Current stem cell research & therapy最新文献

{"title":"Menstrual Blood-Derived Mesenchymal Stem Cell Therapy for Severe COVID-19 Patients.","authors":"Fezzeh Heidari, Reza Heidari, Mehrdad Nasrollahzadeh Sabet, Amir Ali Hamidieh, Zohreh Saltanatpour","doi":"10.2174/1574888X18666230417085117","DOIUrl":"10.2174/1574888X18666230417085117","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), was declared a global pandemic in March 2020 and resulted in more than 6 million deaths worldwide to date. Although several vaccines were produced against COVID-19 and many therapeutic protocols were developed for the management of this respiratory infection, COVID-19 pandemic has still remained an unresolved problem with the emergence of new variants of SARS-CoV-2, especially vaccine-resistant variants. Probably, end of the COVID-19 needs effective and certain treatments which were undiscovered to date. According to immunomodulatory and regenerative properties, mesenchymal stem cells (MSCs) have been considered a therapeutic approach to suppressing cytokine storm caused by SARS-CoV-2 and the treatmet of severe COVID-19. Following intravenous (IV) infusion of MSCs, cells entrap in the lung, guard alveolar epithelial cells, suppress pulmonary fibrosis and improve lung dysfunction. The human menstrual blood-derived stem cells (hMenSCs) as a novel source of MSCs are collected by noninvasive, painless, and easy way without ethical issues. MenScs are an abundant and cheap source with a high proliferation rate and differentiation ability into multiple cell lineages. Regarding immunomodulatory and anti-inflammatory properties, regenerative ability and low immunogenicity, these cells exhibit great potential in the treatment of various diseases. Some clinical trial studies have begun using MenSCs to treat severe COVID-19. According to these trials, MenSC therapy showed promising and encouraging results in treating severe COVID-19. We reviewed published clinical trials and summarized the effects of MenSC therapy on severe COVID-19 with a focus on clinical and laboratory data, immune and inflammatory factors and concluded the advantages and possible risks of this procedure.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751819","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":"Corneal Epithelial Development and the Role of Induced Pluripotent Stem Cells for Regeneration.","authors":"Komathi Selvarajah, Jun Jie Tan, Bakiah Shaharuddin","doi":"10.2174/1574888X18666230313094121","DOIUrl":"10.2174/1574888X18666230313094121","url":null,"abstract":"<p><p>Severe corneal disorders due to infective aetiologies, trauma, chemical injuries, and chronic cicatricial inflammations, are among vision-threatening pathologies leading to permanent corneal scarring. The whole cornea or lamellar corneal transplantation is often used as a last resort to restore vision. However, limited autologous tissue sources and potential adverse post-allotransplantation sequalae urge the need for more robust and strategic alternatives. Contemporary management using cultivated corneal epithelial transplantation has paved the way for utilizing stem cells as a regenerative potential. Humaninduced pluripotent stem cells (hiPSCs) can generate ectodermal progenitors and potentially be used for ocular surface regeneration. This review summarizes the process of corneal morphogenesis and the signaling pathways underlying the development of corneal epithelium, which is key to translating the maturation and differentiation process of hiPSCs in vitro. The current state of knowledge and methodology for driving efficient corneal epithelial cell differentiation from pluripotent stem cells are highlighted.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9157838","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":"Revisiting Recent Tissue Engineering Technologies in Alveolar Cleft Reconstruction.","authors":"Faraz Sedaghat, Parham Mahamed, Ali Sharifi Sultani, Mobina Bagherian, Mohammad Biglari, Anisa Mohammadzadeh, Shabnam Ghasemzadeh, Ghasem Barati, Ehsan Saburi","doi":"10.2174/1574888X18666230717152556","DOIUrl":"10.2174/1574888X18666230717152556","url":null,"abstract":"<p><p>Tissue engineering and regenerative medicine have received significant attention in treating degenerative disorders and presented unique opportunities for researchers. The latest research on tissue engineering and regenerative medicine to reconstruct the alveolar cleft has been reviewed in this study. Three approaches have been used to reconstruct alveolar cleft: Studies that used only stem cells or biomaterials and studies that reconstructed alveolar defects by tissue engineering using a combination of stem cells and biomaterials. Stem cells, biomaterials, and tissue-engineered constructs have shown promising results in the reconstruction of alveolar defects. However, some contrary issues, including stem cell durability and scaffold stability, were also observed. It seems that more prospective and comprehensive studies should be conducted to fully clarify the exact dimensions of the stem cells and tissue engineering reconstruction method in the therapy of alveolar cleft.