Tissue-resident C1q + macrophages exert anti-aging potential through the Sirt1 pathway.

OBJECTIVE: Resident immune cells are at the forefront of sensory organ-specific signals, and changes in these cells are closely related to the aging process. The Sirt pathway can regulate NAD + metabolism during aging, thereby affecting the accumulation of ROS. However, the role of the Sirt pathway in resident immune cells in aged tissues is currently unclear. METHODS: We investigated Sirt1 signalling in resident immune cells during chronic inflammation in an aged mouse model. Integrated single-cell RNA sequencing data from young and aged mice were used to refine the characterization of immune cells in aged tissues RESULTS: We found that C1q + macrophages could affect chronic inflammation during aging. C1q + macrophages acted in an opposing manner to Il1b + macrophages and were responsible for anti-inflammatory effects during aging. Sirt1 agonists inhibited the decrease in C1qb in macrophages during aging, and anti-aging drugs could affect the expression of C1qb in macrophages via the Sirt1 pathway. CONCLUSIONS: In this study, we first identified the relevance of C1q + macrophages in chronic inflammation during aging. The potential anti-aging effect of C1q + macrophages was mediated by the Sirt1 pathway, suggesting new strategies for aging immunotherapy.

MiR-18a-5p aggravates homocysteine-induced myocardial injury via autophagy. / MiR-18a-5pé€šè¿‡ä»‹å¯¼è‡ªå™¬åŠ é‡åŒåž‹åŠèƒ±æ°¨é ¸è¯±å¯¼çš„å¿ƒè‚ŒæŸä¼¤.

OBJECTIVES: Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury. METHODS: H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2. RESULTS: Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p. CONCLUSIONS: MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.

De-Escalation Dual Antiplatelet Therapy Prevail over Potent P2Y12 Inhibitor Monotherapy in Patients with Acute Coronary Syndrome Undergone Percutaneous Coronary Intervention: A Network Meta-Analysis.

Background: Dual antiplatelet therapy (DAPT) with potent P2Y12 inhibitor is the cornerstone of acute coronary syndrome (ACS) management. Balancing the effects of different strategies of antiplatelet therapy including DAPT de-escalation, potent P2Y12 inhibitor monotherapy, and conventional DAPT is a hot topic. Methods: A systematic search was conducted from the MEDLINE, PubMed, and Embase through October 2021 to identify various DAPT strategies in randomized controlled trials (RCTs) for treatment of ACS patients after undergoing PCI with drug-eluting stent (DES). The network meta-analysis was performed to investigate the net clinic benefit of the DAPT de-escalation, potent P2Y12 inhibitor monotherapy, as well as conventional DAPT. The primary outcome was net adverse clinical events, defined as a composite of major bleeding and cardiac death, myocardial infarction, stroke, stent thrombosis, or target-vessel revascularization. The secondary outcomes include major adverse cardiac events and trial-defined major or minor bleeding. Results: A total of 14 RCTs with 63,982 patients were included. The DAPT de-escalation was associated with a lower risk of the primary outcome compared with potent P2Y12 inhibitor monotherapy (De-escalation vs monotherapy odds ratio (OR): 0.72 95% confidence interval (CI): 0.55-0.96), and other antiplatelet strategies (De-escalation vs clopidogrel + aspirin OR: 0.49 95% CI: 0.39-0.63; De-escalation vs prasugrel + aspirin OR: 0.76 95% CI: 0.59-0.98; De-escalation vs ticagrelor + aspirin OR: 0.76 95% CI: 0.55-0.90). There were no statistical differences in the incidence of bleeding (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.73 95% CI: 0.47-1.12) and major adverse cardiac events (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.79 95% CI: 0.59-1.08) between DAPT de-escalation and potent P2Y12 inhibitor monotherapy. Conclusions: This network meta-analysis showed that DAPT de-escalation would reduce the net adverse clinical events, compared with potent P2Y12 inhibitor monotherapy, for ACS patients undergone PCI treatment.

