Potential nutritional strategies to prevent and reverse sarcopenia in aging process: Role of fish oil-derived ω-3 polyunsaturated fatty acids, wheat oligopeptide and their combined intervention.

INTRODUCTION: Nutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. OBJECTIVES: This study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. METHODS: One hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. RESULTS: All intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. CONCLUSIONS: The combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength.

Association between socio-demographic factors, lifestyle, eating habits and hypertension risk among middle-aged and older rural Chinese adults.

BACKGROUND AND AIMS: Hypertension is a global health issue with increasing prevalence. This study aimed to understand the epidemiological characteristics and influencing factors of hypertension in rural Chinese populations and help develop effective prevention and control strategies. METHODS AND RESULTS: This cross-sectional study used database from the Early Diagnosis and Early Treatment Project of Esophageal Cancer conducted in a rural population from September 2012 to December 2017. A total of 10,111 subjects aged 35-75 years residing in Huai'an District, Huai'an City, Jiangsu Province for at least three years were included. Unconditional univariate and multivariate logistic regression models were performed to evaluate the association between socio-demographic information, lifestyle habits, dietary characteristics and the risk of hypertension. The prevalence of hypertension was 34.32 % in this rural population. Men and older individuals are more likely to have hypertension when compared with women and young individuals, respectively. Factors associated with an increased risk of hypertension included: fast eating speed, a high-salt diet (both currently and ten years ago), a high-spicy diet ten years ago, high BMI, poor educational attainment, preference for fatty meats, hot diet, green tea drinking, intake of pickled potherb mustard and corn flour, family smoking and alcohol consumption. Light smoking in males, consumption of fruits, adzuki bean, and pork liver were associated with reduced risk of hypertension. CONCLUSIONS: The study identified some factors, including eat habits and lifestyle, associated with hypertension risk, and highlighted the need for targeted policies and interventions in rural China to address potential risk factors for hypertension.

Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.

Exploring the Interplay Between Vitamin B12-related Biomarkers, DNA Methylation, and Gene-Nutrition Interaction in Esophageal Precancerous Lesions.

BACKGROUND: Vitamin B12 depletion has been suggested to be associated with esophageal precancerous lesions (EPL). However, the potential mechanisms remain unclear. AIMS: This study aims to evaluate the role of vitamin B12 and its regulated epigenetic modification in EPL and provide preliminary information on the identification of potential molecular biomarkers for the early prediction of EPL. METHODS: We collected information and samples from the Early Diagnosis and Early Treatment Project of Esophageal Cancer database from 200 EPL cases and 200 matched controls. Vitamin B12, one-carbon metabolism biomarkers, genetic polymorphism of TCN2 C776G, and DNA methylation were compared. Preliminarily identified candidate promoters of differentially methylated CpG positions were further verified by targeted bisulfite sequencing. RESULTS: EPL cases had significantly lower serum levels of vitamin B12 and transcobalamin II, and higher serum levels of homocysteine and 5-methyltetrahydrofolate than controls. The TCN2 C776G polymorphism was found to be associated with susceptibility to EPL and may interact with vitamin B12 nutritional status to influence the risk of EPL in male subjects. In addition, global hypomethylation related to vitamin B12 depletion was observed in EPL cases, along with region-specific hypermethylation of UGT2B15 and FGFR2 promoters. CONCLUSIONS: This study suggests that vitamin B12 depletion may be associated with aberrant DNA methylation and increased risk of EPL through the one-carbon metabolism pathway, presents that the TCN2 C776G polymorphism may interact with vitamin B12 nutritional status to affect EPL risk in males, and also identifies specific locations in the UGT2B15 and FGFR2 promoters with potential as promising molecular biomarkers.

Effects of Omega-3 Fatty Acids Supplementation on Serum Lipid Profile and Blood Pressure in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this study was to explore the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. We searched PubMed, Web of Science, Embase, and the Cochrane library from database inception to 30 April 2022. This meta-analysis included eight trials with 387 participants. We found that supplementation of n-3 PUFAs has no significant reduction in TC level (SMD = -0.02; 95% CI: -0.22 ~ 0.18, I2 = 23.7%) and LDL-c level in serum (SMD = 0.18; 95% CI: -0.18 ~ 0.53, I2 = 54.9%) of patients with metabolic syndrome. Moreover, we found no significant increase in serum high-density lipoprotein cholesterol level (SMD = 0.02; 95% CI: -0.21 ~ 0.25, I2 = 0%) in patients with metabolic syndrome after consuming n-3 PUFAs. In addition, we found that n-3 PUFAs can significantly decrease serum triglyceride levels (SMD= -0.39; 95% CI: -0.59 ~ -0.18, I2 = 17.2%), systolic blood pressure (SMD = -0.54; 95% CI: -0.86 ~ -0.22, I2 = 48.6%), and diastolic blood pressure (SMD = -0.56; 95% CI: -0.79 ~ 0.33, I2 = 14.0%) in patients with metabolic syndrome. The results from the sensitivity analysis confirmed that our results were robust. These findings suggest that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in metabolic syndrome. Given the quality of the included studies, further studies are still needed to verify our findings.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

