Relationship Between the Frequency of Bowel Movements and Fecal Bacteroides in Japanese Women.

The intestinal microbiota is involved in many diseases, such as constipation, obesity, and inflammatory bowel disease. To determine the associations between the gut microbiome and the frequency of bowel movements, we performed cross-sectional correlation analysis at the baseline and longitudinal correlation analysis after the intervention. Forty-three women were enrolled in this study. All participants ingested soymilk-okara powder (15 g) daily for 12 weeks. They recorded the ingested okara powder amounts and their frequency of bowel movements during the entire 12 weeks of the intervention. The fecal microbiota percentages were measured at baseline and after 12 weeks of intervention. Two women who did not completely record the frequency of bowel movements were excluded. In the cross-sectional correlation analysis at the baseline, there was a significant positive correlation between the relative abundance of the Bacteroides genus in the feces and the frequency of bowel movements per week (R = 0.429, p = 0.005) and a significant negative correlation between the relative abundance of Clostridium cluster XI in the feces and the frequency of bowel movements per week (R = -0.315, p = 0.045). Moreover, in the longitudinal correlation analysis, the difference in the relative abundance of Bacteroides genus in feces between the baseline and after the intervention significantly correlated with the changes in the frequency of bowel movements per week (R = 0.492, p = 0.001). Therefore, it was suggested that there was a relationship between the gut relative abundance of the Bacteroides genus and the frequency of bowel movements.

Development of an Oral Immunotherapy-Related Parental Burden Scale.

INTRODUCTION: Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems. This study modified OIT-PB and verified its reliability and validity. METHODS: A 20-item draft covering the physical and mental burdens caused by OIT was prepared jointly with multiple allergists. The Food Allergy Quality of Life Questionnaire-Parental Burden (FAQLQ-PB) and Stress Response Scale-18 (SRS-18) were used to verify concurrent validity. A questionnaire survey was administered during treatment to parents of FA children who had started OIT for the first time. An additional OIT-PB survey was performed at one specific institution 1 week after the posttreatment survey. RESULTS: The responses of 64 of the 76 recruited parents were analyzed. Of the 20 questions, 1 item was excluded owing to the floor effect, 1 was excluded because its commonality was less than 0.2, and 2 were excluded because their factor loading values were less than 0.4. Factor analysis was used to classify the OIT-PB into the following 4 subscales: "burden caused by adherence to treatment plan," "anxiety about symptom-induced risk," "burden due to patient's eating behavior," and "anxiety about treatment effect." The Cronbach's α for all 16 items of the OIT-PB was 0.893; Cronbach's α for each subscale was 0.876, 0.898, 0.874, and 0.717. The re-test reliability coefficient was 0.864 (95% confidence interval [CI]: 0.720-0.937, p < 0.001). A significant positive correlation was found between the OIT-PB and FAQLQ-PB (R = 0.610 [95% CI: 0.422-0.747], p < 0.001) and the SRS-18 (R = 0.522 [95% CI: 0.306-0.687], p < 0.001). A significant negative correlation was found between the rate of increase in OIT food intake and the "anxiety about treatment effect" score (R = -0.355 [95% CI: -0.558-0.112], p < 0.001). Parents of children on the hen's egg OIT treatment scored higher on the "burden due to patient's eating behavior" subscale than did parents of children on the milk and wheat OIT treatment. CONCLUSION: The burden of OIT experienced by parents can be broadly classified into four categories. The modified OIT-PB was able to evaluate them individually and was shown to have reliability and validity. This scale is expected to be useful in the development of OIT that considers not only therapeutic effect but also the burden experienced by FA children and their parents.

Fullerene derivatives as inhibitors of the SARS-CoV-2 main protease.

COVID-19 is an ongoing worldwide pandemic. Even today, there is a need for the development of effective therapeutic agents. SARS-CoV-2 is known as the causative virus of COVID-19, and its main protease is one of the enzymes essential for its growth and is considered a drug discovery target. In this study, we evaluated the inhibitory activities of a variety of fullerene derivatives, including newly synthesized derivatives, against the main protease of SARS-CoV-2. As a result, the malonic acid-type fullerene derivatives showed the strongest inhibitory activity.

