Current stem cell research & therapy最新文献

{"title":"Mesenchymal Stem Cell Therapy for Treating the Underlying Causes of Diabetes Mellitus and Its Consequences.","authors":"Diana Esquivel, Rangnath Mishra, Anand Srivastava","doi":"10.2174/1574888X18666230411111320","DOIUrl":"10.2174/1574888X18666230411111320","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a multifaceted pathological condition, which at present is being considered an epidemic disease keeping the rampant rate of its increase in almost all population groups of the world in consideration. Out of the two types of DM described, T1D is characterized as an autoimmune condition that leads to the destruction of pancreatic β-cells by macrophages and T-cells, thereby, adversely affecting the production of insulin. On the other hand, T2D, often caused by insulin resistance, is commonly related to unhealthy habits, and therefore, it can be prevented in most cases. In both of the conditions, high levels of proinflammatory cytokines like IL-6, TNF-α, and INF-ƴ, lead to chronic inflammation, and elevated oxidative stress resulting in apoptosis and destruction of tissues. Although several treatments are available to treat the symptoms, the underlying causes are not well addressed. One of the most promising approaches to tackle the ill effects and the primary causes of DM is mesenchymal stem cell (MSC) therapy. The use of MSC therapy, because of the immunomodulatory and regenerative properties recorded in this type of cells in a number of experiments carried out in animal models and clinical trials of the disease, has reported positive outcomes. This review covers the principal mechanisms of action induced during MSC therapy in reference to the described pathophysiological pathways of both T1D and T2D. In addition, how this therapeutic intervention can counteract the ill effects of this condition leading to the promotion of tissue regeneration has been covered.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"662-668"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9648478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle-derived <i>miR-27b- 3p</i> activates the Wnt/Β-catenin Pathway by Targeting SMAD4 and Aggravates Hepatic Ischemia-reperfusion Injury.","authors":"Hongnan Li, Weidong Lin, Yunlei Li, Jiayang Zhang, Runsheng Liu, Minghai Qu, Ruihua Wang, Xiaomin Kang, Xuekun Xing","doi":"10.2174/1574888X19666230901140628","DOIUrl":"10.2174/1574888X19666230901140628","url":null,"abstract":"<p><strong>Background: </strong>To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and <i>miR-27</i> (highly expressed in BMSC EVs) in hepatic ischemia‒ reperfusion injury (HIRI).</p><p><strong>Approaches and results: </strong>We constructed a HIRI mouse model and pretreated it with an injection of agomir-<i>miR-27-3p</i>, agomir-NC, BMSC-EVs or control normal PBS into the abdominal cavity. Compared with the HIRI group, HIRI mice preinjected with BMSC-EVs had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P<0.05). However, compared with HIRI+NC mice, HIRI+<i>miR-27b</i> mice had significantly increased ALT and AST levels, aggravated liver necrosis, and increased apoptosis-related protein expression (P<0.05). The proliferation and apoptosis of AML-12 cells transfected with <i>miR-27</i> were significantly higher than the proliferation and apoptosis of AML-12 cells in the mimic NC group (P<0.01) after hypoxia induction. SMAD4 was proven to be a <i>miR-27</i> target gene. Furthermore, compared to HIRI+NC mice, HIRI+<i>miR-27</i> mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, β-catenin, c-Myc, and Cyclin D1.</p><p><strong>Conclusion: </strong>Our findings reveal the role and mechanism of <i>miR-27</i> in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with <i>antimiR- 27</i> might demonstrate better protection against HIRI.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"755-766"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10553356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Stem Cells in Carcinogenesis and Potential Role in Pancreatic Cancer.","authors":"Rishav Sharma, Rishabha Malviya","doi":"10.2174/1574888X19666230914103420","DOIUrl":"10.2174/1574888X19666230914103420","url":null,"abstract":"<p><p>A poor prognosis is associated with pancreatic cancer because of resistance during treatment and early distant metastases. The discovery of cancer stem cells has opened up novel avenues for research into the biology and treatment of cancer. Many investigations have pointed out the role of these types of stem cells in the oncogenesis and progression of hematologic and solid malignancies, specifically. Due to the existence of cancer stem cells in the proliferation and preservation of pancreatic tumors, such malignancies could be difficult to eradicate using conventional treatment techniques like chemotherapy and radiotherapy. It is hypothesized that pancreatic malignancies originate from a limited population of aberrant cancer stem cells to promote carcinogenesis, tumour metastasis, and therapeutic resistance. This review examines the role of pancreatic cancer stem cells in this disease and their significance in carcinogenesis, as well as the signals which modulate them, and also examines the ongoing clinical studies that are now being conducted with pancreatic stem cells.