Whether vitamin D deficiency causes atrial fibrillation and ischemic stroke of young onset was unknown. We derived a Genetic Risk Score for vitamin D from 3,922 subjects in Hong Kong and applied it in an independent sample ( = 1,297) for clinical outcomes. Primary endpoint was a composite of atrial fibrillation and/or ischemic stroke. A second study was performed in the UK Biobank ( = 392,010; 46% men; 14,878 atrial fibrillation and 4,050 ischemic stroke cases, vs 374,102 controls). After 76 ± 46 months, 240 primary endpoints (18.5%) were adjudicated. Higher genetically-predicted vitamin D independently predicted reduced primary endpoint [odds ratio = 0.83 (0.72 to 0.95),  = 0.008]. Mendelian randomization analyses indicated vitamin D was causally protective against the primary endpoint [odds ratio = 0.81 (95% CI: 0.65 to 0.98)]. Independent analyses in the UK Biobank revealed that vitamin D was protective against young-onset ischemic stroke <50 years and atrial fibrillation combined [odds ratio = 0.36 (95% CI 0.14 to 0.94)], with predominant effect amongst men [odds ratio = 0.28 (95% CI 0.09 to 0.91)] compared to women [odds ratio = 0.60 (95% CI: 0.11 to 3.22)]. In conclusion, vitamin D may protect against young-onset ischemic stroke through preventing atrial fibrillation. Investigating the sex-specifc effects of vitamin D deficiency may elucidate sex disparities of atrial fibrillation in the young.

Liposome lipid peroxidation induced by cold atmospheric pressure plasma jet (CAPPJ) irradiation was investigated. The formation of thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation final products, as a function of irradiation was observed. Lipid radicals, peroxidation reaction intermediates generated by CAPPJ irradiation, were confirmed by increased NBD-pen fluorescence intensity. Additionally, lipid peroxidation products, liposomal phosphatidylcholine (PC) isomers, were analyzed by LC-MS/MS. Products specific to singlet oxygen (O) oxidation, 16:0/10-hydroperoxy-8,12-octadecanoic acid (10-8,12-HpODE) PC and 16:0/12-9,13-HpODE PC, were not detected, but radical oxidation specific products 16:0/13-9,11-HpODE PC and 16:0/9-10,12-HpODE PC were. This suggests that during CAPPJ irradiation, radicals, rather than O, are the primary reactive species of lipid peroxidation. This is also supported by the β-carotene quenching of O not suppressing TBARS and lipid radical generation. Also, neither TBARS formation nor lipid radical generation were suppressed by SOD, indicating that the superoxide radical (O ) is not responsible for the lipid peroxidation reaction. As the CAPPJ irradiation of water produces large quantities of hydroxyl radical (OH) and OH scavengers decreased the amount of TBARS produced by CAPPJ irradiation, it is highly plausible that OH is the primary species involved in CAPPJ-induced liposome lipid peroxidation.

Type 1 diabetes mellitus (T1DM) may be associated with other autoimmune diseases. Celiac disease (CD), another autoimmune disorder that mainly affects the small intestine, is caused by intolerance to gluten ingestion. CD has a higher prevalence in patients with T1DM than in the general population. However, the prevalence of CD in patients with T1DM in Japan is unknown. This study investigated the prevalence of CD in Japanese patients with T1DM. We included 115 patients with T1DM treated at Hyogo Brain and Heart Center from December 2020 to April 2021. A questionnaire survey about dietary habits and abdominal symptoms was administered, and serum anti-tissue transglutaminase (TTG) antibody titers were determined for all participants. A CD (CD-seropositive) diagnosis was based on TTG levels >10 U/ml. Fifty-eight patients (50.4%) had some abdominal symptoms (such as constipation, diarrhea, and abdominal pain). The average TTG-IgA antibody titer was 0.75 ± 0.49 U/ml and negative (<10 U/ml) in all patients. In conclusion, the prevalence of CD among patients with T1DM at our hospital was 0%. Thus, the prevalence of CD in Japan is low compared to that in other countries, even among patients with T1DM, who are considered to have high comorbidity rates.

