Association between consumption of flavonol and its subclasses and chronic kidney disease in US adults: an analysis based on National Health and Nutrition Examination Survey data from 2007-2008, 2009-2010, and 2017-2018.

Background: There is little research on the relationship between flavonol consumption and chronic kidney disease (CKD). This study aimed to examine the link between flavonol consumption and the risk of CKD among US adults, using data from the 2007-2008, 2009-2010 and 2017-2018 National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional approach was used, drawing on data from three NHANES cycles. The flavonol consumption of the participants in this study was assessed using a 48 h dietary recall interview. CKD was diagnosed based on an estimated glomerular filtration rate below 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio of 30 mg/g or higher. Results: Compared to the lowest quartile of flavonol intake (Q1), the odds ratios for CKD were 0.598 (95% CI: 0.349, 1.023) for the second quartile (Q2), 0.679 (95% CI: 0.404, 1.142) for the third quartile (Q3), and 0.628 (95% CI: 0.395, 0.998) for the fourth quartile (Q4), with a p value for trend significance of 0.190. In addition, there was a significant trend in CKD risk with isorhamnetin intake, with the odds ratios for CKD decreasing to 0.860 (95% CI: 0.546, 1.354) in the second quartile, 0.778 (95% CI: 0.515, 1.177) in the third quartile, and 0.637 (95% CI: 0.515, 1.177) in the fourth quartile (p for trend = 0.013). Conclusion: Our analysis of the NHANES data spanning 2007-2008, 2009-2010, and 2017-2018 suggests that high consumption of dietary flavonol, especially isorhamnetin, might be linked to a lower risk of CKD in US adults. These findings offer new avenues for exploring strategies for managing CKD.

Combinative predictive effect of left ventricular mass index, ratio of HDL and CRP for progression of chronic kidney disease in non-dialysis patient.

PURPOSE: This current study scrutinized the association among left ventricular mass index (LVMI), ratio of high-density lipoprotein (HDL) and C-reactive protein (CRP), and renal function. Furthermore, we examined the predictive effects of left ventricular mass index and HDL/CRP on progression of non-dialysis chronic kidney disease. METHODS: We enrolled adult patients with chronic kidney disease (CKD) who were not receiving dialysis and obtained follow-up data on them. We extracted and compared data between different groups. To investigate the relationship between left ventricular mass index (LVMI), high-density lipoprotein (HDL)/C-reactive protein (CRP) levels, and CKD, we employed linear regression analysis, Kaplan-Meier analysis, and Cox proportional hazards regression analysis. RESULTS: Our study enrolled a total of 2351 patients. Compared with those in the non-progression group, subjects in the CKD progression group had lower ln(HDL/CRP) levels (- 1.56 ± 1.78 vs. - 1.14 ± 1.77, P < 0.001) but higher left ventricular mass index (LVMI) values (115.45 ± 29.8 vs. 102.8 ± 26.31 g/m2, P < 0.001). Moreover, after adjusting for demographic factors, ln(HDL/CRP) was found to be positively associated with estimated glomerular filtration rate (eGFR) (B = 1.18, P < 0.001), while LVMI was negatively associated with eGFR (B = - 0.15, P < 0.001). In the end, we found that both LVH (HR = 1.53, 95% CI 1.15 to 2.05, P = 0.004) and lower ln(HDL/CRP) (HR = 1.46, 95% CI 1.08 to 1.96, P = 0.013) independently predicted CKD progression. Notably, the combined predictive power of these variables was stronger than either variable alone (HR = 1.98, 95% CI 1.5 to 2.62, P < 0.001). CONCLUSION: Our study findings indicate that in pre-dialysis patients, both HDL/CRP and LVMI are associated with basic renal function and are independently correlated with CKD progression. These variables may serve as predictors for CKD progression, and their combined predictive power is stronger than that of either variable alone.

Metabolic implications of amino acid metabolites in chronic kidney disease progression: a metabolomics analysis using OPLS-DA and MBRole2.0 database.