Functional metabolomics revealed functional metabolic-characteristics of chronic hepatitis that is significantly differentiated from acute hepatitis in mice.

Diagnosis and therapeutics of acute- and chronic- hepatitis (A-H and C-H) cannot be distinguished during clinical practice because functional molecular-characteristics of two conditions remains elusive. Here, we employed a functional metabolomics strategy to discover functional metabolites that can readily distinguish C-H from A-H in CCl4 treated mice. Metabolic-differentiation between A-H and C-H was identified as A-H was largely characterized by the dysregulated purine cycle and amino acid metabolism, while the disorders of hepatic taurine-conjugated bile acids and glycerolipid biosynthesis were observed with C-H. Excitingly, we found that the enhanced conversation of C18-22 PUFA-containing TAGs to MUFA-containing TAGs promoted the development of C-H, which was also closely associated with the changes of TCA intermediates regulated by gut microbiota (Muribaculaceae and Prevotellaceae). Such metabolic discovery on hepatitis was validated by the functional annotation of metabolic genes, as the decreased expressions of Slc27a2, Acaa1a and Acaa1b mostly account for the dysregulation of purine degradation with AH, then the lowered expressions of Cyp2e1, Cat, Slc27a5 and Klb are significantly related to the dysregulated bile acids with C-H. Collecting clinical samples from the patients with hepatitis to compare serum metabolomes with A-H and C-H mice, the determinant functional metabolites were identified to significantly distinguish C-H from A-H in both experimental and clinical settings, suggesting metabolic discovery with CCl4 treated mice could be further efficiently explored to guide clinical research of A-H and C-H. Collectively, our study is providing novel insight into distinctive metabolic-characteristics of A-H and C-H underlying the innovative diagnosis and therapeutics of hepatitis.

Lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients: an integrated bioinformatic analysis.

BACKGROUND: Hyperlipidaemia is an important factor that induces coronary artery disease (CAD). This study aimed to explore the lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients. METHODS: In the current study, datasets were fetched from the Gene Expression Omnibus (GEO) database and nonnegative matrix factorization clustering was used to establish a new CAD classification based on the gene expression profile of lipid metabolism genes. In addition, this study carried out bioinformatics analysis to explore intrinsic biological and clinical characteristics of the subgroups. RESULTS: Data for a total of 615 samples were extracted from the Gene Expression Omnibus database and were associated with clinical information. Then, this study used nonnegative matrix factorization clustering for RNA sequencing data of 581 lipid metabolism relevant genes, and the 296 patients with CAD were classified into three subgroups (NMF1, NMF2, and NMF3). Subjects in subgroup NMF2 tended to have an increased severity of CAD. The CAD index and age of group NMF1 were similar to those of group NMF3, but their intrinsic biological characteristics exhibited significant differences. In addition, weighted gene coexpression network analysis (WGCNA) was used to determine the most important modules and screen lipid metabolism related genes, followed by further analysis of the DEGs in which the significant genes were identified based on clinical information. The progression of coronary atherosclerosis may be influenced by genes such as PTGDS and DGKE. CONCLUSION: Different CAD subgroups have their own intrinsic biological characteristics, indicating that more personalized treatment should be provided to patients in each subgroup, and some lipid metabolism related genes (PDGTS, DGKE and so on) were related significantly with clinical characteristics.

FUNCTIONAL METABOLOMICS DECIPHER BIOCHEMICAL FUNCTIONS AND ASSOCIATED MECHANISMS UNDERLIE SMALL-MOLECULE METABOLISM.

