Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase...Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.展开更多
Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation ...Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.展开更多
We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis fac...We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase content were increased. Rats injected with Xuebijing, a Chinese herb compound preparation, exhibited normal cellular structure and morphology, dense neuronal cytoplasm, and decreased tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase expression at 24 hours following cardiopulmonary resuscitation. These data suggest that Xuebijing can attenuate neuronal injury induced by hypoxia and reperfusion during cardiopulmonary resuscitation.展开更多
Objective To investigate the protective effects of hydrogen peroxide preconditioning （HPP） on the pheochromocytoma （PC12） cells treated with 1-methyl-4-phenylpyridinium （MPP^＋） and to explore the potential mech...Objective To investigate the protective effects of hydrogen peroxide preconditioning （HPP） on the pheochromocytoma （PC12） cells treated with 1-methyl-4-phenylpyridinium （MPP^＋） and to explore the potential mechanisms. Methods The viability and apoptosis of PC 12 cells were determinded by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay and 4′,6′-diamidino-2-phenylindole （DAPI） staining, respectively. The expressions of 14-3-3 protein and phospholylated p38 mitogen-activated protein kinase （MAPK） were determined by Western blot. Enzyme-linked immunosorbent assay （ELISA） was used to measure the activity of extracellular signal-regulated protein kinase 1/2 （ERK1/2）. Results The cell viability decreased and the number of apoptotic cells increased dramatically in MPP^＋ group compared with that in Control group. HPP induced a significant increase in cell viability and a marked decrease in population of apoptotic cells of the MPP^＋- treated PC 12 cells, accompanied with up-regulation of 14-3-3 protein and increase of ERK 1/2 and p38 MAPK activities. The 14-3-3 protein expression was positively correlated with the phosphorylation of ERK1/2. Furthermore, inhibition of the ERK1/2 with PD98059 abolished the 14-3-3 protein up-regulation in PC 12 cells induced by HPP. Conclusion HPP protects PC 12 cells against MPP＋ toxicity by up-regulating 14-3-3 protein expression through the ERK1/2 and p38 MAPK signaling pathways.展开更多
The American Heart Association and the European Resuscitation Council recently recommend- ed that vasopressin can be used for cardiopulmonary resuscitation, instead of epinephrine. However, the guidelines do not discu...The American Heart Association and the European Resuscitation Council recently recommend- ed that vasopressin can be used for cardiopulmonary resuscitation, instead of epinephrine. However, the guidelines do not discuss the effects of vasopressin during cerebral resuscitation. In this study, we intraperitoneally injected epinephrine and/or vasopressin during cardiopul- monary resuscitation in a rat model of asphyxial cardiac arrest. The results demonstrated that, compared with epinephrine alone, the pathological damage to nerve cells was lessened, and the levels of c-Iun N-terminal kinase and p38 expression were significantly decreased in the hippo- campus after treatment with vasopressin alone or the vasopressin and epinephrine combination. No significant difference in resuscitation effects was detected between vasopressin alone and the vasopressin and epinephrine combination. These results suggest that vasopressin alone or the vasopressin and epinephrine combination suppress the activation of mitogen-activated protein kinase and c-Iun N-terminal kinase signaling pathways and reduce neuronal apoptosis during cardiopulmonary resuscitation.展开更多
Ninety male Wistar rats were selected under the ＂Guide for the Care and Use of Laboratory Animals＂ for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38...Ninety male Wistar rats were selected under the ＂Guide for the Care and Use of Laboratory Animals＂ for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38 MAPK （mitogen activated protein kinase） SB 203580 and JNK inhibitor SP 600125, and a control. Light microscopy, immunohistochemistry, and tensometry revealed that the inhibition of p38 or JNK cascades have modified the formation of the connective tissue scar. The degree of connective tissue growth in the area of surgical wound had been significantly reduced by the end of observation （30 d） as the SB 203580 was applied （% volume of collagen 43.60 （41.05 - 60.15） vs. 73.54 （66.87 - 78.01） in control, p = 0.002）. Conversely, when we have applied the JNK blocker, the density of collagen in scar tissue increased （78.14 （72.77 - 81.14）, p = 0.022 vs. control）. SB203580 inhibits the expression of p38, c-Jun and c-Fos. When we have used the JNK blocker, the expression of c-Fos and c-Jun decreased, but the expression of p38 increased. This determines the high functional activity of fibroblasts after using SP 600125. Obtained results show the importance of studying regulators of cell differentiation as potential drugs, which significantly affect the outcome of the pathological processes.展开更多
Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine(TCM)for conditions such as rheumatism,arthralgia,and gynecological ailments.It has been offici...Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine(TCM)for conditions such as rheumatism,arthralgia,and gynecological ailments.It has been officially recognized as a protected variety of TCM by the state.The aim of this study was to investigate the therapeutic potential of Qianjinba polysaccharide(QJBDT)in treating rheumatoid arthritis(RA)in mice,along with a preliminary exploration of its mechanisms for inhibiting RA in these animals.Kunming mice(KM)were randomly divided into several groups,including a normal group,a model group(LPS group),low-dose,medium-dose,and high-dose QJBDT groups,as well as a positive control group(TGP group),each consisting of 10 mice.To induce inflammation and create an RA model,type II collagen was injected into the right hind foot joint.Following a 7-day modeling period,various concentrations of QJBDT and the positive control drug total glycoside of peony were administered via gavage once a day for 21 consecutive days.Throughout the study,we monitored and recorded the mice's weight,measured foot swelling,and assessed the arthritis index on a weekly basis.We also conducted pathological examinations of joint tissues and analyzed the signal pathway of p38 mitogen-activated protein kinase(MAPK)as well as the protein expression of nuclear factor NF-κB in the mice’s right foot joint tissues.Additionally,we employed ELISA to detect the levels of interleukin-β(IL-β),IL-17,and tumor necrosis factor-α(TNF-α)in the mice’s serum.The results of this study revealed that QJBDT effectively reduced the degree of foot swelling and the arthritis index in collagen-induced arthritis mice while improving their weight loss(P<0.05).Furthermore,it alleviated the pathological damage observed in the mice’s joints.Notably,the expression of transcription factors p38 and NF-κB proteins was down-regulated(P<0.05),and the levels of inflammatory cytokines IL-β,IL-17,and TNF-αin the mice’s serum were decreased(P<0.05).In conclusion,this study demonstrated that polysaccharides could inhibit the expression of transcription factors p38 and NF-κB,reduce the production of inflammatory factors,and alleviate the progression of RA to a certain extent.展开更多
Although there are many therapeutic strategies such as surgery and chemotherapy,the prognosis of osteosarcoma(OS)is still far from being satisfactory.It is urgent to develop more effective,tolerable and safe drugs for...Although there are many therapeutic strategies such as surgery and chemotherapy,the prognosis of osteosarcoma(OS)is still far from being satisfactory.It is urgent to develop more effective,tolerable and safe drugs for the treatment of OS.In the present study,we investigated the anti-OS activity of Alantolactone(ALT),a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium,and probed the possible mechanism involved.We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells.Then,we validated that ALT reduced migration,decreased invasion possibly through reversing epithelial mesenchymal transition(EMT)process and suppressing Matrix metalloproteinases(MMPs).Moreover,we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells in vitro.In addition,we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model in vivo.Mechanistically,ALT inhibited the activity of Wnt/β-catenin and p38,ERK1/2 and JNK Mitogen Activated Protein Kinases(MAPKs)signal pathway.Notably,the combination of ALT and Wnt/β-catenin inhibitor,as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation,migration and invasion of OS cells.Collectively,our results validate the ALT may inhibit proliferation,metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/β-Catenin and MAPKs signaling pathways.展开更多
基金supported in part by grants from the Young Scientists Awards Foundation of Shandong Province of China,No.BS2013YY049the China Postdoctoral Science Foundation,No.2012M511036
文摘Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.
