As a member of mucins family,MUC2 is an important component of mucus,which is characterized by tandem and irregular repeat sequences rich in threonine and serine.It is strongly expressed by goblet cells that are invol...As a member of mucins family,MUC2 is an important component of mucus,which is characterized by tandem and irregular repeat sequences rich in threonine and serine.It is strongly expressed by goblet cells that are involved in innate immunity.Japanese flounder is an economically important marine flatfish.In this study,two homologous genes of MUC2 were identified,named MUC2-1 and MUC2-2.Depending on phylogenetic and structural analysis,MUC2-1 and MUC2-2 were clustered in two clades,respectively.Paralichthys olivaceus MUC2-1 showed a closer relationship with MUC2 in the higher vertebrates.Various healthy tissues were analyzed to determine the expression patterns,and both MUC2 genes showed high expression levels in the gills and intestines.Following Edwardsiella tarda challenge,P.olivaceus MUC2-1 and MUC2-2 both showed significant up-regulated expression in intestine and kidney.Moreover,MUC2-1 was significantly up-regulated in gill cell lines following PGN and polyI:C stimulation,and MUC2-2 was significantly up-regulated in gill cell lines following LPS stimulation.In addition,ISH results revealed that MUC2-1 and MUC2-2 showed the same tissue localization in intestine tissues,but displayed different localization in gill.The siRNA-mediated knockdown of MUC2-1 and MUC2-2 genes in the gill cell lines of Japanese flounder affected the expressions of galnt family genes and smad pathway members that are related to mucosal immunity.The results provided a valuable insight into understanding the functions of MUC2 on mucosal immune system in response to the invasion of bacterial pathogen.展开更多
Objective： To evaluate the association between mucin 2 （MUC2） expression and clinicopathological characters of colorectal cancer. Methods： A literature search was performed on December 31, 2010 according to define...Objective： To evaluate the association between mucin 2 （MUC2） expression and clinicopathological characters of colorectal cancer. Methods： A literature search was performed on December 31, 2010 according to defined selection criteria. We evaluated the correlation between MUC2 （detected by immunohistochemistry） and clinicopathological characters of colorectal cancer. According to the tumor histological type, differentiation, location and TNM staging of colorectal carcinoma, we divided the clinicopathological characteristics into different subgroups. Fixed and random effects models were applied for estimation of the summarized risk ratios （RRs） and 95% confidence intervals （CIs） in different subgroups. Finally, forest plots and funnel plots were created to allow for visual comparison of the results or the effect of publication bias. Results： According with the inclusive criteria, fourteen studies （n=1,558） were eligible for the meta-analysis. We observed a trend towards a correlation of MUC2 higher positivity in mucinous than non-mucinous carcinoma （RR, 2.10; 95% CI, 1.30-3.40; P=0.002） and less positivity in distal than proximal colon （RR, 0.74; 95% CI, 0.64-0.85; P=0.000）. There was no statistically significance for the association between MUC2 expression and differentiation or TNM staging of colorectal cancer, but MUC2 overexpression tended to be associated with the presence of T stage tumor （RR, 1.17; P=0.052）. Conclusion： MUC2 overexpression was associated with the mucinous and proximal colorectal cancer.展开更多
BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factor...BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.展开更多
A 69-year-old woman from a kindred with familial atypical multiple mole melanoma and carrier of a germline mutation in CDKN2A, presented with abdominal pain caused by a solid-cystic pancreatic mass. The patient had an...A 69-year-old woman from a kindred with familial atypical multiple mole melanoma and carrier of a germline mutation in CDKN2A, presented with abdominal pain caused by a solid-cystic pancreatic mass. The patient had an abdominal computed tomography three years before in which there was no evidence of pancreatic lesion. The endoscopic ultrasound guided fine needle aspiration showed adenocarcinoma with squamous component. After surgical resection the final diagnosis was adenosquamous pancreatic carcinoma(ASPC) arising in an intraductal papillar mucinous neoplasm(IPMN). Adenosquamous carcinomas