Antiproliferative and anti-inflammatory effects of fractionated crude lectins from boiled kidney beans (Phaseolus vulgaris).

In this study, we investigated the biological profile of lectins isolated from raw and boiled Japanese red Kintoki beans (red kidney beans [RKB]; Phaseolus vulgaris). Lectins in beans showing agglutination activity were retained after heating. Raw and boiled RKB lectins were fractionated using carboxymethyl- and diethylaminoethyl-Sepharose, respectively. Boiled RKB lectins were evaluated for carbohydrate specificity as well as cytokine-inducing and antiproliferative activities against cancer cells and compared with raw RKB lectins. Raw RKB lectins showed specificity for thyroglobulin and fetuin, whereas boiled lectins showed specificity for N-acetylneuraminic acid. Raw RKB lectins showed low resistance to proteases and tolerated temperatures greater than 80°C for 5 min. Notably, lectins from raw and boiled beans showed antiproliferative activity against five types of cancer cells B16, LM8, HeLa, HepG2, and Colo 679. In particular, lectins from raw beans exhibited a significantly stronger activity than those from boiled beans. Anti-inflammatory effects were notably observed in crude extracts from raw and boiled beans. Specifically, lectins fractionated from boiled beans markedly inhibited the expression of tumor necrosis factor-α and interleukin-6. Overall, our results showed that RKB lectins from boiled beans exert anti-inflammatory and anticancer effects and could be developed as potential chemopreventive agents. PRACTICAL APPLICATION: Japanese red kidney beans (RKB) are cultivated in numerous parts of the temperate zone and consumed in many countries. Lectins from boiled beans exhibited anticancer activity, similar to lectins from raw beans. Additionally, crude and fractionated lectins from boiled beans showed anti-inflammatory activity. Thus, boiled RKB lectins have the potential to be used as a bioactive protein for medical research and could be developed as anticancer agents.

The impact of COVID-19 on Japanese patients with eosinophilic gastrointestinal disorders during the vaccination era.

Background: Eosinophilic gastrointestinal disorders (EGIDs) are chronic allergic diseases categorized as eosinophilic esophagitis (EoE) and non-EoE EGIDs. Few studies regarding the association between EGIDs and coronavirus disease 2019 (COVID-19) have been reported. Although most Japanese individuals received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, the incidence of COVID-19 remained high in 2022. This study examines the incidence of COVID-19 in patients with EGIDs during the vaccination era. Methods: Patients with EGIDs who visited our department between October and December 2022 were enrolled in the study. The incidence and severity of COVID-19 prior to October 1, 2022 were determined. Patients who reported having COVID-19 also reported their hospitalization history, intensive care unit admissions, and EGID flares. The number of SARS-CoV-2 vaccinations received and treatment for EGIDs were obtained from the patients' medical records. Results: Of 111 patients with EGIDs (65 with EoE and 46 with non-EoE EGIDs) included in this study, 31 (28%) patients reported having COVID-19, including 14 (22%) with EoE and 17 (37%) with non-EoE EGIDs. Fifty-nine (84%) patients received two or more vaccinations, and 11 (16%) patients received no vaccinations. COVID-19 was mild in all but one patient who had moderate symptoms. COVID-19 was not associated with EGID flares. EGID treatments and an unvaccinated status were not associated with an increased risk of COVID-19. Conclusion: COVID-19 was mild in patients with EGIDs and not associated with EGIDs flares during the vaccination era. There was a relatively high incidence of COVID-19 among patients with non-EoE EGIDs.

Impact of the COVID-19 Pandemic on the Lifestyle and Psychosocial Behavior of Patients with Inflammatory Bowel Diseases: A Narrative Review.

The coronavirus disease (COVID-19) pandemic has had a considerable impact on the global healthcare system and potentially the clinical course of patients with inflammatory bowel disease (IBD). Although IBD is a chronic disease, its therapy (except steroid therapy) does not increase the risk of contracting or aggravating COVID-19. However, the clinical course of patients is significantly influenced by environmental factors. Social restrictions due to the pandemic or the fear of contracting the virus have influenced lifestyle and psychosocial behaviors that may worsen the clinical course of patients with IBD. This narrative literature review summarizes the current evidence on the impact of the COVID-19 pandemic on the lifestyle and psychosocial behaviors of patients with IBD. The COVID-19 pandemic negatively affected the lifestyle and psychosocial behaviors of patients with IBD. Furthermore, patients with IBD failed to maintain medication adherence, thus affecting the clinical course of their condition.

