T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling

SummaryIntermittent administration of parathyroid hormone (iPTH) is used to treat osteoporosis because it improves bone architecture and strength, but the underlying cellular and molecular mechanisms are unclear. Here, we show that iPTH increases the production of Wnt10b by bone marrow CD8+ T cells and induces these lymphocytes to activate canonical Wnt signaling in preosteoblasts. Accordingly, in responses to iPTH, T cell null mice display diminished Wnt signaling in preosteoblasts and blunted osteoblastic commitment, proliferation, differentiation, and life span, which result in decreased trabecular bone anabolism and no increase in strength. Demonstrating the specific role of lymphocytic Wnt10b, iPTH has no anabolic activity in mice lacking T-cell-produced Wnt10b. Therefore, T-cell-mediated activation of Wnt signaling in osteoblastic cells plays a key permissive role in the mechanism by which iPTH increases bone strength, suggesting that T cell osteoblast crosstalk pathways may provide pharmacological targets for bone anabolism

Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population

Age-related macular degeneration (AMD) is a common cause of blindness in the elderly. Caucasian patients are predominantly affected by the dry form of AMD, whereas Japanese patients have predominantly the wet form of AMD and/or polypoidal choroidal vasculopathy (PCV). Although genetic association in the 10q26 (ARMS2/HTRA1) region has been established in many ethnic groups for dry-type AMD, typical wet-type AMD, and PCV, the contribution of the 1q32 (CFH) region seem to differ among these groups. Here we show a single nucleotide polymorphism (SNP) in the ARMS2/HTRA1 locus is associated in the whole genome for Japanese typical wet-type AMD (rs10490924: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 4.1 \times 10 ^{ - 4}$$\end{document}, OR = 4.16) and PCV (rs10490924: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 3.7 \times 10 ^{ -8}$$\end{document}, OR = 2.72) followed by CFH (rs800292: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 7.4 \times 10 ^{ -5}$$\end{document}, OR = 2.08; \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 2.6 \times {10^{ - 4}}$$\end{document}, OR = 2.00), which differs from previous studies in Caucasian populations. Moreover, a SNP (rs2241394) in complement component C3 gene showed significant association with PCV (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 2.5 \times {10^{ - 3}}$$\end{document}, OR = 3.47). We conclude that dry-type AMD, typical wet-type AMD, and PCV have both common and distinct genetic risks that become apparent when comparing Japanese versus Caucasian populations

Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study

Aims To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol = 2.59 to = 100 to = 2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy

The Diverse Efficacy of Food-Derived Proanthocyanidins for Middle-Aged and Elderly Women

Middle-aged and elderly women are affected by various symptoms and diseases induced by estrogen deficiency. Proanthocyanidins, widely present in many kinds of fruits and berries, have many beneficial effects, such as antioxidative, anti-inflammatory, and antimicrobial activities. We researched the effects of proanthocyanidins for middle-aged and elderly women, finding that it has been revealed in many clinical trials and cohort studies that proanthocyanidins contribute to the prevention of cardiovascular disease, hypertension, obesity, cancer, osteoporosis, and urinary tract infection, as well as the improvement of menopausal symptoms, renal function, and skin damage. Thus, proanthocyanidins can be considered one of the potent representatives of complementary alternative therapy

Unsalted tomato juice intake improves blood pressure and serum low‐density lipoprotein cholesterol level in local Japanese residents at risk of cardiovascular disease

The aim of this study was to investigate the effects of unsalted tomato juice intake on cardiovascular risk markers in local Japanese residents. Four hundred and eighty‐one local residents in Kuriyama, Japan, were enrolled in this study. Throughout the year of the study, they were provided with as much unsalted tomato juice as they wanted. Participants were screened for cardiovascular risk markers, such as blood pressure (BP), serum lipid profile, and glucose tolerance, before and after the study period. Of the study participants, 260 participated in a detailed study of their lifestyle factors. The average ages of the 184 male and 297 female participants were 56.3 ± 13.3 (mean ± SD) and 58.4 ± 11.7 years, respectively. BP in 94 participants with untreated prehypertension or hypertension was significantly lowered (systolic BP, 141.2 ± 12.1–137.0 ± 16.3 mmHg, p = 0.003; diastolic BP, 83.3 ± 10.1–80.9 ± 11.1 mmHg, p = 0.012, paired t test). Further, the serum low‐density lipoprotein cholesterol (LDL‐C) level in 125 participants with untreated dyslipidemia significantly decreased (155.0 ± 23.2–149.9 ± 25.0 mg/dl, p = 0.005, paired t test). These beneficial effects were not different between sexes and among the different age groups. No significant difference in lifestyle was found before and after the study. Unsalted tomato juice intake improved systolic and diastolic BP and serum LDL‐C level in local Japanese residents at risk of cardiovascular conditions

