Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the seve...Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease.However,the mechanism of C3 a/C4 a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3 a/C4 a in vitro.RNA-seq analysis was used to screen the potential pathways affecting osteoclasts,and the results were verified by Western blot,q RT-PCR,and pathway inhibitors.Results:The osteoclast area per view induced by 1μg/m L(mean±SD:50.828±12.984%)and 10μg/m L(53.663±12.685%)of C3 a was significantly increased compared to the control group(0μg/m L)(34.635±8.916%)(P<0.001 and P<0.001,respectively).The relative m RNA expressions of genes,OSCAR/TRAP/RANKL/cathepsin K,induced by 1μg/m L(median:5.041,3.726,1.638,and 4.752,respectively)and 10μg/m L(median:5.140,3.702,2.250,and 5.172,respectively)of C3 a was significantly increased compared to the control group(median:3.137,2.004,0.573,and 2.257,respectively)(1μg/m L P=0.001,P=0.003,P<0.001,and P=0.008,respectively;10μg/m L:P<0.001,P=0.019,P<0.001,and P=0.002,respectively).The absorption areas of the osteoclast resorption pits per view induced by 1μg/m L(mean±SD:51.464±11.983%)and 10μg/m L(50.219±12.067%)of C3 a was also significantly increased(33.845±8.331%)(P<0.001 and P<0.001,respectively)compared to the control.There was no difference between the C4 a and control groups.RNA-seq analysis showed that C3 a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase(PI3 K)signaling pathway.The relative expressions of PIK3 CA/phosphoinositide dependent kinase-1(PDK1)/serum and glucocorticoid inducible protein kinases(SGK3)genes and PI3 K/PDK1/p-SGK3 protein in the C3 a group were significantly higher than in the control group.The activation role of C3 a in osteoclasts of MM patients was reduced by the SGK inhibitor(EMD638683).Conclusions:C3 a activated osteoclasts by regulating the PI3 K/PDK1/SGK3 pathways in MM patients,which was reduced using a SGK inhibitor.Overall,our results identified potential therapeutic targets and strategies for MBD patients。展开更多
Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed...Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed that TRPV1(transient receptor potential vanilloid type 1)is involved in epilepsy.Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood.We found that in a mouse model of status epilepticus(SE),complement C3 derived from astrocytes was increased and aggravated neuronal injury,and that TRPV 1-knockout rescued neurons from the injury induced by complement C3.Circular RNAs are abundant in the brain,and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV 1 and exacerbated neuronal injury.Mechanistically,disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury.This study provides support for the hypothesis that the C3-TRFV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.展开更多
In the sarcoma S180 ascitic mice, the effects of moxa-cone moxibustion at Guanyuan (CV 4) on erythrocytic immunity and its regulative function were investigated. The results indicated that moxibustion at Guanyuan (CV ...In the sarcoma S180 ascitic mice, the effects of moxa-cone moxibustion at Guanyuan (CV 4) on erythrocytic immunity and its regulative function were investigated. The results indicated that moxibustion at Guanyuan (CV 4) could significantly increase the decreased erythrocytic C3b receptor rosette forming rate (RBC-C3bRR), lower the raised erythrocytic immunocomplex rosette forming rate (RBC-ICR, P展开更多
BACKGROUND： Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury. OBJECTIVE： To investigate the effects of different Naoxintong doses on expressi...BACKGROUND： Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury. OBJECTIVE： To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B （ kB）, interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia. DESIGN, TIME AND SETTING： The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIALS： A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320g, were selected. Naoxintong powder （mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis） was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608. METHODS： The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 g/kg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage All rats were administered by gavage at 5 and 23 hours following surgery, and subsequently, once per day. MAIN OUTCOME MEASURES： At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor- α, and complement 3 was examined by immunohistochemistry. RESULTS： A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as well as the high-dose, moderate-dose, and