Intake of Soymilk-Okara Powder for 12 Weeks Decreases Body Fat and Increases Body Muscle in Japanese Adults: a Single-Arm Intervention Study.

Okara is a by-product of soymilk manufacturing and a rich source of protein and dietary fiber. This study investigates whether dietary soymilk-okara powder intake in the long term affects the body composition and gut microbiota flora in healthy Japanese adults. In total, 46 subjects (43 women) were enrolled. All subjects ingested 15 g of soymilk-okara powder every day for 12 weeks. Subjects' body composition was assessed over four weeks. At baseline and after intervention for 12 weeks, fecal short-chain fatty acid concentrations and microbiota percentages were measured. The body muscle weight significantly increased, and the percentage of body fat significantly decreased at 4, 8, and 12 weeks after the intervention. The increase in body muscle after 12 weeks was 0.6 kg (interquartile range:-0.03 to 1.0). The decrease in body fat was -0.9% (interquartile range: -1.6 to -0.2). There was a significant negative correlation between the changes in body fat and body muscle. For the fecal percentages of Coriobacteriaceae, Lactobacillales, Bacteroides, Clostridium cluster IV, and Clostridium cluster XI, there were significant differences between the baseline and 12 weeks after the intervention. Furthermore, there were significant negative correlations between the changes in body fat percentage and fecal acetic acid and propionic acid levels. Therefore, a dietary intake of 15 g of soymilk-okara powder for 12 weeks induced a decrease in body fat, an increase in body muscle, and a change in fecal microbiota flora. Soymilk-okara powder is effective in improving body composition and changing the intestinal microbiota flora in healthy Japanese adults.

Pannexin1 channel-dependent secretome from apoptotic tumor cells shapes immune-escape microenvironment.

Apoptotic cell death is a critical step in organism development and tissue homeostasis. Apoptotic cells affect immune cell activities in normal tissues. It is not clear whether similar cell death machinery causes tumor environments to evade anti-tumor immune responses. Here, using a mouse transplant model, we found a large number of tumor cells undergoing intrinsic apoptosis in tumors derived from the 4T1 breast cancer cell line, where neutrophils significantly accumulated. Interestingly, these apoptotic 4T1 tumor cells directly induced neutrophil extracellular traps (NETs) in a pannexin 1 (Panx1) channel-dependent manner, and knockdown of Panx1 in 4T1 cells led to a reduction in tumor size. Spermidine released through Panx1 from apoptotic 4T1 cells induced NETs in bone marrow-derived neutrophils in vitro. In addition, inhibition of spermidine synthesis suppressed tumor growth in the mouse transplant model. Collectively, our data suggested a new immune-escape mechanism for tumors by Panx1-mediated secretome from intrinsic apoptotic cells, which may provide a new therapeutic target for cancer.

Novel Mechanism by a Bis-Pyridinium Fullerene Derivative to Induce Apoptosis by Enhancing the MEK-ERK Pathway in a Reactive Oxygen Species-Independent Manner in BCR-ABL-Positive Chronic Myeloid Leukemia-Derived K562 Cells.

In the treatment of breakpoint cluster region-Abelson (BCR-ABL)-positive chronic myeloid leukemia (CML) using BCR-ABL inhibitors, the appearance of a gatekeeper mutation (T315I) in BCR-ABL is a serious issue. Therefore, the development of novel drugs that overcome acquired resistance to BCR-ABL inhibitors by CML cells is required. We previously demonstrated that a bis-pyridinium fullerene derivative (BPF) induced apoptosis in human chronic myeloid leukemia (CML)-derived K562 cells partially through the generation of reactive oxygen species (ROS). We herein show that BPF enhanced the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase (MEK-ERK) pathway in a ROS-independent manner. BPF-induced apoptosis was attenuated by trametinib, suggesting the functional involvement of the MEK-ERK pathway in apoptosis in K562 cells. In addition, the constitutive activation of the MEK-ERK pathway by the enforced expression of the BRAFV600E mutant significantly increased the sensitivity of K562 cells to BPF. These results confirmed for the first time that BPF induces apoptosis in K562 cells through dual pathways-ROS production and the activation of the MEK-ERK pathway. Furthermore, BPF induced cell death in transformed Ba/F3 cells expressing not only BCR-ABL but also T315I mutant through the activation of the MEK-ERK pathway. These results indicate that BPF is as an effective CML drug that overcomes resistance to BCR-ABL inhibitors.

