Search

In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated as an antifungal active compound from Aspergillus burnettii. However, the antifungal activity of 1 has been revealed in only one fungal species, and the mechanism of action of 1 remains unknown. After the validation of mitochondrial function inhibitory of 1, we envisioned a new antimalarial drug discovery platform based on mitochondrial function inhibitory activity. We evaluated antimalarial activity and 1 showed antimalarial activity against Plasmodium falciparum FCR3 (chloroquine sensitive) and the K1 strain (chloroquine resistant). Our study revealed the utility of our original screening system based on a multidrug-sensitive yeast and mitochondrial function inhibitory activity for the discovery of new antimalarial drug candidates., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Previously, we successfully introduced laeA gene into a fungal strain in order to significantly increase the production of a bioactive compound, allowing use to discover novel biological activity. To demonstrate the universal applicability of the laeA gene introduction strategy for taping the potential of fungal secondary metabolism, in this present study, we created a library of microorganisms which we had the laeA gene inserted, and from that library we aimed to isolate compounds which are produced at significantly greater quantities compared to the respective wild type strains. From this investigation, we were able to isolate sclerotinin A (1) from Pochonia sp. KTF-0504 strain. We revealed that 1 showed anti-malarial activity against Plasmodium falciparum parasite strains. On the other hands, 1 showed no anti-fungal activity against multidrug-sensitive budding yeast. Our study implies that the utilization of the laeA gene in fungi is a versatile method for the discovery of drug candidates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y.A., T.T., and K.I. are employees of Kikkoman Corporation. Kitasato University received research funding from Kikkoman Corporation., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and anti-diarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogs, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicines, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The gut-skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage (CSD) on mouse intestines. Following the CSD model, 4% sodium dodecyl sulfate was applied to the back-shaved murine skin six times for 2 weeks after tape stripping. The small and large intestines were analyzed histologically and immunologically, respectively. Intestinal permeability was measured using fluorescein isothiocyanate-conjugated-dextran. The role of interleukin-13 (IL-13) in the ileum was investigated using an anti-IL-13 antibody. Apoptotic intestinal cells were analyzed using TUNEL staining. Villus atrophy was observed in the small intestine in the CSD model, along with increased permeability. Mast cells, but not T cells, eosinophils, or innate lymph cell-2, were increased in the intestinal mucosa. However, no significant changes were observed in the large intestine. mRNA expression of IL-13 was increased only in the ileum of the CSD model. Apoptotic intestinal epithelial cells were significantly increased in the ileum of the CSD model. Administration of an anti-IL-13 antibody ameliorated the intestinal damage caused by CSD, along with decreased apoptotic cells and mast cell infiltration. Skin damage causes morphological changes in the small intestine, accompanied by increased intestinal permeability, possibly through the IL-13-induced apoptosis of mast cells in the epithelium. Surfactant-mediated mechanical skin damage can cause a leaky gut., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP)., Methods: Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) ≦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score ≧3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated., Results: Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15-17.7]; p = 0.03)., Conclusion: The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although the involvement of intestinal microbiota in innate immunity has been reported recently, the pathogenicity of autoimmune pancreatitis (AIP) remains unclear. This study aimed to investigate whether probiotics ameliorate inflammation in AIP through interactions with innate immunity., Materials and Methods: The AIP mouse model was generated by intraperitoneal administration of Escherichia coli to C56BL/6 female mice. Alterations in the intestinal microbiota in the AIP group were evaluated using high-throughput sequencing. Peritoneal macrophages (PMs) were collected and cocultured in vitro with Lactobacillus gasseri (LG) or ligands of Toll-like receptors (TLRs). LG was administered intraperitoneally to AIP model mice, and pancreatitis activity was evaluated to examine the ameliorative effects of LG., Results: In the AIP model mice, inflammation was significantly induced in the pancreas, and the intestinal microbiota was altered with decreased LG. Antimicrobial treatment suppressed pancreatitis. In vitro, E. coli stimulation increased inflammatory cytokine expression, which was significantly decreased when the LG or TLR7 ligand was cocultured with PMs. Intraperitoneal administration of LG to AIP model mice significantly suppressed pancreatitis., Conclusion: The mouse model demonstrated the involvement of intestinal microbiota in pancreatitis, and LG administration suppressed pancreatitis, possibly through TLR7 signaling in PMs. LG may be a helpful probiotic for treating AIP., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A new polyene macrolide, machidamycin (1), and a known compound YS-822A (2), were obtained by physicochemical screening from a culture broth of Streptomyces sp. K22-0017. The structures were elucidated using MS and 1D/2D NMR analyses. Compound 1 exhibited weak antifungal activity against Candida albicans and Mucor racemosus. Furthermore, 1 showed stronger antileishmanial activity than the existing drug paromomycin., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background/aims: Recent studies indicate that probiotics, which have attracted attention as a treatment for irritable bowel syndrome, affect intestinal homeostasis. In this study, we investigated whether Zygosaccharomyces sapae (strain I-6), a probiotic yeast isolated from miso (a traditional Japanese fermented food), could improve irritable bowel syndrome symptoms., Methods: Male Wistar rats were exposed to water avoidance stress (WAS). The number of defecations during WAS and the visceral hypersensitivity before and after WAS were evaluated using colorectal distension. Tight junction changes were assessed by Western blotting. Some rats were fed with strain I-6 or β-glucan from strain I-6. Changes in the intestinal microbiota were analyzed. The effect of fecal microbiota transplantation after WAS was evaluated similarly. Caco-2 cells were stimulated with interleukin-1β and tight junction changes were investigated after coculture with strain I-6., Results: The increased number of stool pellets and visceral hypersensitivity induced by WAS were suppressed by administering strain I-6. The decrease in tight junction protein occludin by WAS was reversed by the administration of strain I-6. β-Glucan from strain I-6 also suppressed those changes induced by WAS. In the rat intestinal microbiota, treatment with strain I-6 altered the β-diversity and induced changes in bacterial occupancy. Upon fecal microbiota transplantation, some symptoms caused by WAS were ameliorated., Conclusions: These results suggest that traditional fermented foods such as miso in Japan are valuable sources of probiotic yeast candidates, which may be useful for preventing and treating stress-induced visceral hypersensitivity.

