Molecular Biology Reports最新文献

{"title":"Protein subinteractomes of human microsomal cytochromes P450.","authors":"Pavel V Ershov, Evgeniy O Yablokov, Yuri V Mezentsev, Alexis S Ivanov","doi":"10.1007/s11033-025-10341-5","DOIUrl":"https://doi.org/10.1007/s11033-025-10341-5","url":null,"abstract":"<p><p>Microsomal cytochromes P450 (micCYPs) are monooxygenases located in the endoplasmic reticulum and other endomembranes of human cells. micCYPs receive electrons from specific redox partners and perform enzymatic transformations of drugs and different endogenous substrates. The large biodiversity of micCYPs leads to the idea that protein-protein interactions (PPIs) involving micCYPs are not limited to classical redox partners. This review aims to perform a systems biology analysis of the complete set of PPIs for all 33 micCYPs studied, as well as to examine the subinteractome of each micCYP. We have retrieved 287 PPIs from interactomic databases, involving 246 unique protein interactors that share a similar profile of subcellular localization with micCYPs. The number of protein interactors per micCYP unevenly varies from one to 47. Interactors of micCYPs are involved in cellular metabolism, signal transduction, cell-cell junctions, cytoskeleton organization, and intracellular or transmembrane transport. Notably, up to one-third of all interactors belong to the latter group, half of which consists of membrane transporters of compounds, metabolites, and ions (e.g., CACNA2D1, ORAI1, SCN3B, SLC7A2, SLC19A3, and SLC11A2). The CYP2C8 subinteractome is enriched with proteins involved in autophagy; CYP2S1- ERBB2 and EPH-Ephrin signaling; CYP3A4- glucuronidation. Proteins UBC, PGRMC1, and FANCG are the most frequent common interactors across various micCYPs. Nine and 12 interactors of micCYPs are involved in phosphorylation and ubiquitination, respectively; 20 interactors are 'moonlighting' proteins that are represented in the CYP3A4 subinteractome. Furthermore, micCYPs such as CYP2C9, 3A5, 2E1, 2A6, 4F2, and 4A11 may be involved in potentially binary interactions with other micCYPs. The functional implication of these CYP-CYP pairs is likely associated with modulation of their activity. Analysis of transcriptomic data revealed that some micCYP/interactor pairs exhibit tissue-, time-, and disease-specific gene expression patterns. Drugs that are metabolized by micCYPs in some cases can influence the expression of corresponding interactors at the gene or protein levels. These findings suggest that micCYPs may play roles in functions beyond their monooxygenase activity, as indicated by the spectrum of PPIs analyzed.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"226"},"PeriodicalIF":2.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Ca²⁺ overload caused by STIM1/ORAI1 activation of store-operated Ca²⁺ entry (SOCE) in hydrogen peroxide-induced mitochondrial damage and apoptosis in human primary melanocytes.","authors":"Ziyu Li, Yongkai Yu, Xuechen Cao, Yidan Wang, Jiawei Lu, Yifei Feng, Yali Jiang, Yan Lu","doi":"10.1007/s11033-025-10329-1","DOIUrl":"https://doi.org/10.1007/s11033-025-10329-1","url":null,"abstract":"<p><strong>Background: </strong>Vitiligo is a common depigmentation disorder. Oxidative stress in melanocytes is thought to be the primary cause of vitiligo. Imbalances in cellular calcium ion (Ca²⁺) levels may be associated with the onset and progression of various diseases through a process that has been linked to oxidative stress. The purpose of this study was to investigate the regulatory mechanism by which Ca²⁺ levels change in normal human melanocytes (NHMs) under oxidative stress, thereby providing new insights and potential clinical therapeutic targets for the pathogenesis and treatment of vitiligo.</p><p><strong>Methods and results: </strong>Single-cell RNA sequencing data from vitiligo patients were analyzed using bioinformatics techniques. NHMs were treated with hydrogen peroxide (H₂O₂), store-operated Ca²⁺ entry (SOCE) blocker BTP2, and SOCE agonist cyclopiazonic acid. Flow cytometry was used to detect Ca²⁺ levels, apoptosis rates, intra-mitochondrial reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) damage. The expression levels of target proteins were detected using immunofluorescence, quantitative real-time PCR, and western blotting. We found that H₂O₂-induced oxidative stress resulted in significantly increased intracellular Ca²⁺ levels, upregulation of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein (ORAI1), and mitochondrial dysfunction. Inhibition of SOCE and small interfering RNA-mediated silencing of STIM1/ORAI1 expression lowered mitochondrial levels of ROS and oxidative stress-induced intracellular Ca²⁺ overload and restored MMP, ultimately terminating oxidative stress-induced apoptosis.