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| 1 | Wnt/b-catenin signaling plays an ever-expanding role in stem cell self-renewal,tumorigenesis and cancer chemoresistance显示文摘Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance. | Maryam K.Mohammed Connie Shao Jing Wang Qiang Wei Xin Wang Zachary Collier Shengli Tang Hao Liu Fugui Zhang Jiayi Huang Dan Guo Minpeng Lu Feng Liu Jianxiang Liu Chao Ma Lewis L.Shi Aravind Athiviraham Tong-Chuan He Michael J.Lee | 2016 | Genes & Diseases2016，3，1： | 70 |
| 2 | Multifaceted signaling regulators of chondrogenesis:Implications in cartilage regeneration and tissue engineering显示文摘Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature.Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue.Here,we review the current understanding of the most important biological regulators of chondrogenesis and their interactions,to provide insight into potential applications for cartilage tissue engineering.These include various signaling pathways,including fibroblast growth factors(FGFs),transforming growth factor b(TGF-b)/bone morphogenic proteins(BMPs),Wnt/b-catenin,Hedgehog,Notch,hypoxia,and angiogenic signaling pathways.Transcriptional and epigenetic regulation of chondrogenesis will also be discussed.Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering. | Jordan D.Green Viktor Tollemar Mark Dougherty Zhengjian Yan Liangjun Yin Jixing Ye Zachary Collier Maryam K.Mohammed Rex C.Haydon Hue H.Luu Richard Kang Michael J.Lee Sherwin H.Ho Tong-Chuan He Lewis L.Shi Aravind Athiviraham | 2015 | Genes & Diseases2015，2，4： | 9 |
| 3 | Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells(MSCs)显示文摘Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes.Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries.Bone morphogenetic protein 2(BMP2)induces effective chondrogenesis of mesenchymal stem cells(MSCs)and can thus be explored as a potential therapeutic agent for cartilage defect repair.However,BMP2 also induces robust endochondral ossification.Although the precise mechanisms through which BMP2 governs the divergence of chondrogenesis and osteogenesis remain to be fully understood,blocking endochondral ossification during BMP2-induced cartilage formation may have practical significance for cartilage tissue engineering.Here,we investigate the role of Sox9-donwregulated Smad7 in BMP2-induced chondrogenic differentiation of MSCs.We find that overexpression of Sox9 leads to a decrease in BMP2-induced Smad7 expression in MSCs.Sox9 inhibits BMP2-induced expression of osteopontin while enhancing the expression of chondrogenic marker Col2a1 in MSCs.Forced expression of Sox9 in MSCs promotes BMP2-induced chondrogenesis and suppresses BMP2-induced endochondral ossification.Constitutive Smad7 expression inhibits BMP2-induced chondrogenesis in stem cell implantation assay.Mouse limb explant assay reveals that Sox9 expands BMP2-stimulated chondrocyte proliferating zone while Smad7 promotes BMP2-intitated hypertrophic zone of the growth plate.Cell cycle analysis indicates that Smad7 induces significant early apoptosis in BMP2-stimulated MSCs.Taken together,our results strongly suggest that Sox9 may facilitate BMP2-induced chondrogenesis by downregulating Smad7,which can be exploited for effective cartilage tissue engineering. | Chen Zhao Wei Jiang Nian Zhou Junyi Liao Mingming Yang Ning Hu Xi Liang Wei Xu Hong Chen Wei Liu Lewis L.Shi Leonardo Oliveira Jennifer Moriatis Wolf Sherwin Ho Aravind Athiviraham H.M.Tsai Tong-Chuan He Wei Huang | 2017 | Genes & Diseases2017，4，4： | 7 |
| 4 | Stem cell therapy for chronic skin wounds in the era of personalized medicine:From bench to bedside显示文摘With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care. | Elam Coalson Elliot Bishop Wei Liu Yixiao Feng Mia Spezia Bo Liu Yi Shen Di Wu Scott Du Alexander J.Li Zhenyu Ye Ling Zhao Daigui Cao Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Rex C.Haydon Lewis Shi Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He Russell R.Reid | 2019 | Genes & Diseases2019，6，4： | 6 |
| 5 | 强化降压对高血压患者左心室肥厚的影响显示文摘目前尚不清楚超出推荐值的强化降压是否更能降低高血压患者的左心室肥厚(left ventricular hypertrophy,LVH)发生风险,以及LVH风险降低能否解释强化降压的益处。Soliman等纳入收缩压干预试验(systolic blood pressure intervention,SPRINT)中患有高血压但无糖尿病的8164例受试者(平均年龄67.9岁,女性35.3%,31.2%为非洲裔), | 刘莉 叶鹏 Soliman EZ Ambrosius WT Cushman WC Zhang ZM Bates JT Neyra JA Carson TY Tamariz L Ghazi L Cho ME Shapiro BP He J Fine LJ Lewis CE SPRINT Research Study Group | 2017 | 中华高血压杂志2017，25，6： | 2 |
