The arsenic-lowering effect of inulin-type prebiotics in end-stage renal disease: a randomized crossover trial.

Background: Circulatory imbalance of trace elements is frequent in end-stage renal disease (ESRD), leading to a deficiency of essential elements and excess of toxic elements. The present study aimed to investigate whether inulin-type fructans (ITFs) could ameliorate the circulatory imbalance by modulating gut microbiota and regulating the absorption and elimination of trace elements. Methods: Peritoneal dialysis patients were enrolled in a randomized crossover trial, undergoing interventions with ITFs (10 g d-1) and maltodextrin (placebo) over a 9-month period (with a 3-month washout). The primary outcomes included essential elements Mn, Fe, Co, Cu, Zn, Se, Sr, and Mo and potential toxic elements V, Cr, Ni, As, Cd, Ba, Tl, Pb, Th, and U in plasma. Secondary outcomes included the gut microbiome, short chain fatty acids (SCFAs), bile acids (BAs), and daily removal of trace elements through urine, dialysate and feces. Results: Among the 44 participants initially randomized, 29 completed the prebiotic, placebo or both interventions. The daily dietary intake of macronutrients and trace elements remained consistent throughout the study. The administration of 10 g d-1 ITFs significantly reduced plasma arsenic (As) by 1.03 µg L-1 (95%CI: -1.74, -0.33) (FDR-adjusted P = 0.045) down from the baseline of 3.54 µg L-1 (IQRs: 2.61-4.40) and increased the As clearance rate by urine and dialysis (P = 0.033). Positive changes in gut microbiota were also observed, including an increase in the Firmicutes/Bacteroidetes ratio (P = 0.050), a trend towards higher fecal SCFAs (P = 0.082), and elevated excretion of primary BAs (P = 0.035). However, there were no significant changes in plasma concentrations of other trace elements or their daily removal by urine, dialysis and feces. Conclusions: The daily administration of 10 g d-1 ITFs proved to be effective in reducing the circulating retention of As but demonstrated to be ineffective for other trace elements in ESRD. These sentences are ok to include but as "The clinical trial registry number is ChiCTR-INR-17013739 (https://www.chictr.org.cn/showproj.aspx?proj=21228)".

Dietary Polyphenol Intake and Risk of Hypertension: An 18-y Nationwide Cohort Study in China.

BACKGROUND: Although increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still lacking. OBJECTIVES: This study aimed to investigate the association between dietary polyphenol and hypertension risk in the China Health and Nutrition Survey (N = 11,056). METHODS: Food intake was assessed using 3-d, 24-h dietary recalls and household weighing method; polyphenol intake was calculated by multiplying consumption of each food and its polyphenol content. Hypertension was defined as BP ≥ 140/90 mmHg, physicians' diagnosis, or taking antihypertension medications. HR and 95% CI were estimated using mixed-effects Cox models. RESULTS: During 91,561 person-years of follow-up, a total of 3866 participants developed hypertension (35%). The lowest multivariable-adjusted HR (95% CI) of hypertension risk occurred in the third quartile intake, which was 0.63 (0.57, 0.70) for total polyphenol, 0.61 (0.55, 0.68) for flavonoid, 0.62 (0.56, 0.69) for phenolic acid, 0.46 (0.42, 0.51) for lignan, and 0.58 (0.52, 0.64) for stilbene, compared with the lowest quartile. The polyphenol-hypertension associations were nonlinear (all Pnonlinearity < 0.001), and different patterns were observed. U-shaped relations with hypertension were observed for total polyphenol, flavonoid, and phenolic acid, whereas L-shaped associations were observed for lignan and stilbene. Moreover, higher fiber intake strengthened the polyphenol-hypertension association, especially for lignan (P-interaction = 0.002) and stilbene (P-interaction = 0.004). Polyphenol-containing food, particularly vegetables and fruits rich in lignan and stilbene, were significantly associated with lower hypertension risk. CONCLUSIONS: This study demonstrated an inverse and nonlinear association between dietary polyphenol, especially lignan and stilbene, and hypertension risk. The findings provide implications for hypertension prevention.

