No abstract

A switch from autophagy to apoptosis is implicated in chondrocytes during the osteoarthritis (OA) progression with currently unknown mechanism(s). In this study we utilized a flow fluid shear stress (FFSS) model in cultured chondrocytes and a unilateral anterior crossbite (UAC) animal model. We found that both FFSS and UAC actively induced endoplasmic reticulum stress (ERS) in the temporomandibular joints (TMJ) chondrocytes, as demonstrated by dramatic increases in expression of HSPA5, p-EIF2AK3, p-ERN1 and ATF6. Interestingly, both FFSS and UAC activated not only pro-death p-EIF2AK3-mediated ERS-apoptosis programs but also pro-survival p-ERN1-mediated autophagic flux in chondrocytes. Data from FFSS demonstrated that MTORC1, a downstream of p-ERN1, suppressed autophagy but promoted p-EIF2AK3 mediated ERS-apoptosis. Data from UAC model demonstrated that at early stage both the p-ERN1 and p-EIF2AK3 were activated and MTORC1 was inhibited in TMJ chondrocytes. At late stage, MTORC1-p-EIF2AK3-mediated ERS apoptosis were predominant, while p-ERN1 and autophagic flux were inhibited. Inhibition of MTORC1 by TMJ local injection of rapamycin in rats or inducible ablation of MTORC1 expression selectively in chondrocytes in mice promoted chondrocyte autophagy and suppressed apoptosis, and reduced TMJ cartilage loss induced by UAC. In contrast, MTORC1 activation by TMJ local administration of MHY1485 or genetic deletion of Tsc1, an upstream MTORC1 suppressor, resulted in opposite effects. Collectively, our results establish that aberrant mechanical loading causes cartilage degeneration by activating, at least in part, the MTORC1 signaling which modulates the autophagy and apoptosis programs in TMJ chondrocytes. Thus, inhibition of MTORC1 provides a novel therapeutic strategy for prevention and treatment of OA.

Research on the association between dental caries and body mass index (BMI) in children has shown contradictory results; thus we aimed to examine the association between dental caries and the full range of BMI classes among children. We comprehensively searched PubMed, Embase, and the Cochrane Library for studies published prior to March 2017. Articles comparing dental caries among the full range of BMI classes for children below 18 years of both genders were included. Fourteen studies were eligible for this study. Basic information - i.e., first author, published year, study design, country, sample size, age, type of dental caries index and BMI, main results and conclusions, and means and standard deviations of the dental caries indexes used - was pooled. The weighted mean differences and corresponding 95% confidence intervals for dental caries between children with abnormal weight and those with normal weight were analyzed. Generally, no significant differences in caries were found between any abnormal-weight group and the normal-weight group for both primary and permanent teeth. Sensitivity analyses showed that the obese group had more caries than the normal-weight group in their primary teeth. Significantly more caries was found among the overweight and obese children in both primary and permanent teeth in high-income countries, but not in low- and middle-income countries. We recommend that further studies use suitable sample sizes, unify the criteria for BMI categorization and the dental caries index, and investigate the confounding factors that might influence dental caries and BMI.

Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation of the APOE gene, characterized by proteinuria and nephrotic syndrome with elevated serum apoE. Since its treatment and outcome are unknown, we retrospectively studied 35 patients within 31 unrelated Han families with biopsy-proven lipoprotein glomerulopathy residing in the same county in southwest China. DNA sequencing detected the APOE Kyoto mutation (p. Arg25Cys) in all patients and 28 asymptomatic relatives. All shared the same ɛ3 allele. The patients presented with proteinuria, higher total triglyceride, and serum apoE levels relative to non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers were between those of the patients and non-carriers. Sixteen patients received fenofibrate treatment for over 12 months. Six reached complete remission (proteinuria under 0.3 g/day with stable serum creatinine) with intensive control of their lipid profile (normalized serum apoE and triglycerides under 100 mg/dl). Eight reached partial remission. At 3 years of follow-up, patients treated with fenofibrate had superior survival and stable renal function. Thus, fenofibrate can induce lipoprotein glomerulopathy remission and the fibrate effects depend on the degree of lipid control and baseline proteinuria. Moreover, normalization of serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering treatment.