Depressive symptoms at postpartum are associated with those at the second trimester of pregnancy and the antioxidant activity immediately after delivery

Objective This study aimed to investigate whether depressive symptoms at postpartum are associated with oxidative stress and antioxidant activity, as well as the symptoms during pregnancy. Methods This longitudinal study enrolled 84 women in their second trimester of pregnancy. Their depressive symptoms were assessed using Edinburgh postnatal depression scale (EPDS), and their oxidative stress and antioxidant activity were assessed using reactive oxygen metabolites/8-hydroxy-2′-deoxyguanosine and biological antioxidant potential (BAP) at around 26 and 36 weeks (time points 1 and 2) of gestation, and 3–6 days and 1 month (time points 3 and 4) postpartum. We evaluated the associations between EPDS at time point 4 and various parameters at the other time points. Results Multiple regression analysis revealed that EPDS at time point 1 (adjusted odds ratio: 1.06 per 0.1 point increase; 95% confidence interval [CI]: 1.03–1.11) and BAP at time point 3 (adjusted odds ratio: 0.93 per 10 μmol/L increase; 95% CI: 0.87–0.97) were independent predictors of EPDS at time point 4. Conclusion Depressive symptoms at the second trimester of pregnancy and the antioxidant activity immediately after delivery could predict postpartum depression. TRIAL REGISTRATION UMIN-CTR UMIN00002236

Effects of Grape Seed Proanthocyanidin Extract on Vascular Endothelial Function in Participants with Prehypertension: A Randomized, Double-Blind, Placebo-Controlled Study

This study aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on blood pressure and vascular endothelial function in middle-aged Japanese adults with prehypertension. We conducted a randomized, double-blind, placebo-controlled study on 6 men and 24 women aged 40&ndash;64 years old. The participants were randomized to receive tablets containing either low-dose (200 mg/day) or high-dose (400 mg/day) GSPE, or placebo, for 12 weeks. Systolic and diastolic blood pressures (SBP and DBP, respectively), brachial flow-mediated dilation (FMD), and other cardiovascular parameters were measured before and after 4, 8, and 12 weeks of treatment. The mean SBP in the high-dose group significantly decreased by 13 mmHg after 12 weeks (P = 0.028), although FMD did not change. In an ad hoc analysis of non-smoking participants (n = 21), the mean SBP, DBP, stiffness parameter &beta;, distensibility, incremental elastic modulus (Einc), and pulse wave velocity (PWV) also significantly improved in the high-dose group after 12 weeks. Changes in Einc and PWV from baseline to 12 weeks were significantly greater in the high-dose group than in the placebo group (Einc, P = 0.023; PWV, P = 0.03). GSPE consumption could help maintain vascular elasticity and normal blood pressure in this population

The Inverse Correlation of Isoflavone Dietary Intake and Headache in Peri- and Post-Menopausal Women

This study investigated the relationship between headache and dietary consumption of a variety of nutrients in middle-aged women. This cross-sectional analysis used first-visit records of 405 women aged 40&ndash;59 years. The frequency of headaches was assessed using the Menopausal Health-Related Quality of Life Questionnaire. Of the 43 major nutrient intakes surveyed using the brief-type self-administered diet history questionnaire, those that were not shared between women with and without frequent headaches were selected. Multiple logistic regression analysis was used to identify nutrients independently associated with frequent headaches. After adjusting for background factors related to frequent headache (vasomotor, insomnia, anxiety, and depression symptoms), the estimated dietary intake of isoflavones (daidzein + genistein) (mg/1000 kcal/day) was negatively associated with frequent headaches (adjusted odds, 0.974; 95% confidence interval, 0.950&ndash;0.999). Moreover, the estimated isoflavone intake was not significantly associated with headache frequency in the premenopausal group, whereas it significantly correlated with that in the peri- and post-menopausal groups. Headache in peri- and post-menopausal women was inversely correlated with the dietary intake of isoflavones. Diets rich in isoflavones may improve headaches in middle-aged women