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Review : Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside
( Lei Zhang ),( Jun Song ),( Xiaohua Hou ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.2
Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients. (J Neurogastroenterol Motil 2016;22:181-192)
( Yuhua Chen ),( Lei Zhang ),( Yongbo Zhang ),( Tao Bai ),( Jun Song ),( Wei Qian ),( Xiaohua Hou ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2020 Journal of Neurogastroenterology and Motility (JNM Vol.26 No.3
Background/Aims Lipopolysaccharide (LPS) is the key factor inducing mucosal and systemic inflammation in various intestinal and parenteral diseases, which could initially disrupt the epithelial barrier function. EphrinA1/ephA2 is speculated to increase the epithelial permeability for its “repulsive interaction” between adjacent cells. This study aim to investigate the role of ephrinA1/ephA2 in LPS-induced epithelial hyperpermeability. Methods In vivo model challenged with oral LPS in C57BL/6 mice and in vitro model exposed to LPS in Caco2 monolayer were established. The barrier function was assessed including expression of tight junction proteins (occludin and claudin-1), transepithelial electrical resistance, and permeability to macromolecules (fluorescein isothiocyanate-labeled fluorescent dextran 4 kDa [FD4]). Moreover, the expression and phosphorylation of ephrinA1/ephA2 were quantified, and its roles in the process of epithelial barrier disruption were confirmed via stimulating ephA2 with ephrinA1-Fc chimera (ephrinA1-Fc) and inactivating ephA2 with ephA2-Fc chimera (ephA2-Fc), or ephA2 monoclonal antibody (ephA2-mab), as well as inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) with PD98059. Results LPS induced significant barrier dysfunction with dismissed occludin and claudin-1 expression, reduced transepithelial electrical resistance and increased FD4 permeability, accompanied by upregulated ephrinA1/ephA2 pathway and phosphorylation of ephA2 receptor. Furthermore, ephA2-Fc, and ephA2-mab ameliorated LPS-induced epithelial hyperpermeability, which was also inhibited by PD98059. Additionally, ephrinA1-Fc led to apparent epithelial leakage in Caco2 monolayer by promoting the phosphorylation of ERK1/2, which could be obviously blocked by ephA2-mab and PD98059. Conclusion EphrinA1/ephA2 promotes epithelial hyperpermeability with an ERK1/2-dependent pathway, which involves in LPS-induced intestinal barrier dysfunction. (J Neurogastroenterol Motil 2020;26:397-409)
Dongke Wang,Chaofan Duan,Xiaohao Zhang,Junying Xu,Xiaohua Hou,Xuelian Xiang 대한소화기 기능성질환∙운동학회 2022 Journal of Neurogastroenterology and Motility (JNM Vol.28 No.4
Background/Aims Lyon consensus differentiates acid exposure time (AET) as physiological, borderline, and pathological. Mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPWi) are believed to increase diagnostic yield of gastroesophageal reflux disease (GERD) and correlate with symptom outcome of proton pump inhibitor (PPI) treatment. We aim to explore the clinical characteristics and the correlation of pH-impedance parameters with PPI response in Chinese patients with different AET levels. Methods We retrospectively investigated 177 patients with typical reflux symptoms who received esophageal function tests. The demographics, GERD questionnaire scores, the proportion of esophagitis and PPI responders, and manometric and pH-impedance parameters were compared among patients with AET < 4%, 4-6%, and > 6%. In patients with AET ≥ 4%, manometric and pH-impedance parameters were compared between PPI responders and non-responders. Results Among 177 patients, 69 (39.0%) had AET 4-6%, and 53 (29.9%) had AET > 6%. The demographics, esophagogastric junction type, and occurrence of ineffective esophageal motility were similar between patients with AET 4-6% and > 6%, but different from AET < 4%. MNBI and PSPWi were different among different AET levels, but similar between PPI responders and non-responders in patients with AET ≥ 4%. Conclusions It is reasonable to set 4% as a threshold to define pathological AET in Chinese patients. MNBI and PSPWi could identify GERD patients, but may not correlate with PPI response of Chinese GERD patients.