Metabolism is the collection of biochemical reactions enabled by chemically diverse metabolites, which facilitate different physiological processes to exchange substances and synthesize energy in diverse living organisms. Metabolomics has emerged as a cutting-edge method to qualify and quantify the metabolites in different biological matrixes, and it has the extraordinary capacity to interrogate the biological significance that underlies metabolic modification and modulation. Liquid chromatography combined with mass spectrometry (LC/MS), as a robust platform for metabolomics analysis, has increased in popularity over the past 10 years due to its excellent sensitivity, throughput, and versatility. However, metabolomics investigation currently provides us with only phenotype data without revealing the biochemical functions and associated mechanisms. This limitation indeed weakens the core value of metabolomics data in a broad spectrum of the life sciences. In recent years, the scientific community has actively explored the functional features of metabolomics and translated this cutting-edge approach to be used to solve key multifaceted questions, such as disease pathogenesis, the therapeutic discovery of drugs, nutritional issues, agricultural problems, environmental toxicology, and microbial evolution. Here, we are the first to briefly review the history and applicable progression of LC/MS-based metabolomics, with an emphasis on the applications of metabolic phenotyping. Furthermore, we specifically highlight the next era of LC/MS-based metabolomics to target functional metabolomes, through which we can answer phenotype-related questions to elucidate biochemical functions and associated mechanisms implicated in dysregulated metabolism. Finally, we propose many strategies to enhance the research capacity of functional metabolomics by enabling the combination of contemporary omics technologies and cutting-edge biochemical techniques. The main purpose of this review is to improve the understanding of LC/MS-based metabolomics, extending beyond the conventional metabolic phenotype toward biochemical functions and associated mechanisms, to enhance research capability and to enlarge the applicable scope of functional metabolomics in small-molecule metabolism in different living organisms.

Visceral Adiposity Index Is Inversely Associated with Renal Function in Normal-Weight Adults with Hypertension: The China H-Type Hypertension Registry Study.

BACKGROUND: Risk of chronic kidney disease (CKD) is higher in normal-weight metabolically unhealthy people, especially when combined with hypertension. In this context, whether the visceral adiposity index (VAI), which reflects body fat distribution and metabolism, can be used to identify the risk of CKD among normal-weight hypertensive patients is unclear. OBJECTIVES: This study aimed to evaluate the association between VAI and renal function in normal-weight hypertensive patients. METHODS: In this cross-sectional study, 8591 hypertensive patients with normal BMI from the China H-type Hypertension Registry Study were analyzed. The VAI was calculated with serum triglycerides, serum HDL cholesterol, waist circumference, and BMI. VAI was ln-transformed for analysis on account of the skewed distribution. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL · min-1 · 1.73 m-2. Multivariable linear and multivariable logistic regression analyses were performed to evaluate the association of VAI with eGFR and CKD. RESULTS: The prevalence rate of CKD was 10.1%. Multivariable linear regression analyses showed that an elevated lnVAI reduced eGFR by 2.63 mL · min-1 · 1.73 m-2 (95% CI: -3.54, -1.72 mL · min-1 · 1.73 m-2). Multivariable logistic regression analysis showed that an elevated lnVAI was independently associated with the prevalence of CKD (OR: 1.59; 95% CI: 1.31, 1.93). As possible confounding factors were removed the association became greater. The higher the VAI was, the greater the decrease in eGFR and the higher the risk of CKD. No significant interactions were found in any of the subgroups (age, sex, physical activity, current smoking, current drinking, fasting glucose, LDL cholesterol, blood pressure, and antihypertensive drugs). CONCLUSIONS: VAI, as a simple surrogate measure of visceral fat accumulation, is independently and inversely associated with renal function in normal-weight Chinese hypertensive adults.This trial was registered at chictr.org.cn as ChiCTR1800017274.

Dihydromyricetin improves DSS-induced colitis in mice via modulation of fecal-bacteria-related bile acid metabolism.

