Ulcerative colitis(UC)manifests as an etiologically complicated and relapsing gastrointestinal disease.The enteric nervous system(ENS)plays a pivotal role in rectifying and orchestrating the inflammatory responses in ...Ulcerative colitis(UC)manifests as an etiologically complicated and relapsing gastrointestinal disease.The enteric nervous system(ENS)plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract.Berberine,an isoquinoline alkaloid,is known as its antiinflammatory and therapeutic effects in experimental colitis.However,little research focused on its regulatory function on ENS.Therefore,we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions.Functional defects of enteric glial cells(EGCs),with decreased glial fibrillary acidic protein(GFAP)and increased substance P expression,were observed in DSS-induced murine UC.Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC,closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation.In vitro,berberine showed direct protective effects on monoculture of EGCs,bone marrowderived dendritic cells(BMDCs),T cells,and intestinal epithelial cells(IECs)in the simulated inflammatory conditions.Furthermore,berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems.In summary,our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.展开更多
We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regi...We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRIJIpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus （SLE）. When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/Ipr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies （ANAs） and of the pathogenic cytokines IL-6, IL-10 and I L-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/Ipr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell （PC） numbers. Ex vivo, SM934 suppressed the Toll-like receptor （TLR）-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-KB phosphorylation. In human peripheral blood mononuclear cells （PBMCs）, consistent with the results in MRIJIprmice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/Iprmice by suppressing B cell activation and plasma cell formation.展开更多
Network virtualization is a promising approach for resource management that allows customized Virtual Networks （VNs） to be multiplexed on a shared physical infrastructure. A key function that network virtualization ...Network virtualization is a promising approach for resource management that allows customized Virtual Networks （VNs） to be multiplexed on a shared physical infrastructure. A key function that network virtualization can provide is Virtual Network Embedding （VNE）, which maps virtual networks requested by users to a shared substrate network maintained by an Internet service provider. Existing research has worked on this, but has primarily focused on maximizing the revenue of the Internet service provider. In this paper, we consider energy-aware virtual network embedding, which aims at minimizing the energy consumption for embedding virtual networks in a substrate network. In our optimization model, we consider energy consumption of both links and nodes. We propose an efficient heuristic to assign virtual nodes to appropriate substrate nodes based on priority, where existing activated nodes have higher priority for hosting newly arrived virtual nodes. In addition, our proposed algorithm can take advantage of activated links for embedding virtual links so as to minimize total energy consumption. The simulation results show that, for all the cases considered, our algorithm can improve upon previous work by an average of 12.6% on acceptance rate, while the consumed energy can be reduced by 12.34% on average.展开更多
基金supported by Science and Technology Commission of Shanghai Municipality,China(No.18431907100)technical assistance from the Platform of Molecular Imaging and Research,SIMM,CAS,Beijing,China.
文摘Ulcerative colitis(UC)manifests as an etiologically complicated and relapsing gastrointestinal disease.The enteric nervous system(ENS)plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract.Berberine,an isoquinoline alkaloid,is known as its antiinflammatory and therapeutic effects in experimental colitis.However,little research focused on its regulatory function on ENS.Therefore,we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions.Functional defects of enteric glial cells(EGCs),with decreased glial fibrillary acidic protein(GFAP)and increased substance P expression,were observed in DSS-induced murine UC.Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC,closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation.In vitro,berberine showed direct protective effects on monoculture of EGCs,bone marrowderived dendritic cells(BMDCs),T cells,and intestinal epithelial cells(IECs)in the simulated inflammatory conditions.Furthermore,berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems.In summary,our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.
文摘We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRIJIpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus （SLE）. When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/Ipr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies （ANAs） and of the pathogenic cytokines IL-6, IL-10 and I L-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/Ipr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell （PC） numbers. Ex vivo, SM934 suppressed the Toll-like receptor （TLR）-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-KB phosphorylation. In human peripheral blood mononuclear cells （PBMCs）, consistent with the results in MRIJIprmice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/Iprmice by suppressing B cell activation and plasma cell formation.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20131201110002)the Key Laboratory of Computer Architecture Opening Topic Fund Subsidization(No.CARCH201303)
文摘Network virtualization is a promising approach for resource management that allows customized Virtual Networks （VNs） to be multiplexed on a shared physical infrastructure. A key function that network virtualization can provide is Virtual Network Embedding （VNE）, which maps virtual networks requested by users to a shared substrate network maintained by an Internet service provider. Existing research has worked on this, but has primarily focused on maximizing the revenue of the Internet service provider. In this paper, we consider energy-aware virtual network embedding, which aims at minimizing the energy consumption for embedding virtual networks in a substrate network. In our optimization model, we consider energy consumption of both links and nodes. We propose an efficient heuristic to assign virtual nodes to appropriate substrate nodes based on priority, where existing activated nodes have higher priority for hosting newly arrived virtual nodes. In addition, our proposed algorithm can take advantage of activated links for embedding virtual links so as to minimize total energy consumption. The simulation results show that, for all the cases considered, our algorithm can improve upon previous work by an average of 12.6% on acceptance rate, while the consumed energy can be reduced by 12.34% on average.