BACKGROUND: As chronic kidney disease (CKD) progresses, metabolites undergo diverse transformations. Nevertheless, the impact of these metabolic changes on the etiology, progression, and prognosis of CKD remains uncertain. Our objective is to conduct a metabolomics analysis to scrutinize metabolites and identify significant metabolic pathways implicated in CKD progression, thereby pinpointing potential therapeutic targets for CKD management. METHODS: We recruited 145 patients with CKD and determined their mGFR by measuring the plasma iohexol clearance, whereupon we partitioned them into four groups based on their mGFR values. Non-targeted metabolomics analysis was conducted using UPLC-MS/MS assays. Differential metabolites were identified via one-way ANOVA, PCA, PLS-DA, and OPLS-DA analyses employing the MetaboAnalyst 5.0 platform. Ultimately, we performed differential metabolite pathway enrichment analysis, using both the MetaboAnalyst 5.0 platform and the MBRole2.0 database. RESULTS: According to the findings of the MBRole2.0 and MetaboAnalyst 5.0 enrichment analysis, six amino acid metabolism pathways were discovered to have significant roles in the progression of CKD, with the glycine, serine, and threonine metabolism pathway being the most prominent. The latter enriched 14 differential metabolites, of which six decreased while two increased concomitantly with renal function deterioration. CONCLUSIONS: The metabolic analysis unveiled that glycine, serine, and threonine metabolism plays a pivotal role in the progression of CKD. Specifically, glycine was found to increase while serine decreased with the deterioration of CKD.

Predictive Effect of System Inflammation Response Index for Progression of Chronic Kidney Disease in Non-Dialyzing Patient.

Purpose: Scant research has been conducted on the interplay between the systemic inflammation response index (SIRI) and chronic kidney disease (CKD). The present study endeavors to meticulously scrutinize the association between SIRI and renal function. Additionally, we aim to assess its efficacy in predicting the progression of CKD in non-dialysis patients. Patients and Methods: Adult patients with CKD who were not undergoing dialysis were enrolled, and follow-up data were obtained. Data from distinct groups were extracted and meticulously compared. A comprehensive analytical approach was adopted, including logistic regression analysis, Kaplan-Meier analysis, Cox proportional hazards regression analysis, and subgroup analysis. Results: Our study included 1420 patients, with a mean age of 61 ± 17 years, and 63% were male. 244 (17.2%) patients experienced the progression of CKD. As the level of ln(SIRI) increased, patients tended to be older, with a higher proportion of males, and increased prevalence rates of hypertension, stroke, heart failure, and progression of CKD. Additionally, the levels of baseline creatinine and C-reactive protein were elevated, while the levels of estimated glomerular filtration rate and hemoglobin decreased. Upon adjusting for demographic and biochemical variables, logistic regression analysis indicated that ln(SIRI) was independently associated with advanced CKD in pre-dialysis patients (OR=1.59, 95% CI: 1.29-1.95, P<0.001). Moreover, Cox proportional-hazard analysis revealed that ln(SIRI) independently predicted CKD progression (HR: 1.3, 95% CI: 1.07-1.59, P=0.009). Conducting a subgroup analysis, we observed significant interactions between ln(SIRI) levels and gender (p<0.001), age (p=0.046), and hypertension (p=0.028) in relation to the progression of CKD. Conclusion: Our study's findings demonstrate a significant association between SIRI and fundamental renal function, and independently establish a correlation between SIRI and the progression of CKD in pre-dialysis patients. These observations suggest that SIRI holds promise as a potential predictor for CKD progression.

Apolipoprotein B is associated with CT-angiographic progression beyond low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in patients with coronary artery disease.

BACKGROUND: Accumulating evidence indicated that apolipoprotein B (apoB) was the principal lipid determinant of coronary artery disease (CAD). Nevertheless, the connection between apoB and angiographic progression of CAD remained undetermined. METHODS: Five hundred and forty-four CAD patients with twice coronary computed tomography angiography experiences were enrolled. The Gensini scoring system was used to assess angiographic progression. Incident angiographic progression was defined as an annual change rate of the Gensini score of > 1 point. The predictive efficacy of baseline apoB levels for angiographic progression was assessed using a receiver operating characteristic (ROC) curve. For comparative purposes, patients were categorized into three groups according to their baseline apoB tertiles. Furthermore, discordance analyses defined by the median were performed to assess the superiority of apoB over lipoprotein cholesterol in predicting angiographic progression of CAD. RESULTS: Angiographic progression was observed in 184 patients (33.8%) during a follow-up period of 2.2-year. The area under the ROC curve was 0.565 (0.522-0.607, P = 0.013). The incidence of angiographic progression was elevated with increasing apoB tertile after adjusting for confounding factors [odds ratio (OR) for the medium apoB tertile: 1.92, 95% confidence interval (CI): 1.15-3.19, P = 0.012; OR for the high apoB tertile: 2.05, 95%CI:1.17-3.60, P = 0.013]. Additionally, discordance analyses showed that the higher apoB group had a significantly higher risk of CAD progression in the fully adjusted model (all P < 0.05). CONCLUSIONS: ApoB could be used as an accurate and comprehensive indicator of angiographic progression in patients with CAD.

