The impact of exercise on the gut microbiota in middle-aged amateur serious runners: a comparative study.

Introduction: Exercise, health, and the gut microbiota (GM) are strongly correlated. Research indicates that professional athletes, especially ultra-marathon runners, have unique GM characteristics. However, more research has focused on elite athletes, with little attention given to amateur sports enthusiasts, especially those in the middle-aged population. Therefore, this study focuses on the impact of long-term running on the composition and potential functions of the GM in middle-aged individuals. Methods: We compared the GM of 25 middle-aged serious runnerswith 22 sedentary healthy controls who had minimal exercise habitsusing 16S rRNA gene sequencing. Additionally, we assessed dietary habits using a food frequency questionnaire. Results and Discussion: Statistical analysis indicates that there is no significant difference in dietary patterns between the control group and serious runners. Diversity analysis results indicate that there is no significant difference in α diversity between the two groups of GM, but there is a significant difference in ß diversity. Analysis of the composition of GM reveals that Ruminococcus and Coprococcus are significantly enriched in serious runners, whereas Bacteroides, Lachnoclostridium, and Lachnospira are enriched in the control group. Differential analysis of functional pathway prediction results reveals significant differences in the functional metabolism levels of GM between serious runners and the control group. Further correlation analysis results indicate that this difference may be closely related to variations in GM. In conclusion, our results suggest that long-term exercise can lead to changes in the composition of the GM. These changes have the potential to impact the overall health of the individual by influencing metabolic regulation.

Structural characteristics of gut microbiota in longevity from Changshou town, Hubei, China.

The gut microbiota (GM) and its potential functions play a crucial role in maintaining host health and longevity. The aim of this study was to investigate the potential relationship between GM and longevity. We collected fecal samples from 92 healthy volunteers (middle-aged and elderly: 43-79 years old; longevity: ≥ 90 years old) from Changshou Town, Zhongxiang City, Hubei, China. In addition, we collected samples from 30 healthy middle-aged and elderly controls (aged 51-70 years) from Wuhan, Hubei. The 16S rDNA V3 + V4 region of the fecal samples was sequenced using high-throughput sequencing technology. Diversity analysis results showed that the elderly group with longevity and the elderly group with low body mass index (BMI) exhibited higher α diversity. However, no significant difference was observed in ß diversity. The results of the microbiome composition indicate that Firmicutes, Proteobacteria, and Bacteroidota are the core phyla in all groups. Compared to younger elderly individuals, Akkermansia and Lactobacillus are significantly enriched in the long-lived elderly group, while Megamonas is significantly reduced. In addition, a high abundance of Akkermansia is a significant characteristic of elderly populations with low BMI values. Furthermore, the functional prediction results showed that the elderly longevity group had higher abilities in short-chain fatty acid metabolism, amino acid metabolism, and xenobiotic biodegradation. Taken together, our study provides characteristic information on GM in the long-lived elderly population in Changshou Town. This study can serve as a valuable addition to the current research on age-related GM. KEY POINTS: • The gut microbiota of elderly individuals with longevity and low BMI exhibit higher alpha diversity • Gut microbiota diversity did not differ significantly between genders in the elderly population • Several potentially beneficial bacteria (e.g., Akkermansia and Lactobacillus) are enriched in long-lived individuals.

Analysis of differentially expressed lncRNAs and mRNAs associated with slow­transit constipation.

Slow transit constipation (STC) is a refractory gastrointestinal disease, accounting for approximately 13 âˆ¼ 37 % of chronic constipation. However, the molecular mechanism of STC remains poorly understood. Herein, this study aims to identify the key mRNAs and lncRNAs associated with STC. To this end, we performed high-throughput RNA sequencing to identify differentially expressed (DE) mRNAs and lncRNAs in the whole-layer sigmoid intestinal tissues from 4 STC patients and 4 non-STC patients. The identified DE lncRNAs and mRNAs were validated through quantitative real-time PCR. Weighted gene co-expression network analysis (WGCNA) and Pearson correlation analysis were conducted to determine the significantly correlated DE mRNA-lncRNA pairs. A total of 1420 DE lncRNAs and 1634 DE mRNAs were identified. Kyoto Encyclopedia of Genes and Genomes analysis of DE mRNAs indicated that these DE mRNAs might be associated with systemic lupus erythematosus, alcoholism, intestinal immune network for IgA production, inflammatory bowel disease, NF-kappa B signaling pathway. WGCNA and Pearson correlation analyses jointly identified 16,577 significantly correlated DE mRNA-lncRNA pairs. Furthermore, lncRNAs LINC00641, LINC02268, LINC03013 were identified as hub lncRNAs. The protein-protein interaction (PPI) network of proteins encoded by DE mRNAs was established, and PPI-based analysis revealed that Interleukin 2(IL2), CD80 molecule (CD80), interleukin-17A (IL-17A) might play significant roles in the development of STC. This study analyzes the expression profiles of lncRNAs and mRNAs associated with STC. Our findings will contribute to further understanding of the molecular mechanism of STC and provide potential diagnostic or therapeutic biomarkers for STC.

