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| 1 | Recent advances in the diagnosis and treatment of acute myocardial infarction显示文摘The Third Universal Definition of Myocardial Infarction(MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin(cT n) with at least one cT n measurement greater than the 99 th percentile of the upper normal reference limit during:(1) symptoms of myocardialischemia;(2) new significant electrocardiogram(ECG) ST-segment/T-wave changes or left bundle branch block;(3) the development of pathological ECG Q waves;(4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or(5) identification of intracoronary thrombus by angiography or autopsy.Myocardial infarction,when diagnosed,is now classified into five types.Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI.However,high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis.The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated,especially if the initial ECG is not diagnostic of MI.There have been significant advances in adjunctive pharmacotherapy,procedural techniques and stent technology in the treatment of patients with MIs.The routine use of antiplatelet agents such as clopidogrel,prasugrel or ticagrelor,in addition to aspirin,reduces patient morbidity and mortality.Percutaneous coronary intervention(PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI.Drug eluting coronary stents are safe and beneficial with primary coronary intervention.Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein Ⅱb/Ⅲa receptor antagonists and is associated with a significant reduction in bleeding.The intra-coronary use of a glycoprotein Ⅱb/Ⅲa antagonist can reduce infarct size.Pre- and post-conditioning techniques can provide additional cardioprotection.However,the incidence and mortality due to MI continues to be high despite all these recent advances.The initial ten year experience with autologous human bone marrow mononuclear cells(BMCs) in patients with MI showed modest but significant increases in left ventricular(LV) ejection fraction,decreases in LV endsystolic volume and reductions in MI size.These studies established that the intramyocardial or intracoronary administration of stem cells is safe.However,many of these studies consisted of small numbers of patients who were not randomized to BMCs or placebo.The recent LateT ime,Time,and Swiss Multicenter Trials in patientswith MI did not demonstrate significant improvement in patient LV ejection fraction with BMCs in comparison with placebo.Possible explanations include the early use of PCI in these patients,heterogeneous BMC populations which died prematurely from patients with chronic ischemic disease,red blood cell contamination which decreases BMC renewal,and heparin which decreases BMC migration.In contrast,cardiac stem cells from the right atrial appendage and ventricular septum and apex in the SCIPIO and CADUCEUS Trials appear to reduce patient MI size and increase viable myocardium.Additional clinical studies with cardiac stem cells are in progress. | Koushik Reddy Asma Khaliq Robert J Henning | 2015 | World Journal of Cardiology2015，7，5： | 107 |
| 2 | Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms显示文摘Osteoporosis,a global age-related health problem in both male and female elderly,insidiously deteriorates the microstructure of bone,particularly at trabecular sites,such as vertebrae,ribs and hips,culminating in fragility fractures,pain and disability.Although osteoporosis is normally associated with senescence and estrogen deficiency,diabetes mellitus(DM),especially type 1 DM,also contributes to and/or aggravates bone loss in osteoporotic patients.This topic highlight article focuses on DM-induced osteoporosis and DM/ osteoporosis comorbidity,covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including,insulin,insulin-like growth factor-1 and angiogenesis.Cellular and molecular mechanisms of DM-related bone loss are also discussed.This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients. | Kannikar Wongdee Narattaphol Charoenphandhu | 2011 | World Journal of Diabetes2011，2，3： | 51 |
