Background: Myostatin (Mstn) is a secreted TGF-β family member that controls skeletal muscle growth, and binds with high af.nity to the activin type IIB receptor (ActRIIB). The soluble ligand-binding domain of ActRIIB fused to the Fc domain of IgG (ActRIIB-Fc) potently binds and inhibits TGF-β family members in muscle, leading to rapid and marked muscle growth. The present study was designed to assess the combinative effects of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc on murine myoblast in vitro and in vivo. Materials and Methods: C2C12 cells were treated by Mstn-siRNA with or without ActRIIB-Fc at 0 and 48 h after differentiation. Myotube size was measured, and gene expression of Mstn, MuRF-1, MyoD and myogenin were analyzed. Furthermore, 11-week-old, male C57BL/6 mice were injected with atelocollagen (ATCOL)-mediated Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc locally into the masseter muscle twice a week. Histological and biochemical analyses were performed using the dissected muscles. Results: Transfection of Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc resulted in signi.cant increases in the myotube diameter of the C2C12 cells compared with untreated control. Also, treatment with Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc could lead to an upregulation of MyoD and myogenin gene expression and downregulation of Mstn and MuRF-1. In vivo, muscle fibril hypertrophy was observed in both Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc treated groups. Moreover, western blotting analysis showed that the p-Smad2/3 expression level was decreased by treatment of Mstn-siRNA/ActRIIB-Fc. In contrast, MyoD and myogenin protein levels were increased by combined treatment, compared with the other groups. Conclusions: These suggest that double inhibition of myostain is potentially useful for myogenesis and muscle growth promotion. This may be a good as new treatment remedy for patients with various muscle atrophies, including muscular dystrophy.
OBJECTIVE:Lactobacillus reuteri is one of the probiotics that possesses preventive effects on oral infections including dental caries and periodontal disease. Reuterin is a bacteriocin-like compound produced by L. reuteri and plays an important role in the probiotic effects. However, it is difficult to obtain reuterin due to the general lability of its aldehyde moiety. Therefore, fourteen stable reuterin-related compounds (RRCs) were chemically synthesized. Here, we investigated the effects of RRCs on periodontopathic bacteria. MATERIALS AND METHODS: The antibacterial activity of RRCs on pathogenic microorganisms including periodontopathic bacteria was determined. Moreover, the effects of RRCs on biofilm formation by Fusobacterium nucleatum were examined by a crystal violet biofilm formation assay. Cytotoxicity of RRCs was evaluated by a lactate dehydrogenase assay using oral keratinocytes. RESULTS: Among synthesized RRCs, RRC-04,-05,-09,-10,-12,-13, and -14, exhibited antibacterial activities against periodontopathic bacteria. RRCs, except for RRC-06,-07,-08, and -11, significantly suppressed biofilm formation to 60-80 % of the control. Most RRCs, except for RRC-12 and -13, were not cytotoxic to human oral keratinocytes. CONCLUSIONS: The synthesized RRCs can be potent novel oral care products for the prevention of periodontitis without adverse effects.
Background: Early detection and response to sarcopenia and presbyphagia are needed to address the problems experienced by an aging population. Objective: We aimed to clarify morphological changes in the geniohyoid (GH) muscle and associated aging-related factors, and to examine if changes in the GH muscle predict reduced swallowing function. Materials and Methods: 103 participants (57 women and 46 men, mean age 59.4 ± 19.5 years) were recruited. GH muscle cross-sectional area (CSA) and contraction velocity were measured using ultrasonography. Body height and weight, neck circumference, body mass index, remaining teeth number, occluding teeth number, tongue pressure, and jaw-opening strength were measured. Swallowing function was evaluated using the swallowing screening assessment questionnaire and by measuring swallowing sound duration. Results: GH muscle CSA significantly affected age, gender, body height and weight, neck circumference, remaining teeth number, occluding teeth number, tongue pressure, jaw-opening strength, duration of swallowing sounds, and GH muscle velocity. Covariance structure analysis showed that GH muscle CSA directly influenced swallowing sound duration. Conclusion: Morphological changes in the GH muscle are predictive of decline in swallowing function.
The maternal immune system during pregnancy is largely changed to maintain immune tolerance against the embryo. Although thymus tissues, which generate T cells, are also dynamically altered during pregnancy, the precise phenotype of thymic T cells and gene alteration in thymus tissues remain to be completely elucidated. In this study, we performed a comprehensive analysis of gene expression and assessed T-cell phenotypic changes in the thymus of mice during pregnancy. Thymus tissues of female C57BL/6 mice during pregnancy were resected to investigate T-cell phenotypes using flow cytometric and immunofluorescence analyses and gene expression using a DNA microarray. Decreased weight of thymus tissues was observed during gestation. Cell numbers of total populations of thymic T cells in pregnant mice were significantly decreased compared with those in non-pregnant mice. DNA microarray and RT-PCR analyses revealed several upregulated genes in the thymus tissues of pregnant mice. Among them, the insulin growth factor-binding protein 5 (IGFBP5) was the most upregulated gene, and its increased protein expression of macrophages was confirmed by immunofluorescence analysis. In summary, a unique change in gene expression was observed in transient atrophy of thymus tissues during pregnancy. The change in gene expression, including that in IGFBP5 of macrophages, may influence thymic differentiation of T cells to maintain an immunological tolerance during pregnancy.
In the process of carcinogenesis, abnormal regulation of cell cycle regulators is essential. Cell cycle is driven by the activity of Cyclin/Cyclin-dependent kinase (Cdk) complex. The activity of Cyclin/Cdk1 is regulated by the ubiquitin-proteasome pathway via controlling protein level of Cyclins. In addition to Cyclins, the protein level of various cell cycle regulators is strictly and precisely regulated by the ubiquitin-proteasome pathway. In particular, SCF (Skp1-Cullin-F-box) and anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex are involved in ubiquitylation of cell cycle regulators. It recently has been shown that overexpression of oncogenic cell cycle regulators and reduced expression of tumor suppressive cell cycle regulators are caused by abnormal regulation of ubiquitin-mediated proteolysis in cancer. In this review, we introduce abnormal regulation of cell cycle regulators in cancer.
Twenty years have passed since our division (clinic of the challenged) was organized in our institution. During this period, we have been engaged in dental care for patients with disability, contributing to this area of special needs dentistry in Tokushima Prefecture. Although the situation has consequently improved, the service remains insufficient to treat all such patients in the prefecture. This review discusses the current statuses of individuals with disabilities in and outside Japan and dental care for them in Tokushima Prefecture, with future perspectives on the latter.