Recent studies show that the nutraceutical supplement dihydromyricetin (DHM) can alleviate IBD in murine models by downregulating the inflammatory pathways. However, the molecular mechanistic link between the therapeutic efficiency of DHM, gut microbiota, and the metabolism of microbial BAs remains elusive. In this study, we explored the improvement of DHM on the dysregulated gut microbiota of mice with dextran sulfate sodium (DSS)-induced colitis. We found that DHM could markedly improve colitis symptoms, gut barrier disruption, and colonic inflammation in DSS-treated mice. In addition, bacterial 16S rDNA sequencing assay demonstrated that DHM could alleviate gut dysbiosis in mice with colitis. Furthermore, antibiotic-mediated depletion of the gut microflora and fecal microbiome transplantation (FMT) demonstrated that the therapeutic efficiency of DHM was closely associated with gut microbiota. BA-targeted metabolomics analysis revealed that DHM restored the metabolism of microbial BAs in the gastrointestinal tract during the development of colitis. DHM significantly enriched the proportion of the beneficial Lactobacillus and Akkermansia genera, which were correlated with increased gastrointestinal levels of unconjugated BAs involving chenodeoxycholic acid and lithocholic acid, enabling the BAs to activate specific receptors, such as FXR and TGR5, and maintaining intestinal integrity. Taken together, DHM could alleviate DSS-induced colitis in mice by restoring the dysregulated gut microbiota and BA metabolism, leading to improvements in intestinal barrier function and colonic inflammation. Increased microbiota-BAs-FXR/TGR5 signaling may be the potential targets of DHM in colitis. Therefore, our findings provide novel insights into the development of novel DHM-derived drugs for the management of IBD.

The relationship between the atherogenic index of plasma and arterial stiffness in essential hypertensive patients from China: a cross-sectional study.

BACKGROUND: The atherogenic index of plasma (AIP) always remains in a potential association with arterial stiffness, however, this association has not been fully discovered and needs to be studied in depth in large hypertensive patient populations. The present analysis thus sought to further explore the association that exists between AIP and arterial stiffness in Chinese patients diagnosed with arterial hypertension. METHODS: This cross-sectional study analyzed 4744 Chinese individuals with essential hypertension. AIP was defined as the base 10 logarithm of the ratio of plasma of triglycerides to high-density lipoprotein cholesterol levels indicated in molar concentrations. Measurement of arterial stiffness was carried out via brachial-ankle pulse wave velocity (baPWV). RESULTS: Data were adjusted for potential confounding variables, and multivariate linear regression analysis revealed AIP to be positively correlated with baPWV (ß = 1.34, 95% CI: 0.96 to 1.72, P < 0.001). When AIP was instead treated as a categorical variable divided into quartiles, the same relationship was observed (P for trend < 0.001). We additionally found AIP and baPWV had a stronger positive association in individuals with a body mass index (BMI) < 24 kg/m2 (P for interaction < 0.05). CONCLUSION: AIP and arterial stiffness were positively correlated in essential hypertension patients in China, especially in those with a BMI < 24 kg/m2. Clinical trial registration ChiCTR1800017274.

Association between baseline serum uric acid and development of LDL-C level in patients with first acute myocardial infarction.

BACKGROUND: Data on the relationship of baseline serum uric acid (SUA) with development of low-density lipoprotein cholesterol (LDL-C) level in patients with first acute myocardial infarction (AMI) are limited. The present study is to evaluate whether elevated SUA predicts the development of LDL-C in the first AMI. METHODS: This is a retrospective 6-month cohort study of 475 hospitalized Chinese patients who underwent first AMI between January 2015 and December 2019 and were reevaluated half a year later at the Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The associations of baseline SUA with the percentage decrease of LDL-C (%) and LDL-C control were analyzed by using logistic regression analyses, multivariate linear regression analyses and the restricted cubic spline. RESULTS: Over the 6-month follow-up, baseline SUA was independently and positively associated with the percentage decrease of LDL-C (%) and LDL-C control in a dose response fashion. After multivariable adjustment, per SD increment of baseline SUA (120.58 µmol/L) was associated with 3.96% higher percentage decrease of LDL-C(%). The adjusted OR (95% CI) for LDL-C control was 5.62 (2.05, 15.36) when comparing the highest tertile (SUA ≥ 437.0 µmol/L) to the lowest tertile (< 341.7 µmol/L) of baseline SUA. CONCLUSIONS: Among Chinese patients with first AMI, higher baseline SUA was associated with higher LDL-C deduction percentage (%), and higher rate of LDL-C control in the short-term follow-up, respectively. SUA acquired when AMI occurred was prone to be profitable in predicting the risk stratification of uncontrolled LDL-C and dyslipidemia management.

