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Opening the LOX to bone metastasis: The role of secreted lysyl oxidase in skeletal recurrence of breast cancers

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Genes & Diseases 2015年第4期2卷 288-290页

作者： Maryam K.Mohammed Connie Shao Hue H.Luu Rex C.Haydon The University of Chicago Pritzker School of Medicine and Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Breast cancer is the second-most prevalent cancer in the United States,with 234,190 new cases projected to be diagnosed in *** initial diagnosis is commonly made early in its disease course due to the use of routine screening mammography.1 Combined with advances in adjuvant chemotherapy,this has led to promising overall outcomes,including a 5-year survival rate of 89.4%and a 10%e12%rate of locoregional recurrence at 20 years for stage I/II disease.1-3 By comparison,prognosis remains poor for patients with metastatic disease at diagnosis or for those who present after initial cure of disease with distant recurrence.4 Among cases of distant recurrence,skeletal recurrence occurs frequently and can be accompanied by hypercalcemia,pain,and functional compromise often requiring a protracted course of palliative therapy.

关键词： diagnosis metastasis chemotherapy

Engineered nucleus-free mesenchymal stem cells (MSCs) for the targeted delivery of therapeutics to disease site

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Genes & Diseases 2023年第2期10卷 310-312,I0001页

作者： Zander Schwartz Piao Zhao Annie Wang Guozhi Zhao Wei Zeng Yonghui Wang Hue H. Luu Rex C. Haydon Tong-Chuan He Russell R. Reid Jason Strelzow School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA departments of orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent article published in Nature Biomedical Engineering revealed an innovative strategy to engineer nucleus-free human mesenchymal stem cells (MSCs) for targeted delivery of therapeutics to disease site.1 MSCs have emerged as promising vehicles of therapeutic delivery.2,3 MSCs are undifferentiated pluripotent stem cells derived from areas such as bone marrow and adipose tissue.4,5 MSCs are sought after for their chemotaxis, or ability to home towards a chemical stimulus, and capacity for modification with elements such as chemoattractant receptors and adhesion molecules.1 These properties allow for site-specific and minimally-invasive therapeutic administration and treatment.

关键词： targeted delivery sought

Methylene blue enhances polyethylene glycol-fusion repair of completely severed rat sciatic nerves

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Neural Regeneration research 2021年第10期16卷 2056-2063页

作者： Cameron L.Ghergherehchi Jaimie T.Shores Joseph Alderete Erik K.Weitzel George D.Bittner institute for Cellular and Molecular Biology University of Texas at AustinAustinTXUSA department of Plastic and Reconstructive Surgery Johns Hopkins University School of MedicineBaltimoreMDUSA department of Surgery RESTOR LaboratorySan AntonioTXUSA department of Neuroscience University of Texas at AustinAustinTXUSA

Complete transection of peripheral mixed nerves immediately produces loss of sensory perception,muscle contractions and voluntary behavior mediated by the severed distal *** contrast to natural regeneration(~1 mm/d)of proximal axons that may eventually reinnervate denervated targets,re-innervation is restored within minutes by PEG-fusion that consists of neurorrhaphy and a sequence of well specified hypo-and isotonic calcium-free or calcium-containing solutions,the anti-oxidant methylene blue(MB)and the membrane fusogen polyethylene glycol(PEG).In this study,we examined the relative efficacy of PEG-fusion with no MB(0%),0.5%MB,or 1%MB on the recovery of voluntary behaviors by female Sprague-Dawley rats with a complete mid-thigh severance of their sciatic nerve bathed in extracellular fluid or calcium-containing isotonic *** recovery of voluntary behaviors is the most relevant measure of success of any technique to repair peripheral nerve *** assessed recovery by the sciatic functional index,a commonly used measure of voluntary hindlimb behaviors following complete sciatic *** reported that both 1%MB and 0.5%MB in sterile distilled water in our PEG-fusion protocol with neurorrhaphy significantly increased the rate and extent of behavioral recovery compared to PEG plus neurorrhaphy ***,0.5%MB was as effective as 1%MB in voluntary behavioral recovery as assessed by the sciatic functional *** sterile 1%MB is no longer clinically available,we therefore recommend that 0.5%MB be included in upcoming human clinical trials to evaluate the safety and efficacy of *** animal procedures were approved by the University of Texas Institutional Animal Care and Use Committee(AUP-2019-00225)on September 9,2020.

