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92 result(s) for "Li, Hongfan"
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Gut microbiota-derived metabolite isovalerylcarnitine modulates salt sensitivity of blood pressure and incident hypertension: a multicenter dietary salt intervention trial
This study aims to investigate the roles of gut microbiota and plasma metabolites in salt sensitivity (SS) of blood pressure (SSBP) and hypertension. A 23-day, multicenter, dietary salt intervention trial (the MetaSalt study) recruited 528 participants who underwent a baseline observation, low-salt, and high-salt interventions. SSBP was assessed and used as the primary outcome, and fecal shotgun metagenome and plasma targeted metabolome were measured. We found that high salt significantly altered 85 gut-microbial species ( p  < 9.42 × 10 −5 ) and 70 metabolites ( p  < 2.26 × 10 −4 ). Among them, the changes in 22 species and 8 metabolites were associated with SSBP ( p  < 0.05), and a gut microbiota-acylcarnitine network implicated in SSBP was identified, with a gut microbiota-derived metabolite, isovalerylcarnitine, as the core metabolite. Isovalerylcarnitine was also inversely associated with SSBP in the GenSalt study ( p  = 0.0102). Importantly, increased isovalerylcarnitine attenuated SS hypertension and improved endothelial function in rats, and was associated with reduced risk (ranging from 13% to 19%) of BP progression and incident hypertension in a prospective cohort (n = 3907, median follow-up = 5.5 years). This study demonstrated that the gut-acylcarnitine axis may play roles in the development of SS hypertension. Trial number: ChiCTR1900025171. Here, combining data from a clinical trial and animal models, the authors show a role for a gut-acylcarnitine axis in the development of salt-sensitive hypertension, and identify isovalerylcarnitine as a key microbiota-derived modulator and potential target for the precision prevention of hypertension.
Plasma miR-122 and miR-3149 Potentially Novel Biomarkers for Acute Coronary Syndrome
We evaluated the potentiality of plasma microRNAs (miRNAs, or miRs) that were considered as novel biomarkers for acute coronary syndrome (ACS), including acute myocardial infarction (AMI) and unstable angina (UA). We initially identified plasma miR-122, -140-3p, -144, -720, -1225-3p, -2861, and -3149 as candidate miRNAs associated with AMI (≥2 fold and P < 0.05) by comparing expression differences of miRNAs among AMI, non-coronary heart disease (non-CHD) and stable angina (SA) groups, using miRNA microarrays (n = 8 independent arrays in each group). Those seven plasma miRNAs were further examined with qRT-PCR analyses in two replications including 111 and 428 patients separately, and the results demonstrated that plasma miR-122, -140-3p, -720, -2861, and -3149 were elevated in the ACS group vs. the non-ACS (non-CHD + SA) group (P < 0.01). The area under the receiver operating characteristic curve (AUC) of the five miRNAs for ACS classification was 0.838, 0.818, 0.865, 0.852, and 0.670, respectively (all P < 0.001), while the values reached 0.843 and 0.925 when simultaneously with miR-122 and -3149 or with miR-122, -2861, and -3149 together (all P < 0.001). In plasma of pigs after coronary ligation, miR-122 was increased from 180 min to 240 min and miR-3149 was augmented from 30 min to 240 min compared with the sham pigs (all P < 0.05). Plasma miR-122, -140-3p, -720, -2861, and -3149 were associated with and potentially novel biomarkers for ACS.