Potential Target Genes in the Development of Atrial Fibrillation: A Comprehensive Bioinformatics Analysis.

BACKGROUND Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. Although it is not life-threatening, the accompanying rapid and irregular ventricular rate can lead to hemodynamic deterioration and obvious symptoms, especially the risk of cerebrovascular embolism. Our study aimed to identify novel and promising genes that could explain the underlying mechanism of AF development. MATERIAL AND METHODS Expression profiles GSE41177, GSE79768, and GSE14975 were acquired from the Gene Expression Omnibus Database. R software was used for identifying differentially expressed genes (DEGs), and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were subsequently performed. A protein-protein interaction network was constructed in Cytoscape software. Next, a least absolute shrinkage and selection operator (LASSO) model was constructed and receiver-operating characteristic curve analysis was conducted to assess the specificity and sensitivity of the key genes. RESULTS We obtained 204 DEGs from the datasets. The DEGs were mostly involved in immune response and cell communication. The primary pathways of the DEGs were related to the course or maintenance of autoimmune and chronic inflammatory diseases. The top 20 hub genes (high scores in cytoHubba) were selected in the PPI network. Finally, we identified 6 key genes (FCGR3B, CLEC10A, FPR2, IGSF6, S100A9, and S100A12) via the LASSO model. CONCLUSIONS We present 6 target genes that are potentially involved in the molecular mechanisms of AF development. In addition, these genes are likely to serve as potential therapeutic targets.

Association of TyG index and central obesity with hypertension in middle-aged and elderly Chinese adults: a prospective cohort study.

Triglyceride glucose index (TyG) and waist circumstance have been well documented to be highly correlated with hypertension. However, the joint effect of waist circumstance and TyG on the risk of hypertension is unknown in middle-aged and elderly Chinese adults. The purpose of this study was to investigate the association between TyG and the risk of new-onset hypertension in middle-aged and elderly Chinese individuals with different waist circumstances. The multicentred prospective cohort study was conducted in 28 provinces of China including a total of 5865 eligible participants aged ≥ 45 years old. Cox regression was performed to examine the relationship of TyG index and hypertension with adjustments for the pertinent variables. Besides, the relationship was explored in different groups on the basis of waist circumstance. There was no significant correlation between TyG index and new-onset hypertension after adjustment for pertinent variables (hazards ratio [HR]: 0.99; 95% confidence interval [CI]: 0.80-1.24). When the association was explored in different waist circumstance groups, multivariate cox regression analyses revealed that TyG was an independent factor positively associated with the risk of hypertension in central obesity prophase group (HR: 1.57; 95% CI 1.13-2.16). Among individuals with central obesity, relative to population with lower TyG (Q1: 4.96-8.18), people who had higher TyG (Q3: 8.52-8.95; Q4: 8.95-12.14) were associated with significantly lower HR for hypertension. There was no conspicuous correlation between TyG index with new-onset hypertension in normal waist circumstance (HR: 1.05; 95% CI 0.84-1.30). The research demonstrated the positive relationship of TyG with risk of hypertension among individuals with central obesity prophase, negative relationship of TyG with hypertension among population with central obesity and inconspicuous correlation of TyG with hypertension among individuals with normal waist. In conclusion, the study findings supported the combined effects of TyG index and waist circumference in predicting hypertension in middle-aged and elderly Chinese individuals.

Association between body shape index and coronary heart disease in individuals over 20 years old with obese.