关键词： axotomy methylene blue nerve repair neurorrhaphy peripheral nerve injury polyethylene glycol fusion sciatic nerve

Biopolymer-nanotube nerve guidance conduit drug delivery for peripheral nerve regeneration:In vivo structural and functional assessment

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Bioactive Materials 2021年第9期6卷 2881-2893页

作者： Ohan S.Manoukian Swetha Rudraiah Michael R.Arul Jenna M.Bartley Jiana T.Baker Xiaojun Yu Sangamesh G.Kumbar department of Biomedical Engineering University of ConnecticutStorrsCTUSA department of Orthopedic Surgery University of Connecticut HealthFarmingtonCTUSA department of Pharmaceutical Sciences University of Saint JosephHartfordCTUSA department of Immunology Center on AgingUniversity of Connecticut HealthFarmingtonCTUSA department of Biomedical Engineering Stevens Institute of TechnologyHobokenNJUSA

Peripheral nerve injuries account for roughly 3%of all trauma patients with over 900,000 repair procedures annually in the *** all extremity peripheral nerve injuries,51%require nerve repair with a transected *** current gold-standard treatment for peripheral nerve injuries,autograft repair,has several *** constructs are currently only suitable for short gaps or small diameter ***,we investigate novel nerve guidance conduits with aligned microchannel porosity that deliver sustained-release of neurogenic 4-aminopyridine(4-AP)for peripheral nerve regeneration in a critical-size(15 mm)rat sciatic nerve transection *** results of functional walking track analysis,morphometric evaluations of myelin development,and histological assessments of various markers confirmed the equivalency of our drug-conduit with autograft *** nerves showed formation of thick myelin,presence of S100 and neurofilament markers,and promising functional *** conduit’s aligned microchannel architecture may play a vital role in physically guiding axons for distal target reinnervation,while the sustained release of 4-AP may increase nerve conduction,and in turn synaptic neurotransmitter release and upregulation of critical Schwann cell neurotrophic ***,our nerve construct design facilitates efficient and efficacious peripheral nerve regeneration via a drug delivery system that is feasible for clinical applications.

关键词： Peripheral nerve regeneration Nerve guidance conduit Sciatic nerve transection Small-molecule drug delivery Neurotrophic factor Functional recovery

Comparison of complications and clinical outcomes between extreme lateral/posterior and open anterior/posterior approaches in the treatment of adult scoliosis

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中国骨科临床与基础研究杂志 2017年第6期9卷 331-343页

作者： Honglei YI Jiawei LIAO Oheneba Boachie-Adjei Zenghui WU Hong XIA department of orthopaedics Guangzhou General Hospital of PLAGuangzhouGuangdong510010China Scoliosis service Hospital for special surgeryNew York10021United States of America

