OBJECTIVE:To investigate the hypoglycemic mechanism of modified Gegen Qinlian decoction(加味葛根芩连汤,MGQD)by examining its regulation of cholesterol transporter expression and DNA methylation,specifically the low-de...OBJECTIVE:To investigate the hypoglycemic mechanism of modified Gegen Qinlian decoction(加味葛根芩连汤,MGQD)by examining its regulation of cholesterol transporter expression and DNA methylation,specifically the low-density lipoprotein receptor(LDLR)and scavenger receptor class B type 1(SR-B1),in epididymal white adipose tissue(e WAT)and inguinal white adipose tissue(i WAT)of rats with type 2 diabetes mellitus(T2DM).METHODS:The control group(CON)consisted of ten Sprague-Dawley(SD)rats fed a standard chow diet,while 80 SD rats were fed a high-fat diet and administered streptozotocin intraperitoneally to induce diabetes.The diabetic rats were randomly assigned to four groups:T2DM,metformin(MET,200 mg/kg),low-dose MGQD(MGQDL,5 g/kg),and high-dose MGQD(MGQDH,10 g/kg),and received treatment via gavage for 14 weeks.Western blot(WB),quantitative real-time polymerase chain reaction(q PCR),and bisulfite sequencing PCR(BSP)were used to analyze protein levels,m RNA expression,and DNA methylation of Ldlr(gene encoding LDLR)and Srb1(gene encoding SR-B1).RESULTS:MGQD and metformin treatment significantly reduced blood glucose levels,restored LDLR and SR-B1 protein levels in e WAT,and effectively regulated the m RNA expression and non-cytosine-p-guanine(nonCp G)methylation of Srb1 in e WAT.A significant negative correlation was observed between the methylation of Srb1 in e WAT and its m RNA expression.However,MGQD and metformin had no significant effect on the protein levels,m RNA expression,or DNA methylation of Ldlr and Srb1 in i WAT.CONCLUSIONS:MGQD did not significantly affect LDLR and SR-B1 expression or gene methylation in i WAT.However,its hypoglycemic effect may be linked to cholesterol regulation in e WAT.Potential mechanisms include increased LDLR protein levels,which may enhance cholesterol uptake,and increased Srb1 methylation,which may suppress its expression and consequently reduce cholesterol efflux.展开更多
BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.Howeve...BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.展开更多
Modified Da-chai-hu Decoction(MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis(SAP) for decades. The ai...Modified Da-chai-hu Decoction(MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis(SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD(23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase(DAO), pulmonary surfactant protein-A(SP-A), and C-reactive protein(CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase(MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB(NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and monocyte chemoattractant protein-1(MCP-1) were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4±585.5) U·L^(-1) vs(5626.4±795.1) U·L^(-1)], DAO[(1100.1±334.3) U·L^(-1) vs(1666.4±525.3) U·L^(-1)] and CRP [(7.6±1.2) μg·mL^(-1) vs(17.8±3.8) μg·mL^(-1)]. However, the serum SP-A concentration [(106.1±16.6) pg·mL^(-1) vs(90.1±14.9) pg·mL^(-1)] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.展开更多
AIM： To observe the effect of modified Si-Miao-San （mSMS） on advanced glycation end products （AGEs）-induced pancreatic B cell dysfunction, as well as examining the underlying mechanisms.METHOD： Pancreatic B cel...AIM： To observe the effect of modified Si-Miao-San （mSMS） on advanced glycation end products （AGEs）-induced pancreatic B cell dysfunction, as well as examining the underlying mechanisms.METHOD： Pancreatic B cells （INS-l） were stimulated with advanced glycation end products （AGEs, 200 μg.mL^-1） for 24 h to produce dysfunction in pancreatic B cells and the effects of mSMS observed on insulin secretion, NF-κB （p65） phosphorylation, reactive oxygen species （ROS） production, mitochondria membrane potential （△ψm）, cell apoptosis, phosphorylation of AMP-kinase （AMPK）, and caspase 3 activity. RESULTS： The AGEs challenge resulted in increased basal insulin secretion, but decreased insulin secretion in response to high glucose, whereas this situation was reversed by mSMS treatment. AGEs stimulation induced NF-κB （p65） phosphorylation and reactive oxygen species （ROS） production, as well as Agtm collapse and cell apoptosis, mSMS inhibited ROS production and inhibited NF-κB activation by attenuating p65 phosphorylation. Meanwhile, AGEs-induced A^m collapse and cell apoptosis were also reversed by mSMS treatment. Compound C, an inhibitor of AMP-Kinase （AMPK）, abolished the beneficial effects of mSMS on the regulation of B cell fimction, indicatin~ the involvement of AMPK. cONCLUSION： mSMS ameliorated AGEs-induced B cell dysfimction by suppressing ROS-associated inflammation, and this action was related to its beneficial regulation of AMPK activity.展开更多
