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Background and Aim: This study aimed to clarify whether several single‐nucleotide polymorphisms (SNPs)‐related chronic pancreatitis such as carboxypeptidase A1 (CPA1), carboxypeptidase B1 (CPB1), Gamma‐glutamyltransferase 1 (GGT1), G‐protein‐coupled receptor Class C Group 6 Member A (GPRC6A), and serine protease inhibitor, Kazal type 1 (SPINK‐1) genotypes were associated with clinical characteristics of patients with intraductal papillary mucinous neoplasm (IPMN) and worrisome features of IPMN. Methods: We enrolled 100 patients with IPMN and 116 patients as a control. Serum p‐amylase, lipase, trypsin, phospholipase A2 (PLA2), and elastase‐1 levels were measured. An Olympus EUS (GF‐UCT 260) was used to perform endosonography in 100 patients with IPMN. Total EUS score was evaluated using endosonography. DNA was isolated from the duodenal tissue using a commercial system and polymerase chain reaction (PCR) was performed on 7500 Fast PCR System. Results: There were no associations between glucose tolerances, lipid levels and genotypes of CPA1, GGT1, GPRC6A, and SPINK‐1 in patients with IPMN. CPA1 genotype was significantly associated with the pathophysiology of IPMN. Then, GGT1 genotype was also significantly associated with EUS total score and the size of cyst more than 20 mm and more than 30 mm as one of worrisome features of IPMN. Conclusion: Genotypes of carboxypeptidase A1 and gamma‐glutamyltransferase 1 may be useful tools for the diagnosis and the predictor of worrisome features of IPMN. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluated the psychometric properties of the newly developed chronic constipation-therapeutic efficacy and satisfaction test (CC-TEST) among patients with chronic constipation. Methods: Japanese patients with moderate or severe chronic constipation underwent a 4-week remedy. The baseline, 2-week, and 4-week assessments included the CC-TEST, Constipation Scoring System (CSS), Medical Outcome Study Short Form-8 Health Survey (SF-8), and Hospital Anxiety and Depression Scale (HADS). The CC-TEST comprises three domains: (1) symptoms; chronic constipation symptom severity (seven items), defecation status (five items), (2) impact for daily life; dissatisfaction with daily life level (DS; four items), and (3) therapeutic response; therapeutic efficacy measured by patients and medication compliance (four items). Results: Of 201 eligible patients at baseline, 110 completed the 4-week treatment and the survey responses. Cronbach's α values for the stool, defecation, and abdominal symptom subscales, as well as the total symptom score and DS subscale, showed good internal consistency reliability (0.72–0.80). Pearson's r for comparisons between corresponding items (CC-TEST symptoms with CSS, and CC-TEST DS with SF-8 physical and mental component summary scores) was significant. After 4 weeks, scores for symptoms, defecation status, and DS items/subscales notably decreased, with a significant effect size (p < 0.005, Cohen's d; 0.30–1.16). Statistically significant differences emerged between treatment responders and nonresponders using the three responder definitions, in changes in scores for most CC-TEST symptoms, defecation status, and DS items/subscales (p < 0.05). Conclusion: CC-TEST demonstrates commendable reliability, convergent and known-group validity, and responsiveness to treatment effects. As a simple, comprehensive, and versatile patient-reported outcome measure, CC-TEST may be well suited for clinical trials and primary care of Japanese patients with chronic constipation. [ABSTRACT FROM AUTHOR]

Background and Aim: Apolipoprotein A2 (apoA2) isoforms have been reported to undergo the aberrant processing in pancreatic cancer and pancreatic risk populations compared with that in healthy subjects. This study aimed to clarify whether apoA2 isoforms were as useful as N‐benzoyl‐p‐aminobenzoic acid (BT‐PABA) test for exocrine pancreatic dysfunction markers in patients with early chronic pancreatitis (ECP). Methods: Fifty consecutive patients with functional dyspepsia with pancreatic enzyme abnormalities (FD‐P) (n = 18), with ECP (n = 20), and asymptomatic patients with pancreatic enzyme abnormalities (AP‐P) (n = 12) based on the Rome IV classification and the Japan Pancreatic Association were enrolled in this study. The enrolled patients were evaluated using endoscopic ultrasonography and endoscopic ultrasonography elastography. Five pancreatic enzymes were estimated. Pancreatic exocrine function was analyzed using the BT‐PABA test. Lighter and heavier apoA2 isoforms, AT and ATQ levels were measured by enzyme‐linked immunosorbent assay methods. Results: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption and smoking among patients with AP‐P, FD‐P, and ECP. The BT‐PABA test and lighter apoA2 isoform, AT level in the enrolled patients had a significant correlation (P < 0.01). The BT‐PABA test in patients with ECP was significantly lower (P = 0.04) than that in AP‐P. ApoA2‐AT level in patients with ECP was lower than that in AP‐P, albeit, insignificantly. Interestingly, apo A2‐AT level was significantly (P = 0.041) associated with exocrine pancreatic insufficiency by multiple logistic regression analysis. Conclusions: ApoA2‐AT level is a useful tool to evaluate exocrine pancreatic insufficiency in the early stage of chronic pancreatitis. [ABSTRACT FROM AUTHOR]

