A Brief, Individualized Exercise Program at Intensities Below the Ventilatory Threshold Exerts Therapeutic Effects for Depression: A Pilot Study.

Due to the fact that existing pharmacological treatments for depression are not ideal, effort has been devoted to the development of complementary, alternative therapies such as physical exercise. The antidepressant effect of exercise is well documented. However, current recommendations and prescriptions of exercise may be too demanding for depressed patients, as some complain about the design of exercise programs and depression is associated with reduced motivation and capacity to exercise. Therefore, appropriately designed, patient-friendly exercise programs may prove critical for the long-term maintenance and therapeutic effects of exercise. In this pilot study, we developed an exercise program based on patients' individual level of ventilatory threshold (VT), a submaximal index of aerobic capacity measured by Cardiopulmonary Exercise Testing (CPX). Compared to traditional measures, CPX provides more trustable indices of aerobic capacity and more homogenous exercise prescriptions. The main episode of the program consisted of 15-25 min of cycling twice a week at an intensity that approached but never went higher than subjects' VT (considered low to moderate in intensity). We found that in patients diagnosed with major depressive disorder or persistent depressive disorder (n = 8), the program resulted in a significant reduction in depressive symptoms at week 8, which was maintained at week 16. Meanwhile, patients' social functioning, quality of life, and cognitive functions improved. Although we used a single arm, non-randomized design, our results suggest that even a brief, low to moderate intensity exercise program may exert therapeutic effects for depression and CPX may be a useful tool for exercise prescriptions.

Responder Analysis of Daikenchuto Treatment for Constipation in Poststroke Patients: A Subanalysis of a Randomized Control Trial.

A traditional Japanese medicine, daikenchuto (DKT), is used for treating abdominal bloating and pain with coldness. In modern medicine, it is used to treat postoperative intestinal dysfunction and ileus. We previously showed the effective improvement in functional constipation with DKT in poststroke patients. However, response prediction for the treatment has not been elucidated. We investigated the data from the prior trial (UMIN000007393) to predict the DKT treatment response. We assessed the efficacy of DKT for chronic constipation in poststroke patients. Neurogenic bowel dysfunction score (NBDS) and the Gastrointestinal Symptom Rating Scale-constipation subscale (GSRS-C) score were newly analyzed comparing the pre- and postintervention data after intake of 15 g of DKT extract granule daily for 4 weeks. Single and multiple regression analyses were performed to examine the correlations between the changes in NBDS, GSRS-C score, patient characteristics, clinical symptom score, gas volume in the gut, and serum calcitonin gene-related peptide level. The total NBDS and GSRS-C score were significantly reduced after DKT administration. The total NBDS, GSRS-C score, and gas volume score at baseline were significantly correlated with the change in these scores. Higher NBDS and GSRS-C scores and more gas volume in the gut may be possible predictors of response to DKT when treating constipation.

Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.

Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSBm/m) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSBm/m hippocampus, but not in CSBm/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSBm/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging.

Fucoidan alleviates high-fat diet-induced dyslipidemia and atherosclerosis in ApoE(shl) mice deficient in apolipoprotein E expression.

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, possesses many biological activities including anti-inflammatory and antioxidant activities. We aimed to investigate the protective effects of fucoidan on dyslipidemia and atherosclerosis in apolipoprotein E-deficient mice (ApoE(shl) mice) and to elucidate its molecular targets in the liver by using a transcriptomic approach. For 12weeks, ApoE(shl) mice were fed a high-fat diet (HFD) supplemented with either 1% or 5% fucoidan. Fucoidan supplementation significantly reduced tissue weight (liver and white adipose tissue), blood lipid, total cholesterol (TC), triglyceride (TG), non-high-density lipoprotein cholesterol (non-HDL-C) and glucose levels in HFD-fed ApoE(shl) mice but increased plasma lipoprotein lipase (LPL) activity and HDL-C levels. Fucoidan also reduced hepatic steatosis levels (liver size, TC and TG levels, and lipid peroxidation) and increased white adipose tissue LPL activity. DNA microarray analysis and quantitative reverse transcription-polymerase chain reaction demonstrated differential expression of genes encoding proteins involved in lipid metabolism, energy homeostasis and insulin sensitivity, by activating Ppara and inactivating Srebf1. Fucoidan supplementation markedly reduced the thickness of the lipid-rich plaque, lipid peroxidation and foaming macrophage accumulation in the aorta in HFD-fed ApoE(shl) mice. Thus, fucoidan supplementation appears to have anti-dyslipidemic and anti-atherosclerotic effects by inducing LPL activity and inhibiting the effects of inflammation and oxidative stress in HFD-fed ApoE(shl) mice.