Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promot...Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.展开更多
Heart failure(HF)is a kind of continuous development syndrome of cardiac insufficiency caused by various heart diseases.Not only does the prevalence continue to rise,but the mortality rate and readmission rate remain ...Heart failure(HF)is a kind of continuous development syndrome of cardiac insufficiency caused by various heart diseases.Not only does the prevalence continue to rise,but the mortality rate and readmission rate remain high.Heart failure is also the end-stage of cardiovascular disease and the main cause of death of patients,which seriously affects the health and quality of life of people all over the world.Ventricular remodeling plays a key role in the occurrence and development of heart failure.Therefore,by improving ventricular remodeling,it is of important research value to explore the intervention of traditional Chinese medicine in the development of heart failure.Studies have shown that the mediation of multiple signaling pathways can lead to progressive aggravation of ventricular remodeling,and experimental studies often confirm the therapeutic effects of traditional Chinese medicine.Traditional Chinese medicine usually achieves the therapeutic effect of heart failure through multiple targets and multiple approaches.In recent years,there have been more and more researches on the role and mechanism of Chinese medicine intervention in heart failure.However,it is concluded that Chinese medicine intervention has less influence on heart failure signal pathways.This article summarizes the understanding of Chinese medicine on heart failure and the five signal pathways related to Chinese medicine intervention in heart failure.The 5 signaling pathways in the world,namely transforming growth factor-β1(TGF-β1)/signal transduction protein(Smads)signaling pathway,Toll-like receptor(TLR)/nuclear transcription factor-κB(NF-κB)inflammation signaling pathway,Renin-angiotensinaldosterone(RAAS)system,phosphoinositide 3-kinase(PI3K)-serine/threonine protein kinase(AKT)signaling pathway and mitogen-activated protein kinase(MAPK)dependent signaling pathway.展开更多
Background: Intramuscular fat(IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs(miRNAs) play an important role in regulating porcine IMF deposition. Here, a nov...Background: Intramuscular fat(IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs(miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.Results: By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4(SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6(TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway.Conclusions: MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.展开更多
The panax notoginseng saponin(PNS) had been clinically used for the treatment of cardiovascular diseases and stroke in China.It had been demonstrated that PNS could protect cardiomyocytes from injury induced by ischem...The panax notoginseng saponin(PNS) had been clinically used for the treatment of cardiovascular diseases and stroke in China.It had been demonstrated that PNS could protect cardiomyocytes from injury induced by ischemi- a,but the underlying molecular mechanisms of this protective effect were still unclear.This study was aimed to investigate the protective effect and molecular mechanisms of PNS on apoptosis in H9c2 cells in vitro and rat myocardial ischemia injury model in vivo.Annexin-V/PI assay shew that PNS could protect H9c2 cells from apoptosis induced by serum, glucose and oxygen deprivation(SGOD) in a dose-dependent manner.However,the anti-apoptotic effect of PNS was reversed by LY294002,a specific PI3K inhibitor.This antiapoptotic effect of PNS was confirmed by JC-1,a specific probe of mitochondrial membrane potential staining.PNS could significantly increase phos-Akt in H9c2 cells by Western blot assays and its effect could be inhibited by LY294002.Furthermore,PNS could improve ischemic-induced left ventricular function as reflected by EF,LVDd and LVDs.PNS could also inhibited cellular apoptosis in myocardial tissues in ischemic rats by TUNEL assay.PNS administration also increased the expression of phos-Akt in rat ischemic myocardial tissues.These results suggested that PNS could protect myocardial cells from apoptosis induced by ischemia in vitro model and in vivo model through activating-PI3K/Akt signal pathway which may be meaningful for further understanding the molecular mechanisms of cardiac protection of PNS.And the results might be useful in treatment of myocardial ischemia in future.展开更多
Objective:To investigate the role of oxidative stress in human renal tubular epithelial cells(HK-2)induced by high glucose and the underlying signal pathway in vitro.Methods:MYPT1,pro-caspase-3,PGC-1α,and Drpl protei...Objective:To investigate the role of oxidative stress in human renal tubular epithelial cells(HK-2)induced by high glucose and the underlying signal pathway in vitro.Methods:MYPT1,pro-caspase-3,PGC-1α,and Drpl protein expressions were measured by Western blot.MnSOD2,Drp1 and PGC-1αmRNA expressions were detected by real time PCR.Results:Results showed that high glucose significantly up-regulated the protein expressions of MYPT1,pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells;while Rho kinase inhibitor fasudil and ROCK1 siRNA inhibited protein expressions of pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells induced by high glucose.Importantly,fasudil and ROCK1 siRNA markedly inhibited the expressions of mitochondrial motor proteins Drp1 and mitochondrial gene PGC-la in HK-2 cell=s induced by high glucose.Conclusions:Our findings suggest that Rho kinase signal pathway is involved in mitochondrial oxidative damage and apoptosis in high glucose-induced renal tubular epithelial cells by regulating mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α.Targeting Rho kinase signal pathway might be a potential strategy for the treatment of diabetic nephropathy.展开更多
