Chronic loss of sleep damages health and disturbs the quality of life.Long-lasting sleep deprivation(SD)as well as sleep abnormalities are substantial risk factors for major depressive disorder,although the underlying...Chronic loss of sleep damages health and disturbs the quality of life.Long-lasting sleep deprivation(SD)as well as sleep abnormalities are substantial risk factors for major depressive disorder,although the underlying mechanisms are not clear.Here,we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP,which activates astroglial P2X7 receptors(P2X7Rs).Activated P2X7Rs,in turn,selectively down-regulated the expression of 5-HT2B receptors(5-HT2BRs)in astrocytes.Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3 a in astrocytes,but not in neurons.The overexpression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs.Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2.This latter cascade promoted the release of arachidonic acid and prostaglandin E2.The depression-like behaviors induced by SD were alleviated in P2X7R-KO mice.Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders.展开更多
Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive as...Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive astrocytes,inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1(UCHL1)-proteasome system post-SCI.However,the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear.Here,we revealed that C3a/C3a receptor(C3aR)signaling activated NF-κB p65,which in turn inhibited Nrf2 activity and UCHL1 expression,resulting in diminished proteasome activity and the accumulation of protein aggregates,and ultimately impaired NSC activation.Both knockdown of NF-κB p65 and Nrf2 upregulation restored UCHL1 expression and proteasome activity in vitro,promoting NSC activation by enhancing protein aggregate clearance.Mechanistically,we found that NF-κB p65 regulated Nrf2 activity through a dual mechanism:(1)promoting Keap1-dependent ubiquitination and proteasome degradation of Nrf2;(2)inhibiting protein kinase C-mediated Nrf2 phosphorylation and nuclear translocation.Using the dual-luciferase reporter assay and chromatin immunoprecipitation(ChIP)analysis,we further identified UCHL1 as a direct transcriptional target of Nrf2.Importantly,in vivo experiments using SCI mice confirmed that either C3aR blockade,NF-κB p65 knockdown,or Nrf2 overexpression could rescue SCI-induced UCHL1 downregulation.Together,this study uncovers the C3a-NF-κB p65-Nrf2-UCHL1-proteasome axis as a critical regulator of NSC activation after SCI.This may provide novel molecular targets and intervention strategies for SCI repair.展开更多
Objective:Multiple sclerosis(MS)is a chronic inflammatory demyelinating disease of the central nervous system(CNS).Soluble interleukin-2 receptor alpha(sIL-2Rα)has been implicated inMS pathogenesis,but its mechanisms...Objective:Multiple sclerosis(MS)is a chronic inflammatory demyelinating disease of the central nervous system(CNS).Soluble interleukin-2 receptor alpha(sIL-2Rα)has been implicated inMS pathogenesis,but its mechanisms remain unclear.This study investigates how sIL-2Rαexacerbates MS by modulating microglial activation and antibody-dependent cellular cytotoxicity(ADCC)in an experimental autoimmune encephalomyelitis(EAE)mouse model.Methods:Female C57BL/6J mice were induced with EAE and treated with sIL-2Rα.Clinical symptoms,histopathology,and molecular changes were analyzed.Microglial activation was assessed via immunohistochemistry,Western blot,and RNA sequencing.In vitro,ADCC-mediated oligodendrocyte injury was evaluated using Fc receptor inhibition and PI3K-Akt pathway blockade.Results:sIL-2Rα accelerated EAE onset and severity,increasingmicroglial M1 polarization and CNS inflammation.RNA-seq revealed PI3K-Akt pathway activation,upregulating Fc receptors(FcγR)on microglia,which enhanced ADCC against oligodendrocytes(p<0.001).Inhibiting FcγR or PI3K-Akt reduced oligodendrocyte damage.Conclusion:sIL-2Rαexacerbates MS by activating microglia via the PI3K-Aktaxis,promoting ADCC and demyelination.Targeting this pathway may offer novel therapeutic strategies for MS.展开更多