( Jun Song ),( Lei Zhang ),( Tao Bai ),( Wei Qian ),( Rui Li ),( Xiaohua Hou ) 대한소화기기능성질환·운동학회 2015 Journal of Neurogastroenterology and Motility (JNM Vol.21 No.2
Background/Aims Mesenteric afferent nerves (MANs) play a pivotal role in the visceral-nociceptive perception. Inappropriate activation of MANs may be involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. We assessed the effects of mucosal mediators from different bowel segments of guinea pigs with PI-IBS on MAN firing and the role of mast cells. Methods PI-IBS was induced in guinea pigs by Trichinella spiralis infection. Inflammation in terminal ileum, proximal and distal colon was scored with hematoxylin-eosin staining, and mast cell infiltration was assessed with immunofluorescence. We determined the effects of supernatant extracted from the mucosa of different bowel segments of PI-IBS on MANs activity, and assessed the role of mast cells in this process. Results Eight weeks after infection, intestinal inflammation resolved, whereas mast cell numbers increased significantly in terminal ileum and proximal colon (P < 0.05) compared with findings in controls. Mucosal supernatant from different bowel segments of PI-IBS models, but not from controls, significantly enhanced the frequency of MAN firing (terminal ileum 41.01 ± 7.60 Hz vs. 26.55 ± 0.67 Hz, P = 0.001; proximal colon 45.90 ± 11.20 Hz vs. 30.88 ± 6.92 Hz, P = 0.002; distal colon 48.25 ± 9.70 Hz vs. 29.47 ± 6.13 Hz, P < 0.001). In addition, the excitatory effects were inhibited by mast cell stabilizer Nasmil (terminal ileum, 32.71 ± 2.52 Hz, P = 0.030; proximal colon, 30.94 ± 4.44 Hz, P = 0.002; distal colon, 27.15 ± 5.83 Hz, P < 0.001). Conclusions Supernatant from the intestinal mucosa of different bowel segments of PI-IBS models markedly enhanced the MAN firing in a mast cell-dependent manner, indicating that mast cell-mediated MAN activation plays an important role in the pathogenesis of PI-IBS. (J Neurogastroenterol Motil 2015;21:236-246)
Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?
( Tao Bai ),( Ying Li ),( Jing Xia ),( Yudong Jiang ),( Lei Zhang ),( Huan Wang ),( Wei Qian ),( Jun Song ),( Xiaohua Hou ) 대한소화기기능성질환·운동학회 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.3
Background/Aims Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins expression and visceral pain threshold. Methods Post-infectious IBS was induced in mice via a Trichinella spiralis infection. Visceral sensitivity was measured with abdominal withdrawal reflex to colorectal distention. Inflammation in the small intestine and colon was scored with H&E staining. Expression location of Piezo proteins was confirmed by immunohistochemistry. Abundance of Piezo proteins were measured with real-time reverse transcriptase polymerase chain reaction. Results Piezo1 and Piezo2 proteins were expressed in the intestinal epithelial cells. The expression levels of Piezo1 and Piezo2 were abundant in the colon than the small intestine (P < 0.001 for Piezo1, P = 0.003 for Piezo2). Expression of Piezo2 in the colon significantly correlated to the visceral sensitivity (r = -0.718, P = 0.001) rather than the mucosal inflammation. Conclusion Piezo2 is a candidate biomarker for visceral hypersensitivity in IBS. (J Neurogastroenterol Motil 2017;23:453-463)
( Kok-ann Gwee ),( Paul Bergmans ),( Jinyong Kim ),( Bogdana Coudsy ),( Angelia Sim ),( Minhu Chen ),( Lin Lin ),( Xiaohua Hou ),( Huahong Wang ),( Khean-lee Goh ),( John A Pangilinan ),( Nayoung Kim 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.2
