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
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
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
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
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.
文摘目的研究急性缺血性脑卒中(acute ischemic stroke,AIS)患者的血清中糖蛋白非转移性黑色素瘤蛋白B(glycoprotein non-metastatic melanoma protein B,GPNMB)浓度和神经功能损伤程度以及预后的关系,筛选潜在生物标志物,为临床诊治提供参考。方法选择2023年6月至2024年3月在南通大学第二附属医院神经内科住院治疗的105例AIS患者作为样本群。入组患者按照入院24 h美国国立卫生研究院脑卒中量表(National Institutes of Health Strobe Scale,NIHSS)评分划分为轻度组(n=42)和中重度组(n=63),以改良Rankin量表(Modified Rankin Scale,mRS)评价出院后3个月功能恢复情况,将样本细分为预后良好组(n=34)和预后不良组(n=71),采用ELISA法检测血清GPNMB蛋白浓度,分析血清GPNMB蛋白浓度与NIHSS、mRS评分的相关性,并用二元Logistic回归模型评估血清GPNMB蛋白浓度对AIS神经功能损害的预测价值和预后评估价值。结果中重度神经功能损伤及预后不良患者血清GPNMB蛋白浓度明显低于轻度及预后良好组(P<0.05),血清GPNMB蛋白浓度与NIHSS评分呈显著负相关(r=-0.196,P<0.05),与mRS评分也呈显著负相关趋势(r=-0.334,P<0.05)。多变量回归分析显示,GPNMB依然是AIS的关键独立危险因素(P<0.05),根据受试者工作特征曲线得出的评估结果表明,血清GPNMB蛋白浓度在预测神经功能损伤以及不良预后方面的有诊断价值(灵敏度达到55.6%,特异度为81.8%,准确率是63.81%,P<0.05)。结论血清GPNMB蛋白浓度降低同AIS患者神经功能损害的程度存在明显的正相关联系,很有可能会成为衡量病情严重程度和长期转归情况的重要生物指标。
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.
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.
