Feasibility of Molecularly Targeted Therapy for Tooth Regeneration

[Extract] The tooth is a complex organ that consists of enamel, dentin, cementum, and pulp. Missing teeth is frequently occurring problem in aging populations. To treat these defects, the current approach involves prostheses, autotransplantation, and dental implants. The exploration of new strategies for tooth replacement has become a hot topic. Using the foundations of experimental embryology, developmental and molecular biology, tooth regeneration is becoming realistic possibility. Several different methods have been proposed to achieve biological tooth replacement. These include scaffold-based tooth regeneration, cell pellet engineering, stimulation of the formation of a third dentition, and gene-manipulated tooth regeneration. The idea that a third dentition might be locally induced to replace missing teeth is an attractive concept (Young et al., 2005; Edward & Mason, 2006; Takahashi et al., 2008, 2013). This approach is generally presented in terms of adding molecules to induce de novo tooth initiation in the mouth. Tooth development is the result of reciprocal and reiterative signaling between oral ectoderm-derived dental epithelium and cranial neural crest cell-derived dental mesenchyme under genetic control (Thesleff, 2006). More than 200 genes are known to be expressed during tooth development (http://bite-it.helsinki.fi/). A number of mouse mutants are now starting to provide some insights into the mechanisms of supernumerary tooth formation. Multiple supernumerary teeth may have genetic components in their etiology and partially represent the third dentition in humans. Such candidate molecules might be those that are involved in embryonic tooth induction, in successional tooth formation, or in the control of the number of teeth. This means that it may be possible to induce de novo tooth formation by the in situ repression or activation of a single candidate molecule. In this review, we provide an overview of the collective knowledge of tooth regeneration, especially regarding the control of the number of teeth for molecularly targeted therapy by the stimulation of a third dentition

Risk for the occupational infection by cytomegalovirus among health-care workers

Background Cytomegalovirus (CMV) are ubiquitously distributed worldwide, causing a wide range of clinical manifestations from congenital infection to a life-threatening disease in immunocompromised individuals. CMV can be transmitted via human-to-human contact through body fluids; however, the risk of CMV infection among healthcare workers (HCWs) has not been fully evaluated. Aim This study aimed to assess the risk of CMV infection among HCWs through daily medical practices. Methods Serum samples from HCWs at Osaka University Hospital (Japan) were analysed. Initially, we compared CMV IgG seropositivity among HCWs (medical doctors, nurses, and others) in 2017, which was examined after 1 year to evaluate seroconversion rates among those with seronegative results. Then, we examined CMV seroconversion rates in HCWs who were exposed to blood and body fluids. Findings We analysed 1153 samples of HCWs (386 medical doctors, 468 nurses, and 299 others), of which CMV seropositivity rates were not significantly different (68.9%, 70.3%, and 70.9%, respectively). Of these, 63.9% (221/346) of CMV seronegative HCWs were followed after 1 year, with CMV seroconversion rates of 3.2% (7/221). Among 72 HCWs who tested negative for CMV IgG when exposed to blood and body fluids, the CMV seroconversion rate was 2.8% (2/72). The CMV seroconversion rates between the two situations were not significantly different. Conclusion Our study indicated that CMV infection through daily patient care seems quite rare. Further well-designed studies with a large sample size are warranted to verify our finding

Effects of enzymatically modified isoquercitrin in supplementary protein powder on athlete body composition: a randomized, placebo-controlled, double-blind trial

BackgroundEnzymatically modified isoquercitrin (EMIQ), a water-soluble quercetin, has been shown to intensify muscle hypertrophy in mice. We investigated the effect of EMIQ in supplementary protein powder on athlete body composition.MethodsForty Japanese males who played American football (age: 19.8 ± 1.4 years; body height: 174.1 ± 6.0 cm; body mass: 75.5 ± 10.7 kg) were assigned to a randomized, placebo-controlled, double-blind trial of parallel group. Participants received either EMIQ in whey protein (EW, n = 19) or contrast whey protein (W, n = 20) 6 days per week over 4 months. Body composition was assessed using dual-energy X-ray absorptiometry. Markers of oxidative stress, derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP), were assessed using a free radical analytical system. Data were analyzed using a univariate and repeated measures general model statistics.ResultsAfter 4 months, changes in lower limb fat-free mass and muscle mass were significantly greater in the EW group than in the W group (mean change ±95% CI; W: 324.1 ± 284.3, EW: 950.3 ± 473.2, p = 0.031, W: 255.7 ± 288.6, EW: 930.9 ± 471.5, p = 0.021, respectively). Moreover, the EW group exhibited a significantly higher BAP/d-ROMs ratio, antioxidation index, than the W group after 4 months (mean change ± SD; W: 8.8 ± 1.1, EW: 10.3 ± 2.8; p = 0.028). No significant differences in body mass, lean body mass, fat mass, or lower limb fat mass were observed between the groups.ConclusionIngestion of EMIQ in supplementary protein powder for 4 months exerts antioxidant effects and increases muscle mass among American football players