Alirocumab effect on preventing periprocedural ischaemic events in coronary heart disease patients undergoing coronary stenting (APPEASE trial): study protocol of a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Percutaneous coronary intervention (PCI)-related myocardial infarction (type 4a MI) and major periprocedural myocardial injury have been demonstrated leading to poor prognosis of patients with coronary heart disease (CHD) undergoing elective PCI and still remain high occurrence even after the therapy of dual antiplatelet agents and statins. Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to be effectively in reducing the risk of acute MI (AMI). However, the effect of alirocumab on preventing PCI-related MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI remains uncertain. METHODS AND ANALYSIS: Alirocumab effect on Preventing Periprocedural ischaemic Events in coronary heart diseAse patients undergoing coronary StEnting trial is a multicentre, open-label, randomised controlled trial aiming to determine whether alirocumab could reduce the incidence of type 4a MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI. In total, 422 non-AMI CHD patients planned to undergo elective PCI will be randomly assigned to receive standard pharmacotherapy of CHD (control group) or additional use of subcutaneous alirocumab 75 mg 1 day before procedure (alirocumab group). The primary outcome is type 4a MI or major periprocedural myocardial injury defined as high-sensitivity cardiac troponin elevating above 5×99 th percentile upper reference limit in 48 hours after PCI. Patients will continue receiving standard pharmacotherapy or additional biweekly subcutaneous alirocumab 75 mg for 3 months according to the initial randomisation group. We will follow up for 3 months and record all the major adverse cardiovascular events (MACEs). Incidence of PCI-related MI or major periprocedural myocardial injury, and MACE in 3 months after PCI will be compared between control group and alirocumab group. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University with approval number: (2022)02-140-01. The results of this study will be reported through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200063191.

Novel Metabolites to Improve Glomerular Filtration Rate Estimation.

INTRODUCTION: The glomerular filtration rate (GFR) is crucial for chronic kidney disease (CKD) diagnosis and therapy. Various studies have sought to recognize ideal endogenous markers to improve the estimated GFR for clinical practice. To screen out potential novel metabolites related to GFR (mGFR) measurement in CKD patients from the Chinese population, we identified more biomarkers for improving GFR estimation. METHODS: Fifty-three CKD participants were recruited from the Third Affiliated Hospital of Sun Yat-sen University in 2020. For each participant, mGFR was evaluated by utilizing the plasma clearance of iohexol and collecting serum samples for untargeted metabolomics analyses by ultrahigh-performance liquid chromatography-tandem mass spectroscopy. All participants were divided into four groups according to mGFR. The metabolite peak area data were uploaded to MetaboAnalyst 5.0 for one-way analysis of variance, principal component analysis, and partial least squares-discriminant analysis and confirmed the metabolites whose levels increased or decreased with mGFR and variable importance in projection (VIP) values >1. Metabolites were ranked by correlation with the original values of mGFR, and metabolites with a correlation coefficient >0.8 and VIP >2 were identified. RESULTS: We screened out 198 metabolites that increased or decreased with mGFR decline. After ranking by correlation with mGFR, the top 50 metabolites were confirmed. Further studies confirmed the 10 most highly correlated metabolites. CONCLUSION: We screened out the metabolites that increased or decreased with mGFR decline in CKD patients from the Chinese population, and 10 of them were highly correlated. They are potential novel metabolites to improve GFR estimation.

Metabolic profiling identifies the significance of caffeine metabolism in CKD.