Inflammation-induced nitric oxide suppresses PPARα expression and function via downregulation of Sp1 transcriptional activity in adipocytes.

The activation of peroxisome proliferator-activated receptor alpha (PPARα), a ligand-dependent transcription factor that regulates lipid oxidation-related genes, has been employed to treat hyperlipidemia. Emerging evidence indicates that Ppara gene expression decreases in adipose tissue under obese conditions; however, the underlying molecular mechanisms remain elusive. Here, we demonstrate that nitric oxide (NO) suppresses Ppara expression by regulating its promoter activity via suppression of specificity protein 1 (Sp1) transcriptional activity in adipocytes. NO derived from lipopolysaccharide (LPS) -activated macrophages or a NO donor (NOR5) treatment, suppressed Ppara mRNA expression in 10T1/2 adipocytes. In addition, Ppara transcript levels were reduced in the white adipose tissue (WAT) in both acute and chronic inflammation mouse models; however, such suppressive effects were attenuated via a nitric oxide synthase 2 (NOS2) inhibitor. Endoplasmic reticulum (ER) stress inhibitors attenuated the NO-induced repressive effects on Ppara gene expression in 10T1/2 adipocytes. Promoter mutagenesis and chromatin immunoprecipitation assays revealed that NO decreased the Sp1 occupancy in the proximal promoter regions of the Ppara gene, which might partially result from the reduced Sp1 expression levels by NO. This study delineated the molecular mechanism that modulates Ppara gene transcription upon NO stimulation in white adipocytes, suggesting a possible mechanism for the transcriptional downregulation of Ppara in WAT under obese conditions.

Pretreatment serum monocyte chemoattractant protein-1 as a predictor of long-term outcome by ustekinumab in patients with Crohn's disease.

BACKGROUND AND AIMS: Ustekinumab has been proven to be effective for treatment of patients with Crohn's disease; however, 30-40% of patients have been reported to lose clinical response within 2 years. We aimed to evaluate the efficacy of ustekinumab and identify predictors of short-term and long-term efficacy in Crohn's disease. METHODS: Patients with Crohn's disease receiving their first ustekinumab infusion in our hospital between June 2017 and September 2020 were prospectively enrolled. Concentrations of serum cytokines and chemokines were measured using a multiplex bead array assay. RESULTS: Fifty-nine Crohn's disease patients were enrolled in this study. Among 34 clinically active patients, 38.2% achieved a clinical response at week 8. None of the assayed factors were associated with short-term clinical response. Cumulative persistence rates of ustekinumab were 77.6% at 1 year and 58.9% at 2 years. Univariate Cox regression analysis revealed that Harvey-Bradshaw Index scores at baseline, concomitant immunomodulator treatment, and concentrations of interferon gamma-induced protein-10, monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-1RA, IL-4, IL-6, and IL-8 were significantly associated with loss of efficacy. Multivariate Cox regression analysis found that biologic naïve status (hazard ratio [HR]: 0.1191, 95% confidence interval [CI]: 0.02458-0.5774) and MCP-1 concentrations (HR: 1.038, 95% CI: 1.015-1.062) were significantly and associated with loss of sustained efficacy for ustekinumab treatment. CONCLUSIONS: Our findings suggest that pretreatment serum MCP-1 analysis, combined with a history of biologic use, could be a novel biomarker for predicting the long-term efficacy of ustekinumab in patients with Crohn's disease.

Neutrophil-to-lymphocyte ratio may predict clinical relapse in ulcerative colitis patients with mucosal healing.

