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| 1 | Human urokinase-type plasminogen activator gene-modifiedbone marrow-derived mesenchymal stem cells attenuateliver fibrosis in rats by down-regulating the Wnt signalingpathway显示文摘AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway. | Zhi-Gang Ma Xiao-Dan Lv Ling-Ling Zhan Lan Chen Qi-Yuan Zou Ji-Qiao Xiang Jiao-Li Qin Wei-Wei Zhang Zhao-Jing Zeng Hui Jin Hai-Xing Jiang Xiao-Ping Lv | 2016 | World Journal of Gastroenterology2016，22，6： | 21 |
| 2 | Extracellular signal-regulated protein kinase activation in spinal cord contributes to pain hypersensitivity in a mouse model of type 2 diabetes显示文摘Painful peripheral neuropathy is a common complication of diabetes mellitus. The symptom of pain can become a major factor that decreases the quality of life of patients with diabetes, while effective treatment is lacking. In the present study, we aimed to investigate the changes of pain threshold in the early stage of diabetes in db/db mice, an animal model of type 2 diabetes mellitus, and the underlying molecular mechanisms. We found that (1) db/db mice (with a leptin receptor-null mutation and characterized by obesity and hyperglycemia) showed hypersensitivity to mechanical and thermal stimuli at the early stage of diabetes; (2) phosphorylated extracellular signalregulated kinase (pERK), but not total ERK in the spinal cord and dorsal root ganglia in db/db mice significantly increased compared with wild-type mice. The increased pERK immunoreactivity occurred in both NeuN-expressing neurons and GFAPexpressing astrocytes, but not in Iba-1-expressing microglia; (3) both single and consecutive (for 5 days) intrathecal injections of U0126 (2 nmol per day), a selective MEK (an ERK kinase) inhibitor beginning at 8 weeks of age, attenuated the bilateral mechanical allodynia in the von-Frey test and heat hyperalgesia in Hargreave's test; and (4) db/db mice also displayed increased nocifensive behavior during the formalin test, and this was blocked by intrathecal injection of U0126. Also, the expression of pERK1 and pERK2 was upregulated following the formalin injection. Our results suggested that the activation of ERK in spinal neurons and astrocytes is correlated with pain hypersensitivity of the type 2 diabetes animal model. Inhibiting the ERK pathway may provide a new therapy for pain control in type 2 diabetes. | Xiang Xu Hui Chen Bing-Yu Ling Lan Xu Hong Cao Yu-Qiu Zhang | 2014 | Neuroscience Bulletin2014，30，1： | 8 |
| 3 | TLR2 signaling subpathways regulate TLR9 signaling for the effective induction of IL-12 upon stimulation by heat-killed Brucella abortus显示文摘Brucella 流产胎是在 dentritic 房间(DC ) 和随后的保护的 Th1 有免疫力的回答导致 MyD88 依赖的 IL-12 生产的一个克否定的细胞内部的细菌。以前的研究证明了像使用费的受体(TLR2 ) 2 为肿瘤坏死被要求因素(TNF ) 生产,而 TLR9 为在在到杀死热的 Brucella 流产胎(HKBA ) 的暴露以后的 DC 感应的 IL-12 负责。TLR2 位于房间表面并且被天生的有免疫力的房间为最佳的导致微生物的吞噬作用要求;因此,吞噬作用是为由在 late-endosomal 分隔空间的 TLR9 的细菌的 genomic DNA 识别的不可缺少的初步的步。这里,我们假设了那在通过 DC 的吞噬细胞的函数的间接调整或 cytokine 的直接调整发信号的 HKBA 刺激力量跨 regulate TLR9 以后的被触发 TLR2 的信号基因表示。我们的结果显示那个 HKBA 吞噬作用是 TLR2 依赖的并且为 IL-12p40 的必要的步感应。另外, HKBA 暴露触发了 p38 和细胞外的调整信号的 kinase 1/2 (ERK1/2 ) 的调停 TLR2 的激活。有趣地,尽管 p38 为 HKBA 吞噬作用和 phagosome 成熟被要求, ERK1/2 没影响这些过程,但是否定地调整 IL-12 生产。尽管 p38 禁止者 tempered 对 HKBA 的 TNF 和 IL-12 回答,有一个 ERK1/2 禁止者的预告的处理显著地增加了 IL-12p40 并且在刺激 HKBA 的 DC 废除了 TNF 生产。进一步的实验证明在 TLR2 被触发以后的那调停的 ERK1/2 激活也要求了的发信号的事件导致 HKBA 的地岬激活。而且, Ras-guanine 释放核苷酸的蛋白质(RasGRP1 ) 1 调停了导致 TLR2 的 ERK1/2 激活和 IL-12p40 的抑制生产。一起拿,我们的结果证明调停 HKBA 的被触发 TLR2 激活 p38 和 ERK1/2 发信号 subpathways,它分叉地在几个层次调整 TLR9 激活导致适当保护的 IL-12 回答。 | Chun-Yan Zhang Nan Bai Zhu-Hong Zhang Ning Liang Lan Dong Rong Xiang Cheng-Hu Liu | 2012 | Cellular & Molecular Immunology2012，9，4： | 7 |
| 4 | Ophthalmic drug-loaded N,O-carboxymethyl chitosan hydrogels: synthesis, in vitro and in vivo evaluation显示文摘 | Li-qun YANG Yu-qing LAN Hui GUO Liang-zheng CHENG Ji-zhou FAN Xiang CAI Li-ming ZHANG Ru-fu CHEN Huai-sheng ZHOU | 2010 | Acta Pharmacologica Sinica2010，31，12： | 6 |
