Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. METHODS: A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model. RESULTS: Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate. CONCLUSIONS: The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.

Impact of sarcopenia and sarcopenic obesity on survival in patients with primary liver cancer: a systematic review and meta-analysis.

Background: Sarcopenia and sarcopenic obesity are associated with an increased possibility of adverse clinical outcomes; however, the effects of sarcopenia and sarcopenic obesity on patients with primary liver cancer remain controversial. Therefore, the present study aimed to determine the impact of sarcopenia and sarcopenic obesity on survival in patients with primary liver cancer. Methods: We searched studies published in English in PubMed, Embase, Web of Science, and Cochrane Library databases up to 13 November 2022. Cohort studies that reported the association among sarcopenia, sarcopenic obesity, and patient survival were included. Results: A total of 64 cohort studies with data on 11,970 patients with primary liver cancer were included in the meta-analysis. Sarcopenia was associated with poor overall survival in patients with primary liver cancer [adjusted hazard ratio (HR) 2.11, 95% confidence interval (CI): 1.89-2.36, P < 0.0001], with similar findings for sarcopenic obesity (adjusted HR: 2.87, 95% CI: 2.23-3.70, P < 0.0001). Sarcopenia was also associated with poor overall survival across the subgroups analyzed by ethnicity, type of liver cancer, treatment modalities, method used to define sarcopenia, and etiology of liver cancer. We also found a negative correlation among sarcopenia, sarcopenic obesity, and recurrence-free/disease-free survival (adjusted HR: 1.73, 95% CI: 1.50-1.99, P < 0.001; adjusted HR: 2.28, 95% CI: 1.54-3.35, P < 0.001, respectively). Conclusion: Sarcopenia and sarcopenic obesity were significantly associated with poor overall survival and recurrence-free/disease-free survival in patients with primary liver cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=378433, PROSPERO [42022378433].

Selenium deficiency causes hypertension by increasing renal AT1 receptor expression via GPx1/H2O2/NF-κB pathway.

Epidemiological studies show an association between low body selenium and the risk of hypertension. However, whether selenium deficiency causes hypertension remains unknown. Here, we report that Sprague-Dawley rats fed a selenium-deficient diet for 16 weeks developed hypertension, accompanied with decreased sodium excretion. The hypertension of selenium-deficient rats was associated with increased renal angiotensin II type 1 receptor (AT1R) expression and function that was reflected by the increase in sodium excretion after the intrarenal infusion of the AT1R antagonist candesartan. Selenium-deficient rats had increased systemic and renal oxidative stress; treatment with the antioxidant tempol for 4 weeks decreased the elevated blood pressure, increased sodium excretion, and normalized renal AT1R expression. Among the altered selenoproteins in selenium-deficient rats, the decrease in renal glutathione peroxidase 1 (GPx1) expression was most prominent. GPx1, via regulation of NF-κB p65 expression and activity, was involved in the regulation of renal AT1R expression because treatment with dithiocarbamate (PDTC), an NF-κB inhibitor, reversed the up-regulation of AT1R expression in selenium-deficient renal proximal tubule (RPT) cells. The up-regulation of AT1R expression with GPx1 silencing was restored by PDTC. Moreover, treatment with ebselen, a GPX1 mimic, reduced the increased renal AT1R expression, Na+-K+-ATPase activity, hydrogen peroxide (H2O2) generation, and the nuclear translocation of NF-κB p65 protein in selenium-deficient RPT cells. Our results demonstrated that long-term selenium deficiency causes hypertension, which is due, at least in part, to decreased urine sodium excretion. Selenium deficiency increases H2O2 production by reducing GPx1 expression, which enhances NF-κB activity, increases renal AT1R expression, causes sodium retention and consequently increases blood pressure.

Resveratrol Inhibits Insulin-Induced Vascular Smooth Muscle Cell Proliferation and Migration by Activating SIRT1.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are essential for the development of hypertension. Insulin has been identified to promote VSMC proliferation and migration; resveratrol has been shown to have protective effects against cardiovascular diseases. This study aimed to investigate the effect of resveratrol on insulin-induced VSMC proliferation and migration and its potential mechanism. VSMC proliferation was measured by Cell Counting Kit-8 (CCK-8), cell counting method, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Cell migration was detected by wound healing assay and transwell method. Expression of silent information regulator of transcription 1 (SIRT1) and phosphorylation levels of signaling molecules, such as phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), in VSMCs were detected by Western blotting. Resveratrol (25-150 µM) was found to inhibit insulin-induced VSMC proliferation. Pretreatment with 100 µM resveratrol reduced insulin (100 nM)-mediated VSMC migration. LY294002, an inhibitor of PI3K, inhibited the stimulatory effect of insulin (100 nM) on the proliferation of VSMCs. Treatment with resveratrol also decreased insulin-induced stimulatory effect on PI3K and Akt phosphorylation levels. Moreover, resveratrol treatment increased SIRT1 protein expression in VSMCs. A SIRT1 inhibitor, EX527, reversed the inhibitory effect of resveratrol on insulin-induced VSMC proliferation and migration and activation of PI3K and Akt phosphorylation levels. In conclusion, our study revealed that treatment with resveratrol inhibited insulin-mediated VSMC proliferation and migration, possibly by activating SIRT1 and downregulating the PI3K/AKT pathway.

Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors in overweight and obese adults: A meta-analysis of randomized controlled trials.

Background and aims: Low-carbohydrate diets (LCD) and low-fat diets (LFD) have shown beneficial effects on the management of obesity. Epidemiological studies were conducted to compare the effects of the two diets. However, the results were not always consistent. This study aimed to conduct a meta-analysis to compare the long-term effects of LCD and LFD on metabolic risk factors and weight loss in overweight and obese adults. Methods: We performed a systematic literature search up to 30 March, 2022 in PubMed, EMBASE, and Cochrane Library. The meta-analysis compared the effects of LCD (carbohydrate intake ≤ 40%) with LFD (fat intake < 30%) on metabolic risk factors and weight loss for ≥6 months. Subgroup analyses were performed based on participant characteristics, dietary energy intake, and the proportions of carbohydrates. Results: 33 studies involving a total of 3,939 participants were included. Compared with participants on LFD, participants on LCD had a greater reduction in triglycerides (-0.14 mmol/L; 95% CI, -0.18 to -0.10 mmol/L), diastolic blood pressure (-0.87 mmHg; 95% CI, -1.41 to -0.32 mmHg), weight loss (-1.33 kg; 95% CI, -1.79 to -0.87 kg), and a greater increase in high-density lipoprotein cholesterol (0.07 mmol/L; 95% CI, 0.06 to 0.09 mmol/L) in 6-23 months. However, the decrease of total cholesterol (0.14 mmol/L; 95% CI, 0.07 to 0.20 mmol/L) and low-density lipoprotein cholesterol (0.10 mmol/L; 95% CI, 0.06 to 0.14 mmol/L) was more conducive to LFD in 6-23 months. There was no difference in benefits between the two diets after 24 months. Subgroup analyses showed no significant difference in the reduction of total cholesterol, low-density lipoprotein cholesterol, and blood pressure between the two diets in participants with diabetes, hypertension, or hyperlipidemia. Conclusion: The results suggest that LCD and LFD may have specific effects on metabolic risk factors and weight loss in overweight and obese adults over 6 months. At 24 months, the effects on weight loss and improvement of metabolic risk factors were at least the same. These indicated that we might choose different diets to manage the overweight and obese subjects. However, the long-term clinical efficacy and effects of various sources of carbohydrates or fat in the two diets need to be studied in the future.

G-protein-coupled receptor kinase 4 causes renal angiotensin II type 2 receptor dysfunction by increasing its phosphorylation.

Activation of the angiotensin II type 2 receptor (AT2R) induces diuresis and natriuresis. Increased expression or/and activity of G-protein-coupled receptor kinase 4 (GRK4) or genetic variants (e.g., GRK4γ142V) cause sodium retention and hypertension. Whether GRK4 plays a role in the regulation of AT2R in the kidney remains unknown. In the present study, we found that spontaneously hypertensive rats (SHRs) had increased AT2R phosphorylation and impaired AT2R-mediated diuretic and natriuretic effects, as compared with normotensive Wistar-Kyoto (WKY) rats. The regulation by GRK4 of renal AT2R phosphorylation and function was studied in human (h) GRK4γ transgenic mice. hGRK4γ142V transgenic mice had increased renal AT2R phosphorylation and impaired AT2R-mediated natriuresis, relative to hGRK4γ wild-type (WT) littermates. These were confirmed in vitro; AT2R phosphorylation was increased and AT2R-mediated inhibition of Na+-K+-ATPase activity was decreased in hGRK4γ142V, relative to hGRK4γ WT-transfected renal proximal tubule (RPT) cells. There was a direct physical interaction between renal GRK4 and AT2R that was increased in SHRs, relative to WKY rats. Ultrasound-targeted microbubble destruction of renal GRK4 decreased the renal AT2R phosphorylation and restored the impaired AT2R-mediated diuresis and natriuresis in SHRs. In vitro studies showed that GRK4 siRNA reduced AT2R phosphorylation and reversed the impaired AT2R-mediated inhibition of Na+-K+-ATPase activity in SHR RPT cells. Our present study shows that GRK4, at least in part, impairs renal AT2R-mediated diuresis and natriuresis by increasing its phosphorylation; inhibition of GRK4 expression and/or activity may be a potential strategy to improve the renal function of AT2R.