Endoscopic mucosal healing (MH) is an important treatment goal for patients with ulcerative colitis (UC). The neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and has been reported to be a useful predictive marker for UC. This study aimed to evaluate the clinical utility of the NLR for predicting clinical relapse in UC patients with MH. We retrospectively enrolled patients with UC who underwent colonoscopy at the Osaka City University Hospital between January 2010 and December 2010, whose Mayo Endoscopic Subscore was 0 or 1. The correlation between the incidence of relapse and demographic factors, including the NLR, was analyzed. We included 129 patients in the present study. The median NLR at the time of endoscopy was 1.98, and differences in the high NLR group and the low NLR group were compared. During a median follow-up period of 46.4 months, 58 patients (45.0%) experienced relapse. The cumulative relapse-free rate was significantly higher in the low NLR group than in the high NLR group (P = 0.03, log-rank test). Multivariate analysis identified high NLR as an independent prognostic factor for clinical relapse (hazard ratio, 1.74; 95% confidence interval, 1.02-2.98; P = 0.04). NLR is a novel and useful predictor of clinical relapse in UC patients with MH, and it can potentially be a strong indicator to determine the appropriate treatment strategy and decision-making in clinical practice.

Hepatic phosphatidylcholine catabolism driven by PNPLA7 and PNPLA8 supplies endogenous choline to replenish the methionine cycle with methyl groups.

Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here, we report that the catabolism of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency, including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased fibroblast growth factor 21 (FGF21), and an altered histone/DNA methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display decreased hepatic triglyceride, likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver.

Analysis of autonomic function during natural defecation in patients with irritable bowel syndrome using real-time recording with a wearable device.

BACKGROUND: Autonomic dysfunction is a factor in irritable bowel syndrome (IBS). However, there are no reports of autonomic nervous system (ANS) activity during natural defecation in patients with IBS. We aimed to clarify the relationship between ANS activity and life events, such as defecation and abdominal symptoms, using real-time recording. METHODS: Six patients with IBS and 14 healthy controls were enrolled in this prospective multicenter study. ANS activity was recorded for 24 h using a T-shirt wearable device, and life events were recorded simultaneously in real time using a smartphone application software. Low frequency/high frequency (LF/HF) and HF calculated by power spectrum analysis were defined as activity indicators of the sympathetic and parasympathetic nerves, respectively. RESULTS: The means of LF/HF and HF in the period with positive symptoms were comparable between the groups; however, the sum of LF/HF, sum of ΔLF/HF, and the maximum variation in ΔLF/HF were significantly higher in the IBS group. In the IBS group, the sum of ΔLF/HF and LF/HF increased significantly from 2 min before defecation, and the sum of LF/HF remained significantly higher until 9 min after defecation. The sum of ΔLF/HF at 2 min before defecation was significantly positively correlated with the intensity of abdominal pain and diarrhea and constipation scores. In contrast, it was significantly negatively correlated with defecation satisfaction and health-related quality of life. CONCLUSIONS: In patients with IBS, sympathetic nerve activity was activated 2 min before defecation, which was correlated with abdominal symptoms and lower QOL.

[Current real-world treatments for Japanese patients with eosinophilic esophagitis].

A total of 306 patients with eosinophilic esophagitis (EoE) were analyzed at our department. Proton pump inhibitors or potassium-competitive acid blockers were used as the first-line treatment in 286 (93.5%) patients. Fifty-five (18.0%) patients received topical steroid swallowing therapy. During 17.7-month mean follow-up, 46.4% of the patients were followed-up with no medications, 37.3% of the patients received maintenance or on-demand therapy using acid-suppressive drugs, and 9.8% of the patients received maintenance therapy with steroid swallowing. The majority of patients with EoE were treated using a therapeutic strategy similar to that used for gastroesophageal reflux disease. However, some patients were refractory to the treatment. Current real-world treatment strategies for Japanese patients with EoE are clarified.

Effect of the Coronavirus Disease 2019 Lockdown on Lifestyle Factors in Japanese Patients with Inflammatory Bowel Disease.