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9827176","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 Scaffold Materials in Periodontal and Tooth-supporting Tissue Regeneration: A Review.","authors":"Mahmood Jahangirnezhad, Sadaf Sadat Mahmoudinezhad, Melika Moradi, Kooshan Moradi, Ali Rohani, Lobat Tayebi","doi":"10.2174/1574888X18666221227142055","DOIUrl":"10.2174/1574888X18666221227142055","url":null,"abstract":"<p><strong>Background and objectives: </strong>Periodontium is an important tooth-supporting tissue composed of both hard (alveolar bone and cementum) and soft (gingival and periodontal ligament) sections. Due to the multi-tissue architecture of periodontium, reconstruction of each part can be influenced by others. This review focuses on the bone section of the periodontium and presents the materials used in tissue engineering scaffolds for its reconstruction.</p><p><strong>Materials and methods: </strong>The following databases (2015 to 2021) were electronically searched: ProQuest, EMBASE, SciFinder, MRS Online Proceedings Library, Medline, and Compendex. The search was limited to English-language publications and <i>in vivo</i> studies.</p><p><strong>Results: </strong>Eighty-three articles were found in primary searching. After applying the inclusion criteria, seventeen articles were incorporated into this study.</p><p><strong>Conclusion: </strong>In complex periodontal defects, various types of scaffolds, including multilayered ones, have been used for the functional reconstruction of different parts of periodontium. While there are some multilayered scaffolds designed to regenerate alveolar bone/periodontal ligament/cementum tissues of periodontium in a hierarchically organized construct, no scaffold could so far consider all four tissues involved in a complete periodontal defect. The progress and material considerations in the regeneration of the bony part of periodontium are presented in this work to help investigators develop tissue engineering scaffolds suitable for complete periodontal regeneration.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10440447","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":"Role of Extracellular Vesicles in Stem Cell Therapy.","authors":"Michael Kaiser, Luis Rodriguez-Menocal, Evangelos V Badiavas","doi":"10.2174/1574888X17666220630162836","DOIUrl":"10.2174/1574888X17666220630162836","url":null,"abstract":"<p><p>Burn wounds are a major source of morbidity and mortality in both the military and civilian settings. Research about the pathophysiology of thermal injury has revealed possible interventions that can aid this process to reduce scarring and wound contracture. Bone Marrow derived Mesenchymal Stem Cells (BM-MSCs) have been an exciting topic in research for many years. They have been shown to facilitate wound healing and tissue regeneration, two areas that are vital in the healing process, especially in burn wounds. More recently the discovery of Extracellular Vesicles (EVs) has allowed us to further characterize the immunomodulatory roles and understand the cellular pathways implicated in wound healing. The purpose of this review is to discuss the role of EVs in wound healing, and to propose that EVs are the main mechanism that deliver cellular materials to target cells to coordinate wound healing following tissue injury.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9236065","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":"Delayed Wound Healing in the Elderly and a New Therapeutic Target: CD271.","authors":"Hongqing Zhao, Sirui Fan, Jiachen Sun","doi":"10.2174/1574888X18666230403083603","DOIUrl":"10.2174/1574888X18666230403083603","url":null,"abstract":"<p><p>With the development of society, the global population is showing a trend of aging. It is well known that age is one of the factors affecting wound healing. Aging compromises the normal physiological process of wound healing, such as the change of skin structure, the decrease of growth factors, the deceleration of cell proliferation, and the weakening of migration ability, hence delaying wound healing. At present, research in adult stem cell-related technology and its derived regenerative medicine provides a novel idea for the treatment of senile wounds. Studies have confirmed that CD271 (P75 neurotropism receptor/P75NTR)-positive cells (CD271⁺ cells) are a kind of stem cells with a stronger ability of proliferation, differentiation, migration and secretion than CD271 negative (CD271^- cells). Meanwhile, the total amount and distribution of CD271 positive cells in different ages of skin are also different, which may be related to the delayed wound healing of aging skin. Therefore, this article reviews the relationship between CD271⁺ cells and senile wounds and discusses a new scheme for the treatment of senile wounds.