Bismethylmercury sulfide (MeHg)2S has been found to be a detoxified metabolite of methylmercury (MeHg) that is produced by SH-SY5Y cells and in livers of rats exposed to MeHg. (MeHg)2S could be formed through the interactions between MeHg and sulfur species such as hydrogen sulfide (H2S or HS(-)), but the origin of its sulfur has not been fully identified. We herein examined the formation of (MeHg)2S through interactions between MeHg and persulfides, polysulfides, and protein preparations. Investigations using HPLC/atomic absorption spectrophotometry and EI-MS revealed that NaHS and Na2S4 react readily with MeHg to give (MeHg)2S, and similar results were found using GSH persulfide (GSSH) formed endogenously or generated enzymatically in vitro. (MeHg)2S was also formed by incubation of MeHg with liver and heart cytosolic fractions prepared from wild-type mice but not with those from mice lacking cystathionine γ-lyase (CSE) that catalyzes the formation of cysteine persulfide. Consistent with this, (MeHg)2S was detected in a variety of tissues taken from wild-type mice intraperitoneally injected with MeHg in vivo but not in those from MeHg-injected CSE knockout mice. By separating liver fractions by column chromatography, we found numerous proteins that contain persulfides: one of the proteins was identified as being glutathione S-transferase pi 1. These results indicate that the formation of (MeHg)2S can be attributed to interactions between MeHg and endogenous free persulfide species, as well as protein-bound cysteine persulfide.

BackgroundRecently, natural mutation of Tyrosine kinase 2 (Tyk2) gene has been shown to determine susceptibility to murine virus-induced diabetes. In addition, a previous human genome-wide study suggested the type 1 diabetes (T1D) susceptibility region to be 19p13, where the human TYK2 gene is located (19p13.2).MethodsPolymorphisms of TYK2 gene at the promoter region and exons were studied among 331 healthy controls, and 302 patients with T1D and 314 with type 2 diabetes (T2D) in the Japanese.FindingsA TYK2 promoter haplotype with multiple genetic polymorphisms, which are in complete linkage disequilibrium, named TYK2 promoter variant, presenting decreased promoter activity, is associated with an increased risk of not only T1D (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2 to 4.6; P = 0.01), but also T2D (OR, 2.1; 95% CI, 1.1 to 4.1; P = 0.03). The risk is high in patients with T1D associated with flu-like syndrome at diabetes onset and also those without anti-glutamic acid decarboxylase autoantibody.InterpretationThe TYK2 promoter variant is associated with an overall risk for diabetes, serving a good candidate as a virus-induced diabetes susceptibility gene in humans.FundingMinistry of Education, Culture, Sports, Science and Technology and of Health, Labor and Welfare of Japan.

Methylmercury (MeHg) covalently modifies cellular proteins through their SH groups, resulting in cytotoxicity. We report that cystathionine β-synthase (CBS), which catalyzes the production of hydrogen sulfide, contributes to cellular protection against MeHg. Pretreatment with NaHS or overexpression of CBS reduced MeHg cytotoxicity, whereas transfection with CBS small interfering RNA enhanced MeHg toxicity in human neuroblastoma SH-SY5Y cells. Bismethylmercury sulfide ((MeHg)(2)S) was identified as a metabolite of MeHg in SH-SY5Y cells exposed to MeHg and in the livers of rats treated with MeHg. (MeHg)(2)S had little chemical protein modification capability and little cytotoxicity compared with MeHg in vitro and in vivo.

The purpose of this study was to clarify whether masticatory movements during chewing of a wax cube associate with food mixing ability. Twenty-six dentate subjects (mean age 25.3 years) were directed to chew a two-coloured paraffin wax cube for 10 strokes on preferred chewing side. Mixing Ability Index (MAI) was determined from the colour mixture and shape of the chewed wax cube. MAI was employed as an estimate of food mixing ability. Mandibular movements during chewing of the wax cube were recorded using a six-degrees-of freedom jaw movements recording system, and motion of a lower incisal point of the mandible was computed. Twelve parameters of masticatory movements in relation to mandibular excursion, angle, velocity, cycle duration, duration of each phase were measured for each masticatory cycle. In addition, unilateral maximum biting was performed, and the maximum force during biting was measured using a force-transducer. A multiple regression analysis identified vertical amplitude, closing duration, closing angle and maximum bite force as significant predictors accounting for 63% of inter-subject variation (adjusted R(2)) in the MAI (P < 0.05). Only some parameters of masticatory movements seem to have an influence on the MAI in dentate subjects.

