Background: Vascular calcification (VC), in which vascular smooth muscle cells (VSMCs) undergo a phenotypic transformation into osteoblast-like cells, is one of the emergent risk factors for the accelerated atherosclerosis process characteristic of chronic kidney disease (CKD). Phosphate is an important regulator of VC. Methods: The expression of different smooth muscle cell or osteogenesis markers in response to high concentrations of phosphate or exogenous bone morphogenetic protein 2 (BMP-2) was examined by qRT-PCR and western blotting in rat VSMCs. Osteocalcin secretion was measured by radioimmunoassay. Differentiation and calcification of VSMCs were examined by alkaline phosphatase (ALP) activity assay and Alizarin staining. Short hairpin RNA-mediated silencing of β-catenin was performed to examine the involvement of Wnt/β-catenin signaling in VSMC calcification and osteoblastic differentiation induced by high phosphate or BMP-2. Apoptosis was determined by TUNEL assay and immunofluorescence imaging. Results: BMP-2 serum levels were significantly higher in CKD patients than in controls. High phosphate concentrations and BMP-2 induced VSMC apoptosis and upregulated the expression of β-catenin, Msx2, Runx2 and the phosphate cotransporter Pit1, whereas a BMP-2 neutralization antibody reversed these effects. Knockdown of β-catenin abolished the effect of high phosphate and BMP-2 on VSMC apoptosis and calcification. Conclusions: BMP-2 plays a crucial role in calcium deposition in VSMCs and VC in CKD patients via a mechanism involving the Wnt/β-catenin pathway.

In neonatal rats, precocious introduction of dietary fructose significantly enhances brush-border fructose transport rates and GLUT-5 mRNA levels during early weaning. In this study, these rates and levels were more than two times higher in the anastomosed intestine compared with those in the bypassed loop of weaning pups that underwent Thiry-Vella surgery and consumed high-fructose (HF) diets. In Thiry-Vella pups fed fructose-free (NF) diets, uptake rates and mRNA levels in the anastomosed intestine were very low and similar to those in the bypassed loop. In sham-operated littermates, transport rates and mRNA levels were similar between intestinal regions that corresponded to anastomosed and bypassed loops in Thiry-Vella pups and were two to three times greater in pups fed HF than in those fed NF diet. In contrast, rates of brush-border glucose transport and levels of SGLT-1 and of GLUT-2 mRNA were independent of diet and were similar between bypassed and anastomosed regions. Changes in GLUT-5 expression did not follow a distinct diurnal rhythm. When pups were fed HF diet after 12 h of starvation to empty the intestinal lumen, fructose transport rates increased with feeding duration and reached a plateau 12–24 h after feeding; in contrast, GLUT-5 mRNA levels were highest within 4 h after arrival of chyme in the jejunum and then decreased gradually and returned to baseline levels 24 h later. In littermates fed NF diet, mRNA levels and uptake rates were each independent of feeding duration. Luminal, and not endocrine, signals regulate GLUT-5 expression in weaning pups.

Objective: The aim of this work was to estimate the present periodontal problems of people in China, based on an epidemiological investigation of adults. Material and Methods: The data were collected from the northwest, southwest, northeast and east regions (400 subjects from each region) of China. All subjects were over 25 years of age. About half of the subjects were farmers and about half were urban professionals. Everyone was asked to fill out a questionnaire and to undergo a professional oral examination. Periodontal health status was evaluated by a simplified oral hygiene index (OHI-S), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PD), clinical attachment loss (CAL), and tooth mobility. Results: Of the 1590 subjects enrolled in this investigation, 45.7% were male, 45.5% were farmers, and the remaining were urban professionals, and 27.7% of the subjects were smokers. There was a significant difference in the educational background but not smoking between the rural and urban groups. While 34.9% of the subjects in the urban group brushed only once per day, 56.1% of the subjects in the rural group did so. The prevalence of bleeding during brushing was 71.1%, while about 61.4% of the subjects know nothing about scaling. All periodontal indices were significantly higher in males than in females and higher in the rural group than in the urban group. PD, CAL and tooth mobility increased with age. The percentage of sites with CAL43 mm in the rural group (49.5%) was significantly higher than that in the urban group (37.5%). Both current and former smokers showed increased CAL than non-smokers. Conclusion: Gingivitis and periodontitis are common findings in China. Most Chinese have no knowledge of common periodontal prevention and treatment and very few have regular dental care. The data of this study suggest that age, smoking, and limited education are significantly associated with Chinese adult periodontal attachment loss. Preventive periodontal care and education should be reinforced in the future by establishing relevant oral health projects.