</p><p><strong>Conclusions: </strong>Oxidative stress upregulates STIM1/ORAI1 expression, leading to melanocyte apoptosis via increased Ca²⁺ influx, whereas inhibition of SOCE protects melanocytes against oxidative stress-induced damage.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"223"},"PeriodicalIF":2.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Edaravone reduces brain injury in hepatic encephalopathy by upregulation of Nrf2/HO-1 and inhibition of NF-κB, iNOS/NO and inflammatory cytokines.","authors":"Keyvan Amirshahrokhi, Mahsa Imani","doi":"10.1007/s11033-025-10343-3","DOIUrl":"https://doi.org/10.1007/s11033-025-10343-3","url":null,"abstract":"<p><strong>Background: </strong>Brain damage is the most important complication in patients with hepatic encephalopathy (HE). Oxidative stress and inflammation are essential factors in the progression of brain injury caused by HE. The aim of this study was to investigate the potential therapeutic effect of edaravone and its underlying mechanisms against brain injury associated with HE in mice.</p><p><strong>Methods and results: </strong>HE was induced by the injection of thioacetamide (200 mg/kg) for 2 days and then mice treated with edaravone (10 or 20 mg/kg/day, ip) for four consecutive days. The brain tissues were dissected for histopathological, biochemical, ELISA, RT-qPCR and immunofluorescence analysis. The results showed that edaravone improved the locomotor function and ameliorated brain histopathological changes in mice with HE. Edaravone inhibited oxidative stress markers by increasing the levels of glutathione, catalase, superoxide dismutase, glutathione reductase and the upregulation of nuclear erythroid 2-related factor (Nrf2)/HO-1 pathway in the brain tissue. Administration of edaravone significantly decreased the expression of p-NF-κB and iNOS. Edaravone treatment reduced the levels of NO, MPO and MMP-9 in the brain of mice. Additionally, the brain levels and expressions of inflammatory cytokines IL-1β, IL-6, TNF-α and IFN-γ were downregulated in mice treated with edaravone.</p><p><strong>Conclusions: </strong>These results suggest that edaravone exerts significant neuroprotection by modulating of inflammatory and oxidative responses in HE and may serve as a promising agent for the treatment of brain injury associated with HE.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"222"},"PeriodicalIF":2.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering bacteriophages for targeted superbug eradication.","authors":"Ghazal Ghaznavi, Parisa Vosough, Abdolmajid Ghasemian, Mohammad Mahdi Mokhtari Tabar, Lobat Tayebi, Saeed Taghizadeh, Amir Savardashtaki","doi":"10.1007/s11033-025-10332-6","DOIUrl":"https://doi.org/10.1007/s11033-025-10332-6","url":null,"abstract":"<p><p>The rise of antibiotic-resistant bacteria, termed \"superbugs,\" presents a formidable challenge to global health. These pathogens, often responsible for persistent nosocomial infections, threaten the effectiveness of conventional antibiotic therapies. This review delves into the potential of bacteriophages, viruses specifically targeting bacteria, as a powerful tool to combat superbugs. We examined the latest developments in genetic engineering that improve the efficacy of bacteriophages, focusing on modifications in host range, lysis mechanisms, and their ability to overcome bacterial defense systems. This review article highlights the CRISPR-Cas system as a promising method for precisely manipulating phage genomes, enabling the development of novel phage therapies with enhanced efficacy and specificity. Furthermore, we discussed developing novel phage-based strategies, such as phage cocktails and phage-antibiotic combinations. We also analyzed the challenges and ethical considerations associated with phage engineering, emphasizing the need for responsible and rigorous research to ensure this technology's safe and effective deployment to combat the growing threat of antibiotic resistance.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"221"},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Minimal residue disease detection in early-stage breast cancer: a review.","authors":"Yuan Zhang, Xiaoying Yuan","doi":"10.1007/s11033-025-10295-8","DOIUrl":"https://doi.org/10.1007/s11033-025-10295-8","url":null,"abstract":"","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"219"},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of SIGMAR1 hinders oral cancer cell growth via modulation of mitochondrial Ca²⁺ dynamics.","authors":"Pablo Shimaoka Chagas, Cristiana Bernadelli Garcia, Henrique Izumi Shimaoka Chagas, W Andrew Yeudall, Jack C Yu, Babak Baban, Andréia Machado Leopoldino","doi":"10.1007/s11033-025-10336-2","DOIUrl":"https://doi.org/10.1007/s11033-025-10336-2","url":null,"abstract":"<p><strong>Background: </strong>Oral cancer is the most common malignancy of the oral cavity and facial region, affecting the mucosal and epithelial surfaces in the mouth and lips. Unfortunately, OC is often associated with a high mortality rate and limited treatment options for patients.