Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have s...Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have shown that endothelial activation contributes to the pathophysiology of cardiovascular diseases such as atherosclero- sis, diabetic vasculopathy, heart failure and hypertension. In the present study, the effects of MLB on endothelial activation were investigated. Lipopolysaccharide （LPS） 1 mg L^-1 was employed to induce endothelial activation, which was determined by relative gene expression and endothelial adhesion assay. Results showed that pretreatment with MLB attenuated LPS-induced ICAM1, VCAM1 and TNF-α upregulation in human dermal microvascular endo- thelial cells （HMEC-1） in dose-dependent manner, which contributed to the reduction of THP-1 adhesion to HMEC-1. Furthermore, it was revealed that 100 μmol · L^-1 MLB significantly decreased the nuclear translocation of NF-KB p65, a critical transcription factor in LPS-indueed inflammatory response, through the inhibition of IKBμ degradation. Besides, the transcriptional activity of NF-KB p65 was also inhibited by the pretreatment of MLB. Mo- reover, MLB pretreatment considerably inhibited LPS-induced p38 phosphorylation, which at least partly contribu- ted to the reduction of ICAM1 expression. In conclusion, these findings suggest that MLB inhibits LPS-induced nu- clear translocation and transcripitional activity of NF-KB, thus attenuates the increased expression of adhesion mole- cules and inflammatory factors, protects endothelial cells from LPS-induced activation.展开更多
This study aimed to explore the effect of DT-13 （25（R,S）-ruscogenin- 1-O- [ β-d-glucopyranosyl- （1→2） ] [ β-d-xylopyranosyl-（ 1→3） 1-β -d- fucopyranoside） on tumor necrosis factor （TNF）-α-induced vascu...This study aimed to explore the effect of DT-13 （25（R,S）-ruscogenin- 1-O- [ β-d-glucopyranosyl- （1→2） ] [ β-d-xylopyranosyl-（ 1→3） 1-β -d- fucopyranoside） on tumor necrosis factor （TNF）-α-induced vascular inflamma- tion and the potential molecular mechanisms. In vitro, DT-β suppressed TNF-α-induced adhesion and migration of human umbilical vein endothelial cells （HUVECs） by inhibiting the expression of intercellular adhesion molecule-1 （ ICAM-1 ） and vascular cell adhesion molecule-1 （VCAM-1）. DT-β markedly suppressed NF-KB p65 phosphoryl- ation, and when NF-KB p65 was over-expressed, the inhibitory effect of DT-β on adhesion molecular decreased. DT-β also suppressed TNF-α induced luciferase activities of ICAM-1 and VCAM-1 promoter containing NF-KB binding sites. Furthermore DT-β markedly suppressed p38 phosphorylation and Src degradation induced by TNF-α DT-β at 4 mg·kg- 1 prevented vascular , whereas had no significant effect on ERK and JNK activation. In-vivo, inflammation and the expression of adhesion molecules induced by TNF-α in mice. These findings suggest that DT- β abrogates vascular inflammation by down-regulating adhesion molecules associated with modulating the NF-KB, p38MAPK, Src signaling pathways, and NF-KB binding site is at least one of the targets of DT-β. This study pro- vides novel information regarding the mechanism by which DT-β exerts its effects on vascular inflammation, which is important for the onset and progression of various diseases.展开更多
The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new functio...The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new function of the subcortical pathway involved in the fast processing of non-emotional object perception.Rapid object processing is a critical function of visual system.Topological perception theory proposes that the initial perception of objects begins with the extraction of topological property(TP).However,the mechanism of rapid TP processing remains unclear.The researchers investigated the subcortical mechanism of TP processing with transcranial magnetic stimulation(TMS).They find that a subcortical magnocellular pathway is responsible for the early processing of TP,and this subcortical processing of TP accelerates object recognition.Based on their findings,we propose a novel training approach called subcortical magnocellular pathway training(SMPT),aimed at improving the efficiency of the subcortical M pathway to restore visual and attentional functions in disorders associated with subcortical pathway dysfunction.展开更多
