Protective Effects of Japanese Soybean Paste (Miso) on Stroke in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP)

[BACKGROUND AND HYPOTHESIS] Soybean isoflavones have been shown to reduce the risk of cerebral infarction in humans according to epidemiological studies. However, whether intake of miso can reduce the incidence of stroke in animal models remains unknown. In this study, we investigated the effects of soybean paste (miso) in an animal model of stroke. [METHODS] Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a miso diet (normal diet 90%, miso 10%; final NaCl content 2.8%), a high salt diet (normal diet and NaCl 2.5%; final NaCl content 2.8%), or a low salt diet (normal diet; final NaCl content 0.3%). [RESULTS] Kaplan–Meier survival curves revealed a significantly lower survival rate in the high salt group compared to the miso group (P = 0.002) and the low salt group (P ≤ 0.001). Large hemorrhagic macules were found in the cerebrum in the high salt group, whereas none were found in the other 2 groups. There were also fewer histological and immunohistochemical changes in the brain and kidneys in the miso group compared to the high salt group. [CONCLUSION] Our results suggest that miso may have protective effects against stroke despite its high salt content.This work was supported by a grant-in-aid from the Central Miso Institute, Tokyo, Japa

Extensive mitochondrial genomic analyses reveal dynamic gene order rearrangements in the class Octocorallia (Cnidaria: Anthozoa)

The class Octocorallia comprises two major clades corresponding to the orders Scleralcyonacea and Malacalcyonacea, including over 3500 species that occur in various marine habitats. Unlike other animals, octocorallians possess two unusual mitochondrial genomic characters: a mismatch repair gene (mt-mutS) common to both clades and gene order rearrangements involving inversions of protein-coding genes known only in the Scleralcyonacea. mt-mutS is considered a major driver of gene order arrangements; however, it is not clear why gene order rearrangements are restricted to the Scleralcyonacea. Here, we report 83 mitochondrial genomes of the Malacalcyonacea. Mitochondrial genome sizes range from 18 to 20 Kbp due to insertion of non-coding sequences rather than gene duplications, and genome size is strictly conserved within genera/families. We discovered four novel mitochondrial gene order rearrangement patterns in Malacalcyonacea. Evidently, mitochondrial gene order rearrangements are common to both orders in octocorals, and mt-mutS may facilitate recombination that causes these dynamic mitochondrial gene order rearrangements.journal articl

Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

Impact of the HCRTR2 gene risk variant on schizotypal personality traits (mean ± SD). (DOC 54 kb

High Levels of Copper, Zinc, Iron and Magnesium, but not Calcium, in the Cerebrospinal Fluid of Patients with Fahr's Disease

Patients with marked calcification of the basal ganglia and cerebellum have traditionally been referred to as having Fahr's disease, but the nomenclature has been criticized for including heterogeneous etiology. We describe 3 patients with idiopathic bilateral striatopallidodentate calcinosis (IBSPDC). The patients were a 24-year-old man with mental deterioration, a 57-year-old man with parkinsonism and dementia, and a 76-year-old woman with dementia and mild parkinsonism. The former 2 patients showed severe calcification of the basal ganglia and cerebellum, and the latter patient showed severe calcification of the cerebellum. We found significantly increased levels of copper (Cu), zinc (Zn), iron (Fe) and magnesium (Mg), using inductively coupled plasma mass spectrometry in the CSF of all these 3 patients. The increased levels of Cu, Zn, Fe and Mg reflect the involvement of metabolism of several metals and/or metal-binding proteins during the progression of IBSPDC. More numerous patients with IBSPDC should be examined in other races to clarify the common mechanism of the disease and to investigate the specific treatment

Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model

Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development

Genome‐wide SNP genotyping reveals hidden population structure of an acroporid species at a subtropical coral island: Implications for coral restoration