Diet supplementation with commercial enzymatically-hydrolyzed egg white peptides ameliorates the severity of allergy in a mouse model of egg white allergy.

BACKGROUND: Commercial spray-dried egg white (S-EW) is often used for oral immunotherapy (OIT). Peptifine® (PF), a commercial preparation of enzymatically-hydrolyzed egg white (EW) peptides, is considered safe OIT food. OBJECTIVE: Here, we examined the therapeutic effect of PF or S-EW in a mouse model of EW allergy. METHODS: Sensitized female BALB/c mice underwent 4-week OIT by supplementation of 19% casein diet with 1% PF (PF group) or S-EW (S-EW group), and non-supplementation of 20% casein diet (non-OIT group). Non-sensitized mice acted as the non-allergy group. Oral and intraperitoneal EW challenges were performed and allergic biomarkers were determined. RESULTS: Changes in rectal temperature after oral challenge were comparable in the allergy groups. However, after intraperitoneal challenge, rectal temperature decrease in the PF and S-EW groups was lower than in the non-OIT group. After 4 weeks, plasma levels of ovalbumin- and ovomucoid-specific antibodies were assessed; IgE levels in the PF and S-EW groups were lower than those in the non-OIT group. Interleukin-4 secretion after EW challenge was significantly lower in splenocyte cultures derived from PF and S-EW groups than in the non-OIT group. Furthermore, the percentage of CD4+ Foxp3+ splenocytes in the PF group was significantly higher than that in the non-OIT and S-EW groups. Oral gavage of 40 mg PF did not induce an allergic response in sensitized mice with EW. CONCLUSIONS: Diet supplementation with 1% PF mildly ameliorated the severity of allergy in mouse with EW allergy, indicating that PF is a safe OIT food.

Development of a Fluorescent-Labeled Trapping Reagent to Detect Reactive Acyl Glucuronides.

Acyl glucuronides are common metabolites of carboxylic acid-containing compounds. Since acyl glucuronides sometimes show high reactivity, they are considered to be involved in drug toxicity. Therefore, it is important to evaluate the risk posed by acyl glucuronides in the development of safe drugs; however, there are no suitable evaluation methods for the early stages of drug discovery. We aimed to develop a trapping reagent that detects reactive acyl glucuronides to assess their risk. We designed a diamine-structured trapping reagent, Dap-Dan, and compared its trapping ability with the reported one that has an amino group, and results showed that Dap-Dan showed higher accuracy. In the trapping assay with 17 medicines containing a carboxylic acid, Dap-Dan trapped acyl glucuronides that had a higher risk of toxicity. In conclusion, Dap-Dan can be useful for evaluating the risk of reactive acyl glucuronides.

Novel pyridinium-type fullerene derivatives as multitargeting inhibitors of HIV-1 reverse transcriptase, HIV-1 protease, and HCV NS5B polymerase.

In the present study, we newly synthesized four types of novel fullerene derivatives: pyridinium/ethyl ester-type derivatives 3b-3l, pyridinium/carboxylic acid-type derivatives 4a, 4e, 4f, pyridinium/amide-type derivative 5a, and pyridinium/2-morpholinone-type derivative 6a. Among the assessed compounds, cis-3c, cis-3d, trans-3e, trans-3h, cis-3l, cis-4e, cis-4f, trans-4f, and cis-5a were found to inhibit HIV-1 reverse transcriptase (HIV-RT), HIV-1 protease (HIV-PR), and HCV NS5B polymerase (HCV NS5B), with IC50 values observed in the micromolar range. Cellular uptake of pyridinium/ethyl ester-type derivatives was higher than that of corresponding pyridinium/carboxylic acid-type derivatives and pyridinium/amide-type derivatives. This result might indicate that pyridinium/ethyl ester-type derivatives are expected to be lead compounds for multitargeting drugs to treat HIV/HCV coinfection.