Objective:To investigate the biological functions and molecular regulatory mechanisms of kinesin family member 11(KIF11)in colorectal cancer(CRC).Methods:The expression of KIF11 in CRC was examined by qRT⁃PCR and publ...Objective:To investigate the biological functions and molecular regulatory mechanisms of kinesin family member 11(KIF11)in colorectal cancer(CRC).Methods:The expression of KIF11 in CRC was examined by qRT⁃PCR and public databases.Functional assays(CCK⁃8,colony formation,EdU,and Transwell)were employed to evaluate KIF11’s roles in CRC progression.Western blot,RIP⁃qPCR,MeRIP⁃qPCR,and RNA stability assays were performed to elucidate the molecular mechanism of N6⁃methyladenosine(m6A)modification for KIF11.RNA sequencing(RNA⁃seq)and correlation analysis were used to examine the downstream mechanism of KIF11 regulation.Results:KIF11 was highly expressed in CRC and promoted CRC proliferation and migration.Mechanistically,methyltransferase⁃like 3(METTL3)/insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)enhanced KIF11 mRNA stability and expression in an m6A⁃dependent way.Furthermore,by means of the PROM1/PI3K/AKT pathway,KIF11 facilitated the progression of CRC.Conclusion:The m6A modification of KIF11 by METTL3/IGF2BP2 contributes to CRC progression via the PI3K/AKT signaling pathway,highlighting its potential as a prognostic biomarker and therapeutic target.展开更多
In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritig...In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritigenin,and licochalcone A,on osteogenic differentiation and mineralization by molecular docking simulation,alkaline phosphatase(ALP)activity and osteocalcin(OCN)content assays,and Runt-related transcription factor 2(Runx2)expression,and explored their potential molecular mechanisms.The results of molecular docking showed that the docking score of liquiritigenin with the estrogen receptor(ER)was the highest.All four flavonoids up-regulated ALP activity and OCN concentration in MC3T3-E1 cells,thereby elevating the mineralization level,among which liquiritigenin was the most effective.Moreover,treatment with a phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002)inhibited liquiritigenin from inducing increased phosphorylation levels in the PI3K/protein kinase B(AKT)signaling pathway and up-regulation of Runx2 expression,suggesting that PI3K and AKT were involved in osteogenic action.Liquiritigenin reversed bone mineral density loss in a zebrafish osteoporosis model.These findings suggest that liquiritigenin has the most significant osteogenic effect among the four estrogen-like flavonoids,stimulating osteoblast differentiation and bone mineralization through the activation of Runx2 via the PI3K/AKT signaling pathways.In conclusion,this study highlights the great potential of liquiritigenin for preventing and treating osteoporosis.展开更多
The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se ...The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se deficiency accusers more frequently in low-Se regions.Therefore,to investigate the Se status and inflammatory response of the mammary gland under marginal dietary Se levels,an lipopolysaccharide(LPS)induced mouse mastitis model was established.Mice were fed with moderate Se diet(0.087 mg•kg^(-1) Se),adequate Se diet(0.15 mg•kg^(-1) Se)or excessive Se diet(1.5 mg•kg^(-1) Se)for 60 days.Se status and inflammatory factors were investigated.Results showed that the Se status of mammary gland correlated with dietary Se levels.Marginal Se deficiency exacerbated mammary tissue histopathology;increased the mRNA level of inflammatory genes tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and cyclooxygenase-2(COX-2);and enhanced the phosphorylation of NF-κB p65 in mammary gland tissues.Supplementation of Se in diet higher than recommended levels reduced the inflammatory reaction of mammary glands in LPS-induced mastitis model and provided a protective effect.展开更多