Objectives To determine the differences of clinical outcome and complications between combined extreme lateral/posterior(X/P)approach and open anterior/posterior(A/P)approach for treatment of adult *** Twelve patients who had X/P fusion for primary adult scoliosis were matched with a cohort of 18 patients who underwent A/P *** anterior fusion was performed via a thoracotomy/thoracoabdominal approach,and extreme lateral interbody fusion(XLIF)was performed using an expandable tubular retractor through a transpsoas access to the target disc *** of the patients were followed up at least 2 *** time,estimate blood loss(EBL)and transfusion volume were noted,radiographic parameters were evaluated before surgery and at final follow-up,and Scoliosis research Society(SRS)-22 score,Oswestry disability index(ODI)as well as complications were *** There were no significant differences between two groups for age,gender,diagnosis,preoperative curve magnitudes and fusion *** was statistically less in X/P than A/P group(2 304 vs 3 176 mL,P=0.04),and there was a trend toward shorter surgical time(493 vs 528 min,P=0.057).Postoperative radiographic coronal correction were almost the same between two *** were 14 complications including 4 perioperative and 10 late in X/P group,comparing to A/P group with 11 perioperative and 12 late complications,which showed no significant differences between two groups(P>0.05).Wound infection was found in 3 A/P patients while no X/P patients was infected(P=0.26).Early revision surgery was performed in 0 X/P patients and 3 A/P patients without significant difference(P=0.26).Pseudarthrosis rates found in X/P versus A/P group(3/12 vs 1/18)were not significantly different(P=0.27).The occurrence rate of proximal junctional kyphosis(PJK)was the same(5/12 vs 7/18)in two ***-22 score and ODI in two groups reflected a similar patient assessment before surgery,and improvement at the las

关键词： Scoliosis Spinal fusion Extreme lateral interbody fusion Anteroposterior fusion Postoperative complications Adult

Pathological mechanisms and therapeutic outlooks for arthrofibrosis

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Bone research 2019年第1期7卷 1-24页

作者： Kayley M.Usher Sipin Zhu Georgios Mavropalias John A.Carrino Jinmin Zhao Jiake Xu School of Biomedical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia department of orthopaedics The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina School of Medical and Health Sciences Edith Cowan UniversityJoondalupWestern AustraliaAustralia Hospital for Special Surgery New YorkNYUSA Guangxi Key Laboratory of Regenerative Medicine Guangxi Medical UniversityNanningGuangxiChina department of orthopaedic Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxiChina

Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury,surgery and *** extracellular matrix and adhesions contract pouches,bursae and tendons,cause pain and prevent a normal range of joint motion,with devastating consequences for patient quality of *** affects people of all ages,with published rates *** risk factors and best management strategies are largely unknown due to a poor understanding of the pathology and lack of diagnostic ***,current research into the pathogenesis of fibrosis in organs now informs the understanding of *** process begins when stress signals stimulate immune *** resulting cascade of cytokines and mediators drives fibroblasts to differentiate into myofibroblasts,which secrete fibrillar collagens and transforming growth factor-β(TGF-β).Positive feedback networks then dysregulate processes that normally terminate healing *** propose two subtypes of arthrofibrosis occur:active arthrofibrosis and residual *** the latter the fibrogenic processes have resolved but the joint remains *** best therapeutic approach for each subtype may differ *** typically involves surgery,however,a pharmacological approach to correct dysregulated cell signalling could be more *** research shows that myofibroblasts are capable of reversing differentiation,and understanding the mechanisms of pathogenesis and resolution will be essential for the development of cell-based *** with significant promise are currently available,with more in development,including those that inhibit TGF-βsignalling and epigenetic *** review focuses on pathogenesis of sterile arthrofibrosis and therapeutic treatments.

关键词： Arthrofibrosis range cell

Top 20 cited Spine Journal articles,1990-2009

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World Journal of Orthopedics 2014年第3期5卷 392-397页

作者： Hossein K Elgafy Jacob D Miller Sohaib Hashmi Steven Ericksen department of orthopaedic Surgery University of Toledo Medical CenterToledoOH 43614United States

AIM:To determine the most cited articles and most published authors in Spine Journal from ***:Spine Journal,established in 1976,is affiliated with 12 spine societies and a leader in spine research *** analysis is a method to determine the impact of a journal and its articles on academia and clinical *** the institute for Scientific Information Web of Knowledge,we determined the most cited articles in Spine Journal *** characteristics and type of article were ***,we evaluated the most published authors during the same time period and calculated the number of citations for each *** number of first authorships for each of these authors was also determined along with the number of citations for those ***:The top 20 cited articles range from 491 to267 total *** top 20 published authors had between 41 and 135 *** of the top 20articles were clinical *** range of citations per lead authorship ratio was 36 to 724 with one author having no lead *** back pain was the most common theme encountered in the top cited *** first-ranked article was not a spine-specific topic rather it was regarding general physical and men-tal health status survey update ***:Spine Journal and its authors have a clear impact on the scientific community based on this review of the top articles and authors in the last 20years.