Donepezil Reduces H2O2-Inflicted Oxidative Stress and Necroptosis in Cardiomyocytes.

OBJECTIVE: Necroptosis, as a form of regulated cell necrosis, could participate in myocardial oxidative damage. We investigated whether donepezil attenuates H2O2-induced oxidative stress injury and necroptosis in rat cardiomyocytes. METHODS: H9c2 cells were incubated with H2O2 (final concentration of 1 mM) and then intervened with donepezil at doses of 2.5 and 10 µM. Subsequently, the necroptosis inhibitor necrostatin-1 (Nec-1) was introduced to treat H9c2 cells. For cell function experiments, cell proliferation; the contents of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA); the protein and mRNA levels of the necroptosis-related proteins receptor-interacting serine-threonine kinase 3 (RIP3) and mixed lineage kinase-like (MLKL); and calcium ion fluorescence intensity were detected using Cell Counting Kit-8, enzyme-linked immunosorbent assay (ELISA), Western blotting, quantitative reverse transcription polymerase chain reaction, and flow cytometry, respectively. RESULTS: Cell viability was conspicuously decreased; CK and LDH contents, RIP3 and MLKL expression levels, and MDA production were preeminently elevated; and the production of SOD, CAT, and GSH was prominently reduced under H2O2 stimulation, which were dose-dependently countered by donepezil intervention. Nec-1 decreased the cell necroptosis, oxidative stress, and calcium overload caused by H2O2. However, on the premise of donepezil intervention, the addition of Nec-1 failed to further improve the situation, suggesting that donepezil exerts cardioprotective effects partly by inhibiting RIP3 and MLKL levels. CONCLUSION: Donepezil reduced H2O2-inflicted oxidative stress and necroptosis in cardiomyocytes by suppressing RIP3 and MLKL levels and calcium ion overload.

LACC1 contributes to inflammation and cognitive disorder after stroke via the AMPK/NLRP3 pathway.

The current study aimed to investigate the effects of LACC1 on cognitive disorder due to stroke, as well as its underlying mechanism. LACC1 promoted inflammation and aggravated cognitive impairment in a mouse model of stroke. In an in vitro model of stroke, inhibition of LACC1 reduced inflammation and ROS­induced oxidative stress by activating AMP­activated protein kinase (AMPK) expression and suppressing NLPR3 expression. Furthermore, our studies revealed that inhibition of AMPK activity reduced the effects of si­LACC1 on cognitive disorder in mice after stroke via the AMPK/NLPR3 pathway. AMPK activation also reduced the effects of LACC1 on inflammation and ROS­induced oxidative stress via the NLPR3 pathway in the in vitro model that we evaluated. Our study suggests that LACC1­aggravated inflammation causes cognitive impairment after stroke via the AMPK/NLRP3 pathway, which may provide a new therapeutic target for stroke and other neurological diseases and their associated complications. In sum, we identified an important role and regulatory mechanism for LACC1 in maintaining stroke­induced cognitive disorder via the AMPK/NLRP3 pathway.

Restoration of Cullin3 gene expression enhances the improved effects of sonic hedgehog signaling activation for hypertension and attenuates the dysfunction of vascular smooth muscle cells.