| 3 | Osteoarticular manifestations of human brucellosis:A review显示文摘Brucellosis is a common global zoonotic disease, which is responsible for a range of clinical manifestations. Fever, sweating and musculoskeletal pains are observed in most patients. The most frequent complication of brucellosis is osteoarticular involvement, with 10% to 85% of patients affected. The sacroiliac(up to 80%) and spinal joints(up to 54%) are the most common affected sites.Spondylitis and spondylodiscitis are the most frequent complications of brucellar spinal involvement. Peripheral arthritis, osteomyelitis, discitis, bursitis and tenosynovitis are other osteoarticular manifestations, but with a lower prevalence. Spinal brucellosis has two forms: focal and diffuse. Epidural abscess is a rare complication of spinal brucellosis but can lead to permanent neurological deficits or even death if not treated promptly. Spondylodiscitis is the most severe form of osteoarticular involvement by brucellosis, and can have single-or multifocal involvement. Early and appropriate diagnosis and treatment of the disease is important in order to have a successful management of the patients with osteoarticular brucellosis. Brucellosis should be considered as a differential diagnosis for sciatic and back pain, especially in endemic regions. Patients with septic arthritis living in endemic areas also need to be evaluated in terms of brucellosis. Physical examination, laboratory tests and imaging techniques are needed to diagnose the disease. Radiography, computed tomography, magnetic resonance imaging(MRI) and bone scintigraphy are imaging techniques for the diagnosis of osteoarticular brucellosis. MRI is helpful to differentiate between pyogenic spondylitis and brucellar spondylitis. Drug medications(antibiotics)and surgery are the only two options for the treatment and cure of osteoarticular brucellosis. | Seyed Mokhtar Esmaeilnejad-Ganji Seyed Mohammad Reza Esmaeilnejad-Ganji | 2019 | World Journal of Orthopedics2019，10，2： | 52 |
| 4 | Mesenchymal stem cells: Molecular characteristics and clinical applications显示文摘Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells with the capacity to differentiate into tissues of both mesenchymal and non-mesenchymal origin. MSCs can differentiate into osteoblastic, chondrogenic, and adipogenic lineages, although recent studies have demonstrated that MSCs are also able to differentiate into other lineages, including neuronal and cardiomyogenic lineages. Since their original isolation from the bone marrow, MSCs have been successfully harvested from many other tissues. Their ease of isolation and ex vivo expansion combined with their immunoprivileged nature has made these cells popular candidates for stem cell therapies. These cells have the potential to alter disease pathophysiology through many modalities including cytokine secretion, capacity to differentiate along various lineages, immune modulation and direct cell-cell interaction with diseased tissue. Here we first review basic features of MSC biology including MSC characteristics in culture, homing mechanisms, differentiation capabilities and immune modulation. We then highlight some in vivo and clinical evidence supporting the therapeutic roles of MSCs and their uses in orthopedic, autoimmune, and ischemic disorders. | Farbod Rastegar Deana Shenaq Eric R Wagner Stephanie H Kim Russell R Reid Hue H Luu Rex C Haydon | 2010 | World Journal of Stem Cells2010，2，4： | 35 |
| 5 | 3D bioactive composite scaffolds for bone tissue engineering显示文摘Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma,cancer,infection and arthritis.Developing bioactive three-dimensional(3D)scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering(BTE).A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts.However,individual groups of materials including polymers,ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone.Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds.This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers,hydrogels,metals,ceramics and bio-glasses in BTE.Scaffold fabrication methodology,mechanical performance,biocompatibility,bioactivity,and potential clinical translations will be discussed. | Gareth Turnbull Jon Clarke Frederic Picard Philip Riches Luanluan Jia Fengxuan Han Bin Li Wenmiao Shu | 2018 | Bioactive Materials2018，3，3： | 40 |
| 6 | Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?显示文摘Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC hominghas been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms. | Ann De Becker Ivan Van Riet | 2016 | World Journal of Stem Cells2016，8，3： | 37 |