AIM:To investigate the feasibility and mechanism of immune tolerance in allergic conjunctivitis.METHODS:The allergic conjunctivitis immune tolerance mice model was established by ragweed pollen(RW)and the related cyto...AIM:To investigate the feasibility and mechanism of immune tolerance in allergic conjunctivitis.METHODS:The allergic conjunctivitis immune tolerance mice model was established by ragweed pollen(RW)and the related cytokines were detected.The mice were divided into 9 groups and the maslinic acid(MA)or PBS were given for different group after modeling.The expression levels of chemokine ligand 5(CCL5)and P-65 in the conjunctival tissue were analyzed by immunohistochemistry,quantitative reverse transcription polymerase chain reaction(q RT-PCR)and Western blot.The percentage of interleukin-17(IL-17)and CD4+CD25+in the splenocyte supernatant was analyzed by flow cytometry.Fur thermore,the serum and splenocyte supernatant concentration of total-IgE,interleukin-10(IL-10),and IL-17 was analyzed by enzyme linked immune response(ELISA).RESULTS:After the model was established,symptoms of conjunctivitis were alleviated,the level of P-65,CCL5,IL-17,and total-IgE was raised,while the expression of IL-10,CD4+CD25+was decreased.This result fully demonstrated that a typical IL-17/regulatory-T-cells(Treg cells)imbalance and NF-κB activation.When the NF-κB signal pathway was suppressed,it showed that there was a further relief of conjunctivitis in mice.At the same time,the expression of total-IgE,IL-17,and CCL5 was decreased and the expression of anti-inflammatory factor(IL-10,CD4+CD25+)was increased.CONCLUSION:In the state of immune tolerance,symptoms of conjunctivitis in mice are alleviated,the Th-17 cells of allergic conjunctivitis mice are inhibited,and Treg cells activity is enhanced.展开更多
Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturb...Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturbance of liver is one of the important pathogenesis of chronic liver disease,the improvement of microcirculation is beneficial to the recovery of liver function and the delay of liver fibrosis.Hepatic stellate cells are the core cells of hepatic fibrosis,and also the most critical cells that affect the microcirculation of the liver.While TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs which are based on the action of hepatic stellate cells are two pathways that have very important influence on the inflammatory response of liver,the proliferation and apoptosis of hepatic stellate cells,and the secretion of fibrogenic cytokines.It was found that Plumbapin,the active ingredient of Guangxi specialty ethnic medicine,has the definite effect of promoting blood circulation and removing blood stasis and anti-hepatic fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived as follows:the pharmacological effect of Plumbapin on anti-hepatic fibrosis,promoting blood circulation and removing stasis was based on the influence of TLR4/MyD88/NF-κB and MAPKs signal pathway.展开更多
[Objectives]To explore the effect and possible mechanism of bergenin in relieving allergic rhinitis(AR)in mice.[Methods]50 C57/BL6 mice were randomly divided into blank group(n=10),model group(n=10)and high(100 mg/kg)...[Objectives]To explore the effect and possible mechanism of bergenin in relieving allergic rhinitis(AR)in mice.[Methods]50 C57/BL6 mice were randomly divided into blank group(n=10),model group(n=10)and high(100 mg/kg),medium(50 mg/kg)and low(25 mg/kg)dose bergenin groups with 10 mice in each group.Except for the blank group,the other mice were sensitized by basic ways combined with attack to replicate the AR model.From the 15th d of modeling(from the second d after the end of the basic modeling),the drug group was given bergenin orally for 15 d,and the blank group and model group were given the same volume of normal saline once a day.24 h after the last establishment of the model,the content of interleukin 4(IL-4),IL-6,TNF-αand IL-1βin nasal lavage fluid and serum of mice in each group was detected by ELISA.The expression of TLR-4,NF-κB and p-NF-κB in nasal mucosa of mice was detected by Western blot.[Results]Compared with the blank group,the content of inflammatory factors IL-4,IL-6,TNF-αand IL-1βin nasal lavage fluid and serum of model group was significantly increased,and the protein expression of TLR-4 and p-NF-κB was significantly increased.After the intervention of bergenin,the content of IL-4,IL-6,TNF-αand IL-1βin nasal lavage fluid and serum and TLR-4 and p-NF-κB protein in tissue was significantly inhibited in bergenin group.[Conclusions]Bergenin can effectively reduce allergic inflammation in AR model mice,and its mechanism may be related to inhibition of inflammation and down-regulation of TLR-4/NF-κB signal pathway.展开更多
Background To investigate the effects and mechanisms of cellular repressor of ElA stimulated genes (CREG) on endothelial cell(EC) migration.Methods vascular endothelial cells(VE),CREG overexpression VEs, CREG suppress...Background To investigate the effects and mechanisms of cellular repressor of ElA stimulated genes (CREG) on endothelial cell(EC) migration.Methods vascular endothelial cells(VE),CREG overexpression VEs, CREG suppression VEs and VEs transfected with CREG gene modified adenovirus(Ad-CREG) were cultured with dulbecco’s modified eagle’s medium contained 10%fetal calf serum. Western blot was used to detect the protein level of CREG and integrin-linked kinase(ILK) in the four kind ECs.Tran-swell migration model was applied to compare the migration cell number of the four kind ECs.Two kinds of ILK mutant plasmids;PCXN2-flag-ILK wt-IRES-GFP(wild-type ILK)and PCXN2-flag-ILK p-parvin-IRES-GFP(P-parvin-binding mutant) were used to transfect VS and VE respectively,then the two kind transfection ECs were named as VS-wtILK and VE-P -parvin which were selected by G418(600ng/ml)for 2 weeks;Transwell migration model was applied to compare migration capability before and after ILK plasmids transfecting VE and VS.Results Western blot analysis showed that CREG overexpression promoted ILK expression in ECs,on the contrary,ILK expression was down-regulated in CREG silent ECs(P【0.05).Further more,ILK expression was up-regulated obviously in VE transfected with Ad-CREG(P【 0.05);Transwell migration model showed that EC’s migration capability was positively correlated with the expression level of CREG in EC,that is,CREG overexpression induced VE migration and CREG silent suppressed VE migration, moreover,Ad-CREG transfecting VE showed better migration capability accompanied with CREG expression increase by transwell migration model(P【0.05).In order to know the relationship between ILK expression and cell migration,we obtained stable transfection cell strains of VS-wtILK and VE-Pparvin, transwell migration model demonstrated that VS-wtILK remarkably corrected the poor migration capability of VS(P【 0.01),butβ-parvin combining site mutation in ILK genes inhibited VE migration markedly(P【0.01).Conclusions ILKp -parvin signal pathway mediated vascular endothelial cell migration induced by CREG.展开更多