BACKGROUND: While body mass index (BMI) defines obesity as a well-established risk factor for cardiovascular disease, the paradoxical theory of BMI suggests that obesity may indeed have a favorable impact on the prognosis of cardiovascular disease. Therefore, this study aims to assess the correlation between body shape index (ABSI), which is a novel measure of obesity, and coronary heart disease (CHD) among obese individuals in the United States. METHODS: The data from the National Health and Nutrition Examination Survey (NHANES) were evaluated by us for 5046 patients. We assessed the exposure variable ABSI, which includes waist circumference (WC), height, and BMI. The outcome variable was CHD. RESULTS: The cross-sectional study included a total of 5046 obese adults aged over 20 years, with an average age (standard deviation: SD) of 49.86 (16.24) years and a male proportion of 44.57%.The odds ratio (OR) values for CHD in Model 1, Model 2, 3 were found to be 2.45 (95%CI: 2.12, 2.83), 1.53 (95%CI:1.30, 1.81) and 1.31 (95%CI:1.09, 1.56) per SD increase in ABSI, respectively. In the fully adjusted model, we designated participants in the T1 group as the reference group. Our findings indicate a significant increase in the prevalence of CHD (OR:1.82, 95%CI: 1.07-3.10) only within the T3 group. Although there is an increased prevalence of CHD (OR:1.32, 95%CI: 0.77-2.29) in the T2 group, no statistically significant difference was observed. CONCLUSIONS: The increase in ABSI is strongly associated with the rise in CHD prevalence among obese individuals in the United States.

New Insights into the Role of HMGB2 in ST-Segment Elevation Myocardial Infarction.

Background: Ischemic heart disease is one of the leading causes of death in the world, of which ST-segment elevation myocardial infarction (STEMI) is an important type. Inappropriate activation and accumulation of platelets typically induced thrombosis, which may result in acute vessel occlusion and STEMI. Multiple cytokines have been shown to regulate platelet activation, but the relationship between HMGB2 and platelet activation has not been elucidated. Methods: We collected peripheral blood of STEMI patients and healthy adults, and mass spectrometry analysis of platelet proteins was conducted. The "edgeR" package was used to identify the differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the significantly changed pathways. Western blot and ELISA were used to detect the expression of a high mobility group box 2 (HMGB2). Flow cytometric analysis and platelet aggregation rate were performed to evaluate the activation of platelets. Results: We identified ALOX5, HIST1H1B, S100A11, HMGB2, and RPS15A were the top five up-regulated proteins by differential expression analysis. Western blot verified that the relative protein expression of HMGB2 in platelet was significantly higher in STEMI patients compared with control adults, and the results of ELISA indicated that the serum HMGB2 level increased and significantly correlated with neutrophil count in STEMI patients. Further investigation showed that the platelet aggregation induced by ADP, the activation of integrin αIIbß3 and CD62P expression on platelet surface were all enhanced by the recombinant HMGB2 (rHMGB2). Conclusion: In conclusion, HMGB2 may be the key molecule to regulate platelet activation in patients with STEMI, which may serve as a potential therapeutic target for STEMI.

Matrine Alleviates Sepsis-Induced Myocardial Injury by Inhibiting Ferroptosis and Apoptosis.

Matrine is a Sophora alkaloid that exerts antitumor effects on a variety of diseases, but few studies have investigated the role of matrine in sepsis-induced myocardial injury. In the present study, we investigated the effects of matrine on septic myocardial injury and the potential mechanisms. Network pharmacology approaches were used to predict the targets of matrine in the treatment of sepsis-induced myocardial injury. A mouse sepsis-induced myocardial injury model was established to determine the effect of matrine. Mouse cardiac function was evaluated by ultrasonography, and cardiac morphology and cardiomyocyte apoptosis were evaluated by HE and TUNEL staining. Oxidative stress was assessed by measuring ROS levels and MDA and SOD activity. Bax, Bcl2, GPX4, ACSL4, PI3K, and AKT protein levels were evaluated by immunohistochemical staining and western blotting. Bioinformatics analysis identified that the potential therapeutic effect of matrine on sepsis-induced myocardial injury is closely related to ferroptosis and apoptosis regulation and showed significant involvement of the PI3K/AKT signaling pathway. In vivo, the matrine group showed improved myocardial function, morphology, and apoptosis ratio and alleviated oxidative stress compared with the LPS group, whereas 25 mg/kg matrine exerted the optimal inhibitory effect. Matrine alleviated LPS-induced cardiomyocyte ferroptosis and apoptosis, resulting in upregulation of Bax/Bcl2 and GPX4 expression and downregulation of ferroptosis marker protein (ACSL4) expression, as shown by immunohistochemistry and western blotting. Moreover, matrine increased PI3K/AKT pathway-related molecule expression and thus modulated ferroptosis and apoptosis. Matrine regulates PI3K/AKT pathway activity to inhibit apoptosis and ferroptosis and thereby alleviates sepsis-induced myocardial injury.