BACKGROUND: Hypertension is known as a major factor for global mortality. We aimed to investigate the role of Cullin3 (CUL3) in the regulation of hypertension. MATERIAL AND METHODS: Human vascular smooth muscle cells (VSMCs) were treated with Angiotensin II (Ang II) to establish a hypertension in vitro model. Cell viability was detected by a cell counting kit-8 (CCK-8) assay. The content of reactive oxygen species (ROS) was evaluated by kit. Transwell assay and TUNEL staining were, respectively, used to assess cell migration and apoptosis. Additionally, the expression of sonic hedgehog (SHH) signaling-related proteins (SHH, smoothened homolog (Smo) and glioblastoma (Gli)) and CUL3 was tested with western blotting. Following treatment with Cyclopamine (Cycl), an inhibitor of SHH signaling, in Ang II-induced VSMCs, cell viability, migration, apoptosis and ROS content were determined again. Then, VSMCs were transfected with CUL3 plasmid or/and treated with sonic hedgehog signaling agonist (SAG) to explore the impacts on Ang II-induced VSMCs damage. In vivo, a hypertensive mouse model was established. Systolic blood pressure and diastolic blood pressure were determined. The histopathologic changes of abdominal aortic tissues were examined using H&E staining. The expression of SHH, Smo, Gli and CUL3 was tested with western blotting. RESULTS: Significantly increased proliferation, migration and apoptosis of VSMCs were observed after Ang II exposure. Moreover, Ang II induced upregulated SHH, Smo and Gli expression, whereas limited increase in CUL3 expression was observed. The content of ROS in Ang II-stimulated VSMCs presented the same results. Following Cycl treatment, the high levels of proliferation and migration in Ang II-treated VSMCs were notably remedied while the apoptosis and ROS concentration were further increased. Moreover, Cycl downregulated SHH, Smo, Gli and CUL3 expression. Above-mentioned changes caused by Ang II were reversed following SAG addition. Indeed, SAG treatment combined with restoration of CUL3 expression inhibited proliferation, migration, apoptosis and ROS level in Ang II-stimulated VSMCs. In vivo, SAG aggravated the histopathological changes of the aorta and with a worse tendency after both SAG intervention and CUL3 silencing. By contrast, SAG treatment and rebound in CUL3 expression alleviated the vascular damage. CONCLUSIONS: Collectively, restoration of CUL3 gene expression protected against hypertension through enhancing the effects of SHH activation in inhibition of apoptosis and oxidative stress for hypertension and alleviating the dysfunction of VSMCs.

Association of lipoprotein (a) and 1 year prognosis in patients with heart failure with reduced ejection fraction.

AIM: Current study was to evaluate relationship between baseline serum lipoprotein (a) [Lp(a)] level and prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and to explore whether the relationship would be modified by baseline high-sensitivity C-reactive protein (Hs-CRP) level. METHODS AND RESULTS: This is an observational prospective study. HFrEF patients from outpatient clinic were consecutively recruited (n = 362). Based on Lp(a) cutoff (30 mg/dL), patients were divided into normal and high Lp(a) groups; and based on Hs-CRP cutoff (3 mg/dL), patients were divided into low-degree and high-degree groups. The 1 year rate of HF rehospitalization was similar between these two groups (22.7% vs. 24.1%, P = 0.18), while the 1 year rate of cardiovascular mortality was higher in Lp(a) ≥ 30 mg/dL versus Lp(a) < 30 mg/dL groups (20.3% vs. 13.3%, P = 0.009), as was composite endpoint (44.4% vs. 36.0%, P < 0.001). After adjusting for covariates, elevated Lp(a) level remained associated with a higher risk of cardiovascular mortality [hazard ratio (HR) 1.22 and 95% confidence interval (CI) 1.04-1.64, P = 0.02] and composite endpoint (HR 1.38 and 95% CI 1.16-2.01, P = 0.006). In Hs-CRP ≥ 3 mg/dL group, elevated Lp(a) level was associated with HF rehospitalization, cardiovascular mortality, and composite endpoint, which was not observed in Hs-CRP < 3 mg/dL group. The association was greater for cardiovascular mortality (P-interaction = 0.04) and composite endpoint (P-interaction = 0.02) in Hs-CRP ≥ 3 mg/dL versus Hs-CRP < 3 mg/dL groups. CONCLUSION: Elevated Lp(a) level is associated with higher risk of cardiovascular mortality in HFrEF patients, which might be due to enhanced systemic inflammation.

Functional analysis of ceRNA network of lncRNA TSIX/miR-34a-5p/RBP2 in acute myocardial infarction based on GEO database.