Psoriasis is a complex skin disease and the pathogenesis of psoriasis is not clear.The purpose of this study is to identify the key driving genes and signal pathways involved in psoriasis and to predict the potential ...Psoriasis is a complex skin disease and the pathogenesis of psoriasis is not clear.The purpose of this study is to identify the key driving genes and signal pathways involved in psoriasis and to predict the potential miRNA,for further understanding the pathogenesis of psoriasis.Methods:Three gene expression profiling chips,including GSE67853,GSE78097,and GSE136757 with a total of 120 samples were collected and analyzed with R software.The protein-protein interaction network of differentially expressed genes was constructed with STRING database and Cytoscape.CIBERSORT was used to evaluate the infiltration of immune cells in psoriasis tissues,and the correlation between diagnostic markers and infiltrating immune cells was analyzed.Further,the key biomarkers were identified and the targeting miRNA of crucial genes was predicted.Results:A total of 201 differentially expressed genes(163 upregulated genes and 38 downregulated genes)were determined.CXCL1,CXCL2,and CXCL8,the critical biomarkers of psoriasis,were identified by different calculation methods.The potential critical signal pathway NOD-like receptor signaling pathway of psoriasis was explored by gene expression profiling chip gene enrichment analysis and differentially expressed gene enrichment analysis.Immune cell infiltration analysis found that CXCL1,CXCL2,CXCL8 was positively correlated with macrophages M1 and T cells CD4 memory activated and negatively correlated with macrophages M2 and mast cells resting.At the same time,through miRNA prediction,we found that hsa-miR-216a-3p and hsa-miR-6750-5p can be used as potential psoriasis targets.Conclusions:This research proposes a new comprehensive strategy to identify psoriasis’s potential biomarkers through cross-validation and significant scores of different calculation methods.In this research,we identified CXCL1,CXCL2,and CXCL8 as potential key biomarkers of psoriasis,and the NOD-like receptor signaling pathway is the critical signal pathway of psoriasis.Hsa-miR-216a-3p and hsa-miR-6750-5p can be used as potential psoriasis targets.展开更多
AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models...AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.展开更多
Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1...Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro.Methods:The experiment was conducted in 4 different mediums:NSCs+PBS(Group A-blank control group),NSCs+SCE with healthy SD rats(Croup B-normal control group),NSCs+SCE with SD rats receiving sham-operation treatment(Croup C-sham-operation group)and NSCs+SCE with SCIs rats(Group D-paraplegic group).Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1,2,3,4 and 5 d,respectively.The expressions of Notch 1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h,respectively.Results:After co-culture for 1,2,3,4 and 5 d respectively,the MTT values of group D were significantly higher than those of group A,group B and group C(P<0.05).However,there were no significantly differences regarding MTT values between group A,group B and group C after co-culture for 1,2,3,4 and 5 d,respectively(P>0.05).Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well(P<0.05).But there was no difference oin expressions of Notch1 and Hes1 mRNA among group A,group B and group C after co-culture for 24 h and 48 h(P>0.05).There was no difference in expressions of Notch1and Hes1 mRNA between 24 h and 48 h treatment in group D.Conclusions:SCE could promote the proliferation of NSCs.It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs.Besides,SCE could increase the expression of Notch1 and Hes1 mRNA of NSC.It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs.This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene.展开更多
Objective:To observe the expression changes of inflammatory markers TGF-β1,Smad3 and IL-6 in patients with atrial fibrillation(AF),and to explore the significance of TGF-β1 signaling pathway in the structural remode...Objective:To observe the expression changes of inflammatory markers TGF-β1,Smad3 and IL-6 in patients with atrial fibrillation(AF),and to explore the significance of TGF-β1 signaling pathway in the structural remodeling of AF.Methods:The expression of TGF-β1,Smad3 and IL-6 in 50 cases with AF and 30 normal cases were detected by RT-PCR and ELISA.Results:The TGF-β1,Smad3 and IL-6 mRNA and protein expression levels in patients with AF were significantly higher than that in the control group(P<0.05),but there was no significantly different between the paroxysmal AF group and the persistent AF group(P>0.05).The TGF-β1mRNA expression in the≥50 years subgroup was significantly higher than that in the<50years subgroups,and it was higher in the NYHAⅢsubgroup than in theⅠ/Ⅱgrade subgroup.It was also higher in the left ventricular ejection fraction(LVEF)<50%subgroup than in LVEF≥50%group,and it was significantly higher in the AF time≥36 months subgroup than that in<36months subgroup(P<0.05).The Smad3 and IL-6 expressions in the in the LVEF<50%subgroup were both high that than that in LVEF≥50%group,and higher in the AF time≥36 months subgroup than that in<36 months subgroup(P<0.05).There were a positive correlation between TGF-β1,Smad3 and IL-6(r=0.687,r=0.547).There were also a positive correlation between Smad3 and IL-6 mRNA(r=0.823).Conclusions:AF is associated with inflammation,and the inflammation is also involved in the fibrillation and sustain of AF.The TGF-β1 signal pathway may be involved in the process of atrial structural remodeling in patients with AF,and iss related with the occurrence and maintenance of AF.展开更多
OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropr...OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.展开更多
Objective: To observe the effect of acupuncture on the expression of ERM/PI3K/Akt signaling pathway in the brain tissue around the infarct focus of ischemic stroke model rats. Methods: According to the block randomiza...Objective: To observe the effect of acupuncture on the expression of ERM/PI3K/Akt signaling pathway in the brain tissue around the infarct focus of ischemic stroke model rats. Methods: According to the block randomization method, 80 male SD rats were divided into normal group (n = 10), sham operation group (n = 24), model group (n = 23) and acupuncture group (n = 23). The normal group was bred routinely without any intervention. In the sham operation group, only the skin was cut to find and the nerves and blood vessels were stripped and sutured. The model group and the acupuncture group were sutured to prepare the MCAO model. After the model was successfully established, acupuncture of the acupuncture group rats was given once a day, and the needles were kept for 30 minutes each time. The rats in the sham operation group and the model group only imitated capture and return, and were treated with acupuncture for 2 consecutive courses, each course was 5 days, and the two courses were rested for 2 days. After that, Western blot was used to detect ERM, changes in the concentration of PI3K and Akt proteins. Results: Compared with the normal group, the expression levels of ERM, PI3K, and Akt proteins in the sham operation group were reduced. Compared with the sham operation group, the expression levels of ERM, PI3K, and Akt proteins in the model group were significantly down-regulated. Compared with the model group, the protein expression levels of ERM, PI3K and Akt were significantly up-regulated in the acupuncture group, and the difference was statistically significant (P < 0.05). Conclusion: Acupuncture can significantly up-regulate the expression of ERM, PI3K and Akt proteins, and its effect mechanism may be related to the transduction of ERM/PI3K/Akt signaling pathway in cells.展开更多