Two new antimalarial compounds, named prenylpyridones A (1) and B (2), were discovered from the actinomycete cultured material of Streptomyces sp. RBL-0292 isolated from the soil on Hamahiga Island in Okinawa prefecture. The structures of 1 and 2 were elucidated as new iromycin analogs having α-pyridone ring by MS and NMR analyses. Compounds 1 and 2 showed moderate in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with IC 50 values ranging from 80.7 to 106.7 µM., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Three new antiplasmodial compounds, named akedanones A ( 1 ), B ( 2 ), and C ( 3 ), were discovered from the cultured material of Streptomyces sp. K20-0187 isolated from a soil sample collected at Takeda, Kofu, Yamanashi prefecture in Japan. The structures of compounds 1 - 3 were elucidated as new 2,3-dihydronaphthoquinones having prenyl and reverse prenyl groups by mass spectrometry and nuclear magnetic resonance analyses. Compound 1 and the known furanonaphthoquinone I ( 4 ) showed potent in vitro antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with half-maximal inhibitory concentration values ranging from 0.06 to 0.3 μM. Compounds 1 and 4 also displayed potent in vivo antiplasmodial activity against drug-sensitive rodent malaria Plasmodium berghei N strain, with inhibition rates of 47.6 and 43.1%, respectively, on intraperitoneal administration at a dose of 5 mg kg -1 day -1 for 4 days.

Two new pramanicin analogs, named virgaricins C (1) and D (2), were discovered by physicochemical screening from a static cultured material of Apiospora sp. FKI-8058. Their structures were elucidated by MS and NMR analyses and chemical derivatization. Compounds 1 and 2 showed moderate antimalarial activity and cytotoxicity., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background and Aim: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC., Methods: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy., Results: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001)., Conclusions: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction Hand hygiene is an infection control measure for COVID-19 in our daily lives; however, the contamination levels of SARS-CoV-2 in the hands of healthy individuals remain unclear. Thus, we aimed to evaluate SARS-CoV-2 contamination levels by detecting viral RNA and viable viruses in samples obtained from the hands of 925 healthy individuals. Methods Swab samples were collected from the palms and fingers of healthy participants, including office workers, public officers, university students, university faculty and staff, and hospital staff between December 2022 and March 2023. The collected swab samples were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for SARS-CoV-2 RNA detection. Viral RNA-positive samples were subjected to plaque assay to detect viable viruses. Results We collected 1,022 swab samples from the hands of healthy participants. According to the criteria for data collection, 97 samples were excluded, and 925 samples were analyzed using RT-qPCR. SARS-CoV-2 RNA was detected in three of the 925 samples. The viral RNA detection rate was 0.32% (3/925), and the viral RNA copy numbers ranged from 5.0×10 3  to 1.7×10 5  copies/mL. The RT-qPCR-positive samples did not contain viable viruses, as confirmed by the plaque assay results. Conclusions The detection rate of SARS-CoV-2 RNA from the hands of healthy individuals was extremely low, and no viable viruses were detected. These results suggest that the risk of contact transmission via hands in a community setting is extremely rare., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Matsui et al.)

