Radiation-induced lung injury(RILI)is a common complication of cancer radiotherapy,yet effective treatments remain elusive.Compound Kushen injection(CKI),a traditional Chinese medicine(TCM)formula,is widely used in cl...Radiation-induced lung injury(RILI)is a common complication of cancer radiotherapy,yet effective treatments remain elusive.Compound Kushen injection(CKI),a traditional Chinese medicine(TCM)formula,is widely used in clinical practice for treating radiation-related diseases and as an adjunct therapy for cancer and has demonstrated some effectiveness.However,the mechanisms underlying CKI intervention in RILI and its role in cancer adjunctive therapy remain unclear.In this study,we refined previous statistical approaches and successfully integrated quantitative data on the compounds in CKI.We constructed a network-based holistic target model and developed modular biological networks to explore the modular regulatory effects of CKI in RILI.Through this network-based analysis,we identified specific alkaloid components of CKI that contribute to its therapeutic effect in alleviating RILI.Furthermore,through transcriptomic analysis,we confirmed that oxidative stress plays a central role in the treatment of RILI by CKI.The modular regulatory effects of CKI have been validated in animal models of irradiation,demonstrating the ability of CKI to alleviate oxidative stress,reduce inflammation,regulate immune responses,and inhibit apoptosis.In addition,we demonstrated that nuclear factor erythroid 2-related factor 2(NRF2)serves as a key mediator of the antioxidant effects of CKI.Matrine and sophoridine,representative alkaloids in CKI,exhibit binding interactions with NRF2.CKI promotes the nuclear translocation of NRF2,and NRF2 activates its downstream targets,such as heme oxygenase-1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1),to suppress oxidative stress in RILI.This,in turn,inhibits the expression of inflammatory molecules,including interleukin(IL)-6,tumor necrosis factor(TNF)-α,and inducible nitric oxide synthase(iNOS),while promoting the activity of antioxidants such as superoxide dismutase(SOD)and glutathione peroxidase-4(GPX-4),thereby exerting therapeutic effects on RILI.展开更多
The anaerobic ammonium oxidation （anammox） process was successfully started up from conventional activated sludge using a hybrid bioreactor within 2 months.The average removal efficiencies of ammonia and nitrite wer...The anaerobic ammonium oxidation （anammox） process was successfully started up from conventional activated sludge using a hybrid bioreactor within 2 months.The average removal efficiencies of ammonia and nitrite were both over 80%,and the maximum total nitrogen removal rate of 1.85 kg N/（m^3 ·day） was obtained on day 362 with the initial sludge concentration of 0.7 g mixed liquor suspended solids （MLSS）/L.Scanning electron microscope （SEM） observation of the granular sludge in the hybrid reactor clearly showed a high degree of compactness and cell sphericity,and the cell size was quite uniform.Transmission electron microscope photos showed that cells were round or oval,the cellular diameter was 0.6-1.0 μm,and the percentage of the anammoxosome compartment was 51%-85% of the whole cell volume.Fluorescence in situ hybridization analysis （FISH） indicated that anammox bacteria became the dominant population in the community （accounting for more than 51% of total bacteria on day 250）.Seven planctomycete 16S rRNA gene sequences were present in the 16S rRNA gene clone library generated from the biomass and affiliated to Candidatus Kuenenia stuttgartiensis and Candidatus Brocadia sp.,a new anammox species.In addition,the average effluent suspended solid （MLSS） concentrations of outlets I （above the non-woven carrier） and II （below the non-woven carrier） were 0.0009 and 0.0035 g/L,respectively.This showed that the non-woven carrier could catch the biomass effectively,which increased biomass and improved the nitrogen removal rate in the reactor.展开更多
BACKGROUND： Human tumor necrosis factor-like molecule 1A （hTL1A） is a strong T helper cell type 1 （Thl） co-stimulator. Guillain-Barre syndrome （GBS） is an autoimmune disorder of the nervous system, which is med...BACKGROUND： Human tumor necrosis factor-like molecule 1A （hTL1A） is a strong T helper cell type 1 （Thl） co-stimulator. Guillain-Barre syndrome （GBS） is an autoimmune disorder of the nervous system, which is mediated by Thl cells. OBJECTIVE： To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ. DESIGN, TIME AND SETTING： A randomized, controlled, neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University, China from November 2005 to November 2007. MATERIALS： Venous blood samples were obtained from 6 healthy