Thiamine tetrahydrofurfuryl disulfide promotes voluntary activity through dopaminergic activation in the medial prefrontal cortex

A physically active lifestyle is associated with better health in body and mind, and it is urgent that supporting agents for such lifestyles be developed. In rodents, voluntary locomotor activity as an active physical behavior may be mediated by dopaminergic neurons (DNs). Thiamine phosphate esters can stimulate DNs, and we thus hypothesized that thiamine tetrahydrofurfuryl disulfide (TTFD), a thiamine derivative, promotes locomotor activity via DNs in rats. Acute i.p. administration of TTFD enhanced rat locomotor activity in a normal cage. In vivo microdialysis revealed that TTFD-enhanced locomotor activity was synchronized with dopamine release in the medial prefrontal cortex (mPFC). Antagonism of the dopamine D1 receptor, but not D2 receptor, in the mPFC fully suppressed TTFD-enhanced locomotor activity. Finally, we found a TTFD dose-dependent increase in voluntary wheel running. Our findings demonstrate that DNs in the mPFC mediates TTFD-enhanced locomotor activity, suggesting the potential of TTFD to induce active physical behavior

IL-12 and IL-18 Induction and Subsequent NKT Activation Effects of the Japanese Botanical Medicine Juzentaihoto

In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT). Of the cytokines measured interleukin (IL) -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT) cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM) observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours) induction of interferon (IFN)-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects

PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy

Defective mitochondrial quality control is shown to be a mechanism for neurodegeneration in some forms of Parkinson's disease

Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models

Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in actively respiring cells has also been shown to trigger metabolic collapse mediated by the depletion of nicotinamide adenine dinucleotide (NAD) pools, resulting in cell death. Here we found that the deficit in the autophagy-NAD axis underpins the loss of viability in cell models of a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease. Defective autophagic flux in NPC1 cells resulted in mitochondrial dysfunction due to impairment of mitophagy, leading to the depletion of both the reduced and oxidised forms of NAD as identified via metabolic profiling. Consequently, exhaustion of the NAD pools triggered mitochondrial depolarisation and apoptotic cell death. Our chemical screening identified two FDA-approved drugs, celecoxib and memantine, as autophagy activators which effectively restored autophagic flux, NAD levels, and cell viability of NPC1 cells. Of biomedical relevance, either pharmacological rescue of the autophagy deficiency or NAD precursor supplementation restored NAD levels and improved the viability of NPC1 patient fibroblasts and induced pluripotent stem cell (iPSC)-derived cortical neurons. Together, our findings identify the autophagy-NAD axis as a mechanism of cell death and a target for therapeutic interventions in NPC1 disease, with a potential relevance to other neurodegenerative disorders

Annual report by The Japanese Association for Thoracic Surgery

All data regarding cardiovascular surgery and thoracic surgery were obtained from NCD, whereas data regarding esophageal surgery were collected from survey questionnaire by The Japanese Association for Thoracic Surgery forms because NCD of esophageal surgery does not include non-surgical cases (i.e., patients with adjuvant chemotherapy or radiation alone). Based on the change in data aggregation, there are several differences between this 2015 annual report and previous annual reports: the number of institutions decreased in each category from 578 (2014) to 568 (2015) in cardiovascular, from 762 to 714 in general thoracic and from 626 to 571 in esophageal surgery. Because more than two departments in the same institute registered their data to NCD individually, we cannot calculate correct number of institutes in this survey. Then, the response rate is not indicated in the category of cardiovascular surgery (Table 1), and the number of institutions classified by the operation number is also not calculated in the category of cardiovascular surgery (Table 2)

Degenerative changes in the appendicular joints of ancient human populations from the Japan Islands

Degenerative changes in six major limb joints were investigated to compare their prevalence among five ancient skeletal populations from the Japan Islands. The populations assessed in this study consisted of the farmers in the northern Kyushu/Yamaguchi area and the foragers from the northwestern Kyushu area from the Yayoi period (5th century BC to 3rd century AD); the Okhotsk (5th to 12th centuries AD) foragers from Hokkaido and Sakhalin; the common people from medieval Kamakura (12th to 14th centuries AD) in Kanto, central Japan; and the early-modern farmers (17th to 19th centuries AD) from Kumejima, in the southernmost island chain (Ryukyu Islands). Crude prevalence comparisons showed that the shoulder and hip joints were principally affected in early-modern Kumejima and medieval Kamakura, which contrasted with the high prevalence of elbow and knee joint changes in the Okhotsk people. The heavy dependence on marine mammals and fish for dietary protein intake probably required flexion and extension movements of the most severely degenerated joints in the Okhotsk people. The northern Kyushu/Yamaguchi and northwestern Kyushu Yayoi peoples were more affected by degeneration in the wrist joints than others, possibly due to their use of innovative tools such as stone or shell knives and harpoons. A multivariate logistic regression analysis, adjusted for age, region, and sex as the predictor variables for degenerative changes in joints, was applied to only the two samples from Kumejima and Kamakura (including previously reported spine data) because of their better preservation. This revealed differences in the prevalence of changes in some joints; for example, age-related changes were recognized. The Kumejima people were more commonly affected by hip and knee joint changes, whereas the Kamakura people were more commonly affected by changes to apophyseal joints. Because a stable isotope analysis indicated that the trophic levels of the two populations were almost the same, the pattern of degenerative changes would have reflected differences in their specific workloads, such as wet rice cultivation using a peculiar hoe by the Kumejima people. This study, combining multivariate logistic regression analysis of degenerative joint changes and stable isotope analyses, uses large skeletal populations to add clarity to the actual rigors of ancient life. © 2015 Elsevier Ltd and INQUA