OBJECTIVE:To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction(加味黄芪赤风汤,MHCD)in immunoglobulin A nephropathy(IgAN)rats.METHODS:To establish the IgAN rat model,the bovine serum albumin,...OBJECTIVE:To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction(加味黄芪赤风汤,MHCD)in immunoglobulin A nephropathy(IgAN)rats.METHODS:To establish the IgAN rat model,the bovine serum albumin,lipopolysaccharide,and carbon tetrachloride 4 method was employed.The rats were then randomly assigned to the control,model,telmisartan,and high-,medium-,and low-dose MHCD groups,and were administered the respective treatments via intragastric administration for 8 weeks.The levels of 24-h urinary protein,serum creatinine(CRE),and blood urea nitrogen(BUN)were measured in each group.Pathological alterations were detected.IgA deposition was visualized through the use of immunofluorescence staining.The ultrastructure of the kidney was observed using a transmission electron microscope.The expression levels of interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),and transforming growth factor-β1(TGF-β1)were examined by immunohistochemistry and quantitative polymerase chain reaction.Levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear factor-kappa B(NF-κB)P65,were examined by immunohistochemistry,Western blotting,and quantitative polymerase chain reaction.RESULTS:The 24-h urine protein level in each group increased significantly at week 6,and worsen from then on.But this process can be reversed by treatments of telmisartan,and high-,medium-,and low-dose of MHCD,and these treatments did not affect renal function.Telmisartan,and high-,and medium-dose of MHCD reduced IgA deposition.Renal histopathology demonstrated the protective effect of high-,medium-,and low-dose of MHCD against kidney injury.The expression levels of MCP-1,IL-6,and TGF-β1 in kidney tissues were downregulated by low,medium and high doses of MHCD treatment.Additionally,treatment of low,medium and high doses of MHCD decreased the protein and mRNA levels of TLR4,MyD88,and NF-κB.CONCLUSIONS:MHCD exerted nephroprotective effects on IgAN rats,and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway,thereby alleviating renal inflammation by inhibiting MCP-1,IL-6 expressions,and ameliorating renal fibrosis by inhibiting TGF-β1 expression.展开更多
A simple modified analytic EAM model for bcc Fe and fcc Al was used to calculate the lattice constant and elastic constants of B2 FeAl and DO3 Fe3Al alloys. The formation energies of ...A simple modified analytic EAM model for bcc Fe and fcc Al was used to calculate the lattice constant and elastic constants of B2 FeAl and DO3 Fe3Al alloys. The formation energies of vacancy and antisite were also calculated. The present calculations are in agreement with the experimental data and the theoretical results obtained by other authors.展开更多
The purpose of this work is to study the possibility of anionic dyes Reactive Red M-8B（RR） and Direct Green B（DG） adsorbed on chitosan-modified diatomite. The characteristics of adsorbent, adsorption isotherms and...The purpose of this work is to study the possibility of anionic dyes Reactive Red M-8B（RR） and Direct Green B（DG） adsorbed on chitosan-modified diatomite. The characteristics of adsorbent, adsorption isotherms and the influence of adsorption time, temperature and pH were researched in this work. The results show that the mo- dified diatomite had a much better adsorption capability than the natural diatomite. The adsorption capacities of chitosan-modified diatomite for RR and DG were 94.46 and 137.0 mg/g, respectively. Both adsorption time and adsorption temperature provided a positive effect on the dye adsorption. Within the experimental pH range, the adsorbance was enhanced at lower pH but reduced sharply at high pH. On the basis of the experimental results and discussion, electrostatic attraction is considered as the main mechanism of this chemisorption.展开更多
OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brai...OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brain barrier(BBB).METHODS In the present study,dendrimer,polyamidoamine(PAMAM),was synthesized as the nano-drug carriers.Angiopep-2,which has been proved excellent ability to cross the BBB,was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethylene glycol(PEG).Then scutellarin(STA)was encapsulated into the functionalized nanoparticles(NPs)to formulate Angiopep-2 modified STA-loaded PEG-PAMAM NPs.Ischemic stroke model was established to evaluate the treatment efficacy and protective mechanism of Angiopep-2-STA-PEG-PAMAM NPs.RESULTS The pharmacokinetics and biodistribu-tion demonstrated that Angiopep-2-STA-PEG-PAMAM NPs exhibited significantly higher plasma concentration from 1 h to 10 h after intravenous administration and improve accumulation in brain(4.7-fold)compared with STA solution.Moreover,prolonged elimination half-life(4.8-fold)and lower clearance(3.4-fold)were observed.The brain uptake study of 6-coumarin confirmed that Angiopep-2-PEG-PAMAM NPs possessed better brain targeting efficacy(3.2-fold)than PEG-PAMAM NPs.Angiopep-2-STA-PEG-PAMAM NPs obviously ameliorated infarct volume,neurological deficit,histopathological severity and neuronal apoptosis.In addition,Angiopep-2-STA-PEG-PAMAM NPs markedly inhibited the calcium content and the levels of IL-12p40,IL-13,IL-17 and IL-23.Furthermore,Angiopep-2-STA-PEG-PAMAM NPs significantly decreased the m RNA and protein expressions of HMGB1,TLR2,TLR4,TLR5,My D88,TRIF,TRAM,IRAK-4,TRAF6,IкBα,IKKβand NF-кBp65.CONCLUSION The results suggested that Angiopep-2modified scutellarin-loaded PEG-PAMAM nanocarriers possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and HMGB1/TLRs/MyD 88-induced NF-κB activation pathways.展开更多
基金National Natural Science Foundation of China:Investigation on the Mechanism of Gegen Qinlian Decoction in Lowering Blood Glucose Based on Improving Cholesterol Homeostasis of Lipid Rafts in Adipocytes(No.82060741)Study on the Cause of“Dampness Stagnating in Pi”in Type 2 Diabetes Mellitus by Overeating High Fat and Sugar Diet Based on Glycerol Transport Which Is Affected by Methylation/Hormones Signal(No.82160830)+4 种基金Investigation on the Mechanism of Gegen Qinlian Decoction in Lowering Blood Glucose Based on Improving Phosphatidylcholine Biosynthesis in Adipose Tissue(No.82360799)Jiangxi Provincial Administration of Traditional Chinese Medicine Science and Technology Program:the Relationship between Adipose Tissue and Spleen Image Based on Multivariate Analysis of Modern Literature(No.2020B0328)Ganpo Juncai-Training Program for Academic and Technical Leaders in Major Disciplines of the Province(Leading Talents-Academic Category)(20232BCJ22022)Jiangxi University of Chinese Medicine,First-level Discipline of Integrative Medicine(Jiangxi Province Double First-class Discipline)(zxyylxk20220103)Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program(CXTD22007)。
文摘OBJECTIVE:To investigate the hypoglycemic mechanism of modified Gegen Qinlian decoction(加味葛根芩连汤,MGQD)by examining its regulation of cholesterol transporter expression and DNA methylation,specifically the low-density lipoprotein receptor(LDLR)and scavenger receptor class B type 1(SR-B1),in epididymal white adipose tissue(e WAT)and inguinal white adipose tissue(i WAT)of rats with type 2 diabetes mellitus(T2DM).METHODS:The control group(CON)consisted of ten Sprague-Dawley(SD)rats fed a standard chow diet,while 80 SD rats were fed a high-fat diet and administered streptozotocin intraperitoneally to induce diabetes.The diabetic rats were randomly assigned to four groups:T2DM,metformin(MET,200 mg/kg),low-dose MGQD(MGQDL,5 g/kg),and high-dose MGQD(MGQDH,10 g/kg),and received treatment via gavage for 14 weeks.Western blot(WB),quantitative real-time polymerase chain reaction(q PCR),and bisulfite sequencing PCR(BSP)were used to analyze protein levels,m RNA expression,and DNA methylation of Ldlr(gene encoding LDLR)and Srb1(gene encoding SR-B1).RESULTS:MGQD and metformin treatment significantly reduced blood glucose levels,restored LDLR and SR-B1 protein levels in e WAT,and effectively regulated the m RNA expression and non-cytosine-p-guanine(nonCp G)methylation of Srb1 in e WAT.A significant negative correlation was observed between the methylation of Srb1 in e WAT and its m RNA expression.However,MGQD and metformin had no significant effect on the protein levels,m RNA expression,or DNA methylation of Ldlr and Srb1 in i WAT.CONCLUSIONS:MGQD did not significantly affect LDLR and SR-B1 expression or gene methylation in i WAT.However,its hypoglycemic effect may be linked to cholesterol regulation in e WAT.Potential mechanisms include increased LDLR protein levels,which may enhance cholesterol uptake,and increased Srb1 methylation,which may suppress its expression and consequently reduce cholesterol efflux.