low-dose Naoxintong groups at 24 hours, which reached a peak at 48 hours. At 6, 24, 48, 72 hours, and 7 days, brain water content was greater in the ischemic hemisphere of rats from the saline, as well as the high-dose, moderate-dose, and low-dose Naoxintong groups, compared with the sham operation group （P 〈 0.05）. At 24 and 48 hours, brain water content was reduced in the high-dose and moderate-dose Naoxintong groups, compared to the saline and low-dose Naoxintong groups （P 〈 0.05）. In the saline, as well as high-dose, moderate-dose, and low-dose Naoxintong groups, neuronal edema was observed at 6 hours surrounding the ischemic sites. Inflammatory cells appeared at 24 hours, reached a peak at 48 hours, and gradually diminished. A small amount of glial cell proliferation and neuronal degeneration were observed in the hippocampus at 72 hours following infarction. Microglial proliferation and aggregation were detected at 7 days after infarction. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor-α, and complement 3 was significantly less in the high-dose, moderate-dose, and low-dose Naoxintong groups, compared to the sham operation group （P 〈 0.05）. Expression of the above-mentioned inflammatory cytokines was lower in rat brain tissues of the high-dose Naoxintong group, compared to the low-dose Naoxintong group （P 〈 0.05）. CONCLUSION： High-dose Naoxintong and moderate-dose Naoxintong significantly alleviated rat brain edema and decreased expression of nuclear factor-kB, interleukin-6, tumor necrosis factor-α, and complement 3 in brain tissues. The protective effect of high-dose Naoxintong was most significant.展开更多
The present study was designed to evaluate the protective effects of ethanol extracts of Rabdosia japonica var. glaucocalyx(Maxim.) Hara(RJ) on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice and the po...The present study was designed to evaluate the protective effects of ethanol extracts of Rabdosia japonica var. glaucocalyx(Maxim.) Hara(RJ) on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice and the possible underlying mechanisms of action. The mice were orally administrated with RJ extract(16, 32 or 64 mg?kg–1) daily for consecutive7 days before LPS challenge. The ung specimens and the bronchoalveolar lavage fluid(BALF) were collected for histopathological examinations and biochemical analyses. Pretreatment with RJ significantly enhanced superoxide dismutase(SOD) activity and reduced the wet-to-dry weight(W/D) ratio, the levels of nitric oxide(NO) and protein leakage, and myeloperoxidase(MPO) activity in mice with ALI, in a dose-dependent manner. RJ reduced complement deposition and significantly attenuated LPS-induced ALI by reducing productions of inflammatory mediators, such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). The results demonstrated that RJ may attenuate LPS-induced ALI via reducing the production of pro-inflammatory mediators, and reducing complement deposition and radicals.展开更多
The bimodulus material is a classical model to describe the elastic behavior of materials with tension-compression asymmetry.Due to the inherently nonlinear properties of bimodular materials,traditional iteration meth...The bimodulus material is a classical model to describe the elastic behavior of materials with tension-compression asymmetry.Due to the inherently nonlinear properties of bimodular materials,traditional iteration methods suffer from low convergence efficiency and poor adaptability for large-scale structures in engineering.In this paper,a novel 3D algorithm is established by complementing the three shear moduli of the constitutive equation in principal stress coordinates.In contrast to the existing 3D shear modulus constructed based on experience,in this paper the shear modulus is derived theoretically through a limit process.Then,a theoretically self-consistent complemented algorithm is established and implemented in ABAQUS via UMAT;its good stability and convergence efficiency are verified by using benchmark examples.Numerical analysis shows that the calculation error for bimodulus structures using the traditional linear elastic theory is large,which is not in line with reality.展开更多
A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,...A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81770110,81900131,and 82000219)the Anticancer Major Special Project of Tianjin(Grant No.12ZCDZSY18000)+4 种基金the Tianjin Municipal Natural Science Foundation(Grant Nos.18JCYBJC27200 and 18JCQNJC80400)the Tianjin Education Commission Research Project(Grant Nos.2018KJ043 and 2018KJ045)the Tianjin Health and Family Planning Commission(Grant No.15KG150)the Youth Incubation Fund of Tianjin Medical University General Hospital(Grant No.ZYYFY2019020)the Tianjin Science and Technology Planning Project(Grant No.20YFZCSY00060)。
