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Gene Therapy Activates Retinal Pigment Epithelium Cell Proliferation for Age-related Macular Degeneration in a Mouse Model
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作者 Yun YUAN Wen KONG +1 位作者 xiao-mei liu Guo-hua SHI 《Current Medical Science》 SCIE CAS 2023年第2期384-392,共9页
Objective Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate ... Objective Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus(AAV)vector encodingβ-catenin to treat AMD in a mouse model.Methods Mice were intravitreally injected with AAV2/8-Y733F-VMD2-β-catenin for 2 or 4 weeks,andβ-catenin expression was measured using immunofluorescence staining,real-time quantitative reverse transcription polymerase chain reaction(PCR),and Western blotting.The function ofβ-catenin was determined using retinal flat mounts and laser-induced damage models.Finally,the safety of AAV2/8-Y733F-VMD2-β-catenin was evaluated by multiple intravitreal injections.Results AAV2/8-Y733F-VMD2-β-catenin induced the expression ofβ-catenin in RPE cells.It activated the proliferation of RPE cells and increased cyclin D1 expression.It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells.Furthermore,it could induce apoptosis of RPE cells by increasing the expression of Trp53,Bax and caspase3 while decreasing the expression of Bcl-2.Conclusion AAV2/8-Y733F-VMD2-β-catenin increasedβ-catenin expression in RPE cells,activated RPE cell proliferation,and helped mice heal from laser-induced eye injury.Furthermore,it could induce the apoptosis of RPE cells.Therefore,it may be a safe approach for AMD treatment. 展开更多
关键词 gene therapy adeno-associated virus age-related macular degeneration retinal pigment epithelium cells Β-CATENIN
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难治性肺炎支原体肺炎危险因素分析 被引量:43
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作者 刘晓梅 崔振泽 杨光 《中国现代医学杂志》 CAS 2020年第2期55-59,共5页
目的探讨难治性肺炎支原体肺炎(RMPP)的相关危险因素。方法选取2016年1月-2016年12月在大连市儿童医院呼吸科诊治的153例普通肺炎支原体肺炎(GMPP)患儿和32例RMPP患儿的一般资料、发热时间、实验室指标及影像学特点。绘制ROC曲线分析各... 目的探讨难治性肺炎支原体肺炎(RMPP)的相关危险因素。方法选取2016年1月-2016年12月在大连市儿童医院呼吸科诊治的153例普通肺炎支原体肺炎(GMPP)患儿和32例RMPP患儿的一般资料、发热时间、实验室指标及影像学特点。绘制ROC曲线分析各独立危险因素在RMPP中的预测价值;采用多因素Logistic回归分析RMPP发生的相关危险因素。结果RMPP组发热时间、乳酸脱氢酶(LDH)、中性粒细胞百分比、C反应蛋白(CRP)及降钙素原(PCT)水平高于GMPP组(P<0.05)。RMPP组肺部浸润影≥2/3肺、胸腔积液、肺实变、肺不张、合并感染及肺外并发症比例高于GMPP组(P<0.05)。ROC曲线分析显示,发热时间、LDH、中性粒细胞百分比、淋巴细胞百分比、CRP及PCT可鉴别RMPP和GMPP(P<0.05),其最佳分割点分别为10.5 d、342.5 IU/L、59.85%、25.55%、22.86 mg/L及0.1 ng/ml。多因素Logistic回归分析提示,发热时间[OR=6.939(95%CI:2.016,22.885)]、肺部浸润影≥2/3肺[OR=48.045(95%CI:5.880,392.561)]及LDH[OR=10.075(95%CI:2.770,36.640)]是RMPP发生的危险因素。结论发热时间、肺部浸润影≥2/3肺,合并感染、肺外并发症、LDH及CRP水平升高有助于早期识别RMPP。发热时间、肺部浸润影≥2/3肺及LDH是RMPP发生的独立危险因素。 展开更多
关键词 支原体 肺炎 儿童 危险因素
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Employing a random forest model to forecast the likelihood of coronary artery lesions in Kawasaki disease: a study centered on four biomarkers
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作者 Chu-Xiong Gong Yue-Wen Li +3 位作者 Ya-Min Li Zi-Yu Wang Hui-Qing Gao xiao-mei liu 《Medical Data Mining》 2024年第3期1-7,共7页
Background:Kawasaki disease is an acute immune vasculitis,which is more common in children under 5 years old.Kawasaki disease mainly affects the cardiovascular system,especially the coronary arteries.Once coronary art... Background:Kawasaki disease is an acute immune vasculitis,which is more common in children under 5 years old.Kawasaki disease mainly affects the cardiovascular system,especially the coronary arteries.Once coronary artery damage occurs,it can significantly impact the patient’s prognosis.Therefore,in some countries and regions,Kawasaki disease has become a common acquired heart disease.Methods:First,univariate analysis was conducted on each predictive factor.Then,Least Absolute Shrinkage and Selection Operator and random forest algorithms were used to screen all predictive factors,and the prediction model was evaluated using receiver operating characteristic curve,calibration curve,and Decision Curve Analysis.Results:This study,based on data from 228 Kawasaki disease patients,utilized a random forest model to identify four predictive factors:white blood cell count,creatine kinase isoenzyme MB,albumin,and neutrophil count.These factors were used to construct a prediction model,which achieved an area under the curve of 0.743.Conclusions:We developed a forest plot based on white blood cell count,creatine kinase isoenzyme MB,albumin,and neutrophil count to effectively predict the occurrence of coronary artery lesions in Kawasaki disease. 展开更多
