Objective of the present study was to evaluate the effect of vitamin D supplementation on glycose homeostasis, islet function, and diabetes progress. Literatures were searched via electronic databases, websites, and previous reviews from the earliest available time to the end of May 2020. Randomized controlled trials initially designed for diabetes and prediabetes with 25-dihydroxyvitamin D [25(OH)D]<30 ng/ml were included. All data were analyzed and presented based on the Cochrane guidelines and PRISMA guidelines. In total, 27 articles (n = 1,932) were enrolled in this study. Vitamin D supplementation significantly improved fasting blood glucose, postprandial blood glucose, and quantitative insulin sensitivity check index in diabetes and prediabetes with baseline 25(OH)D<30 ng/ml. Higher percentages regressing from prediabetes to normal glucose status [1.60 (1.19, 2.17), p = 0.002, n = 564] and lower percentage progressing from prediabetes to diabetes [0.68 (0.36, 1.27), p = 0.23, n = 569] were found in the supplementation group. The positive effects of vitamin D supplementation on body mass index, waist, HDL-C, LDL-C, and CRP were also demonstrated. In conclusion, modest improvements in vitamin D supplementation on short-term glycose homeostasis, insulin sensitivity, and disease development in diabetes and prediabetes with 25(OH)D<30 ng/ml were demonstrated, but more research needs to be conducted in the future to support the clinical application. (Register ID: CRD42020186004)

Although 5-fluorouracil (5-FU) is currently used as an anti-cancer chemotherapy, adverse effects such as oral mucositis potentially limit its clinical application. Additionally, the prevention of 5-FU-induced side effects are scarce. Resveratrol is known to decrease oxidative damage and inflammation. In this study, we examined the protective effects of resveratrol on 5-FU-induced oxidative stress and inflammatory responses in normal human keratinocytes (HaCaT cell) as in vitro oral mucositis model. HaCaT cells were exposed to 5-FU and simultaneously treated with resveratrol. The effects of resveratrol on 5-FU-induced cytotoxicity were evaluated using cell viability assay. The production of reactive oxygen species (ROS) was measured using a fluorescence spectrophotometer. The effects of resveratrol on nuclear factor erythroid 2-related factor 2 (Nrf2), silent information regulator transcript-1 (SIRT-1), and nuclear factor kappa B (NF-κB) signaling and inflammatory cytokine expression were examined. Resveratrol suppressed 5-FU-induced overproduction of ROS by upregulating anti-oxidant defense genes through Nrf2 activation and SIRT-1 expression. Concerning inflammatory responses, resveratrol suppressed the 5-FU-induced expression of pro-inflammatory cytokines via NF-κB nuclear translocation. Conversely, N-acetylcysteine reduced ROS levels without affecting the expression of pro-inflammatory cytokines. Resveratrol might be useful for preventing 5-FU-induced adverse effects by activating anti-oxidant and anti-inflammatory responses.

Cellular senescence is an intricate and multifactorial phenomenon, which is characterized by an irreversible cellular growth arrest, it is caused in response to irretrievably DNA damage, telomere shorting, activation of oncogene, and oxidative stress. Human diploid fibroblasts are a well-established experimental model for premature senescence-related studies, and exposure of fibroblasts to H₂O₂ is widely used as a SIPS model. Recently, it has been reported many studies of CoQ₁₀ as to anti-aging effects, however the effect of CoQ₁₀ on H₂O₂-induced SIPS model of human skin fibroblasts has not been understood. So that, we investigated that human skin fibroblasts were used to investigate the prevention effect of CoQ₁₀ against H₂O₂-induced SIPS model. We created SIPS model fibroblasts with treatment of 100 μM H₂O₂ for 2 h. In this study, CoQ₁₀ also increased cell viability and mRNA levels of type I, IV collagen and protein level of type I collagen. Moreover, it is shown that CoQ₁₀ suppressed oxidative stress, degradation of collagen by increasing MMP expression, and decreasing senescence-associated phenotypes (e.g. SA-βgal positive staining and SASP) for preventing skin aging via H₂O₂-induced SIPS model. These results suggested that CoQ₁₀ has possibility to be contributory for extension of healthy life expectancy in Japan.

Obesity induces severe disorders such as type 2 diabetes and cardiovascular events, and the number of people with obesity is increasing all over the world. Furthermore, it is possible that obesity increases the risk of cognitive dysfunction via the acceleration of oxidative damage. Tocotrienols, which are part of the vitamin E family, have antioxidant and anti-obesity effects. However, the effects of tocotrienols on high-fat diet-treated mice have not been completely elucidated. In this study, we assessed changes in body weight, spatial reference memory acquisition, liver lipid droplet size, blood brain barrier-related protein expressions and antioxidative defense systems in high-fat diet-treated mice in the presence or absence of tocotrienols. The results showed that tocotrienols significantly inhibited body weight gain and lipid droplet synthesis. Although the amount was very small, it was confirmed that tocotrienols surely reached the brain in the perfused brain. Treatment with tocotrienols was tended to improve cognitive function in the control mice. However, tocotrienols did not modulate blood brain barrier-related protein expressions or antioxidative defense systems. These results indicate that treatment with tocotrienols could be effective for the prevention of obesity and cognitive dysfunction. Further extended research is needed to elucidate the relationship between anti-obesity and antioxidant effects of tocotrienols, especially in the brain.