Little is known about iatrogenic splenic injury (SI) as an adverse event after colonoscopy. SI is sometimes fatal because of hemorrhaging. We herein report a man who developed SI after colonoscopy. He recovered conservatively. His history of left hydronephrosis and insertion with a maximally stiffened scope were suspected as possible risk factors. Endoscopists should consider the possibility of SI when they encounter patients suffering from left-sided abdominal pain after colonoscopy. Careful interview concerning the medical history and gentle maneuvering around the splenic flexure can help avoid SI.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p  = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p  = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p  = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p  = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p  = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2024 JCBN.)

Introduction: We examined the associations among disease-related symptoms, health-related quality of life (HRQOL), and sense of coherence (SOC) in Japanese patients with ulcerative colitis (UC)., Methods: This cross-sectional survey involved patients and physicians at 23 hospitals specializing in UC treatment in Japan (December 2019-December 2020). Multiple linear regression analysis was performed using scores on the Mental Health and General Health subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey as outcomes and SOC as the main independent variable. Scores on the Inflammatory Bowel Disease Questionnaire (IBDQ) and Fecal Incontinence Quality of Life Scale (FIQL) were used to measure the effect of disease-related symptoms. The moderating effect of symptoms on the association between HRQOL and SOC was also tested., Results: SOC was positively and independently associated with HRQOL (Mental Health: β = 0.43, 95% confidence interval [CI] = 0.24-0.61, p &lt; 0.001; General Health: β = 0.41, 95% CI = 0.23-0.59, p &lt; 0.001). The association of SOC with Mental Health scores did not differ by symptoms, whereas its association with General Health was attenuated by symptoms (interaction term of IBDQ by SOC: β = -0.0082, 95% CI = -0.017 to 0.00064, p = 0.07; that of FIQL by SOC: β = -0.0052, 95% CI = -0.011 to 0.0010, p = 0.10)., Conclusions: SOC affected mental health independently, and its protective association with general health perception was affected by symptoms. Further research is required to determine the most effective use of SOC in interventions to improve HRQOL in patients with UC., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The filamentous fungus Synnemellisia sp. strain FKR-0921 was obtained from soil collected on Kume Island, Okinawa. The MeOH extract of FKR-0921 cultured on a solid rice medium yielded a new aromatic compound, synnemellisitriol A (1). The structure, including the absolute configuration, was elucidated by spectroscopic analysis (FT-IR, NMR, and HR-ESI-MS), and the absolute configuration at C-9 of 1 was determined using the modified Mosher's method. Additionally, 1 was evaluated for its biological activities, including metallo-β-lactamase inhibitory activity, type III secretion system inhibitory activity, antimicrobial activity, antimalarial activity, and cytotoxicity., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background: Mild blast-induced traumatic brain injury (bTBI) induces various gut symptoms resembling human irritable bowel syndrome (IBS) as one of mental and behavioral disorders. However, the underlying mechanisms remain unclear. We investigated whether the extremely localized brain impact extracranially induced by laser-induced shock wave (LISW) evoked IBS-like phenomenon including visceral hypersensitivity and intestinal hyperpermeability in rats., Methods: The rats were subjected to LISW on the scalp to shock the entire brain. Visceral hypersensitivity was evaluated by the threshold pressure of abdominal withdrawal reflex (AWR) using a colorectal distension test. Permeability was evaluated by the concentration of penetrating FITC-dextran from intestine and the mRNA expression levels of tight junction family proteins. Involvement of corticotropin-releasing factor receptor (CRFR) 1 and 2 was examined by evaluating mRNA expression and modulating CRFR function with agonist, recombinant CRF (10 μg/kg), and antagonist, astressin (33 μg/kg). High-throughput sequencing of the gut microbiota was performed by MiSeqIII instrument and QIIME tool., Key Results: The thresholds of the AWR were significantly lowered after LISW. Permeability was increased in small intestine by LISW along with decreased expression of tight junction ZO-1. LISW significantly increased CRFR1 expression and decreased CRFR2 expression. Visceral hypersensitivity was significantly aggravated by CRFR agonist and suppressed by CRFR antagonist. The α- and β-diversity of the fecal microbiota was altered after LISW., Conclusions and Inferences: LISW provoked visceral hypersensitivity, small intestinal hyperpermeability, altered expression of CRFRs and changes in the microbiota, suggesting that genuine bTBI caused by LISW can induce a pathophysiology comparable to that of human IBS., (© 2023 John Wiley & Sons Ltd.)