| 5 | Grade classification of neuroepithelial tumors using high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and pattern recognition显示文摘Clinical data have shown that survival rates vary considerably among brain tumor patients,according to the type and grade of the tumor.Metabolite profiles of intact tumor tissues measured with high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy (HRMAS 1H NMRS) can provide important information on tumor biology and metabolism.These metabolic fingerprints can then be used for tumor classification and grading,with great potential value for tumor diagnosis.We studied the metabolic characteristics of 30 neuroepithelial tumor biopsies,including two astrocytomas (grade I),12 astrocytomas (grade II),eight anaplastic astrocytomas (grade III),three glioblastomas (grade IV) and five medulloblastomas (grade IV) from 30 patients using HRMAS 1H NMRS.The results were correlated with pathological features using multivariate data analysis,including principal component analysis (PCA).There were significant differences in the levels of N-acetyl-aspartate (NAA),creatine,myo-inositol,glycine and lactate between tumors of different grades (P<0.05).There were also significant differences in the ratios of NAA/creatine,lactate/creatine,myo-inositol/creatine,glycine/creatine,scyllo-inositol/creatine and alanine/creatine (P<0.05).A soft independent modeling of class analogy model produced a predictive accuracy of 87% for high-grade (grade III-IV) brain tumors with a sensitivity of 87% and a specificity of 93%.HRMAS 1H NMR spectroscopy in conjunction with pattern recognition thus provides a potentially useful tool for the rapid and accurate classification of human brain tumor grades. | CHEN WenXue LOU HaiYan ZHANG HongPing NIE Xiu LAN WenXian YANG YongXia XIANG Yun QI JianPin LEI Hao TANG HuiRu CHEN FenEr DENG Feng | 2011 | Science China(Life Sciences)2011，54，7： | 5 |
| 6 | Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis显示文摘OBJECTIVE: To treat patients with vascular mild cognitive impairment(VMCI) using traditional Chinese medicine(TCM), it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis(LTA).METHOD: A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules.RESULTS: Eight syndrome types are identified: Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types.CONCLUSION: A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI. | Chen Fu Nevin Lianwen Zhang Bao-xin Chen Zhou Rong Chen Xiang Lan Jin Rong-juan Guo Zhi-gang Chen Yun-ling Zhang | 2017 | Journal of Integrative Medicine2017，15，3： | 4 |
| 7 | Comparison of the Structural Evolution ofβPolypropylene during the Sequential and Simultaneous Biaxial Stretching Process显示文摘In this work,the lamellar structural evolution and microvoids variations of βpolypropylene(β-PP)during the processing of two different stretching methods,sequential biaxial stretching and simultaneous biaxial stretching,were investigated in detail.It was found that different stretching methods led to significantly different lamellae deformation modes,and the microporous membranes obtained from the simultaneous biaxial stretching exhibited better mechanical properties.For the sequential biaxial stretching,abundant coarse fibers originated from the tight accumulation of the lamellae parallel to the longitudinal stretching direction,whereas the lamellae perpendicular to the stretching direction were easily deformed and separated.Those coarse fibers were difficult to be separated to form micropores during the subsequent transverse stretching process,resulting in a poor micropores distribution.However,for the simultaneous biaxial stretching,theβcrystal had the same deformation mode,that is,the lamellae distributed in different directions were all destroyed,forming abundant microvoids and little coarse fibers. | Dao-Xin Zhang Lei Ding Feng Yang Fang Lan Ya Cao Ming Xiang | 2021 | Chinese Journal of Polymer Science2021，39，5： | 3 |
