Current stem cell research & therapy最新文献

{"title":"The Influence of Renal Stem/Progenitor Cells in Kidney Diseases.","authors":"Fabio Sallustio","doi":"10.2174/011574888X393000250617102301","DOIUrl":"10.2174/011574888X393000250617102301","url":null,"abstract":"","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"709-712"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Stem Cell-derived Extracellular Vesicles in the Treatment of Alzheimer's Disease Model Mice: A Systematic Review and Meta-analysis.","authors":"Qinpin Zheng, Sensen Wang, Tian Wang, Guirong Zhang","doi":"10.2174/011574888X352270250407170235","DOIUrl":"10.2174/011574888X352270250407170235","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disease that is still incurable. Therapy with stem cell or extracellular vesicles is a promising strategy for AD treatment. Therefore, we evaluated whether stem cell-derived extracellular vesicles could improve cognitive function and pathological features in AD model mice.</p><p><strong>Methods: </strong>PubMed, Web of Science, Embase, and The Cochrane Library were searched for studies reporting stem cell-derived extracellular vesicles treatment of AD mice from the establishment of each database to 1st August 2023. SYRCLE was used to assess the risk of bias. The extracted data were analyzed using RevMan 5.4 and Stata 15 software.</p><p><strong>Results: </strong>19 studies were included in the analysis. Meta-analysis showed that treatment with stem cell-derived extracellular vesicles significantly improved cognitive performance of AD mice in the Morris water maze test and the novel object recognition test, reduced β-amyloid deposition, alleviated neuroinflammation and decreased levels of the proinflammatory cytokines and glial fibrillary acidic protein (GFAP) in the brain of AD mice. However, stem cell-derived extracellular vesicle did not affect the level of brain phosphorylated tau (p-Tau).</p><p><strong>Conclusion: </strong>stem cell-derived extracellular vesicles may promote the degradation of β-amyloid plaques in the brain, regulate immunity and protect nerves, which result in cognitive improvement in AD mice.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"728-747"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraarticular Injection of Stem Cell and Related Exosome Targeting Synovial Macrophages in Osteoarthritis.","authors":"Zheng Li, Yuanchi Huang, Weisong Zhang, Wensen Jing","doi":"10.2174/011574888X338318241213055616","DOIUrl":"10.2174/011574888X338318241213055616","url":null,"abstract":"<p><p>Osteoarthritis is a costly and debilitating condition, especially as the population ages and more people are affected. The primary osteoarthritis targets in the joint cavity are chondrocytes and synovial cells. Researchers are increasingly convinced that macrophages play a crucial role in the development or therapy of osteoarthritis despite being largely ignored in earlier studies due to their capacity to switch from a pro-inflammatory to an anti-inflammatory phenotype. Stem cell or similar extracellular vesicle intraarticular injection offers fresh promise for treating osteoarthritis. However, the mechanism by which this works needs further investigation. It is important to investigate the intricate cellular interactions between mesenchymal stem cells (MSCs) and macrophages. Emerging routes using extracellular vesicles (EVs) are garnering more and more attention in intercellular communication, which has historically focused on cytokines and soluble mediators. Therefore, we focus on the polarization of macrophages as a primary consideration in our study of stem cells and associated EVs utilization in treating knee osteoarthritis.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"719-727"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Future Therapeutic Application of Mesenchymal Stem Cell-derived Exosomes in Ulcerative Colitis.","authors":"Huiting Qu, Shoukai He, Jie He, Chengfei Wang, Kewei Wang, Chao Deng, Ting Liu, Haibing Hua, Youyi Liu","doi":"10.2174/011574888X340609241220053638","DOIUrl":"10.2174/011574888X340609241220053638","url":null,"abstract":"<p><p>Exosomes, a subclass of Extracellular Vesicles (EVs), are pivotal mediators of intercellular communication. Exosomes derived from Mesenchymal Stem Cells (MSCs) exhibit anti-inflammatory and immunomodulatory activities similar to that of their parental cells, which makes them a cell-free treatment strategy against Ulcerative Colitis (UC). Engineered MSC Exosomes (MSC-Exos) hold the potential to impart multifunctionality to MSCs and optimize their therapeutic effectiveness. This study provides a comprehensive overview of the research progress, mechanisms of action, and potential applications of MSC-Exos and engineered MSC-Exos in the treatment of UC.