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| 1 | Adenovirus-mediated gene delivery:Potential applications for gene and cell-based therapies in the new era of personalized medicine显示文摘With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology,it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies.Despite numerous setbacks,efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases.It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies.There has been a long-lasting interest in using viral vectors,especially adenoviral vectors,to deliver therapeutic genes for the past two decades.Among all currently available viral vectors,adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types.The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development.In fact,among over 2000 gene therapy clinical trials approved worldwide since 1989,a significant portion of the trials have utilized adenoviral vectors.This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors,including adenoviral biology,approaches to engineering adenoviral vectors,and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment,vaccination and regenerative medicine.Current challenges and future directions regarding the use of adenoviral vectors are also discussed.It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine. | Cody S.Lee Elliot S.Bishop Ruyi Zhang Xinyi Yu Evan M.Farina Shujuan Yan Chen Zhao Zongyue Zeng Yi Shu Xingye Wu Jiayan Lei Yasha Li Wenwen Zhang Chao Yang Ke Wu Ying Wu Sherwin Ho Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Russell R.Reid Tong-Chuan He | 2017 | Genes & Diseases2017，4，2： | 19 |
| 2 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 3 | Limbal stem cells: Central concepts of corneal epithelial homeostasis显示文摘A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent stud-ies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal | Jinny J Yoon Salim Ismail Trevor Sherwin | 2014 | World Journal of Stem Cells2014，6，4： | 11 |
| 4 | 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 |
| 5 | Neuroimaging the brain-gut axis in patients with irritable bowel syndrome显示文摘AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population. | Kristen R Weaver Lee Anne B Sherwin Brian Walitt Gail D'Eramo Melkus Wendy A Henderson | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，2： | 8 |
| 6 | Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis显示文摘AIM: To investigate the vasoactive intestinal peptides(VIP) expression in irritable bowel syndrome(IBS) and trinitrobenzene sulfonic acid(TNBS) induced colitis.METHODS: The VIP gene expression and protein plasma levels were measured in adult participants(45.8% male) who met Rome Ⅲ criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS.Plasma and colons were collected from naive and inflamed rats.Markers assessing inflammation(i.e.,weight changes and myeloperoxidase levels) were assessed on days 2,7,14 and 28 and compared to controls.Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws.IBS patients(n = 12) were age,gender,race,and BMI-matched with healthy controls(n = 12).Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay.Human gene expression of VIP was analyzed using a custom PCR array.RESULTS: TNBS induced colitis in the rats was confirmed with weight loss(13.7 ± 3.2 g) and increased myeloperoxidase activity.Visceral hypersensitivity tocolo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28.Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis.The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naive rats.This confirmed the induction of inflammation in rats following TNBS treatment.VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naive animals(P < 0.05).Likewise,the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls(P < 0.00001; 95%CI).VIP plasma protein was not significantly different when compared with controls(P = 0.193).CONCLUSION: Alterations in VIP expression may play a role in IBS.Therefore,a better understanding of the physiology of VIP could lead to new therapeutics. | Arseima Y Del Valle-Pinero LeeAnne B Sherwin Ethan M Anderson Robert M Caudle Wendy A Henderson | 2015 | World Journal of Gastroenterology2015，21，1： | 7 |