This study was conducted to find the differentially expressed genes and understand the transcriptome change characteristics in the testis of tilapia(Oreochromis niloticus) stressed by methomyl.The tilapia were exposed...This study was conducted to find the differentially expressed genes and understand the transcriptome change characteristics in the testis of tilapia(Oreochromis niloticus) stressed by methomyl.The tilapia were exposed to 200 μg/L methomyl for 30 d,and then the testis samples were collected and used for the highthroughput sequencing.The results showed that 369 significant differentially expressed genes were obtained,including 160 significantly down-regulated genes,and209 significantly up-regulated genes.The enrichment of the differentially expressed genes in ECM-receptor interaction signaling pathway and MAPK signaling pathway was obvious.The adhesion of testis tissue cells was influenced by methomyl stress,which induced the expression of related gene in ECM-receptor interaction up-regulating,such as laminins,integrin α6 and integrin β1,in order to stabilize testis tissue structure.JNK,MAP3 K and MKK4 in the JNK pathway were significantly up-regulated,which enhanced transcription factor AP-1 to promote the expression of P53,Bax and other pro-apoptotic proteins.The expression of growth-related factors in the ERK pathway of MAPK signal pathway was influenced by methomyl stress.The apoptosis-related genes and pregnancy-related genes have significant differential expression under methomyl stress,and thereby,the proliferation of reproduction cells in the testis tissue may be affected.展开更多
Objective:To study the effects of different administration routes of neoadjuvant chemotherapy on cancer cell growth signal pathway function in cervical cancer.Methods: Patients with cervical cancer who received neoadj...Objective:To study the effects of different administration routes of neoadjuvant chemotherapy on cancer cell growth signal pathway function in cervical cancer.Methods: Patients with cervical cancer who received neoadjuvant chemotherapy in Fufeng People's Hospital between July 2008 and July 2016 were selected as the research subjects and randomly divided into intervention group and intravenous group who accepted the neoadjuvant interventional arterial chemotherapy and neoadjuvant intravenous chemotherapy respectively. After surgical resection, the contents of PI3K/AKT/mTOR, Wnt/β-catenin and MEK/ERK signaling pathway in cervical cancer lesions were determined.Results:p-PI3K, p-AKT, mTOR, MMP2, VEGF,β-catenin, CyclinD1, Twist, Slug, Snail, MEK1, MEK2, ERK1/2 and Bcl-2 protein levels in cervical cancer lesion of intervention group were significantly lower than those of intravenous group whereas E-cadherin and Bax protein levels were significantly higher than those of intravenous group.Conclusion: Neoadjuvant interventional arterial chemotherapy can be more effective than neoadjuvant intravenous chemotherapy to inhibit the cancer cell growth mediated by PI3K/AKT/mTOR, Wnt/β-catenin and MEK/ERK signaling pathway in cervical cancer.展开更多
Objective The purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mou...Objective The purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line(EL-4 cells) was used. The expressions of CD4,CD25,Nrp1,calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-β1,IL-10,PKA and cAMP were estimated with ELISA. Results At 12 h after irradiation,the expression of Nrp1 increased significantly in 4.0 Gy group,compared with sham-irradiation group(P<0.05) in the spleen and thymus,respectively,when ICR mice received whole-body irradiation(WBI). Meanwhile the synthesis of Interleukin 10(IL-10) and transforming growth factor-β1(TGF-β1) increased significantly after high dose irradiation(HDR)(> or = 1.0 Gy). In addition,the expression of cAMP and PKA protein increased,while PKC-α,calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation,this did not limit the up-regulation of CD4+CD25+Nrp1+Treg cells after ionizing radiation. Conclusion These results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.展开更多
To explore the intracellular signal pathways for β-VLDL induced very low density lipoprotein receptor (VLDL-R) transcription up-regulation and their effects on lipid accumulation in macrophages, Western Blot was used...To explore the intracellular signal pathways for β-VLDL induced very low density lipoprotein receptor (VLDL-R) transcription up-regulation and their effects on lipid accumulation in macrophages, Western Blot was used to examine phosphorylated ERK1/2 protein and regulated effects by different singal kinase inhibitants. It was found that β-VLDL induced an increase in ERK1/2 activity in a protein kinase C (PKC)-dependent manner in murine RAW264.7 macrophages. By using different protein kinases inhibitors or activators, it was observed that the effect of β-VLDL induced VLDL receptor transcription, which was monitored by RT-PCR analysis of VLDL receptor mRNA, was not affected by the inhibitor of p38 kinase and cAMP analog, but extremely abolished by pretreating cells with PD98059, an inhibitor of ERK and GF 109203X, an inhibitor of PKC. These results demonstrated that the PKC-ERK1/2 cascade is the essential signaling pathway by which β-VLDL activated VLDL-R mRNA expression. Inhibition of the ERK1/2 signaling cascade resulted in suppression of the cellular lipid accumulation induced by β-VLDL in macrophages.展开更多
Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the
基金supported by the National Natural Science Foundation of China(81960851)Jiangxi Natural Science Foundation(20202BABL206132)Key Research Office of Traditional Chinese Medicine Syndrome Foundation of Jiangxi Administration of Traditional Chinese Medicine(8-4),and Science and Technology Innovation Team Development Program of Jiangxi University of Chinese Medicine(CXTD22016).