As society becomes smarter, advanced optical sensing and imaging technologies utilizing visible and near-infrared regions have become increasingly prevalent. Wire-grid polarizers, which are available for broadband electromagnetic waves, are effective in improving the signal-to-noise ratio of such optical systems and enabling more advanced object detection and analysis. However, to be implemented in everyday products, low-cost manufacturing methods must be developed while maintaining high-performance optical functions. To meet these requirements, we conducted an analysis of the geometry of wire-grid polarizers, and designed and developed a wire-grid polarizer with a nano-triangular wave-shaped structure that can be fabricated using general-purpose manufacturing equipment. Once the mould is prepared, this polarizer can be fabricated via nanoimprinting and metal deposition with a normal angle or electroless plating processes. The polarizer fabricated through electroless Ni plating achieves a transmittance of 40%, which is approximately 1.4 times higher than that achieved in a previous study using electroless Ni plating on a rectangular structure with the same period. In addition, the polarizer fabricated through normal angle Al deposition operates over a wide range of wavelengths from visible light to near-infrared, and achieves a polarization extinction ratio of 24 dB at a wavelength of 550 nm and a high transmittance of 81%. High-performance polarizers can be obtained through normal-angle deposition using general-purpose equipment in contrast to the oblique-angle deposition method employed in the manufacture of conventional rectangular structure-based wire-grid polarizers, thereby contributing to cost reduction and improved manufacturability., (© 2023. Springer Nature Limited.)

Two new antimalarial compounds, named deacetyl fusarochromene (1) and 4'-O-acetyl fusarochromanone (2), were discovered from the static fungal cultured material of Fusarium sp. FKI-9521 isolated from feces of a stick insect (Ramulus mikado) together with three known compounds fusarochromanone (3), 3'-N-acetyl fusarochromanone (4), and 5 (fusarochromene or banchromene). The structures of 1 and 2 were elucidated as new analogs of 3 by MS and NMR analyses. The absolute configurations of 1, 2, and 4 were determined by chemical derivatization. All five compounds showed moderate in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with IC 50 values ranging from 0.08 to 6.35 µM., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Objective: Bleeding occurs after liver biopsy in up to 10.9% cases, and patients with impaired hemostasis or ascites are considered to have absolute or relative contraindications. N-butyl cyanoacrylate enables immediate hemostasis, even in lethal situations. Therefore, percutaneous liver biopsy combined with tract embolization using N-butyl cyanoacrylate is expected to enable safe biopsy, even in patients for whom conventional biopsy is contraindicated. Here we describe our initial experience with coaxial percutaneous biopsy with tract embolization using N-butyl cyanoacrylate., Materials and Methods: Eighty-six patients who underwent tract embolization using N-butyl cyanoacrylate between October 2014 and July 2020, including 21 patients who had absolute or relative contraindications for liver biopsy, were retrospectively analyzed. Tract embolization using N-butyl cyanoacrylate comprised two steps: (1) liver biopsy with a biopsy needle inserted via a coaxial introducer needle and (2) embolization of the puncture route by injecting N-butyl cyanoacrylate via the coaxial needle., Results: No complications occurred in any patient. The mean number of biopsies per patient was 3.30 (range, 1-7). Histologically adequate samples were acquired in all cases, and pathological diagnoses were obtained. The mean time required for tract embolization was 52.8 s (range, 6-132 s). The mean peak skin dose was 9.97 mGy (range, 2-68 mGy), which is far below the 3-Gy threshold dose for temporary erythema., Conclusions: This proposed technique may be a promising and straightforward alternative to improve the management of patients with severe liver disease by allowing safer biopsy, including patients for whom conventional liver biopsy is contraindicated.

