The DsbA-L gene is associated with respiratory function of the elderly via its adiponectin multimeric or antioxidant properties

Oxidative stress and inflammation play a key role in the age-related decline in the respiratory function. Adipokine in relation to the metabolic and inflammatory systems is attracting growing interest in the field of respiratory dysfunction. The present clinical and experimental studies investigated the role of the disulfide bond-forming oxidoreductase A-like protein (DsbA-L) gene, which has antioxidant and adiponectin multimeric (i.e. activation) properties, on the respiratory function of the elderly. We performed a retrospective longitudinal genotype-phenotype relationship analysis of 318 Japanese relatively elderly participants (mean age ± standard deviation: 67.0 ± 5.8 years) during a health screening program and an in vitro DsbA-L knock-down evaluation using 16HBE14o-cells, a commonly evaluated human airway epithelial cell line. The DsbA-L rs1917760 polymorphism was associated with a reduction in the ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) and %FEV1 and with the elevation of the prevalence of FEV1/FVC < 70%. We also confirmed that the polymorphism was associated with a decreased respiratory function in relation to a decrease in the ratio of high-molecular-weight adiponectin/total adiponectin (as a marker of adiponectin multimerization) and an increase in the oxidized human serum albumin (as an oxidative stress marker). Furthermore, we clarified that DsbA-L knock-down induced oxidative stress and up-regulated the mucus production in human airway epithelial cells. These findings suggest that the DsbA-L gene may play a role in protecting the respiratory function of the elderly, possibly via increased systemic adiponectin functions secreted from adipocytes or through systemic and/or local pulmonary antioxidant properties

Involvement of focal adhesion kinase in inhibition of motility of human breast cancer cells by sphingosine 1-phosphate

Sphingosine 1-phosphate (SPP), a bioactive sphingolipid metabolite, inhibits chemoinvasiveness of the aggressive, estrogen-independent MDA-MB-231 human breast cancer cell line. As in many other cell types, SPP stimulated proliferation of MDA-MB-231 cells, albeit to a lesser extent. Treatment of MDA-MB-231 cells with SPP had no significant effect on their adhesiveness to Matrigel, and only high concentrations of SPP partially inhibited matrix metalloproteinase-2 activation induced by Con A. However, SPP at a concentration that strongly inhibited invasiveness also markedly reduced chemotactic motility. To investigate the molecular mechanisms by which SPP interferes with cell motility, we examined tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, which are important for organization of focal adhesions and cell motility. SPP rapidly increased tyrosine phosphorylation of FAK and paxillin and of the paxillin-associated protein Crk. Overexpression of FAK and kinase-defective FAK in MDA-MB-231 cells resulted in a slight increase in motility without affecting the inhibitory effect of SPP, whereas expression of FAK with a mutation of the major autophosphorylation site (F397) abolished the inhibitory effect of SPP on cell motility. In contrast, the phosphoinositide 3'-kinase inhibitor, wortmannin, inhibited chemotactic motility in both vector and FAK-F397- transfected cells. Our results suggest that autophosphorylation of FAK on Y397 may play an important role in SPP signaling leading to decreased cell motility

Effect of a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin on immune function in Male NC/Nga mice

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces immunosuppression in humans and animals. However, the effect of TCDD on Th2-type immune responses such as allergic reactions has been unclear. Using NC/Nga mice that developed atopic dermatitis-like skin lesions with marked elevation in plasma of total IgE when bred under conventional conditions, we investigated the effects of a single oral dose of TCDD on immune responses. NC/Nga mice received a single oral dose (0 or 20 microg/kg body weight) of TCDD. On day 7, treatment with TCDD alone decreased the cellularity of thymus. However, treatment with TCDD modified the cellularity of spleens and mesenteric lymph nodes (MLNs) but not of the thymus on day 28. When NC/Nga mice received ip immunization with OVA and alum on the same day as the TCDD treatment (0, 5, or 20 microg/kg body weight), TCDD markedly suppressed the concentrations of Th2-type cytokines (e.g., IL-4 and IL-5) in culture supernatants of spleen cells, whereas IFN-gamma production significantly increased. TCDD exposure reduced anti-OVA and total IgE antibody titers in plasma and did not induce the development of atopic dermatitis-like lesions in the pinnae or dorsal skin of NC/Nga mice. These results suggest that in NC/Nga mice, exposure to TCDD may impair the induction of Th2-type immune responses

