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.

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.

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.

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.

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.

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.

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 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.

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.

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 (n = 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 (n = 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), p = 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.

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.

Heart failure is a major manifestation of vitamin B₁ deficiency; beriberi. We have previously reported that even vitamin B₁ 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 B₁ and plasma brain natriuretic peptide (BNP) concentrations, a sensitive marker of heart failure, as well as their ‍dietary intake. Whole blood vitamin B₁ concentration was significantly correlated with plasma BNP level in vitamin B₁-deficient/insufficient patients (whole blood vitamin B₁<28 ‍‍ng/ml) but not in sufficient patients. Whole blood vitamin B₁ concen­tration was significantly lower in loop diuretics users than non-users. Multiple regression analysis has identified whole blood vitamin B₁ 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 B₁ concentration. ROC analysis has shown the significant predictability of whole blood vitamin B₁ for plasma BNP ≥100 pg/ml with the cut-off value of 23.5 ‍‍ng/ml. Vitamin B₁ 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.