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9254175","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":"Identification of Novel Stemness-based Subtypes and Construction of a Prognostic Risk Model for Patients with Lung Squamous Cell Carcinoma.","authors":"Fangfang Shen, Feng Li, Yong Ma, Xia Song, Wei Guo","doi":"10.2174/1574888X18666230714142835","DOIUrl":"10.2174/1574888X18666230714142835","url":null,"abstract":"<p><strong>Background: </strong>Although cancer stem cells (CSCs) contribute to tumorigenesis, progression, and drug resistance, stemness-based classification and prognostic signatures of lung squamous cell carcinoma (LUSC) remain unclarified. This study attempted to identify stemness-based subtypes and develop a prognostic risk model for LUSC.</p><p><strong>Methods: </strong>Based on RNA-seq data from The Cancer Genome Atlas (TCGA), Gene-Expression Omnibus (GEO) and Progenitor Cell Biology Consortium (PCBC), mRNA expression-based stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR) algorithm. A weighted gene coexpression network (WGCNA) was employed to identify stemness subtypes. Differences in mutation, clinical characteristics, immune cell infiltration, and antitumor therapy responses were determined. We constructed a prognostic risk model, followed by validations in GEO cohort, pan-cancer and immunotherapy datasets.</p><p><strong>Results: </strong>LUSC patients with subtype C2 had a better prognosis, manifested by higher mRNAsi, higher tumor protein 53 (TP53) and Titin (TTN) mutation frequencies, lower immune scores and decreased immune checkpoints. Patients with subtype C2 were more sensitive to Imatinib, Pyrimethamine, and Paclitaxel therapy, whereas those with subtype C1 were more sensitive to Sunitinib, Saracatinib, and Dasatinib. Moreover, we constructed stemness-based signatures using seven genes (BMI1, CCDC51, CTNS, EIF1AX, FAM43A, THBD, and TRIM68) and found high-risk patients had a poorer prognosis in the TCGA cohort. Similar results were found in the GEO cohort. We verified the good performance of risk scores in prognosis prediction and therapy responses.</p><p><strong>Conclusion: </strong>The stemness-based subtypes shed novel insights into the potential roles of LUSC-stemness in tumor heterogeneity, and our prognostic signatures offer a promising tool for prognosis prediction and guide therapeutic decisions in LUSC.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771236","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":"Human Mesenchymal Stem Cells Improve Angiogenesis and Bone Formation in Severed Finger Rats through SIRT1/Nrf2 Signaling.","authors":"Hao Wu, Weixue Sun, Gong Cheng, Mingdi Zheng, Yuchi Zhao, Zhilin Cao","doi":"10.2174/1574888X18666230512112735","DOIUrl":"10.2174/1574888X18666230512112735","url":null,"abstract":"<p><strong>Background: </strong>This study employed a severed finger rat model to analyze the effects of human mesenchymal stem cells (MSCs) on angiogenesis, inflammatory response, apoptosis, and oxidative stress, to evaluate the possible mechanism of the repair effect of MSCs on severed finger (SF) rats.</p><p><strong>Methods: </strong>Sixty Sprague-Dawley (SD) rats were categorized into five groups (n = 12). The pathological changes of severed finger tissues were investigated by Hematoxylin and eosin (H&E) staining on day 14 after the rats were sacrificed. The levels of inflammatory factors and oxidative stress factors were detected by ELISA. Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick End Labeling (TUNEL) was employed to assess the apoptosis of chondrocytes in severed finger tissues. The expression of osteocalcin (OCN), osteopontin (OPN), Collagen I (Col-1), and CD31 were detected by immunohistochemistry or immunofluorescence assay, respectively. The expression levels of related proteins were determined by western blot.</p><p><strong>Result: </strong>Our study presented evidence that MSCs treatment improved pathological changes of skin and bone tissue, diminished the inflammatory response, prevented oxidative stress injury, suppressed chondrocyte apoptosis, and promoted angiogenesis, and bone formation compared to the model group. In addition, EX527 treatment attenuated the effect of MSCs, SRT1720 and ML385 co-treatment also attenuated the effect of MSCs. Importantly, the MSCs treatment increased the expression of Sirtuin 1(SIRT1)/Nuclear factor erythroid2-related factor 2(Nrf2) relate proteins.</p><p><strong>Conclusion: </strong>Our study indicated that the mechanism of the effect of MSCs on a severed finger was related to the SIRT1/ Nrf2 signaling pathway.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9832923","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":"Comparison of Periodontal Ligament Stem Cells with Mesenchymal Stem Cells from Other Sources: A Scoping Systematic Review of <i>In vitro</i> and <i>In vivo</i> Studies.","authors":"Zeinab Kadkhoda, Parisa Motie, Maryam Rezaei Rad, Sadra Mohaghegh, Farnaz Kouhestani, Saeed Reza Motamedian","doi":"10.2174/1574888X17666220429123319","DOIUrl":"10.2174/1574888X17666220429123319","url":null,"abstract":"<p><strong>Objective: </strong>The application of stem cells in regenerative medicine depends on their biological properties. This scoping review aimed to compare the features of periodontal ligament stem cells (PDLSSCs) with stem cells derived from other sources.