文摘Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease.However,the mechanism of C3 a/C4 a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3 a/C4 a in vitro.RNA-seq analysis was used to screen the potential pathways affecting osteoclasts,and the results were verified by Western blot,q RT-PCR,and pathway inhibitors.Results:The osteoclast area per view induced by 1μg/m L(mean±SD:50.828±12.984%)and 10μg/m L(53.663±12.685%)of C3 a was significantly increased compared to the control group(0μg/m L)(34.635±8.916%)(P<0.001 and P<0.001,respectively).The relative m RNA expressions of genes,OSCAR/TRAP/RANKL/cathepsin K,induced by 1μg/m L(median:5.041,3.726,1.638,and 4.752,respectively)and 10μg/m L(median:5.140,3.702,2.250,and 5.172,respectively)of C3 a was significantly increased compared to the control group(median:3.137,2.004,0.573,and 2.257,respectively)(1μg/m L P=0.001,P=0.003,P<0.001,and P=0.008,respectively;10μg/m L:P<0.001,P=0.019,P<0.001,and P=0.002,respectively).The absorption areas of the osteoclast resorption pits per view induced by 1μg/m L(mean±SD:51.464±11.983%)and 10μg/m L(50.219±12.067%)of C3 a was also significantly increased(33.845±8.331%)(P<0.001 and P<0.001,respectively)compared to the control.There was no difference between the C4 a and control groups.RNA-seq analysis showed that C3 a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase(PI3 K)signaling pathway.The relative expressions of PIK3 CA/phosphoinositide dependent kinase-1(PDK1)/serum and glucocorticoid inducible protein kinases(SGK3)genes and PI3 K/PDK1/p-SGK3 protein in the C3 a group were significantly higher than in the control group.The activation role of C3 a in osteoclasts of MM patients was reduced by the SGK inhibitor(EMD638683).Conclusions:C3 a activated osteoclasts by regulating the PI3 K/PDK1/SGK3 pathways in MM patients,which was reduced using a SGK inhibitor.Overall,our results identified potential therapeutic targets and strategies for MBD patients。
基金by the National Natural Science Foundation of China(81571481 and 82060588)the Natural Science Foundation of Hubei Province,China(2017CFA017)+1 种基金the Wuhan Science and Technology Project(2019020701011444)the Medical Science Advancement Program of Wuhan University(TFJC2018001 and TFLC2018001).
文摘Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed that TRPV1(transient receptor potential vanilloid type 1)is involved in epilepsy.Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood.We found that in a mouse model of status epilepticus(SE),complement C3 derived from astrocytes was increased and aggravated neuronal injury,and that TRPV 1-knockout rescued neurons from the injury induced by complement C3.Circular RNAs are abundant in the brain,and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV 1 and exacerbated neuronal injury.Mechanistically,disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury.This study provides support for the hypothesis that the C3-TRFV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
文摘In the sarcoma S180 ascitic mice, the effects of moxa-cone moxibustion at Guanyuan (CV 4) on erythrocytic immunity and its regulative function were investigated. The results indicated that moxibustion at Guanyuan (CV 4) could significantly increase the decreased erythrocytic C3b receptor rosette forming rate (RBC-C3bRR), lower the raised erythrocytic immunocomplex rosette forming rate (RBC-ICR, P
基金Supported by: the Scientific Technology Research and Development Plan of Hebei Province, No. 06276103Dthe Natural Science Foundation of Hebei Province, No. C2006000915
文摘BACKGROUND： Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury. OBJECTIVE： To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B （ kB）, interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia. DESIGN, TIME AND SETTING： The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIALS： A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320g, were selected. Naoxintong powder （mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis） was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608. METHODS： The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 g/kg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage All rats were administered by gavage at 5 and 23 hours following surgery, and subsequently, once per day. MAIN OUTCOME