A warming-yang herbal decoction protects against high-altitude hypoxia–induced osteoblast injury through modulation of HIF-1 signaling
This paper systematically explored dental osteoblast injury at high altitude hypoxic condition and examined the protective role of warming-yang traditional medicine, Aconitum carm michaelii and Zingiber officinale decoction (GAWD) in this condition. We constructed an high-altitude hypoxic model (4,500 m) with MC3T3-E1 osteoblastic cells and conducted RNA-seq analysis for Differentially Expressed Genes (DEGs). We performed enrichment analyses (GO, KEGG, and the Reactome pathway mapping) to reveal the relationships among the DEGs and key pathways. To further verify our results, we conducted a series of functional assays, including Cell Counting Kit-8 (CCK-8) for cell viability; flow cytometry assessment of reactive oxygen species (ROS); jc-10-based evaluation of mitochondrial membrane potential (MMP), and alkaline phosphatase (ALP) activity serum. Transcriptome profiling revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was central in the mediator role of osteoblast injury. High altitude hypoxia greatly suppressed the expression of HIF-1α, HIF-1β, von Hippel-Lindau tumor suppressor gene (VHL) and vascular endothelial growth factor (VEGF), resulting in increased intracellular ROS, calcium overload, mitochondrial distress, G -phase cell cycle arrest, apoptosis, and decreased proliferation. Rehabilitation by GAWD recovered these impairment effects: cell viability and apoptotic protein expression were improved, ROS and intracellular Ca were reduced, and mitochondrial membrane potential was regained, HIF-1/VEGF axis was recovered, apoptotic signaling and gross morphological injury were attenuated, and overall osteoblastic function was restored. The findings implicated HIF-1 signaling dysregulation in inducing high-altitude hypoxia-induced osteoblast injury and osteoporosis. GAWD may reduce hypoxia-induced cellular stress through recovering redox homeostasis and adjusting HIF-1/VEGF signaling. Collectively, this, study offers early molecular evidence supporting the utility of GAWD as a traditional Chinese medicine-based intervention for the prevention of bone metabolic disorders due to chronic hypoxic exposure.
The Relationship between Insecure Attachment to Depression: Mediating Role of Sleep and Cognitive Reappraisal
Previously, we have shown that neuromodulators are important factors in stress-induced emotional disorders, such as depression, for example, serotonin is the major substance for depression. Many psychological studies have proved that depression is due to insecure attachment. In addition, sleep is a major symptom of depression. Furthermore, serotonin is the substrate for both sleep and depression. To explore the role of sleep in the relationships between insecure attachment and depression, we investigated 755 college students with Close Relationship Inventory, Emotion Regulation Questionnaire, Self-rated Depression Scale, and Pittsburgh Sleep Quality Index. The results showed that (1) insecure attachment positively predicted poor sleep quality; (2) sleep quality partially affected depression, possibly due the same stress neuromodulators such as norepinephrine and cortisol; and (3) cognitive reappraisal moderated the mediating path leading from attachment anxiety to poor sleep quality. These findings highlight the moderating role of cognitive reappraisal in the effects of attachment anxiety on sleep quality and finally on depression. In conclusion, sleep quality links attachment anxiety and emotional disorders.
Fruit and vegetable intake and the risk of arterial hypertension in China: A prospective cohort study
Background Population‐based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent. This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new‐onset hypertension. Methods Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China‐PAR), 58,981 Chinese adults without hypertension at baseline were included. Information on fruit and vegetable intake was collected using a food‐frequency questionnaire. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension. Results During 640,795 person‐years of follow‐up, 21,008 new cases of hypertension were recorded. Compared with participants in the lowest quintile (Q1) of total fruit and vegetable (TFV) intake, the HRs (95% CIs) of incident hypertension were 0.90 (0.86–0.95), 0.85 (0.81–0.90), 0.82 (0.78–0.86), and 0.83 (0.78–0.88) for the Q2 to Q5 group (ptrend < 0.001), respectively. In further analyses categorizing participants according to the recommended intake level (500 g/day), we found that increasing the intake of TFV, even though it was still insufficient for the recommendation, also had a protective effect against the incident hypertension. When considering the intake of fruit or vegetable separately, we found similar trends as the TFV intake. Conclusion These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults. Restricted cubic spline curves of the association between total fruit and vegetable (TFV) consumption and risk of incident hypertension. Adjusted for age (continuous), sex (male or female), residence (urban or rural), region (south or north), education level (less than high school or not), body mass index (continuous), family history of hypertension (yes or no), legume consumption (≥125 g/day or not), red meat consumption (≥75 g/day or not), fish consumption (≥200 g/week or not), smoking status (current, former, never), current drinker (yes or no), cohort sources, physical activity (quartiles), diabetes (yes or no), hypercholesterolemia (yes or no), and high‐normal blood pressure (yes or no). With the exception of TFV intake, models also mutually adjusted for fruit intake and vegetable intake. Solid lines represented point estimates of the hazard ratios (HRs) and dashed lines represented 95% confidence intervals (CIs). Key points Inverse and nonlinear dose–response relationships existed between the intakes of total fruit and vegetable, fruit, and vegetable and the risk of new‐onset hypertension. Sufficient intake of fruit and vegetable can significantly reduce the risk of new‐onset hypertension. Small increases in the consumption of fruit and vegetable, even if still far below the recommended levels, could also reduce the risk of new‐onset hypertension.
