Oral Biosciences

Identification and characterization of novel human papillomaviruses in oral rinse samples from oral cavity and oropharyngeal cancer patients Publication date: Available online 24 May 2019 Source: Journal of Oral Biosciences Author(s): Juliet Dang, Gregory A. Bruce, Qing Zhang, Nancy B. Kiviat Abstract Objectives The objectives of this study were to: I) discover novel human papillomaviruses (HPVs) using next generation sequencing (NGS) technology in oral rinse samples collected from oral cavity cancer (OCC) and oropharyngeal cancer (OPC) patients; II) determine the prevalence of novel HPVs in archived OCC and OPC tissue samples; and III) examine the frequency of novel oncogenic HPVs in cancer and non-cancer oral rinse samples using real-time PCR. Methods Oral rinse samples were collected from 100 head and neck cancer patients, and 110 healthy individuals. NGS techniques were used to detect novel HPVs. Results Three potentially new types of HPV were discovered. Novel virus (NV) 14.4 was closely related to HPV76 with an 89% homology and is a member of the genus Beta-papillomavirus (β-PV); NV69.1 was distantly related to the genus Alpha-papillomavirus (α-PV), and NV95 was closely related to HPV147 with a 65–77% homology and is part of the genus Gamma-papillomavirus (γ-PV). In archived oral tissue samples, NV14.4 was detected in a single patient with OCC. Of the oral rinse samples, NV69.1 was more prevalent than the other two NVs. Conclusions Our results demonstrated that there are novel HPVs present in oral rinse samples that may be associated with OCC and OPC. These novel HPVs can be identified and characterized using NGS techniques.

Analysis of oral microbiota in Japanese oral cancer patients using 16S rRNA sequencing Publication date: Available online 16 May 2019 Source: Journal of Oral Biosciences Author(s): Yasuharu Takahashi, Jonguk Park, Koji Hosomi, Tomonori Yamada, Ayaka Kobayashi, Yuji Yamaguchi, Susumu Iketani, Jun Kunisawa, Kenji Mizuguchi, Nobuko Maeda, Tomoko Ohshima Abstract Objectives It is important to determine the cause of increasing oral cancer occurrence and mortality rates in Japan, because the mortality rate has recently decreased in other developed countries. The impact of microbiota in carcinogenesis, especially in the digestive tract has been reported. This study aimed to clarify the relationship between oral cancer and oral microbiota in Japanese patients. Methods DNA was extracted from salivary samples of 60 oral cancer patients and 80 non-cancer individuals as controls. We performed metagenomic analysis using 16S rRNA amplicon sequencing. Statistical analysis in this study was performed using R (version 3.5.0). Results Oral cancer patients showed higher α-diversity compared to the control group, and the β-diversity between the two groups differed significantly. Further, there was a significant difference in the abundance ratio of bacterial genera between the two groups. Peptostreptococcus, Fusobacterium, Alloprevotella, and Capnocytophaga were more abundant in the cancer group compared to the control, whereas Rothia and Haemophilus were less abundant (p < 0.01). A negative correlation in the microbiota composition was confirmed between the operational taxonomic units (OTU) of genus Rothia and T-stage progression using the TNM classification method. We performed logistic regression analysis to investigate the impact factor for the oral cancer group, and the result showed that Chao 1 index and sex are statistically significant variables. Conclusions In this study, we observed an increased bacterial diversity in oral cancer patients and found distribution changes for some bacteria.

Alternating lamellar structure in human cellular cementum and rat compact bone: Its structure and formation Publication date: Available online 15 May 2019 Source: Journal of Oral Biosciences Author(s): Tsuneyuki Yamamoto, Tomoka Hasegawa, Hiromi Hongo, Norio Amizuka Abstract Background Human cellular cementum and compact bone exhibit an alternating lamellar structure, in which intensely and faintly stainable lamellae are stratified in an alternating manner. Many investigators, including our group, have accumulated considerable data regarding lamellar structure. In this review, we summarize the alternating lamellar structure, based on available data, and introduce our hypothesis regarding its formation. Highlight We implemented 10% and 24% NaOH maceration methods for scanning electron microscopy. The 10% NaOH maceration method was used for detailed examination of the collagen fibril arrangement, whereas the 24% NaOH maceration method was used for examination of cell morphology in the absence of collagen fibrils. The following findings were obtained: (1) sections of cementum and bone showed two types of alternating lamellae—those comprising longitudinally and nearly longitudinally arranged fibril arrays, and those comprising transversely and nearly transversely arranged fibril arrays; (2) the fibril arrays appeared to shift arrangement in a regular and periodic manner, such that the alternating lamellar structure appeared in sections; (3) where the alternating lamellar structure was being formed, osteoblasts and cementoblasts extended slender processes alongside newly deposited fibrils. Conclusion Our data showed that the alternating lamellar structure was consistent with the twisted plywood model previously proposed for osteonal lamellae. For the formation of this structure, there have been two major hypotheses: a self-assembly hypothesis and a cellular control hypothesis. Our data support the latter; osteoblasts and cementoblasts move their processes synchronously and periodically to control fibril arrangement, thereby forming the alternating lamellar structure.