The nuclear receptors pregnane X receptor(PXR) and constitutive androstane receptor(CAR) were cloned and/or established as xenobiotic receptors in 1998.Due to their activities in the transcriptional regulation of phas...The nuclear receptors pregnane X receptor(PXR) and constitutive androstane receptor(CAR) were cloned and/or established as xenobiotic receptors in 1998.Due to their activities in the transcriptional regulation of phase I and phase II enzymes as well as drug transporters,PXR and CAR have been defined as the master regulators of xenobiotic responses.The discovery of PXR and CAR provides the essential molecular basis by which drugs and other xenobiotic compounds regulate the expression of xenobiotic enzymes and transporters.This article is intended to provide a historical overview on the discovery of PXR and CAR as xenobiotic receptors.展开更多
Phagocytosis of opsonized pathogens by circulating non-adherent neutrophils is an essential step in host defense, which when overwhelmed contributes to sepsis. To investigate the role played by ligation of complement ...Phagocytosis of opsonized pathogens by circulating non-adherent neutrophils is an essential step in host defense, which when overwhelmed contributes to sepsis. To investigate the role played by ligation of complement receptors CR3 and CR4 in non-adherent neutrophils, we designed a novel assay system utilizing dual optical traps, respectively, holding a suspended unactivated cell and presenting a specific ligand-coated bead to the cell surface. We chose anti-CD 18 as an example ligand, mimicking the bacterial opsonizing complement fragment iC3b. Presentation of anti-CD 18-coated beads elicited both pseudopodial protrusion and subsequent phagocytosis. This is in sharp contrast to previously reported responses of adherent neutrophils, which phagocytize opsonized particles without pseudopod formation. We used this same new assay to probe actomyosin pathways in the neutrophil＇s pseudopodial and phagocytic response. Disruption of actin or inhibition of myosin light-chain kinase dose-dependently reduced pseudopod formation and phagocytosis rates. In summary, i） the new dual trap assay can be used to study the responses of suspended neutrophils to a variety of ligands, and ii） in a first application of this technique, we found that local ligation of CR3/4 in unactivated neutrophils in suspension induces pseudopod formation and phagocytosis at that site, and that these events occur via an actomyosindependent pathway.展开更多
Objective： Our previous study has showed that △DNMT3B is the predominant form of DNMT3B in non-small cell lung cancer （NSCLC）. In this study, we aimed to explore the expression patterns of the △DNMT3B variants in...Objective： Our previous study has showed that △DNMT3B is the predominant form of DNMT3B in non-small cell lung cancer （NSCLC）. In this study, we aimed to explore the expression patterns of the △DNMT3B variants in breast cancer and to identify whether the pattern was similar to that in NSCLC or not and its clinical significance. Methods： Expression of seven △DNMT3B variants in 59 breast cancer and the corresponding normal tissue was measured using RT-PCR. The correlations between the expressions of △DNMT3B variants and the clinical parameters including ER/PR status, clincopathologic feature and survivals were analyzed. Results： There were significant differences in the expression ratios of △DNMT3B1-7 variants between breast cancer tissues and normal tissues （P〈0.001）. The positive ratio of △DNMT3B1-7 variants were 66%, 71%, 17%, 51%, 76.2%, 50% and 61% in tumor tissue, respectively; while 16%, 8.4%, 3.38%, 3.38%, 11.8%, 13.5% and 5.08% in the corresponding normal tissue, which was different from the pattern of △DNMT3B1-7 expression in NSCLC （62%, 76%, 2.5%, 46%, 18%, 27% and 16% in tumor tissue, respectively; while 18%, 11%, 0%, 3.3%, 0%, 0% and 0% in normal lung tissue, respectively; P〈0.0001）. Expressions of △DNMT3B2, 3B4 and 3B7 were higher in the patients with negative estrogen receptor （ER） than those with positive estrogen receptor （P=0.035, P=0.0141 and P=0.0219, respectively）. △DNMT3B7 expression was higher for the patients with negative progestogen receptor （PR） compared to those with positive progestogen receptor （P=0.0379）. Expression ratio of △DNMT3B5 in stage Ⅲ tumors is lower than that in stage Ⅰ/Ⅱ ones （P= 0.041）. But we did not find any relation between the △DNMT3B variants and the patients＇ survival. Conclusion： The pattern of △DNMT3B variants in breast cancer is different from that in NSCLC. Expressions of △DNMT3B2, 3B4 and 3B7 are associated with estrogen receptors status. While △DNMT3B7 is associated with progestogen receptor. No relation between the △DNMT3B variants and the patients＇ survival were found.展开更多