donors, aged 6-12 years （all routine blood examination items were normal）, and 6 additional children with acute GBS, aged 6-12 years. The GBS children fell ill within 1 week and were not treated with hormones or immunoglobulin Purified recombinant human soluble tumor necrosis factor-like molecule 1A （rhsTL1A, 1 mg/mL, relative molecular mass 22 000, 6× His tag, soluble form） was supplied by the Central Laboratory of First Hospital of Jilin University, China. METHODS： Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates. The cells were assigned to the following groups： control （2 μg/mL phytohemagglutinin）, 2μg/mL phytohemagglutinin ＋ 25, 100 and 400 ng/mL rhsTL1A. T cell proliferation was quantified using the tritiated thymidine （3H-TdR） method. Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay （ELISA）. The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry. Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin, the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTLIA. Finally, peripheral blood mononuclear cell-secreted interferon-γlevels were measured by ELISA. MAIN OUTCOME MEASURES： The following parameters were measured： rhsTLIA stimulation index to stimulate proliferation of T cells; the serum interferon-γ levels in acute GBS children; the ratio of hTL1A-positive cells to CD3-positive cells; the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children, as well as rhsTL1A-stimulated interferon-γ levels. RESULTS： T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group. The stimulation index of the 400 ng/mL rhsTL1A group was the greatest. Serum interferon-γ levels in acute GBS children were significantly greater than the control group （P 〈 0.05）. The ratio of hTLIA＋ CD3＋ T cells to CD3＋ T cells in acute GBS children was significantly greater than the control group （P 〈 0.01 ）. Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group, and the secreted interferon-γ levels were significantly increased （P 〈 0.05）. CONCLUSION： In T cells pre-activated with 2 μg/mL phytohemagglutinin, proliferation was effectively increased with 400 ng/mL rhsTL1A treatment. Expression of hTLIA was increased in activated T cells from peripheral blood of acute GBS children, followed by increased interferon-γ secretion. These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.展开更多
基金supported by the Innovation Team and Talent Support Program Project of Traditional Chinese Medicine(ZYYCXTD-D-202405)from National Administration of Traditional Chinese Medicine,the National Natural Science Foundation of China(T2341008)the Pilot Project for Disciplinary Breakthroughs of Ministry of Education(Prevention and Treatment of Multi-System Comorbid Diseases with Traditional Chinese Medicine).
文摘Radiation-induced lung injury(RILI)is a common complication of cancer radiotherapy,yet effective treatments remain elusive.Compound Kushen injection(CKI),a traditional Chinese medicine(TCM)formula,is widely used in clinical practice for treating radiation-related diseases and as an adjunct therapy for cancer and has demonstrated some effectiveness.However,the mechanisms underlying CKI intervention in RILI and its role in cancer adjunctive therapy remain unclear.In this study,we refined previous statistical approaches and successfully integrated quantitative data on the compounds in CKI.We constructed a network-based holistic target model and developed modular biological networks to explore the modular regulatory effects of CKI in RILI.Through this network-based analysis,we identified specific alkaloid components of CKI that contribute to its therapeutic effect in alleviating RILI.Furthermore,through transcriptomic analysis,we confirmed that oxidative stress plays a central role in the treatment of RILI by CKI.The modular regulatory effects of CKI have been validated in animal models of irradiation,demonstrating the ability of CKI to alleviate oxidative stress,reduce inflammation,regulate immune responses,and inhibit apoptosis.In addition,we demonstrated that nuclear factor erythroid 2-related factor 2(NRF2)serves as a key mediator of the antioxidant effects of CKI.Matrine and sophoridine,representative alkaloids in CKI,exhibit binding interactions with NRF2.CKI promotes the nuclear translocation of NRF2,and NRF2 activates its downstream targets,such as heme oxygenase-1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1),to suppress oxidative stress in RILI.This,in turn,inhibits the expression of inflammatory molecules,including interleukin(IL)-6,tumor necrosis factor(TNF)-α,and inducible nitric oxide synthase(iNOS),while promoting the activity of antioxidants such as superoxide dismutase(SOD)and glutathione peroxidase-4(GPX-4),thereby exerting therapeutic effects on RILI.