The use of metal nanoparticles such as cerium oxide nanoparticles (nanoceria) in living organisms is attracting increasing attention. We administered nanoceria to chronic kidney disease model rats, including a 5/6 nephrectomy model and adenine administration model rats, and reported high phosphorus adsorption capacity and renal function improvement effects of nanoceria. However, the iron ion concentration in the serum fluctuated significantly after administration. Therefore, we investigated changes in proteins related to iron metabolism following administration of nanoceria to normal mice without chronic kidney disease over different periods of time. Nanoceria were administered to 10-week-old C57BL/6 mice for 4 or 12 weeks. Another group was administrated lanthanum carbonate, which is currently used as a phosphorus adsorbent. The amount of iron in the serum and the concentration of transferrin in the liver were significantly increased following nanoceria administration, and the amount of iron in the liver was significantly decreased. There were no changes in serum hepcidin, ferroportin, cholesterol, or low-density lipoprotein levels. These results indicate that nanoceria administration can affect iron metabolism in mice. Although the detailed mechanism remains unknown, caution is warranted when considering biological utilization in the future.

Heart failure is a major manifestation of vitamin B deficiency; beriberi. We have previously reported that even vitamin B insufficiency, milder than deficiency, is a risk for heart failure in the institutionalized elderly. Then in this cross-sectional study, sixty-eight cardiology outpatients were evaluated for their whole blood vitamin B and plasma brain natriuretic peptide (BNP) concentrations, a sensitive marker of heart failure, as well as their dietary intake. Whole blood vitamin B concentration was significantly correlated with plasma BNP level in vitamin B-deficient/insufficient patients (whole blood vitamin B<28 ‍ng/ml) but not in sufficient patients. Whole blood vitamin B concentration was significantly lower in loop diuretics users than non-users. Multiple regression analysis has identified whole blood vitamin B concentration and eGFR as the significant contributors to log-transformed plasm BNP level, and loop diuretics use, serum albumin level, and eGFR as the contributors to whole blood vitamin B concentration. ROC analysis has shown the significant predictability of whole blood vitamin B for plasma BNP ≥100 pg/ml with the cut-off value of 23.5 ‍ng/ml. Vitamin B insufficiency is a risk of heart failure in the cardiology outpatients, and the therapeutic use of loop diuretics aggravates heart failure and possibly forms a vicious cycle.

The role of the gut microbiota, especially bacterial flora, in the pathogenesis of inflammatory bowel disease (IBD) is becoming clearer. Advances in gut microbiota analysis and the use of gnotobiotics models have underscored the importance of gut bacteria and their metabolites in the progression of IBD. Fecal microbiota transplantation has shown promise in clinical trials for ulcerative colitis started as Advanced Medical Care B in Japan, raising expectations for its outcomes. This review explores the gut microbiota's role in IBD, encompassing both current knowledge and future prospects.

The present study examined factors in subjects diagnosed with hyperglycemia during periodic medical checkups. In total, 9,324 subjects (males: 4,532, females: 4,792) visited the Takagi Hospital for medical checkups in 2019. Eighty-two subjects (59 males) whose fasting blood glucose exceeded 126 mg/dl for the first time during the annual or biannual follow-up were included. Sex- and age-matched controls were used. Data from cases with hyperglycemia were compared to data from themselves one or two years before hyperglycemia. Body mass index (BMI), waist circumference, fatty liver, and blood pressure were higher in cases than in controls. Fasting blood glucose and hemoglobin A1c were higher in cases. Blood test results indicated that triglyceride, low-density lipoprotein (LDL) cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (γ-GTP), were significantly enhanced in cases. Multiple logistic regression analysis revealed that BMI, waist circumference, blood pressure, triglyceride, ALT, and γ-GTP were significant independent risk factors for cases with hyperglycemia. These risk factors were already enhanced in the cases of themselves in one or two years before hyperglycemia. In conclusion, BMI, waist circumference, blood pressure, and fatty liver indicated by ALT and γ-GTP were exacerbated concomitant with hyperglycemia, and increases in these factors preceded hyperglycemia.