The identification of innovative gene biomarkers with clinical efficacy is warranted for the treatment of acute myocardial infarction (AMI). The current study sought to screen potential target genes in AMI via bioinformatic analysis and analyze their effects on cardiomyocyte apoptosis. The differentially expressed long non-coding RNAs (lncRNAs) of AMI were screened, and the downstream microRNAs (miRNAs) and mRNAs of lncRNA antisense for X-inactive-specific transcript (lncRNA TSIX) were predicted accordingly. The diagnostic relationship between the 12 differentially expressed lncRNAs and AMI was analyzed by receiver operating characteristic (ROC). Next, the expressions of 12 lncRNAs, including miR-34a-5p and retinol binding protein 2 (RBP2) were all detected. The targeting relationships of miR-34a-5p with lncRNA TSIX and RBP2 were verified. AMI model was established and treated with Ad-TSIX and/or agomiR-34a-5p to evaluate the cardiac function and cardiomyocyte apoptosis of AMI mice. LncRNA TSIX was identified as the most differentially expressed lncRNA in AMI. Our findings revealed that LncRNA TSIX could function as an AMI diagnostic marker. LncRNA TSIX could target miR-34a-5p and miR-34a-5p could target RBP2. Upregulation of lncRNA TSIX could ameliorate cardiac injury inflicted by AMI and mitigate cardiomyocyte apoptosis. Upregulation of miR-34a-5p reversed the effect of lncRNA TSIX overexpression to ameliorate cardiomyocyte apoptosis in AMI mice. Overall, the overexpression of lncRNA TSIX inhibits cardiomyocyte apoptosis by competing with RBP2 to bind to miR-34a-5p and promoting RBP2.

Sex-specific cardiac and vascular responses to hypertension in Chinese populations without overt cardiovascular diseases.

OBJECTIVE: The aim of current study was to evaluate sex-specific cardiac and vascular responses to hypertension in Chinese populations without overt cardiovascular disease. METHODS: This was a cross-sectional study and participants were enrolled in outpatient clinic between January 2017 and December 2019. Transthoracic echocardiographic measurements were performed to evaluate cardiac and vascular structure and function. RESULTS: Among 486 participants, women account for 36.2% (n = 176). Compared to men, women were younger, had shorter duration of hypertension, and more likely to be abdominal obesity. Mean systolic and diastolic blood pressure (SBP and DBP) were similar, but women had higher mean pulse pressure (PP) than men. After adjustment for covariates, women had higher E/e' ratio and arterial elastance (Ea). The proportion of patients with concentric remodeling was higher in women (14.7% vs 9.5%). Increased SBP was associated with relative wall thickness (RWT), stroke volume (SV) index, E/e' ratio and Ea in both women and men, and the magnitude of the association between SBP and E/e' ratio was greater in women than in men (Pinteraction = 0.04). Increased DBP was associated with RWT and Ea in both women and men with similar magnitude. Increased PP was associated with RWT, E/e' ratio and Ea in both women and men, and the magnitude of the association between PP and Ea was greater in women than in men (Pinteraction = 0.03). CONCLUSION: In conclusion, the current study indicates cardiac and vascular responses to hypertension are greater in women than in men, manifesting as an increased estimated LV filling pressure and arterial elastance in women.

miR-20a/Foxj2 Axis Mediates Growth and Metastasis of Colorectal Cancer Cells as Identified by Integrated Analysis.

BACKGROUND MicroRNAs (miRNAs) have a significant regulatory effect on the proliferation, migration, and invasion of cells, and have been widely reported to have oncogenic or tumor-suppressive impacts on various tumors. In the present study we assessed the regulation and function of miR-20a on colorectal cancer (CRC) cell lines. MATERIAL AND METHODS qPCR was used to quantify miR-20a expression. Luciferase reporter assay was conducted to confirm Foxj2 3'UTR associations. In addition, the function of miR-20a and Foxj2 in CRC was detected using MTT, colony formation, transwell assays, and cell cycle analysis. RESULTS Our data revealed that miR-20a expression was elevated in the CRC cell lines, and cell migration, proliferation, and invasion abilities were promoted by the overexpression of miR-20a. Moreover, Foxj2 was authenticated as a direct target gene of miR-20a in CRC cells. Furthermore, we found that the ectopic Foxj2 dramatically suppressed miR-20a-promoted proliferation, migration, invasion, and xenografts in vitro and in vivo, and induced cell cycle arrest at G1 stage. CONCLUSIONS Our results showing the roles of miR-20a/Foxj2 in carcinogenesis of CRC may help improve treatment of CRC.

Early Right Ventricular Apical Pacing-Induced Gene Expression Alterations Are Associated with Deterioration of Left Ventricular Systolic Function.

