Cells最新文献

{"title":"Integrating Multi-Omics in Endometrial Cancer: From Molecular Insights to Clinical Applications.","authors":"Hye Kyeong Kim, Taejin Kim","doi":"10.3390/cells14171404","DOIUrl":"10.3390/cells14171404","url":null,"abstract":"<p><p>Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries, and its incidence is increasing globally. While early-stage ECs generally show good prognosis, advanced or recurrent cases and those with aggressive histologic subtypes exhibit poor outcomes. Traditional histopathologic classification, however, fails to reflect the molecular heterogeneity of EC, limiting its role in guiding treatment. Recent developments in multi-omics have enhanced our understanding of EC biology, which supports more personalized treatment strategies. The Cancer Genome Atlas (TCGA) classification has provided a more systematic molecular framework for stratifying risk and identifying prognostic and therapeutic biomarkers. This review discusses the latest developments in multi-omics-based classification of EC, highlights emerging diagnostic and therapeutic strategies, and summarizes ongoing clinical trials that aim to translate molecular discoveries into improved outcomes.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-451 Is a Driver of Lipotoxic Injury in Patients with Diabetic Cardiomyopathy.","authors":"Sarah Costantino, Shafeeq A Mohammed, Federico Ranocchi, Francesco Zito, Valentina Delfine, Nazha Hamdani, Maria Cristina Vinci, Giovanni Melina, Francesco Paneni","doi":"10.3390/cells14171401","DOIUrl":"10.3390/cells14171401","url":null,"abstract":"<p><p>MicroRNA 451 (miR-451) is emerging as a pivotal mediator of cardiac damage in experimental models of diabetic cardiomyopathy. Whether miR-451 plays a detrimental role in the human diabetic myocardium is unknown. The present study investigates miR-451's role in patients with type 2 diabetes (T2D). We show that miR-451 is upregulated in myocardial specimens from T2D patients compared to controls without diabetes and correlates with cardiometabolic parameters, the myocardial triglyceride content and cardiac expression of lipotoxic genes as well as echocardiographic indices of left ventricular dysfunction. Calcium-binding protein 39 (Cab39)-a known target of miR-451 in mouse hearts-was downregulated in T2D patients vs. controls, and its expression negatively correlated with that of miR-451. In cultured human cardiomyocytes (CMs), Ago2 immunoprecipitation confirmed Cab39 to be a direct target of miR-451. Treatment with a high amount of glucose (25mM) and palmitic acid (PA) mimicked miR-451 upregulation and Cab39 downregulation in human CMs. These changes were associated with increased TGs and markers of lipotoxic injury, such as elevated oxidative stress levels, mitochondrial dysfunction and apoptosis. Targeting miR-451 led to restoration of Cab39 levels while rescuing diabetes-induced lipotoxic injury and metabolic dysfunction. By contrast, miR-451 overexpression recapitulated features of lipotoxic damage. Our findings indicate miR-451 to be a potential target for the prevention of myocardial lipotoxic injury in diabetes.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the NO-sGC-cGMP Pathway: Mechanisms of Action of Vericiguat in Chronic Heart Failure.","authors":"Tine Bajec, Gregor Poglajen","doi":"10.3390/cells14171400","DOIUrl":"10.3390/cells14171400","url":null,"abstract":"<p><p>The recent advancements in the medical management of patients with chronic heart failure with reduced ejection fraction (HFrEF) is the soluble guanylate cyclase (sGC) stimulator, vericiguat. Clinical trials have demonstrated that vericiguat effectively lowers plasma levels of NT-proBNP and reduces the risk of cardiovascular death or hospitalization in HFrEF patients, making it a class IIb recommendation for patients with worsening heart failure despite receiving guideline-directed medical therapy. However, the precise pathophysiological mechanisms underlying these clinical benefits remain unexplored. This review aims to present the signalling pathways associated with maladaptive remodeling and heart failure progression that can be modulated by sGC stimulators, focusing on the antihypertrophic, antifibrotic, and anti-inflammatory effects of NO-sGC-cGMP signalling observed in preclinical studies. A better understanding of the mechanisms of action of sGC stimulators could optimize heart failure treatment strategies and enable tailoring of therapies to individual patient profiles.