Background: Although crowds are considered to be a risk factor for SARS-CoV-2 transmission, little is known about the changes in environmental surface contamination with the virus when a large number of people attend an event. In this study, we evaluated the changes in environmental surface contamination with SARS-CoV-2., Methods: Environmental samples were collected from concert halls and banquet rooms before and after events in February to April 2022 when the 7-day moving average of new COVID-19 cases in Tokyo was reported to be 5000-18000 cases per day. In total, 632 samples were examined for SARS-CoV-2 by quantitative reverse transcription polymerase chain reaction (RT-qPCR) tests, and RT-qPCR-positive samples were subjected to a plaque assay., Results: The SARS-CoV-2 RNA detection rate before and after the events ranged from 0% to 2.6% versus 0%-5.0% in environmental surface samples, respectively. However, no viable viruses were isolated from all RT-qPCR-positive samples by the plaque assay. There was no significant increase in the environmental surface contamination with SARS-CoV-2 after these events., Conclusions: These findings revealed that indirect contact transmission from environmental fomite does not seem to be of great magnitude in a community setting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, the mechanism of which is involved in oxidative stress, can be lethal due to hemorrhage. Thus, we aimed to investigate the effect of hydrogen-rich water (HRW), in terms of oxidative stress, on intestinal mucosal damage as well as changes in the gut microbiome and the short-chain fatty acids (SCFAs) content in feces., Methods: Hydrogen-rich water was orally administered for 5 days to investigate the effectiveness of indomethacin-induced enteropathy in mice. Small intestinal damage and luminal reactive oxygen species (ROS) were evaluated to investigate the ameliorating effects of hydrogen. Then, components of the gut microbiome were analyzed; fecal microbiota transplantation (FMT) was performed using the cecal contents obtained from mice drinking HRW. The cecal contents were analyzed for the SCFAs content. Finally, cells from the macrophage cell line RAW264 were co-cultured with the supernatants of cecal contents., Results: Hydrogen-rich water significantly ameliorated IND-induced enteropathy histologically and reduced the expression of IND-induced inflammatory cytokines. Microscopic evaluation revealed that luminal ROS was significantly reduced and that HRW did not change the gut microbiota; however, FMT from HRW-treated animals ameliorated IND-induced enteropathy. The SCFA content in the cecal contents of HRW-treated animals was significantly higher than that in control animals. The supernatant had significantly increased interleukin-10 expression in RAW264 cells in vitro., Conclusion: Hydrogen-rich water ameliorated NSAID-induced enteropathy, not only via direct antioxidant effects but also via anti-inflammatory effects by increasing luminal SCFAs. These results suggest that hydrogen may have therapeutic potential in small intestinal inflammatory diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Luminal antigens, nutrients, metabolites from commensal bacteria, bile acids, or neuropeptides influence the function and trafficking of immune cells in the intestine. Among the immune cells in the gut, innate lymphoid cells, including macrophages, neutrophils, dendritic cells, mast cells, and innate lymphoid cells, play an important role for the maintenance of intestinal homeostasis through a rapid immune response to luminal pathogens. These innate cells are influenced by several luminal factors, possibly leading to dysregulated gut immunity and intestinal disorders such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and intestinal allergy. Luminal factors are sensed by distinct neuro-immune cell units, which also have a strong impact on immunoregulation of the gut. Immune cell trafficking from the blood stream through the lymphatic organ to lymphatics, an essential function for immune responses, is also modulated by luminal factors. This mini-review examines knowledge of luminal and neural factors that regulate and modulate response and migration of leukocytes including innate immune cells, some of which are clinically associated with pathological intestinal inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Higashiyama, Miura and Hokari.)