文摘Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.
基金a grant from the Science and Technology Department of Jilin Province,No. 200705172
文摘We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase content were increased. Rats injected with Xuebijing, a Chinese herb compound preparation, exhibited normal cellular structure and morphology, dense neuronal cytoplasm, and decreased tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase expression at 24 hours following cardiopulmonary resuscitation. These data suggest that Xuebijing can attenuate neuronal injury induced by hypoxia and reperfusion during cardiopulmonary resuscitation.
基金the National Natural Science Foundation of China (No. 30570627)
文摘Objective To investigate the protective effects of hydrogen peroxide preconditioning （HPP） on the pheochromocytoma （PC12） cells treated with 1-methyl-4-phenylpyridinium （MPP^＋） and to explore the potential mechanisms. Methods The viability and apoptosis of PC 12 cells were determinded by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay and 4′,6′-diamidino-2-phenylindole （DAPI） staining, respectively. The expressions of 14-3-3 protein and phospholylated p38 mitogen-activated protein kinase （MAPK） were determined by Western blot. Enzyme-linked immunosorbent assay （ELISA） was used to measure the activity of extracellular signal-regulated protein kinase 1/2 （ERK1/2）. Results The cell viability decreased and the number of apoptotic cells increased dramatically in MPP^＋ group compared with that in Control group. HPP induced a significant increase in cell viability and a marked decrease in population of apoptotic cells of the MPP^＋- treated PC 12 cells, accompanied with up-regulation of 14-3-3 protein and increase of ERK 1/2 and p38 MAPK activities. The 14-3-3 protein expression was positively correlated with the phosphorylation of ERK1/2. Furthermore, inhibition of the ERK1/2 with PD98059 abolished the 14-3-3 protein up-regulation in PC 12 cells induced by HPP. Conclusion HPP protects PC 12 cells against MPP＋ toxicity by up-regulating 14-3-3 protein expression through the ERK1/2 and p38 MAPK signaling pathways.
文摘The American Heart Association and the European Resuscitation Council recently recommend- ed that vasopressin can be used for cardiopulmonary resuscitation, instead of epinephrine. However, the guidelines do not discuss the effects of vasopressin during cerebral resuscitation. In this study, we intraperitoneally injected epinephrine and/or vasopressin during cardiopul- monary resuscitation in a rat model of asphyxial cardiac arrest. The results demonstrated that, compared with epinephrine alone, the pathological damage to nerve cells was lessened, and the levels of c-Iun N-terminal kinase and p38 expression were significantly decreased in the hippo- campus after treatment with vasopressin alone or the vasopressin and epinephrine combination. No significant difference in resuscitation effects was detected between vasopressin alone and the vasopressin and epinephrine combination. These results suggest that vasopressin alone or the vasopressin and epinephrine combination suppress the activation of mitogen-activated protein kinase and c-Iun N-terminal kinase signaling pathways and reduce neuronal apoptosis during cardiopulmonary resuscitation.
文摘Ninety male Wistar rats were selected under the ＂Guide for the Care and Use of Laboratory Animals＂ for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38 MAPK （mitogen activated protein kinase） SB 203580 and JNK inhibitor SP 600125, and a control. Light microscopy, immunohistochemistry, and tensometry revealed that the inhibition of p38 or JNK cascades have modified the formation of the connective tissue scar. The degree of connective tissue growth in the area of surgical wound had been significantly reduced by the end of observation （30 d） as the SB 203580 was applied （% volume of collagen 43.60 （41.05 - 60.15） vs. 73.54 （66.87 - 78.01） in control, p = 0.002）. Conversely, when we have applied the JNK blocker, the density of collagen in scar tissue increased （78.14 （72.77 - 81.14）, p = 0.022 vs. control）. SB203580 inhibits the expression of p38, c-Jun and c-Fos. When we have used the JNK blocker, the expression of c-Fos and c-Jun decreased, but the expression of p38 increased. This determines the high functional activity of fibroblasts after using SP 600125. Obtained results show the importance of studying regulators of cell differentiation as potential drugs, which significantly affect the outcome of the pathological processes.
