Search

The importance of oral health in type 2 diabetes mellitus (T2DM) is widely recognized; however, oral microbiota characteristics associated with T2DM in the elderly population are not well-understood. This study was conducted to evaluate the characteristics of the salivary microbiota in elderly Japanese patients with T2DM. Saliva samples were collected from 42 elderly Japanese patients with T2DM and 42 age- and sex-matched subjects without T2DM (control). 16S ribosomal RNA metagenomic analysis and comparative analysis of both groups were performed. Random forest classification by machine learning was performed to discriminate between the salivary microbiota in the two groups. There were significant differences in the overall salivary microbiota structure between the T2DM and control groups (beta diversity; unweighted UniFrac distances, p = 0.001; weighted UniFrac distances, p = 0.001). The phylum Firmicutes was abundant in patients with T2DM, whereas the phylum Bacteroidetes was abundant in controls. The T2DM prediction model by random forest based on salivary microbiota data was verified with a high predictive potential in five cross-validation tests (area under the curve (AUC) = 0.938 (95% CI, 0.824–1.000)). Characterization revealed that the salivary microbiota profile of the elderly patients with T2DM is significantly distinct from that of the controls. These data indicate the necessity of oral health management based on the characteristics of the salivary microbiota in elderly patients with T2DM. Our findings will contribute to future research on the development of new diagnostic and therapeutic methods for this purpose.

Background Recently, the gut microbiota has been shown to play an important role in the response and resistance to chemotherapy. Although there is much knowledge about chemotherapy-induced changes in the gut microbiota, chemotherapy-associated changes in the oral microbiota remain unclear. Herein, we aimed to evaluate the changes in oral microbiota associated with the initiation of chemotherapy in patients with malignant hematopoietic tumors. Methods Oral samples were collected before and 8–20 days after the start of chemotherapy from 50 patients with malignant hematopoietic tumors who were starting chemotherapy for the first time. The 16S ribosomal RNA gene sequencing of bacterial DNA extracted from oral samples was performed to compare the oral microbiota before and after the initiation of chemotherapy. Results The richness or evenness of diversity in the ‘after start of chemotherapy’ group decreased significantly, compared with the ‘before start of chemotherapy’ group (alpha-diversity; observed operational taxonomic units (OTUs) index, p p p = 0.001; and weighted UniFrac distances, p = 0.003). Linear discriminant analysis effect size analysis demonstrated an increased abundance of species of certain genera, such as Staphylococcus, and decreased abundance of species of some genera, such as Streptococcus and Neisseria, in the ‘after-chemotherapy’ group, compared with those in the ‘before-chemotherapy’ group. The amounts and trends of change in the oral microbiota before and after the start of chemotherapy differed among the subjects. Of the 25 bacterial genera whose prevalence changed significantly before and after the start of chemotherapy, the proportion of oral commensals such as Streptococcus and Neisseria decreased in many subjects. In contrast, Staphylococcus and Pseudomonas were detected only in a few subjects, but their relative abundance increased significantly after the start of chemotherapy. Conclusions The oral microbiota of patients with hematopoietic tumors changed markedly after the initiation of chemotherapy. Our findings are expected to aid the elucidation of the pathogenesis of oral mucositis, which is an adverse event of chemotherapy, and the development of treatment methods for this condition.

Recently, a large number of Japanese macaques (Macaca fuscata) died of an unknown hemorrhagic syndrome at Kyoto University Primate Research Institute (KUPRI) and an external breeding facility for National Institute for Physiological Sciences (NIPS). We previously reported that the hemorrhagic syndrome of Japanese macaques at KUPRI was caused by infection with simian retrovirus 4 (SRV-4); however, the cause of similar diseases that occurred at the external breeding facility for NIPS was still unknown. In this study, we isolated SRV-5 from Japanese macaques exhibiting thrombocytopenia and then constructed an infectious molecular clone of the SRV-5 isolate. When the SRV-5 isolate was inoculated into two Japanese macaques, severe thrombocytopenia was induced in one of two macaques within 22 days after inoculation. Similarly, the clone-derived virus was inoculated into the other two Japanese macaques, and one of two macaques developed severe thrombocytopenia within 22 days. On the other hand, the remaining two of four macaques survived as asymptomatic carriers even after administering an immunosuppressive agent, dexamethasone. As determined by real-time PCR, SRV-5 infected a variety of tissues in Japanese macaques, especially in digestive and lymph organs. We also identified the SRV-5 receptor as ASCT2, a neutral amino acid transporter in Japanese macaques. Taken together, we conclude that the causative agent of hemorrhagic syndrome occurred at the external breeding facility for NIPS was SRV-5.

The cerebellar lesions of bovine spongiform encephalopathy (BSE)-infected guinea pigs were characterized as severe atrophy of the cerebellar cortex associated with the loss of granule cells, decrease in the width of the molecular layer, and intense protease-resistant prion protein (PrPSc ) accumulations that are similar to cerebellar lesions in kuru and the VV2 type of sporadic Creutzfeldt-Jakob disease. The aim of this study is to assess the relationships between the distribution and localization of PrPSc and synapses expressing neurotransmitter transporters in order to reveal the pathogenesis of the disease. We used cell-type-specific immunohistochemical makers recognizing glutamatergic and γ-aminobutylic acid (GABA)ergic terminals to identify terminals impaired with PrPSc accumulations. The distribution of PrPSc accumulations and immunoreactivity of synaptic vesicles were studied throughout the neuroanatomical pathways in cerebellar lesions. Time course study demonstrated that PrPSc accumulation showed a tendency to spread from granular layer to molecular layer. The immunoreactivity of vesicular glutamate transporter 1 (VGluT1) was localized in axon terminals of cerebellar granule cells, and decreased in association with the severity of PrPSc accumulations and loss of granule cells. Immunoreactivities of vesicular glutamate transporter 2 (VGluT2) and vesicular GABA transporter (VGAT) that exist in axon terminals of inferior olivary neurons and GABAergic synapses of Purkinje cells, respectively, were preserved well in these lesions. In brainstem, VGluT1 immunoreactivity decreased selectively in pontine nuclei that are a component of the pontocerebellar pathway, although other neurotransmitter immunoreactivities were preserved well. Our findings suggest that the selective loss of VGluT1-immunoreactive synapses subsequent to PrPSc accumulations can contribute to the pathogenesis of cerebellar lesions of BSE-infected guinea pigs.