| 7 | 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 |
| 8 | Utilizing pharmacotherapy and mesenchymal stem cell therapy to reduce inflammation following traumatic brain injury显示文摘The pathologic process of chronic phase traumatic brain injury is associated with spreading inflammation,cell death,and neural dysfunction.It is thought that sequestration of inflammatory mediators can facilitate recovery and promote an environment that fosters cellular regeneration.Studies have targeted post-traumatic brain injury inflammation with the use of pharmacotherapy and cell therapy.These therapeutic options are aimed at reducing the edematous and neurodegenerative inflammation that have been associated with compromising the integrity of the blood-brain barrier.Although studies have yielded positive results from anti-inflammatory pharmacotherapy and cell therapy individually,emerging research has begun to target inflammation using combination therapy.The joint use of anti-inflammatory drugs alongside stem cell transplantation may provide better clinical outcomes for traumatic brain injury patients.Despite the promising results in this field of research,it is important to note that most of the studies mentioned in this review have completed their studies using animal models.Translation of this research into a clinical setting will require additional laboratory experiments and larger preclinical trials. | Sherwin Mashkouri Marci G.Crowley Michael G.Liska Sydney Corey Cesar V.Borlongan | 2016 | Neural Regeneration Research2016，11，9： | 5 |
| 9 | Notch signaling:Its essential roles in bone and craniofacial development显示文摘Notch is a cellecell signaling pathway that is involved in a host of activities including development,oncogenesis,skeletal homeostasis,and much more.More specifically,recent research has demonstrated the importance of Notch signaling in osteogenic differentiation,bone healing,and in the development of the skeleton.The craniofacial skeleton is complex and understanding its development has remained an important focus in biology.In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton,skull,and face develop.We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system,and what importance it may play in the future. | Mikhail Pakvasa Pranav Haravu Michael Boachie-Mensah Alonzo Jones Elam Coalson Junyi Liao Zongyue Zeng Di Wu Kevin Qin Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Yongtao Zhang Changchun Niu Meng Wu Xia Zhao Hao Wang Linjuan Huang Deyao Shi Qing Liu Na Ni Kai Fu Michael J.Lee Jennifer Moriatis Wolf Aravind Athiviraham Sherwin S.Ho Tong-Chuan He Kelly Hynes Jason Strelzow Mostafa El Dafrawy Russell R.Reid | 2021 | Genes & Diseases2021，8，1： | 4 |
| 10 | Nutrient supplemented serum-free medium increases cardiomyogenesis efficiency of human pluripotent stem cells显示文摘AIM: To development of an improved p38 MAPK inhibitor-based serum-free medium for embryoid body cardiomyocyte differentiation of human pluripotent stem cells. METHODS: Human embryonic stem cells (hESC) differentiated to cardiomyocytes (CM) using a p38 MAPK inhibitor (SB203580) based serum-free medium (SB media). Nutrient supplements known to increase cell viability were added to SB medium. The ability of these supplements to improve cardiomyogenesis was evaluated by measurements of cell viability, total cell count, and the expression of cardiac markers via flow cytometry. An improved medium containing Soy hydrolysate (HySoy) and bovine serum albumin (BSA) (SupSB media) was developed and tested on 2 additional cell lines (H1 and Siu-hiPSC). Characterization of the cardiomyocytes was done by immunohistochemistry, electrophysiology and quantitative real-time reverse transcriptionpolymerase chain reaction. RESULTS: hESC cell line, HES-3, differentiating in SB medium for 16 d resulted in a cardiomyocyte yield of 0.07 ± 0.03 CM/hESC. A new medium (SupSB media) was developed with the addition of HySoy and BSA to SB medium. This medium resulted in 2.6 fold increase in