MEASURES： At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor- α, and complement 3 was examined by immunohistochemistry. RESULTS： A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as well as the high-dose, moderate-dose, and low-dose Naoxintong groups at 24 hours, which reached a peak at 48 hours. At 6, 24, 48, 72 hours, and 7 days, brain water content was greater in the ischemic hemisphere of rats from the saline, as well as the high-dose, moderate-dose, and low-dose Naoxintong groups, compared with the sham operation group （P 〈 0.05）. At 24 and 48 hours, brain water content was reduced in the high-dose and moderate-dose Naoxintong groups, compared to the saline and low-dose Naoxintong groups （P 〈 0.05）. In the saline, as well as high-dose, moderate-dose, and low-dose Naoxintong groups, neuronal edema was observed at 6 hours surrounding the ischemic sites. Inflammatory cells appeared at 24 hours, reached a peak at 48 hours, and gradually diminished. A small amount of glial cell proliferation and neuronal degeneration were observed in the hippocampus at 72 hours following infarction. Microglial proliferation and aggregation were detected at 7 days after infarction. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor-α, and complement 3 was significantly less in the high-dose, moderate-dose, and low-dose Naoxintong groups, compared to the sham operation group （P 〈 0.05）. Expression of the above-mentioned inflammatory cytokines was lower in rat brain tissues of the high-dose Naoxintong group, compared to the low-dose Naoxintong group （P 〈 0.05）. CONCLUSION： High-dose Naoxintong and moderate-dose Naoxintong significantly alleviated rat brain edema and decreased expression of nuclear factor-kB, interleukin-6, tumor necrosis factor-α, and complement 3 in brain tissues. The protective effect of high-dose Naoxintong was most significant.
基金supported by China Postdoctoral Science Foundation(No.20100471390)Natural Science Foundation of Jiangsu Province(No.BK2011296)+1 种基金Foundation of Suzhou Science and Technology Bureau(No.SYS201206)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘The present study was designed to evaluate the protective effects of ethanol extracts of Rabdosia japonica var. glaucocalyx(Maxim.) Hara(RJ) on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice and the possible underlying mechanisms of action. The mice were orally administrated with RJ extract(16, 32 or 64 mg?kg–1) daily for consecutive7 days before LPS challenge. The ung specimens and the bronchoalveolar lavage fluid(BALF) were collected for histopathological examinations and biochemical analyses. Pretreatment with RJ significantly enhanced superoxide dismutase(SOD) activity and reduced the wet-to-dry weight(W/D) ratio, the levels of nitric oxide(NO) and protein leakage, and myeloperoxidase(MPO) activity in mice with ALI, in a dose-dependent manner. RJ reduced complement deposition and significantly attenuated LPS-induced ALI by reducing productions of inflammatory mediators, such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). The results demonstrated that RJ may attenuate LPS-induced ALI via reducing the production of pro-inflammatory mediators, and reducing complement deposition and radicals.
基金the National Natural Science Foundation of China(Grant 51908071)Scientific Research Project of Education Department of Hunan Province(Grant 18C0194)Open Fund of Key Laboratory of Road Structure and Material of Ministry of Transport,Changsha University of Science&Technology(Grant kfi 170303).
文摘The bimodulus material is a classical model to describe the elastic behavior of materials with tension-compression asymmetry.Due to the inherently nonlinear properties of bimodular materials,traditional iteration methods suffer from low convergence efficiency and poor adaptability for large-scale structures in engineering.In this paper,a novel 3D algorithm is established by complementing the three shear moduli of the constitutive equation in principal stress coordinates.In contrast to the existing 3D shear modulus constructed based on experience,in this paper the shear modulus is derived theoretically through a limit process.Then,a theoretically self-consistent complemented algorithm is established and implemented in ABAQUS via UMAT;its good stability and convergence efficiency are verified by using benchmark examples.Numerical analysis shows that the calculation error for bimodulus structures using the traditional linear elastic theory is large,which is not in line with reality.
文摘A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.