Objective To study the effect of Asparagus officinalis polysaccharide on the number and activity of erythrocyte complement receptor 1 in S180 mice.Methods Red blood cells from mice venous blood were labeled by rat ant...Objective To study the effect of Asparagus officinalis polysaccharide on the number and activity of erythrocyte complement receptor 1 in S180 mice.Methods Red blood cells from mice venous blood were labeled by rat anti-mouse CD35 monoclonal antibody and FITC-conjugated goat anti-mouse antibody.Using flow cytometry,we determined the number of ECR1.Using microscope,we studied the adherence between erythrocyte immunity and C3b receptor or tumor-cell by RBC-C3bRR and DTER.Results Comparing the mean value of the number of CR1 on each RBC of high and middle groups with control groups,the mean value of the number of CR1,RBC-C3bRR and DTER of Asparagus officinalis polysaccharide groups are increased significantly.Conclusions Asparagus officinalis polysaccharide can improve the erythrocyte function of S180 mice,which may be one of its most important antitumor mechanisms.展开更多
A plant material consisted by Family Poaceae was fermented by Yeast and Lactobaccilli (U-164). This material was proved by as safe in animal safety experiment for oral administration. In order to prove the effect of U...A plant material consisted by Family Poaceae was fermented by Yeast and Lactobaccilli (U-164). This material was proved by as safe in animal safety experiment for oral administration. In order to prove the effect of U-164 against physiological function, the animal and human trials were set up to look into mainly leukocyte functions. In animal experiment, anti-oxidative effect and antibody response in immune-compromised host and diabetes meritus were made up. For human use, peripheral lymphocyte in number and subset ratio were followed up to one month after administration. In order to understand its effect, human complement component analysis was made by immune-electrophoresis. Our results showed that U-164 augmented the level of lymphocytes, while U-164 down regulated the level of granulocytes. In our clinical study with 19 healthy volunteers, granulocyte and lymphocyte ratio was obtained as neutral in peripheral blood being increased significantly 30 days after the ingestion of U-164. In experimental animal study, the compromised host as well as normal animal was administered with cancer chemotherapeutic agent (Mytomycin-C). Our observations showed against antibody producing cell, this material recovered the antibody production in the host compromising the immure responsiveness. We also proposed an idea that U-164 exhibited tonic effects via activating complement components. Moreover, we tried to access further to the anti-oxidative activities of this U-164. This modification brought to the significant lifted up for anti-oxidative activity for phagocytic cell.展开更多
Objective:To investigate the hemostatic effect of modified Sijunzi Granules(MSG)in primary immune thrombocytopenia(ITP)zebrafish model and explore the potential mechanism.Methods:AB strain wild type zebrafish were tre...Objective:To investigate the hemostatic effect of modified Sijunzi Granules(MSG)in primary immune thrombocytopenia(ITP)zebrafish model and explore the potential mechanism.Methods:AB strain wild type zebrafish were treated with simvastatin(6μmol/L)for 24 h to establish the hemorrhage model(model control group).The zebrafish were treated with MSG at different doses(55.6,167,and 500μg/mL),respectively.The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate.5-hydroxytryptamine(5-HT)content was determined