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"1185-1194"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation of Pancreatic Beta Cells: Dual Acting of Inflammatory Factors.","authors":"Faeze Shahedi, Arron Munggela Foma, Azam Mahmoudi-Aznaveh, Mohammad Ali Mazlomi, Zahra Azizi, Mohammad Reza Khorramizadeh","doi":"10.2174/1574888X18666230504093649","DOIUrl":"10.2174/1574888X18666230504093649","url":null,"abstract":"<p><p>In the past decades, scientists have made outstanding efforts to treat diabetes. However, diabetes treatment is still far from satisfactory due to the complex nature of the disease and the challenges encountered in resolving it. Inflammatory factors are key regulators of the immune system's response to pathological insults, organ neogenesis, rejuvenation of novel cells to replace injured cells and overwhelming disease conditions. Currently, the available treatments for type 1 diabetes include daily insulin injection, pancreatic beta cell or tissue transplantation, and gene therapy. Cell therapy, exploiting differentiation, and reprogramming various types of cells to generate pancreatic insulin-producing cells are novel approaches for the treatment of type 1 diabetes. A better understanding of the inflammatory pathways offers valuable and improved therapeutic options to provide more advanced and better treatments for diabetes. In this review, we investigated different types of inflammatory factors that participate in the pathogenesis of type 1 diabetes, their possible dual impacts on the differentiation, reprogramming, and fusion of other stem cell lines into pancreatic insulin-producing beta cells, and the possibility of applying these factors to improve the treatment of this disease.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"832-839"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9418175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.","authors":"Hanan Fouad, Ibrahim A Albahlol, Hazim A Wahab, Eman H Nadwa, Heba M Galal, Mohamed Abouelkheir, Ahmed E Taha, Abdelkarim G Kamel, Hassan A Abdelmawlla","doi":"10.2174/1574888X18666230713121530","DOIUrl":"10.2174/1574888X18666230713121530","url":null,"abstract":"<p><strong>Background: </strong>Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis.</p><p><strong>Objectives: </strong>The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage.</p><p><strong>Methods: </strong>Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (10⁶ cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted.</p><p><strong>Results: </strong>BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs.</p><p><strong>Conclusion: </strong>The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"725-734"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9832285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Advances in Wound Healing and Regenerative Medicine.","authors":"Nesa Fani, Maryam Moradi, Roxana Zavari, Farzad Parvizpour, Adele Soltani, Zohreh Arabpour, Arefeh Jafarian","doi":"10.2174/1574888X18666230301140659","DOIUrl":"10.2174/1574888X18666230301140659","url":null,"abstract":"<p><p>Treating chronic wounds is a common and costly challenge worldwide. More advanced treatments are needed to improve wound healing and prevent severe complications such as infection and amputation. Like other medical fields, there have been advances in new technologies promoting wound healing potential. Regenerative medicine as a new method has aroused hope in treating chronic wounds. The technology improving wound healing includes using customizable matrices based on synthetic and natural polymers, different types of autologous and allogeneic cells at different differentiation phases, small molecules, peptides, and proteins as a growth factor, RNA interference, and gene therapy. In the last decade, various types of wound dressings have been designed. Emerging dressings include a variety of interactive/ bioactive dressings and tissue-engineering skin options. However, there is still no suitable and effective dressing to treat all chronic wounds. This article reviews different wounds and common treatments, advanced technologies and wound dressings, the advanced wound care market, and some interactive/bioactive wound dressings in the market.