Analysis of Chemical Constituents of Chrysanthemum morifolium Extract and Its Effect on Postprandial Lipid Metabolism in Healthy Adults.

Chrysanthemum extract possesses antioxidant potential and carbohydrate and fat digestive enzyme inhibitory in vitro. However, no evidence supporting chrysanthemum in modulation of postprandial lipemia and antioxidant status in humans presently exists. This study was to analyze the composition of Imperial Chrysanthemum (IC) extract and determine the effect on changes in postprandial glycemic and lipemic response and antioxidant status in adults after consumption of a high-fat (HF) meal. UHPLC-MS method was used to analyze the components of two kinds of IC extracts (IC-P/IC-E) and in vitro antioxidant activities were evaluated using 1,1-diphenyl-2-picrylhydraxyl (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and Hydroxyl radical (HR) radical scavenging assays. Following a randomized design, 37 healthy adults (age, 25.2 ± 2.6 years, and BMI, 20.9 ± 1.5 kg/m2) were assigned to two groups that consumed the HF meal, or HF meal supplemented by IC extract. Blood samples were collected at fasting state and then at 0.5, 1, 2, 4, 6 and 8 h after the meal consumption. There were 12 compounds with relative content of more than 1% of the extracts, of which amino acid and derivatives, flavonoids, carboxylic acids and derivatives were the main components. Compared with IC-E, the contents of flavonoids in IC-P increased significantly (p < 0.05), and the cynaroside content exceeded 30%. In addition, IC-P showed strong free radical scavenging activity against DPPH, ABTS and HR radicals. Furthermore, according to repeated−measures ANOVA, significant differences were observed in the maximal changes for postprandial glucose, TG, T-AOC and MDA among the two groups. Postprandial glucose has significant difference between the two groups at 1 h after meal and the level in IC group was significantly lower than that in control group. No significant differences were observed in the incremental area under the curve (iAUC) among the two groups. IC significantly improved the serum antioxidant status, as characterized by increased postprandial serum T-AOC, SOD, GSH and decreased MDA. This finding suggests that IC can be used as a natural ingredient for reducing postprandial lipemia and improving the antioxidant status after consuming a HF meal.

Effects of Additional Dietary Fiber Supplements on Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

The efficacy of different types and doses of dietary fiber supplementation in the treatment of gestational diabetes (GDM) remains controversial. The purpose of this study is to investigate the effect of dietary fiber on blood glucose control in pregnant women with gestational diabetes mellitus, and further observe the effect on their blood lipids and pregnancy outcomes. We searched on Web of Science, PubMed, Embase, Scopus, and Cochrane, and included several articles on additional fortification with dietary fiber for gestational diabetes interventions. This meta-analysis included 8 trials. We found that additional dietary fiber supplements significantly reduced fasting glucose (Hedges'g = −0.3; 95% CI [−0.49, −0.1]), two-hour postprandial glucose (Hedges'g = −0.69; 95% CI [−0.88, −0.51]), glycated hemoglobin (Hedges'g = −0.5; 95% CI [−0.68, −0.31]), TC (Hedges'g = −0.44; 95% CI [−0.69, −0.19]), TG (Hedges'g = −0.3; 95% CI [−0.4, −0.2]) and LDL-C (Hedges'g = −0.48; 95% CI [−0.63, −0.33]). It also significantly reduced preterm delivery (Hedges'g = 0.4, 95% CI [0.19~0.84]), cesarean delivery (Hedges'g = 0.6; 95% CI [0.37~0.97]), fetal distress (Hedges'g = 0.51; 95% CI [0.22~1.19]), and neonatal weight (Hedges'g = −0.17; 95% CI [−0.27~−0.07]). In a subgroup analysis comparing dietary fiber type and dose, insoluble dietary fiber was more effective than soluble dietary fiber in reducing fasting glucose (Hedges'g = −0.44; 95% CI [−0.52, −0.35]). ≥12 g fiber per day may be more effective in improving glycemic lipid and pregnancy outcomes than <12 g/day, but the difference was not statistically significant. In conclusion, our meta-analysis showed that dietary fiber supplementation significantly improved glycolipid metabolism and pregnancy outcomes in gestational diabetes. Dietary fiber may be considered adjunctive therapy for gestational diabetes, and an additional supplement with insoluble dietary fiber is more recommended for those with poor fasting glucose. However, more high-quality studies are needed on the further effect of fiber type and the dose-effect relationship.