using enzyme-linked immunosorbent assay(ELISA)assay.The expressions of5-HT2aR,5-HT2bR,and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR).The protein expressions of protein kinase B(Akt),p-Akt,extracellular regulated protein kinases(Erk),and p-Erk were examined using Western blot analysis.Results:The intestinal bleeding rate was 37%,40%,and 80%in the55.6,167,and 500μg/mL dose of MSG,respectively,in which 55.6 and 167μg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group(70%,P<0.05).Significantly higher hemostatic rates were also observed in the 55.6μg/mL(54%)and 167μg/mL(52%)MSG dose groups(P<0.05).MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR,5-HT2bR,and SERT(P<0.05).In addition,caspase3/7 activity was inhibited(P<0.05).Significant increase in p-Akt and p-Erk was also detected after treatment with MSG(P<0.05).Conclusions:MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors,which may provide evidence for the treatment of ITP.展开更多
目的探讨膝关节骨关节炎患者血清可溶性核因子-κB受体激活剂配体(soluble receptor regulator of the nuclear factor-kappa B ligand,sRANKL)、巨噬细胞炎性蛋白-1β(macrophage inflammatory protein-1β,MIP-1β)、C1q肿瘤坏死因子...目的探讨膝关节骨关节炎患者血清可溶性核因子-κB受体激活剂配体(soluble receptor regulator of the nuclear factor-kappa B ligand,sRANKL)、巨噬细胞炎性蛋白-1β(macrophage inflammatory protein-1β,MIP-1β)、C1q肿瘤坏死因子相关蛋白-3(C1q/tumor necrosis factor-related protein 3,CTRP3)水平与病情严重程度及术后疾病转归的相关性。方法根据纳入及排除标准,选取2022年6月至2024年7月大庆油田总医院进行关节镜手术的106例膝关节骨关节炎患者为患病组,其中男56例,女50例;年龄56~73岁,平均(65.95±6.89)岁。根据MRI分级并结合患者病情程度分为2级组37例,3级组44例,4级组25例。根据术后疾病转归情况分为预后良好组74例,预后不良组32例。选择同期在本院体检的健康者106例为对照组,其中男53例,女53例;年龄53~72岁,平均(65.02±6.77)岁。经ELISA检测后,比较两组的血清sRANKL、MIP-1β、CTRP3水平,Spearman等级相关分析血清sRANKL、MIP-1β、CTRP3水平与病情严重程度相关性。Logistic回归分析患者预后不良的影响因素,绘制受试者工作特征(receiver operating characteristic,ROC)曲线分析血清sRANKL、MIP-1β、CTRP3对疾病转归的预测价值。结果患病组的血清sRANKL、MIP-1β显著高于对照组,CTRP3显著低于对照组(P<0.05)。3级、4级组的血清sRANKL、MIP-1β水平显著高于2级组,CTRP3水平显著低于2级组(P<0.05);且4级组的血清sRANKL、MIP-1β水平显著高于3级组,CTRP3水平显著低于3级组(P<0.05);sRANKL、MIP-1β与病情程度呈正相关(r=0.523,0.503,P<0.05),CTRP3水平与病情程度呈负相关(r=-0.508,P<0.05)。预后不良组受累间室个数、sRANKL、MIP-1β水平显著高于预后良好组(P<0.05),CTRP3显著低于预后良好组(P<0.05)。血清sRANKL、MIP-1β、CTRP3联合预测患者预后的曲线下面积(area under curve,AUC)为0.962,显著优于sRANKL(Z=2.532,P=0.011)、MIP-1β(Z=2.595,P=0.010)、CTRP3(Z=2.950,P=0.003)单独预测。sRANKL、MIP-1β水平升高是影响患者预后不良的危险因素,CTRP3水平升高是影响患者预后不良的保护因素(P<0.05)。结论膝关节骨关节炎患者血清sRANKL、MIP-1β水平升高,CTRP3水平降低,与病情程度及术后疾病转归具有一定相关性。展开更多
基金the National Natural Science Foundation of China(81871852,81200935,81671862,and 81871529)Liaoning Revitalization Talents Program(XLYC1807137)+1 种基金the Scientific Research Foundation for Overseas Scholars of the Education Ministry of China(20151098)the Natural Science Foundation of Liaoning Province,China(20170541030)。
文摘Chronic loss of sleep damages health and disturbs the quality of life.Long-lasting sleep deprivation(SD)as well as sleep abnormalities are substantial risk factors for major depressive disorder,although the underlying mechanisms are not clear.Here,we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP,which activates astroglial P2X7 receptors(P2X7Rs).Activated P2X7Rs,in turn,selectively down-regulated the expression of 5-HT2B receptors(5-HT2BRs)in astrocytes.Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3 a in astrocytes,but not in neurons.The overexpression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs.Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2.This latter cascade promoted the release of arachidonic acid and prostaglandin E2.The depression-like behaviors induced by SD were alleviated in P2X7R-KO mice.Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders.
基金supported by the National Natural Science Foundation of China(82071362 and 82270669)Key Project of the Regional Joint Fund of Guangdong Province(2023B1515120077)+3 种基金Basic Research Program of Shenzhen Science and Technology Innovation Commission(JCYJ20210324123001003 and JCYJ20220530144801003)Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research(ZDSYS20230626091402006)the Innovation and Entrepreneurship Training Program for College Students,Sun Yat-sen University(20242150)the Leading Innovation and Entrepreneurship Team Program of Zhejiang Province,China(2023R01005).
