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| 1 | Specific shRNA targeting of FAK influenced collagen metabolism in rat hepatic stellate cells显示文摘AIM:To investigate the effects and mechanism of disruption of focal adhesion kinase(FAK) expression on collagen metabolism in rat hepatic stellate cells(HSC).METHODS:The plasmids expressing FAK short hairpin RNA(shRNA) were transfected into HSC-T6 cells,and the level of FAK expression was determined by both real-time quantitative polymerase chain reaction(QPCR) and Western blotting analysis.The production of type collagen and type collagen in FAK-disrupted cells was analyzed by real-time Q-PCR.The level of collagen metabolism proteins,including matrix metalloproteinases-13(MMP-13) and tissue inhibitors of metalloproteinases-1(TIMP-1) was also determined by both real-time Q-PCR and Western blotting analysis.RESULTS:The transfection of FAK shRNA plasmids into HSC resulted in disrupted FAK expression.Compared with the HK group,the levels of type collagen and type collagen mRNA transcripts in FAK shRNA plas-mid group were signif icantly decreased(0.69 ± 0.03 vs 1.96 ± 0.15,P = 0.000;0.59 ± 0.07 vs 1.62 ± 0.12,P = 0.020).The production of TIMP-1 in this cell type was also signif icantly reduced at both mRNA and protein levels(0.49 ± 0.02 vs 1.72 ± 0.10,P = 0.005;0.76 ± 0.08 vs 2.31 ± 0.24,P = 0.000).However,the expression of MMP-13 mRNA could be significantly up-regulated by the transfection of FAK shRNA plasmids into HSC(1.74 ± 0.20 vs 1.09 ± 0.09,P = 0.000).CONCLUSION:These data support the hypothesis that shRNA-mediated disruption of FAK expression could attenuate extracellular matrix(ECM) synthesis and promote ECM degradation,making FAK a potential target for novel anti-f ibrosis therapies. | Zhi-Na Dun Xiao-Lan Zhang Jun-Yan An Li-Bo Zheng Robert Barrett Shu-Rui Xie | 2010 | World Journal of Gastroenterology2010，16，32： | 8 |
| 2 | Inhibition of growth and metastasis of triple-negative breast cancer targeted by Traditional Chinese Medicine Tubeimu in orthotopic mice models显示文摘Objective: Triple-negative breast cancer(TNBC) is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu(TBM), the rhizome of Bolbostemma paniculatum(Maxim.) Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu(ETBM) on TNBC orthotopic mouse models and cell lines.Methods: We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis applied to explore the pathways influenced by ETBM.Moreover, quantitative real-time polymerase chain reactions(q RT-PCR) and Western blot were delivered to confirm the gene expression changes.Results: ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1(ITGβ1), integrin β8(ITGβ8) and Rho GTPase activating protein 5(ARHGAP5), which disabled the focal adhesion pathway and caused change in cell morphology.Conclusions: This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC. | Jingxiao Wang Xinjie Yang Haibo Han Limin Wang Weiqian Bao Shanshan Wang Robert M.Hoffman Meng Yang Hui Qi Chao An Kaiwen Hu | 2018 | Chinese Journal of Cancer Research2018，30，1： | 8 |
| 3 | Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms显示文摘The infusion of coronavirus disease 2019(COVID-19)patients with mesenchymal stem cells(MSCs)potentially improves clinical symptoms,but the underlying mechanism remains unclear.We conducted a randomized,single-blind,placebo-controlled(29 patients/group)phase II clinical trial to validate previous findings and explore the potential mechanisms.Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay(P=0.0198)and less time required for symptoms remission(P=0.0194)than those who received placebo.Based on chest images,both severe and critical patients treated with MSCs showed improvement by day 7(P=0.0099)and day 21(P=0.0084).MSC-treated patients had fewer adverse events.MSC infusion reduced the levels of C-reactive protein,proinflammatory cytokines,and neutrophil extracellular traps(NETs)and promoted the maintenance of SARS-CoV-2-specific antibodies.To explore how MSCs modulate the immune system,we employed single-cell RNA sequencing analysis on peripheral blood.Our analysis identified a novel subpopulation of VNN2+hematopoietic stem/progenitorlike(HSPC-like)cells expressing CSF3R and PTPRE that were mobilized following MSC infusion.Genes encoding chemotaxis factors—CX3CR1 and