Fullerene derivatives as dual inhibitors of HIV-1 reverse transcriptase and protease.

In the present study, we newly synthesized three types of novel fullerene derivatives: pyridinium-type derivatives trans-3a and 4a-5b, piperidinium-type derivative 9, and proline-type derivatives 10a-12. Among the assessed compounds, 5a, 10e, 10f, 10i, 11a-d, and 12 were found to inhibit both HIV reverse transcriptase and HIV protease (HIV-PR), with IC50 values in the low micromolar range being observed. Regarding HIV-PR inhibition activity, proline-type derivatives 11a-11d and 12, bearing an alkyl chain between the hydroxylmethylcarbonyl (HMC) moiety and pyrrolidine ring, were more potent than other derivatives. This result might indicate that connecting HMC moieties with proline-type fullerene derivatives through properly sized alkyl chain leads to improved HIV-PR inhibitory activity.

Increased corn oil intake during an allergy sensitization period aggravates food allergy severity after oral allergen exposure.

Egg white (EW) allergy model mice underwent 15-day oral immunotherapy (OIT) using diets with different corn-oil content and 1% EW. After OIT, mortality following an oral food challenge in OIT groups was approximately 90%. However, in previous studies, mortality was 0%. This phenomenon is to be associated with increased corn-oil intake during allergy sensitization and allergen exposure for 2 weeks.

Relationship between the outcome of low-dose egg oral immunotherapy and the fold-difference levels of allergen-specific IgE and IgG4 in serum.

BACKGROUND: There are no indices to monitor desensitization by low-dose egg oral immunotherapy (eOIT). OBJECTIVE: We aimed to examine the relationship between desensitization by low-dose eOIT and the changes in allergen-specific immunoglobulin E (IgE) and IgG4 levels. METHODS: We carried out low-dose eOIT in 31 patients with severe egg allergy in our previous two studies. After 4 months of treatment, the patients with no observed allergic symptoms in response to the open hard-boiled egg white challenge tests were classified as the negative group, and the remaining patients, the positive group. The fold-difference levels were calculated using 10 Log (Titer after eOIT/Titer before eOIT). RESULTS: The 28 patients who completed eOIT with sufficient serum collected before and after eOIT were analyzed. The median fold-difference levels of ovomucoid-specific IgE in the negative and positive groups were 0.819 and 0.953, respectively (P = 0.082). The median fold-difference levels of ovalbumin-specific IgG4 in the negative and positive groups were 2.01 and 1.29, respectively (P = 0.057). In the receiver-operating characteristic curves, the area under the curves of fold-difference ovomucoid-specific IgE and ovalbumin-specific IgG4 were 0.701 and 0.719, respectively. The challenge positive predictive values of fold-difference ovomucoid-specific IgE and ovalbumin-specific IgG4 were 83.8% (cut-off point: 0.934) and 77.8% (cut-off point: 1.87), respectively. Moreover, the challenge positive predictive value in patients with both 0.934 < ovomucoid-specific IgE and ovalbumin-specific IgG4 <1.87 was 100%. CONCLUSIONS: The fold-difference levels of allergen-specific IgE and IgG4 in serum are considered useful for monitoring desensitization by low-dose OIT.

[Changes in trends of diseases requiring long-term care in an aging community].