</p><p><strong>Methods and results: </strong>Herein, we used in silico analysis and in vitro assays to investigate the impact of the Sigma-1 receptor (SIGMAR1) in OC progression by evaluating mitochondrial function, calcium signaling and clonogenic growth. First, the data from the TCGA pan-cancer analysis revealed that SIGMAR1 was overexpressed in OC versus healthy tissue and related to a worse survival rate. Furthermore, we demonstrated that SIGMAR1 silencing led to an increase in mitochondrial membrane potential, a reduction in cellular ATP levels, inhibition of Ca²⁺ influx, and a significant decrease in the clonogenic growth of OC cells.</p><p><strong>Conclusions: </strong>Based on these findings, we suggest that SIGMAR1 may influence mitochondrial membrane potential and energy production by modulating Ca²⁺ uptake, which is critically important to cellular survival. In addition, SIGMAR1 knockdown may offer a potential strategy to be further explored as treatment for OC.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"220"},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel role of GRK2 in isoprenaline-induced activation of Na⁺/H⁺ exchanger 3 independent of β2-adrenergic receptor signaling.","authors":"Yongfa Dai, Hong Wen, Xiaomei Lai, Jing Huang, Jianling Li","doi":"10.1007/s11033-025-10326-4","DOIUrl":"https://doi.org/10.1007/s11033-025-10326-4","url":null,"abstract":"<p><strong>Background: </strong>The activation of Na⁺/H⁺ exchanger 3 (NHE3) by β2-adrenergic receptor (β2-AR) signaling is well-established. Our research indicates that isoprenaline (ISO) induces activation of NHE3 independent of β2AR signaling but through a different way that has not been elucidated before.</p><p><strong>Methods: </strong>The activation of NHE3 in HK-2 cell lines was quantified using the fluorescence probe BCECF/AM. The expression levels of G protein-coupled receptor kinase 2 (GRK2) and its downstream effector, β-arrestin 1 (ARRB1), were assessed through Western blot analysis and immunohistochemical staining. ISO-induced β2-AR signaling was blocked by ICI 118,551, a β2-AR antagonist, in HK-2 cells.</p><p><strong>Results: </strong>ISO treatment significantly enhanced NHE3 activity, which was reduced by 64.5% with a GRK2 inhibitor (GRK2-IN) and completely inhibited by propranolol (PRO), a non-selective β-adrenergic receptor blocker. Neither GRK2-IN nor PRO impacted NHE3 activity in the absence of ISO. Additionally, while GRK2 expression remained unchanged, ISO markedly decreased ARRB1 expression. This decrease was mitigated by 64.08% with GRK2-IN and entirely blocked by PRO. GRK2-IN and PRO alone did not significantly alter ARRB1 expression.</p><p><strong>Conclusion: </strong>Our study suggests that ISO triggers downstream GRK2/ARRB1 signaling to increase NHE3 activity independent of traditional β2AR signaling. Given the fundamental role of NHE3 in renal water-sodium reabsorption, these insights may contribute to new strategies for the prevention and treatment of hypertension.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"218"},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding gene expression profiles of Hippo signaling pathway components in breast cancer.","authors":"Hunayna M Bhavnagari, Franky D Shah","doi":"10.1007/s11033-025-10299-4","DOIUrl":"10.1007/s11033-025-10299-4","url":null,"abstract":"<p><strong>Introduction: </strong>The Hippo signaling pathway is an evolutionarily conserved, tumor suppressor, stem cell pathway. This is the very less explored pathway in Breast Cancer. It is a crucial regulator of several biological processes, such as organ size, differentiation, tissue homeostasis, cellular proliferation, and stemness. Interestingly, deregulation of this pathway leads to tumorigenesis. Hence, the present study aims to identify the role of the Hippo signaling pathway in Breast Cancer.</p><p><strong>Materials and methods: </strong>The mRNA expression of the Hippo signaling pathway molecules was evaluated in 120 pre-therapeutic patients by quantitative real-time PCR. Statistical analysis was carried out using SPSS 23. The association between the gene expression and clinicopathological parameters was analyzed by the paired sample t-test, and Pearson chi-square test. ROC curve analysis was carried out using Med Cal. A p-value of ≤ 0.05 was considered statistically significant.