Objective To examine the effect of the coronavirus disease 2019 (COVID-19) lockdown on lifestyle factors and psychological stress in patients with inflammatory bowel disease (IBD). Methods A retrospective study was conducted on patients with IBD in Japan 2 months after the initiation of the first state of emergency (June 16 to August 21, 2020). A self-reported questionnaire was used to collect data, and lifestyle factors and psychological stress levels before and after the state of emergency were compared. Patients Patients with IBD who were followed up regularly at Osaka City University Hospital from June 16 to August 21, 2020, were included and were classified into elderly (≥65 years old) and non-elderly groups (<65 years old). Results The study sample comprised 451 responders (241, ulcerative colitis; 210, Crohn's disease; 0, COVID-19). The sleep duration increased, whereas the exercise, working, and walking durations decreased during the COVID-19 lockdown. The proportion of patients with psychological stress due to COVID-19, those with an inability to exercise, and those staying indoors increased significantly during COVID-19 lockdown. Lifestyle factors changed more markedly in non-elderly patients, those who were more stressed due to COVID-19, those with the inability to exercise, and those staying indoors during COVID-19 lockdown. Among elderly patients, no significant changes were identified in stress-causing factors. Conclusion The COVID-19 lockdown affected lifestyle factors and psychological stress in patients with IBD, particularly non-elderly patients. These findings may be helpful in suggesting favorable lifestyle changes for patients with IBD.

Pyogenic Spondylitis Caused by Staphylococcus schleiferi in a Patient with Crohn's Disease.

Staphylococcus schleiferi has rarely been reported to cause pyogenic spondylitis. A 42-year-old man had been treated for Crohn's disease with immunosuppressive agents and home parenteral nutrition via a central vein (CV) port. The patient was admitted to our hospital, presenting with neck pain and a fever. A neurological examination showed slight weakness in his left-hand muscles, and he was diagnosed with pyogenic spondylitis of C6 and C7 vertebral bodies due to catheter-related blood stream infection caused by S. schleiferi. An early diagnosis by magnetic resonance imaging, CV port removal and antibiotic therapy targeting S. schleiferi improved his symptoms.

Impact of the Lockdown Due to the COVID-19 Pandemic on Patients With Inflammatory Bowel Disease.

Background: The government of Japan declared a state of emergency on April 16, 2020, owing to the coronavirus disease 2019 (COVID-19) pandemic. The subsequent lockdown altered lifestyles and worsened mental illnesses. Inflammatory bowel disease (IBD) is an intestinal disorder that is affected by environmental factors. Therefore, we aimed to assess the effects of COVID-19 and the state of emergency on the lifestyle and disease activity of patients with IBD. Methods: We conducted a questionnaire survey on patients with IBD from June 16 to August 21, 2020 during their regular follow-up at our hospital, 2 months after the state of emergency was declared. Results: Overall, 241 patients with ulcerative colitis (UC) and 210 with Crohn's disease (CD) completed the survey, of which 82 (34%) and 97 (46%) patients, respectively, reported disease exacerbation within 2 months after the lockdown. Multivariate logistic regression analysis identified age at enrollment (odds ratio, OR 0.98, 95% CI 0.96-0.99; P < 0.05), sleep hours (OR, 0.74; 95% CI, 0.57-0.97; P < 0.05), and increased stress due to the COVID-19 pandemic (OR, 6.06; 95% CI, 1.79-20.50; P < 0.01) as independent factors associated with UC exacerbation. Patients with exacerbated CD were younger at CD onset and had higher patient-reported outcome 2 scores before the state of emergency than patients with non-exacerbated CD. On multivariate analysis, age (OR, 0.97; 95% CI, 0.95-0.99; P < 0.01) and active disease before the state of emergency (OR, 2.20; 95% CI, 1.23-3.95; P < 0.01) were independently associated with CD exacerbation. Conclusions: Improving sleep quality and preventing psychological stress may be crucial in IBD management during a pandemic, especially in young patients.

Time-Restricted Feeding Regulates Circadian Rhythm of Murine Uterine Clock.