文摘Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.
基金National Natural Science Foundation of China(No.81673891,No.81560760)Guangxi Medical and Health Appropriate Technology Research and Development Project(No.S201532)Guangxi Zhuang Yao Pharmaceutical Preparation Improvement Project of Traditional Chinese Medicine(No.GZZJ16-03)。
文摘Heart failure(HF)is a kind of continuous development syndrome of cardiac insufficiency caused by various heart diseases.Not only does the prevalence continue to rise,but the mortality rate and readmission rate remain high.Heart failure is also the end-stage of cardiovascular disease and the main cause of death of patients,which seriously affects the health and quality of life of people all over the world.Ventricular remodeling plays a key role in the occurrence and development of heart failure.Therefore,by improving ventricular remodeling,it is of important research value to explore the intervention of traditional Chinese medicine in the development of heart failure.Studies have shown that the mediation of multiple signaling pathways can lead to progressive aggravation of ventricular remodeling,and experimental studies often confirm the therapeutic effects of traditional Chinese medicine.Traditional Chinese medicine usually achieves the therapeutic effect of heart failure through multiple targets and multiple approaches.In recent years,there have been more and more researches on the role and mechanism of Chinese medicine intervention in heart failure.However,it is concluded that Chinese medicine intervention has less influence on heart failure signal pathways.This article summarizes the understanding of Chinese medicine on heart failure and the five signal pathways related to Chinese medicine intervention in heart failure.The 5 signaling pathways in the world,namely transforming growth factor-β1(TGF-β1)/signal transduction protein(Smads)signaling pathway,Toll-like receptor(TLR)/nuclear transcription factor-κB(NF-κB)inflammation signaling pathway,Renin-angiotensinaldosterone(RAAS)system,phosphoinositide 3-kinase(PI3K)-serine/threonine protein kinase(AKT)signaling pathway and mitogen-activated protein kinase(MAPK)dependent signaling pathway.
基金supported by grants from the National Natural Science Foundation (31872979, 31572366)the National Key Research and Development Program of China (2017YFD0502002)the National Basic Research Programs of China (2015CB943102)。
文摘Background: Intramuscular fat(IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs(miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.Results: By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4(SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6(TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway.Conclusions: MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.
文摘The panax notoginseng saponin(PNS) had been clinically used for the treatment of cardiovascular diseases and stroke in China.It had been demonstrated that PNS could protect cardiomyocytes from injury induced by ischemi- a,but the underlying molecular mechanisms of this protective effect were still unclear.This study was aimed to investigate the protective effect and molecular mechanisms of PNS on apoptosis in H9c2 cells in vitro and rat myocardial ischemia injury model in vivo.Annexin-V/PI assay shew that PNS could protect H9c2 cells from apoptosis induced by serum, glucose and oxygen deprivation(SGOD) in a dose-dependent manner.However,the anti-apoptotic effect of PNS was reversed by LY294002,a specific PI3K inhibitor.This antiapoptotic effect of PNS was confirmed by JC-1,a specific probe of mitochondrial membrane potential staining.PNS could significantly increase phos-Akt in H9c2 cells by Western blot assays and its effect could be inhibited by LY294002.Furthermore,PNS could improve ischemic-induced left ventricular function as reflected by EF,LVDd and LVDs.PNS could also inhibited cellular apoptosis in myocardial tissues in ischemic rats by TUNEL assay.PNS administration also increased the expression of phos-Akt in rat ischemic myocardial tissues.These results suggested that PNS could protect myocardial cells from apoptosis induced by ischemia in vitro model and in vivo model through activating-PI3K/Akt signal pathway which may be meaningful for further understanding the molecular mechanisms of cardiac protection of PNS.And the results might be useful in treatment of myocardial ischemia in future.
基金supported by National Natural Science Foundation of China(No.81560124)Hainan Key Research and Development Projects(ZDYF2018131,ZDYF2017113,ZDYF2017114)+1 种基金Hainan Science and Technology Planned Project of Youth Outstanding Ability of Innovation(201704)Hainan Health Family Planning Industry Project(13A210277)
文摘Objective:To investigate the role of oxidative stress in human renal tubular epithelial cells(HK-2)induced by high glucose and the underlying signal pathway in vitro.Methods:MYPT1,pro-caspase-3,PGC-1α,and Drpl protein expressions were measured by Western blot.MnSOD2,Drp1 and PGC-1αmRNA expressions were detected by real time PCR.Results:Results showed that high glucose significantly up-regulated the protein expressions of MYPT1,pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells;while Rho kinase inhibitor fasudil and ROCK1 siRNA inhibited protein expressions of pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells induced by high glucose.Importantly,fasudil and ROCK1 siRNA markedly inhibited the expressions of mitochondrial motor proteins Drp1 and mitochondrial gene PGC-la in HK-2 cell=s induced by high glucose.Conclusions:Our findings suggest that Rho kinase signal pathway is involved in mitochondrial oxidative damage and apoptosis in high glucose-induced renal tubular epithelial cells by regulating mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α.Targeting Rho kinase signal pathway might be a potential strategy for the treatment of diabetic nephropathy.