Rosiglitazone reduces diabetes angiopathy by inhibiting mitochondrial dysfunction dependent on regulating HSP22 expression.

The effects of rosiglitazone (RSG) in patients with type 2 diabetes mellitus (T2DM) remain controversial. Here, we first used network pharmacology to identify the common targets of RSG in the treatment of diabetes angiopathy (DA). Enrichment analysis found that the common genes were involved in the inflammatory response, leukocyte cell-cell adhesion, mitochondrion organization and oxidative stress. Our previous research confirmed that heat shock protein 22 (HSP22) suppresses diabetes-induced endothelial activation and injury by inhibiting mitochondrial reactive oxygen species (mtROS) formation and dysfunction. We then constructed HSP22 knockout mice with T2DM to investigate whether RSG protected the vascular endothelium by upregulating HSP22. Our study suggested that RSG reduced vascular endothelial cell activation and injury by decreasing monocyte adhesion and cytokine secretion and simultaneously upregulating HSP22 expression. Mechanistically, RSG inhibited mitochondrial oxidative stress and dysfunction by regulating PPAR-γ in a manner partially dependent on expression of HSP22, resulting in reduced DA.

Protective Effect of Nicorandil on Contrast-Induced Acute Kidney Injury After Emergency Percutaneous Coronary Intervention.

Objective: To investigate the protective effect of nicorandil on contrast-induced acute kidney injury (CIAKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). Methods: This is a single-center, retrospective control study. A total of 156 patients with STEMI were divided into the nicorandil group (n = 55) and the control group (n = 101). The incidence of CIAKI, defined as an increase of >25% or absolute values > 44.2 µmol/L in serum creatinine (Scr) from baseline within 72 h of exposure to a contrast agent after exclusion of other causes, was the primary endpoint. The secondary endpoints were: (1) changes of Scr, estimated glomerular filtration rate (eGFR), uric acid, and ß2-microglobulin at 24/48/72 h and 5 to 7 days after PCI; (2) the peak value difference of creatine kinase isoenzymes (CK-MB) after PCI; (3) adverse events within 6 months after PCI. Results: The overall incidence of CIAKI was 21.8%; the incidence of CIAKI in the nicorandil group was significantly lower (12.7% [7/55]) than in the control group (26.7% [27/101]) (P = .043). Compared with the control group, Scr, uric acid, and ß2-microglobulin levels were lower, and the level of eGFR was higher in nicorandil group (P all < .05). The peak value of CK-MB in the nicorandil group was lower than that in the control group (105.30 [56.61, 232.04] vs 178.00 [77.08, 271.91]U/L, P = .042). There was no significant difference in adverse events between the 2 groups within 6 months after PCI. Moreover, multivariate logistic regression analysis showed that hypertension and diabetes were independent risk factors for CIAKI, while nicorandil treatment was a protective factor. Conclusion: Our data suggest that intravenous nicorandil after emergency PCI has a protective effect on the occurrence of CIAKI in STEMI patients.