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2021B1515140043,No.2022A1515140124 and No.2023A1515140115.
文摘BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.
基金supported by the Key Research Lab of State Administration of Traditional ChineseComprehensive Investment Subject Construction Project of Tianjin Medical University(2016-2020)the National Natural Science Foundation of China(No.81703846)
文摘Modified Da-chai-hu Decoction(MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis(SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD(23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase(DAO), pulmonary surfactant protein-A(SP-A), and C-reactive protein(CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase(MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB(NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and monocyte chemoattractant protein-1(MCP-1) were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4±585.5) U·L^(-1) vs(5626.4±795.1) U·L^(-1)], DAO[(1100.1±334.3) U·L^(-1) vs(1666.4±525.3) U·L^(-1)] and CRP [(7.6±1.2) μg·mL^(-1) vs(17.8±3.8) μg·mL^(-1)]. However, the serum SP-A concentration [(106.1±16.6) pg·mL^(-1) vs(90.1±14.9) pg·mL^(-1)] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.
基金supported by the National Natural Science Foundation of China(Nos.81072976,81173623)the Fundamental Research Funds for the Central Universities(No.JKY2011063)+1 种基金the 2011 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher EducationJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization
文摘AIM： To observe the effect of modified Si-Miao-San （mSMS） on advanced glycation end products （AGEs）-induced pancreatic B cell dysfunction, as well as examining the underlying mechanisms.METHOD： Pancreatic B cells （INS-l） were stimulated with advanced glycation end products （AGEs, 200 μg.mL^-1） for 24 h to produce dysfunction in pancreatic B cells and the effects of mSMS observed on insulin secretion, NF-κB （p65） phosphorylation, reactive oxygen species （ROS） production, mitochondria membrane potential （△ψm）, cell apoptosis, phosphorylation of AMP-kinase （AMPK）, and caspase 3 activity. RESULTS： The AGEs challenge resulted in increased basal insulin secretion, but decreased insulin secretion in response to high glucose, whereas this situation was reversed by mSMS treatment. AGEs stimulation induced NF-κB （p65） phosphorylation and reactive oxygen species （ROS） production, as well as Agtm collapse and cell apoptosis, mSMS inhibited ROS production and inhibited NF-κB activation by attenuating p65 phosphorylation. Meanwhile, AGEs-induced A^m collapse and cell apoptosis were also reversed by mSMS treatment. Compound C, an inhibitor of AMP-Kinase （AMPK）, abolished the beneficial effects of mSMS on the regulation of B cell fimction, indicatin~ the involvement of AMPK. cONCLUSION： mSMS ameliorated AGEs-induced B cell dysfimction by suppressing ROS-associated inflammation, and this action was related to its beneficial regulation of AMPK activity.
基金Joint Innovation Fundation of JIICM:Health Management of Chronic Kidney Disease Based on Integrated Traditional Chinese And Western Medicine(No.2021IR009)Natural Science Foundation-funded Project:the Mechanism of Modified Huangqi Chifeng Decoction Protect Damaged Podocyte via Cross-Talking of PI3K/AKT/mTOR and AMPK/mTOR/ULK1 Signaling Pathway Regulate Autophapy(No.81873300)+1 种基金the Central Publicinterest Scientific Institution Basal Research Fund of the China Academy of Chinese Medical Sciences:Comprehensive Evaluation of Clinical efficacy of Modified Huangqi Chifeng Decoction on IgA Nephropathy(No.ZZ11-023)the Beijing Municipal of Science and Technology Major Project:Evaluation of Clinical Efficacy of Modified Huangqi Chifeng Decoction in Treating Proteinuria in IgA Nephropathy Based on"Deficiency-Wind-Blood-Stasis-Toxicity"Mechanism in Chinese Medicine(No.Z191100006619063)。
文摘OBJECTIVE:To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction(加味黄芪赤风汤,MHCD)in immunoglobulin A nephropathy(IgAN)rats.METHODS:To establish the IgAN rat model,the bovine serum albumin,lipopolysaccharide,and carbon tetrachloride 4 method was employed.The rats were then randomly assigned to the control,model,telmisartan,and high-,medium-,and low-dose MHCD groups,and were administered the respective treatments via intragastric administration for 8 weeks.The levels of 24-h urinary protein,serum creatinine(CRE),and blood urea nitrogen(BUN)were measured in each group.Pathological alterations were detected.IgA deposition was visualized through the use of immunofluorescence staining.The ultrastructure of the kidney was observed using a transmission electron microscope.The expression levels of interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),and transforming growth factor-β1(TGF-β1)were examined by immunohistochemistry and quantitative polymerase chain reaction.Levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear factor-kappa B(NF-κB)P65,were examined by immunohistochemistry,Western blotting,and quantitative polymerase chain reaction.RESULTS:The 24-h urine protein level in each group increased significantly at week 6,and worsen from then on.But this process can be reversed by treatments of telmisartan,and high-,medium-,and low-dose of MHCD,and these treatments did not affect renal function.Telmisartan,and high-,and medium-dose of MHCD reduced IgA deposition.Renal histopathology demonstrated the protective effect of high-,medium-,and low-dose of MHCD against kidney injury.The expression levels of MCP-1,IL-6,and TGF-β1 in kidney tissues were downregulated by low,medium and high doses of MHCD treatment.Additionally,treatment of low,medium and high doses of MHCD decreased the protein and mRNA levels of TLR4,MyD88,and NF-κB.CONCLUSIONS:MHCD exerted nephroprotective effects on IgAN rats,and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway,thereby alleviating renal inflammation by inhibiting MCP-1,IL-6 expressions,and ameliorating renal fibrosis by inhibiting TGF-β1 expression.