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"277-291"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10794285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Mesenchymal Stem/Stromal Cells Secretome in Macrophage Polarization: Perspectives on Treating Inflammatory Diseases.","authors":"Dongdong Ti, Jun Yi, Huihua Chen, Haojie Hao, Chunmeng Shi","doi":"10.2174/1574888X18666230811093101","DOIUrl":"10.2174/1574888X18666230811093101","url":null,"abstract":"<p><p>Mesenchymal stem/stromal cells (MSCs) have exhibited potential for treating multiple inflammation- related diseases (IRDs) due to their easy acquisition, unique immunomodulatory and tissue repair properties, and immune-privileged characteristics. It is worth mentioning that MSCs release a wide array of soluble bioactive components in the secretome that modulate host innate and adaptive immune responses and promote the resolution of inflammation. As the first line of defense, macrophages exist throughout the entire inflammation process. They continuously switch their molecular phenotypes accompanied by complementary functional regulation ranging from classically activated pro-inflammatory M1-type (M1) to alternatively activated anti-inflammatory M2-type macrophages (M2). Recent studies have shown that the active intercommunication between MSCs and macrophages is indispensable for the immunomodulatory and regenerative behavior of MSCs in pharmacological cell therapy products. In this review, we systematically summarized the emerging capacities and detailed the molecular mechanisms of the MSC-derived secretome (MSC-SE) in immunomodulating macrophage polarization and preventing excessive inflammation, providing novel insights into the clinical applications of MSC-based therapy in IRD management.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"894-905"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10313062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cell-Derived Exosomes Mitigate Acute Murine Liver Injury via Ets-1 and Heme Oxygenase-1 Up-regulation.","authors":"Ying-Hsien Kao, Chih-Yang Chang, Yu-Chun Lin, Po-Han Chen, Po-Huang Lee, Huoy-Rou Chang, Wen-Yu Chang, Yo-Chen Chang, Shen-Fa Wun, Cheuk-Kwan Sun","doi":"10.2174/1574888X19666230918102826","DOIUrl":"10.2174/1574888X19666230918102826","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs)-derived exosomes have been previously demonstrated to promote tissue regeneration in various animal disease models. This study investigated the protective effect of exosome treatment in carbon tetrachloride (CCl4)-induced acute liver injury and delineated possible underlying mechanism.</p><p><strong>Methods: </strong>Exosomes collected from conditioned media of previously characterized human umbilical cord-derived MSCs were intravenously administered into male CD-1 mice with CCl₄-induced acute liver injury. Biochemical, histological and molecular parameters were used to evaluate the severity of liver injury. A rat hepatocyte cell line, Clone-9, was used to validate the molecular changes by exosome treatment.</p><p><strong>Results: </strong>Exosome treatment significantly suppressed plasma levels of AST, ALT, and pro-inflammatory cytokines, including IL-6 and TNF-α, in the mice with CCl₄-induced acute liver injury. Histological morphometry revealed a significant reduction in the necropoptic area in the injured livers following exosome therapy. Consistently, western blot analysis indicated marked elevations in hepatic expression of PCNA, c-Met, Ets-1, and HO-1 proteins after exosome treatment. Besides, the phosphorylation level of signaling mediator JNK was significantly increased, and that of p38 was restored by exosome therapy. Immunohistochemistry double staining confirmed nuclear Ets-1 expression and cytoplasmic localization of c-Met and HO-1 proteins. <i>In vitro</i> studies demonstrated that exosome treatment increased the proliferation of Clone-9 hepatocytes and protected them from CCl4-induced cytotoxicity. Kinase inhibition experiment indicated that the exosome-driven hepatoprotection might be mediated through the JNK pathway.</p><p><strong>Conclusion: </strong>Exosome therapy activates the JNK signaling activation pathway as well as up-regulates Ets-1 and HO-1 expression, thereby protecting hepatocytes against hepatotoxin-induced cell death.