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autism Spectrum Disorder Induced Pluripotent Stem Cells Display Dysregulated Calcium Signaling During Neural Differentiation.","authors":"Abdullah J AlShawaf, Sarah A AlNassar, Norah AlGhamdi, Cristiana Mattei, Shiang Y Lim, Mirella Dottori, Futwan A Al-Mohanna","doi":"10.3390/cells14171402","DOIUrl":"10.3390/cells14171402","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects communication, social interaction, and behavior. Calcium (Ca²⁺) signaling dysregulation has been frequently highlighted in genetic studies as a contributing factor to aberrant developmental processes in ASD. Herein, we used ASD and control induced pluripotent stem cells (iPSCs) to investigate transcriptomic and functional Ca²⁺ dynamics at various stages of differentiation to cortical neurons. Idiopathic ASD and control iPSC lines underwent the dual SMAD inhibition differentiation protocol to direct their fate toward cortical neurons. Samples from multiple time points along the course of differentiation were processed for bulk RNA sequencing, spanning the following sequential stages: the iPSC stage, neural induction (NI) stage, neurosphere (NSP) stage, and differentiated cortical neuron (Diff) stage. Our transcriptomic analyses suggested that the numbers of Ca²⁺ signaling-relevant differentially expressed genes between ASD and control samples were higher in the iPSC and Diff stages. Accordingly, samples from the iPSC and Diff stages were processed for Ca²⁺ imaging studies. Results revealed that iPSC-stage ASD samples displayed elevated maximum Ca²⁺ levels in response to ATP compared to controls. By contrast, in the Diff stage, ASD neurons showed reduced maximum Ca²⁺ levels in response to ATP but increased maximum Ca²⁺ levels in response to KCl and DHPG relative to controls. Considering the distinct functional signaling contexts of these stimuli, this differential profile of receptor- and ionophore-mediated Ca²⁺ response suggests that aberrant calcium homeostasis underlies the pathophysiology of ASD neurons. Our data provides functional evidence for Ca²⁺ signaling dysregulation during neurogenesis in idiopathic ASD.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12428247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Inflammatory Responses of hiPSC-Derived Endothelial Cells and Cardiomyocytes to Cytokines Involved in Immune Checkpoint Inhibitor-Associated Myocarditis.","authors":"Samantha Conte, Isaure Firoaguer, Simon Lledo, Thi Thom Tran, Claire El Yazidi, Stéphanie Simoncini, Zohra Rebaoui, Claire Guiol, Christophe Chevillard, Régis Guieu, Denis Puthier, Franck Thuny, Jennifer Cautela, Nathalie Lalevée","doi":"10.3390/cells14171397","DOIUrl":"10.3390/cells14171397","url":null,"abstract":"<p><p>Inflammatory cytokines, particularly interferon-γ (IFN-γ), are markedly elevated in the peripheral blood of patients with immune checkpoint inhibitor-induced myocarditis (ICI-M). Endomyocardial biopsies from these patients also show GBP-associated inflammasome overexpression. While both factors are implicated in ICI-M pathophysiology, their interplay and cellular targets remain poorly characterized. Our aim was to elucidate how ICI-M-associated cytokines affect the viability and inflammatory responses of endothelial cells (ECs) and cardiomyocytes (CMs) using human induced pluripotent stem cell (hiPSC)-derived models. ECs and CMs were differentiated from the same hiPSC line derived from a healthy donor. Cells were exposed either to IFN-γ alone or to an inflammatory cytokine cocktail (CCL5, GZMB, IL-1β, IL-2, IL-6, IFN-γ, TNF-α). We assessed large-scale transcriptomic changes via microarray and evaluated inflammatory, apoptotic, and cell death pathways at cellular and molecular levels. hiPSC-ECs were highly sensitive to cytokine exposure, displaying significant mortality and marked transcriptomic changes in immunity- and inflammation-related pathways. In contrast, hiPSC-CM showed limited transcriptional changes and reduced susceptibility to cytokine-induced death. In both cell types, cytokine treatment upregulated key components of the inflammasome pathway, including regulators (GBP5, GBP6, P2X7, NLRC5), a core component (AIM2), and the effector GSDMD. Increased GBP5 expression and CASP-1 cleavage mirrored the findings found elsewhere in endomyocardial biopsies from ICI-M patients. This hiPSC-based model reveals a distinct cellular sensitivity to ICI-M-related inflammation, with endothelial cells showing heightened vulnerability. These results reposition endothelial dysfunction, rather than cardiomyocyte injury alone, as a central mechanism in ICI-induced myocarditis. Modulating endothelial inflammasome activation, particularly via AIM2 inhibition, could offer a novel strategy to mitigate cardiac toxicity while preserving antitumor efficacy.