The chronic high-dose right ventricular apical (RVA) pacing may have deleterious effects on left ventricular (LV) systolic function. We hypothesized that the expression changes of genes regulating cardiomyocyte energy metabolism and contractility were associated with deterioration of LV function in patients who underwent chronic RVA pacing. Sixty patients with complete atrioventricular block and preserved ejection fraction (EF) who underwent pacemaker implantation were randomly assigned to either RVA pacing (n = 30) group or right ventricular outflow tract (RVOT) pacing (n = 30) group. The mRNA levels of OPA1 and SERCA2a were significantly lower in the RVA pacing group at 1 month's follow-up (both p < 0.001). Early changes in the expression of selected genes OPA1 and SERCA2a were associated with deterioration in global longitudinal strain (GLS) that became apparent months later (p = 0.002 and p = 0.026, resp.) The altered expressions of genes that regulate cardiomyocyte energy metabolism and contractility measured in the peripheral blood at one month following pacemaker implantation were associated with subsequent deterioration in LV dyssynchrony and function in patients with preserved LVEF, who underwent RVA pacing.

NLRC5 deficiency promotes myocardial damage induced by high fat diet in mice through activating TLR4/NF-κB.

The metabolic syndrome could be induced by high fat diet, leading to cardiovascular diseases, such as myocardial damage. Inflammation response and oxidative stress have been reported to be involved in high fat-induced heart injury, and the molecular mechanism is not fully understood. The NOD-like protein family member, NLRC5, could interact with IKKα to inhibit IKK complex activation. In our study, high fat diet-feeding mice showed cardiac fibrosis, inflammation and oxidative stress through collagen accumulation, TLR4/NF-κB and MAPKs signaling pathways activation. NLRC5 knockout mice fed with high fat showed accelerated fibrosis and inflammation response by promoting α-SMA, Collagen I, Collagen III, TLR4/MyD88, phosphorylated IKKα, IκBα and NF-κB expression. And no effect on oxidative stress was observed in wild type and NLRC5-deficiency samples in in vivo studies. Moreover, NLRC5-knockout and -knockdown cardiac muscle cells challenged with LPS also exhibited aggravated fibrosis levels and inflammatory response without any influences on ROS production in in vitro studies. In conclusion, the findings indicated that NLRC5 showed important effects on high fat-induced heart injury via fibrosis and inflammation modulation, providing an essential target for improving myocardial damage induced by high fat diet.

Bivalirudin versus Heparin plus Glycoprotein IIb/IIIa Inhibitors in Women Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials.

Bivalirudin has been shown to be safe and efficacious compared with heparin plus glycoprotein IIb/IIIa inhibitor (GPI) in patients undergoing percutaneous coronary intervention (PCI). Whether bivalirudin would have the beneficial effects in female patients undergoing PCI remains unknown. We searched the literature for randomized controlled trials that assessed bivalirudin versus heparin plus GPI therapy in female patients undergoing PCI. The primary efficacy end point was major adverse cardiovascular events (MACE) within 30 days. The secondary efficacy end points were 30-day incidence of all-cause mortality, myocardial infarction (MI), urgent/ischemia-driven revascularization of target vessel. The safety end point was major bleeding up to 30 days. A total of 4,501 female patients were included in five randomized trials. No significant difference in MACE emerged between bivalirudin and heparin plus GPI at 30 days (8.15% vs 8.76%, RR 0.94, 95% CI 0.77-1.16, P = .57). There were no significant differences in rates of mortality (1.28% vs 1.91%, RR 0.74, 95% CI 0.45-1.20, P = .22), MI (5.46% vs 5.25%, RR 1.02, 95% CI 0.79-1.32, p = .88), or target vessel revascularization (2.13% vs 1.65%, RR 1.43, 95% CI 0.88-2.30, P = .15). Compared with heparin plus GPI, bivalirudin was associated with a significant reduction in 30-day major bleeding (5.32% vs 9.20%, RR 0.58, 95% CI 0.47-0.72, P < .0001). In conclusion, bivalirudin is associated with a significant reduction in 30-day major bleeding without increased ischemic events compared with heparin plus GPI in female patients undergoing PCI.

Liquiritigenin attenuates cardiac injury induced by high fructose-feeding through fibrosis and inflammation suppression.