MiR-20b-5p involves in vascular aging induced by hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis (AS). Some reports have shown that homocysteine (Hcy) could accelerate the development of AS by promoting endothelial cell senescence. miRNAs were widely involved in the pathophysiology of HHcy. However, few studies have focused on the changes of miRNA-mRNA networks in the artery of HHcy patients. For this reason, RNA-sequencing was adopted to investigate the expression of miRNA and mRNA in HHcy model mouse arteries. We found that the expression of 216 mRNAs and 48 miRNAs were significantly changed. Using TargetScan and miRDB web tools, 29 miRNA-mRNA pairs were predicted. Notably, miR-20b-5p and FJX1 shared the highest predicted score in TargetScan, and further study indicated that the miR-20b-5p inhibitor significantly upregulated the FJX1 expression in HHcy human umbilical vein endothelial cells (HUVECs) model. PPI analysis revealed an important sub-network which was centered on CDK1. Gene ontology (GO) enrichment analysis showed that HHcy had a significant effect on cell cycle. Further experiments found that Hcy management increased reactive oxygen species (ROS) generation, the activity of senescence associated ß-galactosidase (SA-ß-gal) and the protein expression of p16 and p21 in HUVECs, which were rescued by miR-20b-5p inhibitor. In general, our research indicated the important role of miR-20b-5p in HHcy-related endothelial cell senescence.

Adsorption and immobilization of soil lead by two phosphate-based biochars and phosphorus release risk assessment.

Phosphorus-based biochar can effectively immobilize lead (Pb) in soils, but the effects of soluble and insoluble phosphate on the remediation efficiency of Pb and phosphorus (P) release risks remain largely unknown. In this study, three biochars were produced from reed (Phragmites australis L.) straw, potassium dihydrogen phosphate (PDP, soluble) and hydroxyapatite (HAP, insoluble) modified reed straws and marked as BC, BCP, and BCH, respectively. Pb adsorptions and immobilizations by the three biochars and their P release risks were investigated. The P release kinetics of the three biochars were all fitted with the pseudo-second-order kinetic model and the P-release capacity followed the order of BCP > BCH > BC. The sorption isotherms of Pb2+ by three biochars were better described using the Langmuir model and the maximum adsorption capacities of BCP (59.3 mg/g) and BCH (58.8 mg/g) were higher than that of BC (48.1 mg/g). However, the P concentrations remained in BCP treated solution were significantly higher than those in BCH and BC under initial Pb2+ concentrations in the ranges of 5-25 mg/L. Soil pH and available P were increased with the increasing dosage of BCP and BCH, decreasing CaCl2-extractable Pb concentrations. BCH was more effective to decrease the exchangeable Pb and transform it into iron/manganese oxides and residual fractions. Compared to BC, BCH applications in the range of 2-5% can significantly increase labile P by 15.2-17.7%, but 21.0-33.6% for BCP, indicating BCP had a higher P release risk. The major implication is that HAP-modified biochar can effectively immobilize Pb and decrease P release risks compared to soluble P-modified biochar.

Relationship Between the Triglyceride Glucose Index and the Risk of First Stroke in Elderly Hypertensive Patients.

BACKGROUND: Several recent studies have shown the relationship between the triglyceride glucose (TyG) index and the risk of stroke in the general population and in a few patient cohorts; however, the role of the TyG index on stroke risk in elderly hypertensive patients has not been determined. Thus, we aimed to investigate the association of the TyG index with first stroke and first ischemic stroke in elderly individuals with hypertension. METHODS: We included 8487 elderly subjects with hypertension from the China H-type Hypertension Registry Study for the current analysis. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Outcomes were the first stroke and first ischemic stroke. RESULTS: During a median follow-up of 1.72 years, the first stroke was diagnosed in 82 patients (0.97%), and the first ischemic stroke was diagnosed in 48 patients (0.57%). Multivariable Cox proportional hazards models revealed that the TyG index was positively associated with the risk of first stroke (per 1-unit increment; HR: 1.72; 95% CI: 1.07, 2.76) and first ischemic stroke (HR: 2.31; 95% CI: 1.32, 4.05). When the TyG index was assessed as quartiles, significantly higher risks of first stroke (HR: 1.90; 95% CI: 1.04, 3.45) and first ischemic stroke (HR: 2.45; 95% CI: 1.16, 5.20) were found in participants in quartile 4 compared with those in quartiles 1-3. CONCLUSION: The TyG index is potentially useful in the early identification of elderly hypertensive patients at high risk of experiencing a first stroke.