are uncommon in the pancreas and have rarely been described in association with IPMNs. It has worse prognosis than the ordinary pancreatic ductal adenocarcinoma and some distinct features. We review the clinical, imaging, pathologic and molecular aspects of ASPC. Differential diagnosis with contamination, squamous metaplasia and pancreatic metastases from a distant squamous carcinoma is discussed. Besides, the case is an accelerated model of the adenoma(IPMN)-carcinoma sequence probably due to the CDKN2A ger-mline mutation. Somatic CDKN2A mutations are commonevents in the early steps of sporadic pancreatic cancer, but germline mutation carriers have a significantly higher risk of pancreatic carcinoma.展开更多
Ghrelin, a peptide hormone produced mainly in the stomach, has emerged recently as an important regulator of nitric oxide synthase (NOS) and cyclooxygenase (COX) enzyme systems, the products of which play direct cytop...Ghrelin, a peptide hormone produced mainly in the stomach, has emerged recently as an important regulator of nitric oxide synthase (NOS) and cyclooxygenase (COX) enzyme systems, the products of which play direct cytoprotective function in the maintenance of gastric mucosal integrity. In this study, using gastric mucosal cells, we report on the role of ghrelin in countering the cytotoxic effect of ethanol on mucin synthesis. We show that the countering effect of ghrelin on mucin synthesis was associated with the increase in NO and PGE2 production, and characterized by a marked up-regulation in cytosolic phospholipase A2 (cPLA2) activity. The ghrelin-induced up-regulation in mucin synthesis, like that of cPLA2 activity, was subject to suppression by Src inhibitor, PP2 and ERK inhibitor, PD98059, as well as ascorbate. Moreover, the loss in countering effect of ghrelin on the ethanol cytotoxicity and mucin synthesis was attained with cNOS inhibitor, L-NAME as well as COX-1 inhibitor SC-560. The effect of L-NAME was reflected in the inhibition of ghrelin-induced mucosal cell capacity for NO production, cPLA2 S-nitrosylation and PGE2 generation, whereas COX-1 inhibitor caused only the inhibition in PGE2 generation. Our findings suggest that the activation of gastric mucosal cPLA2 through cNOS-induced S-nitrosylation plays an essential role in the countering effect of ghrelin on the disturbances in gastric mucin synthesis caused by ethanol cytotoxicity.展开更多
基金supported by the Natural Science Foundation of Shandong Province (No.ZR2022QC037)the Shandong Key R&D Program for Academician Team in Shandong (No.2023ZLYS02)+3 种基金the High-Level Talents Research Fund of Qingdao Agricultural University (No.663/1120033)the Young Experts of Taishan Scholars (No.201909130)the Shandong Technical System of Fish Industry (No.SDAIT-12-03)the Science and Technology Support Plan for Youth Innovation of Colleges and Universities in Shandong Province (No.2019KJF003)。
文摘As a member of mucins family,MUC2 is an important component of mucus,which is characterized by tandem and irregular repeat sequences rich in threonine and serine.It is strongly expressed by goblet cells that are involved in innate immunity.Japanese flounder is an economically important marine flatfish.In this study,two homologous genes of MUC2 were identified,named MUC2-1 and MUC2-2.Depending on phylogenetic and structural analysis,MUC2-1 and MUC2-2 were clustered in two clades,respectively.Paralichthys olivaceus MUC2-1 showed a closer relationship with MUC2 in the higher vertebrates.Various healthy tissues were analyzed to determine the expression patterns,and both MUC2 genes showed high expression levels in the gills and intestines.Following Edwardsiella tarda challenge,P.olivaceus MUC2-1 and MUC2-2 both showed significant up-regulated expression in intestine and kidney.Moreover,MUC2-1 was significantly up-regulated in gill cell lines following PGN and polyI:C stimulation,and MUC2-2 was significantly up-regulated in gill cell lines following LPS stimulation.In addition,ISH results revealed that MUC2-1 and MUC2-2 showed the same tissue localization in intestine tissues,but displayed different localization in gill.The siRNA-mediated knockdown of MUC2-1 and MUC2-2 genes in the gill cell lines of Japanese flounder affected the expressions of galnt family genes and smad pathway members that are related to mucosal immunity.The results provided a valuable insight into understanding the functions of MUC2 on mucosal immune system in response to the invasion of bacterial pathogen.