BACKGROUND: Skipping breakfast is associated with dysmenorrhea in young women. This suggests that the delay of food intake in the active phase impairs uterine functions by interfering with circadian rhythms. OBJECTIVES: To examine the relation between the delay of feeding and uterine circadian rhythms, we investigated the effects of the first meal occasion in the active phase on the uterine clock. METHODS: Zeitgeber time (ZT) was defined as ZT0 (08:45) with lights on and ZT12 (20:45) with lights off. Young female mice (8 wk of age) were divided into 3 groups: group I (ad libitum consumption), group II (time-restricted feeding during ZT12-16, initial 4 h of the active period), and group III (time-restricted feeding during ZT20-24, last 4 h of the active period, a breakfast-skipping model). After 2 wk of dietary restriction, mice in each group were killed at 4-h intervals and the expression profiles of uterine clock genes, Bmal1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1), Per1 (period circadian clock 1), Per2, and Cry1 (cryptochrome 1), were examined. RESULTS: qPCR and western blot analyses demonstrated synchronized circadian clock gene expression within the uterus. Immunohistochemical analysis confirmed that BMAL1 protein expression was synchronized among the endometrium and myometrium. In groups I and II, mRNA expression of Bmal1 was elevated after ZT12 at the start of the active phase. In contrast, Bmal1 expression was elevated just after ZT20 in group III, showing that the uterine clock rhythm had shifted 8 h backward. The changes in BMAL1 protein expression were confirmed by western blot analysis. CONCLUSIONS: This study is the first to indicate that time-restricted feeding regulates a circadian rhythm of the uterine clock that is synchronized throughout the uterine body. These findings suggest that the uterine clock system is a new candidate to explain the etiology of breakfast skipping-induced uterine dysfunction.

Successful Eradication of Helicobacter pylori Could Prevent Metachronous Gastric Cancer: A Propensity Matching Analysis.

BACKGROUND AND AIM: Helicobacter pylori is the leading cause of gastric cancer, but it is still uncertain whether eradicating H. pylori in early gastric cancer (EGC) patients who underwent endoscopic resection can prevent metachronous gastric cancer (MGC). This study aimed to investigate the effect of H. pylori eradication to prevent MGC after endoscopic submucosal dissection (ESD). METHODS: In this propensity-matched retrospective observational study, 770 patients with EGC who received ESD were enrolled. The outcome was the incidence of MGC; this was compared between the persistent and eradicated groups. RESULTS: MGC was detected in 27 patients (7.8%) during a median period of 39.0 months (range 26.0-64.0). After propensity matching, 126 pairs of patients in each group were analyzed. The 5-year cumulative incidence rates of MGC were 13.2 and 3.9% in the persistent and eradicated groups, respectively (p= 0.021, log-rank test). On multivariate analysis, H. pylori eradication prevented MGC significantly (hazard ratio [HR] 0.32; p = 0.029). The results remained robust after inverse probability of treatment weighting analysis (HR 0.30; p = 0.020). CONCLUSIONS: Successful H. pylori eradication could prevent MGC after ESD for EGC.

Acceptance of COVID-19 Vaccines among Patients with Inflammatory Bowel Disease in Japan.

Coronavirus disease 2019 (COVID-19) vaccination is recommended for patients with inflammatory bowel disease (IBD). However, the acceptance of COVID-19 vaccines has not been sufficiently evaluated in patients with IBD. We aimed to assess the acceptance and hesitancy of COVID-19 vaccination and related factors among these patients. A retrospective cohort study using a self-reported questionnaire was performed among patients with IBD between 22 June 2021 and 30 August 2021. Of the 187 participants, 10.2% (n = 19) were hesitant to be vaccinated. Patients in the vaccine-hesitant group were younger (p = 0.009) and had a shorter disease duration (p = 0.020). Vedolizumab was prescribed more frequently (p = 0.024) and immunomodulators were less frequently used (p = 0.027) in this group. Multivariable logistic regression analysis identified age (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.92-1.00, p = 0.042) and the use of immunomodulators (OR: 0.08, 95% CI: 0.01-0.66, p = 0.019) as independent significant factors for vaccine hesitancy. The COVID-19 vaccine hesitancy rate in patients with IBD in Japan was 10% in this study. The Japanese COVID-19 vaccination campaign appears to be successful. The risk of COVID-19 among patients with IBD requires adequate measures to ensure that vaccines are accepted by vaccine-hesitant patients. These findings may be helpful in achieving adequate vaccination rates.

Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio.

OBJECTIVES: Pouchitis is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Although there have been many investigations of the neutrophil-to-lymphocyte ratio (NLR) in various diseases, its role in predicting the development of pouchitis remains unclear. We aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in UC patients. MATERIALS AND METHODS: UC patients who underwent IPAA at Osaka City University Hospital between May 2006 and March 2019 were included. The incidence of pouchitis was estimated using the Kaplan-Meier method. Potential preoperative, intraoperative, and postoperative predictors for pouchitis, including various demographic and clinical variables, were analyzed. The combined impact of the NLR and other known prognostic factors were investigated using Cox proportional hazard regression with inverse probability of treatment weighting (IPTW). RESULTS: Forty-nine patients with UC who underwent IPAA were included. The median follow-up period was 18.3 months (interquartile range: 10.7-47.2 months). Eighteen patients (36.7%) developed pouchitis. The incidence of pouchitis was 19.2%, 32.6%, and 45.9% at 1, 2, and 5 years, respectively. NLR was significantly associated with the development of pouchitis in the univariate Cox regression analysis (hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.01-1.28; P = 0.03). The NLR cutoff value of 2.15 was predictive of the development of pouchitis according to receiver operating characteristic analysis (specificity: 67.7%, sensitivity: 72.2%). The incidence of pouchitis was significantly lower in the low NLR group than that in the high NLR group (P = 0.01, log-rank test). Cox regression analyses using IPTW also identified NLR as a prognostic factor for the development of pouchitis by statistically adjusting for background factors (HR, 3.60; 95% CI, 1.31-9.89; P = 0.01). CONCLUSIONS: NLR may be a novel and useful indicator for predicting the development of pouchitis after IPAA in UC and should be introduced in clinical practice.

Supragastric belching in Japan: lower prevalence and relevance for management of gastroesophageal reflux disease compared to United Kingdom.

BACKGROUND: Supragastric belching (SGB) may play a role in the pathophysiology of proton pump inhibitors (PPIs)-refractoriness in gastroesophageal reflux disease (GERD). SGB may be present in up to 40% of reflux symptoms in PPI-refractory GERD. Most reports on SGB have come from Western countries, and little is known about the prevalence and relevance of SGB in Asian refractory GERD patients. This study aimed at comparing the role of SGB in GERD patients in Japan and the UK. METHODS: We re-analyzed impedance-pH monitoring tracings from patients who were referred to tertiary centers in Japan and the UK due to PPI-refractory reflux symptoms. The prevalence of excessive SGB and the impact of SGB on reflux symptoms were compared between the two countries. RESULTS: Impedance-pH tracings from124 Japanese and 83 British patients were re-analyzed. Japanese patients were significantly younger and had smaller body mass index than the British (P < 0.001). Japanese patients had significantly lower prevalence of excessive SGB (18.5%) than the UK (36.1%) irrespective of reflux phenotype (P = 0.006). Logistic regression analysis showed that the geographical/cultural difference was the only factor associated with the different prevalence of SGB (odds ratio; 2.91, 95% CI 1.09-7.73, P = 0.032). SGB were related to typical reflux symptoms very rarely in Japan [0% (0-4.9)] compared to the UK [35% (0-54.1)] (P = 0.071). CONCLUSIONS: The prevalence of SGB and their impact on reflux symptoms is significantly lower in Japan compared to the UK. The difference is not related to reflux parameters but might come from ethnic/cultural factors to be further characterized.

Adolescent Dietary Habit-induced Obstetric and Gynecologic Disease (ADHOGD) as a New Hypothesis-Possible Involvement of Clock System.