目的:探究清肺通络膏对流感病毒诱导的肺炎大鼠肺组织中PI3K/AKT/NF-KB信号传导通路的调控机制。方法:将40只Wistar大鼠随机分为正常组,模型组,清肺通络膏高、中、低剂量组,除正常组外,采用鼻腔接种流感病毒FM1株诱导Wistar幼龄大鼠肺炎...目的:探究清肺通络膏对流感病毒诱导的肺炎大鼠肺组织中PI3K/AKT/NF-KB信号传导通路的调控机制。方法:将40只Wistar大鼠随机分为正常组,模型组,清肺通络膏高、中、低剂量组,除正常组外,采用鼻腔接种流感病毒FM1株诱导Wistar幼龄大鼠肺炎,在感染后各治疗组采用清肺通络膏贴敷于大鼠背部肺脏投影区治疗。观察各组大鼠的一般状态;肺组织形态学;采用免疫组化染色法检测各组大鼠肺组织PI3K,AKT,核因子NFB p65的表达水平。结果:与正常组相比,模型组大鼠肺组织中PI3K,AKT,NF-k B p65的表达显著增高(P<0.05),清肺通络膏高剂量组PI3K,AKT,NF-k B p65的表达较模型组明显降低(P<0.05)。结论:清肺通络膏通过抑制PI3K/AKT信号通路,使NF-k B p65表达降低,从而减轻了肺组织的病理损伤,达到治疗目的。展开更多
目的:探讨蜘蛛香总黄酮对肝癌H22小鼠抗肿瘤作用及对pathways in cancer的影响。方法:建立H22肝癌皮下荷瘤模型,随机分为模型对照组、阳性对照组、蜘蛛香总黄酮高、低剂量组。给药10 d后,解剖称取瘤重,计算抑瘤率,并应用小鼠全基因组基...目的:探讨蜘蛛香总黄酮对肝癌H22小鼠抗肿瘤作用及对pathways in cancer的影响。方法:建立H22肝癌皮下荷瘤模型,随机分为模型对照组、阳性对照组、蜘蛛香总黄酮高、低剂量组。给药10 d后,解剖称取瘤重,计算抑瘤率,并应用小鼠全基因组基因芯片考察蜘蛛香总黄酮对瘤组织pathways in cancer的影响。结果:与模型对照组相比,阳性对照组、蜘蛛香总黄酮高、低剂量组的平均瘤重明显下降(P<0.01,P<0.05,P<0.05),各组抑瘤率分别为45.32%、30.06%、25.97%。给药组pathways in cancer中有17个基因表达同时发生了显著性变化,其中Ccne2、Cdkn2b、Ctbp2、Mmp1a、Myc和Vegfa的表达发生了上调,而Vegfc、Csf1r、Epas1、Figf、Fzd9、Igf1、Pdgfra、Pik3r1、Prkcb、Tcf7l1和Tcf7l2的表达发生了下调,主要从细胞周期调控、PI3K-AKT途径、Wnt途径抑制肿瘤增殖、迁移,促进其凋亡。结论:蜘蛛香总黄酮具有一定的抗肝癌活性,作用机理可能与调节pathways in cancer的信号转导相关。展开更多
Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are current...Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.展开更多
G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways...G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways of GPCRs-adenylyl cyclase(AC)-cyclic adenosine 3',5'-monophosphate(c AMP),including β2 adrenergic receptors(β2-ARs)-AC-c AMP signaling pathways,E-prostanoid2/4(EP2/4)-AC-cA MP signaling pathways.Regulatory proteins,such as G protein coupled receptor kinases(GRKs)andβ-arrestins,play important modulatory roles in GPCRs signaling pathway.GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response.Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response.This article review the advances on GPCRs signaling pathway implicating in the inflammatory and immune response of RA.展开更多
Peaches are subject to flesh softening during postharvest storage and transport,which affects the storage life of the fruit and causes huge economic losses.Previous research has demonstrated that postharvest brassinol...Peaches are subject to flesh softening during postharvest storage and transport,which affects the storage life of the fruit and causes huge economic losses.Previous research has demonstrated that postharvest brassinolide treatment can maintain flesh firmness,ascorbic acid and soluble solids contents,and enhance disease resistance in peach fruits.This study assessed the influence of postharvest brassinolide treatment on the expression of key genes involved in cell wall degradation and the phenylpropanoid pathway in peach fruits by real-time fluorescence quantitative polymerase chain reaction(qPCR).The results showed that brassinolide dipping inhibited the gene expression of pectate lyase 1,polygalacturonase 21 and pectin methylesterase 1,and significantly enhanced the gene expression of peroxidase,cinnamoyl-CoA reductase,phenylalanine ammonia lyase and caffeoyl-CoA-O-methyltransferase 5 in peach fruits.It also increased the gene expression levels of chaleone synthase,chaleone isomerase,dihydroflavonol-4-reductase and flavanone 3-hydroxylase at the early stage of storage.These findings imply that brassinolide can suppress the expression of key genes involved in cell wall degradation and enhance the expression of key genes involved in the phenylpropanoid pathway,thereby delaying peach fruit softening and enhancing disease resistance.展开更多
