs) were used to compare patients with COPD with non-COPD individuals, and the Robust Rank Aggregation (RRA) analysis was also performed. Results revealed a series of potential pathogenic genes of COPD. DEGs were subjected to KEGG, GO, and GSEA analyses. The scRNA dataset of human lung tissues (Human Lung Cell Atlas), and human primary airway epithelial cells (GSE134147) were used to identify the cell subtype localization. The qRT-PCR assay was performed in the human lung tissues, COPD mice model, and primary bronchial epithelial cells at the air-liquid interface (ALI) under cigarette smoke extract (CSE) stimulation to verify the expression of the hub genes. LASSO and GLM analysis with the hub genes were performed to identify the most critical gene. RNA-seq was performed after knocking down the critical gene using siRNA in HBECs at ALI. The potential role of the critical gene was confirmed through qRT-PCR, Western blot, and Immunofluorescence (IF) assays. RESULTS: A total of 98 genes were significantly and differently expressed in 3 GEO datasets. The KEGG and GO analyses showed that most of these genes are responsible for inflammation, immunity, and cell proliferation. The core gene set including 15 genes was screened out and consequently, the MMP1 was the most likely responsible for the progression of COPD. Moreover, we confirmed that MMP1 is significantly related to inflammatory effects and cilia function in human bronchial epithelial cells cultured at the air-liquid interface (ALI). CONCLUSION: In summary, we confirmed that inflammation and cell proliferation are potentially critical processes in COPD occurrence and development. A total of 15 potential hub genes were identified among which MMP1 was the most likely gene responsible for the development of COPD. Therefore, MMP1 is a potential molecular target of COPD therapy.

Smad3-mediated lncRNA HSALR1 enhances the non-classic signalling pathway of TGF-ß1 in human bronchial fibroblasts by binding to HSP90AB1.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the diseases with high mortality and morbidity with complex pathogenesis. Airway remodeling is an unavoidable pathological characteristic. However, the molecular mechanisms of airway remodeling are incompletely defined. METHODS: lncRNAs highly correlated with transforming growth factor beta 1(TGF-ß1) expression were chosen, the lncRNA ENST00000440406 (named HSP90AB1 Assoicated LncRNA 1, HSALR1) was chosen for further functional experiments. Dual luciferase and ChIP assay were used to detect the upstream of HSALR1, transcriptome sequencing, Cck-8, Edu, cell proliferation, cell cycle assay, and WB detection of pathway levels confirmed the effect of HSALR1 on fibroblast proliferation and phosphorylation levels of related pathways. Mice was infected with adeno-associated virus (AAV) to express HSALR1 by intratracheal instillation under anesthesia and was exposure to cigarette smoke, then mouse lung function was performed and the pathological sections of lung tissues were analyzed. RESULTS: Herein, lncRNA HSALR1 was identified as highly correlated with the TGF-ß1 and mainly expressed in human lung fibroblasts. HSALR1 was induced by Smad3 and promoted fibroblasts proliferation. Mechanistically, it could directly bind to HSP90AB1 protein, and acted as a scaffold to stabilize the binding between Akt and HSP90AB1 to promote Akt phosphorylation. In vivo, mice expressed HSALR1 by AAV was exposure to cigarette smoke (CS) for COPD modeling. We found that lung function was worse and airway remodeling was more pronounced in HSLAR1 mice compare to wild type (WT) mice. CONCLUSION: Our results suggest that lncRNA HSALR1 binds to HSP90AB1 and Akt complex component, and enhances activity of the TGF-ß1 smad3-independent pathway. This finding described here suggest that lncRNA can participate in COPD development, and HSLAR1 is a promising molecular target of COPD therapy.

Biomass-related PM2.5 induces mitochondrial fragmentation and dysfunction in human airway epithelial cells.

The use of biomass for cooking and heating is considered an important factor associated with chronic obstructive pulmonary disease (COPD), but few studies have previously addressed its underlying mechanisms. Therefore, this research aimed to evaluate the effects of biomass-related PM2.5 (BRPM2.5) exposure on 16HBE human airway epithelial cells and in mice with regard to mitochondrial dysfunction. Our study indicated that BRPM2.5 exposure of 16HBE cells resulted in mitochondrial dysfunction, including decreased mitochondrial membrane potential, increased expression of fission proteins-phospho-DRP1, increased mitochondrial ROS (mtROS), and decreased levels of ATP. BRPM2.5 altered the mitochondrial metabolism of 16HBE cells by decreasing mitochondrial oxygen consumption and glycolysis. However, Mitochondria targeted peptide SS-31 eliminated mitochondrial ROS and alleviated the ATP deficiency and proinflammatory cytokines release. BRPM2.5 exposure resulted in abnormal mitochondrial morphological alterations both in 16HBE and in lung tissue. Taken together, these results suggest that BRPM2.5 has detrimental effects on human airway epithelial cells, leading to mitochondrial dysfunction, abnormal mitochondrial metabolism and altered mitochondrial dynamics. The present study provides the first evidence that disruption of mitochondrial structure and mitochondrial metabolism may be one of the mechanisms of BRPM2.5-induced respiratory dysfunction.

