Helicobacter pylori (H. pylori) infection promotes the migration of polymorphonuclear leukocytes from the gastric mucosal micro­circulation through chemokine induction, leading to the excessive production of ROS. Like eukaryotes, H. pylori 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. H. pylori-derived virulence factor m1-type VacA induces intracellular ROS accumulation and autophagy, which degrades the H. pylori-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.

In sedentary modern society, disuse osteoporosis is a health issue. Here, we investigate whether prune extract prevents disuse osteoporosis in rats. After feeding a control diet or 10% (wt/wt) prune extract-containing diet for 14 d, we performed sham operation in the left leg and sciatic denervation in the right leg to induce disuse osteoporosis in rats. The rats were fed the same diet prior to surgery for seven days. The rats fed a control diet before sham operation on both legs were set as the control group, and those with sciatic denervation in the right leg fed a control diet or prune extract containing diet were set as the denervation with control diet and denervation with prune extract diet groups, respectively. Femoral bone volume/tissue volume, trabecular number, and trabecular thickness were reduced in the right leg of denervation with control diet group; however, this reduction was not observed in the denervation with prune extract diet group. mRNA levels of osteoblast-related genes, such as osteocalcin, were decreased in the right leg of denervation with control diet group; however, this reduction was not observed in the denervation with prune extract diet group. Overall, prune extract inhibited bone loss by preventing the decrease in osteoblast-related gene expression in disuse osteoporosis, thus showing to improve the bone metabolism and quality of life.

Previous studies have suggested a relationship between the urinary 8-hydroxydeoxyguanosine level and hypertension, but an association between the urinary 8-hydroxydeoxyguanosine level and systolic blood pressure has not been reported. The aim of this cross-sectional study was to examine the association between the 8-hydroxydeoxyguanosine level, a marker of DNA oxidative damage, and arteriosclerosis-related factors in healthy, urban residents aged ≥50 years who participated in annual health promotion activities in Mitaka City, Tokyo from 2008 to 2018. Arteriosclerosis-related factors were used as independent variables and the urinary 8-hydroxydeoxyguanosine creatinine concentration-corrected level (urinary 8-hydroxydeoxyguanosine/creatinine) as the dependent variable in multiple logistic regression. Two hundred and forty-eight participants were divided into two groups using a cutoff point of 6.2/6.3 ng/mg creatinine, which corresponds to the urinary 8-hydroxydeoxyguanosine/creatinine levels in approximately 80% of the participants. A high urinary 8-hydroxydeoxyguanosine/creatinine level was significantly associated with a body mass index ≥25, obesity, and systolic blood pressure ≥140. Our findings suggest that in healthy individuals aged ≥50 years, arteriosclerosis-related factors such as inappropriate weight management and poor systolic blood pressure control may be associated with the urinary 8-hydroxydeoxyguanosine level.

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.

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, P = 0.03) and less mortality in those younger than 75 years old (odd ratio: 0.2, 95% confidence interval: 0.1-0.8, P = 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%; P < 0.03), whereas the mortality rate of bone fractured patients was markedly high in males (females: 28.6% vs males: 76.5%; P = 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.

Single-cell sequencing, which can comprehensively detect the type and number of transcripts per cell, has been widely used. In this study, we used this technique to efficiently stimulate peripheral blood mononuclear cells (PBMCs) of type 1 diabetic patients with overlapping peptides of glutamic acid decarboxylase (GAD), islet antigen 2 (IA-2), and insulin antigens, and performed gene expression analysis by single-cell variable-diversity-joining (VDJ) sequencing and T-cell receptor repertoire analysis. Twenty male patients with type 1 diabetes mellitus (T1DM) participating in the KAMOGAWA-DM cohort were included. Four of them were randomly selected for single cell VDJ sequencing of BD Rhapsody system after reacting PBMCs with overlapping peptides of GAD, IA-2, and insulin antigen. PBMCs were clustered into CD8+ T cells, CD4+ T cells, granulocytes, natural killer cells, dendritic cells, monocytes, and B cells based on Seurat analysis. In the insulin group, gene expression of inflammatory cytokines was elevated in cytotoxic CD8+ T cells and Th1 and Th17 cells, and gene expression related to exhaustion was elevated in regulatory T cells. In T cell receptors of various T cells, the T cell receptor β chain was monoclonally increased in the TRBV28/TRBJ2-7 pairs. This study provides insights into the pathogenesis of T1DM and provides potential targets for the treatment of T1DM.