文摘Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have shown that endothelial activation contributes to the pathophysiology of cardiovascular diseases such as atherosclero- sis, diabetic vasculopathy, heart failure and hypertension. In the present study, the effects of MLB on endothelial activation were investigated. Lipopolysaccharide （LPS） 1 mg L^-1 was employed to induce endothelial activation, which was determined by relative gene expression and endothelial adhesion assay. Results showed that pretreatment with MLB attenuated LPS-induced ICAM1, VCAM1 and TNF-α upregulation in human dermal microvascular endo- thelial cells （HMEC-1） in dose-dependent manner, which contributed to the reduction of THP-1 adhesion to HMEC-1. Furthermore, it was revealed that 100 μmol · L^-1 MLB significantly decreased the nuclear translocation of NF-KB p65, a critical transcription factor in LPS-indueed inflammatory response, through the inhibition of IKBμ degradation. Besides, the transcriptional activity of NF-KB p65 was also inhibited by the pretreatment of MLB. Mo- reover, MLB pretreatment considerably inhibited LPS-induced p38 phosphorylation, which at least partly contribu- ted to the reduction of ICAM1 expression. In conclusion, these findings suggest that MLB inhibits LPS-induced nu- clear translocation and transcripitional activity of NF-KB, thus attenuates the increased expression of adhesion mole- cules and inflammatory factors, protects endothelial cells from LPS-induced activation.
文摘This study aimed to explore the effect of DT-13 （25（R,S）-ruscogenin- 1-O- [ β-d-glucopyranosyl- （1→2） ] [ β-d-xylopyranosyl-（ 1→3） 1-β -d- fucopyranoside） on tumor necrosis factor （TNF）-α-induced vascular inflamma- tion and the potential molecular mechanisms. In vitro, DT-β suppressed TNF-α-induced adhesion and migration of human umbilical vein endothelial cells （HUVECs） by inhibiting the expression of intercellular adhesion molecule-1 （ ICAM-1 ） and vascular cell adhesion molecule-1 （VCAM-1）. DT-β markedly suppressed NF-KB p65 phosphoryl- ation, and when NF-KB p65 was over-expressed, the inhibitory effect of DT-β on adhesion molecular decreased. DT-β also suppressed TNF-α induced luciferase activities of ICAM-1 and VCAM-1 promoter containing NF-KB binding sites. Furthermore DT-β markedly suppressed p38 phosphorylation and Src degradation induced by TNF-α DT-β at 4 mg·kg- 1 prevented vascular , whereas had no significant effect on ERK and JNK activation. In-vivo, inflammation and the expression of adhesion molecules induced by TNF-α in mice. These findings suggest that DT- β abrogates vascular inflammation by down-regulating adhesion molecules associated with modulating the NF-KB, p38MAPK, Src signaling pathways, and NF-KB binding site is at least one of the targets of DT-β. This study pro- vides novel information regarding the mechanism by which DT-β exerts its effects on vascular inflammation, which is important for the onset and progression of various diseases.
文摘The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new function of the subcortical pathway involved in the fast processing of non-emotional object perception.Rapid object processing is a critical function of visual system.Topological perception theory proposes that the initial perception of objects begins with the extraction of topological property(TP).However,the mechanism of rapid TP processing remains unclear.The researchers investigated the subcortical mechanism of TP processing with transcranial magnetic stimulation(TMS).They find that a subcortical magnocellular pathway is responsible for the early processing of TP,and this subcortical processing of TP accelerates object recognition.Based on their findings,we propose a novel training approach called subcortical magnocellular pathway training(SMPT),aimed at improving the efficiency of the subcortical M pathway to restore visual and attentional functions in disorders associated with subcortical pathway dysfunction.