基金Supported by the Provincial Innovation Team for Cataract and Ocular Fundus Disease in the Second People’s Hospital of Yunnan Province(No.2017HC010)the Key Laboratory of Yunnan Province for the Prevention and Treatment of Ophthalmology(No.2017DG008)Expert Workstation of Yao Ke(No.2017IC064)。
文摘AIM:To investigate the feasibility and mechanism of immune tolerance in allergic conjunctivitis.METHODS:The allergic conjunctivitis immune tolerance mice model was established by ragweed pollen(RW)and the related cytokines were detected.The mice were divided into 9 groups and the maslinic acid(MA)or PBS were given for different group after modeling.The expression levels of chemokine ligand 5(CCL5)and P-65 in the conjunctival tissue were analyzed by immunohistochemistry,quantitative reverse transcription polymerase chain reaction(q RT-PCR)and Western blot.The percentage of interleukin-17(IL-17)and CD4+CD25+in the splenocyte supernatant was analyzed by flow cytometry.Fur thermore,the serum and splenocyte supernatant concentration of total-IgE,interleukin-10(IL-10),and IL-17 was analyzed by enzyme linked immune response(ELISA).RESULTS:After the model was established,symptoms of conjunctivitis were alleviated,the level of P-65,CCL5,IL-17,and total-IgE was raised,while the expression of IL-10,CD4+CD25+was decreased.This result fully demonstrated that a typical IL-17/regulatory-T-cells(Treg cells)imbalance and NF-κB activation.When the NF-κB signal pathway was suppressed,it showed that there was a further relief of conjunctivitis in mice.At the same time,the expression of total-IgE,IL-17,and CCL5 was decreased and the expression of anti-inflammatory factor(IL-10,CD4+CD25+)was increased.CONCLUSION:In the state of immune tolerance,symptoms of conjunctivitis in mice are alleviated,the Th-17 cells of allergic conjunctivitis mice are inhibited,and Treg cells activity is enhanced.
基金the Research Project of National Natural Science Foundation of China(81960761,81960751,81680705)Basic Ability Improvement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi(2018KY1149)Natural Science Foundation of Guangxi Province(2020JJA140257).
文摘Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturbance of liver is one of the important pathogenesis of chronic liver disease,the improvement of microcirculation is beneficial to the recovery of liver function and the delay of liver fibrosis.Hepatic stellate cells are the core cells of hepatic fibrosis,and also the most critical cells that affect the microcirculation of the liver.While TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs which are based on the action of hepatic stellate cells are two pathways that have very important influence on the inflammatory response of liver,the proliferation and apoptosis of hepatic stellate cells,and the secretion of fibrogenic cytokines.It was found that Plumbapin,the active ingredient of Guangxi specialty ethnic medicine,has the definite effect of promoting blood circulation and removing blood stasis and anti-hepatic fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived as follows:the pharmacological effect of Plumbapin on anti-hepatic fibrosis,promoting blood circulation and removing stasis was based on the influence of TLR4/MyD88/NF-κB and MAPKs signal pathway.
文摘[Objectives]To explore the effect and possible mechanism of bergenin in relieving allergic rhinitis(AR)in mice.[Methods]50 C57/BL6 mice were randomly divided into blank group(n=10),model group(n=10)and high(100 mg/kg),medium(50 mg/kg)and low(25 mg/kg)dose bergenin groups with 10 mice in each group.Except for the blank group,the other mice were sensitized by basic ways combined with attack to replicate the AR model.From the 15th d of modeling(from the second d after the end of the basic modeling),the drug group was given bergenin orally for 15 d,and the blank group and model group were given the same volume of normal saline once a day.24 h after the last establishment of the model,the content of interleukin 4(IL-4),IL-6,TNF-αand IL-1βin nasal lavage fluid and serum of mice in each group was detected by ELISA.The expression of TLR-4,NF-κB and p-NF-κB in nasal mucosa of mice was detected by Western blot.[Results]Compared with the blank group,the content of inflammatory factors IL-4,IL-6,TNF-αand IL-1βin nasal lavage fluid and serum of model group was significantly increased,and the protein expression of TLR-4 and p-NF-κB was significantly increased.After the intervention of bergenin,the content of IL-4,IL-6,TNF-αand IL-1βin nasal lavage fluid and serum and TLR-4 and p-NF-κB protein in tissue was significantly inhibited in bergenin group.[Conclusions]Bergenin can effectively reduce allergic inflammation in AR model mice,and its mechanism may be related to inhibition of inflammation and down-regulation of TLR-4/NF-κB signal pathway.
文摘Background To investigate the effects and mechanisms of cellular repressor of ElA stimulated genes (CREG) on endothelial cell(EC) migration.Methods vascular endothelial cells(VE),CREG overexpression VEs, CREG suppression VEs and VEs transfected with CREG gene modified adenovirus(Ad-CREG) were cultured with dulbecco’s modified eagle’s medium contained 10%fetal calf serum. Western blot was used to detect the protein level of CREG and integrin-linked kinase(ILK) in the four kind ECs.Tran-swell migration model was applied to compare the migration cell number of the four kind ECs.Two kinds of ILK mutant plasmids;PCXN2-flag-ILK wt-IRES-GFP(wild-type ILK)and PCXN2-flag-ILK p-parvin-IRES-GFP(P-parvin-binding mutant) were used to transfect VS and VE respectively,then the two kind transfection ECs were named as VS-wtILK and VE-P -parvin which were selected by G418(600ng/ml)for 2 weeks;Transwell migration model was applied to compare migration capability before and after ILK plasmids transfecting VE and VS.Results Western blot analysis showed that CREG overexpression promoted ILK expression in ECs,on the contrary,ILK expression was down-regulated in CREG silent ECs(P【0.05).Further more,ILK expression was up-regulated obviously in VE transfected with Ad-CREG(P【 0.05);Transwell migration model showed that EC’s migration capability was positively correlated with the expression level of CREG in EC,that is,CREG overexpression induced VE migration and CREG silent suppressed VE migration, moreover,Ad-CREG transfecting VE showed better migration capability accompanied with CREG expression increase by transwell migration model(P【0.05).In order to know the relationship between ILK expression and cell migration,we obtained stable transfection cell strains of VS-wtILK and VE-Pparvin, transwell migration model demonstrated that VS-wtILK remarkably corrected the poor migration capability of VS(P【 0.01),butβ-parvin combining site mutation in ILK genes inhibited VE migration markedly(P【0.01).Conclusions ILKp -parvin signal pathway mediated vascular endothelial cell migration induced by CREG.