The hypolipidemic mechanism of chrysanthemum flavonoids and its main components, luteolin and luteoloside, based on the gene expression profile.

In this study, the following four groups of mice with hyperlipidemia were involved: the model control group (MC), the Chrysanthemum flavonoids group (CF), the luteolin group, and the luteoloside group. The whole gene expression profile was detected in the liver tissues of each group. Differential genes significantly enriched in the biological process of gene ontology (GO) items and Kyoto Encyclopedia of Genes and Genomes (KEGG) were selected, and 4 differential genes related to lipid metabolism were selected for further real-time quantitative PCR verification. Compared with the MC, 41 differential genes such as Sqle, Gck, and Idi1 were screened in the CF intervention group; 68 differential genes such as Acsl3, Cyp7a1, and Lpin1 were screened in the luteolin intervention group (CF); and 51 differential genes such as Acaca, Cyp7a1, and Lpin1 were screened in the luteoloside group. The mechanism of CF to improve hyperlipidemia is very complex, mainly involving biological processes such as cholesterol and fatty acid metabolism and glycolysis, luteolin mainly involves the synthesis and transport of cholesterol, and luteoloside mainly involves fatty acid metabolism. The functional pathways of CF may not be completely the same as luteolin and luteoloside, and further study is needed on the mechanism of action of other components.

Development of nomogram models of inflammatory markers based on clinical database to predict prognosis for hepatocellular carcinoma after surgical resection.

BACKGROUND: Inflammation plays a significant role in tumour development, progression, and metastasis. In this study, we focused on comparing the predictive potential of inflammatory markers for overall survival (OS), recurrence-free survival (RFS), and 1- and 2-year RFS in hepatocellular carcinoma (HCC) patients. METHODS: A total of 360 HCC patients were included in this study. A LASSO regression analysis model was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors for HCC prognosis. Nomogram prediction models were established and decision curve analysis (DCA) was conducted to determine the clinical utility of the nomogram model. RESULTS: Multivariate Cox regression analysis indicated that the prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS, and aspartate aminotransferase-to-platelet ratio (APRI) was a common independent prognostic factor among RFS, 1-year RFS, and 2-year RFS. The systemic inflammation response index (SIRI) was an independent prognostic factor for 1-year RFS in HCC patients after curative resection. Nomograms established and achieved a better concordance index of 0.772(95% CI: 0.730-0.814), 0.774(95% CI: 0.734-0.815), 0.809(95% CI: 0.766-0.852), and 0.756(95% CI: 0.696-0.816) in predicting OS, RFS, 1-year RFS, and 2-year RFS respectively. The risk scores calculated by nomogram models divided HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram models could augment net benefits and exhibited a wider range of threshold probabilities in the prediction of HCC prognosis. CONCLUSIONS: The nomograms showed high predictive accuracy for OS, RFS, 1-year RFS, and 2-year RFS in HCC patients after surgical resection. The nomograms could be useful clinical tools to guide a rational and personalized treatment approach and prognosis judgement.

The Blood-Pressure-Lowering Effect of Food-Protein-Derived Peptides: A Meta-Analysis of Recent Clinical Trials.

Although clinical trials of food-protein-derived peptides in the management of hypertension have been published, the results are controversial, which compelled us to conduct a meta-analysis to evaluate the pooled effect of peptide intervention. In this study, we searched for studies published between 2010 and 2021 and selected 12 eligible studies for a meta-analysis. The pooled effect of peptide intervention for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was -3.28 mmHg (95% CI: -4.54, -2.03, p < 0.001) and -1.82 mmHg (95% CI: -3.46, -0.18, p = 0.03), respectively. Sub-group analyses showed that the reduction in BP in participants with higher basal BP (>140/85 mmHg) was greater (p = 0.007 for SBP and p = 0.01 for DBP), and the effect was stronger in Asian participants as compared with non-Asian participants (p = 0.01 for SBP and p = 0.04 for DBP). In addition, the effect of peptide intervention was more pronounced on SBP in participant groups with a lower ratio of male to female (≤0.5) as well as in participants with a mean age ≥50 years old. In conclusion, food-protein-derived antihypertensive peptides can significantly reduce BP in prehypertensive and hypertensive patients. Findings from this study could provide guidance for the design of clinical trials of antihypertensive peptides.