| 8 | Public Policy Environment and Entrepreneurial Activities: Evidence from China显示文摘 | Sai Lan Xiang Gao Qing Wang Yilin Zhang | 2018 | China & World Economy2018，26，3： | 2 |
| 9 | rtcisE2F promotes the self-renewal and metastasis of liver tumorinitiating cells via N^(6)-methyladenosine-dependent E2F3/E2F6 mRNA stability显示文摘Liver cancer is highly heterogeneous,and the tumor tissue harbors a variety of cell types.Liver tumor initiating cells(TICs)well contribute to tumor heterogeneity and account for tumor initiation and metastasis,but the molecular mechanisms of liver TIC self-renewal are elusive.Here,we identified a functional read-through rt-circRNA,termed rtcisE2F,that is highly expressed in liver cancer and liver TICs.rtcisE2F plays essential roles in the self-renewal and activities of liver TICs.rtcisE2F targets E2F6 and E2F3 mRNAs,attenuates mRNA turnover,and increases E2F6/E2F3 expression.Mechanistically,rtcisE2F functions as a scaffold of N^(6)-methyladenosine(m^(6)A)reader IGF2BP2 and E2F6/E2F3 mRNA.rtcisE2F promotes the association of E2F6/E2F3 mRNAs with IGF2BP2,and inhibits their association with another m^(6)A reader,YTHDF2.IGF2BP2 inhibits E2F6/E2F3 mRNA decay,whereas YTHDF2 promotes E2F6/E2F3 mRNA decay.By switching m^(6)A readers,rtcisE2F enhances E2F6/E2F3 mRNA stability.E2F6 and E2F3 are both required for liver TIC self-renewal and Wnt/β-catenin activation,and inhibition of these pathways is a potential strategy for preventing liver tumorigenesis and metastasis.In conclusion,the rtcisE2F-IGF2BP2/YTHDF2-E2F6/E2F3-Wnt/β-catenin axis drives liver TIC self-renewal and initiates liver tumorigenesis and metastasis,and may provide a strategy to eliminate liver TICs. | Zhenzhen Chen Lan Huang Kaili Wang Lulu Zhang Xiang Zhong Zhongyi Yan Benyu Liu Pingping Zhu | 2022 | Science China(Life Sciences)2022，65，9： | 2 |
| 10 | Evaluation and Overview of Progress in Farmland Protection Researches显示文摘With rapid advance of urbanization in China,both quantity and quality of farmland are gravely threatened,human-land conflict is growing,and the issue of grain security becomes more serious.Accordingly,practical and feasible protection of farmland has become one of core problems in China's land resource management.From theory,system,effective factors and measures and methods of farmland protection, this paper comprehensively analyzes research achievement and progress in farmland protection,in the hope of providing basis for further indepth research of farmland protection in China. | Lan LUO Guo ZHANG Yuerong ZHENG Xiang NING | 2013 | Asian Agricultural Research2013，5，8： | 2 |
| 11 | Direct interaction between alpha-actinin and hepatitis C virus NS5B显示文摘 | Lan S Wang H Jiang H Mao H Liu X Zhang X Hu Y Xiang L Yuan Z | 2003 | FEBS Lett2003，554，3： | 1 |
| 12 | Flux-assisted thermal conversion route to pore-free high crystallinity magnesium borate nanowhiskers at a relatively low temperature显示文摘 | Zhu Wancheng Zhang Qiang Xiang Lan | 2008 | Crystal Growth & Design2008，8，8： | 1 |
| 13 | Synchronization of Coupled Harmonic Oscillators with Local Instantaneous Interaction显示文摘 | Zhou Jin Zhang Hua Xiang Lan | 2012 | Automatica2012，48，8： | 1 |
| 14 | Flux - Assisted Ther- mal Conversion Route to Pore - Free High Crystallinity Magnesi- um Borate Nanowhiskers at a Relatively lw Temperature 显示文摘 | Zhu Waneheng Zhang Qiang Xiang Lan | 2008 | Crystal Growth &Design2008，8，8： | 1 |