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"966-977"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inducing Neural Fate: The Impact of Phenylacetate and Calcium on Human Adipose-derived Mesenchymal Stem Cells Differentiation.","authors":"Mohsen Ghiasi, Mohammad Hajipur, Marzieh Ghollasi, Abdolreza Dayani, Mohammad-Taher Moradi, Ali Salimi","doi":"10.2174/011574888X355333241203114713","DOIUrl":"10.2174/011574888X355333241203114713","url":null,"abstract":"<p><strong>Introduction: </strong>Human adipose-derived stem cells (hADSCs) are considered a promising source for cell replacement therapy in degenerative and traumatic conditions. This study explores the effects of phenylacetate and calcium on the neural differentiation of hADSCs for regenerative medicine. We assessed cell viability and cytotoxicity using the MTT assay, revealing that treatment with 1μM phenylacetate significantly enhanced cell viability compared to control groups over five days, while higher concentrations resulted in cytotoxic effects.</p><p><strong>Method: </strong>Additionally, qualitative analysis through Acridine orange/ethidium bromide (AO/EB) staining indicated normal cellular characteristics at lower phenylacetate concentrations, whereas higher doses led to observable cell death. A subsequent evaluation of intracellular calcium levels demonstrated a significant increase when hADSCs were treated with both phenylacetate and calcium.</p><p><strong>Results: </strong>The neural differentiation potential was further assessed through the relative quantification of neuronal-specific genes, showing marked upregulation of <i>NSE, Oligo-2, β-tubulin III</i>, and <i>MAP-2</i> in all treatment groups compared to controls. Immunohistochemistry confirmed elevated protein expression of neural markers in cultures supplemented with phenylacetate and calcium.</p><p><strong>Conclusion: </strong>These findings suggest that phenylacetate, particularly in conjunction with calcium, enhances the neural differentiation of hADSCs, highlighting its potential utility in regenerative medicine strategies targeting neurodegenerative conditions.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"915-923"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaphorin 3A Confers Protection against Oxidative Stress-induced Damage in Periodontal Ligament Stem Cells through the Activation of the Wnt/β-catenin Signaling Pathway.","authors":"Haipeng He, Xueshun Yuan, Yanyan Chen, Tianyong Hu, Baohui Cheng, Ruitian Du, Jiamin Huang, Xiaorui Geng, Hongwen Li, Senqing Liu, Zhiqiang Liu","doi":"10.2174/011574888X343230250107145153","DOIUrl":"10.2174/011574888X343230250107145153","url":null,"abstract":"<p><strong>Objectives: </strong>The osteogenic potential of periodontal ligament stem cells (PDLSCs) is crucial for periodontal tissue regeneration. Prolonged and excessive oxidative stress (OS) impairs the osteogenic function of PDLSCs. Recently, Semaphorin 3A (Sema3A) has been reported to have multiple roles in bone protection. This study aimed to investigate the protective effect of Sema3A on the osteogenic differentiation of PDLSCs under OS conditions induced by hydrogen peroxide (H₂O₂).</p><p><strong>Methods: </strong>PDLSCs were subjected to H₂O₂ treatment to induce OS. The OS indices in PDLSCs were evaluated by analyzing levels of reactive oxygen species (ROS), cell viability, and expression of antioxidant factors using relevant assay kits. A small molecule inhibitor, XAV-939, was employed to block the Wnt/β-catenin pathway. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining for mineralized nodules. Expression levels of osteogenic gene markers and β-catenin were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis.</p><p><strong>Results: </strong>The stimulation of H₂O₂ induced OS in PDLSCs, resulting in a downregulation of Sema3A expression and a decrease in osteogenic markers, including ALP activity, mineralized nodule formation, and the expression of osteogenic genes (RUNX2 and ALP). However, the application of recombinant human Sema3A (rhSema3A) counteracted H₂O₂-induced OS and restored these osteogenic markers in PDLSCs under OS induced by H₂O₂. Mechanistic studies revealed that these effects were associated with an upregulation of β-catenin levels. Moreover, inhibiting β- catenin expression compromised the protective effect of Sema3A on osteogenesis in PDLSCs under OS.</p><p><strong>Conclusion: </strong>Sema3A exerts a protective effect against H₂O₂-induced OS and activates the Wnt/β- catenin pathway to restore osteogenic differentiation impaired by OS in PDLSCs.