Systematic Understanding of the Mechanism of Baicalin against Gastric Cancer Using Transcriptome Analysis.

BACKGROUND: Gastric cancer (GC) is the most common type of cancer. It is highly malignant and is characterized by rapid and uncontrolled growth. The antitumour activity of Baicalin was studied in multiple cancers. However, its mechanism of action has not been fully elucidated. We provided a systematic understanding of the mechanism of action of baicalin against GC using a transcriptome analysis of RNA-seq. METHODS: Human GC cells (SGC-7901) were exposed to 200 µg/ml baicalin for 24 h. RNA-seq with a transcriptome, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the antitumour effects of baicalin on SGC-7901 cells in vitro. A protein-protein interaction (PPI) network of differentially expressed genes (DEGs) was constructed. A competitive endogenous RNA (ceRNA) network was constructed and further analysed after validation using qRT-PCR. RESULTS: A total of 68 lncRNAs, 20 miRNAs, and 1648 mRNAs were differentially expressed in baicalin-treated SGC-7901 GC cells. Three lncRNAs, 6 miRNAs, and 7 mRNAs were included in the ceRNA regulatory network. GO analysis revealed that the main DEGs were involved in the biological processes of the cell cycle and cell death. KEGG pathway analysis further suggested that the p53 signalling pathway was involved in the baicalin-induced antitumour effect on SGC-7901 cells. Further confirmation using qPCR indicated that baicalin induced an antitumour effect on SGC-7901 cells, which is consistent with the results of the sequencing data. CONCLUSIONS: In summary, the mechanism of baicalin against GC involves multiple targets and signalling pathways. These results provide new insight into the antitumour mechanism of baicalin and help the development of new strategies to cure GC.

Analysis and Construction of a Competitive Endogenous RNA Regulatory Network of Baicalin-Induced Apoptosis in Human Osteosarcoma Cells.

BACKGROUND: Baicalin is an extract from the traditional Chinese herb Scutellaria baicalensis and has the potential to treat osteosarcoma (OS). However, the transcriptome-level mechanism of baicalin-mediated antitumor effects in OS has not yet been investigated. The aim of this study was to analyze the competitive endogenous RNA (ceRNA) regulatory network involved in baicalin-induced apoptosis of OS cells. METHODS: In this study, CCK-8 and flow cytometry assays were used to detect the antitumor effects of baicalin on human OS MG63 cells. Furthermore, transcriptome sequencing was employed to establish the long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA profiles. RESULTS: Baicalin inhibited MG63 cell proliferation and induced apoptosis. Totals of 58 lncRNAs, 31 miRNAs, and 2136 mRNAs in the baicalin-treated MG63 cells were identified as differentially expressed RNAs compared to those in control cells. Of these, 2 lncRNAs, 3 miRNAs, and 18 mRNAs were included in the ceRNA regulatory network. The differentially expressed RNAs were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSIONS: By identifying the ceRNA network, our results provide new information about the possible molecular basis of baicalin, which has potential applications in OS treatment.

Long noncoding RNA IL6-AS1 is highly expressed in chronic obstructive pulmonary disease and is associated with interleukin 6 by targeting miR-149-5p and early B-cell factor 1.

Chronic obstructive pulmonary disease is a complex condition with multiple etiologies, including inflammation. We identified a novel long noncoding RNA (lncRNA), interleukin 6 antisense RNA 1 (IL6-AS1), which is upregulated in this disease and is associated with airway inflammation. We found that IL6-AS1 promotes the expression of inflammatory factors, especially interleukin (IL) 6. Mechanistically, cytoplasmic IL6-AS1 acts as an endogenous sponge by competitively binding to the microRNA miR-149-5p to stabilize IL-6 mRNA. Nuclear IL6-AS1 promotes IL-6 transcription by recruiting early B-cell factor 1 to the IL-6 promoter, which increases the methylation of the H3K4 histone and acetylation of the H3K27 histone. We propose a model of lncRNA expression in both the nucleus and cytoplasm that exerts similar effects through differing mechanisms, and IL6-AS1 probably increases inflammation via multiple pathways.