Neuroinflammation hinders repair of the central nervous system(CNS).Stem cell transplantation is a very promising approach for treatment of CNS injuries.However,it is difficult to select seed cells that can both facil...Neuroinflammation hinders repair of the central nervous system(CNS).Stem cell transplantation is a very promising approach for treatment of CNS injuries.However,it is difficult to select seed cells that can both facilitate nerve regeneration and improve the microenvironment in the CNS.In this study,we isolated multilineage-differentiating stress-enduring(Muse)cells from bone marrow mesenchymal stem cells.We explored the anti-inflammatory effect and mechanism of Muse cells in vitro by coculture of Muse cells with lipopolysaccharide-stimulated microglia.Our results showed that Muse cells effectively reduced the transcription and secretion of tumor necrosis factorαand interleukin-1βand increased the expression of transforming growth factor-βand interleukin-10 in microglia.In addition,Muse cells decreased the number of M1 microglia and increased the proportion of M2 microglia in an inflammatory environment more effectively than bone marrow mesenchymal stem cells.We also show that Muse cells inhibited the protein expression of toll-like receptor 4(TLR4)and myeloid differentiation primary response protein(MyD88)and inhibited the expression of the phosphorylated forms of transcription factor p65,nuclear factor(NF)-κB inhibitor alpha,and p38 mitogen-activated protein kinase(MAPK)in microglia.Therefore,we suggest Muse cells cause antineuroinflammatory effects by inhibition of the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways in microglia.Our results shed light on the function of Muse cells in relation to CNS diseases and provide insight into the selection of seed cells.展开更多
Acupuncture can reduce cognitive deficits in Alzheimer’s disease.However,whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood.Studies have sho...Acupuncture can reduce cognitive deficits in Alzheimer’s disease.However,whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood.Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline.Therefore,we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications.A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks.Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration.Preventive electroacupuncture alleviated memory impairment,decreased tau hyperphosphorylation,and reduced glycogen synthase kinase-3βprotein and mRNA expression levels in the brainstem dorsal raphe nucleus,where intracellular neurofibrillary tangle lesions first occur.In addition,the DNA methylation level in the promoter region of the glycogen synthase kinase-3βgene was increased.The effects of preventive electroacupuncture were stronger than those of preventive acupuncture.Intraperitoneal injection of 0.4 mg/kg 5-aza-2ʹ-deoxycytidine,an inhibitor of DNA methyltransferase that blocks epigenetic modifications,antagonized the effects of preventive electroacupuncture.Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3βgene in the dorsal raphe nucleus.This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine,China(approval No.HUCMS201712001)on November 28,2017.展开更多
Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of v...Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.展开更多
A method of obtaining the large strain consolidation parameters of dredged clays considering the influence of the initial water content is investigated in this study. According to the test results of remolded clays wi...A method of obtaining the large strain consolidation parameters of dredged clays considering the influence of the initial water content is investigated in this study. According to the test results of remolded clays with high initial water contents reported by Hong et al. (2010), a relationship between the void ratio (e) and effective stress (a3 is established. Furthermore, based on the available permeability data from the literature, a new relationship between the permeability coefficient (k) and the ratio (e/eL) of the void ratio to the void ratio at the liquid limit (eL) is proposed. The new proposed expression considering the initial water content improves the e-k equation established by Nagaraj et al. (1994). Finally, the influence of the initial void ratio and effective stress on the large strain consolidation coefficient g(e) defined by Gibson et al. (1981) and k/(1 +e) in large strain analysis is discussed. The results show that, under a constant effective stress, the value of k/(1 +e) increases with the initial void ratio. The large strain consolidation coefficient shows the law of segmentation change, which decreases with the increase of the effective stress when the effective stress is less than the remolded yield stress, but increases rapidly with the effective stress when the effective stress is larger than the remolded yield stress.展开更多
To the Editor:Since the first IgE monoclonal antibody was approved by the Food and Drug Administration in the USA in 2003,at least 14 kinds of targeted drugs are in the clinical application or pre-clinical trials.The ...To the Editor:Since the first IgE monoclonal antibody was approved by the Food and Drug Administration in the USA in 2003,at least 14 kinds of targeted drugs are in the clinical application or pre-clinical trials.The two monoclonal antibodies targeting IgE are omalizumab and ligelizumab.Four drugs targeting interleukin 4(IL-4)or IL-4R are pascolizumab,pitrakinra,altrakincept,and dupilumab.Three monoclonal antibodies targeting IL-5/IL-5R are mepolizumab,reslizumab,and benralizumab.Two monoclonal antibodies targeting IL-13 are lebrikizumab and tralokinumab.The monoclonal antibody targeting thymic stromal lymphopoietin(TSLP)is tezepelumab.Th2 cytokine inhibitor is mesylate.These targeted drugs have achieved good results,but most of them are still in the pre-clinical stage.This article reviews the history,marketing situation,indications,contraindications,efficacy,and safety of these targeted drugs.展开更多