| 7 | WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Mesenchymal stem cells in the treatment of spinal cord injuries:A review显示文摘With technological advances in basic research,the intricate mechanism of secondary delayed spinal cord injury(SCI)continues to unravel at a rapid pace.However,despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord,the cure for paralysis remains elusive.Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI.R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results.An array of mesenchymal stem cells(MSCs)from various sources with novel and promising strategies are being developed to improve function after SCI.In this review,we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI.We will discuss the progress of MSCs application in research,focusing on the neuroprotective properties of MSCs.Finally,we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI. | Venkata Ramesh Dasari Krishna Kumar Veeravalli Dzung H Dinh | 2014 | World Journal of Stem Cells2014，6，2： | 32 |
| 8 | Bone–cartilage crosstalk:a conversation for understanding osteoarthritis显示文摘Although cartilage degradation is the characteristic feature of osteoarthritis(OA), it is now recognized that the whole joint is involved in the progression of OA. In particular, the interaction(crosstalk) between cartilage and subchondral bone is thought to be a central feature of this process. The interface between articular cartilage and bone of articulating long bones is a unique zone, which comprises articular cartilage,below which is the calcified cartilage sitting on and intercalated into the subchondral bone plate. Below the subchondral plate is the trabecular bone at the end of the respective long bones. In OA, there are welldescribed progressive destructive changes in the articular cartilage, which parallel characteristic changes in the underlying bone. This review examines the evidence that biochemical and biomechanical signaling between these tissue compartments is important in OA disease progression and asks whether such signaling might provide possibilities for therapeutic intervention to halt or slow disease development. | David M Findlay Julia S Kuliwaba | 2016 | Bone Research2016，4，3： | 27 |
| 9 | Evolution,current status and advances in application of platelet concentrate in periodontics and implantology显示文摘Platelet concentrates(PC) [platelet-rich plasma(PRP) and platelet-rich fibrin(PRF)] are frequently used for surgical procedures in medical and dental fields,particularly in oral and maxillofacial surgery,plastic surgery and sports medicine.The objective of all these technologies is to extract all the elements from a blood sample that could be used to improve healing and promote tissue regeneration.Although leukocyte rich and leukocyte poor PRP's have their own place in literature,the importance of non-platelet components in a platelet concentrate remains a mystery.PC have come a long way since its first appearance in 1954 to the T-PRF,A-PRF and i-PRF introduced recently.These PC find varied applications successfully in periodontics and implant dentistry as well.However,the technique of preparation,standing time,transfer process,temperature of centrifuge,vibration,etc.,are the various factors for the mixed results reported in the literature.Until the introduction of a proper classification of terminologies,the PC were known by different names in different countries and by different commercial companies which also created a lot of confusion.This review intends to clarify all these confusion by briefing the exact evolution of PC,their preparation techniques,recent advances and their various clinical and technical aspects and applications. | Amit Arvind Agrawal | 2017 | World Journal of Clinical Cases2017，5，5： | 28 |
| 10 | Role of BMSCs in liver regeneration and metastasis after hepatectomy显示文摘Hepatocellular carcinoma(HCC),which develops from liver cirrhosis,is highly prevalent worldwide and is a malignancy that leads to liver failure and systemic metastasis.While surgery is the preferred treatment for HCC,intervention and liver transplantation are also treatment options for end-stage liver disease.However,the success of partial hepatectomy and intervention is hindered by the decompensation of liver function.Conversely,liver transplantation is difficult to carry out due to its high cost and the lack of donor organs.Fortunately,research into bone-marrow stromal cells(BMSCs)has opened a new door in this field.BMSCs are a type of stem cell with powerful proliferative and differential potential that represent an attractive tool for the establishment of successful stem cell-based therapy for liver diseases.A number of different stromal cells contribute to the therapeutic effects exerted by BMSCs because BMSCs can differentiate into functional hepatic cells and can produce a series of growth factors and cytokines capable of suppressing inflammatory responses,reducing hepatocyte apoptosis,reversing liver fibrosis and enhancing hepatocyte functionality.Additionally,it has been shown that BMSCs can increase the apoptosis rate of cancer cells and inhibit tumor metastasis in some microenvironments.This review focuses on BMSCs and their possible applications in liver regeneration and metastasis after hepatectomy. | Hua-Lian Hang Qiang Xia | 2014 | World Journal of Gastroenterology2014，20，1： | 28 |