Hypolipidemic Effects and Preliminary Mechanism of Chrysanthemum Flavonoids, Its Main Components Luteolin and Luteoloside in Hyperlipidemia Rats.

This study aimed to investigate the key constituents and preliminary mechanism for the hypolipidemic activity of chrysanthemum flavonoids. Hyperlipidemia (HPL) rats were divided into five groups: the model control group (MC); Chrysanthemum flavone intervention group (CF); luteolin intervention group; luteoloside intervention group and simvastatin intervention group. The body weight, organ coefficient, serum lipids, antioxidant activity, and lipid metabolism enzymes were detected. Hematoxylin and eosin (H&E) staining was used to observe the liver and adipose tissue. Chrysanthemum flavonoids, luteolin, and luteoloside can reduce the weight and levels of total cholesterol (TC), triglycerides (TG), and LDL-C, and increase the level of HDL-C in the blood and reduce liver steatosis. Indicators of liver function (AST, ALT, and ALP) improved. The antioxidant activity (GSH-Px, CAT, SOD) and enzymes associated with lipid catabolism (FAßO, CYP7A1, and HL) increased, while lipid peroxidation products (MDA) and enzymes associated with lipid synthesis (FAS, HMG-CoA, and DGAT) decreased. Chrysanthemum flavonoids had a better effect on the antioxidant level and lipid metabolism-related enzyme activity. There was no significant difference in the effects of the chrysanthemum flavonoids, luteolin, and Luteoloside on improving blood lipids and hepatic steatosis-mechanisms that may be related to antioxidant levels and regulating enzymes involved in the metabolism of fatty acids, cholesterol, and triglycerides in the liver. However, chrysanthemum flavonoids had a stronger antioxidant and lipid metabolism regulation ability, and the long-term effects may be better.

Hsa_circ_0037897 may be a risk factor for essential hypertension via hsa-miR-145-5p.

Objectives: This study aims to investigate the association between hsa_circ_0037897 and essential hypertension (EH) and to evaluate the diagnostic value of biomarker hsa_circ_0037897 in EH. Methods: This study included 92 EH patients and 92 sex- and age- (±3 years) matched subjects as control. qRT-PCR was performed to measure the expression level of circRNA and miRNA. Logistic regression analysis model was used to assess independent association between hsa_circ_0037897 and EH. Results: The expression level of hsa_circ_0037897 in EH patients was significantly higher (p < .001) compared to the control group, while hsa-miR-145-5p had significantly lower expression(p = .002) than the control group. The area under the ROC curve (AUC) of hsa_circ_0037897 was 0.656. Furthermore, the AUC increased to 0.714 when hsa_circ_0037897 was combined with hsa-miR-145-5p, BMI and smoking. Conclusion: The present results suggested that the high expression of hsa_circ_0037897 may be a risk factor for EH, and hsa_circ_0037897 has certain diagnostic value for EH.

The microarray identification circular RNA hsa_circ_0105015 up-regulated involving inflammation pathway in essential hypertension.

BACKGROUND: Essential hypertension (EH) is an inflammatory disease, and endothelial dysfunction induced by chronic inflammation is one of the pathogeneses of EH. The expression of some inflammatory mediators may be regulated by the interaction of circular RNAs (circRNAs) and microRNAs (miRNAs). METHODS: An Agilent human circRNA microarray was used to identify the expression profile of circRNAs in EH. qRT-PCR was used to evaluate the relative expression of circRNAs in 48 pairs of human whole blood samples (sex and age ± 3 years matched) and endothelial cells. TNF-α was applied to induce endothelial cells inflammation. CircRNA-miRNA network was predicted by MiRanda software. RESULTS: There were 287 circRNAs differentially expressed in the microarray. The top 10 up-regulated circRNAs in the EH group were hsa_circ_0014243, hsa_circ_0133228, hsa-circRNA14116-3, hsa_circ_0079536, hsa-circRNA13649-1, hsa_circ_0117886, hsa_circ_0007075, hsa-circRNA15285-1, hsa-circRNA10088-9, and hsa-circRNA14119-10; the top 10 down-regulated circRNAs were hsa_circ_0100094, hsa_circ_0127342, hsa_circ_0093773, hsa_circ_0096334, hsa_circ_0131618, hsa_circ_0063886, hsa_circ_0097804, hsa_circ_0126640, hsa-circRNA8935-1, and hsa_circ_0039978 (fold change in descending order). Hsa_circ_0105015 has two predicted binding sites with hsa-miR-637. The relative expression of hsa_circ_0105015 in EH patients was significantly higher than healthy controls (P = .002), and similar results appeared in TNF-α-induced endothelial cells. The area under the curve after hsa_circ_0105015 combined with hsa-miR-637 was 0.703, P < .001. CONCLUSION: Hyperexpression of hsa_circ_0105015 is a significant risk factor of EH and its association with EH involves inflammatory pathways. Hyperexpression of hsa_circ_0105015 combined with hypoexpression of hsa-miR-637 indicates vascular inflammation or endothelial dysfunction and has potential as a biomarker for early diagnosis of EH.