Panax quinquefolius L.(American ginseng)and Panax ginseng C.A.Meyer are famous herbal medicines.Accurate authentication of the species has grown to be a significant impact.This study aims to develop a PCR kit for the ...Panax quinquefolius L.(American ginseng)and Panax ginseng C.A.Meyer are famous herbal medicines.Accurate authentication of the species has grown to be a significant impact.This study aims to develop a PCR kit for the authentication of Panax quinquefolius L.and Panax ginseng based on the nuclear internal transcribed spacer 2(ITS2)gene with the improved PCR-restriction fragment length polymorphism(PCR-RFLP)method.The reagent components in the development work were prepared and determined by the kit consisting of the DNA extraction,PCR amplification,and restriction enzyme digestion systems.A total of 21 batches of Panax quinquefolius L.and Panax ginseng samples collected from different areas were validated.Their specificity,stability,and repeatability were evaluated.The purity of genomic DNA extracted was 1.73±0.13 according to the ratio of A_(260)/A_(280),and the mass concentration was 3.15±0.22μg/g(using the kit).PCR amplicons of Panax quinquefolius L.and Panax ginseng were 122 bp in length.After the PCR products were digested by restriction enzyme Hinf I,a distinct pattern exhibited in the species of Panax quinquefolius L.with two fragments of 40 bp and 80 bp respectively,whereas those from Panax ginseng in addition to adulterated samples could not.Evaluation confirmed that the DNA kit results were stable and repeatable after 10,15,and 20 freeze-thaw cycles:the evaluation was 100%specific.The DNA kit proposed in the study can be used for the identification of Panax quinquefolius L.展开更多
基金supported by the National Natural Science Foundation of China, No. 81501610 (to XC)a grant for Development of Science and Technology of Wuxi, Nos. N20202030 (to XC), N20192025 (to XSW)Postgraduate Research & Practice Innovation Program of Jiangsu Province, No. KYCX20_1960 (to XYY)
文摘Neuroinflammation hinders repair of the central nervous system(CNS).Stem cell transplantation is a very promising approach for treatment of CNS injuries.However,it is difficult to select seed cells that can both facilitate nerve regeneration and improve the microenvironment in the CNS.In this study,we isolated multilineage-differentiating stress-enduring(Muse)cells from bone marrow mesenchymal stem cells.We explored the anti-inflammatory effect and mechanism of Muse cells in vitro by coculture of Muse cells with lipopolysaccharide-stimulated microglia.Our results showed that Muse cells effectively reduced the transcription and secretion of tumor necrosis factorαand interleukin-1βand increased the expression of transforming growth factor-βand interleukin-10 in microglia.In addition,Muse cells decreased the number of M1 microglia and increased the proportion of M2 microglia in an inflammatory environment more effectively than bone marrow mesenchymal stem cells.We also show that Muse cells inhibited the protein expression of toll-like receptor 4(TLR4)and myeloid differentiation primary response protein(MyD88)and inhibited the expression of the phosphorylated forms of transcription factor p65,nuclear factor(NF)-κB inhibitor alpha,and p38 mitogen-activated protein kinase(MAPK)in microglia.Therefore,we suggest Muse cells cause antineuroinflammatory effects by inhibition of the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways in microglia.Our results shed light on the function of Muse cells in relation to CNS diseases and provide insight into the selection of seed cells.
基金This work was supported by the National Natural Science Foundation of China,Nos.81373741(to LHK),81473786(to YJD),81873380(to YJD)Sun Guojie Inheritance Base for TCM Acupuncture-Moxibustion of World Federation of Acupuncture-Moxibustion Societies in Wuhan,China(World Federation of Acupuncture-Moxibustion Societies[2019]No.26)(to YJD)and“Wei Yizong Chiropractic Team”Project Founded by Shenzhen of China,No.SZSM201612059(to YFL).
文摘Acupuncture can reduce cognitive deficits in Alzheimer’s disease.However,whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood.Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline.Therefore,we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications.A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks.Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration.Preventive electroacupuncture alleviated memory impairment,decreased tau hyperphosphorylation,and reduced glycogen synthase kinase-3βprotein and mRNA expression levels in the brainstem dorsal raphe nucleus,where intracellular neurofibrillary tangle lesions first occur.In addition,the DNA methylation level in the promoter region of the glycogen synthase kinase-3βgene was increased.The effects of preventive electroacupuncture were stronger than those of preventive acupuncture.Intraperitoneal injection of 0.4 mg/kg 5-aza-2ʹ-deoxycytidine,an inhibitor of DNA methyltransferase that blocks epigenetic modifications,antagonized the effects of preventive electroacupuncture.Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3βgene in the dorsal raphe nucleus.This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine,China(approval No.HUCMS201712001)on November 28,2017.