Degree of orientations of collagen fibers and bone apatite crystals in rat femora by infrared dichroism imaging Publication date: Available online 15 May 2019 Source: Journal of Oral Biosciences Author(s): Teppei Ito, Hiromi Kimura-Suda Abstract Objectives The degree of orientations of collagen fibers and bone apatite crystals affects bone strength. We demonstrated that collagen fibers were aligned along the long axis of bone and that the degree of collagen fiber orientation changed with aging using infrared (IR) dichroism imaging. In this study, we developed a technique for evaluating bone apatite crystal orientation using IR dichroism imaging to investigate the relationships between collagen fiber and bone apatite crystal orientations. Methods Femora were harvested from male Sprague Dawley rats of different ages (6, 12, and 33 weeks); they were then embedded in poly (methyl methacrylate) and sectioned with a microtome into 3-μm longitudinal sections. The angle-dependent Fourier transform infrared (FTIR) spectra for sections were collected using FTIR imaging, and collagen fiber and bone apatite crystal orientations in the sections were assessed using IR dichroism imaging. Results Collagen fibers and poorly crystalline apatite in the femoral cortical bone were longitudinally aligned; however, the stoichiometric hydroxyapatite crystal and all of the bone apatite were not aligned. The degree of poorly crystalline apatite orientation was higher in 33-week-old rats than in 6-week-old rats. Conclusions Poorly crystalline apatite in the rat femoral cortical bone was aligned along the collagen fibers. The degree of poorly crystalline apatite orientation and collagen fiber orientation in the femoral cortical bone increased until at least 33 weeks; meanwhile, on aging, the stoichiometric hydroxyapatite crystal was not longitudinally aligned.

Phospholipase C-related catalytically inactive protein: A novel signaling molecule for modulating fat metabolism and energy expenditure Publication date: Available online 15 May 2019 Source: Journal of Oral Biosciences Author(s): Takashi Kanematsu, Kana Oue, Toshiya Okumura, Kae Harada, Yosuke Yamawaki, Satoshi Asano, Akiko Mizokami, Masahiro Irifune, Masato Hirata Abstract Background Overweight and obesity are defined as excessive or abnormal fat accumulation in adipose tissues, and increase the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, and stroke, through pathophysiological mechanisms. There is strong evidence that weight loss reduces the risk of metabolic syndrome by limiting blood pressure and improving the levels of serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. To date, several attempts have been made to develop effective anti-obesity medication or weight-loss drugs; however, satisfactory drugs for clinical use have not yet been developed. Therefore, elucidation of the molecular mechanisms driving fat metabolism (adipogenesis and lipolysis) represents the first step in developing clinically useful drugs and/or therapeutic treatments to control obesity. Highlight In our previous study on intracellular signaling of phospholipase C-related catalytically inactive protein (PRIP), we generated and analyzed Prip-double knockout (Prip-DKO) mice. Prip-DKO mice showed tolerance against insulin resistance and a lean phenotype with low fat mass. Here, we therefore reviewed the involvement of PRIP in fat metabolism and energy expenditure. We conclude that PRIP, a protein phosphatase-binding protein, can modulate fat metabolism via phosphoregulation of adipose lipolysis-related molecules, and regulates non-shivering heat generation in brown adipocytes. Conclusion We propose PRIP as a new therapeutic target for controlling obesity or developing novel anti-obesity drugs.

Medication-related osteonecrosis of the jaw: A literature review Publication date: Available online 15 May 2019 Source: Journal of Oral Biosciences Author(s): Shinichiro Kuroshima, Muneteru Sasaki, Takashi Sawase Abstract Background Antiresorptive agents such as bisphosphonates and denosumab, as well as angiogenesis inhibitors, may induce medication-related osteonecrosis of the jaw (MRONJ). However, the exact mechanisms of MRONJ are unclear and definitive treatment strategies have not yet been developed. Moreover, the aging population requiring antiresorptive agents and angiogenesis inhibitors has been increasing worldwide. Therefore, the aim of this literature review was to introduce the latest information on MRONJ. The epidemiology, triggering factors, risk factors, drug holiday, pathoetiology and treatment strategies for each drug-induced ONJ were investigated by conducting a PubMed search. Highlight The prevalence and incidence of ONJ were very low. Some mechanisms of ONJ have been identified, although they were not definitive. Novel treatment strategies have been proposed in basic and clinical research. Several factors, including age and the administration duration of bisphosphonates, are risks for the development of bisphosphonate-related ONJ (BRONJ). Dental implant therapy and peri-implantitis could become risk factors of BRONJ, regardless of the onset timing of bisphosphonates. No reliable information about ONJ induced by denosumab and angiogenesis inhibitors was found. Conclusion Caution should be taken when dental treatment including implant therapy is performed in patients receiving bisphosphonates, denosumab, and angiogenesis inhibitors. There is limited scientific evidence regarding the relationship between MRONJ and older age. Further ONJ-related research on the aging population is required to manage the treatment of such diseases in older people in the future.

