Thyroid hormones def ine basal metabolism throughout the body, particularly in the intestine and viscera. Gastrointestinal manifestations of dysthyroidism are numerous and involve all portions of the tract. Thyroid ho...Thyroid hormones def ine basal metabolism throughout the body, particularly in the intestine and viscera. Gastrointestinal manifestations of dysthyroidism are numerous and involve all portions of the tract. Thyroid hormone action on motility has been widely studied, but more complex pathophysiologic mechanisms have been indicated by some studies although these are not fully understood. Both thyroid hormone excess and def iciency can have similar digestive manifestations, such as diarrhea, although the mechanism is different in each situation. The liver is the most affected organ in both hypo-and hyperthyroidism. Specifi c digestive diseases may be associated with autoimmune thyroid processes, such as Hashimoto's thyroiditis and Grave's disease. Among them, celiac sprue and primary biliary cirrhosis are the most frequent although a clear common mechanism has never been proven. Overall, thyroid-related digestive manifestations were described decades ago but studies are still needed in order to conf irm old concepts or elucidate undiscovered mechanisms. All practitioners must be aware of digestive symptoms due to dysthyroidism in order to avoid misdiagnosis of rare but potentially lethal situations.展开更多
The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the ...The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.展开更多
A novel immune algorithm suitable for dynamic environments (AIDE) was proposed based on a biological immune response principle.The dynamic process of artificial immune response with operators such as immune cloning,mu...A novel immune algorithm suitable for dynamic environments (AIDE) was proposed based on a biological immune response principle.The dynamic process of artificial immune response with operators such as immune cloning,multi-scale variation and gradient-based diversity was modeled.Because the immune cloning operator was derived from a stimulation and suppression effect between antibodies and antigens,a sigmoid model that can clearly describe clonal proliferation was proposed.In addition,with the introduction of multiple populations and multi-scale variation,the algorithm can well maintain the population diversity during the dynamic searching process.Unlike traditional artificial immune algorithms,which require randomly generated cells added to the current population to explore its fitness landscape,AIDE uses a gradient-based diversity operator to speed up the optimization in the dynamic environments.Several reported algorithms were compared with AIDE by using Moving Peaks Benchmarks.Preliminary experiments show that AIDE can maintain high population diversity during the search process,simultaneously can speed up the optimization.Thus,AIDE is useful for the optimization of dynamic environments.展开更多
MOST cases of encephalitis are caused by viruses but a few have an immunological basis, such as paraneoplastic encephalitis, with specific antibodies identified. One recently characterized encephalitis caused by antib...MOST cases of encephalitis are caused by viruses but a few have an immunological basis, such as paraneoplastic encephalitis, with specific antibodies identified. One recently characterized encephalitis caused by antibodies is anti-N- methyl-D-aspartate (NMDA) receptor encephalitis. It is a form of paraneoplastic limbic encephalitis associated with ovarian teratoma and has recently been described.The NMDA receptor mediates excitatory neurotransmission. It is important for synaptic plasticity, and thus for higher function such as learning and memory. This disorder results in prominent psychiatric symptoms followed by a rapid decline of the level of consciousness, central hypoventilation, seizures, involuntary movements and dysautonomia.展开更多
Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged...Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged with Vibrio splendidus by injection at 1.0×108 cfu/sea cucumber for 15 days.Phagocytic capacity (PC), intracellular superoxide anion production (ISAP), ly-sozyme (LSZ) activity and superoxide dismutase (SOD) activity in the coelomic fluid were analyzed on the 0th, 5th, 10th and 15th days after injection.Results showed that after the 45-day feeding period, PC, ISAP, LSZ activity and SOD activity in sea cucumbers fed with dietary β-glucan or glycyrrhizin were significantly higher than in those fed with the basal diet.On the 5th day after infection, all the immune parameters examined in the sea cucumbers injected with V.splendidus decreased in value significantly.On the 15th day, PC, ISAP and LSZ activity returned to levels similar to those on the 0th day.For the sea cucumbers injected with saline, there were no significant differences in all the immune parameters examined and in the cumulative morbidity during the 15-day challenging trial.After injecting with V.splendidus, the cumulative morbidity of sea cucumbers fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin when challenged with V.splendidus challenged sea cucumber fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin.There was no significant difference in cumulative morbidity between the dietary β-glucan and glycyrrhizin treatments over time.展开更多