| 6 | Responses of Tree Species to Climate Warming at Different Spatial Scales显示文摘Tree species respond to climate change at multiple scales,such as species physiological response at fine scale and species distribution (quantified by percent area) at broader spatial scale.At a given spatial scale,species physiological response and distribution can be correlated positively or negatively.The consistency of such correlation relationships at different spatial scales determines whether species responses derived from local scales can be extrapo-lated to broader spatial scales.In this study,we used a coupled modeling approach that coupled a plot-level ecosystem process model (LINKAGES) with a spatially explicit landscape model (LANDIS).We investigated species physio-logical responses and distribution responses to climate warming at the local,zonal and landscape scales respectively,and examined how species physiological response and distribution correlated at each corresponding scale and whether the correlations were consistent among these scales.The results indicate that for zonal and warming-sensitive species,the correlations between species physiological response and distribution are consistent at these spatial scales,and therefore the research results of vegetation response to climate warming at the local scale can be extrapolated to the zonal and landscape scales.By contrast,for zonal and warming-insensitive species the correlations among different spatial scales are consistent at some spatial scales but at other scales.The results also suggest that the results of azonal species at the local scale near their distribution boundaries can not be extrapolated simply to broader scales due to stronger responses to climate warming in those boundary regions. | LIANG Yu HE Hong S LEWIS Bernard L | 2011 | Chinese Geographical Science2011，21，4： | 2 |
| 7 | Sleep disturbances and falls in older people显示文摘 | Latimer HE Cumming RG Lewis R | 2007 | J Gerontol A Biol Sci Med Sci2007，62，1： | 1 |
| 8 | The use of DiI-marked Hepato-cytes to demonstrate or orthotopic intrahepaticeng raftment following hepatoeellular transplantation显示文摘 | Soriano HE Lewis D Legner M | 1992 | Transplantation1992，54，4： | 1 |
| 9 | Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5显示文摘 | Espinoza Lewis R A Yu L He F | 2009 | DevBiol2009，327，2： | 1 |
| 10 | Aerodynamics of the human micro-environment显示文摘 | Lewis HE Foster AR Mullan B J | 1969 | Lancet1969，322，7609： | 1 |
| 11 | A Phase 1 study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia显示文摘 | Simon Z. He Samantha Busfield David S. Ritchie Mark S. Hertzberg Simon Durrant Ian D. Lewis Paula Marlton Andrew J. McLachlan Ian Kerridge Kenneth F. Bradstock Glen Kennedy Andrew W. Boyd Trina M. Yeadon Angel F. Lopez Hayley S. Ramshaw Harry Iland Simone | 2015 | Leukemia & Lymphoma2015，，： | 1 |
| 12 | The use of Dil-marked hepatocytes to demonstrate orthotopic, intrahepatic engraftment following hepatocellular transplantation显示文摘 | Soriano HE Lewis D Legner M | 1992 | Transplantation1992，54，4： | 1 |
| 13 | Vascular imaging of solid tumors in ratswith a radioactive arsenic-labeled antibody that bindsexposed phosphatidylserine显示文摘 | Jennewein M Lewis M A Zhao D Tsyganov E SlavineN He J | 2008 | Clin Cancer Res2008，14，： | 1 |
| 14 | The use of Dil-marked hepatocyteso to demonstrate orthoto-pic,intrahepatic engraftment following hepatocellular transplantation显示文摘 | Soriano HE Lewis D Legner M | 1992 | Transplantation1992，54，4： | 1 |
| 15 | A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes显示文摘 | Lewis AD Menezes DA McDermott HE | 2009 | BMC Med Educ2009，13，9： | 1 |
| 16 | The clinical effectiveness and cost-effectiveness of management strategies for sciatica:systematic review and economic model显示文摘 | Lewis R Williams N Matar HE | | 0，，39： | 1 |
| 17 | A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes显示文摘 | Lewis AD Menezes DA McDermott HE | 2009 | BMC Med Educ2009，9，： | 1 |
| 18 | Expression of HIV transgene aggravates kidney injury in diabetic mice显示文摘 | Sandeep K Mallipattu Ruijie Liu Yifei Zhong Ed Y Chen Vivet te D'Agati Lewis Kaufman Avi Ma'ayan Paul E Klotman Peter Y Chuang John C He | 2013 | Kidney international2013，83，4： | 1 |
| 19 | The clinical effectiveness and cost-effectiveness of management strategies for sciatica: systematic review and economic model显示文摘 | Lewis R Williams N Matar HE | 2011 | Health Technol Assess2011，15，39： | 1 |
| 20 | Long noncoding RNA(lncRNA)H19:An essential developmental regulator with expanding roles in cancer,stem cell differentiation,and metabolic diseases显示文摘Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions. | Junyi Liao Bowen Chen Zhenglin Zhu Chengcheng Du Shengqiang Gao Guozhi Zhao Piao Zhao Yonghui Wang Annie Wang Zander Schwartz Lily Song Jeffrey Hong William Wagstaff Rex CHaydon Hue HLuu Jiaming Fan Russell RReid Tong-Chuan He Lewis Shi Ning Hu Wei Huang | 2023 | Genes & Diseases2023，10，4： | 1 |
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