A novel virus related to the Enterovirus/Sapelovirus supergroup in the family Picornaviridae was identified in healthy porcine feces in Japan by using a metagenomics approach. The genome of the virus, named Sapelo-like porcine picornavirus Japan (SPPVJ) Pig/Isi-Im1/JPN/2016, had a type-IV internal ribosomal entry site and carried a 6978-nucleotide-long single open reading frame encoding a 2326 amino acids (aa) polyprotein precursor. The coding sequence region consisted of leader protein (68 aa), a structural protein region P1 (824 aa), and the non-structural protein regions P2 (672 aa) and P3 (762 aa). Among representative picornaviruses, the P1, 2C, and 3CD regions of SPPVJ had the highest aa identities of 64.4%, 61.9%, and 73.3%, respectively, with the corresponding regions of sapelo-like bat picornavirus BtVs-PicoV/SC2013. Sequencing analysis of the RT-PCR products derived from the 5' untranslated and 3D regions revealed the presence of SPPVJ in 17.8% (19/107) of the feces from healthy and diarrheal pigs in 12 farms in 2015-2016. Further studies are needed to determine the origin and pathogenic potential of SPPJV in pigs and other mammals.

To study the genetic diversity of enterovirus G (EV-G) among Japanese pigs, metagenomics sequencing was performed on fecal samples from pigs with or without diarrhea, collected between 2014 and 2016. Fifty-nine EV-G sequences, which were >5,000 nucleotides long, were obtained. By complete VP1 sequence analysis, Japanese EV-G isolates were classified into G1 (17 strains), G2 (four strains), G3 (22 strains), G4 (two strains), G6 (two strains), G9 (six strains), G10 (five strains), and a new genotype (one strain). Remarkably, 16 G1 and one G2 strain identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal samples possessed a papain-like cysteine protease (PL-CP) sequence, which was recently found in the USA and Belgium in the EV-G genome, at the 2C–3A junction site. This paper presents the first report of the high prevalence of viruses carrying PL-CP in the EV-G population. Furthermore, possible inter- and intragenotype recombination events were found among EV-G strains, including G1-PL-CP strains. Our findings may advance the understanding of the molecular epidemiology and genetic evolution of EV-Gs.

Uric acid exerts an important antioxidant effect against external oxidative stress under physiological conditions. However, uric acid itself can increase oxidative stress via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation in adipocytes and vascular cells. Uric acid transporter 1 is involved in the generation of this oxidative stress. Furthermore, uric acid locally activates the renin-angiotensin system, thus producing angiotensin II and subsequently increasing intracellular oxidative stress. Benzbromarone has been reported to suppress uric acid reabsorption via uric acid transporter 1 inhibition in renal tubular cells. In this study we evaluated the in vitro antioxidant effect of benzbromarone from several perspectives. First, the direct radical-trapping capacity of benzbromarone was measured by chemiluminescence assay and electron paramagnetic resonance spectroscopy. Second, the intracellular antioxidant activity of benzbromarone in hyperuricemia was evaluated using endothelial cells. In light of these results, benzbromarone is hypothesized directly to scavenge the superoxide anion radical. In addition, benzbromarone inhibited reactive oxygen species production that was induced by angiotensin II or uric acid in endothelial cells. These findings suggest that benzbromarone possesses the ability directly to scavenge radicals and may act as an antioxidant against uric acid and angiotensin II-induced oxidative stresses in endothelial cells at therapeutically achievable levels in blood.

Feline morbillivirus (FmoPV) is an emerging virus in domestic cats and considered to be one of the causes of chronic renal failure in cats. In this study, we established a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of FmoPV. The results indicated that the detection limit of the assay was 10 50% tissue culture infective dose (TCID50)/ml in the original sample, and sensitivity of the assay was calculated as 0.12 TCID50 per one RT-LAMP reaction. We also detected FmoPV in clinical urine samples from cats infected with FmoPV. The FmoPV RT-LAMP assay is rapid, simple and highly specific for the detection of FmoPV, and thus, it would be a reliable detection method for FmoPV.

Feline morbillivirus (FmoPV) is an emerging virus that was recently discovered in domestic cats with chronic nephritis. Despite the potential role of FmoPV in chronic nephritis, little is known about its biological characteristics. In this study, we established a quantitative assay of FmoPV by using an indirect immunofluorescence technique. Viral titers of FmoPV were determined in one week. Treatment with polybrene® or trypsin which was previously used in virus isolation did not augment the virus titers. FmoPV was notably stable at 4°C, retaining high titers for at least 12 days. Heat-treatment at 60°C and 70°C effectively inactivated FmoPV in 10 and 2 min, respectively. The biological characteristics of FmoPV reported here will be beneficial for establishing an efficient virus isolation method and will provide important information to take a measure to reduce the risk of FmoPV infection.