The use of metal nanoparticles such as cerium oxide nanoparticles (nanoceria) in living organisms is attracting increasing attention. Nanoceria are being considered for use in living organisms due to their high ion adsorption ability and antioxidant effects. We administered nanoceria to chronic kidney disease (CKD) 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. Iron is an essential mineral and one of the most important elements for living organisms. Therefore, in this study, we investigated changes in proteins related to iron metabolism following administration of nanoceria to normal mice without CKD 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.

Choline is an essential nutrient for normal brain function, but its bioavailability is not as high as choline esters. Among choline esters, lysophosphatidylcholine (LPC) has unexplored potential as a choline source and cognitive enhancer in humans. This placebo-controlled, double-blinded study, involving healthy participants aged 40–74 years, aimed to assess the effects of an 8-week intake of lysolecithin containing 480 mg LPC on cognitive function and plasma levels of choline and LPC. Twenty-three participants were assigned to both the placebo and lysolecithin groups, and memory was assessed as the primary outcome. Additionally, subjective mental function was assessed. Plasma levels of derivatives of reactive oxygen metabolites were also evaluated for a safety assessment. No significant between-group differences were observed in the memory or mental function score, but a post-hoc analysis yielded significant within-group increases from baseline in subjective mental acuity and calmness in the lysolecithin group. Lysolecithin intake slightly increased plasma choline and LPC18:2 concentrations over 8 weeks, but plasma levels of saturated and total LPC concentrations, associated with inflammation, and derivatives of reactive oxygen metabolites remained unchanged. No adverse events were attributed to lysolecithin supplementation. This study demonstrated lysolecithin’s good tolerability and potential as a new choline supplement.

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.

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 in vivo, 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.

Frequent or long-term circadian disorders can lead to a range of health problems, including chronic insomnia, depression, chronic diseases, and cancer. It has also been shown that altering the feeding time of mice from night to day can result in circadian disorder. Recent studies have revealed complex interactions between circadian rhythm and oxidative stress. However, little is known about the impact of circadian rhythm disorders caused by time-restricted feeding on mental state, immune function, and oxidative DNA damage. In this study, we investigated the effects of circadian rhythm disruption by controlling the timing of feeding and exercise on oxidative DNA damage and immune responses in 8-week-old mice for 14 days. Body weight, daytime running wheel activity, serum interleukin-6 levels, urinary 8-hydroxy-2’-deoxyguanosine levels, and nuclear DNA (liver, lung, testes, and pancreas) were significantly increased in the night-restricted group compared with the control group. Additionally, the mice in the night-restricted group exhibited anxiety-like behavior. These results indicated that the circadian rhythm disruption due to abnormal dietary timing can lead to obesity, mental state dysregulation, immune function changes and oxidative DNA damage in mice. This oxidative DNA damage may contribute to the initiation and increased risk of cancer.

The present study examined factors in subjects diagnosed with hyperglycemia during periodic medical checkups. In total, 9,324 subjects (males: 4532, females: 4792) 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 selected from subjects without hyperglycemia. Data from cases with hyperglycemia were compared to data from themselves one or two years before hyperglycemia. BMI, waist circumference, echo and/or CT-detected 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, LDL cholesterol, AST, ALT, and 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.

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 (LSA), 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 LSA or placebo candy and their saliva secretion was measured over 20 minutes. 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 LSA 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 LSA candy use than by placebo. LSA 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.