The Effect of Inulin-Type Fructans on Plasma Trimethylamine N-Oxide Levels in Peritoneal Dialysis Patients: A Randomized Crossover Trial.

SCOPE: Trimethylamine N-oxide (TMAO), an important proatherogenic uremic toxin, is oxidized by hepatic-flavin monooxygenases from gut microbiome-generated trimethylamine (TMA). The present study aims to explore whether manipulating the gut microbiota by inulin-type fructans (ITFs) can reduce circulating TMAO levels in peritoneal dialysis patients. METHODS AND RESULTS: This is a randomized, double-blind, placebo-controlled, crossover trial with 10 g day-1 ITFs intervention for 3 months in continuous ambulatory peritoneal dialysis patients. The gut microbiome is measured, and TMA-producing gene clusters are annotated using shotgun metagenomic sequencing. Fecal and plasma TMA, plasma TMAO, and daily urine excretion and dialysis removal of TMAO are measured. Finally, 22 participants complete the trial. The daily intake of macronutrients and TMAO precursors is comparable during the prebiotics, washout, and placebo interventions. The ITFs intervention increases the Firmicutes/Bacteroidetes (F/B) ratio (p = 0.049) of gut microbiome. However, no significant influences are observed on fecal TMA content, circulating TMAO levels, or TMA-producing gene clusters, including choline TMA-lyase (CutC/D), carnitine monooxygenase (CntA/B), and betaine reductase (GrdH). CONCLUSIONS: Intervention with 10 g day-1 of ITFs for 3 months is not sufficient to reduce plasma TMAO levels in peritoneal dialysis patients, but it improves the gut microbiome composition.

Increased risk of modality failure with higher serum uric acid level in continuous ambulatory peritoneal dialysis patients: a prospective cohort study.

BACKGROUND: Peritoneal dialysis (PD) is one of the most important kidney replacement therapies for patients with end-stage kidney disease (ESKD). PD technique failure can lead to an escalated cost and increased infectious and cardiovascular risk, up and including to death. The accumulation of uric acid (UA) was associated with adverse outcomes in ESKD patients. However, the relationship between serum UA and technique failure is little explored. METHODS: Here, a total of 266 continuous ambulatory peritoneal dialysis (CAPD) patients (age, 41.8 ± 12.6 years; 125 males) were enrolled and followed up for 31.7 months. Serum UA levels were examined at baseline and each visit. Subjects were divided into three groups according to their baseline serum UA concentrations. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of PD technique failure. RESULTS: The level of serum UA increased gradually as time prolonged. During the follow-up period, 77 (28.9%) patients occurred PD technique failure, of which 56 (21.1%) transferred to hemodialysis (HD) and 21 (7.9%) died. Compared to the lowest UA tertile, after adjusting for potential confounders, HRs of technique failure in tertile 2 and tertile 3 were 1.82 (95% CI: 0.95-3.49) and 2.03 (95% CI: 1.05-3.92), respectively, and p for trend was 0.043. Adjusted HRs of all-cause technique failure, transferring to HD and mortality with each 1 mg/dL increase in serum UA were 1.20 (95% CI: 1.03-1.40, p = 0.019), 1.22 (95% CI: 1.01-1.48, p = 0.039), and 1.25 (95% CI: 0.94-1.67, p = 0.128), respectively. CONCLUSION: Higher serum UA level predicted higher risk of technique failure in CAPD patients.

The Accumulation of Gut Microbiome-derived Indoxyl Sulfate and P-Cresyl Sulfate in Patients With End-stage Renal Disease.

