AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were ...AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were obtained,including 54 cases of intestinal-type GC,41 high-grade intraepithelial neoplasia,57low-grade intraepithelial neoplasia,31 intestinal metaplasia,and 36 normal gastric mucosa.Specimens were fixed in 10%paraformaldehyde,conventionally dehydrated,embedded in paraffin,and sliced in 4-μm-thick serial sections.Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen(PCNA)expression.Correlation analysis was conducted between Msi-1 and PCNA expression.The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically.RESULTS:There were significant differences in Msi-1and PCNA expression in different pathological tissues(χ2=15.37,P<0.01;χ2=115.36,P<0.01).Msi-1and PCNA-positive cells were restricted to the isthmus of normal gastric glands.Expression levels of Msi-1and PCNA in intestinal metaplasia were significantly higher than in normal mucosa(U=392.0,P<0.05;U=40.50,P<0.01),whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia.Msi-1 and PCNA expression in intestinaltype GC was higher than in high-grade intraepithelial neoplasia(U=798.0,P<0.05;U=688.0,P<0.01).There was a significantly positive correlation between Msi-1 and PCNA expression(rs=0.20,P<0.01).Msi-1expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage(χ2=12.62,P<0.01;χ2=11.24,P<0.05),but not with depth of invasion and the presence of distant metastasis.CONCLUSION:Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.展开更多
Inflammatory bowel disease(IBD) is a chronic recurrent condition whose etiology is unknown,and it includes ulcerative colitis,Crohn's disease,and microscopic colitis. These three diseases differ in clinical manife...Inflammatory bowel disease(IBD) is a chronic recurrent condition whose etiology is unknown,and it includes ulcerative colitis,Crohn's disease,and microscopic colitis. These three diseases differ in clinical manifestations,courses,and prognoses. IBD reduces the patients' quality of life and is an economic burden to both the patients and society. Interactions between the gastrointestinal(GI) neuroendocrine peptides/amines(NEPA) and the immune system are believed to play an important role in the pathophysiology of IBD. Moreover,the interaction between GI NEPA and intestinal microbiota appears to play also a pivotal role in the pathophysiology of IBD. This review summarizes the available data on GI NEPA in IBD,and speculates on their possible role in the pathophysiology and the potential use of this information when developing treatments. GI NEPA serotonin,the neuropeptide Y family,and substance P are proinflammatory,while the chromogranin/secretogranin family,vasoactive intestinal peptide,somatostatin,and ghrelin are antiinflammatory. Several innate and adaptive immune cells express these NEPA and/or have receptors to them. The GI NEPA are affected in patients with IBD and in animal models of human IBD. The GI NEPA are potentially useful for the diagnosis and follow-up of the activity of IBD,and are candidate targets for treatments of this disease.展开更多
AIM: To determine whether the decreased density of duodenal endocrine cells in irritable bowel syndrome(IBS) is associated with abnormalities in stem cell differentiation.METHODS: The study sample comprised 203 patien...AIM: To determine whether the decreased density of duodenal endocrine cells in irritable bowel syndrome(IBS) is associated with abnormalities in stem cell differentiation.METHODS: The study sample comprised 203 patients with IBS(180 females and 23 males with a mean age of 36 years) and a control group of 86 healthy subjects without gastrointestinal complaints(77 females and 9 males with a mean age of 38 years). The patients included 80 with mostly diarrhoea(IBS-D), 47 with both diarrhoea and constipation(IBS-M), and 76 with mostly constipation(IBS-C). Both the patients and controls underwent gastroscopy and four biopsy samples were taken from the descending part of the duodenum, proximal to the papilla of Vater. The biopsy samples were sectioned and immunostained for Musashi 1(Msi-1), neurogenin 3(NEUROG3), secretin, cholecystokinin(CCK), gastric inhibitory peptide(GIP), somatostatin and serotonin. Immunostainingwas performed with an ultra View Universal DAB Detection Kit(v1.02.0018, Venata Medical Systems, Basal, Switzerl and) using the Bench Mark Ult ra immunohistochemistry/in situ hybridization staining module(Venata Medical Systems). Endocrine cell densities were quantified by computerized image analysis using the Olympus cell Sens imaging program.RESULTS: The densities of Msi-1 and NEUROG3 cells were significantly lower in IBS patients, regardless of the subtype, than in the controls(77 ± 17 vs 8 ± 2; P = 0.0001, and 351 ± 33 vs 103 ± 22; P = 0.00002, respectively). Furthermore, the densities of secretin, and CCK cells were significantly lower in patients with diarrhoea as the predominant IBS symptom(IBS-D) than in the controls(161 ± 11 vs 88 ± 8; P = 0.00007, and 325 ± 41 vs 118 ± 10; P = 0.00006, respectively), but not in patients with constipation as the predominant IBS symptom(IBS-C) or those with both diarrhoea and constipation(IBS-M). The GIP cell density was significantly reduced in both IBS-D(152 ± 12 vs 82 ± 7; P = 0.00003), and IBS-C(152 ± 12 vs 107 ± 8; P = 0.01), but not in IBS-M. The展开更多
Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactiv...Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins （RBPs）, which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs our recent knowledge of the Musashi proteins in spermatogenesis. within the scope of male germ cell development, focusing on The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.展开更多
基金Supported by Jinan Science and Technology Bureau for Independent Innovation Projects of Universities and Research Institutes in Jinan city,China,No.201102060
文摘AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were obtained,including 54 cases of intestinal-type GC,41 high-grade intraepithelial neoplasia,57low-grade intraepithelial neoplasia,31 intestinal metaplasia,and 36 normal gastric mucosa.Specimens were fixed in 10%paraformaldehyde,conventionally dehydrated,embedded in paraffin,and sliced in 4-μm-thick serial sections.Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen(PCNA)expression.Correlation analysis was conducted between Msi-1 and PCNA expression.The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically.RESULTS:There were significant differences in Msi-1and PCNA expression in different pathological tissues(χ2=15.37,P<0.01;χ2=115.36,P<0.01).Msi-1and PCNA-positive cells were restricted to the isthmus of normal gastric glands.Expression levels of Msi-1and PCNA in intestinal metaplasia were significantly higher than in normal mucosa(U=392.0,P<0.05;U=40.50,P<0.01),whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia.Msi-1 and PCNA expression in intestinaltype GC was higher than in high-grade intraepithelial neoplasia(U=798.0,P<0.05;U=688.0,P<0.01).There was a significantly positive correlation between Msi-1 and PCNA expression(rs=0.20,P<0.01).Msi-1expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage(χ2=12.62,P<0.01;χ2=11.24,P<0.05),but not with depth of invasion and the presence of distant metastasis.CONCLUSION:Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.
文摘Inflammatory bowel disease(IBD) is a chronic recurrent condition whose etiology is unknown,and it includes ulcerative colitis,Crohn's disease,and microscopic colitis. These three diseases differ in clinical manifestations,courses,and prognoses. IBD reduces the patients' quality of life and is an economic burden to both the patients and society. Interactions between the gastrointestinal(GI) neuroendocrine peptides/amines(NEPA) and the immune system are believed to play an important role in the pathophysiology of IBD. Moreover,the interaction between GI NEPA and intestinal microbiota appears to play also a pivotal role in the pathophysiology of IBD. This review summarizes the available data on GI NEPA in IBD,and speculates on their possible role in the pathophysiology and the potential use of this information when developing treatments. GI NEPA serotonin,the neuropeptide Y family,and substance P are proinflammatory,while the chromogranin/secretogranin family,vasoactive intestinal peptide,somatostatin,and ghrelin are antiinflammatory. Several innate and adaptive immune cells express these NEPA and/or have receptors to them. The GI NEPA are affected in patients with IBD and in animal models of human IBD. The GI NEPA are potentially useful for the diagnosis and follow-up of the activity of IBD,and are candidate targets for treatments of this disease.
文摘AIM: To determine whether the decreased density of duodenal endocrine cells in irritable bowel syndrome(IBS) is associated with abnormalities in stem cell differentiation.METHODS: The study sample comprised 203 patients with IBS(180 females and 23 males with a mean age of 36 years) and a control group of 86 healthy subjects without gastrointestinal complaints(77 females and 9 males with a mean age of 38 years). The patients included 80 with mostly diarrhoea(IBS-D), 47 with both diarrhoea and constipation(IBS-M), and 76 with mostly constipation(IBS-C). Both the patients and controls underwent gastroscopy and four biopsy samples were taken from the descending part of the duodenum, proximal to the papilla of Vater. The biopsy samples were sectioned and immunostained for Musashi 1(Msi-1), neurogenin 3(NEUROG3), secretin, cholecystokinin(CCK), gastric inhibitory peptide(GIP), somatostatin and serotonin. Immunostainingwas performed with an ultra View Universal DAB Detection Kit(v1.02.0018, Venata Medical Systems, Basal, Switzerl and) using the Bench Mark Ult ra immunohistochemistry/in situ hybridization staining module(Venata Medical Systems). Endocrine cell densities were quantified by computerized image analysis using the Olympus cell Sens imaging program.RESULTS: The densities of Msi-1 and NEUROG3 cells were significantly lower in IBS patients, regardless of the subtype, than in the controls(77 ± 17 vs 8 ± 2; P = 0.0001, and 351 ± 33 vs 103 ± 22; P = 0.00002, respectively). Furthermore, the densities of secretin, and CCK cells were significantly lower in patients with diarrhoea as the predominant IBS symptom(IBS-D) than in the controls(161 ± 11 vs 88 ± 8; P = 0.00007, and 325 ± 41 vs 118 ± 10; P = 0.00006, respectively), but not in patients with constipation as the predominant IBS symptom(IBS-C) or those with both diarrhoea and constipation(IBS-M). The GIP cell density was significantly reduced in both IBS-D(152 ± 12 vs 82 ± 7; P = 0.00003), and IBS-C(152 ± 12 vs 107 ± 8; P = 0.01), but not in IBS-M. The
文摘Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins （RBPs）, which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs our recent knowledge of the Musashi proteins in spermatogenesis. within the scope of male germ cell development, focusing on The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.