No abstract

A new hemodialysis membrane manufactured by a blend of polyethersulfone (PES) and polyvinylpyrrolidone (PVP) was evaluated in vitro and in vivo. Goat was selected as the experimental animal. The clearance and the reduction ratio after the hemodialysis of small molecules (urea, creatinine, phosphate) for the PES membrane were higher in vitro than that in vivo. The reduction ratio of beta(2)-microglobulin was about 50% after the treatment for 4 h. The biocompatibility profiles of the membranes indicated slight neutropenia and platelet adhesion at the initial stage of the hemodialysis. Electrolyte, blood gas, and blood biochemistry were also analyzed before and after the treatment. The results indicated that PES hollow fiber membrane had a potential widely use for hemodialysis.

BackgroundSocial support might play a role in helping people adopt healthy behaviors and improve their health. Stronger social support from mothers has been found to be positively related to higher tooth brushing frequency in 1- to 3-year-old children. However, little is known regarding the relationship between the caregiver’s social support and the oral health-related behaviors of 5-year-old children in China. This study aimed to investigate this relationship.MethodsA cross-sectional study was conducted among 1332 5-year-old children and their caregivers in Guangzhou, southern China. Data were collected using questionnaires that were completed by the caregivers and the children’s caries status were examined. The caregivers’ social support was measured using the Social Support Rating Scale. The measurements of the children’s oral health-related behaviors included the frequencies of sugary snack intake and tooth brushing, utilization of dental services, and patterns of dental visits. Univariate and multiple logistic regression analyses were used to analyze the relationships between the variables.ResultsNo association was found between the caregiver’s social support and the child’s oral health-related behaviors in a multiple logistic regression analysis. However, other factors, particularly the oral health-related behaviors of the caregiver, were found to be significantly linked to the child’s oral health-related behaviors.ConclusionsThe oral health-related behaviors of 5-year-old children in Guangzhou are unrelated to the caregiver’s social support but are related to other specific factors, particularly the caregiver’s oral health-related behaviors.

There are signs that amyloid fibers exist in Streptococcus mutans biofilm recently. However, the characteristics of amyloid fibers and fibrillation influencing factors are unknown. In this study, we firstly used transmission electron microscopy (TEM) and atomic force microscopy (AFM) to observe the morphology of amyloid fibers in S. mutans . Then the extracted amyloid fibers from biofilm were studied for their characteristics. Further, the influencing factors, PH, temperature and eDNA, were investigated. Results showed there were mainly two morphologies of amyloid fibers in S. mutans , different in width. Amyloid fibers inhibitor-EGCG obviously destroyed biofilm at different stages, which is dose-dependent. The amount of amyloid fibers positively correlated with biofilm biomass in clinical isolates. Acidic pH and high temperature obviously accelerated amyloid fibrillation. During amyloid fibrillation, amyloid growth morphologies were observed by TEM and results showed two growth morphologies. Amyloid fibers formed complex with eDNA, which we call (a)eDNA. The molecular weight of (a)eDNA was similar to genomic DNA, greatly larger than that of eDNA in matrix. Combined use of DNase I and EGCG was more efficiently in inhibiting amyloid fibers and biofilm biomass. In conclusion, amyloid fibers are the crucial structures for S. mutans biofilm formation, showing two types of morphology. Acidic pH and temperature can obviously accelerate amyloid fibrillation. Amyloid fibers form complex with (a)eDNA and combined use of DNase and amyloid fiber inhibitor is more efficiently in inhibiting S. mutans biofilm formation. Electronic supplementary material The online version of this article (10.1186/s13568-019-0753-1) contains supplementary material, which is available to authorized users.