() infection promotes the migration of polymorphonuclear leukocytes from the gastric mucosal microcirculation through chemokine induction, leading to the excessive production of ROS. Like eukaryotes, possesses superoxide dismutase and catalase, and is resistant to ROS from host polymorphonuclear leukocytes. Oxidants such as monochloramine produced by ROS cause chronic inflammation in the gastric mucosa. -derived virulence factor m1-type VacA induces intracellular ROS accumulation and autophagy, which degrades the -derived oncoprotein, CagA. In CD44v9-positive gastric cancer stem-like cells, reduced-type glutathione levels increase within the cell because of the cystine transporter on the cell surface, wherein oxidative stress-induced autophagy no longer occurs. As a result, the oncoprotein CagA accumulates in the cells, thus becoming tumorigenic.

This study aimed to evaluate gender differences of hemodialysis patients in adverse events, gastrointestinal bleeding, and bone fractures during 5 year longitudinal follow-up period in the regional core hospital in Japan. This study included 151 patients with maintenance hemodialysis for end-stage renal failure at Takagi Hospital in December 2017. All the patients, divided into females-group of 61 and males-group of 90. Data were evaluated in the electronic medical record. Multivariate analysis indicated a decrease in diabetes mellitus (odd ratio: 2.3, 95% confidence interval: 1.1-4.8,  = 0.03) and less mortality in those younger than 75 years old (odd ratio: 0.2, 95% confidence interval: 0.1-0.8,  = 0.02) were characterized factors in females. Gastrointestinal bleeding were not different between genders. Bone fractures were high in females (females: 34.4% vs males: 18.9%; <0.03), whereas the mortality rate of bone fractured patients was markedly high in males (females: 28.6% vs males: 76.5%;  = 0.003) with lower body bone fractures. In conclusion, diabetes mellitus-induced end-stage renal failure was less common in females. The mortality rate during hemodialysis was higher in males less than 75 years old with increased mortality with lower bone fractures.

Photodynamic therapy (PDT) is a noninvasive cancer treatment modality that involves the administration of photosensitizers and light irradiation. Previously, we established a polycation-containing hematoporphyrin (aHP) formulation that demonstrated superior antitumor efficacy , than the original hematoporphyrin (HP). In this study, we investigated underlining mechanisms of the high antitumor effect of aHP using cell experiments. Time-lapse imaging of rat gastric cancerous cell line (RGK45) treated with aHP exhibited swelling, cell rupture, and subsequent scattering of small vesicles upon light irradiation, in contrast to the small changes in morphology of RGK45 treated with HP. Furthermore, aHP presented concentrated localization on the cell membranes to a greater extent than HP. Additionally, neither aHP nor HP induced morphological changes in rat gastric mucosa cell line (RGM1). Flow cytometry analysis demonstrated a higher fluorescence of wheat germ agglutinin-conjugated dye in RGK45 than in RGM1, suggesting differential glycan expression patterns. These findings collectively suggest that the cellular toxicity of aHP may be augmented in RGK45 cells owing to its heightened affinity toward negatively charged structures on cellular membranes and its preferential localization on them. The observed membrane rupture and release of extracellular vesicles may confer an abscopal effect, in addition to direct PDT effect, thereby positioning aHP as a promising next-generation photosensitizer.

Saliva has antioxidant properties, washes away food residues, and helps maintain the oral environment; thus, decreased saliva secretion can have negative consequences. This study examined how slow-soluble innovative candy, named low-solubility amorphous material, affects oral indices such as saliva secretion and halitosis in a randomized, double-blind, placebo-controlled, crossover comparative study. Twenty-four healthy individuals with low saliva production were given one piece of low-solubility amorphous material or placebo candy and their saliva secretion was measured over 20 min. Before and after participants used the test food, we measured the concentrations of three volatile sulfur compounds involved in halitosis and the secretion rate of secretory immunoglobulin A, and participants completed the Profile of Mood States Second Edition (POMS2) and a visual analog scale (VAS). As a result, saliva secretion increased significantly in low-solubility amorphous material candy condition, compared to placebo candy. Furthermore, changes in the hydrogen sulfide concentration, POMS2 Total Mood Disturbance and Vigor-Activity scores, and oral "moisture" and "refreshed feeling" scores on the VAS were improved more by low-solubility amorphous material candy use than by placebo. Low-solubility amorphous material candy may help improve the oral environment by increasing saliva secretion and reducing halitosis-related substances and may improve mood.

Omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) have been reported to improve sleep quality in several studies, but meta-analyses have been inconclusive. We conducted this study to investigate the effects of omega-3 LC-PUFAs on sleep in clinical trials. The study was planned in accordance with the criteria of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-2020), and was performed by searching PubMed, The Cochrane Library, and Ichushi-web databases. Randomized controlled trials and clinical trials with control groups were included. Finally, eight studies were selected for inclusion in this study. Sleep efficiency was significantly higher in the omega-3 LC-PUFA group than in the control group, while sleep latency and total sleep duration did not differ significantly. Subjectively assessed sleep was significantly improved by omega-3 LC-PUFA, but heterogeneity was so high that a subgroup analysis based on dose of omega-3 supplementation was performed. It showed low heterogeneity and significant improvement in the omega-3 LC-PUFA group compared with the control group. Omega-3 LC-PUFAs have been shown to may improve sleep quality. Further studies are needed to confirm the relationship between omega-3 LC-PUFAs and sleep. The protocol for this review was registered in UMIN000052527.

Hepatocellular carcinoma has high fatality and poor prognosis. For curing hepatocellular carcinoma, the demand for effective therapeutic reagents with low toxicity is urgent. Herein, we investigated plasma-activated medium, an emerging reagent obtained via irradiation of cell-free medium with cold atmospheric plasma. Plasma-activated medium exerts inhibitory effect on many types of tumor cells with little toxicity to non-cancerous cells. In present study, we verified the tumor-specific inhibition of plasma-activated medium on hepatocellular carcinoma cell lines. Under the effect of plasma-activated medium, oxidative stress, mitochondrial dysfunction, and loss of intracellular NAD and ATP were detected inside cells, suggesting an energy depletion. Through investigating the salvage pathway which synthesizes NAD and maintains the respiratory chain in hepatocellular carcinoma, we found that the energy failure was resulted by the blockage of the salvage pathway. Moreover, nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway, was determined as an important target to be inactivated by the effect of plasma-activated medium. Additionally, the blockage of the salvage pathway activates AMPKα and suppresses mTOR pathway, which reinforces the cell growth inhibition. Overall, our findings demonstrated that the disruption of functions of nicotinamide phosphoribosyltransferase and the salvage pathway contribute to the tumor-specific cytotoxicity of plasma-activated medium.

Drinking alcohol is considered one of the risk factors for development of diabetes mellitus. Recently, it was reported that selenoprotein P levels in blood are increased by ethanol intake. However, the mechanism by which ethanol increases selenoprotein P has not been elucidated. The expression of selenoprotein P protein and its mRNA were increased in a concentration- and time-dependent manner when human liver-derived HepG2 cells were treated with ethanol. Levels of AMPK and JNK proteins, which have been known to regulate selenoprotein P transcription, were unchanged by ethanol treatment. However, the amount of nuclear FoxO3a, a transcription factor of SeP, was increased. This was associated with dephosphorylation of ERK1 but not ERK2. It was found that ERK1 was dephosphorylated by activation of dual-specific phosphatase 5 and dual-specific phosphatase 6. However, the phosphorylation of MEK by ERK phosphokinase was not affected by ethanol treatment. These results suggest that the ethanol-induced increase in SeP levels occurs by enhanced transcription of SeP mRNA via the DUSP5/6-ERK1-FoxO3a pathway.

Types of fats and oils affect the onset of lifestyle diseases. In this study, we investigated the relationship between the postprandial hyperglycemia and fatty acids content in the skeletal muscle of C57BL/6 mice given 20% lard, palm oil, corn oil, safflower oil, and flaxseed oil for 16 weeks. Lard increased plasma glucose and insulin levels at the end of feeding period, whereas flaxseed oil did not. It was noteworthy that there is a positive correlation between palmitic acid content in the muscle and postprandial hyperglycemia, and a negative correlation between α-linolenic acid content and hyperglycemia. Alternatively, mice were given 30% lard for 16 weeks. When lard was partially substituted with flaxseed oil (10-50% substitution), flaxseed oil dose-dependently prevented lard-induced hyperglycemia and hyperinsulinemia. In conclusion, flaxseed oil prevents the adverse effects of lard through increasing in α-linolenic acid content in the muscle.