基金Shandong Provincial Key Project of TCM Science and Technology(Grant No.2021Z051)Shandong Medical and Health Science and Technology Development Program(Grant No.202102040972)supported by Binzhou Medical College Student Innovation and Entrepreneurship Training Program(Grant No.X202210440354).
文摘Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine(TCM)for conditions such as rheumatism,arthralgia,and gynecological ailments.It has been officially recognized as a protected variety of TCM by the state.The aim of this study was to investigate the therapeutic potential of Qianjinba polysaccharide(QJBDT)in treating rheumatoid arthritis(RA)in mice,along with a preliminary exploration of its mechanisms for inhibiting RA in these animals.Kunming mice(KM)were randomly divided into several groups,including a normal group,a model group(LPS group),low-dose,medium-dose,and high-dose QJBDT groups,as well as a positive control group(TGP group),each consisting of 10 mice.To induce inflammation and create an RA model,type II collagen was injected into the right hind foot joint.Following a 7-day modeling period,various concentrations of QJBDT and the positive control drug total glycoside of peony were administered via gavage once a day for 21 consecutive days.Throughout the study,we monitored and recorded the mice's weight,measured foot swelling,and assessed the arthritis index on a weekly basis.We also conducted pathological examinations of joint tissues and analyzed the signal pathway of p38 mitogen-activated protein kinase(MAPK)as well as the protein expression of nuclear factor NF-κB in the mice’s right foot joint tissues.Additionally,we employed ELISA to detect the levels of interleukin-β(IL-β),IL-17,and tumor necrosis factor-α(TNF-α)in the mice’s serum.The results of this study revealed that QJBDT effectively reduced the degree of foot swelling and the arthritis index in collagen-induced arthritis mice while improving their weight loss(P<0.05).Furthermore,it alleviated the pathological damage observed in the mice’s joints.Notably,the expression of transcription factors p38 and NF-κB proteins was down-regulated(P<0.05),and the levels of inflammatory cytokines IL-β,IL-17,and TNF-αin the mice’s serum were decreased(P<0.05).In conclusion,this study demonstrated that polysaccharides could inhibit the expression of transcription factors p38 and NF-κB,reduce the production of inflammatory factors,and alleviate the progression of RA to a certain extent.
基金The present research was supported by the National Natural Science Foundation of China(No.81874001)the Natural Science Foundation Project of Chongqing Science and Technology Commission(No.cstc2017jcyjAX0196).
文摘Although there are many therapeutic strategies such as surgery and chemotherapy,the prognosis of osteosarcoma(OS)is still far from being satisfactory.It is urgent to develop more effective,tolerable and safe drugs for the treatment of OS.In the present study,we investigated the anti-OS activity of Alantolactone(ALT),a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium,and probed the possible mechanism involved.We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells.Then,we validated that ALT reduced migration,decreased invasion possibly through reversing epithelial mesenchymal transition(EMT)process and suppressing Matrix metalloproteinases(MMPs).Moreover,we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells in vitro.In addition,we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model in vivo.Mechanistically,ALT inhibited the activity of Wnt/β-catenin and p38,ERK1/2 and JNK Mitogen Activated Protein Kinases(MAPKs)signal pathway.Notably,the combination of ALT and Wnt/β-catenin inhibitor,as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation,migration and invasion of OS cells.Collectively,our results validate the ALT may inhibit proliferation,metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/β-Catenin and MAPKs signaling pathways.
