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Bin Gu,1 Meng Li,2 Yan Zhang,3 Lingyun Li,4 Kun Yao,5 Shizhi Wang3 1Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; 2Department of Neurosurgery, Suqian First Hospital, Suqian, China; 3Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China; 4Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China; 5Department of Developmental Genetics, Nanjing Medical University, Nanjing, China Purpose: We previously identified human herpesvirus 6 (HHV-6) infection in the pathogenesis of glioma. Direct repeat (DR)7, encoded by HHV-6, has been reported to possess malignant transforming activity and involved in Hodgkin’s lymphoma carcinogenesis. Here, we aimed to determine the role of DR7 in the development and progression of glioma. Patients and methods: A total of 27 glioma and 30 normal brain tissues were collected for detection of DR7. Glioma cell proliferation, colony formation, cell cycle, migration, invasion and angiogenesis were evaluated by Cell Counting Kit-8 (CCK-8), soft agar, propidium iodide staining, wound healing, Transwell and chick embryo chorioallantoic membrane assays, respectively. The potential mRNA targets of DR7 were determined using mRNA microarray and validated via Western blot and ELISA. Results: DR7 could be detected in the 13 glioma tissues with a positive rate of 48.15%, but only the 5 normal brain tissues with a lower positive rate of 16.7%. The two strains of cells isolated from glioma tissues were also found to express DR7. CCK-8 and soft agar assays showed enhanced proliferation and colony formation in the cells expressing DR7 which might be in relation to acceleration of the G1/S phase transition by DR7. Further analyses showed that DR7 could promote glioma cell migration, invasion and angiogenesis. Expression profiles identified hundreds of differentially expressed mRNAs, among which P53, extracellular matrix (ECM) fibronectin, integrin receptor ITGβ5 and specific inhibitors of MMPs, tissue inhibitor of MMPs (TIMP)-2 and TIMP-4, were downregulated, whereas ECM-degrading proteinase MMP-3, proinflammatory cytokines IL-1β, IL-6 and IL-8, were upregulated by DR7, respectively. Conclusion: We observed existence of DR7 in the glioma tissues, and overexpression of DR7 could promote glioma cell development and progression, which might be through creating an inflammatory microenvironment and enhancing degradation of ECM. Keywords: HHV-6, DR7, development, progression, glioma

Seventy-nine patients were observed prospectively during their initial period of treatment with conventional bovine insulins. Insulin antibody levels 6 months after starting insulin therapy did not correlate with age, gender or β cell function at onset of treatment. Patients who required soluble insulin in addition to isophane insulin developed higher levels of insulin antibody. Patients bearing the HLA-B8, DR3 and C4AQO alleles had lower levels of insulin antibody, whereas those bearing DR7 produced significantly higher levels. Other alleles at the C4A, C4B, C2, factor B or Gm loci did not appear to have a significant effect on insulin antibody production. The hyporesponsiveness of B8/DR3/C4AQO-positive individuals probably reflects a non-specific abnormality of immunity whereas the enhanced responsiveness of those positive for DR7 suggests the presence of a specific immune response gene for insulin [ABSTRACT FROM AUTHOR]

Probiotics have been reported to exert beneficial effects along the gut-brain axis. This randomised, double-blind and placebo-controlled human study aimed to evaluate such properties of Lactobacillus plantarum DR7 and its accompanying mechanisms in stressed adults. One hundred and eleven (n=111; DR7 n=56, placebo n=55) stressed adults were recruited based on moderate stress levels using the PSS-10 questionnaire. The consumption of DR7 (1×10 9 cfu/day) for 12 weeks reduced symptoms of stress ( P =0.024), anxiety ( P =0.001), and total psychological scores ( P =0.022) as early as 8 weeks among stressed adults compared to the placebo group as assessed by the DASS-42 questionnaire. Plasma cortisol level was reduced among DR7 subjects as compared to the placebo, accompanied by reduced plasma pro-inflammatory cytokines, such as interferon-γ and transforming growth factor-α and increased plasma anti-inflammatory cytokines, such as interleukin 10 ( P <0.05). DR7 better improved cognitive and memory functions in normal adults (>30 years old), such as basic attention, emotional cognition, and associate learning ( P <0.05), as compared to the placebo and young adults (<30 years old). The administration of DR7 enhanced the serotonin pathway, as observed by lowered expressions of plasma dopamine β-hydroxylase (DBH), tyrosine hydroxylase (TH), indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase accompanied by increased expressions of tryptophan hydroxylase-2 and 5-hydroxytryptamine receptor-6, while stabilising the dopamine pathway as observed via stabilised expressions of TH and DBH over 12 weeks as compared to the placebo ( P <0.05). Our results indicated that DR7 fulfil the requirement of a probiotic strain as per recommendation of FAO/WHO and could be applicable as a natural strategy to improve psychological functions, cognitive health and memory in stressed adults.