Objective:Triple-negative breast cancer(estrogen receptor-negative,progesterone receptor-negative and Her2-negative) can be classified into two subtypes:basal and non-basal phenotype.And the basal phenotype is associa...Objective:Triple-negative breast cancer(estrogen receptor-negative,progesterone receptor-negative and Her2-negative) can be classified into two subtypes:basal and non-basal phenotype.And the basal phenotype is associated with poor outcome.The purpose of this study was to figure out the differences of clinicopathological characters and related factors of prognosis between these two subtypes.Methods:Immunohistochemical staining was performed for the CK5/6,CK17 basal markers and EGFR on biopsy samples from 40 triple-negative patients and the clinicopathology features of these samples were investigated.Results:Seventy percent of the patients were diagnosed as the basal phenotype.Compared with the non-basal phenotype,the basal phenotype lesions were significantly larger in diameter with a high nuclear grade.In the node-negative group the basal phenotype clearly showed the same clinicopathological differences.There was statistically significant concordance among all three antibodies.Conclusion:Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors,justifying the use of basal markers to define the basal or the non-basal phenotype.It is important to help the doctor deciding the therapeutic strategy for patient with triple-negative breast cancer.展开更多
Interleukin-2 (IL)-2 signaling plays a pivotal role in the activation of immune responses, and drugs that block this pathway have been shown to be effective for the immunosuppression in patients with organ transplan...Interleukin-2 (IL)-2 signaling plays a pivotal role in the activation of immune responses, and drugs that block this pathway have been shown to be effective for the immunosuppression in patients with organ transplantation to alleviate/eliminate allograft rejection. The first humanized monoclonal antibody (mAb) daclizumab falls into this category and shows high specificity and affinity against a key component of the IL-2 receptor complex, namely IL-2Ra. To reveal the molecular mechanism of the inhibition of the IL-2 signaling pathway by dacllzumab, we determined the crystal structures of the daclizumab Fab in free form and in complex with the IL-2Ra ectodomain at 2.6 and 2.8 A resolution, respectively. The daclizumab Fab adopts a similar conformation in the presence or absence of the IL- 2Ra ectodomain. The antigen-binding site of daclizumab is mainly composed of live complementarity determining regions (CDRs) that form a large positively charged surface depression and two flanking patches that are generally hydrophobic. The conformational epitope consists of several discontinuous segments of the IL-2Ru ectodomain, a large portion of which overlaps with the regions that interact with IL-2, suggesting that the binding of daclizumab to IL-2Ra would prevent the IL-2 binding to IL-2Ra and the subsequent formation of the IL-2fIL-2Ra[~/c complex, and therefore block the IL-2 signaling pathway. These results also have implications for the design and development of improved mAb drugs targeting IL-2Ra.展开更多
In order to quantitate the bovine immunodeficiency virus line (BIVL) was established by transfecting baby hamster kidney (BIV) cells infection in vitro, a BIV indicator cell with reporter plasmids containing the f...In order to quantitate the bovine immunodeficiency virus line (BIVL) was established by transfecting baby hamster kidney (BIV) cells infection in vitro, a BIV indicator cell with reporter plasmids containing the firefly luciferase gene driven by a BIV long terminal repeat promoter. The BIV activates promoter activity of the LTR to express luciferase upon infection. BIV infection could therefore by quantified by detection of luciferase activity. Compared to standard assays used to detect BIV infection, the BIVL-based assay is 10 times more sensitive than the the CPE-based assay, and has similar sensitivity with the viral capsid protein Western blot assay BIV indicator cell line could detect BIV infection specifically. Luciferase activity of BIV infected BIVL cells showed a time dependent manner, and 60 h post infection is the optimal time to detect BIV infection. Luciferase activity of BIVL cells correlates with the BIV capsid protein expression. Moreover, a linear relationship was found between MOI and the activated intensity of luciferase expression. In brief, the BIV indicator cell line is an easy, robust and quantitive method for monitoring BIV infection.展开更多