L-selectin—were upregulated in various immune cells.MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro.In addition,an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling.Together,our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis. | Rongjia Zhu Tingdong Yan Yingmei Feng Yan Liu Hongcui Cao Gongxin Peng Yanlei Yang Zhen Xu Jingqi Liu Wei Hou Xiaoyue Wang Zhe Li Luchan Deng Shihua Wang Jing Li Qin Han Hongling Li Guangliang Shan Yinghao Cao Xingyan An Jianshe Yan Zhonghui Zhang Huafei Li Xuebin Qu Jiaqi Zhu Shumin Zhou Jiao Wang Fengchun Zhang Jinming Gao Ronghua Jin Dayong Xu Yan-Qing Ma Tao Huang Shuang Peng Zhi Zheng Ilia Stambler Eric Gilson Lee Wei Lim Alexey Moskalev Antonio Cano Sasanka Chakrabarti Brun Ulfhake Huanxing Su Haoying Xu Sihuan Xu Feng Wei Holly MBrown-Borg Kyung-Jin Min Georgina Ellison-Hughes Calogero Caruso Kunlin Jin Robert Chunhua Zhao | 2021 | Cell Research2021，31，12： | 5 |
| 4 | High prevalence of epilepsy in onchocerciasis endemic health areas in Democratic Republic of the Congo显示文摘Background:A high prevalence of epilepsy has been observed in many onchocerciasis endemic regions.This study is to estimate the prevalence of active epilepsy and exposure to Onchocerca volvulus infection in a rural population in Ituri province,Democratic Republic of Congo.Methods:In August 2016,a community-based cross-sectional study was conducted in an onchocerciasis endemic area in the rural health zone of Logo,Ituri Province.Households within two neighbouring health areas were randomly sampled.To identify persons with epilepsy,a three-stage approach was used.In the first stage,all individuals of the selected households were screened for epilepsy by non-medical field workers using a validated 5-item questionnaire.In the second and third stage,suspected cases of epilepsy were examined by non-specialist medical doctors,and by a neurologist,respectively.A case of epilepsy was defined according to the 2014 International League Against Epilepsy(ILAE)guidelines.Exposure to O.volvulus was assessed by testing for IgG4 antibodies to an O.volvulus antigen(OV16 Rapid Test,)in individuals aged 3 years and older.Results:Out of 1389 participants included in the survey,64 were considered to have active epilepsy(prevalence 4.6%)(95%confidence interval[CI]:3.6-5.8).The highest age-specific epilepsy prevalence estimate was observed in those aged 20 to 29 years(8.2%).Median age of epilepsy onset was 10 years,with a peak incidence of epilepsy in the 10 to 15 year-old age group.OV16 test results were available for 912 participants,of whom 30.5%(95%CI,27.6-33.6)tested positive.The prevalence of OV16 positivity in a village ranged from 8.6 to 68.0%.After adjusting for age,gender and ivermectin use,a significant association between exposure to onchocerciasis and epilepsy was observed(adjusted odds ratio=3.19,95%CI:1.63-5.64)(P<0.001).Conclusions:A high prevalence of epilepsy and a significant association between epilepsy and exposure to O.volvulus were observed in the population in Ituri province,Democratic Republic of Congo.There is an urgent need to implement a CDTI programme and to scale up an epilepsy treatment and care programme. | Evy Lenaerts Michel Mandro Deby Mukendi Patrick Suykerbuyk Housseini Dolo Deogratias Wonya’Rossi Françoise Ngave Chellafe Ensoy-Musoro Anne Laudisoit An Hotterbeekx Robert Colebunders | 2018 | Infectious Diseases of Poverty2018，7，1： | 5 |
| 5 | Intervertebral disc development and disease-related genetic polymorphisms显示文摘The intervertebral disc(IVD)comprises a gelatinous inner core(nucleus pulposus;NP)and concentric rings(annulus fibrosus;AF).The NP,an important structure for shock absorption in the vertebrate spinal motion segment,can be traced back to the notochord in ontogenetic lineage.In vertebrates,the notochord undergoes mucinoid changes,and had been considered vestigial until recently.However,observed correlations between IVD degeneration and back pain in humans have renewed interest in the IVD in biomedical fields.Beyond its mechanical contribution to development,the notochord is also an essential signaling center,which coordinates formation of the neural tube and somites.The pertinent signaling molecules,particularly TGF-b and bone morphogenetic proteins(BMPs),continue to play roles in the adult tissues and