关键词： Citation analysis Back pain Spine Journal

Dysfunctional stem and progenitor cells impair fracture healing with age

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World Journal of Stem Cells 2019年第6期11卷 281-296页

作者： Diane R Wagner Sonali Karnik Zachary J Gunderson Jeffery J Nielsen Alanna Fennimore Hunter J Promer Jonathan W Lowery M Terry Loghmani Philip S Low Todd O McKinley Melissa A Kacena Matthias Clauss Jiliang Li department of Mechanical and Energy Engineering Indiana University-Purdue University IndianapolisIndianapolisIN 46202United States department of orthopaedic Surgery Indiana University School of MedicineIndianapolisIN 46202United States department of Medicinal Chemistry and Molecular Pharmacology Purdue UniversityWest LafayetteIN 47907United States department of Physical Therapy Indiana University- Purdue University IndianapolisIndianapolisIN 46202United States Division of Biomedical Science Marian University College of Osteopathic MedicineIndianapolisIN 46222United States department of Chemistry Purdue UniversityWest LafayetteIN 47907 United States Richard L. Roudebush VA Medical Center IndianapolisIN 46202United States department of Medicine Indiana University School of MedicineIndianapolisIN 46202United States department of Biology Indiana University-Purdue University IndianapolisIndianapolisIN 46202United States

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature;mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging;a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.

关键词： Fracture healing Aging Bone Angiogenesis Mesenchymal stem cells Endothelial progenitor cells

具有涡流热效应的液态金属微球用于磁热增强的癌症栓塞-免疫联合治疗

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Science Bulletin 2023年第16期68卷 1772-1783,M0004页

作者：杨乃霖孙兴伟周杨楷杨笑远尤嘉熙虞泽鹏葛隽巩飞肖志晟靳勇刘庄程亮 institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials and DevicesSoochow UniversitySuzhou 215123China department of Intervention The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Nuclear Medicine department The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Center for Medical Ultrasound Suzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215001China department of orthopaedic Surgery The First Affiliated Hospital of Soochow UniversitySuzhou 215006China

肝细胞癌患者由于肝癌的高转移性和高复发率表现出预后差的特征.本文提出了一种通过磁热疗法(MHT)增强癌症免疫治疗联合经导管动脉栓塞(TAE)治疗肝癌肿瘤的有效策略.通过微流控技术制备的尺寸均匀液态金属微球(LM MSs),由于在交变磁场... 详细信息

肝细胞癌患者由于肝癌的高转移性和高复发率表现出预后差的特征.本文提出了一种通过磁热疗法(MHT)增强癌症免疫治疗联合经导管动脉栓塞(TAE)治疗肝癌肿瘤的有效策略.通过微流控技术制备的尺寸均匀液态金属微球(LM MSs),由于在交变磁场下的涡流热效应表现出显著的磁感应加热能力,可同时作为MHT和TAE两种癌症治疗策略的有效药物.一方面,LM MSs优异的涡流磁热效应表现出高效的MHT治疗疗效.另一方面,LM MSs引发的MHT可以显著增强免疫系统激活,促进免疫细胞的浸润;与免疫检查点阻断(ICB)治疗联合后可以进一步刺激强大的免疫应答,从而抑制远端肿瘤的生长.此外,LM MSs-碘油栓塞剂在兔子原位肝癌模型中表现出优异的栓塞-磁热联合治疗效果.总之,该工作不仅证明了LM MSs可以作为有效的MHT试剂实现MHT-免疫联合治疗,而且还展示了TAE与MHT联合治疗在原位大型肝肿瘤治疗中的重要应用前景.

关键词：癌症治疗高复发率 TAE 微流控技术液态金属免疫细胞免疫应答交变磁场