Background: With the development of chronic kidney disease (CKD), there are various changes in metabolites. However, the effect of these metabolites on the etiology, progression and prognosis of CKD remains unclear. Objective: We aimed to identify significant metabolic pathways in CKD progression by screening metabolites through metabolic profiling, thus identifying potential targets for CKD treatment. Methods: Clinical data were collected from 145 CKD participants. GFR (mGFR) was measured by the iohexol method and participants were divided into four groups according to their mGFR. Untargeted metabolomics analysis was performed via UPLC-MS/MSUPLC-MSMS/MS assays. Metabolomic data were analyzed by MetaboAnalyst 5.0, one-way ANOVA, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) to identify differential metabolites for further analysis. The open database sources of MBRole2.0, including KEGG and HMDB, were used to identify significant metabolic pathways in CKD progression. Results: Four metabolic pathways were classified as important in CKD progression, among which the most significant was caffeine metabolism. A total of 12 differential metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of the CKD stage, and two of which increased with the deterioration of the CKD stage. Of the four decreased metabolites, the most important was caffeine. Conclusion: Caffeine metabolism appears to be the most important pathway in the progression of CKD as identified by metabolic profiling. Caffeine is the most important metabolite that decreases with the deterioration of the CKD stage.

Association between recovery/occurrence of metabolic syndrome and rapid estimated glomerular filtration rate decline in middle-aged and older populations: evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVES: Few studies have explored correlations between metabolic syndrome (MetS) alterations and renal deterioration in longitudinal cohorts. We aim to investigate associations between MetS recovery/development and rapid estimated glomerular filtration rate (eGFR) decline in the China Health and Retirement Longitudinal Study (CHARLS). DESIGN: Longitudinal cohort study. SETTING: This study is a secondary analysis of CHARLS. PARTICIPANTS: After excluding individuals with age <45 years old, eGFR <60 mL/min/1.73 m2 and clinician-reported malignant tumour, heart disease, stroke or kidney disease at baseline, 4142 participants with complete data were selected from the CHARLS during the 4-year follow-up period (2011-2015). OUTCOME MEASURES: MetS were measured at 2011 and 2015 in CHARLS. A rapid eGFR decline was defined as an average annual eGFR decline of >3 mL/min/1.73 m2. The associations between rapid eGFR decline and MetS recovery/development were analysed using multivariable adjusted logistic models. RESULTS: According to MetS baseline status and follow-up, participants were divided into four groups: (1) 2460 (59.4%) in the MetS-free group, (2) 361 (8.7%) in the MetS-developed group, (3) 499 (12.0%) in the MetS recovery group and (4) 822 (19.8%) in the MetS chronic group. When compared with the MetS chronic group, the multivariable adjusted OR of rapid eGFR decline in the MetS recovery group was 0.64 (OR: 0.64; 95% CI 0.45 to 0.90, p=0.01). In contrast, when compared with the MetS-free group, the multivariable adjusted OR of rapid eGFR decline in the MetS-developed group was 1.00 (OR: 1.00; 95% CI 0.73 to 1.38, p=0.98). CONCLUSIONS: Over the 4-year follow-up period, we found that MetS recovery was associated with a reduced risk of rapid eGFR decline in middle-aged and older adults, while MetS occurrence was not related to rapid eGFR decline. Recovery from MetS appeared to protect against a rapid decline in eGFR.

lncRNA NBR2 attenuates angiotensin II-induced myocardial hypertrophy through repressing ER stress via activating LKB1/AMPK/Sirt1 pathway.

Myocardial hypertrophy leads to heart failure (HF), and emerging researchers have illustrated that long noncoding RNAs (lncRNAs) modulate myocardial hypertrophy. Here, we explored the role and mechanism of a novel lncRNA, NBR2, in modulating angiotensin II (Ang II)-induced myocardial hypertrophy. First, we examined plasma NBR2 levels in 25 patients with HF and myocardial hypertrophy and ten healthy donors and analyzed the correlation between NBR2 profiles and patients' clinical indicators. In addition, the overexpression experiment of NBR2 was carried out to probe the influence of NBR2 on myocardial hypertrophy. lncRNA NBR2 was down-regulated in plasma of patients with HF and myocardial hypertrophy (vs. healthy controls), and its level was negatively correlated with cardiac function (represented by left ventricular end-diastolic diameter and left ventricular ejection fraction) and degree of myocardial hypertrophy. Besides, Ang II treatment intensified the hypertrophy of human myocardial cell lines (HCM and AC16) and curbed the NBR2 expression. Overexpressing lncRNA NBR2 alleviated Angiotension II-induced myocardial hypertrophy and declined the profiles of hypertrophic markers. Moreover, up-regulating lncRNA NBR2 weakened Ang II-mediated endoplasmic reticulum (ER) stress and activated the LKB1/AMPK/Sirt1 pathway. Interfering with the LKB1/AMPK/Sirt1 axis abated the lncRNA NBR2-mediated inhibitory effect on myocardial hypertrophy and ER stress. This study confirmed that lncRNA NBR2 dampened myocardial hypertrophy and ER stress by modulating the LKB1/AMPK/Sirt1 pathway. Our study provides the first evidence that lncRNA NBR2 is positively associated with myocardial hypertrophy.