1. It is essential to consider genetic composition for both conventional coral restoration management and for initiating new interventions to counter the significant global decline in living corals. Population genetic structure at a fine spatial scale should be carefully evaluated before implementing strategies to achieve self-sustaining ecosystems via coral restoration. 2. This study investigated the population genetic structure of two acroporid species at Kume Island, Okinawa, Japan. There were 140 colonies of Acropora digitifera collected from seven study sites, and 81 colonies of Acropora tenuis from six sites. In total, 384 single nucleotide polymorphism (SNP) loci for A. digitifera and 470 SNPs for A. tenuis were obtained using a comparatively economical technique, Multiplexed ISSR Genotyping by sequencing. 3. Observed heterozygosity was significantly lower than expected heterozygosity at all SNP sites in both acroporid species, suggesting deficient genetic diversity possibly caused by past massive coral bleaching. Even though both species are broadcast spawners, the population structure was different in the two species. No detectable structure was evident in A. digitifera, but two distinct clades were found in A. tenuis. The genetic homogeneity of A. digitifera at Kume Island suggests that this species could be used as a focal species for active restoration in terms of genetic differentiation at this island. By contrast, A. tenuis unexpectedly included two distinct clades with little or no admixture within a small study area, possibly representing two reproductively isolated cryptic species. Thus, when using A. tenuis, it would be prudent to avoid disturbing the genetic composition of wild populations until this question is answered.journal articl

Female Reproductive Events and Subclinical Atherosclerosis of the Brain and Carotid Arteriopathy: the Ohasama Study

Aims: Few studies have investigated the subclinical atherosclerotic changes in the brain and carotid artery, and in East Asian populations. We sought to investigate whether gravidity, delivery, the age at menarche and menopause and estrogen exposure period are associated with subclinical atherosclerosis of the brain and carotid arteriopathy.Methods: This cross-sectional study formed part of a cohort study of Ohasama residents initiated in 1986. Brain atherosclerosis and carotid arteriopathy were diagnosed as white matter hyperintensity (WMH) and lacunae evident on brain magnetic resonance imaging (MRI) and carotid intimal media thickness (IMT) or plaque revealed by ultrasound, respectively. The effect of the reproductive events on brain atherosclerosis and carotid arteriopathy was investigated using logistic regression and general linear regression models after adjusting for covariates.Results: Among 966 women aged ≥ 55 years in 1998, we identified 622 and 711 women (mean age: 69.2 and 69.7 years, respectively) who underwent either MRI or carotid ultrasound between 1992–2008 or 1993–2018, respectively. The highest quartile of gravidity (≥ 5 vs. 3) and delivery (≥ 4 vs. 2), and the highest and second highest (3 vs. 2) quartiles of delivery were associated with an increased risk of WMH and carotid artery plaque, respectively. Neither of age at menarche, menopause, and estrogen exposure period estimated by subtracting age at menarche from age at menopause was associated with atherosclerotic changes of brain and carotid arteries.Conclusions: Higher gravidity and delivery are associated with subclinical atherosclerosis of the brain and carotid plaque

Association between KCNJ6 (GIRK2) Gene Polymorphisms and Postoperative Analgesic Requirements after Major Abdominal Surgery

Opioids are commonly used as effective analgesics for the treatment of acute and chronic pain. However, considerable individual differences have been widely observed in sensitivity to opioid analgesics. We focused on a G-protein-activated inwardly rectifying potassium (GIRK) channel subunit, GIRK2, that is an important molecule in opioid transmission. In our initial polymorphism search, a total of nine single-nucleotide polymorphisms (SNPs) were identified in the whole exon, 5′-flanking, and exon-intron boundary regions of the KCNJ6 gene encoding GIRK2. Among them, G-1250A and A1032G were selected as representative SNPs for further association studies. In an association study of 129 subjects who underwent major open abdominal surgery, the A/A genotype in the A1032G SNP and -1250G/1032A haplotype were significantly associated with increased postoperative analgesic requirements compared with other genotypes and haplotypes. The total dose (mean±SEM) of rescue analgesics converted to equivalent oral morphine doses was 20.45±9.27 mg, 10.84±2.24 mg, and 13.07±2.39 mg for the A/A, A/G, and G/G genotypes in the A1032G SNP, respectively. Additionally, KCNJ6 gene expression levels in the 1032A/A subjects were significantly decreased compared with the 1032A/G and 1032G/G subjects in a real-time quantitative PCR analysis using human brain tissues, suggesting that the 1032A/A subjects required more analgesics because of lower KCNJ6 gene expression levels and consequently insufficient analgesic effects. The results indicate that the A1032G SNP and G-1250A/A1032G haplotype could serve as markers that predict increased analgesic requirements. Our findings will provide valuable information for achieving satisfactory pain control and open new avenues for personalized pain treatment