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 (¹O₂) oxidation, 16:0/10-hydroperoxy-8E,12Z-octadecanoic acid (10-8E,12Z-HpODE) PC and 16:0/12-9E,13E-HpODE PC, were not detected, but radical oxidation specific products 16:0/13-9E,11E-HpODE PC and 16:0/9-10E,12E-HpODE PC were. This suggests that during CAPPJ irradiation, radicals, rather than ¹O₂, are the primary reactive species of lipid peroxidation. This is also supported by the β-carotene quenching of ¹O₂ not suppressing TBARS and lipid radical generation. Also, neither TBARS formation nor lipid radical generation were suppressed by SOD, indicating that the superoxide radical (O₂^•–) 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.

3-(4-Hydroxy-3-methoxyphenyl) propionic acid (HMPA) is an in vivo metabolite of 4-hydroxy-3-methoxycinnamic acid (HMCA) which is abundantly found in coffee bean, rice bran, fruits, and vegetables. Previous studies reported that polyphenols and their metabolites exhibit positive effects on muscle health. Thus, the effect of HMPA on muscle atrophy induced by dexamethasone (Dex) was investigated using mouse C2C12 skeletal myotubes. Dex treatment (10 μM) reduced the diameter and myosin heavy chain protein expression in C2C12 myotubes; it also increased muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/Atrogin-1 and muscle ring finger protein-1 (MuRF-1), along with their upstream regulator Krüppel-like factor 15 (KLF15). Dex dephosphorylated FoxO3a transcription factor and increased total FoxO3a expression. Interestingly, 10 μM HMPA treatment significantly attenuated Dex-induced reduction in myotube thickness and muscle protein degradation and suppressed muscle atrophy-associated ubiquitin ligases. HMPA also prevented Dex-induced KLF15 and FoxO3a expression. In conclusion, these results suggest that in vivo metabolite of polyphenols per se could be the real origin of the anti-muscular atrophy activity, as HMPA ameliorated glucocorticoid-induced muscle atrophy by suppressing Atrogin-1 and MuRF-1.

Background: Whether vitamin D deficiency causes atrial fibrillation and ischemic stroke of young onset <50 years was unknown.

Methods: We derived a Genetic Risk Score for vitamin D by high-throughput exome chip analysis from 3922 subjects in the University of Hong Kong-Theme Based Research Cohort (rs2060793, rs4588, rs7041, [F-statistic=50.5, P<0.001]), and applied it in an independent sample of 1297 Chinese subjects (age: 67.0 ±10.6 years, 73% male) on clinical outcomes. Primary endpoint was a composite of atrial fibrillation and/ or ischemic stroke. A second study was performed to investigate generalisability and sex-specific effects in the UK Biobank (n=392,010; 46% men; 14,878 atrial fibrillation and 4,050 ischemic stroke cases, versus 374,102 controls).

Results: After follow-up over 76±46 months, 240 primary endpoints (18.5%) were adjudicated. Higher genetically-predicted vitamin D independently predicted reduced odds of atrial fibrillation and/or ischemic stroke (OR=0.83 [0.72 to 0.95], P=0.008). Mendelian randomization analyses indicated vitamin D was causally protective against primary endpoint in Chinese (OR=0.81 [95%CI: 0.65 to 0.98]). An independent analysis in the UK Biobank revealed that vitamin D was generally protective against pre-specified 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]).

Conclusions: Vitamin D may protect against young-onset ischemic stroke through preventing atrial fibrillation. Investigating the sex-specifc effects of vitamin D deficiency may potentially elucidate sex disparities of atrial fibrillation in the young.