基金supported by Medical Science and Technology Development Foundation of Nanjing, China (No.YKK10096)
文摘Objective： To evaluate the association between mucin 2 （MUC2） expression and clinicopathological characters of colorectal cancer. Methods： A literature search was performed on December 31, 2010 according to defined selection criteria. We evaluated the correlation between MUC2 （detected by immunohistochemistry） and clinicopathological characters of colorectal cancer. According to the tumor histological type, differentiation, location and TNM staging of colorectal carcinoma, we divided the clinicopathological characteristics into different subgroups. Fixed and random effects models were applied for estimation of the summarized risk ratios （RRs） and 95% confidence intervals （CIs） in different subgroups. Finally, forest plots and funnel plots were created to allow for visual comparison of the results or the effect of publication bias. Results： According with the inclusive criteria, fourteen studies （n=1,558） were eligible for the meta-analysis. We observed a trend towards a correlation of MUC2 higher positivity in mucinous than non-mucinous carcinoma （RR, 2.10; 95% CI, 1.30-3.40; P=0.002） and less positivity in distal than proximal colon （RR, 0.74; 95% CI, 0.64-0.85; P=0.000）. There was no statistically significance for the association between MUC2 expression and differentiation or TNM staging of colorectal cancer, but MUC2 overexpression tended to be associated with the presence of T stage tumor （RR, 1.17; P=0.052）. Conclusion： MUC2 overexpression was associated with the mucinous and proximal colorectal cancer.
基金Supported by National Natural Science Foundation of China,No.81501539the Natural Science Foundation of Guangdong Province,China,No.2016A030312008+2 种基金Science and Technology Planning Project of Shantou,China,No.200617105260368Medical Scientific Research Foundation of Guangdong,China,No.A2020627“Dengfeng Project”for the Construction of High-level Hospital in Guangdong Province-The First Affiliated Hospital of Shantou University College Supporting Funding,No.202003-10.
文摘BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.
文摘A 69-year-old woman from a kindred with familial atypical multiple mole melanoma and carrier of a germline mutation in CDKN2A, presented with abdominal pain caused by a solid-cystic pancreatic mass. The patient had an abdominal computed tomography three years before in which there was no evidence of pancreatic lesion. The endoscopic ultrasound guided fine needle aspiration showed adenocarcinoma with squamous component. After surgical resection the final diagnosis was adenosquamous pancreatic carcinoma(ASPC) arising in an intraductal papillar mucinous neoplasm(IPMN). Adenosquamous carcinomas are uncommon in the pancreas and have rarely been described in association with IPMNs. It has worse prognosis than the ordinary pancreatic ductal adenocarcinoma and some distinct features. We review the clinical, imaging, pathologic and molecular aspects of ASPC. Differential diagnosis with contamination, squamous metaplasia and pancreatic metastases from a distant squamous carcinoma is discussed. Besides, the case is an accelerated model of the adenoma(IPMN)-carcinoma sequence probably due to the CDKN2A ger-mline mutation. Somatic CDKN2A mutations are commonevents in the early steps of sporadic pancreatic cancer, but germline mutation carriers have a significantly higher risk of pancreatic carcinoma.
文摘Ghrelin, a peptide hormone produced mainly in the stomach, has emerged recently as an important regulator of nitric oxide synthase (NOS) and cyclooxygenase (COX) enzyme systems, the products of which play direct cytoprotective function in the maintenance of gastric mucosal integrity. In this study, using gastric mucosal cells, we report on the role of ghrelin in countering the cytotoxic effect of ethanol on mucin synthesis. We show that the countering effect of ghrelin on mucin synthesis was associated with the increase in NO and PGE2 production, and characterized by a marked up-regulation in cytosolic phospholipase A2 (cPLA2) activity. The ghrelin-induced up-regulation in mucin synthesis, like that of cPLA2 activity, was subject to suppression by Src inhibitor, PP2 and ERK inhibitor, PD98059, as well as ascorbate. Moreover, the loss in countering effect of ghrelin on the ethanol cytotoxicity and mucin synthesis was attained with cNOS inhibitor, L-NAME as well as COX-1 inhibitor SC-560. The effect of L-NAME was reflected in the inhibition of ghrelin-induced mucosal cell capacity for NO production, cPLA2 S-nitrosylation and PGE2 generation, whereas COX-1 inhibitor caused only the inhibition in PGE2 generation. Our findings suggest that the activation of gastric mucosal cPLA2 through cNOS-induced S-nitrosylation plays an essential role in the countering effect of ghrelin on the disturbances in gastric mucin synthesis caused by ethanol cytotoxicity.