We validated a radioimmunoassay-based method quantifying fecal glucocorticoid metabolites (FGMs) from captive male and female Richardson's ground squirrels Urocitellus richardsonii. Blood samples were drawn to expl...We validated a radioimmunoassay-based method quantifying fecal glucocorticoid metabolites (FGMs) from captive male and female Richardson's ground squirrels Urocitellus richardsonii. Blood samples were drawn to explore the correlation between plasma cortisol and FGM concentrations. We also injected groups of squirrels with normal saline (CTL; control), adre- nocorticotropic hormone (ACTH; stimulating adrenal activity), or dexamethasone (DEX; suppressing adrenal activity). Potential correlations between stress and behaviour were explored through quantification of fecal pellet production and the intervention necessary to elicit defecation, as well as the behaviour of subjects in the context of handling. Changes in plasma cortisol concen- tration between capture (baseline), and following handling (stress-induced) were also quantified for free-living squirrels. While glucocorticoid concentrations recovered from feces during our captive-animal study were not well correlated with plasma eortisol concentrations, and uncorrelated with defecation or behaviour, FGM concentrations did reflect the activation of the hypothalamic- pituitary-adrenal (HPA) axis. FGM concentrations increased significantly during initial captivity, but declined to baseline level as individuals acclimated to the novel environment. Injection of subjects with ACTH increased FGMs above baseline, confirming activation of the HPA axis. Plasma cortisol concentrations increased significantly with induced stress, indicating that capture and handling activated the glucocorticoid stress response even among previously handled, free-living subjects. Our findings validate a non-invasive tool that will afford new insight into the physiological processes underlying social, reproductive and antipredator behaviour of Richardson's ground squirrels [Current Zoology 60 (5): 591-601, 2014 ].展开更多
Natural killer(NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex(MHC) matching, play pivotal roles in immune defence against tumors. However, tumo...Natural killer(NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex(MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor(CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.展开更多
文摘Thyroid hormones def ine basal metabolism throughout the body, particularly in the intestine and viscera. Gastrointestinal manifestations of dysthyroidism are numerous and involve all portions of the tract. Thyroid hormone action on motility has been widely studied, but more complex pathophysiologic mechanisms have been indicated by some studies although these are not fully understood. Both thyroid hormone excess and def iciency can have similar digestive manifestations, such as diarrhea, although the mechanism is different in each situation. The liver is the most affected organ in both hypo-and hyperthyroidism. Specifi c digestive diseases may be associated with autoimmune thyroid processes, such as Hashimoto's thyroiditis and Grave's disease. Among them, celiac sprue and primary biliary cirrhosis are the most frequent although a clear common mechanism has never been proven. Overall, thyroid-related digestive manifestations were described decades ago but studies are still needed in order to conf irm old concepts or elucidate undiscovered mechanisms. All practitioners must be aware of digestive symptoms due to dysthyroidism in order to avoid misdiagnosis of rare but potentially lethal situations.
文摘The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.
基金Project(60625302) supported by the National Natural Science Foundation for Distinguished Young Scholars of ChinaProject(2009CB320603) supported by the National Basic Research Program of China+5 种基金Projects(10dz1121900,10JC1403400) supported by Shanghai Key Technologies R & D ProgramProject supported by the Fundamental Research Funds for the Central Universities in ChinaProject(200802511011) supported by the New Teacher Program of Specialized Research Fund for the Doctoral Program of Higher Education in ChinaProject(Y1090548) supported by Zhejiang Provincial Natural Science Fund,ChinaProject(2011C21077) supported by Zhejiang Technology Programme,ChinaProject(2011A610173) supported by Ningbo Natural Science Fund,China
文摘A novel immune algorithm suitable for dynamic environments (AIDE) was proposed based on a biological immune response principle.The dynamic process of artificial immune response with operators such as immune cloning,multi-scale variation and gradient-based diversity was modeled.Because the immune cloning operator was derived from a stimulation and suppression effect between antibodies and antigens,a sigmoid model that can clearly describe clonal proliferation was proposed.In addition,with the introduction of multiple populations and multi-scale variation,the algorithm can well maintain the population diversity during the dynamic searching process.Unlike traditional artificial immune algorithms,which require randomly generated cells added to the current population to explore its fitness landscape,AIDE uses a gradient-based diversity operator to speed up the optimization in the dynamic environments.Several reported algorithms were compared with AIDE by using Moving Peaks Benchmarks.Preliminary experiments show that AIDE can maintain high population diversity during the search process,simultaneously can speed up the optimization.Thus,AIDE is useful for the optimization of dynamic environments.