文摘A simple modified analytic EAM model for bcc Fe and fcc Al was used to calculate the lattice constant and elastic constants of B2 FeAl and DO3 Fe3Al alloys. The formation energies of vacancy and antisite were also calculated. The present calculations are in agreement with the experimental data and the theoretical results obtained by other authors.
基金Supported by the Research Fund of Environmental Protection Bureau in Jilin Province,China(No.2007-13)
文摘The purpose of this work is to study the possibility of anionic dyes Reactive Red M-8B（RR） and Direct Green B（DG） adsorbed on chitosan-modified diatomite. The characteristics of adsorbent, adsorption isotherms and the influence of adsorption time, temperature and pH were researched in this work. The results show that the mo- dified diatomite had a much better adsorption capability than the natural diatomite. The adsorption capacities of chitosan-modified diatomite for RR and DG were 94.46 and 137.0 mg/g, respectively. Both adsorption time and adsorption temperature provided a positive effect on the dye adsorption. Within the experimental pH range, the adsorbance was enhanced at lower pH but reduced sharply at high pH. On the basis of the experimental results and discussion, electrostatic attraction is considered as the main mechanism of this chemisorption.
基金The project supported by National Natural Science Foundation of China(NSFC 21476054)the Natural Science Foundation of Heilongjiang Province(B201407)
文摘OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brain barrier(BBB).METHODS In the present study,dendrimer,polyamidoamine(PAMAM),was synthesized as the nano-drug carriers.Angiopep-2,which has been proved excellent ability to cross the BBB,was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethylene glycol(PEG).Then scutellarin(STA)was encapsulated into the functionalized nanoparticles(NPs)to formulate Angiopep-2 modified STA-loaded PEG-PAMAM NPs.Ischemic stroke model was established to evaluate the treatment efficacy and protective mechanism of Angiopep-2-STA-PEG-PAMAM NPs.RESULTS The pharmacokinetics and biodistribu-tion demonstrated that Angiopep-2-STA-PEG-PAMAM NPs exhibited significantly higher plasma concentration from 1 h to 10 h after intravenous administration and improve accumulation in brain(4.7-fold)compared with STA solution.Moreover,prolonged elimination half-life(4.8-fold)and lower clearance(3.4-fold)were observed.The brain uptake study of 6-coumarin confirmed that Angiopep-2-PEG-PAMAM NPs possessed better brain targeting efficacy(3.2-fold)than PEG-PAMAM NPs.Angiopep-2-STA-PEG-PAMAM NPs obviously ameliorated infarct volume,neurological deficit,histopathological severity and neuronal apoptosis.In addition,Angiopep-2-STA-PEG-PAMAM NPs markedly inhibited the calcium content and the levels of IL-12p40,IL-13,IL-17 and IL-23.Furthermore,Angiopep-2-STA-PEG-PAMAM NPs significantly decreased the m RNA and protein expressions of HMGB1,TLR2,TLR4,TLR5,My D88,TRIF,TRAM,IRAK-4,TRAF6,IкBα,IKKβand NF-кBp65.CONCLUSION The results suggested that Angiopep-2modified scutellarin-loaded PEG-PAMAM nanocarriers possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and HMGB1/TLRs/MyD 88-induced NF-κB activation pathways.