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"1012-1023"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Human Umbilical Cord Mesenchymal Stem Cells in Improving Fertility in Polycystic Ovary Syndrome Mice.","authors":"Lukuo Jin, Chenchen Ren, Li Yang, Yuanhang Zhu, Genxia Li, Yun Chang, Junxiao Du, Zhaoyuan Yang, Yuchao Yuan","doi":"10.2174/011574888X287937240424074937","DOIUrl":"https://doi.org/10.2174/011574888X287937240424074937","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrine illness in women of reproductive age and is one of the most important causes of female infertility. The pathogenesis of PCOS is complex. Although mesenchymal stem cell therapy is anticipated to be a successful treatment for PCOS, its long-term safety, including tumorigenesis in patients, remains unknown.</p><p><strong>Objective: </strong>This study aimed to confirm the efficacy and safety of human umbilical cord mesenchymal stem cells in improving fertility in PCOS mice.</p><p><strong>Methods: </strong>In this study, dehydroepiandrosterone (DHEA) was used to construct a C56BL/6 mouse PCOS model, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used as a treatment, and the reproductive phenotype was observed in parallel breeding experiments to confirm the efficacy of the treatment. A 4-month follow-up period, final blood tests, and organ histology were carried out to confirm the long-term safety of the treatment.</p><p><strong>Results: </strong>After hUC-MSCs treatment, the sex hormone disorder of mice was corrected, the morphology and function of the ovary were improved, the number of offspring was significantly increased compared to the control group, and no adverse reactions related to stem cell transplantation such as tumor formation were found within 4 months.</p><p><strong>Conclusion: </strong>The treatment of hUC-MSCs is safe and effective in treating PCOS over the long term.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":"20 3","pages":"279-290"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Zhengsui Wan in the Treatment of Acute Lymphoblastic Leukemia Based on Network Pharmacology and Experimental Validation.","authors":"Xiangdong Yang, Fujun Yang, Pengying Yuan, Juan Xie, Lijun Fang, Weilong Sun, Xia Tao, Dixuan Li, Chenyang Fan, Ning Ji","doi":"10.2174/011574888X327937241129062944","DOIUrl":"10.2174/011574888X327937241129062944","url":null,"abstract":"<p><strong>Background: </strong>Zhengsui Wan (ZSW) is a commonly used traditional Chinese medicine formula for treating Acute Lymphatic Leukemia (ALL) in our institution, and it has shown potential efficacy. However, its mechanism of action (MoA) remains unclear. In this study, we systematically explored the ZSW in ALL (in vitro and in vivo) using network pharmacology and molecular docking techniques.</p><p><strong>Methods: </strong>Mass spectrometry was conducted to analyze possible active components in ZSW. BALB/c mice were treated by ZSW aqueous decoction, and mesenchymal stem cells (MSCs) were extracted for proteomic analysis to evaluate differentially expressed proteins. Moreover, proteins associated with acute lymphoblastic leukemia in SwissTargetPrediction and GeneCards databases were screened, and they intersected with differentially expressed proteins to obtain potential targets for ZSW. Protein interactions were constructed for the selected targets. Then, we performed GO and KEGG enrichment analysis on its basis and screened the core target through K-core. We validated it by molecular docking with the top three actives in the molecular network in degree value. Finally, we detected the regulation of ICAM1 in MSCs by ZSW by qRT-PCR.</p><p><strong>Results: </strong>We detected 182 active ingredients in ZSW and identified 725 differential proteins in ZSWtreated mice, of which 25 were potential targets. Furthermore, MMP2, ICAM1, PSEN1, SLC9A1, and MMP14 were identified as core targets using the PPI network and K-core screening. Moreover, ZSW significantly downregulated ICAM1 expression in MSCs. GO and KEGG enrichment analyses showed that the results of ZSW were coordinated through immunomodulatory, inflammation-related, and drug resistance-related genes, including the PI3K-Akt, cAMP, and Wnt signaling pathways. Molecular docking and molecular dynamics simulations indicated moderate binding capacity between the active compounds and the screened target.</p><p><strong>Conclusion: </strong>In this study, we successfully identified possible active ingredients and predicted potential targets and pathways for ZSW for the treatment of ALL. We provide a new strategy for further research on the molecular basis of ZSW biological effects in ALL. In addition, the potential active ingredients could provide new leads for drug discovery in ALL investigations.