Association of serum sclerostin and osteoprotegerin levels with the presence, severity and prognosis in patients with acute myocardial infarction.

BACKGROUND: Bone-related proteins (such as sclerostin and osteoprotegerin [OPG]) are involved in the development of atherosclerosis. However, the relationship between bone-related proteins and acute myocardial infarction (AMI) has not been extensively evaluated. The purpose of this study was to assess the association of serum sclerostin and OPG with the presence, severity and prognosis in patients with AMI. METHODS: This study prospectively enrolled 152 patients attacked by acute chest pain. Serum sclerostin and OPG were detected within the first 24 h after AMI diagnosis by ELISA kits. The AMI predictive efficacy of sclerostin and OPG were analyzed by receiver operating characteristics (ROC) curve. Univariable and multivariable linear regression analyses were performed to determine the association between bone-related proteins and scores indicating the severity of coronary artery occlusion. Moreover, prognostic values were assessed by Kaplan-Meier curves and Cox regression analysis. RESULTS: There were 92 patients in AMI group, 60 in non-AMI group. Serum levels of sclerostin and OPG were significantly higher in AMI group than in non-AMI group (all p < 0.001), which showed predictive value for the presence of AMI (all p < 0.001). The area under the ROC curve values of sclerostin and OPG were 0.744 and 0.897, respectively. A multivariable linear regression analysis demonstrated that Ln-transformed sclerostin (ß = 0.288, p = 0.009) and Ln-transformed OPG (Ln-OPG: ß = 0.295, p = 0.019) levels were associated with GENISINI score, independently of conventional clinical parameters. In addition, Ln-OPG levels were still positively associated with GRACE score after adjustments (ß = 0.320, p = 0.001). During a 1-year follow-up, patients above the median of sclerostin levels had higher incidence of major adverse cardiac events (MACE) than those below the median (p = 0.028). It was also observed that the MACE rates were higher in patients above the median of OPG levels, though no statistic importance (p = 0.060). After adjusting conventional risk factors by multivariate Cox regression, Ln-OPG was associated with incident MACE (hazard ratio = 2.188 [95% confidence intervals 1.102-4.344], p = 0.025). CONCLUSIONS: Bone-related proteins could exert a potential role in early risk stratification and prognosis assessment in patients with AMI.

Association of Atherogenic Index of Plasma With Angiographic Progression in Patients With Suspected Coronary Artery Disease.

The present study aimed to explore the correlation of atherogenic index of plasma (AIP) with angiographic progression of coronary artery disease (CAD). AIP was defined as the base 10 logarithm of the ratio of the triglyceride to high-density lipoprotein cholesterol concentration. The extent of coronary lesion was assessed by the Gensini Score (GS) system and angiographic progression was defined as the GS rate of change per year >1 point. A total of 896 patients with suspected CAD who underwent coronary computed tomography angiography twice at intervals of >6 months were included. Baseline AIP was positively correlated with remnant cholesterol (r = .644, P < .001). When patients were assigned into four groups according to baseline AIP quartiles, the incidence of CAD progression significantly increased across the quartiles of AIP (Q1 [lowest]: 23.7 vs Q2: 29.9 vs Q3: 33.9 vs Q4 [highest]: 34.8%; P = .042). After multivariate adjustment, the odds ratio for CAD progression was 1.89 when comparing the highest to the lowest quartile of AIP (95% confidence interval: 1.18-3.02; P = .008). Therefore, AIP was independently correlated with angiographic progression of CAD beyond conventional risk factors, suggesting that AIP may play a role in early risk stratification as a simple surrogate of residual risk.

COVID-19 in a young man with hypertension: A case study of missed opportunities in intensive progression.

We report the case of a young patient diagnosed with coronavirus disease 2019 with a history of hypertension. The patient improved after antiviral treatment but eventually developed severe respiratory distress syndrome and cardiac insufficiency. His respiratory secretions were tested for nucleic acids and returned negative twice. Computed tomography imaging of the patient showed evidence of viral pneumonia on the 11th day of onset and continued to worsen. The patient was finally intubated and transferred to a higher-level care centre for further treatment. We were very focused on infectious disease protection throughout the treatment, however, suboptimal treatment was provided due to the switch in antihypertensive medication, lack of early nutritional support and fluid restriction management.