The up-regulated hsa-circRNA9102-5 may be a risk factor for essential hypertension.

BACKGROUND: The present study was aimed to investigate the expression levels of circular RNAs (circRNAs) in the peripheral blood of essential hypertension (EH) patients and healthy controls (HC). On this basis, we tried to explain the possible role of circRNAs in the progression of EH and their potential as diagnostic biomarkers of EH. METHODS: First, we analyzed the differentially expressed circRNAs in peripheral blood obtained from the finished microarray analysis and selected four circRNAs under strict standards. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression levels of the selected circRNAs in a total of 192 blood samples, consisting of 96 HC and 96 diagnosed EH patients. Bioinformatics prediction of the target microRNAs (miRNAs) was performed for differentially expressed circRNAs, and the circulating vascular-related miRNAs were selected for qRT-PCR analysis to determine their expression levels. RESULTS: Hsa-circRNA9102-5 (11.7 ± 1.06 vs 12.13 ± 1.11, P = .007) was up-regulated in the patients group which was diagnosed with EH, as compared to the HC group, and was involved in the regulation of EH by sponging hsa-miR-150-5p. The area under the ROC curve (AUC) of the model was 0.620, using hsa-circRNA9102-5 as an independent predictor. Furthermore, the AUC was increased to 0.728 when hsa-circRNA9102-5 was combined with hsa-miR-150-5p and multiple other factors, as a combined predictor. CONCLUSIONS: The present results suggested that hsa-circRNA9102-5 may have played a crucial role in the development of EH by sponging hsa-miR-150-5p, which showed great potential as a novel target.

A potential risk factor of essential hypertension in case-control study: MicroRNAs miR-10a-5p.

Background: Essential hypertension is a multifactorial disease with high morbidity. The researches on the influence of genes on the disease are still in its infancy, and the mechanism of gene regulation is not clear. MiRNAs are key molecules that regulate the expression control of protein-coding or protein-non-coding RNA. It may be an important biological molecule risk factor for essential hypertension.Methods: A case-control study with 98 EH and 98 non-EH was conducted in our experiment. The candidate miRNAs including miR-10a-5p and miR-497-5p were detected and verified by qRT-PCR.Results: The expression level of miRNA in EH cases was significantly lower than the healthy control (P = 0.005). In addition, the relative expression of miR-10a-5p was closely positive correlated with DBP (r = 0.162, P = 0.023) and SBP (r = 0.223, P = 0.002). After adjusting confound factors, the result of the logistic regression indicated that hypo-expression of miR-10a-5p is a risk factor for EH (OR(95%CI) = 1.676(1.302,2.157), adjusted P < 0.0001). And the ROC analysis shows that the combined line with BMI and miR-10a-5p was a values marker for EH (AUC: 0.728, P < 0.0001).Conclusions: Lower expression of miR-10a-5p, as the key role, is significantly related to the risk of EH and maybe as a potential biomolecule for EH.

Up-regulation of circular RNA hsa_circ_0037909 promotes essential hypertension.