Background and Aim: The study of the impact of environmental factors during pregnancy on fetal development has so far been focused primarily on those negatively affecting human health; however, little is known about the effects of probiotic treatment during pregnancy on inflammatory bowel diseases (IBD). In this study, we investigated whether oral administration of heat-killed probiotics isolated from fermented foods decreased the vulnerability of offspring to IBD., Methods: Probiotics were administered to the pregnant mice until the birth of pups, after which the parent mice were maintained with autoclaved water. Partial pups were evaluated for dextran sodium sulfate-induced colitis. The influence of CD11c + CD103 + dendritic cells (DCs) and regulatory T cells (Tregs) in mesenteric lymph nodes of parent mice and their pups was analyzed., Results: Oral administration of heat-killed probiotics to pregnant dams significantly decreased inflammation induced by dextran sodium sulfate in pups. Probiotic treatment increased the number of CD103 + DCs, and the expression of β8-integrin in CD103 + DCs and Tregs in mesenteric lymph nodes, not only in dams themselves but also in their offspring., Conclusions: Oral administration of probiotics during gestation induced transgenerational immunomodulatory effects on the gut-associated immune system and resilience to experimental colitis in the offspring. Our results suggest that consumption of fermented foods during pregnancy can be effective in preventing inflammatory diseases such as IBD beyond generation., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The specific etiopathogenesis of inflammatory bowel disease (IBD) is still unknown. Although the conventional anti-inflammatory or immunomodulatory drugs relatively nonspecific to pathogenesis have been quite useful in many cases, elucidating the pathogenesis has gradually facilitated developments of disease-specific therapies for refractory cases in the last 2 decades., Summary: With a greater understanding of the multiple overactive signaling pathways of the gut mucosal immune response and enhanced leukocyte trafficking, several biological agents or small molecule drugs following the first novel biologic, anti-tumor necrosis factor α (anti-TNFα), have been developed against several modes of action including adhesion molecules, sphingosine-1-phospate receptors, cytokines (IL-12/23, TL1A, and IL-36), Janus kinase (JAK), and phosphodiesterase. Although preceding biological agents have dramatically changed the IBD treatment strategy, many patients still require alternative therapies due to failure or side effects. Newer treatments are now expected to be provided for better efficacy with an improved adverse event profile. In addition, translational studies have highlighted the new therapeutic concepts' potential, including modulation of host-microbiome interactions, stem therapy for perianal fistula, regulation of fibrosis, regulation of the gut-brain axis, and control of previously less targeted immune cells (B cells and innate lymphoid cells). This paper comprehensively reviewed not only the latest already or shortly available therapies but also emerging promising treatments that will be hopefully established in the future for IBD., Key Messages: Many kinds of new treatments are available, and promising treatments with new perspectives are expected to emerge for refractory IBD in the future., (© 2022 S. Karger AG, Basel.)

In near-infrared systems for optical sensing and imaging technologies, an improved signal-to-noise ratio and more advanced object detection and analysis using polarizers are required. Such polarizers are limited, and broadband wire-grid polarizers are potential candidates. However, their high reflectivity and high cost limit their application. Herein, we fabricated a low-reflectivity wire-grid polarizer sheet that can be used in visible and near-infrared regions by a simple process using only nanoimprinting and nickel electroless plating; further, metal removal steps such as chemical mechanical polishing were not required. The results obtained by optimizing the structural shape of the mold and precisely controlling the thickness of the electroless plating confirmed that the polarizer could be used for visible and near-infrared light. Because the sheets can be manufactured using general-purpose equipment upon mold preparation, they can be employed in wide-ranging applications with small capital investment.

Two new antiplasmodial peptides, named koshidacins A ( 1 ) and B ( 2 ), were discovered from the culture broth of the Okinawan fungus Pochonia boninensis FKR-0564. Their structures, including absolute configurations, were elucidated by a combination of spectroscopic methods and chemical derivatization. Both compounds showed moderate in vitro antiplasmodial activity against Plasmodium falciparum strains, with IC 50 values ranging from 17.1 to 0.83 μM. In addition, compound 2 suppressed 41% of malaria parasites in vivo when administered intraperitoneally at a dose of 30 mg/kg/day for 4 days.