Diabetes combined with cardiomyopathy is considered as an essential complication, showing diastolic persistently and causing cardiac injury, which is linked to fibrosis progression and inflammation response. Fibrosis and inflammation response are two markers for cardiomyopathy. Liquiritigenin is a flavanone, isolated from Radix glycyrrhiza, which exhibits various biological properties, including anti-cancer and anti-inflammatory activities. Here, in our study, the protective effects and anti-inflammatory activity of liquiritigenin were explored in mice and cardiac muscle cells treated by fructose to reveal the possible mechanism by which liquiritigenin attenuates cardiac injury. The mice were separated into five groups. The diabetic model of mouse was established with 30% high fructose feeding. Liquiritigenin dramatically reduced the lipid accumulation induced by high fructose diet. Compared to mice only treated with high fructose, mice in the presence of liquiritigenin after fructose feeding developed less cardiac fibrosis with lower levels of alpha smooth muscle-actin (α-SMA), Collagen type I, Collagen type II, TGF-ß1 and Procol1a1. Additionally, liquiritigenin markedly down-regulated inflammatory cytokines secretion and phosphorylated NF-κB via inhibiting IKKα/IκBα signaling pathway. Our results indicate that liquiritigenin has a protective role in high fructose feeding-triggered cardiac injury through fibrosis and inflammation response suppression by inactivating NF-κB signaling pathway. Thus, liquiritigenin may be a potential candidate for diabetes-associated cardiac injury.

Efficacy and Safety of Percutaneous Left Atrial Appendage Occlusion for Stroke Prevention in Nonvalvular Atrial Fibrillation: A Meta-analysis of Contemporary Studies.

BACKGROUND: Percutaneous left atrial appendage (LAA) occlusion has emerged as an important treatment for patients with nonvalvular atrial fibrillation (NVAF) who are at high stroke risk and have contraindications for anticoagulation. However, literature about the efficacy and safety of LAA occlusion is minimal to date. We performed a meta-analysis to assess the rates of stroke events and adverse events for patients treated with occlusion devices. METHODS: We conducted a comprehensive search on PubMed, Web of Science, OVID, SCOPUS databases and the Cochrane Central Register of Controlled Trials databases from inception to December 31, 2014 for studies of percutaneous LAA occlusion for patients with NVAF. Studies were included in the meta-analysis if at least 10 patients were studied with six months or more of follow-up period and reported at least one outcome of interest. RESULTS: A total of 2779 patients in 25 studies were included in the meta-analysis. Two were randomised control trials (RCTs), others were cohort studies. The adjusted incidence rate of stroke was 1.2/100 person-years (PY) (95% confidence interval [CI], 0.9-1.6/100 PY). The ischaemic and haemorrhagic stroke rates were 1.1/100 PY (95% CI, 0.8-1.4/100 PY) and 0.2/100 PY (95% CI, 0.1-0.3/100 PY), respectively. The combined efficacy outcomes (stroke or transient ischaemic attacks [TIAs], systemic embolism, or cardiovascular death) was 2.7/100 PY (95% CI, 1.9- 3.4/100 PY). Major bleeding and pericardial effusions were the most commonly observed adverse events at a rate of 2.6% (95% CI, 1.5%-3.6%) and 2.5% (95% CI, 1.8%-3.2%), respectively. CONCLUSIONS: Percutaneous LAA occlusion is a reasonably efficacious and safe therapeutic option in patients with NVAF who are at high risk for stroke and contraindicated for long-term anticoagulation.

Relation between development of cardiovascular disease and the C242T CYBA polymorphism of the NADPH oxidase in ESRD patients.

BACKGROUND: The development of cardiovascular disease in ESRD patients is considered to be associated with oxidative stress. NAD(P)H oxidase has attracted attention as mechanisms of generating oxidative stress. We investigated the relation between the genotype of the C242T CYBA polymorphism of the NADPH oxidase and the development of cardiovascular disease in ESRD patients. METHODS: A total of 289 ESRD patients were recruited and allocated to one of the two groups: patients without cardiovascular disease (group N; n=192) and patients developing cardiovascular disease (group D; n=97). The C242T CYBA polymorphism was determined by RFLP-PCR methods. RESULTS: The frequency of the C242T CT+TT genotype was significantly lower in group D than in group N (9.1 vs. 20.2%). In multiple Logistic regression analysis, systolic blood pressure, smoking history and this gene polymorphism were shown to be independent variables for the development of cardiovascular disease in ESRD patients. CONCLUSIONS: These results suggest that assessment of the C242T CYBA polymorphism of the NADPH oxidase may be useful in identifying the risk for developing cardiovascular disease in ESRD patients.