文摘Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive astrocytes,inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1(UCHL1)-proteasome system post-SCI.However,the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear.Here,we revealed that C3a/C3a receptor(C3aR)signaling activated NF-κB p65,which in turn inhibited Nrf2 activity and UCHL1 expression,resulting in diminished proteasome activity and the accumulation of protein aggregates,and ultimately impaired NSC activation.Both knockdown of NF-κB p65 and Nrf2 upregulation restored UCHL1 expression and proteasome activity in vitro,promoting NSC activation by enhancing protein aggregate clearance.Mechanistically,we found that NF-κB p65 regulated Nrf2 activity through a dual mechanism:(1)promoting Keap1-dependent ubiquitination and proteasome degradation of Nrf2;(2)inhibiting protein kinase C-mediated Nrf2 phosphorylation and nuclear translocation.Using the dual-luciferase reporter assay and chromatin immunoprecipitation(ChIP)analysis,we further identified UCHL1 as a direct transcriptional target of Nrf2.Importantly,in vivo experiments using SCI mice confirmed that either C3aR blockade,NF-κB p65 knockdown,or Nrf2 overexpression could rescue SCI-induced UCHL1 downregulation.Together,this study uncovers the C3a-NF-κB p65-Nrf2-UCHL1-proteasome axis as a critical regulator of NSC activation after SCI.This may provide novel molecular targets and intervention strategies for SCI repair.
基金supported by the National Natural Science Foundation of China[82201489,2022].
文摘Objective:Multiple sclerosis(MS)is a chronic inflammatory demyelinating disease of the central nervous system(CNS).Soluble interleukin-2 receptor alpha(sIL-2Rα)has been implicated inMS pathogenesis,but its mechanisms remain unclear.This study investigates how sIL-2Rαexacerbates MS by modulating microglial activation and antibody-dependent cellular cytotoxicity(ADCC)in an experimental autoimmune encephalomyelitis(EAE)mouse model.Methods:Female C57BL/6J mice were induced with EAE and treated with sIL-2Rα.Clinical symptoms,histopathology,and molecular changes were analyzed.Microglial activation was assessed via immunohistochemistry,Western blot,and RNA sequencing.In vitro,ADCC-mediated oligodendrocyte injury was evaluated using Fc receptor inhibition and PI3K-Akt pathway blockade.Results:sIL-2Rα accelerated EAE onset and severity,increasingmicroglial M1 polarization and CNS inflammation.RNA-seq revealed PI3K-Akt pathway activation,upregulating Fc receptors(FcγR)on microglia,which enhanced ADCC against oligodendrocytes(p<0.001).Inhibiting FcγR or PI3K-Akt reduced oligodendrocyte damage.Conclusion:sIL-2Rαexacerbates MS by activating microglia via the PI3K-Aktaxis,promoting ADCC and demyelination.Targeting this pathway may offer novel therapeutic strategies for MS.
基金supported in part by the Joseph Koslow Endowed Professorship from the University of Pittsburgh School of Pharmacy
文摘The nuclear receptors pregnane X receptor(PXR) and constitutive androstane receptor(CAR) were cloned and/or established as xenobiotic receptors in 1998.Due to their activities in the transcriptional regulation of phase I and phase II enzymes as well as drug transporters,PXR and CAR have been defined as the master regulators of xenobiotic responses.The discovery of PXR and CAR provides the essential molecular basis by which drugs and other xenobiotic compounds regulate the expression of xenobiotic enzymes and transporters.This article is intended to provide a historical overview on the discovery of PXR and CAR as xenobiotic receptors.
文摘Phagocytosis of opsonized pathogens by circulating non-adherent neutrophils is an essential step in host defense, which when overwhelmed contributes to sepsis. To investigate the role played by ligation of complement receptors CR3 and CR4 in non-adherent neutrophils, we designed a novel assay system utilizing dual optical traps, respectively, holding a suspended unactivated cell and presenting a specific ligand-coated bead to the cell surface. We chose anti-CD 18 as an example ligand, mimicking the bacterial opsonizing complement fragment iC3b. Presentation of anti-CD 18-coated beads elicited both pseudopodial protrusion and subsequent phagocytosis. This is in sharp contrast to previously reported responses of adherent neutrophils, which phagocytize opsonized particles without pseudopod formation. We used this same new assay to probe actomyosin pathways in the neutrophil＇s pseudopodial and phagocytic response. Disruption of actin or inhibition of myosin light-chain kinase dose-dependently reduced pseudopod formation and phagocytosis rates. In summary, i） the new dual trap assay can be used to study the responses of suspended neutrophils to a variety of ligands, and ii） in a first application of this technique, we found that local ligation of CR3/4 in unactivated neutrophils in suspension induces pseudopod formation and phagocytosis at that site, and that these events occur via an actomyosindependent pathway.