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12428595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-Associated Fibroblasts in Solid Tumors and Sarcomas: Heterogeneity, Function, and Therapeutic Implications.","authors":"Omar Badran, Idan Cohen, Gil Bar-Sela","doi":"10.3390/cells14171398","DOIUrl":"10.3390/cells14171398","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are crucial regulators of the tumor microenvironment (TME), promoting cancer progression, immune suppression, and therapy resistance. Single-cell transcriptomics has identified at least five distinct CAF subtypes: myofibroblastic (myCAFs), inflammatory (iCAFs), antigen-presenting (apCAFs), metabolic (meCAFs), and vascular/developmental (vCAFs/dCAFs), each with unique localization, signaling, and functions. While CAFs are well studied in epithelial cancers, their roles in sarcomas are less understood despite the shared mesenchymal origin of tumor and stromal cells. This overlap blurs the line between malignant and non-malignant fibroblasts, raising fundamental questions about the identity of CAFs in mesenchymal tumors. In this narrative review, we explore the heterogeneity and plasticity of CAFs across solid tumors, focusing on their role in immune evasion, epithelial-to-mesenchymal transition (EMT), and resistance to chemotherapy, targeted therapy, and immunotherapy. We highlight emerging evidence on CAF-like cells in sarcomas and their contribution to tumor invasion, immune exclusion, and metastatic niche formation. We also assess new strategies to target or reprogram CAFs and suggest that CAF profiling may serve as a potential biomarker for patient stratification. Understanding CAF biology across various tumor types, including those with dense stroma and immunologically cold sarcomas, is crucial for developing more effective, personalized cancer treatments.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunophenotypic Profile of Normal Hematopoietic Populations in Human Bone Marrow: Influence of Gender and Aging as a Basis for Reference Value Establishment.","authors":"Flavia Arandas de Sousa, Rodolfo Patussi Correa, Laiz Cameirão Bento, Luiz Fabiano Presente Taniguchi, Nydia Strachman Bacal, Luciana Cavalheiro Marti","doi":"10.3390/cells14171392","DOIUrl":"10.3390/cells14171392","url":null,"abstract":"<p><p>The purpose of this study was to evaluate normal values of healthy human bone marrow (<i>n</i> = 56) and identify gender- and age-related variations using cell lineage markers and maturational curves. Using 10-color quantitative flow cytometry, various cell types were identified, including B cells, T cells, NK cells, granulocytes, monocytes, erythroblasts, plasma cells, basophils, mast cells, and dendritic cells. Results revealed significant age-related declines in the absolute counts of nucleated cells (<i>p</i> = 0.001), including CD34+ immature B cells (<i>p</i> = 0.006) and CD34- immature B cells (<i>p</i> = 0.004). Declines were also observed for T cells (<i>p</i> = 0.002), cytotoxic T cells (<i>p</i> < 0.001), double-negative T cells (<i>p</i> = 0.0001), NK cells (<i>p</i> = 0.007), CD16- NK cells (<i>p</i> < 0.001), metamyelocytes (<i>p</i> = 0.002), neutrophils (<i>p</i> = 0.001), basophils (<i>p</i> = 0.009), promonocytes (<i>p</i> = 0.001), mature monocytes (<i>p</i> = 0.007), and plasmacytoid dendritic cells (<i>p</i> = 0.001). Gender differences showed males had more intermediate monocytes (<i>p</i> = 0.009) compared to females. In summary, this study provides normal values for hematopoietic cells, highlighting age- and gender-related disparities critical for understanding hematopoietic dynamics.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Macrophages into Human-Engineered Cardiac Tissue.","authors":"Yi Peng Zhao, Barry M Fine","doi":"10.3390/cells14171393","DOIUrl":"10.3390/cells14171393","url":null,"abstract":"<p><p>Heart disease remains a leading cause of morbidity and mortality worldwide, necessitating the development of in vivo models for therapeutic development. Advances in biomedical engineering in the past decade have led to the promising rise of human-based engineered cardiac tissues (hECTs) using novel scaffolds and pluripotent stem cell derivatives. This has led to a new frontier of human-based models for improved preclinical development. At the same time, there has been significant progress in elucidating the importance of the immune system and, in particular, macrophages, particularly during myocardial injury. This review summarizes new methods and findings for deriving macrophages from human pluripotent stem cells (hPSCs) and advances in integrating these cells into cardiac tissue. Key challenges include immune cell infiltration in 3D constructs, maintenance of tissue architecture, and modeling aged or diseased cardiac microenvironments. By integrating immune components, hECTs can serve as powerful tools to unravel the complexities of cardiac pathology and develop targeted therapeutic strategies.