Berberine (BBR) is considered a multi-target drug that has significant advantages. In contrast to its significant pharmacological effects in clinic, the plasma level of BBR is very low. Our previous work revealed that dihydroberberine (dhBBR) could be an absorbable form of BBR in the intestine, and butyrate is an active metabolite that is generated by gut bacteria in rats. In this study, for the first time we describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR by single (50 mg/kg) or multiple doses (50 mg/kg/d) for 7 days. GC-MS, GC, LC-MS/MS, and LC/MSn-IT-TOF were used to detect dhBBR, butyrate and BBR as well as its Phase I and II metabolites, respectively. The results showed that dhBBR was not detected in dog plasma but was excreted in small amounts in the feces of dogs examined on days 3 and 7. Butyrate was generated by gut bacteria and increased by 1.3- and 1.2-fold in plasma or feces, respectively, after 7 days of BBR treatment compared to the levels before treatment. Changes of intestinal bacterial composition were analyzed by 16S rRNA genes analysis. The results presented that dogs treated with BBR for 7 days increased both the abundance of the butyrate- and the nitroreductases- producing bacteria. We also identified chemical structures of the Phase I and II metabolites and analyzed their contents in beagle dogs. Eleven metabolites were detected in plasma and feces after BBR oral administration (50 mg/kg) to dogs, including 8 metabolites of Phase I and III metabolites of Phase II. The pharmacokinetic profile indicated that the concentration of BBR in plasma was low, with a Cmax value of 36.88 ± 23.45 ng/mL. The relative content of glucuronic acid conjugates (M11) was higher than those of other metabolites (M1, M2, M12, and M14) in plasma. BBR was detected in feces, with high excreted amounts on day 3 (2625.04 ± 1726.94 μg/g) and day 7 (2793.43 ± 488.10 μg/g). In summary, this is the first study to describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR, which is beneficial for discovery of drugs with poor absorption but good therapeutic efficacy.

ObjectiveAutosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration.MethodsTo analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥30 ml/min/1.73 m2. Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI). Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). A linear regression model was developed to analyze the factors which determine eGFR and TKV changes.ResultsThe age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3±10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline log10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (r = 0.222) and higher TKV (r = 0.134).ConclusionsThis large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression.

Advanced glycation end products (AGEs) are protein-bound uremic toxins and are elevated in patients with the end-stage of renal disease. The present study sought to develop an effective method to remove the circulating AGEs from patients using the combination of hemodialysis (HD) and hemoperfusion (HP). Thirty-six patients undergoing maintenance HD for 3 months were randomly divided into two groups. Patients in Group 1 received HD, followed by the combined HP + HD treatment once, whereas patients in Group 2 were first treated with HP + HD and then they received the HD treatment alone. Patients treated with HD alone did not alter higher levels of serum AGEs. In contrast, patients treated with the combined HP + HD exhibited significantly lower levels of serum AGEs and TNF-α. Results from this study demonstrate that the combination of HD + HP treatment may be an effective and better approach to remove the protein-bound uremic toxins and inflammatory cytokines.

Ultrasonic tissue characterization with integrated backscatter (IBS) offers a promising method for the noninvasive assessment of myocardial fibrosis and contractile performance. The aim of this study was to investigate the effect of thrice-weekly in-center nocturnal hemodialysis (INHD) and conventional hemodialysis (CHD) on myocardial fibrosis and left ventricular function in end-stage renal disease patients. Thirty-two INHD and 58 matched CHD patients were enrolled; baseline and 12-month measures of blood pressure (BP), serum calcium and phosphorus, echocardiographic left ventricular mass index (LVMI) and left ventricular function, the myocardial calibrated IBS (C-IBS), and systodiastolic cyclical variations in IBS (CV-IBS) were collected. The baseline characteristics were similar between groups, except that serum phosphorus and calcium × phosphorus were higher in the INHD group. At 12-month follow-up, there was a significant decrease in the mean C-IBS (-20.2 ± 3.7 to -28.1 ± 4.0 dB, P<0.01) and a significant increase in CV-IBS (5.0 ± 1.5 to 7.1 ± 1.6 dB, P<0.01) in INHD patients. Multivariate analysis showed that the mean C-IBS was positively related to SBP, DBP, LVMI, serum phosphorus, and left atrial volume index and inversely related to midwall fractional shortening, transmitral E/A ratio, and E(m) . The mean CV-IBS was positively correlated with left ventricular midwall fractional shortening, E/A ratio, E(m) and inversely correlated with SBP, DBP, LVMI, serum phosphorus, E/E(m) , and left atrial volume index. There was no significant change in the mean C-IBS, mean CV-IBS, and LVMI in the CHD group. Compared with CHD, INHD improves myocardial fibrosis and left ventricular function, and control of serum phosphorus is associated with the improvement of myocardial fibrosis. Improvement of myocardial fibrosis contributes to the reduction of left ventricle hypertrophy.

Background: Cardiovascular events (CVE) are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. These patients are often excluded from CV clinical trials, and the prognostic factors associated with CVE in patients with ESRD have not been fully explored. We investigated the role of BNP and NT-proBNP in predicting the outcome and prognostic value in hemodialysis with ESRD patients. Methods: Baseline NT-proBNP and BNP, indices of dialysis adequacy, and biochemical characteristics were assessed in 217 dialysis patients with ESRD who were followed prospectively for 2 years or until death. CVE included cardiovascular death, myocardial infarction, heart failure and stroke. Results: Using multivariable Cox regression analysis, BNP and NT-proBNP remained predictive of cardiovascular mortality (BNP: hazard ratio 1.22, 95% confidence interval (CI) 1.21–11.04, p < 0.05; NT-proBNP hazard ratio 1.86, 95% CI 1.14–9.36, p < 0.05), fatal/nonfatal CHF (BNP: 1.35, 1.33–11.78, p < 0.05; NT-proBNP: 2.25, 1.54–12.68, p < 0.001) and fatal/nonfatal MI (BNP: 0.61, 2.38–19.53, p = 0.42; NT-proBNP: 1.90, 3.28–20.17, p < 0.001). NT-proBNP had better predictive value than BNP for mortality (area under the ROC curve (AUC) 0.83 vs. 0.61; p < 0.05). Conclusion: These data showed that BNP and NT-proBNP are very sensitive and specific predictors of CVE in dialysis patients.