Background and Aim: The functions of basophils have not been elucidated until recently because of their rarity. However, with recent developments in basophil-specific antibodies and basophil-deficient animals, the roles of basophils in various diseases related to chronic inflammation have been clarified. In this study, we aimed to investigate the roles of basophils in human ulcerative colitis (UC) and oxazolone (OXA) colitis using genetically engineered Mcpt8 DTR mice., Methods: Immunohistochemical staining of human colon specimens was performed to examine the involvement of basophils in the pathogenesis of UC. We examined the correlation between the number of infiltrating basophils and the UC endoscopic index of severity (UCEIS), Mayo score, and Matts score. We also examined the correlation between eosinophil count and basophil infiltration. In murine experiments, we examined whether basophil infiltration was involved in OXA-induced colitis and whether basophil depletion improved inflammation in Mcpt8 DTR mice., Results: Colonic basophil infiltration was significantly increased in patients with UC. There were significant correlations between UCEIS, Mayo score, Matts score, and the number of infiltrating basophils. In murine OXA-induced colitis, a significant increase in basophil infiltration was observed. When basophils were depleted by diphtheria toxin in Mcpt8 DTR mice, inflammation improved significantly and mRNA expression of some proinflammatory cytokines, including Tnf-α and Ifn-γ decreased significantly., Conclusion: Basophil infiltration correlated with endoscopic, clinical, and pathological scores in human UC independently of eosinophil infiltration, and depletion of basophils ameliorated mucosal inflammation in murine OXA-induced colitis, collectively suggesting that basophils exert a proinflammatory role in chronic intestinal inflammation such as UC., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk., Methods: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index., Results: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008)., Conclusions: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Most natural products derived from microorganisms have been sought from actinomycetes and filamentous fungi. As an attempt to develop new microbial resources in the exploratory research for natural products, we searched for new compounds from unexploited microbial taxa presumed to have biosynthetic gene clusters. A new compound confluenine G (1) and a known compound (2Z)-2-octyl-2-pentenedioic acid (2) were isolated from a cultured broth of basidiomycetous yeast, Moesziomyces sp. FKI-9540, derived from the gut of a moth Acherontia lachesis (Lepidoptera, Sphingidae). Based on the results of HR-ESI-MS and NMR analyses, the planar structure of 1 was elucidated. Confluenine G (1) was a new analog of nitrogen-oxidized isoleucine and had rare substructures with oxime and hydroxamic acid in molecule., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

A 78-year-old man presented to our hospital with a history of 10 kg weight loss within 6 months previously and general fatigue and fever for 2 and 1 months, respectively. On hospitalisation, the patient was diagnosed with polyarteritis nodosa after multiple microaneurysms were observed in the liver, kidney, pancreas, and mesenteries. He achieved remission with the administration of 1000 mg methylprednisolone for 3 days, followed by prednisolone (55 mg/day). Steroids were successfully tapered with no re-elevation in inflammation. Two months after the administration of steroids, the patient complained of acute abdominal pain and developed severe acute pancreatitis. During treatment for pancreatitis, the patient died due to septic shock and disseminated intravascular coagulation. An autopsy revealed necrotising vasculitis in the intrapancreatic arteries and ischaemia of the downstream arterioles resulting in acute pancreatitis., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sattahipmycin was isolated from the mycelium of marine-derived Streptomyces sp. GKU 257-1 by following the antibiofilm activity against E. coli NBRC 3972 throughout the purification steps. The structure of sattahipmycin was determined to be a new polycyclic xanthone related to xantholipin but lacking a dioxymethylene and a chlorinated carbon. This compound showed activity toward Gram-positive bacteria and Plasmodium falciparum , antibiofilm formation of Escherichia coli , and cytotoxicity to human cancer cell lines. Using genome sequence data, a biosynthetic pathway leading to sattahipmycin has been proposed involving an uncharacterized type II polyketide synthase biosynthetic gene cluster.

Background and Aim: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC., Methods: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls., Results: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003)., Conclusions: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Four new tricyclic macrolides, named shikinefragalides A (1), B (2), C (3) and D (4), were isolated by physicochemical (PC) screening from a static culture material of Stachybotryaceae sp. FKI-9632. Their structures were elucidated as new analogs of colletofragarones by MS and NMR analyses. Compounds 1 and 2 showed weak antimalarial activity and cytotoxicity., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Takayasu arteritis (TA) sometimes presents with colitis, which may be diagnosed as inflammatory bowel disease unclassified (IBDU) because of atypical or mixed findings of ulcerative colitis (UC) and Crohn's disease. We herein report an 18-year-old girl presenting with colitis with an occasional high fever eventually diagnosed as TA with IBDU. Colonic inflammation was initially discontinuous and stronger in the proximal colon, atypical of UC. However, over 10-year observation, the distribution of colonic inflammation varied and became UC-like. Variations in TA-related colonic inflammations over time have been unclear. Our long-term observation might help clarify the details of TA-related colonic inflammation.