Neutrophils play an important role in innate immunity and produce reactive oxygen species, but they can also cause inflammation and oxidative stress that can damage their own tissues. We have developed neutrophil activity evaluation systems that simultaneously monitors superoxide radicals and hypochlorite ions secreted by stimulated neutrophils in a few microliters of whole blood and have conducted clinical studies in humans. Here, we report normal reference intervals with our systems based on the results of 3,082 persons who underwent comprehensive cancer screening between February 2020 and March 2022. A total of 344 were extracted as reference individuals based on the results of the cancer screening and the reference intervals of the two systems were interim estimated considering gender and age. Reference intervals can be used as a marker of sub-clinical inflam-mation, which is difficult to detect with other blood markers.

In strategies to extend a healthy lifespan, early detection and prevention of frailty are critical. The purpose of this study was to analyze the current state and clinical risk factors of frailty among community-dwelling older to conduct a cross-sectional analysis of the individuals, correlation between frailty and nutrient intake, dietary diversity, and dietary patterns, and to elucidate the correlation between frailty-related dietary factors and the gut microbiota. The study included 786 participants aged ≥65 years from the Kyotango Multipurpose Cohort Study who had available data on their gut microbiota. Frailty was quantitatively assessed by selecting 32 items from the previously reported frailty index, with those scoring ≥0.21 classified as frailty ( = 119) and those with scores <0.21 as non-frailty ( = 667), followed by group comparisons. The frailty group had significantly higher values and rates than the non-frailty group for the following items: age, obesity (in females only), diabetes, hypertension, history of cancer treatment, polypharmacy, disturbed sleep quality, low physical activity, serum insulin levels, and high-sensitivity C-reactive protein. The frailty group had significantly lower levels of nutrients, including plant proteins, potassium (K), magnesium (Mg), iron (Fe), copper (Cu), vitamins B and C, folic acid, and total, soluble, and insoluble dietary fiber. When analyzed by food groups of dietary fiber, the frailty group had significantly lower intakes of soy products and non-green-yellow vegetables, specifically. The Japanese Diet Index score (rJDI12) was significantly lower in the frailty group, with significant deficiencies in soy products and mushrooms included in the rJDI12. Cluster analysis of the Spearman correlation values between nutrient intake related to frailty and the gut microbiota abundance revealed a positive correlation between the cluster containing dietary fiber and the abundance of the phylum Bacillota, including the []__group. In conclusion, our findings clarify the current state of frailty among older community residents and suggest the importance of a diverse range of plant-based foods, including soy products and non-green yellow vegetables, through correlation analysis with nutrients and food groups, and partially reveal the involvement of the gut microbiota.

Neurological and skeletal muscle properties are suggested causes of dynapenia. This study aimed to evaluate the relationship between upper limb muscle quality (grip strength/upper extremity muscle mass) and knee osteoarthritis in dynapenia, and to identify dynapenia-associated factors. Elderly individuals who responded to a public call for screening in Wakasa Town, Fukui Prefecture between June 2019 and November 2021 were included. The analysis included 433 participants (304 women aged 76.0 ± 7.1 years). Examination comprised (consecutively) a basic interview, physical function measurement, body composition measurement, and explanation of results. Dynapenia was observed in 67 patients. Binomial logistic regression analysis revealed that age, upper limb muscle quality score, and knee osteoarthritis were independent factors for dynapenia. Receiver operating characteristic analysis of the relationship between dynapenia and upper limb muscle quality showed an area under the curve of 0.806 (95% confidence interval: 0.658-0.953) for men (cut-off value, 14.3 kg/kg) and 0.849 for women (95% confidence interval: 0.858-0.968; cut-off value, 14.0 kg/kg). In conclusion, age, upper limb muscle quality, and knee osteoarthritis were independent factors of dynapenia. We demonstrated that upper limb muscle quality has good accuracy in detecting dynapenia in both men and women.