关键词 Kawasaki disease coronary artery lesions NOMOGRAM machine learning
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HBx activates FasL and mediates HepG2 cell apoptosis through MLK3-MKK7-JNKs signal module 被引量:15
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作者 Ren-Xian Tang Fan-Yun Kong +4 位作者 Bao-Feng Fan xiao-mei liu Hong-Juan You Peng Zhang Kui-Yang Zheng 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第13期1485-1495,共11页
AIM: To investigate the possible mechanism by which hepatitis B virus X protein (HBx) mediates apoptosis of HepG2 cells. METHODS: HBx expression vector pcDNA3.1-X was transfected into HepG2 cells to establish an H... AIM: To investigate the possible mechanism by which hepatitis B virus X protein (HBx) mediates apoptosis of HepG2 cells. METHODS: HBx expression vector pcDNA3.1-X was transfected into HepG2 cells to establish an HBx high- expression cellular model as pcDNA3.1-X transfected group. The pcDNA3.1-X and pSilencer3.1-shHBX (HBx antagonist) were cotransfected into HepG2 cells to es- tablish an HBx low-expression model as RNAi group. Untransfected HepG2 cells and HepG2 cells transfected with negative control plasmid were used as controls. Apoptosis rate, the expression of Fas/FasL signaling pathway-related proteins and the phosphorylation lev- els of MLK3, MKK7 and JNKs, which are upstream molecules of death receptor pathways and belong to the family of mitogen-activated protein kinases (MAPKs),were measured in each group RESULTS: Compared with HepG2 cell group and RNAi group, apoptosis rate, the expression of Fas and FasL proteins, and the activation of MLK3, MKK7 and 3NKs were increased in the pcDNA3.1-X transfected group. The activation of JNKs and expression of FasL protein were inhibited in the pcDNA3.1-X transfected group when treated with a known JNK inhibitor, SP600125. When authors treated pcDNA3.1-X transfected group with K252a, a known MLK3 inhibitor, the activation of MLK3, MKK7 and 3NKs as well as expression of FasL protein was inhibited. Furthermore, cell apoptosis rate was also significantly declined in the presence of K252a in the pcDNA3.1-X transfected group. CONCLUSION: HBx can induce HepG2 cell apoptosis via a novel active MLK3-MKK7-JNKs signaling module to upregulate FasL protein expression. 展开更多
关键词 Hepatitis B virus X protein MLK3 FASL HepG2cell APOPTOSIS
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Human hair follicle-derived mesenchymal stem cells:Isolation,expansion,and differentiation 被引量:9
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作者 Bo Wang xiao-mei liu +6 位作者 Zi-Nan liu Yuan Wang Xing Han Ao-Bo Lian Ying Mu Ming-Hua Jin Jin-Yu liu 《World Journal of Stem Cells》 SCIE CAS 2020年第6期462-470,共9页
Hair follicles are easily accessible skin appendages that protect against cold and potential injuries.Hair follicles contain various pools of stem cells,such as epithelial,melanocyte,and mesenchymal stem cells(MSCs)th... Hair follicles are easily accessible skin appendages that protect against cold and potential injuries.Hair follicles contain various pools of stem cells,such as epithelial,melanocyte,and mesenchymal stem cells(MSCs)that continuously self-renew,differentiate,regulate hair growth,and maintain skin homeostasis.Recently,MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential.In this review,we describe the applications of human hair follicle-derived MSCs(hHF-MSCs)in tissue engineering and regenerative medicine.We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail.We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages,including supplementation of growth factors,3D suspension culture technology,and 3D aggregates of MSCs.In addition,we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels,regenerated hair follicles,induced red blood cells,and induced pluripotent stem cells.In summary,the abundance,convenient accessibility,and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy. 展开更多
关键词 Human hair follicle Regenerative therapy Mesenchymal stem cell Tissue engineering Cell differentiation
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Glucose Metabolic and Gluconeogenic Pathways Disturbance in the Intrauterine Growth Restricted Adult Male Rats 被引量:2
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作者 xiao-mei liu Jing Kong +1 位作者 Wei-wei Song Yan Lu 《Chinese Medical Sciences Journal》 CAS CSCD 2009年第4期208-212,共5页
Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intraut... Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes. 展开更多
关键词 intrauterine growth restriction insulin resistance GLUCONEOGENESIS