Predictive value of P wave terminal force in lead V1 for atrial fibrillation: A meta-analysis.

BACKGROUND: Several studies have explored the association between P wave terminal force in lead V1 (PTFV1) and risk of atrial fibrillation (AF) occurrence, but the results were controversial. This meta-analysis aimed to examine whether abnormal PTFV1 could predict AF occurrence. METHODS: We searched PubMed, Embase, and Cochrane Library databases for articles published before August 25, 2018. Pooled odds ratios (ORs) of AF occurrence were calculated using random-effects models to explore the significance of PTFV1. RESULTS: A total of 12 studies examining 51,372 participants were included, with 9 studies analyzing PTFV1 as a categorical variable and 4 studies analyzing PTFV1 as a continuous variable. As a categorical variable, abnormal PTFV1 (>0.04 mm s) was significantly associated with AF occurrence with a pooled OR of 1.39 (95% confidence interval [CI] 1.08-1.79, p = .01). Subgroup analysis found that ORs of studies in hemodialysis patients (OR = 4.89, 95% CI 2.54-9.90, p < .001) and acute ischemic stroke patients (OR = 1.60, 95% CI 1.14-2.25, p = .007) were higher than general population (OR = 1.15, 95% CI 1.03-1.29, p = .01). Studies from Europe (OR = 1.05, 95% CI 0.91-1.20, p = .51) yielded lower OR of endpoints compared with Asia (OR = 1.89, 95% CI 1.38-2.60, p < .001) and United States (OR = 1.43, 95% CI 1.19-1.72, p < .001). As a continuous variable, PTFV1 was also significantly associated with AF occurrence with a polled OR per 1 standard deviation (SD) change of 1.27 (95% CI 1.02-1.59, p = .03). CONCLUSIONS: PTFV1 was significantly associated with the risk of AF and was considered to be a good predictor of AF occurrence in population with or without cardiovascular diseases.

The protective effects of orexin a against high glucose-induced activation of NLRP3 inflammasome in human vascular endothelial cells.

Vascular disease is one of the most significant threats to the lives of patients suffering from diabetes, and chronic exposure of vascular endothelial cells to high glucose has been shown to significantly contribute to the process of endothelial cell dysfunction, one of the earliest events in diabetes-associated vascular disease. Nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in initiating the inflammatory process by facilitating the production of interleukin-1ß (IL-1ß) and IL-18. ASC and caspase 1 are also implicated in NLRP3 inflammasome-mediated chronic inflammation. While under normal conditions, a balance exists between oxidants and antioxidants, exposure to high glucose significantly increases the production of ROS, which is enhanced by NOX4 expression. In the present study, we explored the role of orexin A, an endogenous peptide produced in the hypothalamus, in high glucose-induced activation of the NLRP3 inflammasome, oxidative stress, and expression of several key cytokines. Our findings demonstrate that orexin A exerts potent antioxidant effects in human aortic endothelial cells exposed to high glucose by inhibiting mitochondrial ROS and expression of NOX4 at both the mRNA and protein levels as revealed by MitoSOX staining, real-time PCR, and Western blot analysis. We also show that orexin A inhibits high glucose-induced expression of TxNIP, which is crucial to the activation of the NLRP3 inflammasome, as well as that of HMGB1. We confirmed via real-time PCR and Western blot analysis that orexin A suppressed the production of the inflammatory cytokines IL-1ß and IL-18. Additionally, through SIRT1 knockdown siRNA experimentation, we confirmed that SIRT1 knockdown abolishes the effects of orexin A described above, thereby indicating a critical role of SIRT in the capacity of orexin A to ameliorate high glucose-induced oxidative stress and activation of NLRP3 inflammasome.