Objectives　The purpose of this study was to identify the changes in trends of leading diseases that require long-term care within a 5-year period in an area with a rapidly growing aging population.Methods　Data were obtained from newly registered primary insured individuals for long-term care insurance in Sapporo Minami Ward. There were 2,538 participants in FY2018 and 4,089 in FY2013 and FY2014.　Disorders diagnosed by a primary doctor were categorized into groups using a long-term care questionnaire survey from the Comprehensive Survey of Living Conditions. The difference in the frequency of diseases between the survey years was examined using a chi-square test.Results　In men, there was no significant change in the frequency of diseases that require long-term care within the 5-year period. In women, the frequency of cerebrovascular diseases significantly reduced (7.8% for FY2013 and 2014 vs. 5.6% for FY2018; P=0.008) and fractures and falls significantly increased (9.5% vs. 13.8%; P=0.001).　Regarding the diseases in the severe-level category of long-term care insurance, malignancy was the most frequent disorder in men, followed by stroke. In women, the frequency of fractures and falls increased (10.5% vs. 17.7%; P=0.002) and subsequently became the most frequently occurring disorder. Similarly, the frequency of fractures and falls increased significantly (9.2% vs. 12.5%; P=0.004) in the mild-level long-term care insurance category.Conclusion　For women, fractures and falls increased within the 5-year period, indicating the need to introduce a prompt preventive program. Lifestyle-related diseases such as malignancy and cerebrovascular diseases have become the main reason for shortening a healthy lifespan. This finding highlights the importance of preventing lifestyle-related diseases.

Impact of endoplasmic reticulum stress on oocyte aging mechanisms.

Endoplasmic reticulum (ER) stress is associated with several aging-related diseases; however, the mechanism underlying age-related deterioration of oocyte quality is unclear. Here, we used post-ovulatory, in vivo aged mouse oocytes as a model. Super-ovulated oocytes harvested from the oviduct at 14 h and 20 h post-hCG injection were designated as 'fresh' and 'aged', respectively. Embryo development following IVF was compared between fresh, aged and ER stress-induced oocytes. Expression of the ER stress marker GRP78 was examined at each stage. To evaluate the effect of salubrinal, an ER stress suppressor, on embryo development following IVF, expression levels of GRP78 and phospho-eukaryotic initiation factor 2 alpha were compared between aged and salubrinal-treated aged oocytes. Embryo transfer of salubrinal-treated aged oocytes was performed to examine the safety of salubrinal. Similar to aged oocytes, ER stress-induced oocytes showed lower fertilization rates and poor embryo development. Following IVF, expression of GRP78 decreased with embryo development. GRP78 expression was significantly higher in aged oocytes than in fresh oocytes. Salubrinal lowered GRP78 levels and improved embryo development. No adverse effect of salubrinal treatment was found on the birth weight of pups or on organogenesis in mice. The limitation of this study was that protein kinase-like ER kinase was the only ER stress pathway examined; the role of IRE1 and ATF6 pathways was not considered. Nevertheless, salubrinal can significantly improve embryo development in in vivo aged oocytes undergoing ER stress. Hence, regulation of ER stress might represent a promising therapeutic strategy to overcome poor oocyte quality.

Alzheimer's deterioration in intellectual and neurobiological staging supports the retrogenesis model: a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal glucose metabolism. A retrospective data analysis from the Tajiri Project.

BACKGROUND: Alzheimer disease (AD) patients demonstrate various clinical features reminiscent of children (the retrogenesis model). The Binet test is available for assessing mental development and deterioration. However, neuroimaging correlations remain to be clarified. Although AD patients also manifest social judgment disability, there are few cognitive tests, contrary to so many memory tests. Among the database, we noticed that the Binet test includes the subscale of social judgement using illogical sentences and pictures. The aim of this study is to clarify the neuroimaging correlations for the Binet test, especially for the illogical questions. METHODS: Forty participants were selected from the database of the Tajiri Project. The Tanaka-Binet test was used to evaluate the mental age and the basic age. The latter is the age level at which the patient can completely accomplish all questions at the immediately lower age level and is used for calculating the mental age. Using the subtests of illogical sentences/pictures, logical judgment abilities were assessed. Using magnetic resonance imaging, we performed four-grade visual evaluation for cortical atrophy. The cerebral metabolic rate for glucose (CMRglc) was measured using an autoradiographic method of 18 F-fluoreodeoxyglucose - positron emission tomography (FDG-PET). RESULTS: There was a significant Spearman's correlation between the clinical stage and the basic age. Degree of frontal, temporal and hippocampal atrophy were correlated with the basic age. The entire grey matter and frontal and temporal CMRglc were associated with the basic age. The illogical sentences scores were correlated with the bilateral temporal, hippocampal and the left parieto-temporal CMRglc, whereas the illogical picture scores were correlated with the right parieto-temporal CMRglc. CONCLUSIONS: We found that frontal and temporal atrophy as well as hypometabolism were associated with the basic age. Regarding the illogical judgment, the current PET data analysis disclosed that there may be a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal areas.