Background: Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD., Methods: Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance., Results: In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%)., Conclusions: Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether luminal UA is increased under hyperuricemia and plays a protective role in a dose-dependent manner as well as the mechanism by which luminal UA exerts its protective effects on enteropathy remains unknown., Methods: Inosinic acid (IMP) (1000 mg/kg, i.p.) was administered to obtain high serum UA (HUA) and moderate serum UA (500 mg/kg IMP, i.p.) mice. UA concentrations and levels of oxidative stress markers in the serum and intestine were measured. Mice received indomethacin (20 mg/kg, i.p.) to evaluate the effects of UA on indomethacin-induced enteropathy. Reactive oxygen species (ROS) on the ileal mucosa were analyzed. The fecal microbiota of HUA mice was transplanted to investigate its effect on indomethacin-induced enteropathy., Results: IMP increased luminal UA dose-dependently, with higher levels of luminal antioxidant markers. Indomethacin-induced enteropathy was significantly ameliorated in both UA-elevated groups, with decreased indomethacin-induced luminal ROS. The microbiota of HUA mice showed a significant increase in α-diversity and a significant difference in β-diversity from the control. Fecal microbiota transplantation from HUA mice ameliorated indomethacin-induced enteropathy., Conclusions: The protective role of luminal UA in intestinal injury is likely exerted via oxidative stress elimination and microbiota composition modulation, preferably for gut immunity. Therefore, enhancing anaerobic conditions using antioxidants is a potential therapeutic target., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background and Aim: The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease-like ileitis. We aimed to investigate the effect of ACK on the intestinal mucosa and gut microbiota of normal mice., Methods: Acesulfame potassium was administered to C57BL/6J mice (8 weeks old) via free drinking. Intestinal damage was evaluated histologically, and messenger RNA (mRNA) levels of TNF-α, IFN-γ, IL1-β, MAdCAM-1, GLP1R, and GLP2R were determined with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed to examine the expression of MAdCAM-1 in the small intestine. The composition of gut microbiota was assessed using high-throughput sequencing. We performed intravital microscopic observation to examine if ACK altered lymphocyte migration to the intestinal microvessels., Results: Acesulfame potassium increased the expression of proinflammatory cytokines, decreased the expression of GLP-1R and GLP-2R, and induced small intestinal injury with an increase in intestinal permeability, and ACK treatment induced microbial changes, but the transfer of feces alone from ACK mice did not reproduce intestinal damage in recipient mice. ACK treatment significantly increased the migration of lymphocytes to intestinal microvessels., Conclusion: Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. Massive use of non-caloric artificial sweeteners may not be as safe as we think., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objectives: Oxidative stress is considered one of the etiologic factors involved in ulcerative colitis (UC), yet there is limited epidemiologic information regarding the relationship between antioxidant intake and the risk of UC. The aim of the present case-control study in Japan was to examine the association between intake of green and yellow vegetables, other vegetables, fruit, vitamin C, vitamin E, retinol, alpha-carotene, beta-carotene, and cryptoxanthin and UC risk., Methods: A total of 384 cases within 4 y of diagnosis with UC and 665 controls were included in the study. Data on dietary intake and confounders were obtained using a self-reported questionnaire. Information on dietary factors was collected using a 169-item semiquantitative food-frequency questionnaire. Adjustment was made for sex, age, pack-y of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index., Results: Higher intake levels of other vegetables, vitamin C, and retinol were independently associated with a reduced risk of UC. The adjusted odds ratio between extreme quartiles was 0.51 (95% confidence interval [CI], 0.34-0.76; P for trend ≤ 0.001) for other vegetables, 0.45 (95% CI, 0.30-0.69, P for trend ≤ 0.001) for vitamin C, and 0.64 (95% CI, 0.43-0.95, P for trend = 0.04) for retinol. There were no associations between intake of green and yellow vegetables, fruit, vitamin E, alpha-carotene, beta-carotene, or cryptoxanthin and UC risk (P for trend = 0.29, 0.56, 0.89, 0.20, 0.69, and 0.22, respectively)., Conclusions: Intake of other vegetables, vitamin C, and retinol was inversely associated with UC risk., Competing Interests: Declaration of Competing Interest All authors have no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)