OBJECTIVES: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two important gut microbiota-generated protein-bound uremic toxins. The present study aims to explore the alterations of serum IS and pCS concentrations, their production, and daily removal in end-stage renal disease (ESRD). METHODS: A case-controlled study was conducted based on 11 patients with ESRD and 11 healthy volunteers. The metabolic processes for IS and pCS were compared in these two groups, including gut microbiome, fecal indole and p-cresol, indole-producing bacteria and p-cresol-producing bacteria, serum total IS and pCS concentrations, and their daily removal by urine and spent dialyzate. RESULTS: Compared with healthy controls, patients with ESRD exhibited higher relative abundance of the indole-producing bacteria Escherichia coli (P < .001) and Bacteroides fragilis (P = .010) and p-cresol-producing bacteria Bacteroides fragilis (P = .010) and Bacteroides caccae (P = .047). The predicted functional profiles of gut microbiome based on 16S rRNA gene PhyloChip analysis showed that the microbial tryptophan metabolism pathway (map00380, P = .0006) was significantly enriched in patients with ESRD. However, the fecal precursors indole (P = .332) and p-cresol concentrations (P = .699) were comparable between the two groups. The serum IS (P < .001) and pCS (P < .001) concentrations were far higher in patients with ESRD than those in healthy controls, whereas the daily total removal by urine and dialyzate was much lower for the former than that for the latter (P = .019 for IS, P = .016 for pCS). CONCLUSIONS: The present study showed serious IS and pCS accumulation in patients with ESRD, with significant expansion of indole-producing bacteria and p-cresol-producing bacteria, upregulation of the bacterial tryptophan metabolism pathway, and greatly increased serum IS and pCS concentrations, whereas significant decline of daily IS and pCS removal.

Inulin-type prebiotics reduce serum uric acid levels via gut microbiota modulation: a randomized, controlled crossover trial in peritoneal dialysis patients.

PURPOSE: Increased levels of uric acid (UA), which is mainly excreted through the kidneys, are independently associated with higher mortality in end-stage renal disease (ESRD) patients. The uricolysis of gut microbiota plays an important role in extrarenal excretion of UA. This study aimed to examine the effect of inulin-type prebiotics (a type of fermentable dietary fiber) on intestinal microbiota modulation and serum UA levels in ESRD patients. METHODS: Continuous ambulatory peritoneal dialysis (CAPD) patients were recruited to a randomized, double-blind, placebo-controlled crossover trial of 12-week inulin-type prebiotics. Participants were visited before and after treatment with prebiotics or placebo. Serum UA levels, dietary purine intake, serum xanthine oxidase (XO) activity, daily "renal excretion" of UA, and fecal UA degradation capability were measured at each visit. Fecal metagenomic analysis was conducted to assess microbial composition and function. RESULTS: Sixteen participants (mean age = 37 y; 10 men and 6 women) completed the trial, and 64 specimens were analyzed. The average concentration of serum UA decreased by approximately 10% in the prebiotic intervention group in comparison to the placebo group (p = 0.047) without an increase in daily "renal excretion" of UA via urine and dialysate. There were no significant changes in purine intake or activity of XO. Notably, enhanced fecal UA degradation was observed after prebiotic intervention (p = 0.041), and the ratio of Firmicutes/Bacteroidetes, which was positively associated with fecal UA degradation, increased in the prebiotic period (p = 0.032). Furthermore, prebiotics enriched purine-degrading species in the gut microbiota, including unclassified_o_Clostridiales, Clostridium sp. CAG:7, Clostridium sp. FS41, Clostridium citroniae, Anaerostipes caccae, and Clostridium botulinum. CONCLUSIONS: Inulin-type prebiotics is a promising therapeutic candidate to reduce serum UA levels in renal failure patients, and this urate-lowering effect could possibly be attributed to intestinal microbial degradation of UA. TRIAL REGISTRY: This study was registered at the Chinese Clinical Trials Registry ( http://www.chictr.org.cn/ ), registration ID: ChiCTR-INR-17013739, registration date: 6th Dec 2017.