Background and Aim: Some patients with functional gastrointestinal disorders exhibit pancreatic dysfunctions and pancreatic enzyme abnormalities. Thus, we aimed to clarify whether significant differences in clinical characteristics, prevalence of pancreatic enzyme abnormalities, duodenal inflammation, and protease‐activated receptor 2 (PAR2) expression levels related to hypersensitivity exist between functional dyspepsia (FD) alone and FD‐irritable bowel syndrome (IBS) overlap group. Methods: Ninety‐three patients based on the Rome IV criteria, FD alone (n = 44) and FD overlapped with IBS (n = 49) group were enrolled. The patients scored their own clinical symptoms after consuming high‐fat meals. Serum trypsin, PLA2, lipase, p‐amylase, and elastase‐1 levels were measured. PAR2, eotaxin‐3, and TRPV4 mRNA levels in duodenum were determined using real‐time polymerase chain reaction methods. PRG2‐ and PAR2 in the duodenum were evaluated using immunostaining. Results: FD score and global GSRS in patients with FD‐IBS overlap were significantly higher than FD alone. Although the prevalence of pancreatic enzyme abnormalities in patients with FD alone was significantly (P < 0.01) higher than that in FD‐IBS overlap, the ratio of aggravation of clinical symptoms following high‐fat intake in patients with FD‐IBS overlap was significantly higher (P = 0.007) than that in patients with FD alone. PAR2‐ and PRG2‐double positive cells were localized in the degranulated eosinophils in the duodenum of patients with FD‐IBS overlap. The number of PAR2‐ and PRG2‐double positive cells in FD‐IBS overlap was significantly (P < 0.01) higher than FD alone. Conclusions: Pancreatic enzyme abnormalities and PAR2 expression on degranulated eosinophils infiltrations in the duodenum may be associated with the pathophysiology of patients with FD‐IBS overlap in Asian populations. [ABSTRACT FROM AUTHOR]

Messenger ribonucleic acid (mRNA) vaccination against coronavirus disease 2019 (COVID‐19) is an effective prevention strategy, despite a limited understanding of the molecular mechanisms underlying the host immune system and individual heterogeneity of the variable effects of mRNA vaccination. We assessed the time‐series changes in the comprehensive gene expression profiles of 200 vaccinated healthcare workers by performing bulk transcriptome and bioinformatics analyses, including dimensionality reduction utilizing the uniform manifold approximation and projection (UMAP) technique. For these analyses, blood samples, including peripheral blood mononuclear cells (PBMCs), were collected from 214 vaccine recipients before vaccination (T1) and on Days 22 (T2, after second dose), 90, 180 (T3, before a booster dose), and 360 (T4, after a booster dose) after receiving the first dose of BNT162b2 vaccine (UMIN000043851). UMAP successfully visualized the main cluster of gene expression at each time point in PBMC samples (T1–T4). Through differentially expressed gene (DEG) analysis, we identified genes that showed fluctuating expression levels and gradual increases in expression levels from T1 to T4, as well as genes with increased expression levels at T4 alone. We also succeeded in dividing these cases into five types based on the changes in gene expression levels. High‐throughput and temporal bulk RNA‐based transcriptome analysis is a useful approach for inclusive, diverse, and cost‐effective large‐scale clinical studies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to clarify whether any risk factors including clinical characteristics, endosonographic features, and exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis. Methods: A total of 163 consecutive patients that presented with functional dyspepsia with pancreatic enzyme abnormalities (FD‐P) (n = 46), early chronic pancreatitis (ECP) (n = 47), and asymptomatic patients with pancreatic enzyme abnormalities (AP‐P) (n = 70) based on the Rome III classification and the Japan Pancreatic Association were included in this study. The enrolled patients were evaluated using endosonography (EUS) and EUS elastography. The levels of the five pancreatic enzymes were measured. Pancreatic exocrine function was analyzed using N‐benzoyl‐l‐tyrosyl‐p‐aminobenzoic acid (BT‐PABA). Results: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption, and smoking among patients with AP‐P, FD‐P, and ECP. The ratio of BT‐PABA test less than 35% in patients with ECP was significantly (P = 0.043) higher than in AP‐P patients. Elastic score was a useful tool to differentiate the FD‐P group from the ECP group. The high‐density cholesterol levels in patients with ECP were significantly lower than those in AP‐P. In addition, the combination of total and high‐density cholesterol levels, BT‐PABA test, and elastic score has a higher area under the curve value (0.708) of patients with ECP than in the other groups. Conclusions: The combination of high‐density cholesterol levels, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with ECP. [ABSTRACT FROM AUTHOR]

