Decreased Abundance of Genus Slackia in Individuals With Obesity and Colorectal Adenoma.

Background and Aims: The increasing prevalence of obesity has significantly contributed to the global burden of colorectal cancer and the precancerous colorectal adenoma (CRA). Gut microbiota vary at each stage of colorectal carcinogenesis and participate in energy homeostasis. Elucidating gut microbiotal characteristics in obesity-related CRA may help prevent and treat colorectal tumors; however, this remains unclarified. Therefore, this study investigated the gut microbiota profile of patients with obesity-related CRA. Methods: This hospital setting-based cross-sectional study included 113 participants (66 [without CRA control group] and 37 [with CRA group]; each group was divided into obese and nonobese groups) who underwent screening colonoscopy between June 2019 and January 2020. Gut microbiota were analyzed using 16S rRNA and polymerase chain reaction techniques and the data compared between the aforementioned groups. Results: No between-group difference was observed in the diversity index; however, α diversity was the lowest in the obese CRA group. The CRA group had significantly higher and lower numbers of 26 and 17 genera, respectively. Genus Slackia was significantly lower in the obese CRA group than in the nonobese CRA group. Multivariate analysis of the quartiles according to genus Slackia relative abundance rates revealed that the first quartile was an independent risk factor for CRA (odds ratio, 3.57; 95% confidence interval 1.19-10.7). The proportion of equol reductase-positive participants was lowest in the obese CRA group (P = .04). Multivariate odds ratio for CRA was 5.46 (95% confidence interval 1.35-22.0) for genus Slackia and equol reductase-negative participants. Conclusion: Decreased abundance of genus Slackia and absence of equol reductase potentially influence obesity-related CRA development.

Prediction of low-addition segmented refractive intraocular lens position and deviation using anterior-segment optical coherence tomography.

This study aimed to develop and analyze the accuracy of predictive formulae for postoperative anterior chamber depth, tilt, and decentration of low-added-segment refractive intraocular lenses. This single-center, retrospective, observational study included the right eyes of 96 patients (mean age: 72.43 ± 6.58 years), who underwent a cataract surgery with implantation of a low-added segmented refractive intraocular lens at the Medical University Hospital between July 2019 and January 2021, and were followed up for more than 1 month postoperatively. The participants were divided into an estimation group to create a prediction formula and a validation group to verify the accuracy of the formula. Anterior segment optical coherence tomography (CASIA 2, Tomey Corporation, Japan) and swept-source optical coherence tomography biometry (IOL Master 700, Carl Zeiss Meditec AG) were used to measure the anterior ocular components. A predictive formula was devised for postoperative anterior chamber depth, intraocular lens tilt, and intraocular lens decentration (p <0.01) in the estimation group. A significant positive correlation was observed between the estimated values calculated using the prediction formula and the measured values for postoperative anterior chamber depth (r = 0.792), amount of intraocular lens tilt (r = 0.610), direction of intraocular lens tilt (r = 0.668), and amount of intraocular lens decentration (r = 0.431) (p < 0.01) in the validation group. In conclusion, our findings reveal that predicting the position of the low-added segmented refractive intraocular lens enables the prognosis of postoperative refractive values with a greater accuracy in determining the intraocular lens adaptation.

Discovery of a Pentapeptide Antagonist to Human Neuromedin U Receptor 1.

Neuromedin U (NMU) activates two types of receptors (NMUR1 and NMUR2), and the former is mainly expressed in the peripheral tissues, including the intestinal tract and lung tissues. Since NMUR1 contributes to the promotion of type 2 inflammation in these tissues, it is a potential target to suppress inflammatory responses. However, promising antagonist candidates for human NMUR1 have not yet been developed. Here we successfully identified pentapeptide antagonist 9a through a structure-activity relationship study based on hexapeptide lead 1. Its antagonistic activity against human NMUR1 was 10 times greater than that against NMUR2. This is a breakthrough in the development of NMUR1-selective antagonists. Although 9a was relatively stable in the plasma, the C-terminal amide was rapidly degraded to the carboxylic acid by the serum endopeptidase thrombin, which acted as an amidase. This basic information would aid in sample handling in future biological evaluations.

Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons.

Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages peripheral nerves in Minamata patients, causing more damage to sensory nerves than motor nerves. Peripheral nerves are composed of three cell types: dorsal root ganglion (DRG) cells, anterior horn cells (AHCs), and Schwann cells. In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 lower in DRG cells compared with those in AHC and Schwann cells. Additionally, decreased cell viability caused by methylmercury was significantly reduced by either the LAT1 inhibitor, JPH203, or siRNA-mediated knockdown of LAT1. On the other hand, an MRP2 inhibitor, MK571, significantly intensified the decrease in the cell viability caused by methylmercury. Our results provide a cellular basis for sensory neve predominant injury in the peripheral nerves of Minamata disease patients.

Young Patient with X-linked Agammaglobulinemia Presents with Advanced Gastric Cancer and Extensive Atrophic Gastritis.

X-linked agammaglobulinemia (XLA) is associated with an increased risk of gastrointestinal cancers including gastric cancer (GC). We herein report the case of a 30-year-old male patient with XLA who developed GC and extensive atrophic gastritis. He tested positive in the urea breath test, thus indicating the presence of Helicobacter pylori. Distal gastrectomy and chemotherapy were performed without any complications; however, the died two years after this diagnosis. Immunoglobulin deficiency makes these patients susceptible to progressive atrophic gastritis and the associated risk of GC. Therefore, patients with XLA are advised to undergo an evaluation for Helicobacter pylori infection as well as monitoring for GC.

Long-term course of untreated asymptomatic esophageal eosinophilia and minimally symptomatic eosinophilic esophagitis.

Background and study aims The long-term course of untreated asymptomatic esophageal eosinophilia (aEE) and minimally symptomatic eosinophilic esophagitis (mEoE) are not well understood. This study aimed to clarify this course. Patients and methods A total of 36 patients with EE who were endoscopically followed up for more than 5 years, and who underwent more than one endoscopy evaluation after the first diagnosis, were investigated. These patients were divided into two groups according to the presence or absence of the continuous treatment: no treatment group (NT group, n=22) and proton pump inhibitor/potassium competitive acid blocker group (Tx group, n=14). Symptoms and endoscopic and histological findings were retrospectively reviewed according to endoscopic phenotypes. Endoscopic assessment was performed using the EoE endoscopic reference score (EREFS). Results The median follow-up period was 84.5 months in the Tx group and 92 months in the NT group. During the follow-up period, about half of the patients in the Tx-diffuse group persisted EREFS >3, while the remaining half had EREFS ≤2. The total EREFS in the NT-diffuse group remained almost unchanged (median: 2-4) without apparent exacerbation. In contrast, EREFS in the NT-localized group exhibited an unchanged or gradually decreasing trend, with statistical significance from the first diagnosis to 72 to 83 months after. Conclusions Untreated aEE and mEoE are not likely to worsen even without treatment at least for a median follow-up of 7 years. Instead, the localized type may spontaneously improve, implying a different pathogenesis in the presence of the diffuse type. Further studies should clarify the long-term prognosis.

Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

Multiple gastric neuroendocrine tumors in a patient with parietal cell dysfunction and adenosine triphosphatase H+/K+ transporting subunit alpha gene variant.