Nutritional predictors associated with malnutrition in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: Currently in China, out of the total dialysis population, approximately 20% represents continuous ambulatory peritoneal dialysis (CAPD) and almost half of CAPD patients was affected by malnutrition. This study aimed to investigate the association between nutritional predictors and malnutrition with 5.1 years of dialysis according to the subjective global assessment (SGA) in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: A cross-sectional study was conducted from April 2013 to May 2018 and included 70 CAPD patients. The relationship between anthropometric and biochemical parameters with malnutrition was assessed by multiple logistic regression analysis. RESULTS: The prevalence of malnutrition in CAPD patients was 52.9%. Our result revealed a 7.05-fold increased odds of malnutrition for patients with protein equivalent of total nitrogen appearance normalized to body weight (nPNA) < 1.0 g/kg per day (d) versus patients with normal nPNA (confidence interval (CI) 1.33-37.34; p < 0.05). Patients whose normalized protein catabolic rate (nPCR) was <1.2 g/(kg/d) had a significant positive association with malnutrition versus patients with normal nPCR (adjusted odds ratio (OR) 7.99; p < 0.05). Patients with dietary protein intake (DPI) < 1.0 g/(kg/d) had a higher likelihood of malnutrition than those with normal DPI (OR 12.73; p < 0.05). CAPD patients with upper arm circumference (UAC) < 23.2 cm had a high risk of malnutrition versus patients with normal UAC (OR 12.99; p < 0.05). CONCLUSIONS: Our study suggested a close association between nPNA, DPI, nPCR, and UAC and malnutrition in CAPD patients. Further studies can be warranted the use of these variables as predictors and a malnutrition consequence among Chinese CAPD patients.

The Association of Feeding Practices and Sociodemographic Factors on Underweight and Wasting in Children in Ethiopia: A Secondary Analysis of Four Health Surveys from 2000 to 2016.

BACKGROUND: Feeding practices highly influence the nutritional status of children between 6 and 23 months of age in developing countries, including Ethiopia. Therefore, this study was conducted to investigate the association of feeding practices and sociodemographic factors on underweight and wasting of children aged 6-23 months in Ethiopia. METHODS: Data on 8003 children 6-23 months of age from four Ethiopia demographic and health surveys (EDHS) from 2000 to 2016 were analyzed using complex sample crosstabs for multivariate analysis. The association of feeding practices and sociodemographic factors on underweight and wasting was assessed via multiple logistic regression analyses adjusting the covariates. The outcomes were reported based on the adjusted odds ratios (ORs) with 95% confidence interval (CI). RESULTS: Male children, very small at birth size children, diarrhea and fever, and short stature mother were risk factors for underweight and wasting (p < 0.05-0.001). Also, minimum dietary diversity, rich and middle-income families, vitamin A in the previous 6 months and antenatal care visits during pregnancy were protective factors for both underweight and wasting (p < 0.05-0.001). Minimum meal frequency was significantly related to lower odds of wasting (p < 0.001). Higher age of the child was significantly associated with underweight (p < 0.05-0.001); however, it was less likely wasted (p < 0.05-0.01). CONCLUSION: The present study depicted that among infant young children feeding core indicators except breastfed, all the other indicators did not met the required standard; however, sociodemographic factors on four health surveys from 2000 to 2016 were associated with underweight and wasting in children in Ethiopia. LAY SUMMARY: • Over the years the prevalence of underweight in children aged 6-23 months in the country has shown a significant improvement from 40.2% in 2000 to 34.7% in 2005, then further reduced to 28.9% and 20.0% in 2011 and 2016 EDHS, respectively.• In the same manner, the prevalence of wasting in children aged 6-23 months in Ethiopia also observed improvement from 18.9% in 2000 to 16.7% in 2005, then further reduced to 15.4% and 13.9% in 2011 and 2016 EDHS, respectively.• Male children, very small at birth size children, diarrhea and fever (for the last 2 weeks), and short stature mother were risk factors for underweight and wasting.• Minimum dietary diversity, rich and middle-income families, vitamin A in the previous 6 months and antenatal care visits during pregnancy were protective factors for both underweight and wasting.• Minimum meal frequency was significantly related to lower odds of wasting.• Higher age of the children was significantly associated with underweight; however, less likely wasted.

Dietary condition and feeding practices of children aged 6-23 months in Ethiopia: analysis of 2005-2016 demographic and health survey.