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"839-857"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promotion of Epithelial Healing in Oral Mucositis by hESC-derived Mesenchymal Stem Cells <i>via</i> the PI3K/AKT Pathway.","authors":"Kejia Lv, Bicong Gao, Weijia Ye, Chenlu Shen, Tianchi Chen, Chaowei Wang, Hua Yao","doi":"10.2174/011574888X338333241010104024","DOIUrl":"https://doi.org/10.2174/011574888X338333241010104024","url":null,"abstract":"<p><strong>Introduction: </strong>Oral mucositis (OM) is a common and debilitating side effect of cancer therapies such as radiotherapy, chemotherapy, hematopoietic cell transplant, or their combinations. This study focused on the reparative effects of human embryonic stem cell-derived mesenchymal stem cells(hESC-MSCs) in OM and possible mechanisms.</p><p><strong>Methods: </strong>An ulcer model was created in the rat buccal mucosa to mimic an <i>in vivo</i> animal model of OM mucosal injury, and hESC-MSCs were injected 48h later to assess their reparative effects. In vitro, the efficacy of hESC-MSCs in regulating apoptosis and proliferation in LPS- or 5-fluorouracil (5-FU)-injured HaCaT cells was studied using a transwell coculture system. Subsequently, the PI3K inhibitor LY24002 was used to assess whether hESC-MSCs regulated injured HaCaT cells through the PI3K/AKT pathway.</p><p><strong>Results: </strong>In vivo, we found that hESC-MSCs injection promoted OM healing in rats through the acceleration of re-epithelialization and a decrease in apoptosis. In vitro, our findings revealed that the hESC-MSCs treatment led to a reduction in the quantity of HaCaT cells undergoing apoptosis. Western blot analysis revealed that hESC-MSCs activated AKT, resulting in increased protein levels of PCNA and BCL-2 and decreased protein levels of Bax and Caspase-3. Whereas LY294002 reversed these changes.</p><p><strong>Conclusion: </strong>These findings suggest that hESC-MSCs promoted OM wound healing by stimulating the proliferation of epithelial cells and inhibiting their apoptosis in rat models. Furthermore, hESC-MSCs might mediate the PI3K/AKT pathway to modulate apoptosis/proliferation injured by LPS or 5-FU in HaCaT cells.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":"20 7","pages":"810-823"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric Analysis of MSC-based Therapies for Non-COVID-19 ARDS.","authors":"Shengyu Huang, Dan Wang, Yusong Wang, Qimin Ma, Zhihao Zhu, Xiaobin Liu, Tuo Shen, Xin Wang, Guangping Yang, Shaolin Ma, Guanghua Guo, Feng Zhu","doi":"10.2174/011574888X299848240529052619","DOIUrl":"10.2174/011574888X299848240529052619","url":null,"abstract":"<p><strong>Background: </strong>Acute respiratory distress syndrome (ARDS) poses a significant challenge as it lacks specific treatments and can occur due to various etiologies. Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapy for ARDS due to their immunomodulatory, anti-inflammatory, and anti-fibrotic properties. Despite encouraging findings from preclinical studies, clinical evidence supporting the efficacy of MSCs in non-COVID-19 ARDS remains insufficient.</p><p><strong>Methods: </strong>We conducted a systematic search of three major databases (Web of Science Core Collection, Scopus, and PubMed) to identify original articles focusing on MSCs in non-COVID-19 ARDS. Subsequently, we employed the bibliometric package in R Studio to analyze and visualize bibliometric indicators derived from the retrieved articles.</p><p><strong>Results: </strong>Our analysis of 244 original studies revealed a notable trend in research on MSCs and non-COVID-19 ARDS. While the number of publications in this area saw an increase beginning in 2007, it exhibited a decline after 2019, with only 20 articles published in 2022. Notably, a significant proportion (131/244) of these studies originated from Chinese scholars. MSC derivatives emerged as a recent research focus due to their unique advantages as an alternative to MSCs. Specifically, umbilical cord/placental-derived MSCs have gained traction, surpassing the use of bone marrow-derived MSCs by 2022. The route of delivery is still mainly intravenous. Despite the potential advantages of the intratracheal route for lung-related diseases, the intravenous route remains the preferred mode of drug delivery.</p><p><strong>Conclusion: </strong>Research on non-COVID-19 ARDS deserves further attention and investments. Existing studies have primarily focused on MSC derivatives that have shown clinical efficacy. Furthermore, umbilical cord/placental-derived MSCs are expected to replace traditional bone marrow- derived MSCs in research. Intratracheal delivery, which offers advantages for treating pulmonary diseases, still requires extensive experiments to validate.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":"20 6","pages":"660-672"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}