Inflammation is a primary risk factor for cancer. Epidemiological studies previously demonstrated that aspirin decreased the incidence of cancer and specifically reduced the risk of colorectal cancer. However, the number of animal studies that have confirmed the efficacy of aspirin remains limited. Therefore, the purpose of the present study was to investigate the mechanisms by which aspirin prevents colorectal cancer in mice. ICR mice were treated with azoxymethane and the ulcerative colitis inducer, dextran sodium sulfate, to induce colorectal tumors. Aspirin was orally administered three times per week for 12 weeks. Aspirin significantly reduced the number and size of colorectal tumors. Aspirin also significantly decreased tumor necrosis factor alpha and reactive oxygen species (ROS) levels in the plasma. Immunohistochemical analyses and western blots showed that cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), and the active form of Yes-associated protein 1 (YAP1), and cytosolic high mobility group box 1 (HMGB1) were strongly expressed at colorectal tumor sites and clearly suppressed by aspirin. An indicator of inflammation-related DNA damage, 8-nitroguanine, also accumulated in the colorectal tissues and was suppressed by aspirin. The present results suggest that the ingestion of aspirin suppressed carcinogenesis caused by inflammation through decreases in COX2 and ROS levels, resulting in reductions in DNA damage and oncogenic YAP1.

Consumption of yacon (Smallanthus sonchifolius) is associated with beneficial effects such as prevention of metabolic diseases. Yacon root is known to contain various bioactive components including indigestible carbohydrates, but the alteration of intestinal environment after treatment with yacon has not been fully investigated. This study investigated yacon-containing diet effects on the intestinal environment in mice, including microbial composition, short-chain fatty acid levels, and mucus content. After mice were administered yacon-containing diet for 4 weeks, 16S rRNA gene sequencing analyses revealed their fecal microbiota profiles. Organic acid concentrations in cecal contents were measured using an HPLC system. Compared to the control group, yacon-containing diet-received mice had significantly higher the concentrations of succinic acid, lactic acid, acetic acid, and propionic acid. The fecal mucin content was also higher in yacon-containing diet-received mice. Results of 16S rRNA gene sequencing analyses showed that the relative abundances of 27 taxa differed significantly in yacon-containing diet-received mice. Furthermore, results show effects of yacon administration on intestinal inflammation using 2,4,6-trinitrobenzene sulfonic acid induced colitis model in mice. Increased colonic damage and myeloperoxidase activity after 2,4,6-trinitrobenzene sulfonic acid treatment were suppressed in yacon-containing diet-received mice. Results suggest that oral intake of yacon root modulates the intestinal environment, thereby inhibiting intestinal inflammation.

Placental hypoplasia is associated with the pathophysiology of fetal growth restriction and preeclampsia. The placenta consists of differentiated trophoblasts, including cytotrophoblasts, syncytio­trophoblasts, and extravillous trophoblasts. Cytotrophoblasts are thought to have stem-like characteristics and the ability to differentiate into syncytiotrophoblasts and extravillous trophoblasts. However, it is poorly understood whether isolated cytotrophoblasts derived from hypoplastic placentas have specific features compared with those in normal placentas. This study aimed to determine the features of cytotrophoblasts in hypoplastic placentas. Differentially expressed proteins between isolated cytotrophoblasts from hypoplastic placenta with fetal growth restriction and those from the normal placenta were determined by liquid chromatography-tandem mass spectrometry. Among 6,802 proteins, 1,253 and 2,129 proteins were more than 2-fold upregulated and downregulated, respectively. Among them, ENDOU (endonuclease, poly(U) specific), which has high homology with the coronavirus endoribonuclease nonstructural protein 15 (Nsp15), showed a significantly increased expression in cytotrophoblasts from the placenta with fetal growth restriction related to preeclampsia compared with those in normal control placenta. These results provide insight into the pathological mechanisms of placental hypoplasia and additional information on preeclamptic symptoms in cases of SARS-CoV-2 infected placenta, although further investigation is needed.