[Effect of simvastatin on the reserve of heart function and endothelial function in X-syndrome].

OBJECTIVE: To determine the therapeutic effect of simvastatin combined with traditional medicine on patients with X-syndrome, and on the reserve of heart function and endothelial function. METHODS: Forty patients with X-syndrome were recruited from September 2006 to September 2007 and randomly divided into 2 groups (a simvastatin group and a control group). The control group received routine treatment including beta receptor blocker, calcium-channel blocker (CCB) and long active nitrate. The simvastatin group received simvastatin and the routine treatment. The clinical condition and exercise test (TET) were performed before and after the treatment.The levels of triglyeride (TG), total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), endothelin-1 (ET-1) and nitric oxide (NO) were measured. RESULTS: The frequencies of chest pain in the simvastatin group were lower than those in the control group. The levels of ET-1, ET-1/NO, TG, TC, and LDL-C were significantly decreased in the simvastatin group as compared with the control group after the treatment. The levels of HDL-C and NO were significantly increased in the simvastatin group as compared with the control group after the treatment. The time in TET was significantly increased in the simvastatin group as compared with the control group. The frequencies of chest pain were positively related to the level of ET-1/NO and negatively related to the time in TET. CONCLUSION: Simvastatin is effective for patients with X-syndrome and may improve the endothelial function and the reserve of heart function.

Association of angiotensin-converting enzyme and endothelial Nitric Oxide synthase gene polymorphisms with vascular disease in ESRD patients in a Chinese population.

BACKGROUND: The effect of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and endothelial Nitric Oxide synthase (eNOS) gene G894 --> T on vascular disease in end-stage renal disease (ESRD) patients was rarely studied previously. We investigated such effect in a Chinese population. METHODS: A total of 153 ESRD patients with vascular disease (88 men and 65 women; mean age +/- SD: 54.0 +/- 13.2) were recruited. Polymerase chain reaction was used to classify the ACE genotypes as II, ID and DD and the eNOS genotypes as GG, GT, and TT. Analyses were performed in ESRD patients with vascular disease (n = 153) and the age-matched controls (n = 148). RESULTS: The frequencies of ACE DD and eNOS TT genotypes and ACE D and eNOS T alleles in ESRD patients with vascular disease were significantly higher than those in the controls (P < 0.05). There was a significant interaction between ACE I/D alleles and eNOS G894 --> T polymorphism: adjusted odds ratio 2.128 (95%CI 1.022-4.434, P = 0.017). CONCLUSIONS: These results indicated that the etiology of vascular disease in ESRD patients is associated with ACE and eNOS (G894 --> T) gene polymorphisms. Our data also suggest that an interaction effect may exist between ACE (I/D) and eNOS (G894 --> T) polymorphism in increasing the risk of vascular complications in ESRD patients.

[Effect of diet control combined with aerobic exercise on the metabolic syndrome].

OBJECTIVE: To observe the efficacy of diet control and aerobic exercises on the patients with metabolic syndrome(MS). METHODS: Sixty sedentary patients with MS were randomly divided into a diet control group, an aerobic exercise group, and a diet control combined with aerobic exercise group, each group with 20 persons. Patients in the simple diet control group ate a low-salt, low-cholesterol, low-calorie and high-cellulose diet; patients in the simple aerobic exercises group performed aerobic exercise 30 minutes every time, 3-5 times per week for 12 weeks; while patients in the combination therapy group performed aerobic exercises and diet control. Fasting serum insulin and free fatty acid (FFA) were measured by radio immunity and enzyme-colorimetric method. Serum leptin concentration was measured by enzyme linked immunosorbent assay (ELISA). Homeostasis model assessment (HOMA) insulin resistance index was calculated using the homeostasis model assessment equation. Twenty healthy subjects were selected as the control group. RESULTS: Serum concentration of FFA, blood pressure, and leptin and insulin resistance index (IRI)of patients with MS significantly increased compared with those of the controls. After 12 weeks, IRI and body mass index (BMI)significantly decreased but blood fat and leptin did not change significantly in the diet control group. IRI and BMI significantly decreased, and triglyceride, FFA and leptin also significantly decreased in the combination therapy group. CONCLUSION: Simple diet control and aerobic exercises are beneficial for patients with MS. It could significantly improve the effect of diet control combined with aerobic exercises on patients with metabolic syndrome.