BACKGROUND: Childhood malnutrition is well estimated as the major underlying risk factor for morbidity and mortality in children under 5 years. Feeding practices greatly influence the dietary condition of children aged 6-23 months in developing countries. Therefore, this study was performed to determine the association between infant young children feeding (IYCF) practices and the dietary conditions of children aged 6-23 months in Ethiopia. METHOD: A cross-sectional study was conducted based on data on 5638 children aged 6-23 months from three Ethiopia Demographic and Health Surveys (EDHS) (2005, 2011, 2016). Multivariable logistic regression was performed to estimate the odd ratios (ORs) and 95% confidence intervals (CIs) of stunting and anaemia with IYCF practices. RESULT: The prevalence of stunting among children aged 6-23 months in Ethiopia decreased greatly from 49% in 2005 to 32% in 2016. Among the IYCF practices, consumption of iron-rich foods, minimum dietary diversity (MDD), and minimum acceptable diet (MAD) were significant predictors of stunting. In addition, the prevalence of anaemia declined significantly from 26% in 2005 to 16% in 2011, but increased to 29% in 2016. Among the IYCF practices, breastfeeding and minimum meal frequency (MMF) had lower odds of childhood anaemia. CONCLUSIONS: The present study showed that anaemia and stunting among children aged 6-23 months in Ethiopia is critical public health problems that need urgent attention.

Health risk and temporal trend of dietary potentially toxic elements exposure in the residents of the Shenzhen metropolis, China, between 2005 and 2017: a risk assessment based on probabilistic estimation.

Dietary potentially toxic elements (PTEs) exposure in developing countries is of great concern. Probabilistic estimation exhibits great superiority in risk assessment by dealing with the variability and uncertainty of the parameters. Here, a probabilistic estimation based on two dimensions, PTEs in foods and food intake, was conducted. A total of 13 foods were collected from Shenzhen markets during 2005-2017, and the concentrations of Pb, Cd, Hg, and As were detected. A total of 853 residents from 245 households participated in a total diet study. The mean concentrations of Pb, Cd, Hg and As were 0.046, 0.0196, 0.0038, and 0.029 mg kg-1 in cereals, 0.042, 0.0174, 0.0027, and 0.014 mg kg-1 in vegetables, 0.044, 0.0237, 0.0056, and 0.021 mg kg-1 in meat, and 0.081, 0.1035, 0.0257, and 0.680 mg kg-1 in aquatic products, respectively. The probability density function showed that the 95th percentiles of the Pb, Cd, Hg, As hazard quotients (HQ) and the hazard index (HI) were 0.68, 1.57, 0.38, 5.81 and 7.51, respectively. Cumulative probability and sensitivity analysis showed that cereals and vegetables contributed most to Pb and Cd exposure; aquatic products to Hg exposure; and cereals and aquatic products to As exposure. The results showed that Shenzhen residents were at risk of exposure to Cd, As, and four PTEs in combination, although a temporal decreasing trend was observed. The probabilistic estimation used here reveals a complete picture of multiple PTEs exposure risk and identifies major contributing food categories, providing a valuable means for risk assessment.

Inulin-type fructan intervention restricts the increase in gut microbiome-generated indole in patients with peritoneal dialysis: a randomized crossover study.

BACKGROUND: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS), 2 important protein-bound uremic toxins, are independent risk factors for cardiovascular disease in patients with end-stage renal disease. Indole and p-cresol are gut microbiome-generated precursors of IS and pCS. OBJECTIVE: The aim of the present study was to determine whether inulin-type fructans (ITFs) reduce the production of indole and p-cresol by altering their producing bacteria in patients with peritoneal dialysis. METHODS: Patients receiving peritoneal dialysis for >3 mo without diabetes and not using antibiotics were recruited to a randomized, double-blind, placebo-controlled, crossover trial of ITF intervention over 36 wk (12-wk washout). The primary outcomes were gut microbiome, fecal indole and p-cresol, indole-producing bacteria, p-cresol-producing bacteria, and serum IS and pCS. The secondary outcomes were fecal pH, 24-h urine, and dialysis removal of IS and pCS. RESULTS: Of 21 individuals randomly assigned, 15 completed the study. The daily nutrient intakes, including protein, tryptophan, and tyrosine, were isostatic during the prebiotic, washout, and placebo intervention. There were no baseline differences in the outcomes of interest between treatments. For fecal indole, its concentrations did not change significantly in either treatment. However, there was a trend toward the treatment-by-time effect (P = 0.052), with a quantitative reduction in the ITF treatment and an increase in the control. The difference in the changes between the 2 treatments was significant (-10.07 ± 7.48 µg/g vs +13.35 ± 7.66 µg/g; P = 0.040). Similar to Bacteroides thetaiotaomicron, there was a difference over time between the 2 treatments, with a significant treatment and time interaction effect (P = 0.047). There were no treatment, time, or interaction effects for fecal p-cresol, serum IS and pCS, 24-h urine, and dialysis removal of IS and pCS. CONCLUSIONS: Our results suggested that ITFs restricted the increase in gut microbiome-generated indole in patients with peritoneal dialysis. This trial was registered at http://www.chictr.org.cn/showproj.aspx?proj=21228 as ChiCTR-INR-17013739.