基金supported by the grants from the National Natural Science Foundation of China (No.30572104,30772472)
文摘Objective： Our previous study has showed that △DNMT3B is the predominant form of DNMT3B in non-small cell lung cancer （NSCLC）. In this study, we aimed to explore the expression patterns of the △DNMT3B variants in breast cancer and to identify whether the pattern was similar to that in NSCLC or not and its clinical significance. Methods： Expression of seven △DNMT3B variants in 59 breast cancer and the corresponding normal tissue was measured using RT-PCR. The correlations between the expressions of △DNMT3B variants and the clinical parameters including ER/PR status, clincopathologic feature and survivals were analyzed. Results： There were significant differences in the expression ratios of △DNMT3B1-7 variants between breast cancer tissues and normal tissues （P〈0.001）. The positive ratio of △DNMT3B1-7 variants were 66%, 71%, 17%, 51%, 76.2%, 50% and 61% in tumor tissue, respectively; while 16%, 8.4%, 3.38%, 3.38%, 11.8%, 13.5% and 5.08% in the corresponding normal tissue, which was different from the pattern of △DNMT3B1-7 expression in NSCLC （62%, 76%, 2.5%, 46%, 18%, 27% and 16% in tumor tissue, respectively; while 18%, 11%, 0%, 3.3%, 0%, 0% and 0% in normal lung tissue, respectively; P〈0.0001）. Expressions of △DNMT3B2, 3B4 and 3B7 were higher in the patients with negative estrogen receptor （ER） than those with positive estrogen receptor （P=0.035, P=0.0141 and P=0.0219, respectively）. △DNMT3B7 expression was higher for the patients with negative progestogen receptor （PR） compared to those with positive progestogen receptor （P=0.0379）. Expression ratio of △DNMT3B5 in stage Ⅲ tumors is lower than that in stage Ⅰ/Ⅱ ones （P= 0.041）. But we did not find any relation between the △DNMT3B variants and the patients＇ survival. Conclusion： The pattern of △DNMT3B variants in breast cancer is different from that in NSCLC. Expressions of △DNMT3B2, 3B4 and 3B7 are associated with estrogen receptors status. While △DNMT3B7 is associated with progestogen receptor. No relation between the △DNMT3B variants and the patients＇ survival were found.
文摘Objective To study the effect of Asparagus officinalis polysaccharide on the number and activity of erythrocyte complement receptor 1 in S180 mice.Methods Red blood cells from mice venous blood were labeled by rat anti-mouse CD35 monoclonal antibody and FITC-conjugated goat anti-mouse antibody.Using flow cytometry,we determined the number of ECR1.Using microscope,we studied the adherence between erythrocyte immunity and C3b receptor or tumor-cell by RBC-C3bRR and DTER.Results Comparing the mean value of the number of CR1 on each RBC of high and middle groups with control groups,the mean value of the number of CR1,RBC-C3bRR and DTER of Asparagus officinalis polysaccharide groups are increased significantly.Conclusions Asparagus officinalis polysaccharide can improve the erythrocyte function of S180 mice,which may be one of its most important antitumor mechanisms.
文摘A plant material consisted by Family Poaceae was fermented by Yeast and Lactobaccilli (U-164). This material was proved by as safe in animal safety experiment for oral administration. In order to prove the effect of U-164 against physiological function, the animal and human trials were set up to look into mainly leukocyte functions. In animal experiment, anti-oxidative effect and antibody response in immune-compromised host and diabetes meritus were made up. For human use, peripheral lymphocyte in number and subset ratio were followed up to one month after administration. In order to understand its effect, human complement component analysis was made by immune-electrophoresis. Our results showed that U-164 augmented the level of lymphocytes, while U-164 down regulated the level of granulocytes. In our clinical study with 19 healthy volunteers, granulocyte and lymphocyte ratio was obtained as neutral in peripheral blood being increased significantly 30 days after the ingestion of U-164. In experimental animal study, the compromised host as well as normal animal was administered with cancer chemotherapeutic agent (Mytomycin-C). Our observations showed against antibody producing cell, this material recovered the antibody production in the host compromising the immure responsiveness. We also proposed an idea that U-164 exhibited tonic effects via activating complement components. Moreover, we tried to access further to the anti-oxidative activities of this U-164. This modification brought to the significant lifted up for anti-oxidative activity for phagocytic cell.
