Six stroma-based RNA markers diagnostic for prostate cancer in European-Americans validated at the RNA and protein levels in patients in China.

We previously analyzed human prostate tissue containing stroma near to tumor and from cancer-negative tissues of volunteers. Over 100 candidate gene expression differences were identified and used to develop a classifier that could detect nearby tumor with an accuracy of 97% (sensitivity = 98% and specificity = 88%) based on 364 independent test cases from primarily European American cases. These stroma-based gene signatures have the potential to identify cancer patients among those with negative biopsies. In this study, we used prostate tissues from Chinese cases to validate six of these markers (CAV1, COL4A2, HSPB1, ITGB3, MAP1A and MCAM). In validation by real-time PCR, four genes (COL4A2, HSPB1, ITGB3, and MAP1A) demonstrated significantly lower expression in tumor-adjacent stroma compared to normal stroma (p value ≤ 0.05). Next, we tested whether these expression differences could be extended to the protein level. In IHC assays, all six selected proteins showed lower expression in tumor-adjacent stroma compared to the normal stroma, of which COL4A2, HSPB1 and ITGB3 showed significant differences (p value ≤ 0.05). These results suggest that biomarkers for diagnosing prostate cancer based on tumor microenvironment may be applicable across multiple racial groups.

PTPRD silencing by DNA hypermethylation decreases insulin receptor signaling and leads to type 2 diabetes.

Genome-wide association study (GWAS) data showed that the protein tyrosine phosphatase receptor type delta (PTPRD) is associated with increased susceptibility to type 2 diabetes (T2D) in Han Chinese. A replication study indicated that PTPRD is involved in the insulin signaling pathway; however, the underlying mechanism remains unclear. We evaluated PTPRD expression in patients with T2D and controls. PTPRD expression levels were lower in patients and were correlated with the duration of the disease. Overexpression of the human insulin receptor PPARγ2 in HepG2 cells induced overexpression of PTPRD and the insulin receptor. PTPRD knockdown, using a shRNA, resulted in down-regulation of the insulin receptor. These results indicate that PTPRD activates PPARγ2 in the insulin signaling pathway. Similar results for PTPRD expression were found using a T2D mouse model. Silencing of PTPRD was caused by DNA methylation in T2D mice and patients, and correlated with DNMT1 expression. Furthermore, we showed that a DNMT1 SNP (rs78789647) was correlated with susceptibility to T2D. This study shows for the first time that DNMT1 caused PTPRD DNA hypermethylation and induced insulin signaling silencing in T2D patients. Our findings contribute to a better understanding of the crucial roles of these regulatory elements in human T2D.

Potential of Spirulina Platensis as a Nutritional Supplement in Malnourished HIV-Infected Adults in Sub-Saharan Africa: A Randomised, Single-Blind Study.

BACKGROUND: Malnutrition is a major global public health issue and its impact on communities and individuals is more dramatic in Sub-Saharan Africa, where it is compounded by widespread poverty and generalized high prevalence of human immunodeficiency virus (HIV). Therefore, malnutrition should be addressed through a multisectorial approach, and malnourished individuals should have access to nutritional rehabilitation molecules that are affordable, accessible, rich in nutrient and efficient. We thus assessed the efficacy of two affordable and accessible nutritional supplements, spirulina platensis versus soya beans among malnourished HIV-infected adults. METHODS: Undernourished patients, naïve of, but eligible to antiretroviral treatment (ART), aged 18 to 35 years were enrolled and randomly assigned to two groups. The first group received spirulina (Group A) as food supplement and the second received soya beans (Group B). Patients were initiated ART simultaneously with supplements. Food supplements were auto-administered daily, the quantity being calculated according to weight to provide 1.5 g/kg body weight of proteins with 25% from supplements (spirulina and soya beans). Patients were monitored at baseline and followed-up during twelve weeks for anthropometric parameters, body composition, haemoglobin and serum albumin, CD4 count and viral load. RESULTS: Fifty-two patients were enrolled (Group A: 26 and Group B: 26). The mean age was 26.4 ± 4.9 years (Group A) and 28.7 ± 4.8 (Group B) with no significant difference between groups (P = 0.10). After 12 weeks, weight and BMI significantly improved in both groups (P < 0.001 within each group). The mean gain in weight and BMI in Group A and B were 4.8 vs. 6.5 kg, (P = 0.68) and 1.3 vs. 1.90 Kg/m(2), (P = 0.82) respectively. In terms of body composition, fat free mass (FFM) did not significantly increase within each group (40.5 vs. 42.2 Kg, P = 0.56 for Group A; 39.2 vs. 39.0 Kg, P = 0.22 for Group B). But when compared between the two groups at the end of the trial, FFM was significantly higher in the spirulina group (42.2 vs. 39.0 Kg, P = 0.01). The haemoglobin level rose significantly within groups (P < 0.001 for each group) with no difference between groups (P = 0.77). Serum albumin level did not increase significantly within groups (P < 0.90 vs. P < 0.82) with no difference between groups (P = 0.39). The increase in CD4 cell count within groups was significant (P < 0.01 in both groups), with a significantly higher CD4 count in the spirulina group compared to subjects on soya beans at the end of the study (P = 0.02). Within each group, HIV viral load significantly reduced at the end of the study (P < 0.001 and P = 0.04 for spirulina and soya beans groups respectively). Between the groups, the viral load was similar at baseline but significantly reduced in the spirulina group at the end of the study (P = 0.02). CONCLUSION: We therefore conclude in this preliminary study, firstly, that both spirulina and soja improve on nutritional status of malnourished HIV-infected patients but in terms of quality of nutritional improvement, subjects on spirulina were better off than subjects on soya beans. Secondly, nutritional rehabilitation improves on immune status with a consequent drop in viral load but further investigations on the antiviral effects of this alga and its clinical implications are strongly needed.

Guided acoustic traveling wave lens for high-speed optical scanners.

Acoustic traveling wave lenses are useful devices to improve the performances of acoustooptical scanners and other optical scanners. A guided acoustic wave version of the traveling wave lens has been investigated for potential reduction of the power consumption of acoustic traveling wave lenses. Resolution gain as high as 35 has been demonstrated. The smallest focused spot which has been experimentally observed is less than 18 microm. Approximately a factor of 25 in device power saving is feasible over the bulk version devices. Smaller focal spot as well as higher resolution gain is possible according to the theoretical studies. To realize the ultimate guided acoustic traveling wave lens performances, a design procedure is outlined together with a list of potential materials for the optimal design of such devices.

Differential localization of pituitary-adrenal activation and temperature changes following intrahypothalamic microinjection of morphine in rats.

Microinjections of morphine (MOR) into the basal mid-hypothalamus of rats elevate corticosteroid production of adrenal glands in vitro and plasma corticosterone (B) levels. Injections in or close to the rostral part of the arcuate nucleus were most effective in producing pituitary-adrenal activation, without affecting body temperature. Injections of MOR in the anterior hypothalamic area caused hyperthermia or hypothermia, depending on the dose and the site of injection, with little or no effect on piutitary-adrenal activity. The results indicate that piutitary-adrenal activation by MOR is mediated by structures in or close to the rostral part of the arcuate nucleus and that these structures can be distinguished from structures where MOR elicits temperature changes.