AIMS: Essential hypertension (EH) is a high prevalence disease facing a public health challenge. People were little known about the genetics of diagnosing the cause of EH. Circular RNAs that have a continuous cycle of covalent closure, without affected by RNA exonuclease, and are more stable and hard to degrade may involve into the molecule regulation mechanism of EH as an important biomedical. METHODS: qRT-PCR was used to analyze circRNAs in total volume of human blood and the induced human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs). Our case-control study was involved with 48 pairs of case controls with sex and age (±3 years) match. We conducted t test, Pearson's χ2 test, and receiver operating characteristics (ROC) curve analysis for the corresponding analysis. RESULTS: The expression level of hsa_circ_0037909 in EH patients was significantly higher than that in the healthy controls (P = 0.007), and the expression level of hsa-miR-637 in EH patients was significantly lower in than that in the healthy controls (P = 0.039); the same result appears in the HAECs and HUVECs. Hsa-miR-637 (adjusted P = 0.018), hsa_circ_0037909 (adjusted P = 0.005), HDL (adjusted P = 0.024), and serum creatinine (adjusted P = 0.014) were brought into the model which performed logistic regression analysis. The combination of two RNAs was excellent (P < 0.001) through ROC curve analysis. Hsa_circ_0037909 was significantly positively correlated with serum creatinine (P < 0.001) and low-density lipoprotein (LDL) (P = 0.017). CONCLUSIONS: Our findings suggested that the combination of hsa_circ_0037911 and hsa-miR-637 may be a significant important biomarker for early diagnosis of EH. Hsa_circ_0037909 may affect serum creatinine or LDL leading to the formation of EH.

Circular RNA hsa_circ_0014243 may serve as a diagnostic biomarker for essential hypertension.

Circular RNAs (circRNAs) have a great potential as clinical biomarkers; however, specific circRNAs with a diagnostic value for essential hypertension (EH) largely remain to be identified. In the present study, the potential application of Homo sapiens (hsa)_circ_0014243, which was identified to be significantly upregulated in whole blood samples of EH patients in a previous microarray profiling study by our group, in the diagnosis of EH was evaluated. Reverse transcription-quantitative polymerase chain reaction analysis was performed to determine the expression levels of hsa_circ_0014243 and hsa-microRNA (miR)-10a-5p in a total of 178 blood samples collected from 89 healthy controls and 89 patients diagnosed with EH. Divergent primers were designed for circRNAs, while conventional primers were used for miRs. Independent-samples t-tests and bivariate correlation analyses were performed to analyze the association between clinical factors influencing EH and hsa_circ_0014243 expression levels. A receiver operating characteristics (ROC) curve was generated to estimate the diagnostic value of hsa_circ_0014243 for EH. Finally, the expression levels of circRNAs and miRNAs were combined to propose a possible prediction model for EH. The results indicated that hsa_circ_0014243 was upregulated in whole blood samples of EH patients compared with that in the controls (P<0.001). Furthermore, the relative expression levels of hsa_circ_0014243 (Δ quantification cycle) were identified to be significantly correlated with age (r=-0.259, P<0.001), high-density lipoprotein levels (r=0.196, P=0.009) and glucose levels (r=-0.204, P=0.006). The area under the ROC curve (AUC) of the model using hsa_circ_0014243 as a predictor was 0.732. Of note, the AUC increased to 0.781 when hsa_circ_0014243 levels were combined with hsa-miR-10a-5p levels as predictors. The present results suggest that hsa_circ_0014243 has a crucial role in the genesis and development of EH, and presents a certain diagnostic capability for EH.

A potential risk factor of essential hypertension in case-control study: Circular RNA hsa_circ_0037911.

BACKGROUND: Essential hypertension (EH) is a high prevalence with multifactorial diseases. Human studies on the impact of genes on this disease are just in the initial stage, the mechanism of gene regulation is still remains unclear. Circular RNAs (circRNAs) as a continuous cycle of covalent closure, RNA molecules added to the 3'-5' end covalently bound by the formation of incidental event. CircRNAs may be an important biomolecule in revealing the molecule regulate mechanisms of EH. METHODS: The circRNAs were selected and validated with qRT-PCR followed. Our experiment was conducted with case-control studies among 200 EH participants. The t-test was used to evaluate the different expression of circRNAs and miRNAs, the significance of which was set as p < 0.05. RESULTS: The hsa_circ_0037911 expression level in EH cases were significantly higher than healthy controls (p = 0.005). There was still important significance when adjusted by logistic regression (adjusted p = 0.026). We also found that hsa_circ_0037911 was an effective marker of EH (area under curve = 0.627; p = 0.002). The levels of hsa_circ_0037911 were significantly differences in gender, BMI, smoking and drinking among EH cases. There was a positive correlation between Serum creatinine (Scr) and hsa_circ_0037911. CONCLUSIONS: Our findings suggested that higher expression hsa_circ_0037911 may be key circRNAs for EH development by changing the concentration of Scr and could be a stable biomarker for early diagnosis of EH.