cardiomyocyte yield (0.21 ± 0.08 CM/hESC). The robustness of SupSB medium was further demonstrated using two additional pluripotent cell lines (H1, hESC and Siu1, hiPSC), showing a 15 and 9 fold increase in cardiomyocyte yield respectively. The age (passage number) of the pluripotent cells did not affect the cardiomyocyte yields. Embryoid body (EB) cardiomyocytes formed in SupSB medium expressed canonical cardiac markers (sarcomeric α-actinin, myosin heavy chain and troponin-T) and demonstrated all three major phenotypes: nodal-, atrial- and ventricular-like. Electrophysiological characteristics (maximum diastolic potentials and action potential durations) of cardiomyocytes derived from SB and SupSB media were similar. CONCLUSION: The nutrient supplementation (HySoy and BSA) leads to increase in cell viability, cell yield and cardiac marker expression during cardiomyocyte differentiation, translating to an overall increase in cardiomyocyte yield. | Sherwin Ting Marti Lecina Yau-Chi Chan Hung Fat Tse Shaul Reuveny Steve KW Oh | 2013 | World Journal of Stem Cells2013，5，3： | 4 |
| 11 | Tracking invasion and invasiveness in Queensland fruit flies: From classical genetics to 'omics'显示文摘 | William B. SHERWIN Marianne FROMMER John A. SVED Kathryn A. RAPHAEL John G. OAKESHOTT Deborah C.A. SHEARMAN A. Stuart GILCHRIST | 2015 | Current Zoology2015，61，3： | 3 |
| 12 | AN APPROACH TOWARDS HOLISM IN SCIENCE AND ENGINEERING显示文摘This paper posits the desirability of a shift towards a holistic approach over reductionist approaches in the understanding of complex phenomena encountered in science and engineering.An argument based on set theory is used to analyze three examples that illustrate the shortcomings of the reductionist approach.Using these cases as motivational points,a holistic approach to understand complex phenomena is proposed,whereby the human brain acts as a template to do so.Recognizing the need to maintain the transparency of the analysis provided by reductionism,a promising computational approach is offered by which the brain is used as a template for understanding complex phenomena.Some of the details of implementing this approach are also addressed. | Jason SHERWIN | 2010 | Journal of Systems Science and Systems Engineering2010，19，3： | 2 |
| 13 | The Association between Time Spent Outdoors and Myopia in Children and Adolescents显示文摘 | Justin C. Sherwin Mark H. Reacher Ruth H. Keogh Anthony P. Khawaja David A. Mackey Paul J. Foster | 2012 | Ophthalmology2012，，10： | 2 |
| 14 | ADA与EASD对2型糖尿病高血糖处理:治疗启动与评定的新共识方案显示文摘在不到一年时间由同一批专家代表ADA和EASD先后起草和发布了两次关于'2型糖尿病高血糖处理的共识声明'同时发表在2008年1月和12月的《Diabetes Care》和《Diabetologia》上。第一次共识声明内容主要围绕TZDs药物的安全性,本刊作了摘译转载(参阅《中国糖尿病杂志》2008年第7期)。第二次修订的共识声明,关注点为降糖药的新分级,论据及观点比较清晰,故仍摘译供读者参考。 | Nathan DM Buse JB Davidson MB Ferrannini E Holman RR Sherwin R Zinman B 钱荣立(摘译) | 2009 | 中国糖尿病杂志2009，17，1： | 2 |
| 15 | Is there evidence of selection in the dopamine receptor D4 gene in Australian invasive starling populations?显示文摘 | Lee Ann ROLLINS Michael R. WHITEHEAD Andrew R WOOLNOUGH Ron SINCLAIR William B. SHERWIN | 2015 | Current Zoology2015，61，3： | 2 |
| 16 | In vitro culture of enzymatically isolated chondrons:a possible model for the initiation of osteoarthrit 显示文摘 | Ross JM Sherwin AF Poole CA | 2006 | J Anat2006，20，9： | 1 |
| 17 | Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release显示文摘 | AmieI SA Sherwin RS Simonson DC | 1988 | Diabetes1988，17，： | 1 |
| 18 | Epidemiol-ogy of vitamin A deficiency and xerophthalmia in at-risk populations 显示文摘 | Sherwin JC Reacher MH Dean WH | 2012 | Trans R Soc Trop Med Hyg2012，106，4： | 1 |
| 19 | Hedonic Prices and Implicit Markets: Product Differentiation in Pure Competition显示文摘 | Rosen Sherwin | 1974 | Journal of Political Economy1974，82，1： | 1 |
| 20 | Incidence and predictors of glaucoma following surgery for congenital cataract in the first year of life in V ictoria, A ustralia显示文摘 | Jonathan B Ruddle Sandra E Staffieri Jonathan G Crowston Justin C Sherwin David A Mackey | 2013 | Clin Experiment Ophthalmol2013，，7： | 1 |
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