基金Supported by Natural Science Foundation of Zhejiang Province(No.LQ23H270001)。
文摘Objective:To investigate the hemostatic effect of modified Sijunzi Granules(MSG)in primary immune thrombocytopenia(ITP)zebrafish model and explore the potential mechanism.Methods:AB strain wild type zebrafish were treated with simvastatin(6μmol/L)for 24 h to establish the hemorrhage model(model control group).The zebrafish were treated with MSG at different doses(55.6,167,and 500μg/mL),respectively.The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate.5-hydroxytryptamine(5-HT)content was determined using enzyme-linked immunosorbent assay(ELISA)assay.The expressions of5-HT2aR,5-HT2bR,and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR).The protein expressions of protein kinase B(Akt),p-Akt,extracellular regulated protein kinases(Erk),and p-Erk were examined using Western blot analysis.Results:The intestinal bleeding rate was 37%,40%,and 80%in the55.6,167,and 500μg/mL dose of MSG,respectively,in which 55.6 and 167μg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group(70%,P<0.05).Significantly higher hemostatic rates were also observed in the 55.6μg/mL(54%)and 167μg/mL(52%)MSG dose groups(P<0.05).MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR,5-HT2bR,and SERT(P<0.05).In addition,caspase3/7 activity was inhibited(P<0.05).Significant increase in p-Akt and p-Erk was also detected after treatment with MSG(P<0.05).Conclusions:MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors,which may provide evidence for the treatment of ITP.
文摘目的探讨膝关节骨关节炎患者血清可溶性核因子-κB受体激活剂配体(soluble receptor regulator of the nuclear factor-kappa B ligand,sRANKL)、巨噬细胞炎性蛋白-1β(macrophage inflammatory protein-1β,MIP-1β)、C1q肿瘤坏死因子相关蛋白-3(C1q/tumor necrosis factor-related protein 3,CTRP3)水平与病情严重程度及术后疾病转归的相关性。方法根据纳入及排除标准,选取2022年6月至2024年7月大庆油田总医院进行关节镜手术的106例膝关节骨关节炎患者为患病组,其中男56例,女50例;年龄56~73岁,平均(65.95±6.89)岁。根据MRI分级并结合患者病情程度分为2级组37例,3级组44例,4级组25例。根据术后疾病转归情况分为预后良好组74例,预后不良组32例。选择同期在本院体检的健康者106例为对照组,其中男53例,女53例;年龄53~72岁,平均(65.02±6.77)岁。经ELISA检测后,比较两组的血清sRANKL、MIP-1β、CTRP3水平,Spearman等级相关分析血清sRANKL、MIP-1β、CTRP3水平与病情严重程度相关性。Logistic回归分析患者预后不良的影响因素,绘制受试者工作特征(receiver operating characteristic,ROC)曲线分析血清sRANKL、MIP-1β、CTRP3对疾病转归的预测价值。结果患病组的血清sRANKL、MIP-1β显著高于对照组,CTRP3显著低于对照组(P<0.05)。3级、4级组的血清sRANKL、MIP-1β水平显著高于2级组,CTRP3水平显著低于2级组(P<0.05);且4级组的血清sRANKL、MIP-1β水平显著高于3级组,CTRP3水平显著低于3级组(P<0.05);sRANKL、MIP-1β与病情程度呈正相关(r=0.523,0.503,P<0.05),CTRP3水平与病情程度呈负相关(r=-0.508,P<0.05)。预后不良组受累间室个数、sRANKL、MIP-1β水平显著高于预后良好组(P<0.05),CTRP3显著低于预后良好组(P<0.05)。血清sRANKL、MIP-1β、CTRP3联合预测患者预后的曲线下面积(area under curve,AUC)为0.962,显著优于sRANKL(Z=2.532,P=0.011)、MIP-1β(Z=2.595,P=0.010)、CTRP3(Z=2.950,P=0.003)单独预测。sRANKL、MIP-1β水平升高是影响患者预后不良的危险因素,CTRP3水平升高是影响患者预后不良的保护因素(P<0.05)。结论膝关节骨关节炎患者血清sRANKL、MIP-1β水平升高,CTRP3水平降低,与病情程度及术后疾病转归具有一定相关性。