Fatigue in Peritoneal Dialysis Patients and an Exploration of Contributing Factors: A Cross-Sectional Study.

CONTEXT: Fatigue is a common and detrimental symptom in dialysis patients; however, our understanding of it and investigation of its contributing factors is still very limited, especially in peritoneal dialysis (PD) patients. OBJECTIVES: To assess fatigue in PD patients and identify contributing factors. METHODS: One hundred eight PD patients in a comprehensive hospital in China were recruited. The fatigue severity of the participants was assessed using the Chalder Fatigue Scale 11. Demographic factors and results of physiological tests were collected. Quality of sleep, mental health, and social support were assessed with the Pittsburgh Sleep Quality Index, Symptom Checklist 90, and Social Support Rating Scale, respectively. Multiple linear regression models were conducted with candidate variables with a P-value of less than 0.1 on univariate analysis and variables that were clinically relevant to identify contributing factors for fatigue. RESULTS: The fatigue level in PD patients was significantly higher than the community population, and 78.7% of them were suffering from fatigue. The factors that were significantly associated with fatigue were quality of sleep, normalized protein nitrogen appearance, transferrin, alkaline phosphatase, and total cholesterol (adjusted R squared 0.86). Among them, quality of sleep, transferrin, alkaline phosphatase, and total cholesterol were significant contributors for physical fatigue, whereas the quality of sleep and normalized protein nitrogen appearance were contributing factors for mental fatigue. CONCLUSION: Fatigue is a common symptom in PD patients, suggesting that increased awareness of this symptom is required. The identification of correlates by extensive exploration of multidimensional factors in this study may help practitioners to identify patients at higher risk and to develop a multidimensional and targeted intervention plan.

Role of Resveratrol on Indoxyl Sulfate-Induced Endothelial Hyperpermeability via Aryl Hydrocarbon Receptor (AHR)/Src-Dependent Pathway.

Resveratrol (RES), a dietary polyphenol compound, has been shown to possess health benefits due to its anti-inflammatory, antioxidative, and antiatherosclerosis properties. Tryptophan metabolite-derived indoxyl sulfate (IS) is identified as one of the uremic toxins and physiological endogenous ligand/activator of aryl hydrocarbon receptor (AHR), associated with atherosclerosis in chronic kidney disease (CKD) patients. Studies have shown that a high serum level of IS causes deleterious effects on health primarily by inducing oxidative stress and endothelial dysfunction. However, the precise mechanisms are still unclear. Here, we investigated the underlying mechanism of IS effect on endothelial permeability and the role of RES on IS-induced endothelial hyperpermeability via the AHR/Src-dependent pathway. Bovine aorta endothelial cells (BAECs) were cultured and incubated with IS in the presence or absence of RES, and transendothelial electrical resistance (TEER) and permeability of cells were measured. Alongside, AHR, Src kinase, and Vascular Endothelial Cadherin (VE-Cadherin) activation were examined. Our data showed that IS reduced TEER of cells resulting in increased permeability. VE-Cadherin, a vital regulator of endothelial permeability, was also significantly activated in response to IS, which appeared to be associated with changes of endothelial permeability and AHR/Src kinase. Interestingly, in this setting, RES reversed the effect of IS and inhibited the increased activation of Src induced by IS-activated AHR and modulated VE-Cadherin and permeability. CH223191, an inhibitor of AHR, significantly inhibits IS-induced endothelial hyperpermeability. Further analysis with treatment of PP2, an inhibitor of Src abolishing Src activation, suggests downstream factors. All our data indicated that IS upregulated the AHR/Src kinase pathway, and increased endothelial permeability and phosphorylation of VE-Cadherin may be represented and provide new strategies for addressing protective properties of RES against Src kinase involved in AHR-mediated endothelial hyperpermeability. The findings may be crucial for managing diseases in which endothelial permeability is compromised, and the dietary polyphenols are involved.

