Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effe...Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising coimmunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.展开更多
Objective To evaluate the efficacy of Chinese medicine acupoint application(CMAA)combined with Western medicine for perennial allergic rhinitis(PAR)in children.Methods In this prospective,parallel,randomized,placebo-c...Objective To evaluate the efficacy of Chinese medicine acupoint application(CMAA)combined with Western medicine for perennial allergic rhinitis(PAR)in children.Methods In this prospective,parallel,randomized,placebo-controlled and single-blind trial from August to September,2017,180 children with PAR were randomly assigned to an integrative group(CMAA and Montelukast),CMAA group(CMAA and placebo tablet),or Montelukast group(placebo CMAA and Montelukast).Participants were applied with CMAA for 6 sessions over 2 weeks,and/or Montelukast Chewable Tablet orally once daily for 12 weeks.The changes in severity of symptoms were measured by Visual Analog Scale(VAS)and rhinitis control assessment test(RCAT)at 0,2,4 and 12 weeks of treatment.Blood samples were collected for serum interleukin-4,interferon gammaγand T helper type 1(Th1)/Th2 flow cytometric analysis at the time points of 0,4 and 12 weeks.Results Eight cases dropped out from the trial,3 in the integrative group,2 in the CMAA group and 3 in the Montelukast group.The VAS scores decreased significantly while the RCAT scores increased significantly in all three groups at 4 and 12 weeks compared with baseline(P<0.01 or P<0.05).The VAS scores were significantly lower while the RCAT scores were significantly higher in the integrative and CMAA groups than the Montelukast group at 2 and 4 weeks(P<0.01 or P<0.05).At 2,4 and 12 weeks,the scores of nasal congestion,sneezing,sleep problem,and rhinitis symptom control in the integrative and CMAA groups increased significantly compared with baseline(P<0.01 or P<0.05).The least percentages of Th2 and the most alleviated Th2 shift(highest Th1/Th2)were observed in the integrative group at 12 weeks compared with the other two groups(P<0.05).Conclusion The combination of CMAA with Montelukast might be more effective and appropriate than either option alone for children with PAR.(Registered at Chinese Clinical Trial Register,registration No.ChiCTR-IOR-17012434).展开更多
Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SA...Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SAMP8) mice were used as AD models and received EA at Yingxiang(LI 20, bilateral) and Yintang(GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin(2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier(BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid-β(Aβ), and ionized calcium-binding adapter molecule 1(IBa-1) in mouse hippocampus(CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction(qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining.Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining. Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8mice and this was inhibited by EA treatment(P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice(P<0.01), which was reversed by fibrin injection(P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability(P<0.05 or P<0.01).Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8mice, which was reversed by fibrin injection(P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1(HMGB1)/toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE)/nicotinamide adenine dinucleotide phosphate(NADPH) signaling pathways(P<0.01). Conclusion: EA may potentially improve cognitive impairment in AD via inhibition of fibrin/Aβdeposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.展开更多
目的利用分子拓扑结构探讨归肺和大肠经中药成分“印迹模板”的特征,并进行实验验证,确定归肺和大肠经可能的物质基础。方法以普通高等教育“十三五”国家级规划教材《中药学》为基准,为排除其他经络如肝经、肾经等混合归经的影响,对44...目的利用分子拓扑结构探讨归肺和大肠经中药成分“印迹模板”的特征,并进行实验验证,确定归肺和大肠经可能的物质基础。方法以普通高等教育“十三五”国家级规划教材《中药学》为基准,为排除其他经络如肝经、肾经等混合归经的影响,对443味中药(不包含附药)进行归纳且只确定归肺和大肠经中药,再通过查阅中国知网和中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP),归纳总结出归肺和大肠经中药化学成分,并对其中相同的化学成分进行整理、删减、合并,计算分子连接性指数(molecular connectivity index,MCI);运用夹角余弦法计算出各成分MCI与总体平均MCI的相似度,确定成分部位和对照品;建立相似度与保留时间的关系,进行中药与对照品的HPLC指纹图谱的印迹性比较,从而确定归肺和大肠经可能表征的化学结构特征。结果共获得11味中药的886种化学成分,黄酮、蒽醌、鞣质类成分的相似度较高,且在药材中分布集中,故选取其中相似度排名依次为5、8、10、16、40、44、49的7个成分:大黄素-1-O-β-D-葡萄糖苷、大黄酚-8-O-β-D-葡萄糖苷、大黄素-8-O-β-D-吡喃葡萄糖苷、3,3’-二甲基鞣花酸-4’-O-葡萄糖苷、山柰苷、芦丁、山柰酚-3-O-芸香糖苷,平均MCI的相似度为0.99508~0.99920,保留时间为39.63~60.14 min,基于定量结构-性质关系/定量结构-保留时间关系(quantitative structure-property relationship/quantitative structure-retention relationship,QSPR/QSRR)原理,对二者进行线性回归,相关系数R=0.8662(P<0.01);7个成分和9味药材的总量统计矩的一阶矩的15%范围分别为[44.46 min,46.50 min]、[39.70 min,47.08 min],二者重叠,则有85%把握认为可用7个对照品成分表征归肺和大肠经的中药成分的“印迹模板”特征。结论归肺和大肠经的中药成分可以用黄酮、蒽醌和鞣酸类成分进行“印迹模板”特征的表征。展开更多
基金financially supported by the National Natural Science Foundation of China(Grant Nos.:82274603 and 82104946)the Natural Science Foundation of Jiangsu Province,China(Grant No.:BK20210817)+3 种基金the Traditional Chinese Medicine Science and Technology Development Project of Jiangsu Province,China(Project code:QN202008)the Young Scientific and Technological Talents Uplift Project of Jiangsu Association of Integrated Traditional Chinese and Western Medicine,China(Grant No.:JSZXTJ-2024-A05)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(Grant No.:KYCX21_3295)the Yangzhou University Graduate Student International Academic Exchange Special Fund Project,China.Thanks for the Graphical abstract drawn。
文摘Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising coimmunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.