基金supported in part by the National Natural Science Foundation of China,No.81100939 and 81773713(to WH),No.81501610(to XC)the Research Project funded by Jiangsu Provincial Government of China,No.BRA2018223(to DGM)+2 种基金the Public Health Center at Jiangnan University of China,No.JUPH201808(to XSW)the Wuxi Commission of Public Health and Family Planning of China,No.MS201717(to XSW)the Project of Academic Development Program by Governments of Jiangsu Province and Nantong City of China(to DGM)
文摘Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.
基金supported by the Innovation Program for 2011 College Graduates of Jiangsu Province(Grant No.CXZZ_0158)the National Natural Science Foundation of China(Grant No.51178107)
文摘A method of obtaining the large strain consolidation parameters of dredged clays considering the influence of the initial water content is investigated in this study. According to the test results of remolded clays with high initial water contents reported by Hong et al. (2010), a relationship between the void ratio (e) and effective stress (a3 is established. Furthermore, based on the available permeability data from the literature, a new relationship between the permeability coefficient (k) and the ratio (e/eL) of the void ratio to the void ratio at the liquid limit (eL) is proposed. The new proposed expression considering the initial water content improves the e-k equation established by Nagaraj et al. (1994). Finally, the influence of the initial void ratio and effective stress on the large strain consolidation coefficient g(e) defined by Gibson et al. (1981) and k/(1 +e) in large strain analysis is discussed. The results show that, under a constant effective stress, the value of k/(1 +e) increases with the initial void ratio. The large strain consolidation coefficient shows the law of segmentation change, which decreases with the increase of the effective stress when the effective stress is less than the remolded yield stress, but increases rapidly with the effective stress when the effective stress is larger than the remolded yield stress.
基金the Major Project of Hainan Province(No.ZDKJ2016008)the Key Project of Social Development in Hainan Province and Matching Fund from Sanya City of Hainan Province(No.ZDYF2016127)the National Natural Science Foundation of China(Nos.81371074,81670901).
文摘To the Editor:Since the first IgE monoclonal antibody was approved by the Food and Drug Administration in the USA in 2003,at least 14 kinds of targeted drugs are in the clinical application or pre-clinical trials.The two monoclonal antibodies targeting IgE are omalizumab and ligelizumab.Four drugs targeting interleukin 4(IL-4)or IL-4R are pascolizumab,pitrakinra,altrakincept,and dupilumab.Three monoclonal antibodies targeting IL-5/IL-5R are mepolizumab,reslizumab,and benralizumab.Two monoclonal antibodies targeting IL-13 are lebrikizumab and tralokinumab.The monoclonal antibody targeting thymic stromal lymphopoietin(TSLP)is tezepelumab.Th2 cytokine inhibitor is mesylate.These targeted drugs have achieved good results,but most of them are still in the pre-clinical stage.This article reviews the history,marketing situation,indications,contraindications,efficacy,and safety of these targeted drugs.
基金The present project was financially funded by Jilin Provincial Department of Education,China(JJKH20180377KJ)Jilin Provincial Department of Science and Technology,China(20190304108YY,20200404152YY,20200403047SF)TCM Science and Technology Project of Jilin Province,China(2019132).
文摘Panax quinquefolius L.(American ginseng)and Panax ginseng C.A.Meyer are famous herbal medicines.Accurate authentication of the species has grown to be a significant impact.This study aims to develop a PCR kit for the authentication of Panax quinquefolius L.and Panax ginseng based on the nuclear internal transcribed spacer 2(ITS2)gene with the improved PCR-restriction fragment length polymorphism(PCR-RFLP)method.The reagent components in the development work were prepared and determined by the kit consisting of the DNA extraction,PCR amplification,and restriction enzyme digestion systems.A total of 21 batches of Panax quinquefolius L.and Panax ginseng samples collected from different areas were validated.Their specificity,stability,and repeatability were evaluated.The purity of genomic DNA extracted was 1.73±0.13 according to the ratio of A_(260)/A_(280),and the mass concentration was 3.15±0.22μg/g(using the kit).PCR amplicons of Panax quinquefolius L.and Panax ginseng were 122 bp in length.After the PCR products were digested by restriction enzyme Hinf I,a distinct pattern exhibited in the species of Panax quinquefolius L.with two fragments of 40 bp and 80 bp respectively,whereas those from Panax ginseng in addition to adulterated samples could not.Evaluation confirmed that the DNA kit results were stable and repeatable after 10,15,and 20 freeze-thaw cycles:the evaluation was 100%specific.The DNA kit proposed in the study can be used for the identification of Panax quinquefolius L.