文摘Psoriasis is a complex skin disease and the pathogenesis of psoriasis is not clear.The purpose of this study is to identify the key driving genes and signal pathways involved in psoriasis and to predict the potential miRNA,for further understanding the pathogenesis of psoriasis.Methods:Three gene expression profiling chips,including GSE67853,GSE78097,and GSE136757 with a total of 120 samples were collected and analyzed with R software.The protein-protein interaction network of differentially expressed genes was constructed with STRING database and Cytoscape.CIBERSORT was used to evaluate the infiltration of immune cells in psoriasis tissues,and the correlation between diagnostic markers and infiltrating immune cells was analyzed.Further,the key biomarkers were identified and the targeting miRNA of crucial genes was predicted.Results:A total of 201 differentially expressed genes(163 upregulated genes and 38 downregulated genes)were determined.CXCL1,CXCL2,and CXCL8,the critical biomarkers of psoriasis,were identified by different calculation methods.The potential critical signal pathway NOD-like receptor signaling pathway of psoriasis was explored by gene expression profiling chip gene enrichment analysis and differentially expressed gene enrichment analysis.Immune cell infiltration analysis found that CXCL1,CXCL2,CXCL8 was positively correlated with macrophages M1 and T cells CD4 memory activated and negatively correlated with macrophages M2 and mast cells resting.At the same time,through miRNA prediction,we found that hsa-miR-216a-3p and hsa-miR-6750-5p can be used as potential psoriasis targets.Conclusions:This research proposes a new comprehensive strategy to identify psoriasis’s potential biomarkers through cross-validation and significant scores of different calculation methods.In this research,we identified CXCL1,CXCL2,and CXCL8 as potential key biomarkers of psoriasis,and the NOD-like receptor signaling pathway is the critical signal pathway of psoriasis.Hsa-miR-216a-3p and hsa-miR-6750-5p can be used as potential psoriasis targets.
基金Supported by The Natural Science Foundation of Heilongjiang Province, No. 2005-13
文摘AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.
基金supported by Health Bureau of Luzhou No:2012-S-40(1/5)Health Department of Sichuan(120389)
文摘Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro.Methods:The experiment was conducted in 4 different mediums:NSCs+PBS(Group A-blank control group),NSCs+SCE with healthy SD rats(Croup B-normal control group),NSCs+SCE with SD rats receiving sham-operation treatment(Croup C-sham-operation group)and NSCs+SCE with SCIs rats(Group D-paraplegic group).Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1,2,3,4 and 5 d,respectively.The expressions of Notch 1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h,respectively.Results:After co-culture for 1,2,3,4 and 5 d respectively,the MTT values of group D were significantly higher than those of group A,group B and group C(P<0.05).However,there were no significantly differences regarding MTT values between group A,group B and group C after co-culture for 1,2,3,4 and 5 d,respectively(P>0.05).Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well(P<0.05).But there was no difference oin expressions of Notch1 and Hes1 mRNA among group A,group B and group C after co-culture for 24 h and 48 h(P>0.05).There was no difference in expressions of Notch1and Hes1 mRNA between 24 h and 48 h treatment in group D.Conclusions:SCE could promote the proliferation of NSCs.It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs.Besides,SCE could increase the expression of Notch1 and Hes1 mRNA of NSC.It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs.This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene.
基金supported by National Science Funded Project(81060017)
文摘Objective:To observe the expression changes of inflammatory markers TGF-β1,Smad3 and IL-6 in patients with atrial fibrillation(AF),and to explore the significance of TGF-β1 signaling pathway in the structural remodeling of AF.Methods:The expression of TGF-β1,Smad3 and IL-6 in 50 cases with AF and 30 normal cases were detected by RT-PCR and ELISA.Results:The TGF-β1,Smad3 and IL-6 mRNA and protein expression levels in patients with AF were significantly higher than that in the control group(P<0.05),but there was no significantly different between the paroxysmal AF group and the persistent AF group(P>0.05).The TGF-β1mRNA expression in the≥50 years subgroup was significantly higher than that in the<50years subgroups,and it was higher in the NYHAⅢsubgroup than in theⅠ/Ⅱgrade subgroup.It was also higher in the left ventricular ejection fraction(LVEF)<50%subgroup than in LVEF≥50%group,and it was significantly higher in the AF time≥36 months subgroup than that in<36months subgroup(P<0.05).The Smad3 and IL-6 expressions in the in the LVEF<50%subgroup were both high that than that in LVEF≥50%group,and higher in the AF time≥36 months subgroup than that in<36 months subgroup(P<0.05).There were a positive correlation between TGF-β1,Smad3 and IL-6(r=0.687,r=0.547).There were also a positive correlation between Smad3 and IL-6 mRNA(r=0.823).Conclusions:AF is associated with inflammation,and the inflammation is also involved in the fibrillation and sustain of AF.The TGF-β1 signal pathway may be involved in the process of atrial structural remodeling in patients with AF,and iss related with the occurrence and maintenance of AF.
基金The project supported by National Natural Science Foundation of China(81573645,81603101,81473383)
文摘OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.