Effects of Developmental Arsenic Exposure on the Social Behavior and Related Gene Expression in C3H Adult Male Mice

Arsenic is carcinogenic and teratogenic. In addition, it is also a developmental neurotoxicant. Little is known however about the effect of arsenic exposure during brain development on social behavior. This study aimed to detect the effect of developmental arsenic exposure on social behavior and related gene expression in C3H adult male mice. Pregnant C3H mice were exposed to sodium arsenite (NaAsO2, 85 ppm in the drinking water) from gestational day (GD) 8 to 18. The F1 generation male pups from different mothers were taken and social behavior tasks were examined. Social behavioral-related gene expression in the prefrontal cortex was determined by the real-time RT-PCR method. The mice with developmental arsenic exposure showed poor sociability and poor social novelty preference. Glutamate receptor expression (NMDA and AMPA receptor subunits) showed no significant difference, but gene expressions of serotonin receptor 5B (5-HT 5B) and brain-derived neurotrophic factor (BDNF) were significantly decreased (p &lt; 0.05) in the arsenic-exposed group compared to control group. The heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) gene expressions were not significantly different. Our findings indicate that developmental arsenic exposure might affect social behavior by modulating serotonin receptors and reducing BDNF. Some oxidative stress markers and inflammatory markers were not affected

The Mini Nutritional Assessment-Short Form as a predictor of nursing home mortality in Japan: A 30-month longitudinal study

Objectives: We examined whether the Mini Nutritional Assessment-Short Form (MNA (R)-SF) predicted mortality in 367 nursing home residents (82% women; mean age = 84.4 +/- 8.5 years) in Japan. Measurements: We examined participants' basic characteristics (sex, age, height, weight, and medical history), the Barthel index (BI), clinical dementia rating (CDR), and six items of the MNA (R)-SF. The association between the MNA (R)-SF and 30-month mortality was assessed using a Cox proportional regression analysis. Results: During the study, 157 (42.8%) participants died. MNA (R)-SF scores in the Survival group were significantly higher than in the Death group (9.4 +/- 2.1 vs. 8.4 +/- 2.3, respectively; p < .001). After adjusting for age, sex, history of aspiration pneumonia, BI, and CDR, MNA (R)-SF scores were significantly associated with 30-month mortality (hazard ratio: 0.89, 95% confidence interval: 0.82-0.97, p = .005). Conclusion: The MNA (R)-SF was an effective predictor of mortality among nursing home residents in Japan, even after adjusting for potential confounders. These results indicate that periodically evaluating nutritional status using the MNA (R)-SF, and nutritional interventions according to status, may result in maintenance and improvement of nutritional status, as well as lead to reduced mortality

The effects of compression load to the trunk on lipid metabolism in an inactive phase.

The effects of compression load to a specific body part, e.g. leg, arm, or trunk, evoke many functions and are applied in various fields including clinical medicine, sports, and general health care. Nevertheless, little is known about the functional mechanism of compression load, especially regarding its effects on metabolic function. We investigated the effects of compression load to the trunk on the metabolism. We designed adjustable compression clothes for mice and attached them to ten-week-old C57BL/6N male mice in a controlled environment. The mice were divided into compression and no-compression groups, the latter only wearing the clothes without added compression. The evoked metabolic changes were evaluated using indirect calorimetry and transcriptomics with liver tissue to investigate the mechanism of the metabolic changes induced by the compression load. The results indicated decreases in body weight gain, food intake, and respiratory exchange ratio in the compression group compared to the no-compression group, but these effects were limited in the "light period" which was an inactive phase for mice. As a result of the transcriptome analysis after eight hours of compression load to the trunk, several DEGs, e.g., Cpt1A, Hmgcr, were classified into functional categories relating to carbohydrate metabolism, lipid metabolism, or immune response. Lipid metabolism impacts included suppression of fatty acid synthesis and activation of lipolysis and cholesterol synthesis in the compression group. Taken together, our results showed that activation of lipid metabolism processes in an inactive phase was induced by the compression load to the trunk