Background/Aims There is a need for a simple and practical tool adapted for the diagnosis of chronic constipation (CC) in the Asian population. This study compared the Asian Neurogastroenterology and Motility Association (ANMA) CC tool and Rome III criteria for the diagnosis of CC in Asian subjects. Methods This multicenter, cross-sectional study included subjects presenting at outpatient gastrointestinal clinics across Asia. Subjects with CC alert symptoms completed a combination Diagnosis Questionnaire to obtain a diagnosis based on 4 different diagnostic methods: self-defined, investigator`s judgment, ANMA CC tool, and Rome III criteria. The primary endpoint was the level of agreement/ disagreement between the ANMA CC diagnostic tool and Rome III criteria for the diagnosis of CC. Results The primary analysis comprised of 449 subjects, 414 of whom had a positive diagnosis according to the ANMA CC tool. Rome III positive/ANMA positive and Rome III negative/ANMA negative diagnoses were reported in 76.8% and 7.8% of subjects, respectively, resulting in an overall percentage agreement of 84.6% between the 2 diagnostic methods. The overall percentage disagreement between these 2 diagnostic methods was 15.4%. A higher level of agreement was seen between the ANMA CC tool and self-defined (374 subjects [90.3%]) or investigator`s judgment criteria (388 subjects [93.7%]) compared with the Rome III criteria. Conclusion This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC. (J Neurogastroenterol Motil 2017;23:262-272)
Duan, Jinglai,Liu, Jie,Mo, Dan,Yao, Huijun,Maaz, Khan,Chen, Yonghui,Sun, Youmei,Hou, Mingdong,Qu, Xiaohua,Zhang, Ling,Chen, Yanfeng IOP Pub 2010 Nanotechnology Vol.21 No.36
<P>The hallmark of materials science is the ability to tailor the structures of a given material to provide a desired response. In this work, the structures involving crystallinity and crystallographic orientation of Cu nanowires electrochemically fabricated in ion-track templates have been investigated as a function of fabrication condition. Both single crystalline and polycrystalline nanowires were obtained by adjusting applied voltages and temperatures of electrochemical deposition. The anti-Hall–Petch effect was experimentally evidenced in the polycrystalline nanowires. The dominant crystallographic orientations of wires along [111], [100], or [110] directions were obtained by selecting electrochemical deposition conditions, i.e., H<SUB>2</SUB>SO<SUB>4</SUB> concentration in electrolyte, applied voltage, and electrodeposition temperature. </P>
Chen Jiang,Yan Xu,Stuti Sharma,Lei Zhang,Jun Song,Wei Qian,Tao Bai,Xiaohua Hou 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.2
Background/Aims The role of psychosocial factors on irritable bowel syndrome (IBS) in adolescents is incompletely understood. The aim of this study is to investigate the association between the psychosocial factors and the risk of developing IBS in college freshmen. Methods A cross-sectional survey was conducted in a randomly selected freshmen population in Wuhan China (n = 2449). Questionnaire evaluated demographics and psychosocial risks. The population was divided into 3 groups: non-discomfort, chronic abdominal discomfort and IBS. The association between the development of IBS and psychosocial factors was analyzed by ordinal and multiple logistic regression analysis. Results A total of 2053 (83.8%) completed this survey (mean age, 18.2 ± 0.9 years; female, 35.6%). Among them, 82 (4.0%) fulfilled the Rome III criteria for IBS. Female (odds ratio [OR], 3.31; 95% confidence interval [CI], 2.47–4.45), experience of abuse (OR, 2.44; 95% CI, 1.10–5.56), and suicidal intention (OR, 2.17; 95% CI, 1.15–4.17) were more likely to have IBS. Compared with chronic abdominal discomfort, however, depression (OR, 5.55; 95% CI, 1.36–22.71) was the only dependent risk factor for IBS. Conclusion The prevalence of IBS in college freshmen is 4.0%, and to the freshmen, psychosocial factors such as experience of abuse, depression, and suicidal intention were associated with high risk of developing IBS.