Nutritional information on hospitalized patients with COVID-19 is limited. We aimed to (1) investigate the prevalence of nutrition risk defined by the Scored Nutritional Risk Screening (NRS 2002) and malnutrition assessed by prognostic nutritional index (PNI) and controlling nutritional status score (CONUT), (2) observe the nutritional intervention, and (3) explore the predictors of critical condition and mortality. Nutritional risk was 53.00% and the prevalence of malnutrition was 79.09% and 88.79% among 464 patients based on PNI and CONUT, respectively. The area under the receiver operating characteristic curve for hypersensitivity C-reactive protein (hs-CRP), platelet-to-lymphocyte ratio (PLR), PNI, neutrophil/lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and CONUT were 0.714, 0.677, 0.243, 0.778, 0.742, and 0.743, respectively, in discerning critical patients. The mortality-related area under the curve of hs-CRP, PLR, PNI, NLR, SII, and CONUT were 0.740, 0.647, 0.247, 0.814, 0.758, and 0.767, respectively. The results showed that CONUT and NLR were significantly correlated with the critical conditions. Our study revealed a high prevalence of nutritional risk and malnutrition among hospitalized patients with COVID-19. NLR, PLR, hs-CRP, SII, and CONUT are independent predictors of critical conditions and mortality. CONUT and NLR could assist clinicians in discerning critical cases.

Mitophagy plays a vital role in carcinogenesis and tumor progression. However, the research on the mechanism of mitophagy in esophageal cancer metastasis is limited. This study explored the regulatory mechanism of RECQL4 in mitophagy and affects esophageal cancer metastasis. The RECQL4 expression in esophageal cancer tissues and cells was examined by bioinformatics and qRT-PCR. Bioinformatics analysis was used to determine the upstream regulatory factor of RECQL4 and CREB1. Their binding relationship was evaluated by dual luciferase and Chromatin Immunoprecipitation assays. The effects of RECQL4 on esophageal cancer cells viability, metastasis, and mitophagy were examined using CCK-8, Transwell, immunofluorescence, and Western blot assays. The expression of RECQL4 was up-regulated in esophageal cancer tissues and cells. Overexpression of RECQL4 promoted the cells viability, invasion, migration, and epithelial-mesenchymal transition by inhibiting mitophagy. Bioinformatics analysis revealed a positive correlation between RECQL4 and CREB1, their binding relationship was validatied by dual luciferase and ChIP assays. CREB1 knockdown promoted mitophagy and prevented the metastasis of cancer cells, which could be countered by overexpressing RECQL4. In conclusion, CREB1 was found to transcriptionally activate RECQL4 to inhibit mitophagy, thereby promoting esophageal cancer metastasis. Targeting mitophagy could be an effective therapeutic approach for esophageal cancer.

Coenzyme Q10 is an essential lipid in the mitochondrial electron transport system and an important antioxidant. It declines with age and in various diseases, there is a need for a method to compensate for the decrease in coenzyme Q10. Resveratrol, a well-known anti-aging compound, has been shown to undergo metabolism to coenzyme Q10's benzene ring moiety in cells. However, administration of resveratrol did not alter or only slightly increased total intracellular coenzyme Q10 levels in many cell types. Synthesis of coenzyme Q10 requires not only the benzene ring moiety but also the side chain moiety. Biosynthesis of the side chain portion of coenzyme Q10 is mediated by the mevalonic acid pathway. Here, we explore the impact of resveratrol on coenzyme Q10 levels in HepG2 cells, which possess a robust mevalonic acid pathway. As a results, intracellular coenzyme Q10 levels were increased by resveratrol administration. Analysis using C-resveratrol revealed that the benzene ring portion of resveratrol was converted to coenzyme Q10. Inhibition of the mevalonic acid pathway prevented the increase in coenzyme Q10 levels induced by resveratrol administration. These results indicate that resveratrol may be beneficial as a coenzyme Q10-enhancing reagent in cells with a well-developed mevalonic acid pathway.