To investigate the patients’ consciousness regarding the use of metformin and medical cost in Japanese patients with type 2 diabetes taking metformin. This cross-sectional study investigated patients’ general characteristics and consciousness regarding medical cost, kidney function, liver function, and metformin usage, using a self-administered, internet-based questionnaire. Among 1,000 patients, 81.0% felt unsatisfied with treatment for type 2 diabetes, with the main reason for dissatisfaction being high medical cost, with 540 patients reporting this. In addition, 16.8% of patients experienced treatment disruption and among them, 48.2% (81/168) answered that the reason was high medical cost. Over half of the patients did not understand their kidney and liver functions, respectively. Only 8.9% and 7.1% of patients knew both the words and meanings behind sick days and lactic acidosis, respectively. In conclusion, many patients with type 2 diabetes taking metformin were not satisfied with their treatments, with the main reason being high medical cost. Moreover, they did not have sufficient knowledge of sick days and/or lactic acidosis.

It has been reported that oral health is associated with some co-morbid conditions, including cardiovascular disease, in people with type 2 diabetes mellitus. The present study investigated the association between the frequency of toothbrushing and lifestyle in people with type 2 diabetes mellitus. This cross-sectional study included 624 outpatients at the Kyoto Prefectural University of Medicine in Kyoto, Japan from January 2014 to January 2016. Lifestyle was evaluated using a self-administered questionnaire. The average age and hemoglobin A1c level were 67.6 ± 10.9 years and 7.2 ± 1.1%, respectively. The number of patients who brushed their teeth twice or more a day was 189 (50.3%) in men and 198 (79.8%) in women. Among men, the proportion of patients living alone was lower in those who brushed their teeth twice or more a day than those who brushed their teeth never/rarely or once a day. The logistic regression analysis, after adjusting for confounding factors, revealed that living alone (odds ratio 2.88; 95% confidence interval 1.53–5.66) was associated with the increased odds of the low frequency of toothbrushing (never/rarely or once a day) in men, but not in women. In conclusion, the results of our study suggest that living alone was associated with the low frequency of toothbrushing in people with type 2 diabetes mellitus, particularly in men.

This study was conducted to assess the relationship between vitamin D deficiency and anemia, by gender, in Korean adults. The data of 16,060 adults were analyzed (men, 6,840; premenopausal women, 4,916; postmenopausal women, 4,340) from the fifth Korean National Health and Nutrition Examination Survey (KNHANES V) (2010–2012). There were several key findings. First, after adjusting for related variables, the odds ratio (OR) of anemia [hemoglobin (Hb) <13 g/dl in men or Hb <12 g/dl in women] using the vitamin D normal group {25-hydroxyvitamin [25(OH)D] ≥15.0 ng/ml} as reference, was significant for the vitamin D deficient group [25(OH)D <15.0 ng/ml] in the overall population [OR, 1.310; 95% confidence interval (CI), 1.168–1.470]. Second, the OR of anemia, using the vitamin D normal group as reference, was significant for the vitamin D deficient group in premenopausal women (OR, 1.293; 95% CI, 1.105–1.513). However, vitamin D deficiency in the vitamin D normal group in men (OR, 1.093; 95% CI, 0.806–1.484) and postmenopausal women (OR, 1.130; 95% CI, 0.906–1.409) was not significant. In conclusion, Vitamin D deficiency is positively associated with anemia in premenopausal women, but not in men and postmenopausal women.

The spread of coronavirus disease 2019 (COVID-19) has led to drastic changes in people’s lifestyles, including teleworking and restrictions on socializing. In the context of observing social distancing for preventing infection, the need to maintain fitness and health has attracted particular attention. We aimed to determine the relationship between the increase in the number of active users of online diet management applications and COVID-19 infection rates in Japan. A total of 1.5 million rows of log data was analyzed. The active number of users of online diet management applications increased with increase in the number of COVID-19 infections. The active user number in Kanagawa Prefecture, where the first cases of COVID-19 were reported in Japan, was particularly high. Moreover, there was a significant increase in the user number in prefectures under a state of emergency when compared to that in prefectures not under a state of emergency. The social anxiety caused by COVID-19 is expected to increase the demand for online health management applications further. The use of such programs can aid in achieving social distancing while enabling users to maintain healthy lifestyles.

In clinical practice, edoxaban is sometimes prescribed for off-label use based on the hypothesis that it is as safe and effective as warfarin. However, there is limited safety information on off-label use due to lack of clinical trial. We aimed to analyze the tolerability of off-label use of edoxaban and to identify patient characteristics associated with major bleeding as adverse effects. Patients under edoxaban treatment between January 2017 and December 2017 were enrolled in this retrospective cohort study. The incidence of major bleeding with off-label use compared with on-label use was analyzed using by log-rank test. Univariate and multivariate regression analysis were undertaken to detect independent variables with significant odds ratio that associated with major bleeding. After the exclusion criteria were applied, the patients were divided into two groups: off-label group (n = 30) and on-label group (n = 161). Incidence of major bleeding was found to be higher in the off-label group (13.3%) than in the on-label group (3.7%) (p<0.05). Multivariate adjustment showed that the off-label use or portal vein thrombosis and patients with history of major bleeding has significantly higher incidence of major bleeding. We demonstrated that off-label use of edoxaban may be a significant risk factor for major bleeding.