Zinc is an essential element and important for inflammatory bowel disease patients. Herein, we aimed to elucidate the correlation between serum zinc concentration and various parameters, especially the disease activity index and endoscopic scores, in these patients. We measured serum zinc concentrations in 37 patients with Crohn’s disease and 64 with ulcerative colitis and retrospectively analyzed patient characteristics, blood test values, disease activity, and endoscopic scores. Hypozincemia (<80 μg/dl) was observed in 45.9% and 29.7% of patients with Crohn’s disease and ulcerative colitis, respectively. Serum zinc concentration showed a weak negative correlation with Crohn's Disease Activity Index and C-reactive protein levels in Crohn’s disease patients, and a weak negative correlation with white blood cell count in ulcerative colitis patients. The zinc concentrations in ulcerative colitis patients were significantly lower in Mayo endoscopic sub-score grade 2 than in grades 0 and 1. The simple endoscopic score for Crohn’s disease moderately correlated with zinc concentration. In addition, serum zinc concentration showed a moderate correlation with serum albumin and Onodera’s prognostic nutritional index in both Crohn’s disease and ulcerative colitis patients. Serum zinc concentration clearly correlated with inflammatory bowel disease activity, endoscopy scores, and immunonutritional parameters, suggesting the importance of monitoring zinc levels.

Dietary fiber-rich diets are gaining popularity as an alternative therapy for skin health. Plant-based prebiotic partially hydrolyzed guar gum (PHGG) dietary fiber promotes gastrointestinal health, which is imperative for skin health through the gut microbiome. In this randomized, double-blind, and placebo-controlled study, the purpose was to assess the therapeutic effects of PHGG on skin hydration, trans-epidermal water loss (TEWL), and skin viscoelastic properties during the winter season. Healthy male and female subjects (n= 70; M9 & F61; mean age: 45.5 ± 8.1 years) were recruited. They received either the 5 g PHGG dietary fiber (n= 35) or a 5 g placebo (n= 35) for twelve weeks. Skin stratum corneum hydration level (skin moisture), TEWL, skin elasticity parameters, skin color variation, and skin quality and condition were assessed using non-invasive characterization methods at baseline (T0), after 6 weeks (T6), and 12 weeks (T12) as well as questionnaires to evaluate the sustainability of the induced changes to support the study outcomes. The results confirmed that soluble PHGG prebiotic dietary fiber can help improve skin conditions throughout the winter season by restoring skin hydration (p ≤ 0.05), reducing trans-epidermal water loss (p ≤ 0.05), and improving skin texture and elasticity parameters (p ≤ 0.05). After 6 weeks of PHGG dietary fiber intake, there was a substantial decrease in TEWL (p = 0.042*) and continuing improvement in viscoelasticity metrics (p ≤ 0.05) when compared to placebo. Also, a significant relationship (Spearman's correlation; p = 0.048*) between increased skin hydration and reduction of trans-epidermal water loss was observed. Subject satisfaction with efficacy reflected these encouraging findings, and the PHGG dietary fiber was well tolerated, with no adverse events occurring during the study period.

Background: Previous researches have revealed the potential association between dietary niacin intakes and several diseases, but studies assessing the association between dietary niacin intakes and nonalcoholic fatty liver disease (NAFLD) is limited and remains unclear. This study was performed to explore the association.

Methods: In this study, 10,528 participants (male: 5,257) in the 10 NHANES cycles (1999-2018) from the NHANES database were selected for the analyses. We built three logistic regression models to explore the independent association between dietary niacin intakes and NAFLD and to explore whether such association exists. Finally, a restricted cubic spline model was applied to simulate the potential nonlinear association between dietary niacin intakes and the occurrence of NAFLD.

Results: The result of the fully-adjusted model suggested that ln-transformed dietary niacin intakes were significantly associated with the reduced occurrence of NAFLD. The Odd ratio (OR) of the model and its 95% confidence interval (CI) were 0.81 (0.73, 0.90). When taking the lowest quartile as a reference, the level of niacin in the highest quartile was associated with decreased prevalence of NAFLD (OR: 0.76, 95% CI: 0.63, 0.91). The restricted cubic spline plot presented a negative dose-response association between levels of daily niacin consumption and the occurrence of NAFLD (p for nonlinearity = 0.762).

Conclusion: According to the results of this study, dietary niacin intakes may have a negative association with NAFLD, and more well-designed cohort studies are required in the future to confirm the obtained finding.