have been utilized for tissue regeneration.Genetic factors are major determinants of who will develop IVD degeneration and related back pain,and seem to correlate better with disc degeneration and back pain than do external forces on the spine.In summary,the spinal column is a landmark development in evolution.Genes directing the development of the IVD may also contribute to its maintenance,degeneration,and regeneration.Likewise,structural genes as well as genes responsible for maintenance of the structure are related to IVD degeneration.Finally,genes responsible for inflammation may play a dual role in exacerbating degeneration or facilitating repair responses depending on the context. | Jason W.Ashley Motomi Enomoto-Iwamoto Lachlan J.Smith Robert L.Mauck Danny Chan Joseph Lee Martin F.Heyworth Howard An Yejia Zhang | 2016 | Genes & Diseases2016，3，3： | 3 |
| 6 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 7 | A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance显示文摘 | Christopher B. Newgard Jie An James R. Bain Michael J. Muehlbauer Robert D. Stevens Lillian F. Lien Andrea M. Haqq Svati H. Shah Michelle Arlotto Cris A. Slentz James Rochon Dianne Gallup Olga Ilkayeva Brett R. Wenner William S. Yancy Howard Eisenson Gera | 2009 | Cell Metabolism2009，，4： | 2 |
| 8 | Biomarkers of Brain Injury in Neonatal Encephalopathy Treated with Hypothermia显示文摘 | An N. Massaro Taeun Chang Nadja Kadom Tammy Tsuchida Joseph Scafidi Penny Glass Robert McCarter Stephen Baumgart Gilbert Vezina Karin B. Nelson | 2012 | The Journal of Pediatrics2012，，3： | 2 |
| 9 | Effect of stress dependent modulus and poisson' s ratio on structural responses in thin asphalt pavements 显示文摘 | Park Seong-W an Lytton Robert L | 2004 | Journal of Transportation Engineering2004，130，3： | 1 |
| 10 | Investor Protection and Corporate Governance显示文摘 | Rafael La Port Florencio Lopez-de-Silanes An drei Shleifer and Robert Vishny | 2000 | Journal of Financial Economics2000，，58： | 1 |
| 11 | Phosphorot- hioate Oligonueleotide Quantification by Ix-Liquid Chromatogra- phy-Mass Spectrometry 显示文摘 | Robert ER leithner KA Bemkop-Schntlrch AN | 2012 | The AAPS Journal2012，14，4： | 1 |
| 12 | The effect of lignin-related compounds on the growth and production of laccases by the ascomycete,Botryosphaeria sp显示文摘 | Dekker Robert F H Barbosa Aneli M Sargent Keith | 2002 | Enzyme and Microbial Technology2002，30，3： | 1 |
| 13 | Intravitreal Bevacizumab (Avastin) in the Treatment of Proliferative Diabetic Retinopathy显示文摘 | Robert L. Avery Joel Pearlman Dante J. Pieramici Melvin D. Rabena Alessandro A. Castellarin Ma’an A. Nasir Matthew J. Giust Robert Wendel Arun Patel | 2006 | Ophthalmology2006，，10： | 1 |
| 14 | Technology alliances and to research capability 显示文摘 | Pek- Hooi Soh Roberts E networks: an external link B | 2005 | IEEE Transactions on Engineering Management2005，，4： | 1 |
| 15 | Free radicals in chronic fatigue syndrome: cause, or effect 显示文摘 | RICHARDS R S ROBERTS T K DUNSI'AN R H | 2000 | Redox Rep2000，5，23： | 1 |
| 16 | The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study显示文摘 | Guangwei Li Ping Zhang Jinping Wang Edward W Gregg Wenying Yang Qiuhong Gong Hui Li Hongliang Li Yayun Jiang Yali An Ying Shuai Bo Zhang Jingling Zhang Theodore J Thompson Robert B Gerzoff Gojka Roglic Yinghua Hu Peter H Bennett | 2008 | 2008 (9626)2008，，9626： | 1 |
| 17 | Psychological well being inpatients on adequate doses of thyroxine:results of a large,controlled community-based question nair study显示文摘 | SARAVAN AN P CHAU F ROBERTS N | 2002 | Clin Endocrino2002，57，5： | 1 |
| 18 | Hygrothermal performance study of thermal insulation system显示文摘 | Zbysek Pavlik Robert an innovative interior Cerny | 2009 | Applied Thermal Engineering2009，29，： | 1 |
| 19 | Intravitreal Bevacizumab (Avastin) in the Treatment of Proliferative Diabetic Retinopathy显示文摘 | Robert L. Avery Joel Pearlman Dante J. Pieramici Melvin D. Rabena Alessandro A. Castellarin Ma’an A. Nasir Matthew J. Giust Robert Wendel Arun Patel | 2006 | Ophthalmology2006，，10： | 1 |
| 20 | Biomeehanical (Lateral) collateral ligament re-construction using an autogenous semitendinosus graft 显示文摘 | BENJAMIN R ROBERT F analysis of an isolated fibular CHAD J | 2007 | Sports Medicine2007，，35： | 1 |
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