Peroral cholangioscopy was first described in 1970s and has recently gained popularity.Peroral cholangioscopy is appealing to therapeutic endoscopists because a direct intraluminal view of the biliary duct system offe...Peroral cholangioscopy was first described in 1970s and has recently gained popularity.Peroral cholangioscopy is appealing to therapeutic endoscopists because a direct intraluminal view of the biliary duct system offers possibilities for diagnosis and interventions beyond that which other imaging or endoscopic modalities can provide.As the image quality of cholangioscopies improves,so too does their diagnostic capability,and as their durability and maneuverability increases,so too does their potential use for therapeutic applications.This editorial is intended to provide a brief review of recent developments in peroral cholangioscopy and current indications for its use.展开更多
The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, i...The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 （CHI3L1）, a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3Ll-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.展开更多
Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for...Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for the fidelity and robustness of these processes. Activation of receptor tyrosine kinases by their cognate growth factors not only leads to propagation of the signal through various biochemical cascades, but also sets in motion multiple attenuation mechanisms that ulti- mately terminate the active state. Early attenuators pre-exist prior to receptor activation and they act to limit signal propagation. Subsequently, late attenuators, such as Lrig and Sprouty, are transcriptionally induced and further act to dampen the signal. Central to the process of signaling attenuation is the role of the E3 ubiquitin ligase c-Cbl. While Cbl- mediated processes of receptor ubiquitylation and endocytosis are relatively well understood, the links of Cbl to other negative regulators are just now beginning to be appreciated. Here we review some emerging interfaces between Cbl and the transcriptionally induced negative regulators Lrig and Sprouty.展开更多
The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mati...The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mation. IBD including Crohn＇s disease （CD） and ulcerative colitis （UC） is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Thl- mediated inflammatory disorder while UC is regarded as a Th2-1ike disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Thl or Th2 cells, and several cytokines [e.g. interleukin （IL）-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Thl/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.展开更多
Research on learning difficulties in mathematics adopts one of two distinct perspectives. According to the first, learning difficulties are due to the intrinsic characteristics of the student. For supporters of the se...Research on learning difficulties in mathematics adopts one of two distinct perspectives. According to the first, learning difficulties are due to the intrinsic characteristics of the student. For supporters of the second perspective, those difficulties result from the interaction between the student and the school system. The objective of this study is to test the validity of these two perspectives in interpreting learning difficulties in mathematics among at-risk students. To this end, we collaborated with normally achieving （undiagnosed） and at-risk students. Results show that the second perspective is better suited to the interpretation of learning difficulties in mathematics students展开更多
文摘Peroral cholangioscopy was first described in 1970s and has recently gained popularity.Peroral cholangioscopy is appealing to therapeutic endoscopists because a direct intraluminal view of the biliary duct system offers possibilities for diagnosis and interventions beyond that which other imaging or endoscopic modalities can provide.As the image quality of cholangioscopies improves,so too does their diagnostic capability,and as their durability and maneuverability increases,so too does their potential use for therapeutic applications.This editorial is intended to provide a brief review of recent developments in peroral cholangioscopy and current indications for its use.
基金Supported by NIH (DK64289,DK74454,DK43351 and DK80070)grants from the Eli and Edythe L.Broad Medical FoundationAmerican Gastroenterological Association Foundation for Digestive Health and Nutrition to Mizoguchi E
文摘The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 （CHI3L1）, a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3Ll-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.
文摘Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for the fidelity and robustness of these processes. Activation of receptor tyrosine kinases by their cognate growth factors not only leads to propagation of the signal through various biochemical cascades, but also sets in motion multiple attenuation mechanisms that ulti- mately terminate the active state. Early attenuators pre-exist prior to receptor activation and they act to limit signal propagation. Subsequently, late attenuators, such as Lrig and Sprouty, are transcriptionally induced and further act to dampen the signal. Central to the process of signaling attenuation is the role of the E3 ubiquitin ligase c-Cbl. While Cbl- mediated processes of receptor ubiquitylation and endocytosis are relatively well understood, the links of Cbl to other negative regulators are just now beginning to be appreciated. Here we review some emerging interfaces between Cbl and the transcriptionally induced negative regulators Lrig and Sprouty.
基金Supported by Grants From the National Natural Science Foundation of China,No.30770988 and No.30971358
文摘The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mation. IBD including Crohn＇s disease （CD） and ulcerative colitis （UC） is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Thl- mediated inflammatory disorder while UC is regarded as a Th2-1ike disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Thl or Th2 cells, and several cytokines [e.g. interleukin （IL）-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Thl/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.
文摘Research on learning difficulties in mathematics adopts one of two distinct perspectives. According to the first, learning difficulties are due to the intrinsic characteristics of the student. For supporters of the second perspective, those difficulties result from the interaction between the student and the school system. The objective of this study is to test the validity of these two perspectives in interpreting learning difficulties in mathematics among at-risk students. To this end, we collaborated with normally achieving （undiagnosed） and at-risk students. Results show that the second perspective is better suited to the interpretation of learning difficulties in mathematics students