</p><p><strong>Design: </strong>An electronic search in PubMed/Medline, Embase, Scopus, Google Scholar and Science Direct was conducted to identify <i>in vitro</i> and <i>in vivo</i> studies limited to English language.</p><p><strong>Results: </strong>Overall, 65 articles were included. Most comparisons were made between bone marrow stem cells (BMSCs) and PDLSCs. BMSCs were found to have lower proliferation and higher osteogenesis potential <i>in vitro</i> and <i>in vivo</i> than PDLSCs; on the contrary, dental follicle stem cells and umbilical cord mesenchymal stem cells (UCMSCs) had a higher proliferative ability and lower osteogenesis than PDLSCs. Moreover, UCMSCs exhibited a higher apoptotic rate, hTERT expression, and relative telomerase length. The immunomodulatory function of adipose-derived stem cells and BMSCs was comparable to PDLSCs. Gingival mesenchymal stem cells showed less sensitivity to long-term culture. Both pure and mixed gingival cells had lower osteogenic ability compared to PDLSCs. Comparison of dental pulp stem cells (DPSCs) with PDLSCs regarding proliferation rate, osteo/adipogenesis, and immunomodulatory properties was contradictory; however, <i>in vivo</i> bone formation of DPSCs seemed to be lower than PDLSCs.</p><p><strong>Conclusion: </strong>In light of the performed comparative studies, PDLSCs showed comparable results to stem cells derived from other sources; however, further <i>in vivo </i>studies are needed to determine the actual pros and cons of stem cells in comparison to each other.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475306","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":"Photobiomodulation Effects on Periodontal Ligament Stem Cells: A Systematic Review of <i>In Vitro</i> Studies.","authors":"Valina Mylona, Eugenia Anagnostaki, Nasim Chiniforush, Hamidreza Barikani, Edward Lynch, Martin Grootveld","doi":"10.2174/1574888X17666220527090321","DOIUrl":"10.2174/1574888X17666220527090321","url":null,"abstract":"<p><strong>Background: </strong>Stem cell therapy has been considered to play a paramount role in the treatment modalities available for regenerative dentistry. The established beneficial effects of photobiomodulation (PBM) at the cellular level have led to the combined use of these two factors (PBM and stem cells). The main goal of this study was firstly to critically appraise the effects of PBM on periodontal ligament stem cells (PDLSCs), and secondly to explore the most effective PBM protocols applied.</p><p><strong>Methods: </strong>Pubmed, Cochrane, Scopus, Science Direct, and Google Scholar search engines were used to identify experimental <i>in vitro</i> studies in which PBM was applied to cultured PDLSCs. After applying specific keywords, additional filters, and inclusion/exclusion criteria, a preliminary number of 245 articles were narrowed down to 11 in which lasers and LEDs were used within the 630 - 1064 nm wavelength range. Selected articles were further assessed by three independent reviewers for strict compliance with PRISMA guidelines, and a modified Cochrane risk of bias to determine eligibility.</p><p><strong>Statistical analysis: </strong>The dataset analysed was extracted from the studies with sufficient and clearly presented PBM protocols. Simple univariate regression analysis was performed to explore the significance of contributions of potential quantitative predictor variables toward study outcomes, and a one-way ANOVA model was employed for testing differences between the laser or LED sources of the treatments. The significance level for testing was set at α = 0.05.</p><p><strong>Results: </strong>The proliferation rate, osteogenic differentiation, and expression of different indicative genes for osteogenesis and inflammation suppression were found to be positively affected by the application of various types of lasers and LEDs. With regard to the PBM protocol, only the wavelength variable appeared to affect the treatment outcome; indeed, the 940 nm wavelength parameter was found not to exert a favourable effect.</p><p><strong>Conclusions: </strong>Photobiomodulation can enhance the stemness and differentiation capacities of periodontal ligament stem cells. Therefore, for PBM protocols, there remains no consensus amongst the scientific community. Statistical analyses performed here indicated that the employment of a near-infrared (NIR) wavelength of 940 nm may not yield a significant favourable outcome, although those within the 630 - 830 nm range did so. Concerning the fluence, it should not exceed 8 J/cm² when therapy is applied by LED devices, and 4 J/cm² when applied by lasers, respectively.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44546519","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}