Many techniques are available to assess masticatory performance, but not all are appropriate for every population. A proxy suitable for elderly persons suffering from dementia was lacking, and a two-colour chewing gum mixing ability test was investigated for this purpose. A fully automated digital analysis algorithm was applied to a mixing ability test using two-coloured gum samples in a stepwise increased number of chewing cycles protocol (Experiment 1: n = 14; seven men, 19-63 years), a test-retest assessment (Experiment 2: n = 10; four men, 20-49 years) and compared to an established wax cubes mixing ability test (Experiment 3: n = 13; 0 men, 21-31 years). Data were analysed with repeated measures anova (Experiment 1), the calculation of the intraclass correlation coefficient (ICC; Experiment 2) and Spearman's rho correlation coefficient (Experiment 3). The method was sensitive to increasing numbers of chewing cycles (F5,65 = 57·270, P = 0·000) and reliable in the test-retest (ICC value of 0·714, P = 0·004). There was no significant correlation between the two-coloured gum test and the wax cubes test. The two-coloured gum mixing ability test was able to adequately assess masticatory function and is recommended for use in a population of elderly persons with dementia.

The aim of this study was to investigate the relationships between objective masticatory function with respect to masticatory performance and food mixing ability, patients' perception of chewing ability and oral health-related quality of life (OHRQoL). Partially dentate patients with removable partial dentures (n = 131, mean age 67·1 year) participated in the study. Four tests were performed to evaluate objective and subjective masticatory function and OHRQoL. Masticatory performance and food mixing ability were assessed using peanuts or a two-coloured wax cube as test items. Patients' perception of chewing ability was rated using a food intake questionnaire. OHRQoL was measured using the Japanese version of the oral health impact profile. A structural equation model was constructed based on hypothesis in which objective masticatory function would be related to OHRQoL via perceived chewing ability as a mediator. Structural equation modelling analysis found a statistically significant medium effect of perceived chewing ability on OHRQoL and statistically significant medium or small effects of masticatory performance on perceived chewing ability and OHRQoL (P < 0·05); however, the effect of food mixing ability on perceived chewing ability or OHRQoL was not statistically significant (P > 0·05). A fit index indicated that the model fitted well to the data (Goodness-of-fit index = 0·99). These results suggest that perceived chewing ability is a critical factor for OHRQoL and that masticatory performance rather than food mixing ability is important for perceived chewing ability and OHRQoL in patients with removable partial dentures.

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Proteoglycans are macromolecules that consist of a core protein and one or more glycosaminoglycan side chains. A small leucine‐rich dermatan sulfate proteoglycan, biglycan, is one of the predominant types of proteoglycans synthesized by vascular endothelial cells; however, the physiological functions of biglycan are not completely understood. In the present study, bovine aortic endothelial cells in culture were transfected with small interfering RNAs for biglycan, and the expression of other proteoglycans was examined. Transforming growth factor‐β1 signaling was also investigated, because the interaction of biglycan with cytokines has been reported. Biglycan was found to form a complex with either transforming growth factor‐β1 or the transforming growth factor‐β1 type I receptor, ALK5, and to intensify the phosphorylation of Smad2/3, resulting in a lower expression of the transmembrane heparan sulfate proteoglycan, syndecan‐4. This is the first report to clarify the function of biglycan as a regulatory molecule of the ALK5–Smad2/3 TGF‐β1 signaling pathway that mediates the suppression of syndecan‐4 expression in vascular endothelial cells. J. Cell. Biochem. 118: 1087–1096, 2017. © 2016 Wiley Periodicals, Inc.