Carcinogenesis in Mouse Stomach by Simultaneous Activation of the Wnt Signaling and Prostaglandin E2 Pathway

金沢大学がん研究所附属がん幹細胞研究センター　Background & Aims: Accumulating evidence indicates that prostaglandin E2 (PGE2), a downstream product of cyclooxygenase 2 (COX-2), plays a key role in gastric tumorigenesis. The Wnt pathway is also suggested to play a causal role in gastric carcinogenesis. However, the molecular mechanism remains poorly understood of how the Wnt and PGE2 pathways contribute to gastric tumorigenesis. To investigate the role of Wnt and PGE2 in gastric cancer, we have generated transgenic mice that activate both pathways and examined their phenotypes. Methods: We constructed K19-Wnt1 transgenic mice expressing Wnt1 in the gastric mucosa using the keratin 19 promoter. We then crossed K19-Wnt1 mice with another transgenic line, K19-C2mE, to obtain K19-Wnt1/C2mE compound transgenic mice. The K19-C2mE mice express COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) in the stomach, showing an increased gastric PGE2 level. We examined the gastric phenotypes of both K19-Wnt1 and K19-Wnt1/C2mE mice. Results: K19-Wnt1 mice had a significant suppression of epithelial differentiation and developed small preneoplastic lesions consisting of undifferentiated epithelial cells with macrophage accumulation. Importantly, additional expression of COX-2 and mPGES-1 converted the preneoplastic lesions in the K19-Wnt1 mice into dysplastic gastric tumors by 20 weeks of age. Notably, we found mucous cell metaplasia in the glandular stomach of the K19-Wnt1/C2mE mice as early as 5 weeks of age, before the dysplastic tumor development. Conclusions: Wnt signaling keeps the gastric progenitor cells undifferentiated. Simultaneous activation of both Wnt and PGE2 pathways causes dysplastic gastric tumors through the metaplasia-carcinoma sequence. © 2006 American Gastroenterological Association (AGA) Institute

Durability of immunity by hepatitis B vaccine in Japanese health care workers depends on primary response titers and durations

Photograph taken by Salt Lake Tribune staf

Novel and Simple Approach to Estimating the Actual Incidence of Blood and Body Fluid Exposure

This article has been published in Clinical Laboratory

Durability of immunity by hepatitis B vaccine in Japanese health care workers depends on primary response titers and durations

Yoshioka N, Deguchi M, Hagiya H, Kagita M, Tsukamoto H, Takao M, et al. (2017) Durability of immunity by hepatitis B vaccine in Japanese health care workers depends on primary response titers and durations. PLoS ONE 12(11): e0187661

A noncoding RNA gene on chromosome 10p15.3 may function upstream of hTERT

<p>Abstract</p> <p>Background</p> <p>We attempted to clone candidate genes on 10p14–15 which may regulate hTERT expression, through exon trapping using 3 BAC clones covering the region. After obtaining 20 exons, we examined the function of RGM249 (RGM: RNA gene for miRNAs) we cloned from primary cultured human hepatocytes and hepatoma cell lines. We confirmed approximately 20 bp products digested by Dicer, and investigated the function of this cloned gene and its involvement in hTERT expression by transfecting the hepatoma cell lines with full-length dsRNA, gene-specific designed siRNA, and shRNA-generating plasmid.</p> <p>Results</p> <p>RGM249 showed cancer-dominant intense expression similar to hTERT in cancer cell lines, whereas very weak expression was evident in human primary hepatocytes without telomerase activity. This gene was predicted to be a noncoding precursor RNA gene. Interestingly, RGM249 dsRNA, siRNA, and shRNA inhibited more than 80% of hTERT mRNA expression. In contrast, primary cultured cells overexpressing the gene showed no significant change in hTERT mRNA expression; the overexpression of the gene strongly suppressed hTERT mRNA in poorly differentiated cells.</p> <p>Conclusion</p> <p>These findings indicate that RGM249 might be a microRNA precursor gene involved in the differentiation and function upstream of hTERT.</p