Protective effects of salidroside on chronic heart failure in rats and the underlying mechanisms

The present study aimed to investigate the protective effects of salidroside on chronic heart failure (CHF) in rats and to explore the underlying mechanisms. One hundred SD rats were randomly divided into sham-operated, model, and low-, medium- and high-dose salidroside groups. The CHF model was established in later 4 groups. The later 3 groups were intragastrically administrated with 6, 12 and 24 mg/kg salidroside, respectively, once a day, for continuous 4 weeks. Finally, the serum levels of brain natriuretic peptide (BNP) and interleukin 6 (IL-6), cardiac function indexes, and expression levels of myocardial cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein were determined. Results showed that, after treatment, compared with model group, in high-dose salidroside group the heart function indexes were significantly improved (P < 0.05), the serum levels of BNP and IL-6 were significantly decreased (P < 0.05), the expression levels of myocardial Caspase-3, Caspase-9 and MMP-1 protein were significantly decreased (P < 0.05), and the expression level of TIMP-1 protein was significantly increased (P < 0.05). In conclusion, salidroside has obvious protective effects on CHF in rats. The mechanisms may be related to its regulation of cardiomyocyte apoptosis and ventricular remodelingregulation related protein expressions

Recombinant human brain natriuretic peptide regulates PI3K/AKT/mTOR pathway through lncRNA EGOT to attenuate hypoxia-induced injury in H9c2 cardiomyocytes.

This study aimed to investigate whether recombinant human brain natriuretic peptide (rhBNP) regulated hypoxia-induced injury in H9c2 cardiomyocytes through lncRNA EGOT. H9c2 cardiomyocytes were cultured under normoxia and hypoxia (21% and 3% O2) conditions, and whether hypoxia induced injury by assessing cell viability, apoptosis and autophagy. H9c2 cells were then treated with different doses of exogenous rhBNP (200, 600 and 900 nmol/L, respectively) and the effects of rhBNP on hypoxia-induced injury in H9c2 cells as well as the expression of EGOT were studied. In addition, the regulatory relationships between rhBNP and EGOT as well as between rhBNP and PI3K/AKT/mTOR pathway in hypoxia-treated H9c2 cells were investigated. Hypoxia significantly induced injury in H9c2 cells (inhibited cell viability and promoted cell apoptosis and autophagy) and decreased the expression of EGOT. However, administration of rhBNP alleviated hypoxia-induced injury in H9c2 cells and elevated expression of EGOT. Suppression of EGOT significantly reversed the effects of rhBNP on hypoxia-induced injury in H9c2 cells. Further studies showed that the effects of EGOT on cell viability and apoptosis were by positively regulating the expression of Cyclin D1. Moreover, rhBNP alleviated hypoxia-induced cell injury by activating PI3K/AKT/mTOR pathway in H9c2 cells. Our results reveal that rhBNP may play a protective role in attenuating hypoxia-induced injury in H9c2 cardiomyocytes via regulating lncRNA EGOT/Cyclin D1/PI3K/AKT/mTOR pathway axis. The findings will provide a new strategy for the treatment of heart failure induced by hypoxia.

Long noncoding RNA SRA1 attenuates hypoxia-induced injury in H9c2 cardiomyocytes through regulating PPARγ/NF-κB signaling pathway.

This study aimed to investigate the effects and mechanisms of long noncoding RNA SRA1 on regulating hypoxia-induced injury in H9c2 cardiomyocytes. The H9c2 cardiomyocytes were cultured under hypoxic (3% O2) conditions and whether hypoxia induced injury was assessed by detecting cell viability, apoptosis and autophagy. Then, SRA1 was overexpressed and suppressed in H9c2 cardiomyocytes by transfection with pc-SRA1 and sh-SRA1, and the effects of SRA1 dysregulation on cell viability, apoptosis, and autophagy of H9c2 cardiomyocytes under hypoxia condition were detected. Furthermore, the regulatory relationship between SRA1 and PPARγ was explored, as well as the association between SRA1 and NF-κB signaling. Hypoxia induced injury to H9c2 cardiomyocytes, such as inhibiting cell viability, and promoting cell apoptosis and autophagy. Moreover, hypoxia resulted in a decreased expression of SRA1 in H9c2 cardiomyocytes, and overexpression of SRA1 alleviated hypoxia-induced injury, while suppression of SRA1 indicated the contrary results. Further studies showed that SRA1 positively regulated PPARγ. Overexpression of SRA1 alleviated hypoxia injury by activating PPARγ. Besides, suppression of SRA1 activated NF-κB pathway in hypoxia-treated H9c2 cardiomyocytes, which were significantly reversed after suppression of SRA1 and overexpression of PPARγ at the same time. Our findings indicated that suppression of SRA1 may aggravate hypoxia-induced injury to H9c2 cardiomyocytes by positive regulation of PPARγ and activation of NF-κB pathway. SRA1 may serve as a promising perspective for the therapy of heart failure induced by hypoxia.