文摘MOST cases of encephalitis are caused by viruses but a few have an immunological basis, such as paraneoplastic encephalitis, with specific antibodies identified. One recently characterized encephalitis caused by antibodies is anti-N- methyl-D-aspartate (NMDA) receptor encephalitis. It is a form of paraneoplastic limbic encephalitis associated with ovarian teratoma and has recently been described.The NMDA receptor mediates excitatory neurotransmission. It is important for synaptic plasticity, and thus for higher function such as learning and memory. This disorder results in prominent psychiatric symptoms followed by a rapid decline of the level of consciousness, central hypoventilation, seizures, involuntary movements and dysautonomia.
基金supported by grant No.2006AA100313 from the National High Technology Research and Development Project of P.R. China (863 Project)
文摘Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged with Vibrio splendidus by injection at 1.0×108 cfu/sea cucumber for 15 days.Phagocytic capacity (PC), intracellular superoxide anion production (ISAP), ly-sozyme (LSZ) activity and superoxide dismutase (SOD) activity in the coelomic fluid were analyzed on the 0th, 5th, 10th and 15th days after injection.Results showed that after the 45-day feeding period, PC, ISAP, LSZ activity and SOD activity in sea cucumbers fed with dietary β-glucan or glycyrrhizin were significantly higher than in those fed with the basal diet.On the 5th day after infection, all the immune parameters examined in the sea cucumbers injected with V.splendidus decreased in value significantly.On the 15th day, PC, ISAP and LSZ activity returned to levels similar to those on the 0th day.For the sea cucumbers injected with saline, there were no significant differences in all the immune parameters examined and in the cumulative morbidity during the 15-day challenging trial.After injecting with V.splendidus, the cumulative morbidity of sea cucumbers fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin when challenged with V.splendidus challenged sea cucumber fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin.There was no significant difference in cumulative morbidity between the dietary β-glucan and glycyrrhizin treatments over time.
基金Supported by a grant from the National Natural Science Foundation of Hubei Province (No.2009CDB063)
文摘Objective:Triple-negative breast cancer(estrogen receptor-negative,progesterone receptor-negative and Her2-negative) can be classified into two subtypes:basal and non-basal phenotype.And the basal phenotype is associated with poor outcome.The purpose of this study was to figure out the differences of clinicopathological characters and related factors of prognosis between these two subtypes.Methods:Immunohistochemical staining was performed for the CK5/6,CK17 basal markers and EGFR on biopsy samples from 40 triple-negative patients and the clinicopathology features of these samples were investigated.Results:Seventy percent of the patients were diagnosed as the basal phenotype.Compared with the non-basal phenotype,the basal phenotype lesions were significantly larger in diameter with a high nuclear grade.In the node-negative group the basal phenotype clearly showed the same clinicopathological differences.There was statistically significant concordance among all three antibodies.Conclusion:Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors,justifying the use of basal markers to define the basal or the non-basal phenotype.It is important to help the doctor deciding the therapeutic strategy for patient with triple-negative breast cancer.
基金Acknowledgments We are grateful to the staff members at Shanghai Synchrotron Radiation Facility for support in diffraction data collection and other members of our group for helpful discussion. This work was supported by grants from the Ministry of Science and Technology of China (2010CB833601, 2006AA02A313, and 2009ZX09503- 009), the National Natural Science Foundation of China (30730028 and 90713046), and the Chinese Academy of Sciences (KSCX2-YW-R- 107 and SIBS2008002).