基金江苏省卫生健康委员会医学科研重点项目(K2023024)789 Outstanding Talent Program of SAHNMU(789ZYRC202090147)。
文摘Objective:To investigate the biological functions and molecular regulatory mechanisms of kinesin family member 11(KIF11)in colorectal cancer(CRC).Methods:The expression of KIF11 in CRC was examined by qRT⁃PCR and public databases.Functional assays(CCK⁃8,colony formation,EdU,and Transwell)were employed to evaluate KIF11’s roles in CRC progression.Western blot,RIP⁃qPCR,MeRIP⁃qPCR,and RNA stability assays were performed to elucidate the molecular mechanism of N6⁃methyladenosine(m6A)modification for KIF11.RNA sequencing(RNA⁃seq)and correlation analysis were used to examine the downstream mechanism of KIF11 regulation.Results:KIF11 was highly expressed in CRC and promoted CRC proliferation and migration.Mechanistically,methyltransferase⁃like 3(METTL3)/insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)enhanced KIF11 mRNA stability and expression in an m6A⁃dependent way.Furthermore,by means of the PROM1/PI3K/AKT pathway,KIF11 facilitated the progression of CRC.Conclusion:The m6A modification of KIF11 by METTL3/IGF2BP2 contributes to CRC progression via the PI3K/AKT signaling pathway,highlighting its potential as a prognostic biomarker and therapeutic target.
文摘In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritigenin,and licochalcone A,on osteogenic differentiation and mineralization by molecular docking simulation,alkaline phosphatase(ALP)activity and osteocalcin(OCN)content assays,and Runt-related transcription factor 2(Runx2)expression,and explored their potential molecular mechanisms.The results of molecular docking showed that the docking score of liquiritigenin with the estrogen receptor(ER)was the highest.All four flavonoids up-regulated ALP activity and OCN concentration in MC3T3-E1 cells,thereby elevating the mineralization level,among which liquiritigenin was the most effective.Moreover,treatment with a phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002)inhibited liquiritigenin from inducing increased phosphorylation levels in the PI3K/protein kinase B(AKT)signaling pathway and up-regulation of Runx2 expression,suggesting that PI3K and AKT were involved in osteogenic action.Liquiritigenin reversed bone mineral density loss in a zebrafish osteoporosis model.These findings suggest that liquiritigenin has the most significant osteogenic effect among the four estrogen-like flavonoids,stimulating osteoblast differentiation and bone mineralization through the activation of Runx2 via the PI3K/AKT signaling pathways.In conclusion,this study highlights the great potential of liquiritigenin for preventing and treating osteoporosis.
基金Supported by the Natural Science Foundation of the Heilongjiang Province of China(C2016003)China Postdoctoral Science Foundation(2015M581415)Heilongjiang Postdoctoral Fund(LBH-Z15005)。
文摘The trace element selenium(Se)occurs naturally throughout the earth.Se deficiency has been linked to impaired breast health and other diseases in human and animals.Compared to severe Se deficiency,marginal dietary Se deficiency accusers more frequently in low-Se regions.Therefore,to investigate the Se status and inflammatory response of the mammary gland under marginal dietary Se levels,an lipopolysaccharide(LPS)induced mouse mastitis model was established.Mice were fed with moderate Se diet(0.087 mg•kg^(-1) Se),adequate Se diet(0.15 mg•kg^(-1) Se)or excessive Se diet(1.5 mg•kg^(-1) Se)for 60 days.Se status and inflammatory factors were investigated.Results showed that the Se status of mammary gland correlated with dietary Se levels.Marginal Se deficiency exacerbated mammary tissue histopathology;increased the mRNA level of inflammatory genes tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and cyclooxygenase-2(COX-2);and enhanced the phosphorylation of NF-κB p65 in mammary gland tissues.Supplementation of Se in diet higher than recommended levels reduced the inflammatory reaction of mammary glands in LPS-induced mastitis model and provided a protective effect.