Effectiveness and Safety of Double-Blind, Placebo-Controlled, Low-Dose Oral Immunotherapy with Low Allergen Egg-Containing Cookies for Severe Hen's Egg Allergy: A Single-Center Analysis.

INTRODUCTION: The usefulness of low-dose oral immunotherapy (OIT) for the treatment of egg allergy has been unclear. OBJECTIVE: To evaluate the efficacy and safety of OIT with low allergen cookies (LACs) containing a low dose of hen's egg. METHOD: Thirty-three patients with severe hen's egg allergy were randomly administered either OIT with LACs (n = 21) or placebo (n = 12). Two patients in the LACs group withdrew before completing OIT. The primary endpoint was the number of good responders (G-R), patients with negative results in the oral food challenge (OFC) with a final dose of 2 g hard-boiled egg whites after 4 months of OIT, in each group. Total OFC Aichi score for anaphylaxis/cumulative protein dose (TS/Pro) as the marker of severity of food allergy was also compared. Adverse events during OIT were evaluated using patients' diaries. RESULTS: The proportion of G-R in the LACs group was higher than in the placebo group (7/19 [37%] vs. 1/12 [8%], χ2 test; p = 0.077). The TS/Pro after OIT in the LACs group was lower than in the placebo group (median score, 44.2 vs. 104.1, p = 0.059; Mann-Whitney U test). The threshold and TS/Pro before and after OIT significantly improved in the LACs group (p = 0.015, p = 0.027, respectively; Wilcoxon signed-rank test). There were 99 recorded incidences of symptoms of 1,938 intake events in the LACs group during OIT. Of these, 90 were mild; no severe symptoms occurred. CONCLUSIONS: OIT with LACs potentially increases the OFC threshold and decreases allergy severity and is a relatively safe treatment modality.

Transition in Longgu Surface Associated with Decoction Process of Keishikaryukotsuboreito.

We aim to attain the sustainable use of longgu and have investigated the significance of longgu in Keishikaryukotsuboreito (KRB) decoction. We have already reported that longgu alters compound profiles in KRB decoction and hypothesized that it does so by adsorbing foreign organic compounds into its superficial pores. In the present study, we focused on the adsorbability of organic materials onto longgu surface as the cause of component profile alteration. We analyzed the physical changes in longgu through the decoction process by measuring the adsorbed water on longgu surface. 1H magic angle spinning NMR (1H-MASNMR) spectroscopic analysis revealed that raw longgu (R-raw) as well as decocted longgu [whether single (R-r) or KRB (R-krb) decoction] adsorbed water. However, the amount of adsorbed water in R-krb was smaller than that in R-raw and R-r. The nitrogen adsorption isotherms of longgu samples indicated that longgu was macroporous. The Brunauer-Emmett-Teller (BET) surface area of R-krb was smaller than that of R-raw and R-r. Further, thermogravimetric analysis of longgu samples showed that R-krb adsorbed matter that R-raw and R-r did not adsorb. The above findings and the 1H-MASNMR analysis of heated longgu samples suggested that longgu adsorbed organic compounds into the pores. We considered that longgu adsorbed organic compounds during KRB decoction into its superficial pores through the decoction process.

[ACTUAL SITUATIONS OF FOOD ALLERGY RELATED EDUCATION AT NUTRITIONIST TRAINING SCHOOL IN JAPAN].