We have previously shown that the cyclooxygenase (COX)-2/PGE2 pathway plays a key role in VEGF production in gastric fibroblasts. Recent studies have identified three PGE synthase (PGES) isozymes: cytosolic PGES (cPGES) and microsomal PGES (mPGES)-1 and -2, but little is known regarding the expression and roles of these enzymes in gastric fibroblasts. Thus we examined IL-1[beta]-stimulated mPGES-1 and cPGES mRNA and protein expression in gastric fibroblasts by quantitative PCR and Western blot analysis, respectively, and studied both their relationship to COX-1 and -2 and their roles in PGE2 and VEGF production in vitro. IL-1[beta] stimulated increases in both COX-2 and mPGES-1 mRNA and protein expression levels. However, COX-2 mRNA and protein expression were more rapidly induced than mPGES-1 mRNA and protein expression. Furthermore, MK-886, a nonselective mPGES-1 inhibitor, failed to inhibit IL-1[beta]-induced PGE2 release at the 8-h time point, while totally inhibiting PGE2 at the later stage. However, MK-886 did inhibit IL-1[beta]-stimulated PGES activity in vitro by 86.8%. N-(2-cyclohexyloxy-4-nitrophenyl) -methanesulfonamide (NS-398), a selective COX-2 inhibitor, totally inhibited PGE2 production at both the 8-h and 24-h time points, suggesting that COX-2-dependent PGE2 generation does not depend on mPGES-1 activity at the early stage. In contrast, NS-398 did not inhibit VEGF production at 8 h, and only partially at 24 h, whereas MK-886 totally inhibited VEGF production at each time point. These results suggest that IL-1[beta]-induced mPGES-1 protein expression preferentially coupled with COX-2 protein at late stages of PGE2 production and that IL-1[beta]-stimulated VEGF production was totally dependent on membrane-associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) superfamily proteins, which includes mPGES-1, but was partially dependent on the COX-2/PGE2 pathway. interleukin-1[beta]; MK-886; MAPEG superfamily; prostaglandin E synthase activity

VEGF is a highly specific stimulator of endothelial cells and may play an important role in angiogenesis in the process of tissue regeneration. We previously showed that cyclooxygenase-2 (COX-2) expressed in mesenchymal cells of the ulcer bed is involved in the ulcer repair process. To clarify the role of COX-2 in angiogenesis during gastric ulcer healing, we investigated the relation between COX-2 expression and VEGF production in human gastric fibroblasts in vivo and in vitro. Gastric fibroblasts were cultured in RPMI 1640 with and without IL-1[alpha] or IL-1[beta] in the presence or absence of NS-398, a selective COX-2 inhibitor. Supernatant VEGF and PG[E.sub.2] concentrations were measured by enzyme-linked immunosorbent assay. COX-2 expression in fibroblasts was determined by Western blot analysis. VEGF and COX-2 expression in surgical resections of human gastric ulcer tissue was examined immunohistochemically. IL-1 dose dependently enhanced VEGF release in cultured gastric fibroblasts after a 24-h stimulation. IL-1 also stimulated PG[E.sub.2] production in gastric fibroblasts via COX-2 induction. NS-398 significantly suppressed VEGF and PG[E.sub.2] release from IL-1-stimulated gastric fibroblasts; concurrent addition of PG[E.sub.2] restored NS-398-inhibited VEGF release. COX-2 and VEGF immunoreactivity were colocalized in fibroblast-like ceils in the ulcer bed of gastric tissues. These results suggest that COX-2 plays a key role in VEGF production in gastric fibroblasts stimulated by IL-1 in vitro and that anglogenesis induced by the COX-2-VEGF pathway might be involved in gastric ulcer healing. prostaglandin [E.sub.2]; gastric ulcer; angiogenesis; repair process