基金Supported by the Medicine Leading Science and Technology Project of Shanghai Municipal Science and Technology Commission(No.15401933800)。
文摘Objective To evaluate the efficacy of Chinese medicine acupoint application(CMAA)combined with Western medicine for perennial allergic rhinitis(PAR)in children.Methods In this prospective,parallel,randomized,placebo-controlled and single-blind trial from August to September,2017,180 children with PAR were randomly assigned to an integrative group(CMAA and Montelukast),CMAA group(CMAA and placebo tablet),or Montelukast group(placebo CMAA and Montelukast).Participants were applied with CMAA for 6 sessions over 2 weeks,and/or Montelukast Chewable Tablet orally once daily for 12 weeks.The changes in severity of symptoms were measured by Visual Analog Scale(VAS)and rhinitis control assessment test(RCAT)at 0,2,4 and 12 weeks of treatment.Blood samples were collected for serum interleukin-4,interferon gammaγand T helper type 1(Th1)/Th2 flow cytometric analysis at the time points of 0,4 and 12 weeks.Results Eight cases dropped out from the trial,3 in the integrative group,2 in the CMAA group and 3 in the Montelukast group.The VAS scores decreased significantly while the RCAT scores increased significantly in all three groups at 4 and 12 weeks compared with baseline(P<0.01 or P<0.05).The VAS scores were significantly lower while the RCAT scores were significantly higher in the integrative and CMAA groups than the Montelukast group at 2 and 4 weeks(P<0.01 or P<0.05).At 2,4 and 12 weeks,the scores of nasal congestion,sneezing,sleep problem,and rhinitis symptom control in the integrative and CMAA groups increased significantly compared with baseline(P<0.01 or P<0.05).The least percentages of Th2 and the most alleviated Th2 shift(highest Th1/Th2)were observed in the integrative group at 12 weeks compared with the other two groups(P<0.05).Conclusion The combination of CMAA with Montelukast might be more effective and appropriate than either option alone for children with PAR.(Registered at Chinese Clinical Trial Register,registration No.ChiCTR-IOR-17012434).
基金Supported by the National Natural Science Foundation of China (No.82074552)Shaanxi Science and Technology Department Project (No.2018JM7041)Shaanxi Province TCM "Double Chain Integration" Young and Middle-Aged Scientific Research Innovation Team Construction Project (No.2022-SLRH-LJ-012)。
文摘Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SAMP8) mice were used as AD models and received EA at Yingxiang(LI 20, bilateral) and Yintang(GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin(2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier(BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid-β(Aβ), and ionized calcium-binding adapter molecule 1(IBa-1) in mouse hippocampus(CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction(qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining.Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining. Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8mice and this was inhibited by EA treatment(P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice(P<0.01), which was reversed by fibrin injection(P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability(P<0.05 or P<0.01).Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8mice, which was reversed by fibrin injection(P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1(HMGB1)/toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE)/nicotinamide adenine dinucleotide phosphate(NADPH) signaling pathways(P<0.01). Conclusion: EA may potentially improve cognitive impairment in AD via inhibition of fibrin/Aβdeposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.
文摘目的利用分子拓扑结构探讨归肺和大肠经中药成分“印迹模板”的特征,并进行实验验证,确定归肺和大肠经可能的物质基础。方法以普通高等教育“十三五”国家级规划教材《中药学》为基准,为排除其他经络如肝经、肾经等混合归经的影响,对443味中药(不包含附药)进行归纳且只确定归肺和大肠经中药,再通过查阅中国知网和中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP),归纳总结出归肺和大肠经中药化学成分,并对其中相同的化学成分进行整理、删减、合并,计算分子连接性指数(molecular connectivity index,MCI);运用夹角余弦法计算出各成分MCI与总体平均MCI的相似度,确定成分部位和对照品;建立相似度与保留时间的关系,进行中药与对照品的HPLC指纹图谱的印迹性比较,从而确定归肺和大肠经可能表征的化学结构特征。结果共获得11味中药的886种化学成分,黄酮、蒽醌、鞣质类成分的相似度较高,且在药材中分布集中,故选取其中相似度排名依次为5、8、10、16、40、44、49的7个成分:大黄素-1-O-β-D-葡萄糖苷、大黄酚-8-O-β-D-葡萄糖苷、大黄素-8-O-β-D-吡喃葡萄糖苷、3,3’-二甲基鞣花酸-4’-O-葡萄糖苷、山柰苷、芦丁、山柰酚-3-O-芸香糖苷,平均MCI的相似度为0.99508~0.99920,保留时间为39.63~60.14 min,基于定量结构-性质关系/定量结构-保留时间关系(quantitative structure-property relationship/quantitative structure-retention relationship,QSPR/QSRR)原理,对二者进行线性回归,相关系数R=0.8662(P<0.01);7个成分和9味药材的总量统计矩的一阶矩的15%范围分别为[44.46 min,46.50 min]、[39.70 min,47.08 min],二者重叠,则有85%把握认为可用7个对照品成分表征归肺和大肠经的中药成分的“印迹模板”特征。结论归肺和大肠经的中药成分可以用黄酮、蒽醌和鞣酸类成分进行“印迹模板”特征的表征。