A 47-year-old woman presented with multiple gastric tumors, each up to 10 mm in diameter, in the gastric body and fundus without mucosal atrophy. White spots and numerous transparent, light-brownish, small, and rounded spots were observed in the background gastric mucosa. Biopsy specimens obtained from the tumors revealed gastric neuroendocrine tumors. The patient exhibited hypergastrinemia and achlorhydria and tested negative for serum parietal cell antibody, intrinsic factor antibody, and Helicobacter pylori infection. Moreover, no additional lesions were detected on imaging. These findings were inconsistent with Rindi's classification. The tumor was resected via endoscopic submucosal resection. Histopathological examination revealed gastric neuroendocrine tumors G2 infiltrating the submucosa with no atrophy of the gastric mucosa, dilated fundic glands, parietal cell protrusions, and hyperplasia of enterochromaffin-like cells. Immunohistochemically, the parietal cells were negative for both α- and ß-subunits of H+/K+ ATPase, suggesting parietal cell dysfunction. A genomic variant was identified in adenosine triphosphatase H+/K+ transporting subunit alpha. After 7 years of treatment, there was no evidence of residual or metastatic lesions. Modification of adenosine triphosphatase H+/K+ transporting subunit alpha may be a significant factor in the pathogenesis of multiple gastric neuroendocrine tumors in the context of gastric parietal cell dysfunction.

Is blue light imaging without magnification satisfactory as screening for esophageal squamous cell carcinoma? Post-hoc analysis of multicenter randomized controlled trial.

OBJECTIVES: Narrow light observation is currently recommended as an alternative to Lugol chromoendoscopy (LCE) to detect esophageal squamous cell carcinoma (ESCC). Studies revealed little difference in sensitivity between the two modalities in expert settings; however, these included small numbers of cases. We aimed to determine whether blue light imaging (BLI) without magnification is satisfactory for preventing misses of ESCC. METHODS: This was a post-hoc analysis of a multicenter randomized controlled trial targeting patients at high risk of ESCC in expert settings. In this study, BLI without magnification followed by LCE was performed. The evaluation parameters included: (i) the diagnostic abilities of ESCC; (ii) the endoscopic characteristics of lesions with diagnostic differences between the two modalities; and (iii) the color difference between cancerous and noncancerous areas in BLI and LCE. RESULTS: This study identified ESCC in 49 of 699 cases. Of these cases, nine (18.4%) were missed by BLI but detected by LCE. In per-patient analysis, the sensitivity of BLI was lower than that of LCE following BLI (83.7% vs. 100.0%; P = 0.013), whereas the specificity and accuracy of BLI were higher (88.2% vs. 81.2%; P < 0.001 and 87.8% vs. 82.5%; P < 0.001, respectively). No significant endoscopic characteristics were identified, but the color difference was lower in BLI than in LCE (21.4 vs. 25.1; P = 0.003). CONCLUSION: LCE following BLI outperformed BLI in terms of sensitivity in patients with high-risk ESCC. Therefore, LCE, in addition to BLI, would still be required in screening esophagogastroduodenoscopy even by expert endoscopists.

Halogenated Cyclic Monoterpenoids with Anti-Biofouling Activity from the Okinawan Red Marine Algae Portieria Hornemannii.

The red algal genus Portieria is a prolific producer of halogenated monoterpenoids. In this study, we isolated and characterised monoterpenoids from the Okinawan red algae Portieria hornemannii. A new polyhalogenated cyclic monoterpenoid, 2(R)-chloro-1,6(S)-dibromo-3(8)(Z)-ochtoden-4(R)-ol (1), along with three known monoterpenoids, (2R,3(8)E,4S,6R)-6-bromo-2-chloro-1,4-oxido-3(8)-ochtodene (2), 1-bromo-2-chloroochtoda-3(8),5-dien-4-one (3), and 2-chloro-1-hydroxyochtoda-3(8),5-dien-4-one (4) were isolated from the methanol extract of three populations of P. hornemannii. These compounds were characterised using a combination of spectroscopic methods and chemical synthesis, and the absolute stereochemistry of compounds 1 and 2 was determined. In addition, all isolated compounds were screened for their anti-biofouling activity against the mussel Mytilus galloprovincialis, and 1 exhibited strong activity. Therefore, halogenated monoterpenoids have the potential to be used as natural anti-biofouling drugs.