Evaluation of NaTto Red Yeast Rice on Regulating Blood Lipid (ENTRY) Study: A Multicenter, Double‐Placebo, Double‐Blinded, Randomized Controlled Trial in Chinese Adults
Background Statins are the first line of treatment for dyslipidemia, but their side effects often reduce medication compliance. Natto and red yeast rice are natural ingredients with lipid‐lowering effects. However, the efficacy of Natto Red Yeast Rice (NRYR) supplement in combination with statins in regulating blood lipid levels has not been fully evaluated. Methods A multicenter, double‐blinded, randomized‐controlled trial was conducted among individuals with low‐density lipoprotein cholesterol (LDL‐C) of 3.4 to 5.0 mmol/L at six sites in China, of those at moderate risk of cardiovascular disease (CVD) are prioritized. Participants are enrolled and randomly assigned into four groups by a combination of NRYR (or its placebo) and Simvastatin (or its placebo) in a ratio of 1:1:1:1. After examination at baseline, all participants underwent intervention for 3 months and two follow‐up visits at 1 month and 3 months after the intervention. The primary outcome is the change in LDL‐C level at 3 months, and secondary outcomes include changes in levels of other lipid profiles and biomarkers, as well as calculated 10‐year CVD risk. A total of 1136 participants were randomly assigned, of whom 1110 received the intervention. Discussion This study may provide new evidence for the efficacy of NRYR supplement in combination with statins to regulate lipid levels and optimize lipid management. Trial Registration Chinese Clinical Trial Registry database: registration nos. ChiCTR2200064214, ChiCTR2200064215. Study flow chart of the ENTRY study. Summary The control rate of dyslipidemia is not satisfactory in Chinese population, and whether dietary supplements may improve the management of blood lipids is unclear. The present study aims to evaluate the efficacy of Natto Red Yeast Rice (NRYR) supplement in combination with statins in regulating blood lipids, especially in individuals with mild or moderate elevated cholesterol levels using a multicenter, double‐blind, randomized parallel‐controlled trial. This study may provide evidence on the potential role of NRYR supplement in regulation of lipid levels and management of dyslipidemia.