基金supported by the Fundamental Research Funds for the Central Universities (No. DUT09RC(3)304)the Key Laboratory of Industrial Ecology and Environmental Engineering,China Ministry of Education (No.KLIEEE-09-09)the National Natural Science Foundation of China (No. 51008045)
文摘The anaerobic ammonium oxidation （anammox） process was successfully started up from conventional activated sludge using a hybrid bioreactor within 2 months.The average removal efficiencies of ammonia and nitrite were both over 80%,and the maximum total nitrogen removal rate of 1.85 kg N/（m^3 ·day） was obtained on day 362 with the initial sludge concentration of 0.7 g mixed liquor suspended solids （MLSS）/L.Scanning electron microscope （SEM） observation of the granular sludge in the hybrid reactor clearly showed a high degree of compactness and cell sphericity,and the cell size was quite uniform.Transmission electron microscope photos showed that cells were round or oval,the cellular diameter was 0.6-1.0 μm,and the percentage of the anammoxosome compartment was 51%-85% of the whole cell volume.Fluorescence in situ hybridization analysis （FISH） indicated that anammox bacteria became the dominant population in the community （accounting for more than 51% of total bacteria on day 250）.Seven planctomycete 16S rRNA gene sequences were present in the 16S rRNA gene clone library generated from the biomass and affiliated to Candidatus Kuenenia stuttgartiensis and Candidatus Brocadia sp.,a new anammox species.In addition,the average effluent suspended solid （MLSS） concentrations of outlets I （above the non-woven carrier） and II （below the non-woven carrier） were 0.0009 and 0.0035 g/L,respectively.This showed that the non-woven carrier could catch the biomass effectively,which increased biomass and improved the nitrogen removal rate in the reactor.
基金Supported by:the Program of the Key Laboratory of Health Department of Jilin Province, No.2006079the Fortieth National Post-Doctoral Scientific Foundation,No. 20060400893
文摘BACKGROUND： Human tumor necrosis factor-like molecule 1A （hTL1A） is a strong T helper cell type 1 （Thl） co-stimulator. Guillain-Barre syndrome （GBS） is an autoimmune disorder of the nervous system, which is mediated by Thl cells. OBJECTIVE： To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ. DESIGN, TIME AND SETTING： A randomized, controlled, neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University, China from November 2005 to November 2007. MATERIALS： Venous blood samples were obtained from 6 healthy donors, aged 6-12 years （all routine blood examination items were normal）, and 6 additional children with acute GBS, aged 6-12 years. The GBS children fell ill within 1 week and were not treated with hormones or immunoglobulin Purified recombinant human soluble tumor necrosis factor-like molecule 1A （rhsTL1A, 1 mg/mL, relative molecular mass 22 000, 6× His tag, soluble form） was supplied by the Central Laboratory of First Hospital of Jilin University, China. METHODS： Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates. The cells were assigned to the following groups： control （2 μg/mL phytohemagglutinin）, 2μg/mL phytohemagglutinin ＋ 25, 100 and 400 ng/mL rhsTL1A. T cell proliferation was quantified using the tritiated thymidine （3H-TdR） method. Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay （ELISA）. The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry. Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin, the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTLIA. Finally, peripheral blood mononuclear cell-secreted interferon-γlevels were measured by ELISA. MAIN OUTCOME MEASURES： The following parameters were measured： rhsTLIA stimulation index to stimulate proliferation of T cells; the serum interferon-γ levels in acute GBS children; the ratio of hTL1A-positive cells to CD3-positive cells; the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children, as well as rhsTL1A-stimulated interferon-γ levels. RESULTS： T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group. The stimulation index of the 400 ng/mL rhsTL1A group was the greatest. Serum interferon-γ levels in acute GBS children were significantly greater than the control group （P 〈 0.05）. The ratio of hTLIA＋ CD3＋ T cells to CD3＋ T cells in acute GBS children was significantly greater than the control group （P 〈 0.01 ）. Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group, and the secreted interferon-γ levels were significantly increased （P 〈 0.05）. CONCLUSION： In T cells pre-activated with 2 μg/mL phytohemagglutinin, proliferation was effectively increased with 400 ng/mL rhsTL1A treatment. Expression of hTLIA was increased in activated T cells from peripheral blood of acute GBS children, followed by increased interferon-γ secretion. These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.