Dental restorative composite materials: A review Publication date: Available online 15 May 2019 Source: Journal of Oral Biosciences Author(s): Ramkumar Yadav, Mukesh Kumar Abstract Background This review article discusses the effect of reinforcements in the parent dental restorative materials that results in enhanced performance in real-time situations. Highlight The review article includes the details of the properties of different reinforced dental composite materials such as mechanical strength, thermal properties, physical/chemical properties, tribological performance. Conclusion It revealed that nanofiller particles enhance the properties of various dental composite materials. The hybrid dental composites also contribute significantly in increasing the mechanical and tribological properties. A silane-treated filler improved the dental composite bonding strength. Graphical abstract

Recent trends of saliva omics biomarkers for the diagnosis and treatment of oral cancer Publication date: Available online 23 March 2019 Source: Journal of Oral Biosciences Author(s): Indranil Chattopadhyay, Madhusmita Panda Abstract Background Recent advances in surgery, radiotherapy, and chemotherapy have no significant effect on oral cancer survival rates due to late diagnosis, poor tumor response to chemotherapy and radiotherapy, as well as a lack of effective biomarkers for early diagnosis. Highlights Therefore, an investigative study aimed at identifying genomics, proteomics, metagenomics, and, metabolomics derived biomarkers for early diagnosis may improve the survival rate of oral cancer patients. Identification and application of saliva-based ''omics'' biomarkers may overcome painful invasive procedures currently being used for the diagnosis of oral cancer. One single biomarker may not be able to differentiate between oral squamous cell carcinoma (OSCC) and controls. Thus, multiple sensitive and specific biomarkers may be needed for screening high-risk patients and following them up for early signs of OSCC occurrence. Validation of these biomarkers in large patient cohorts is, however, required before they can be used in clinical practice. Conclusion In this review, we summarize the potential of omics derived salivary biomarkers as diagnostic and prognostic tools in oral cancer detection and the future clinical benefits associated with these markers. Graphical abstract

Periodontal disease and hemolysis in glucose-6-phosphate dehydrogenase deficiency: Is there a nexus? Publication date: Available online 22 March 2019 Source: Journal of Oral Biosciences Author(s): Neelesh Singh, Ashita Uppoor, Valliammai Rajendran, Dilip G. Naik Abstract Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an erythrocyte enzyme defect that amplifies the susceptibility of erythrocytes to oxidative stress due to excessive levels of reactive oxygen species. Consequently, erythrocyte destruction and hemolysis occur. Highlight The possible mechanism of oxidative stress-mediated destruction of erythrocytes in G6PD deficient individuals induced by periodontal infection is highlighted. Conclusion Periodontal diseases feature systemic loading of reactive oxygen species, and they may increase the risk of hemolysis in individuals with G6PD deficiency.

Mechanisms underlying the induction of regulatory T cells by sublingual immunotherapy Publication date: Available online 7 March 2019 Source: Journal of Oral Biosciences Author(s): Yukinori Tanaka, Satoshi Fukumoto, Shunji Sugawara Abstract Background Sublingual immunotherapy (SLIT) is used for the treatment of type 1 allergies, such as allergic rhinitis. SLIT leads to tolerance against allergens possibly via the redirection of allergen-specific T helper 2 cells to T helper 1 cells and the generation of peripheral regulatory T (Treg) cells. However, the detailed mechanisms remain unclear. Systemic tolerance to orally administered antigens (oral tolerance) has been extensively investigated. Recent studies have recognized the central role of Treg cells and classical dendritic cells (cDCs) in oral tolerance development. Highlight This review focuses on recent advances in the understanding of the underlying mechanisms of SLIT compared with those of oral tolerance. The sublingual administration of soluble protein antigens has been reported to induce antigen-specific Treg cells in oral mucosa-draining submandibular lymph nodes in mice. The generation of Treg cells is critical for SLIT efficacy because the transfer of SLIT-induced Treg cells confers tolerance against the antigens. A large number of oral cDCs with the CD103−CD11b+ phenotype exert retinoic acid-producing activity and convert naïve CD4+ T cells into Foxp3+ Treg cells in vitro in a transforming growth factor-β-dependent and retinoic acid-dependent manner. Oral CD103−CD11b+ cDCs transport sublingual antigens to submandibular lymph nodes and induce antigen-specific Treg cells. Sublingual antigens enter the mucosa most likely by crossing the sublingual ductal epithelium and are captured by oral antigen-presenting cells, especially macrophages. Conclusion Oral CD103−CD11b+ cDCs are specialized for the induction of Treg cells in mice; thus, targeting their human counterpart may enhance the therapeutic effects of SLIT. Graphical abstract

Alexandros Sfakianakis
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