Renalase gene is a novel susceptibility gene for essential hypertension: a two-stage association study in northern Han Chinese population
Renalase, a novel flavin adenine dinucleotide-dependent amine oxidase, is secreted by the kidney, degrades circulating catecholamines, and modulates cardiac function and systemic blood pressure (BP). Its discovery may provide novel insights into the mechanisms of BP regulation and the pathogenesis of essential hypertension (EH). We designed a two-stage case-control study to investigate whether the renalase gene harbored any genetic variants associated with EH in the northern Han Chinese population. From the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China), 1,317 hypertensive cases and 1,269 normotensive controls were recruited. These total 2,586 subjects were taken as the main study population in this study. In stage 1, all the eight selected single nucleotide polymorphisms (SNPs) of the renalase gene were genotyped and tested within a subsample (503 cases and 490 controls) of the main study population. By single locus analyses, three SNPs, rs2576178, rs2296545, and rs2114406, showed significant associations with EH (P < 0.05). In stage 2, these three SNPs were genotyped on the remaining individuals and analyzed using all the individuals. After Bonferroni correction for multiple comparisons, the associations of rs2576178 and rs2296545 with EH were still significant in stage 2. The cases had higher frequencies of rs2576178 G allele and rs2296545 C allele than the controls (0.55 versus 0.49, P < 0.0001; 0.61 versus 0.55, P < 0.0001). Particularly, under the codominant model, the adjusted odds ratios for rs2576178 GG genotype and rs2296545 CC genotype were 1.58 (95% CI, 1.25 to 2.00; P = 0.0002) and 1.61 (95% CI, 1.26 to 2.04; P = 0.0002), respectively. We also found risk-associated haplotypes and diplotypes, which further confirmed the significant association between the renalase gene and EH. These findings may provide novel genetic susceptibility markers for EH and lead to a better understanding of EH pathophysiology. In addition, further replications in other populations and functional studies would be warranted.
Study design, general characteristics of participants, and preliminary findings from the metabolome, microbiome, and dietary salt intervention study (MetaSalt)
High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation. This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test. A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P < 0.0001) and subsequently increased during the high-salt intervention (96.4 ± 10.0, P < 0.0001). Our dietary salt intervention study has successfully recruited participants and will facilitate to evaluate the effects of gut microbiota and metabolites on BP regulation in response to sodium burden, which will provide important evidence for investigating the underlying mechanisms in the development of hypertension and subsequent cardiovascular diseases. The study was registered in the Chinese Clinical Trial Registry database (ChiCTR1900025171).
Genome-wide association study in Han Chinese identifies three novel loci for human height
Human height is a complex genetic trait with high heritability but discovery efforts in Asian populations are limited. We carried out a meta-analysis of genome-wide association studies (GWAS) for height in 6,534 subjects with in silico replication of 1,881 subjects in Han Chinese. We identified three novel loci reaching the genome-wide significance threshold ( P  < 5 × 10 −8 ), which mapped in or near ZNF638 (rs12612930, P  = 2.02 × 10 −10 ), MAML2 (rs11021504, P  = 7.81 × 10 −9 ), and C18orf12 (rs11082671, P  = 1.87 × 10 −8 ). We also confirmed two loci previously reported in European populations including CS (rs3816804, P  = 2.63 × 10 −9 ) and CYP19A1 (rs3751599, P  = 4.80 × 10 −10 ). In addition, we provided evidence supporting 35 SNPs identified by previous GWAS ( P  < 0.05). Our study provides new insights into the genetic determination of biological regulation of human height.
Association of lipoprotein lipase polymorphism rs2197089 with serum lipid concentrations and LPL gene expression
Many single-nucleotide polymorphisms (SNPs) have been reported to be associated with lipid concentrations in recent genome-wide association studies. The aim of this study was to validate the associations of rs2197089 in the lipoprotein lipase (LPL) gene with serum lipid concentrations and gene expression levels in the Chinese Han population and examine the potential interactions. A total of 9339 participants were recruited and genotyped for rs2197089. Gene expression levels of LPL in blood cells of 309 participants were evaluated by real-time PCR. We observed significant associations between rs2197089 and decreased triglycerides (TG) (P=0.0006), but not high-density lipoprotein cholesterol (HDL-C) concentration (P=0.0881). However, weak evidence of interaction between cigarette smoking and rs2197089 was detected (P=0.0362). In smokers, significant association between rs2197089 and increased HDL-C concentration was found (P=0.0068). Participants with the minor allele A had higher expression levels of LPL (P=0.0243). The results of our study indicated that rs2197089 was significantly associated with TG but it was associated with HDL-C only in smokers. This SNP seemed to have influence on the expression level of LPL.