BACKGROUND & AIM: In the clinical field of food allergies, dietary management towards patients is done inadequately. One plausible reason for this is the possible deficiency of food allergy education during the training courses for registered dietitians. This time, we will investigate the actual situations of food allergy education practiced in the training courses of registered dietitians, and reveal the point at issue. METHOD: We conducted a factual survey via mailing method towards registered dietitian and dietitian nutritionist training facilities throughout the whole country. The survey items include the existence of lectures or practical trainings about food allergies, the pre-graduate education of food allergies, and much more. RESULTS: We got answers from 213 facilities (collection rate 75%). Lectures about food allergies were conducted in 96% of the facilities, and the median of the lecture hour was 210 minutes. Similarly, practical trainings were conducted in 74% of the facilities, and the median was 90 minutes. The rate of people who strongly feel the need for food allergy education was 49%, and the rate for people who felt it was 50%. However, the rate of an ideal educational condition was 32%, and the rate of people who didn't have any plans of increasing the number of lectures and practical trainings were 82%. The major reasons for this were, the crammed condition of the curriculums, and the difficulties conducting lectures and practical trainings that span over several fields of expertise. CONCLUSION: In the training courses of registered dietitians, the practice of food allergy education is hardly adequate, and the educational sites seem to recognize the problem, but they are also pessimistic regarding the improvement of the situation due to the difficult problems that were revealed in this survey. From now on, it is strongly expected for the government and its people to work together to improve the current situation.

Commensal microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4.

The intestinal tract contains many commensal bacteria that modulate various physiological host functions. Dysbiosis of commensal bacteria triggers dysfunction of the intestinal epithelial barrier, leading to the induction or aggravation of intestinal inflammation. To elucidate whether microRNA plays a role in commensal microbiome-dependent intestinal epithelial barrier regulation, we compared transcripts in intestinal epithelial cells (IECs) from conventional and germ-free mice and found that commensal bacteria induced the expression of miR-21-5p in IECs. miR-21-5p increased intestinal epithelial permeability and up-regulated ADP ribosylation factor 4 (ARF4), a small GTPase, in the IEC line Caco-2. We also found that ARF4 expression was up-regulated upon suppression of phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4), which are known miR-21-5p targets, by RNAi. Furthermore, ARF4 expression in epithelial cells of the large intestine was higher in conventional mice than in germ-free mice. ARF4 suppression in the IEC line increased the expression of tight junction proteins and decreased intestinal epithelial permeability. These results indicate that commensal microbiome-dependent miR-21-5p expression in IECs regulates intestinal epithelial permeability via ARF4, which may therefore represent a target for preventing or managing dysfunction of the intestinal epithelial barrier.

Diets Supplemented with 1% Egg White Induce Oral Desensitization and Immune Tolerance in an Egg White-Specific Allergic Mouse Model.

BACKGROUND: The objective of this study was to determine the required concentration of egg white (EW) in the diet to induce oral desensitization and/or immune tolerance within 4 weeks of oral immunotherapy (OIT) in an EW allergic mouse model. METHODS: Female BALB/c mice were systemically sensitized to EW by intraperitoneal injections and subsequently subjected to oral allergen gavage. Sensitized mice were provided 4 weeks of OIT by supplementing with 0 (non-OIT), 0.01, 0.1, or 1% EW in a 20% casein diet. Nonsensitized mice served as the nonallergy group. We performed oral and intraperitoneal EW challenges, assessed vascular permeability in the dorsal skin, and measured allergic biomarkers. RESULTS: The change in rectal temperature after oral challenge was not significantly different between the nonallergy and 1% EW groups, and the frequency of diarrhea in the 1% EW group was lower than that in the non-OIT group. The levels of plasma ovomucoid-specific IgE, IgA, and IgG2a in the 1% EW group at the study endpoint were significantly lower than those in the non-OIT group. IFN-γ and IL-10 secretions of spleen lymphocytes in the 1% EW group were significantly higher than those in the non-OIT group, and the percentage of CD4+Foxp3+ cells in the 1% EW group was higher than that in the non-OIT group. CONCLUSION: These results suggested that diet supplemented with 1% EW can induce oral desensitization and immune tolerance in the EW allergic mouse model.