文摘Objective: To observe the effect of acupuncture on the expression of ERM/PI3K/Akt signaling pathway in the brain tissue around the infarct focus of ischemic stroke model rats. Methods: According to the block randomization method, 80 male SD rats were divided into normal group (n = 10), sham operation group (n = 24), model group (n = 23) and acupuncture group (n = 23). The normal group was bred routinely without any intervention. In the sham operation group, only the skin was cut to find and the nerves and blood vessels were stripped and sutured. The model group and the acupuncture group were sutured to prepare the MCAO model. After the model was successfully established, acupuncture of the acupuncture group rats was given once a day, and the needles were kept for 30 minutes each time. The rats in the sham operation group and the model group only imitated capture and return, and were treated with acupuncture for 2 consecutive courses, each course was 5 days, and the two courses were rested for 2 days. After that, Western blot was used to detect ERM, changes in the concentration of PI3K and Akt proteins. Results: Compared with the normal group, the expression levels of ERM, PI3K, and Akt proteins in the sham operation group were reduced. Compared with the sham operation group, the expression levels of ERM, PI3K, and Akt proteins in the model group were significantly down-regulated. Compared with the model group, the protein expression levels of ERM, PI3K and Akt were significantly up-regulated in the acupuncture group, and the difference was statistically significant (P < 0.05). Conclusion: Acupuncture can significantly up-regulate the expression of ERM, PI3K and Akt proteins, and its effect mechanism may be related to the transduction of ERM/PI3K/Akt signaling pathway in cells.
基金Supported by Fundamental Research Fund of Freshwater Fisheries Research Center of Chinese Academy of Fishery Science(2017JBFM07)Natural Science Foundation of Jiangsu Province(BK20150117)Earmarked Fund for Modern Agro-industry Technology Research System(CARS-46)。
文摘This study was conducted to find the differentially expressed genes and understand the transcriptome change characteristics in the testis of tilapia(Oreochromis niloticus) stressed by methomyl.The tilapia were exposed to 200 μg/L methomyl for 30 d,and then the testis samples were collected and used for the highthroughput sequencing.The results showed that 369 significant differentially expressed genes were obtained,including 160 significantly down-regulated genes,and209 significantly up-regulated genes.The enrichment of the differentially expressed genes in ECM-receptor interaction signaling pathway and MAPK signaling pathway was obvious.The adhesion of testis tissue cells was influenced by methomyl stress,which induced the expression of related gene in ECM-receptor interaction up-regulating,such as laminins,integrin α6 and integrin β1,in order to stabilize testis tissue structure.JNK,MAP3 K and MKK4 in the JNK pathway were significantly up-regulated,which enhanced transcription factor AP-1 to promote the expression of P53,Bax and other pro-apoptotic proteins.The expression of growth-related factors in the ERK pathway of MAPK signal pathway was influenced by methomyl stress.The apoptosis-related genes and pregnancy-related genes have significant differential expression under methomyl stress,and thereby,the proliferation of reproduction cells in the testis tissue may be affected.
文摘Objective:To study the effects of different administration routes of neoadjuvant chemotherapy on cancer cell growth signal pathway function in cervical cancer.Methods: Patients with cervical cancer who received neoadjuvant chemotherapy in Fufeng People's Hospital between July 2008 and July 2016 were selected as the research subjects and randomly divided into intervention group and intravenous group who accepted the neoadjuvant interventional arterial chemotherapy and neoadjuvant intravenous chemotherapy respectively. After surgical resection, the contents of PI3K/AKT/mTOR, Wnt/β-catenin and MEK/ERK signaling pathway in cervical cancer lesions were determined.Results:p-PI3K, p-AKT, mTOR, MMP2, VEGF,β-catenin, CyclinD1, Twist, Slug, Snail, MEK1, MEK2, ERK1/2 and Bcl-2 protein levels in cervical cancer lesion of intervention group were significantly lower than those of intravenous group whereas E-cadherin and Bax protein levels were significantly higher than those of intravenous group.Conclusion: Neoadjuvant interventional arterial chemotherapy can be more effective than neoadjuvant intravenous chemotherapy to inhibit the cancer cell growth mediated by PI3K/AKT/mTOR, Wnt/β-catenin and MEK/ERK signaling pathway in cervical cancer.
基金supported by grants from the National Natural Science Foundation of China(No.30870584,No.81201737)the Doctoral Program Foundation of Institutions of Higher Education of China(No.20120061110063)
文摘Objective The purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line(EL-4 cells) was used. The expressions of CD4,CD25,Nrp1,calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-β1,IL-10,PKA and cAMP were estimated with ELISA. Results At 12 h after irradiation,the expression of Nrp1 increased significantly in 4.0 Gy group,compared with sham-irradiation group(P<0.05) in the spleen and thymus,respectively,when ICR mice received whole-body irradiation(WBI). Meanwhile the synthesis of Interleukin 10(IL-10) and transforming growth factor-β1(TGF-β1) increased significantly after high dose irradiation(HDR)(> or = 1.0 Gy). In addition,the expression of cAMP and PKA protein increased,while PKC-α,calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation,this did not limit the up-regulation of CD4+CD25+Nrp1+Treg cells after ionizing radiation. Conclusion These results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.
文摘To explore the intracellular signal pathways for β-VLDL induced very low density lipoprotein receptor (VLDL-R) transcription up-regulation and their effects on lipid accumulation in macrophages, Western Blot was used to examine phosphorylated ERK1/2 protein and regulated effects by different singal kinase inhibitants. It was found that β-VLDL induced an increase in ERK1/2 activity in a protein kinase C (PKC)-dependent manner in murine RAW264.7 macrophages. By using different protein kinases inhibitors or activators, it was observed that the effect of β-VLDL induced VLDL receptor transcription, which was monitored by RT-PCR analysis of VLDL receptor mRNA, was not affected by the inhibitor of p38 kinase and cAMP analog, but extremely abolished by pretreating cells with PD98059, an inhibitor of ERK and GF 109203X, an inhibitor of PKC. These results demonstrated that the PKC-ERK1/2 cascade is the essential signaling pathway by which β-VLDL activated VLDL-R mRNA expression. Inhibition of the ERK1/2 signaling cascade resulted in suppression of the cellular lipid accumulation induced by β-VLDL in macrophages.
基金supported by grants from National Natural Sciences Foundation of China (to Qinghua ZHOU, No.3007033 )
文摘Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the