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"906-918"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Composite Skin Patch Loaded with Bioactive Functional Factors Derived from Multicellular Spheres of EMSCs for Regeneration of Full-thickness Skin Defects in Rats.","authors":"Xuan Zhang, Wentao Shi, Xun Wang, Yin Zou, Wen Xiang, Naiyan Lu","doi":"10.2174/1574888X19666230908142426","DOIUrl":"10.2174/1574888X19666230908142426","url":null,"abstract":"<p><strong>Background: </strong>Transplantation of stem cells/scaffold is an efficient approach for treating tissue injury including full-thickness skin defects. However, the application of stem cells is limited by preservation issues, ethical restriction, low viability, and immune rejection <i>in vivo</i>. The mesenchymal stem cell conditioned medium is abundant in bioactive functional factors, making it a viable alternative to living cells in regeneration medicine.</p><p><strong>Methods: </strong>Nasal mucosa-derived ecto-mesenchymal stem cells (EMSCs) of rats were identified and grown in suspension sphere-forming 3D culture. The EMSCs-conditioned medium (EMSCs-CM) was collected, lyophilized, and analyzed for its bioactive components. Next, fibrinogen and chitosan were further mixed and cross-linked with the lyophilized powder to obtain functional skin patches. Their capacity to gradually release bioactive substances and biocompatibility with epidermal cells were assessed <i>in vitro</i>. Finally, a full-thickness skin defect model was established to evaluate the therapeutic efficacy of the skin patch.</p><p><strong>Results: </strong>The EMSCs-CM contains abundant bioactive proteins including VEGF, KGF, EGF, bFGF, SHH, IL-10, and fibronectin. The bioactive functional composite skin patch containing EMSCs-CM lyophilized powder showed the network-like microstructure could continuously release the bioactive proteins, and possessed ideal biocompatibility with rat epidermal cells <i>in vitro</i>. Transplantation of the composite skin patch could expedite the healing of the full-thickness skin defect by promoting endogenous epidermal stem cell proliferation and skin appendage regeneration in rats.</p><p><strong>Conclusion: </strong>In summary, the bioactive functional composite skin patch containing EMSCs-CM lyophilized powder can effectively accelerate skin repair, which has promising application prospects in the treatment of skin defects.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"1142-1152"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10554810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compression Promotes the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating METTL14-mediated IGF1","authors":"Zengbo Wu","doi":"10.2174/011574888x244047231012103752","DOIUrl":"https://doi.org/10.2174/011574888x244047231012103752","url":null,"abstract":"Background and Objectives:: Orthodontic treatment involves the application of mechanical force to induce periodontal tissue remodeling and ultimately promote tooth movement. It is essential to study the response mechanisms of human periodontal ligament stem cells (hPDLSCs) to improve orthodontic treatment. Methods:: In this study, hPDLSCs treated with compressive force were used to simulate orthodontic treatment. Cell viability and cell death were assessed using the CCK-8 assay and TUNEL staining. Alkaline phosphatase (ALP) and alizarin red staining were performed to evaluate osteogenic differentiation. The binding relationship between IGF1 and METTL14 was assessed using RIP and dual-luciferase reporter assays. Results:: The compressive force treatment promoted the viability and osteogenic differentiation of hPDLSCs. Additionally, m6A and METTL14 levels in hPDLSCs increased after compressive force treatment, whereas METTL14 knockdown decreased cell viability and inhibited the osteogenic differentiation of hPDLSCs treated with compressive force. Furthermore, the upregulation of METTL14 increased m6A levels, mRNA stability, and IGF1 expression. RIP and dual-luciferase reporter assays confirmed the interaction between METTL14 and IGF1. Furthermore, rescue experiments demonstrated that IGF1 overexpression reversed the effects of METTL14 knockdown in hPDLSCs treated with compressive force. Conclusions:: In conclusion, this study demonstrated that compressive force promotes cell viability and osteogenic differentiation of hPDLSCs by regulating IGF1 levels mediated by METTL14.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"47 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138540719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}