High serum arsenic and cardiovascular risk factors in patients undergoing continuous ambulatory peritoneal dialysis.

The present study aims to assess arsenic accumulation and explore its association with renal function and biomarkers of CVD risk in chronic kidney disease patients receiving continuous ambulatory peritoneal dialysis (CAPD). The serum was collected from 87 CAPD patients and 26 healthy subjects between 2015 and 2016. The arsenic concentration was measured by inductively coupled plasma mass spectrometer. Clinical variables related to CVD risk were determined with automatic biochemical analyzer. Serum arsenic was higher in CAPD patients as compared to healthy volunteers. Moreover, significant differences of BMI, serum phosphorus, eGFR and Ccr were observed among groups. Positive correlation between serum arsenic and serum phosphorus was found (r = 0.453, p < 0.001). While serum arsenic was negatively associated with Ccr (r = -0.328, p = 0.002) and eGFR (r = -0.248, p = 0.020). The logistic regression models revealed that high serum arsenic was related to hyperphosphatemia (ORs, 1.827; 95%CI, 1.145-2.913) after adjusted for the potential confounding factors. Overall, our findings inferred the accumulation of arsenic in CAPD patients. In addition, high serum arsenic was independently associated with the occurrence of hyperphosphatemia, which was a special and ubiquitous CVD risk factor in CAPD patients. This study provided a clue for the association between arsenic and CVD burden in CKD patients. At the same time, it suggested that prevention of arsenic accumulation should be taken into consideration clinically.

Effects of green tea polyphenols on trace metals level of rats on food restriction and high-fat diet.

Little evidence showed the interplay between tea and diet in the regulation of trace metal. Here, we examined the effects of green tea polyphenols (GTPs) on the level of trace elements (TEs) in rats on food restriction or high-fat diet. Thirty-six rats (Wistar, male) were randomly divided into 6 groups and fed on standard diet, food restriction and high-fat diet with or without GTPs (200 mg/kg bw/day) supplementation, respectively. Levels of vanadium (V), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo) and cobalt (Co) in feed, whole blood, femur and urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Blood glucose, total cholesterol (TC), triglycerides (TG), high and low density lipoprotein-cholesterol (LDL-C, HDL-C) in serum were determined. Decreased daily intakes of TEs were observed in rats on food restriction and high-fat diet. Decreased whole blood level of Zn, femur level of Co and increase urinary excretion of Se were observed in rats fed on high-fat diet. GTPs altered the whole blood level of several TEs in rats on food restriction (V, Zn, Co) or high-fat diet (V, Se), respectively, but not in rats fed on standard diet. The level of several TEs in femur and the daily urinary excretion of V and Mo were altered by GTPs in rats on all of the three diets. In addition, rats fed on high-fat diet developed dyslipidemia, which was ameliorated by GTPs. The data indicated that diet status played a role in the effects of GTPs on TEs and lipid metabolism, and trace elements may play a role in the modulation of lipid metabolic disturbances by high-fat diet and GTPs.

Bisphenol A induces proliferative effects on both breast cancer cells and vascular endothelial cells through a shared GPER-dependent pathway in hypoxia.

Based on the breast cancer cells and the vascular endothelial cells are both estrogen-sensitive, we proposed a close reciprocity existed between them in the tumor microenvironment, via shared molecular mechanism affected by environmental endocrine disruptors (EDCs). In this study, bisphenol A (BPA), via triggering G-protein estrogen receptor (GPER), stimulated cell proliferation and migration of bovine vascular endothelial cells (BVECs) and breast cancer cells (SkBr-3 and MDA-MB-231) and enhanced tumor growth in vivo. Moreover, the expression of both hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were up-regulated in a GPER-dependent manner by BPA treatment under hypoxic condition, and the activated GPER induced the HIF-1α expression by competitively binding to caveolin-1 (Cav-1) and facilitating the release of heat shock protein 90 (HSP90). These findings show that in a hypoxic microenvironment, BPA promotes HIF-1α and VEGF expressions through a shared GPER/Cav-1/HSP90 signaling cascade. Our observations provide a probable hypothesis that the effects of BPA on tumor development are copromoting relevant biological responses in both vascular endothelial and breast cancer cells.

Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway.

SCOPE: Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. METHODS AND RESULTS: Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) and sirtuin 3(SIRT3) were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE) level and the acetyl-MnSOD (K122)/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. CONCLUSION: The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.

Resveratrol ameliorates diet-induced dysregulation of lipid metabolism in zebrafish (Danio rerio).

Defective lipid metabolism is associated with increased risk of various chronic diseases, such as obesity, cardiovascular diseases, and diabetes. Resveratrol (RSV), a natural polyphenol, has been shown the potential of ameliorating disregulations of lipid metabolism. The objective of this study was to investigate the effects of feed intake and RSV on lipid metabolism in zebrafish (Danio rerio). The adult males were randomly allocated to 6 groups: control (Con, 8 mg cysts/fish/day), control with 20 µmol/L RSV (Con+RSV), calorie restriction (CR, 5 mg cysts/fish/day), calorie restriction with RSV (CR+RSV), overfeed (OF, 60 mg cysts/fish/day), and overfeed with RSV (OF+RSV) groups. The treatment period was 8 weeks. Results showed that CR reduced body length, body weight, and condition factor of zebrafish. CR reduced levels of plasma triglyceride (TG) and induced protein expression of phosphorylated AMP-activated protein kinase-α (pAMPKα), silent information regulator 2 homolog 1 (Sirt1), and peroxisome proliferator activated receptor gamma coactivator-1α (PGC1α). RSV attenuated CR-induced pAMPKα/AMPKαincreases. RSV increased levels of Sirt1 protein in the OF zebrafish, and decreased OF-induced increase in peroxisome proliferator-activated receptor-γ (PPARγ) protein level. Additionally, RSV down-regulated caveolin-1 and up-regulated microtubule-associated protein 1 light chain 3 -II (LC3-II) protein levels in OF zebrafish. In conclusion, these results suggest that 1) CR reduces plasma TG level through activation of the AMPKα-Sirt1- PGC1α pathway; 2) under different dietary stress conditions RSV might regulate AMPK phosphorylation bi-directionally; 3) RSV might regulate lipid metabolism through the AMPKα-Sirt1-PPARγ pathway in OF zebrafish.

Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux.

Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR) or dietary polyphenols such as green tea polyphenols (GTPs) can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD), DR, high-fat diet (HFD), and three diets plus 200 mg/kg(bw)/day GTPs, respectively. After 18 weeks, HFD group exhibited renal injuries by increased serum cystatin C levels and urinary N-acetyl-ß-d-glucosaminidase activity, which can be ameliorated by GTPs. Meanwhile, autophagy impairment as denoted by autophagy-lysosome related proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1, was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux suppression was detected in palmitic acid (PA)-treated human proximal tubular epithelial cells (HK-2), which was ameliorated by epigallocatechin-3-gallate (EGCG). Furthermore, GTPs (or EGCG) elevated phosphorylation of AMP-activated protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells. These findings revealed that GTPs mimic the effects of DR to induce autophagy and exert a renal protective effect by alleviating HFD-induced autophagy suppression.

Long-term exposure to a 'safe' dose of bisphenol A reduced protein acetylation in adult rat testes.

Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a 'safe' dose of BPA. Twenty adult male rats received either BPA (50 µg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls. Additionally, increased protein expression of deacetylase Sirt1 and reduced binding of Sirt1, together with increased binding of estrogen receptor ß (ERß) to caveolin-1 (Cav-1), a structural protein component of caveolar membranes, were detected in treated rats compared with controls. Moreover, decreased acetylation of Cav-1 was observed in the treated rats for the first time. Our study showed that long-term exposure to a 'safe' dose of BPA reduces histone acetylation in the male reproductive system, which may be related to the phenotypic paternal-to-offspring transmission observed in our previous study. The evidence also suggested that these epigenetic effects may be meditated by Sirt1 via competition with ERß for binding to Cav-1.