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Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke
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作者 Xiao-Wei Cao Hui Yang +6 位作者 xiao-mei liu Shi-Ying Lou Li-Ping Kong Liang-Qun Rong Jun-Jun Shan Yun Xu Qing-Xiu Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第5期1033-1039,共7页
We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More impor... We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke. 展开更多
关键词 a disintegrin and metalloprotease domain 17 cerebral ischemia/reperfusion C-X3-C motif chemokine ligand 1 GW280264x microglia neuroinflammation postsynaptic density-93 Tat-CX3CL1(357–395aa)
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Application of LC-MS based glutathione-trapped reactive metabolites in the discovery of toxicity of traditional Chinese medicine
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作者 xiao-mei liu Hong Lv +3 位作者 Xiao-Ming Wang Ya-Qing Guo Ting-Ting Li Gui-Xiang Pan 《TMR Modern Herbal Medicine》 2018年第4期209-219,共11页
We summarized the discovery of liquid chromatography mass spectrometry (LC-MS) based glutathione (GSH) capture of reactive metabolites in traditional Chinese medicine (TCM), which provides scientific basis for ... We summarized the discovery of liquid chromatography mass spectrometry (LC-MS) based glutathione (GSH) capture of reactive metabolites in traditional Chinese medicine (TCM), which provides scientific basis for further research and clinical application of Chinese medicine toxicity discovery. This dissertation overviews relevant literatures of GSH capture of reactive metabolites in recent years. And then we review the principles and methods of LC-MS based GSH capture of reactive metabolites, as well as the research progress in the discovery of toxicity of TCM including pyrrolizidine alkaloids, furans and quinoid species. The review shows that the representative compounds of TCM includes adonifoline, lasiocarpine, diosbulbin B and safrol are well dctected by LC-MS based GSH capture technique. And the main analytic systems of LC-MS are triple quadrupole and Q-Trap mass spectrometer. Constant neutral loss scan (CNLS), precursor ion scan (PIS) and multiple reaction monitor (MRM) are main detection methods to monitor the characteristic GSH conjugate fragmentations. The approach of LC-MS based GSH-trapped metabolites has a good application prospect in the discovery of toxic components of TCM. 展开更多
关键词 glutathione conjugation Liquid Chromatography Mass Spectrometry Reactive metabolites TOXICITY traditional Chinese medicine
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Herbivore-induced rice resistance against rice blast mediated by salicylic acid 被引量:1
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作者 Kai-Li Zhang Qing-Song liu +4 位作者 Hou-Xiang Kang xiao-mei liu Xiu-Ping Chen Yu-Fa Peng Yun-He Li 《Insect Science》 SCIE CAS CSCD 2020年第1期49-57,共9页
In agro-ecosystems,plants are important mediators of interactions between their associated herbivorous insects and microbes,and any change in plants induced by one species may lead to cascading effects on interactions... In agro-ecosystems,plants are important mediators of interactions between their associated herbivorous insects and microbes,and any change in plants induced by one species may lead to cascading effects on interactions with other species.Often,such effects are regulated by phytohormones such as jasmonic acid(JA)and salicylic acid(SA).Here,we investigated the tripartite interactions among rice plants,three insect herbivores(Chilo suppressalis,Cnaphalocrocis medinalis or Nilapai-vata lugens),and the causal agent of rice blast disease,the fungus Magnaporthe oryzae.We found that pre-infestation of rice by C.suppressalis or N.lugens but not by C.medinalis conferred resistance to M.oryzae.For C.suppressalis and N.lugens,insect infestation without fungal inoculation induced the accumulation of both JA and SA in rice leaves.In contrast,infestation by C.medinalis increased JA levels but reduced SA levels.The exogenous application of SA but not of JA conferred resistance against M.oryzae.These results suggest that preinfestation by C suppressalis or N.lugens conferred resistance against M.oryzae by increasing SA accumulation.These findings enhance our understanding of the interactions among rice plant,insects and pathogens,and provide valuable information for developing an ecologically sound strategy for controlling rice blast. 展开更多
关键词 induced defense jasmonic acid plant-insect-pathogen interaction RICE salicylic acid
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