| 11 | Pilose antler aqueous extract promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells by stimulating the BMP-2/Smad1, 5/Runx2 signaling pathway显示文摘Peptides from Pilose antler aqueous extract(PAAE) have been shown to stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells(BMSCs). However, the underlying molecular mechanisms are not well understood. Here, PAAE was isolated and purified to explore the molecular mechanisms underlying PAAE’s effects on BMSCs as well as its osteoprotective effects in ovariectomized rats. Our results showed that PAAE promoted proliferation and differentiation of BMSCs to become osteoblasts by enhancing ALP activity and increasing extracellular matrix mineralization. The trabecular microarchitecture of ovariectomized rats was also found to be protected by PAAE. Quantitative reverse transcription-polymerase chain reaction(Quantitative RT-PCR) results suggest that PAAE also increased the expression of osteogenic markers including, alkaline phosphatase(ALP), runt-related transcription factor 2(Runx2), osteocalcin(OCN), bone morphogenetic protein-2(BMP-2), and collagen I(COL-I). Immunoblotting results indicated that PAAE upregulated the levels of BMP-2 and Runx2 and was associated with Smad1/5 phosphorylation. PAAE A at the concentration of 200μg·mL^-1 showed the strongest effect on proliferation and osteogenic differentiation of BMSCs after 48 h. Using matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS), we identified the molecular weight of PAAE A and found that it is less than 3000 Da and showed several significant peaks. In conclusion, PAAE activates the BMP-2/Smad1, 5/Runx2 pathway to induce osteoblastic differentiation and mineralization in BMSCs and can inhibit OVX-induced bone loss. These mechanisms are likely responsible for its therapeutic effect on postmenopausal osteoporosis. | REN Cong GONG Wei LI Feng XIE Ming | 2019 | Chinese Journal of Natural Medicines2019，17，10： | 25 |
| 12 | Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism显示文摘AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury. | Zhong-Yang Shen Jing Zhang Hong-Li Song Wei-Ping Zheng | 2013 | World Journal of Gastroenterology2013，19，23： | 23 |
| 13 | Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism显示文摘Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domaincontaining 5(FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue(WAT) and uncoupling protein 1(UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones,including growth plate, trabecular bone, cortical bone, articular cartilage, and bone–tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal(IP) administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-k B ligand(RANKL)-induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice. | Jin Zhang Paloma Valverde Xiaofang Zhu Dana Murray Yuwei Wu Liming Yu Hua Jiang Michel M Dard Jin Huang Zhiwei Xu Qisheng Tu Jake Chen | 2017 | Bone Research2017，5，1： | 23 |
| 14 | Current management of talar osteochondral lesions显示文摘Osteochondral lesions of the talus(OLT) occur in up to 70% of acute ankle sprains and fractures. OLT have become increasingly recognized with the advancements in cartilage-sensitive diagnostic imaging modalities. Although OLT may be treated nonoperatively, a number of surgical techniques have been described for patients whom surgery is indicated. Traditionally, treatment of symptomatic OLT have included either reparative procedures, such as bone marrow stimulation(BMS), or replacement procedures, such as autologous osteochondral transplantation(AOT). Reparative procedures are generally indicated for OLT < 150 mm^2 in area. Replacement strategies are used for large lesions or after failed primary repair procedures. Although shortand medium-term results have been reported, longterm studies on OLT treatment strategies are lacking. Biological augmentation including platelet-rich plasma and concentrated bone marrow aspirate is becoming increasingly popular for the treatment of OLT to enhance the biological environment during healing. In this review, we describe the most up-to-date clinical evidence of surgical outcomes, as well as both the mechanical and biological concerns associated with BMS and AOT. In addition, we will review the recent evidence for biological adjunct therapies that aim to improve outcomes and longevity of both BMS and AOT procedures. | Arianna L Gianakos Youichi Yasui Charles P Hannon John G Kennedy | 2017 | World Journal of Orthopedics2017，8，1： | 23 |