文摘目的:探究清肺通络膏对流感病毒诱导的肺炎大鼠肺组织中PI3K/AKT/NF-KB信号传导通路的调控机制。方法:将40只Wistar大鼠随机分为正常组,模型组,清肺通络膏高、中、低剂量组,除正常组外,采用鼻腔接种流感病毒FM1株诱导Wistar幼龄大鼠肺炎,在感染后各治疗组采用清肺通络膏贴敷于大鼠背部肺脏投影区治疗。观察各组大鼠的一般状态;肺组织形态学;采用免疫组化染色法检测各组大鼠肺组织PI3K,AKT,核因子NFB p65的表达水平。结果:与正常组相比,模型组大鼠肺组织中PI3K,AKT,NF-k B p65的表达显著增高(P<0.05),清肺通络膏高剂量组PI3K,AKT,NF-k B p65的表达较模型组明显降低(P<0.05)。结论:清肺通络膏通过抑制PI3K/AKT信号通路,使NF-k B p65表达降低,从而减轻了肺组织的病理损伤,达到治疗目的。
文摘目的:探讨蜘蛛香总黄酮对肝癌H22小鼠抗肿瘤作用及对pathways in cancer的影响。方法:建立H22肝癌皮下荷瘤模型,随机分为模型对照组、阳性对照组、蜘蛛香总黄酮高、低剂量组。给药10 d后,解剖称取瘤重,计算抑瘤率,并应用小鼠全基因组基因芯片考察蜘蛛香总黄酮对瘤组织pathways in cancer的影响。结果:与模型对照组相比,阳性对照组、蜘蛛香总黄酮高、低剂量组的平均瘤重明显下降(P<0.01,P<0.05,P<0.05),各组抑瘤率分别为45.32%、30.06%、25.97%。给药组pathways in cancer中有17个基因表达同时发生了显著性变化,其中Ccne2、Cdkn2b、Ctbp2、Mmp1a、Myc和Vegfa的表达发生了上调,而Vegfc、Csf1r、Epas1、Figf、Fzd9、Igf1、Pdgfra、Pik3r1、Prkcb、Tcf7l1和Tcf7l2的表达发生了下调,主要从细胞周期调控、PI3K-AKT途径、Wnt途径抑制肿瘤增殖、迁移,促进其凋亡。结论:蜘蛛香总黄酮具有一定的抗肝癌活性,作用机理可能与调节pathways in cancer的信号转导相关。
文摘Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.
基金supported by National Natural Science Foundation of China(81330081,81473223and 81673444)Anhui Province Postdoctoral Science Foundation(2016B134)
文摘G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways of GPCRs-adenylyl cyclase(AC)-cyclic adenosine 3',5'-monophosphate(c AMP),including β2 adrenergic receptors(β2-ARs)-AC-c AMP signaling pathways,E-prostanoid2/4(EP2/4)-AC-cA MP signaling pathways.Regulatory proteins,such as G protein coupled receptor kinases(GRKs)andβ-arrestins,play important modulatory roles in GPCRs signaling pathway.GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response.Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response.This article review the advances on GPCRs signaling pathway implicating in the inflammatory and immune response of RA.
文摘Peaches are subject to flesh softening during postharvest storage and transport,which affects the storage life of the fruit and causes huge economic losses.Previous research has demonstrated that postharvest brassinolide treatment can maintain flesh firmness,ascorbic acid and soluble solids contents,and enhance disease resistance in peach fruits.This study assessed the influence of postharvest brassinolide treatment on the expression of key genes involved in cell wall degradation and the phenylpropanoid pathway in peach fruits by real-time fluorescence quantitative polymerase chain reaction(qPCR).The results showed that brassinolide dipping inhibited the gene expression of pectate lyase 1,polygalacturonase 21 and pectin methylesterase 1,and significantly enhanced the gene expression of peroxidase,cinnamoyl-CoA reductase,phenylalanine ammonia lyase and caffeoyl-CoA-O-methyltransferase 5 in peach fruits.It also increased the gene expression levels of chaleone synthase,chaleone isomerase,dihydroflavonol-4-reductase and flavanone 3-hydroxylase at the early stage of storage.These findings imply that brassinolide can suppress the expression of key genes involved in cell wall degradation and enhance the expression of key genes involved in the phenylpropanoid pathway,thereby delaying peach fruit softening and enhancing disease resistance.