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Characterization of a Novel Lineage of Renal Progenitor Cells for Potential Use in Feline Chronic Kidney Disease: A Preliminary Study.","authors":"Lara Carolina Mario, Juliana de Paula Nhanharelli, Jéssica Borghesi, Rafaela Rodrigues Ribeiro, Hianka Jasmyne Costa de Carvalho, Thamires Santos da Silva, Mariano Del Sol, Rodrigo da Silva Nunes Barreto, Sandra Maria Barbalho, Maria Angelica Miglino","doi":"10.3390/cells14171395","DOIUrl":"10.3390/cells14171395","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a common and serious condition in felines. Accordingly, several cell therapies have been studied over the past decades for effective treatments. This study aimed to develop a new lineage of renal progenitor cells for use in cats with CKD. Metanephric and mesonephric progenitor cells were obtained from mesonephros and metanephros tissues of feline conceptuses at four distinct gestational stages. The cultured cells were characterized by their morphology, tumorigenic potential, immunophenotype determined by flow cytometry, and differentiation potential. We then conducted a pilot study in CKD-affected cats, comparing intraperitoneal injections of cultured metanephric progenitor cells (<i>n</i> = 4) to a placebo solution (<i>n</i> = 3). All four cell types exhibited adhesion and colony formation, but showed no tumorigenic potential. Cells tested positive for renal progenitor markers (CD117, Nephron, and WT1), confirming their identity. Treated cats showed no statistically significant differences (<i>p</i> ≤ 0.05) in any of the data analyzed. However, caregivers reported a voluntary increase in appetite after cell administration. Veterinarians confirmed this information during double-blind evaluations conducted after treatment. Although this data are qualitative, no clinical deterioration was observed in cats. Our results suggest that this new lineage of renal progenitor cells did not induce immediate adverse effects, thus supporting its potential for use in cell-based therapies. However, further studies are needed to evaluate its efficacy in treating renal diseases.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics of Patient-Derived Striatal Medium Spiny Neurons in Multiple System Atrophy.","authors":"Nadine J Smandzich, Andreas Pich, Thomas Gschwendtberger, Stephan Greten, Lan Ye, Martin Klietz, Alessio Di Fonzo, Lisa M Henkel, Florian Wegner","doi":"10.3390/cells14171394","DOIUrl":"10.3390/cells14171394","url":null,"abstract":"<p><p>The rare and rapidly progressive neurodegenerative disease multiple system atrophy (MSA) mainly affects the striatum and other subcortical brain regions. In this atypical Parkinsonian syndrome, the protein alpha-synuclein aggregates and misfolds in neurons as well as glial cells and is released in elevated amounts by hypoexcitable neurons. Mitochondrial dysregulation affects the biosynthesis of coenzyme Q10 and the activity of the respiratory chain, as shown in an induced pluripotent stem cell (iPSC) model. Proteome studies of cerebrospinal fluid and brain tissue from MSA patients yielded inconsistent results regarding possible protein changes due to small and combined groups of atypical Parkinsonian syndromes. In this study, we analysed the cellular proteome of MSA patient-derived striatal GABAergic medium spiny neurons. We observed 25 significantly upregulated and 16 significantly downregulated proteins in MSA cell lines compared to matched healthy controls. Various protein types involved in diverse molecular functions and cellular processes emphasise the multifaceted pathomechanisms of MSA. These data could contribute to the development of novel disease-modifying treatment strategies for MSA patients.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 17","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12428458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}