| 15 | Exogenous bone morphogenetic protein-7 reduces hepatic fibrosis inSchistosoma japonicum-infected micevia transforming growth factor-β/Smad signaling显示文摘AIM: To investigate the antifibrotic effects of bone morphogenetic protein-7 (BMP-7) on Schistosoma japonicum (S. japonicum )-induced hepatic fibrosis in BALB/C mice. METHODS: Sixty BALB/C mice were randomly divided into three groups, including a control group (group A, n = 20), model group (group B, n = 20) and BMP-7 treated group (group C, n = 20). The mice in group B and group C were abdominally infected with S. japonicum cercariae to induce a schistosomal hepatic fibrosis model. The mice in group C were administered human recombinant BMP-7. Liver samples were extracted from mice sacrificed at 9 and 15 wk after modeling. Hepatic histopathological changes were assessed using Masson's staining. Transforming growth factor-beta 1 (TGF-β1), alpha-smooth muscle actin (α-SMA), phosphorylated Smad2/3 (pSmad2/3) and Smad7 protein levels and localization were measured by Western blotting and immunohistochemistry, respectively, and their mRNA expressions were detected by reverse transcriptionpolymerase chain reaction (RT-PCR). RESULTS: The schistosomal hepatic fibrosis mouse model was successfully established, as the livers of mice in group B and group C showed varying degrees of typical schistosomal hepatopathologic changes such as egg granuloma and collagen deposition. The degree of collagen deposition in group C was higher than that in group A (week 9: 22.95±6.66vs 2.02±0.76; week 15: 12.84±4.36 vs 1.74±0.80; P<0.05), but significantly lower than that in group B (week 9: 22.95±6.66 vs 34.43±6.96; week 15: 12.84±4.36 vs 18.90±5.07;P<0.05) at both time points. According to immunohistochemistry data, the expressions of α-SMA, TGF-β1 and pSmad2/3 protein in group C were higher than those in group A (α-SMA: week 9: 21.24±5.73 vs 0.33±0.20; week 15: 12.42±4.88 vs 0.34±0.27; TGF-β1: week 9: 37.00±13.74 vs 3.73±2.14; week 15: 16.71±9.80 vs 3.08±2.35; pSmad2/3: week 9: 12.92±4.81 vs 0.83±0.48; week 15: 7.87±4.09 vs 0.90±0.45; P<0.05), but significantly lower than those in group B (α-SMA: week 9: 21.24±5.73 vs 34.39±5.74; week 15: 12.42±4.88 vs 25.90±7.01; TGF-β1: week 9: 37.00±13.74 vs 55.66±14.88; week 15: 16.71±9.80 vs 37.10±12.51; pSmad2/3: week 9: 12.92±4.81 vs 19.41±6.87; week 15: 7.87±4.09vs 13.00±4.98;P<0.05) at both time points; the expression of Smad7 protein in group B was higher than that in group A and group C at week 9 (8.46±3.95 vs 1.00±0.40 and 8.46±3.95 vs 0.77±0.42; P<0.05), while there were no differences in Smad7 expression between the three groups at week 15 (1.09±0.38 vs 0.97±0.42 vs 0.89±0.39; P>0.05). Although minor discrepancies were observed, the results of RT-PCR and Western blotting were mainly consistentwith the immunohistochemical results. CONCLUSION: Exogenous BMP-7 significantly decreased the degree of hepatic fibrosis in both the acute and chronic stages of hepato-schistosomiasis, and the regulatory mechanism may involve the TGF-β/Smad signaling pathway. | Bo-Lin Chen Jie Peng Qing-Fu Li Min Yang Yuan Wang Wei Chen | 2013 | World Journal of Gastroenterology2013，19，9： | 21 |
| 16 | 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 |
| 17 | Use of bone morphogenetic proteins in mesenchymal stemcell stimulation of cartilage and bone repair显示文摘The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair. | Sonia Scarfì | 2016 | World Journal of Stem Cells2016，8，1： | 21 |