There are growing concerns that poor dietary behaviors at young ages will increase the future risk of chronic diseases in adulthood. We found that female college students who skipped breakfast had higher incidences of dysmenorrhea and irregular menstruation, suggesting that meal skipping affects ovarian and uterine functions. Since dysmenorrhea is more prevalent in those with a past history of dieting, we proposed a novel concept that inadequate dietary habits in adolescence become a trigger for the subsequent development of organic gynecologic diseases. Since inadequate feeding that was limited during the non-active phase impaired reproductive functions in post-adolescent female rats, we hypothesize that circadian rhythm disorders due to breakfast skipping disrupts the hypothalamic-pituitary-ovarian axis, impairs the reproductive rhythm, and leads to ovarian and uterine dysfunction. To explain how reproductive dysfunction is memorized from adolescence to adulthood, we hypothesize that the peripheral clock system also plays a critical role in the latent progression of reproductive diseases together with the central system, and propose naming this concept "adolescent dietary habit-induced obstetric and gynecologic disease (ADHOGD)". This theory will contribute to analyzing the etiologies of and developing prophylaxes for female reproductive diseases from novel aspects. In this article, we describe the precise outline of the above hypotheses with the supporting evidence in the literature.

Slco2a1 deficiency exacerbates experimental colitis via inflammasome activation in macrophages: a possible mechanism of chronic enteropathy associated with SLCO2A1 gene.

Loss-of-function mutations in the solute carrier organic anion transporter family, member 2a1 gene (SLCO2A1), which encodes a prostaglandin (PG) transporter, have been identified as causes of chronic nonspecific multiple ulcers in the small intestine; however, the underlying mechanisms have not been revealed. We, therefore, evaluated the effects of systemic knockout of Slco2a1 (Slco2a1-/-) and conditional knockout in intestinal epithelial cells (Slco2a1ΔIEC) and macrophages (Slco2a1ΔMP) in mice with dextran sodium sulphate (DSS)-induced acute colitis. Slco2a-/- mice were more susceptible to DSS-induced colitis than wild-type (WT) mice, but did not spontaneously develop enteritis or colitis. The nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 (NLRP3) inflammasome was more strongly upregulated in colon tissues of Slco2a-/- mice administered DSS and in macrophages isolated from Slco2a1-/- mice than in the WT counterparts. Slco2a1ΔMP, but not Slco2a1ΔIEC mice, were more susceptible to DSS-induced colitis than WT mice, partly phenocopying Slco2a-/- mice. Concentrations of PGE2 in colon tissues and macrophages from Slco2a1-/- mice were significantly higher than those of WT mice. Blockade of inflammasome activation suppressed the exacerbation of colitis. These results indicated that Slco2a1-deficiency increases the PGE2 concentration, resulting in NLRP3 inflammasome activation in macrophages, thus exacerbating intestinal inflammation.

Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats.

BACKGROUND: We previously reported that skipping breakfast is associated with menstrual disorders of female college students during postadolescent maturation. OBJECTIVE: In this study, we investigated the effects of meal timing during circadian cycle on the ovarian function using young female rats. METHODS: Considering that rats are nocturnally active, 8-wk-old female Wistar rats were classified into 3 groups: fed during the daytime only (nonactive phase), night-time only (active phase), or control group I (without time or calorie restriction, free access to a standard caloric diet, 20.0% protein, 62.9% carbohydrate, and 7.0% fat, 3.95 kcal/g) for 4 wk. The changes in body weight and frequency of ovulation in each group were evaluated by a weight scale and a vaginal smear, respectively. At the end of the period of dietary restriction, ovaries were removed, and the numbers of growing follicles (mean diameter >250 µm) and corpora lutea (>600 µm) were examined using hematoxylin-eosin-stained tissue sections. In addition, 8-wk-old female rats were fed only during the night-time for 4 wk under a 20%-reduced food supply of the control group II (without any restriction). RESULTS: In the daytime-fed group, the frequency and number of ovulations were significantly decreased compared with those in the control group I (P < 0.05), with a reduced body weight gain concomitant with about 20% of reduction in the daily food intake. In contrast, in the night-time-fed group, even when a 20% reduction in the daily food intake was loaded, their estrus cyclicity did not change despite significant reductions in weight gain and food intake compared with control group II. CONCLUSION: These findings indicate that restricting food intake to the inactive phase impairs ovarian function in postadolescent female rats, suggesting that the timing of food intake during circadian cycle is one of the crucial factors interfering with the reproductive function.