文摘Interleukin-2 (IL)-2 signaling plays a pivotal role in the activation of immune responses, and drugs that block this pathway have been shown to be effective for the immunosuppression in patients with organ transplantation to alleviate/eliminate allograft rejection. The first humanized monoclonal antibody (mAb) daclizumab falls into this category and shows high specificity and affinity against a key component of the IL-2 receptor complex, namely IL-2Ra. To reveal the molecular mechanism of the inhibition of the IL-2 signaling pathway by dacllzumab, we determined the crystal structures of the daclizumab Fab in free form and in complex with the IL-2Ra ectodomain at 2.6 and 2.8 A resolution, respectively. The daclizumab Fab adopts a similar conformation in the presence or absence of the IL- 2Ra ectodomain. The antigen-binding site of daclizumab is mainly composed of live complementarity determining regions (CDRs) that form a large positively charged surface depression and two flanking patches that are generally hydrophobic. The conformational epitope consists of several discontinuous segments of the IL-2Ru ectodomain, a large portion of which overlaps with the regions that interact with IL-2, suggesting that the binding of daclizumab to IL-2Ra would prevent the IL-2 binding to IL-2Ra and the subsequent formation of the IL-2fIL-2Ra[~/c complex, and therefore block the IL-2 signaling pathway. These results also have implications for the design and development of improved mAb drugs targeting IL-2Ra.
基金The General Foundation of Tianjin Science Committee for Applied Basic Research (08JCZDJC21000)Chinese Ministry of Education (30770081)
文摘In order to quantitate the bovine immunodeficiency virus line (BIVL) was established by transfecting baby hamster kidney (BIV) cells infection in vitro, a BIV indicator cell with reporter plasmids containing the firefly luciferase gene driven by a BIV long terminal repeat promoter. The BIV activates promoter activity of the LTR to express luciferase upon infection. BIV infection could therefore by quantified by detection of luciferase activity. Compared to standard assays used to detect BIV infection, the BIVL-based assay is 10 times more sensitive than the the CPE-based assay, and has similar sensitivity with the viral capsid protein Western blot assay BIV indicator cell line could detect BIV infection specifically. Luciferase activity of BIV infected BIVL cells showed a time dependent manner, and 60 h post infection is the optimal time to detect BIV infection. Luciferase activity of BIVL cells correlates with the BIV capsid protein expression. Moreover, a linear relationship was found between MOI and the activated intensity of luciferase expression. In brief, the BIV indicator cell line is an easy, robust and quantitive method for monitoring BIV infection.
文摘We validated a radioimmunoassay-based method quantifying fecal glucocorticoid metabolites (FGMs) from captive male and female Richardson's ground squirrels Urocitellus richardsonii. Blood samples were drawn to explore the correlation between plasma cortisol and FGM concentrations. We also injected groups of squirrels with normal saline (CTL; control), adre- nocorticotropic hormone (ACTH; stimulating adrenal activity), or dexamethasone (DEX; suppressing adrenal activity). Potential correlations between stress and behaviour were explored through quantification of fecal pellet production and the intervention necessary to elicit defecation, as well as the behaviour of subjects in the context of handling. Changes in plasma cortisol concen- tration between capture (baseline), and following handling (stress-induced) were also quantified for free-living squirrels. While glucocorticoid concentrations recovered from feces during our captive-animal study were not well correlated with plasma eortisol concentrations, and uncorrelated with defecation or behaviour, FGM concentrations did reflect the activation of the hypothalamic- pituitary-adrenal (HPA) axis. FGM concentrations increased significantly during initial captivity, but declined to baseline level as individuals acclimated to the novel environment. Injection of subjects with ACTH increased FGMs above baseline, confirming activation of the HPA axis. Plasma cortisol concentrations increased significantly with induced stress, indicating that capture and handling activated the glucocorticoid stress response even among previously handled, free-living subjects. Our findings validate a non-invasive tool that will afford new insight into the physiological processes underlying social, reproductive and antipredator behaviour of Richardson's ground squirrels [Current Zoology 60 (5): 591-601, 2014 ].
基金supported by grants from the Ministry of Science and Technology of China(2014CB910104)the National Natural Science Foundation of China(81171899+1 种基金81372230)the Claudia Adams Barr Program for Innovative Cancer Research
文摘Natural killer(NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex(MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor(CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.