| 18 | Historically significant events in the discovery of RANK/RANKL/OPG显示文摘After it was suggested 30 years ago that the osteoblast lineage controlled the formation of osteoclasts, methods were developed that established this to be the case, but the molecular controls were elusive. Over more than a decade much evidence was obtained for signaling mechanisms that regulated the production of a membrane- bound regulator of osteoclastogenesis, in the course of which intercellular communication in bone was revealed in its complexity. The discovery of regulation by tumor necrosis factor ligand and receptor families was made in the last few years of the twentieth century, leading since then to a new physiology of bone, and to exciting drug development. | T John Martin | 2013 | World Journal of Orthopedics2013，4，4： | 21 |
| 19 | Modified porous tantalum rod technique for the treatment of femoral head osteonecrosis显示文摘AIM: To study a modified porous tantalum technique for the treatment of osteonecrosis of the femoral head.METHODS: The porous tantalum rod was combined with endoscopy,curettage,autologous bone grafting and use of bone marrow aspirates from iliac crest aspiration in 49 patients(58 hips) with a mean age of 38 years.The majority of the patients had idiopathic osteonecrosis,followed by corticosteroid-induced osteonecrosis.Thirtyeight hips were of Steinberg stage Ⅱ disease and 20 hips were of stage Ⅲ disease.Patients were followed for 5 years and were evaluated clinically with the Merle D'Aubigne and Postel score and radiologically.The primary outcome of the study was survival based on the conversion to total hip arthroplasty(THA).Secondary outcomes included deterioration of the osteonecrosis to a higher disease stage at 5 years compared to the preoperative period and identification of factors that were associated with survival.The Kaplan-Meier survival analysis was performed to evaluate the survivorship ofthe prosthesis,and the Fisher exact test was performed to test associations between various parameters with survival.RESULTS: No patient developed any serious intraoperative or postoperative complication including implant loosening or migration and donor site morbidity.During the 5-year follow up,1 patient died,7 patients had disease progression and 4 hips were converted to THA.The 5-year survival based on conversion to THA was 93.1% and the respective rate based on disease progression was 87.9%.Stage Ⅱ disease was associated with statistically significant better survival rates compared to stage Ⅲ disease(P = 0.04).The comparison between idiopathic and non-idiopathic osteonecrosis and between steroid-induced and non-steroid-induced osteonecrosis did not showed any statistically significant difference in survival rates.The clinical evaluation revealed statistically significantly improved Merle d'Aubigne scores at 12 mo postoperatively compared to the preoperative period(P < 0.001).The mean preoperative Merle d'Aubigne score was 13.0(SD: 1.8).The respective score at 12 mo improved to 17.0(SD: 2.0).The 12-mo mean score was retained at 5 years.CONCLUSION: The modified porous tantalum rod technique presented here showed encouraging outcomes.The survival rates based on conversion to THA are the lowest reported in the published literature. | Emilios E Pakos Panayiotis Megas Nikolaos K Paschos Spyridon A Syggelos Antonios Kouzelis Georgios Georgiadis Theodoros A Xenakis | 2015 | World Journal of Orthopedics2015，6，10： | 20 |
| 20 | 芪蛭降糖胶囊对糖尿病肾病大鼠肾组织BMP-7及TGF-β_1/smads信号传导通路的影响显示文摘目的:观察芪蛭降糖胶囊对糖尿病肾病(diabetic nephropathy,DN)大鼠肾组织骨形成蛋白-7(bone morpho-genetic protein-7,BMP-7)及转化生长因子(transforming growth factor,TGF)-β1/Smads信号传导通路的影响。方法:48只清洁级雄性Wistar大鼠按体重随机抽取40只,采用切除右肾加腹腔注射链脲菌素( streptozotocin,STZ)的方法制备DN模型,另外8只大鼠行右肾假切术。造模成功后按尿微量白蛋白( microAlbumin,mAlb)高低,两头随机抽取分为模型组、缬沙坦对照组、芪蛭降糖胶囊低剂量组、芪蛭降糖胶囊高剂量组。成模2 d起各组给予相应浓度和剂量的药物,给药12周时观察DN大鼠尿mAlb、α1微球蛋白(α1-MG)和血清肌酐( Scr)、尿素氮( BUN)。然后,处死所有动物,肾组织行HE染色、PAS染色和Masson染色,观察肾组织病理变化并半定量计算肾小管损伤指数(tubulointerstitial injury index,TII),免疫组化法检测BMP-7、TGF-β1、Smad2、Smad7在肾组织的表达。结果:给药12周后,模型组大鼠尿 mAlb、α1-MG较假手术组显著增多( P 〈0.01),3个治疗组DN大鼠尿mAlb、α1-MG较模型组明显减少(P〈0.01),2个中药治疗组的上述4项指标亦较对照组降低(P〈0.05-0.01),且呈剂量依赖性。模型组大鼠Scr、BUN亦较假手术组显著升高(P〈0.01),对照组与模型组相比无明显变化(P〉0.05),但2个中药治疗组较模型组明显降低(P〈0.05-0.01)。 HE染色显示,3个治疗组大鼠肾组织病理损害明显减轻,2个中药治疗组大鼠肾组织病理改善比对照组更明显;PAS染色进行TII评分发现,3个治疗组大鼠TII显著低于模型组(P〈0.01),2个中药治疗组TII明显低于对照组(P〈0.05-0.01);Masson染色观察发现,3个实验组大鼠肾小管间质病变明显轻于模型组,2个中药治疗组大鼠肾小管间质病变轻于对照组;免疫组化法染色并对其灰度值测定发现,3个治疗组大鼠TGF-β1、Smad2在肾组织的表达低于模型组(P〈0.01),2个中药治疗组大鼠TGF-β1、Smad2在肾组织的表达低于对照组(P〈0.05-0.01);3个治疗组大鼠BMP-7、Smad7在肾脏组织的表达高于模型组(P〈0.01),2个中药治疗组大鼠BMP-7、Smad7在肾组织的表达高于对照组(P〈0.05-0.01)。结论:芪蛭降糖胶囊可能通过干预BMP-7/TGF-β1/Smads信号转导通路抑制了TGF-β1信号的细胞内转导,而对DN肾间质纤维化起到治疗作用。 | 武帅 郭兆安 于春江 李悦 姜蓓蓓 肖荣 李敏 刘玉臻 董雄飞 | 2014 | 中国中西医结合肾病杂志2014，15，4： | 20 |
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