| 15 | Amphibian pore-forming proteinβγ-CAT drives metabolite release from small extracellular vesicles through channel formation显示文摘DEAR EDITOR,Pore-forming proteins(PFPs)are widely distributed among all kingdoms of life and can oligomerize to form pores/channels in membrane systems.Extracellular vesicles(EVs)circulate in all biological fluids and can trigger biological responses at a distance,thus emerging as an additional means of intercellular communication through the release of cellular cargo,such as lipids,nucleic acids,metabolites,and proteins.To date,however,the mechanism by which EV contents are released into extracellular space remains unclear.In our previous study on toads(Bombina maxima),we identified a PFP and trefoil factor complexβγ-CAT(βγ-crystallin fused aerolysin-like protein(α-subunit)and trefoil factor(β-subunit)complex,hence namedβγ-CAT),which assembled under strict regulation in response to environmental cues.Here,we observed that the PFPβγ-CAT colocalized with EVs in the skin of B.maxima in vivo.Using small EVs(sEVs)isolated from B.maxima dermal fibroblast cells and murine fibroblast cells,we found thatβγ-CAT could specifically target and oligomerize on purified EVs,rather than disrupt membrane integrity,and promote the release of different metabolites.Our analysis revealed that a secretory PFP drove metabolite release from EVs through channel formation,providing novel clues for the delivery of EV content into extracellular space. | Qi-Quan Wang Xin-Qiang Lan Xue-Song Wei Si-Man Xu Ling-Zhen Liu Xian-Ling Bian Lin Zeng Xiao-Long Guo Ying-Qi Guo Wen-Hui Lee Yang Xiang Yun Zhang | 2023 | Zoological Research2023，44，4： | 1 |
| 16 | Sampled-data synchronization of coupled harmonic oscillators with controller failure and communication delays显示文摘In this letter,a distributed protocol for sampled-data synchronization of coupled harmonic oscillators with controller failure and communication delays is proposed,and a brief procedure of convergence analysis for such algorithm over undirected connected graphs is provided.Furthermore,a simple yet generic criterion is also presented to guarantee synchronized oscillatory motions in coupled harmonic oscillators.Subsequently,the simulation results are worked out to demonstrate the efciency and feasibility of the theoretical results. | Jin Zhou Hua Zhang Lan Xiang Quanjun Wu | 2013 | Theoretical & Applied Mechanics Letters2013，3，6： | 1 |
| 17 | Xiao-Xu-Ming decoction preserves mitochondrial integrity and reduces apoptosis after focal cerebral ischemiaand repeffusion vt'a the mitochondria/ p53 pathway显示文摘 | Lan R Zhang Y Xiang J | 2014 | J Ethnopharmacol2014，151，1： | 1 |
| 18 | Molecular insights into AabZIP1-mediated regulation on artemisinin biosynthesis and drought tolerance in Artemisia annua显示文摘Artemisia annua is the main natural source of artemisinin production.In A.annua,extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid(ABA)treatment can increase artemisinin biosynthesis.ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes.Here,we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1,which AabZIP1 does not directly activate.Subsequently,it was found that AabZIP1 up-regulates AaMYC2expression through direct binding to its promoter,and that AaMYC2 binds to the promoter of AaALDH1to activate its transcription.In addition,AabZIP1 directly transactivates wax biosynthesis genes AaCER1and AaCYP86A1.The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression,whereas they were significantly decreased in RNAi-AabZIP1 plants.Collectively,we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis,which may have general implications.We have also identified AabZIP1 as a promising candidate gene for the development of A.annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding. | Guoping Shu Yueli Tang Mingyuan Yuan Ning Wei Fangyuan Zhang Chunxian Yang Xiaozhong Lan Min Chen Kexuan Tang Lien Xiang Zhihua Liao | 2022 | Acta Pharmaceutica Sinica B2022，12，3： | 1 |
| 19 | Direct interaction between alpha-actinin and hepatitis C virus NSSB显示文摘 | Lan S Wang H Jiang H MaoH LiuX Zhang X HuY Xiang L Yuan Z | 2003 | FEBS Lett2003，554，3： | 1 |
| 20 | Xiao-Xu-Ming decoction pre- serves mitochondrial integrity and reduces apoptosis after focal cerebral ischemia and reperfusion via the mitochondrial p53 path- way显示文摘 | Lan R Zhang Y Xiang J | 2014 | J Ethnopharmacol2014，151，1： | 1 |
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