</p><p><strong>Results: </strong>The hippo signaling pathway contains 10 core components i.e.SAV1, MOB1A, MOB1B, MST1, MST2, LATS1, LATS2, YAP, TAZ, and TEAD1 which were downregulated in malignant tissues as compared to adjacent normal tissue in breast cancer. In the correlation of hippo signaling pathway molecules with clinico pathological parameters, only LATS1, MST1, and SAV1 were found to be significantly negatively associated with stages of Breast Cancer. MOB1B was found to be significantly positively correlated with stages of Breast Cancer. ROC curve analysis of YAP, TAZ, LATS2, and TEAD showed significant discrimination between adjacent normal and malignant tissue.</p><p><strong>Conclusion: </strong>In the current study, all the molecules of the hippo signaling pathway i.e. YAP, TAZ, LATS1, LATS2, MST1, MST2, SAV1, MOB1, MOB1B, TEAD1 were downregulated in BC suggesting the activation of hippo pathway which played a significant role in tumor suppression.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"216"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural drug delivery systems for the treatment of neurodegenerative diseases.","authors":"Greta Kaspute, Arunas Ramanavicius, Urte Prentice","doi":"10.1007/s11033-025-10286-9","DOIUrl":"10.1007/s11033-025-10286-9","url":null,"abstract":"<p><p>Today, herbal drugs are prominent in the pharmaceutical industry due to their well-known therapeutic and side effects. Plant-based compounds often face limitations such as poor solubility, low bioavailability, and instability in physiological environments, restricting their therapeutic efficacy and delivery. Nanotechnology-based solutions, including nanoparticle formulations and advanced delivery systems like liposomes and transfersomes, address these issues by enhancing solubility, stability, bioavailability, and targeted delivery, thereby optimizing the therapeutic potential of phytoactive compounds. Neuroinflammation can be a cause of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, or amyotrophic lateral sclerosis. Consequently, there is a need for the optimal delivery of a pharmacological anti-inflammatory agents to the CNS. Thus, the non-invasive administration of a stable compound at a therapeutic concentration is needed to assure molecule crossing through the blood-brain barrier. Natural resources have more structural diversity and novelty than synthetic compounds, e.g. plant-derived drug products have higher molecular weights, incorporate more oxygen atoms, and are more complex. As a result, plant-derived products have unique features which can be used to effectively modulate neuroinflammation. Therefore, this review aims to identify herbal molecules capable of targeting neuroinflammation and present novel strategies for their efficient delivery.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"217"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic intervention and exercise mitigate inflammation and histopathological alterations in the liver of wistar rats on a high-fat diet.","authors":"Mahsa Pekand, Mandana Gholami, Hossein Abednatanzi, Farshad Ghazalian","doi":"10.1007/s11033-025-10320-w","DOIUrl":"https://doi.org/10.1007/s11033-025-10320-w","url":null,"abstract":"<p><strong>Background: </strong>Controlling intestinal risk factors by consuming probiotics and modifying lifestyle with exercise modulates dietary damage. The aim of the present study was to investigate the effect of 6 weeks of aerobic exercise training and probiotic consumption on the expression of inflammatory genes and histopathological changes in the liver of rats with a high-fat diet model.</p><p><strong>Methods and results: </strong>In this study, 40 male Wistar rats were divided into 5 groups: healthy control, high-fat diet (HFD), HFD with exercise (HFD + Exe), HFD with probiotic consumption (HFD + Prob), and HFD + Exe + Prob. Animals in the HFD group were first exposed to a special diet and after confirming liver tissue damage, they entered the main protocol. Animals in the exercise group performed aerobic exercise on a rodent treadmill for 6 weeks, 5 days a week. Animals in the probiotic group also received Lactobacillus bifidus by oral gavage after exercise. Finally, intestinal and liver tissue were removed and examined for histological and cellular examination. Based on the results, HFD caused tissue damage and fat infiltration in both intestinal and liver tissue. Also, inflammatory factors (IL-6 and IL-1β genes) in the liver tissue of this group increased significantly compared to the control group (p < 0.05). In contrast, probiotic intervention and aerobic exercise caused a significant decrease in IL-6 and IL-1β genes compared to the HFD group (p < 0.05).</p><p><strong>Conclusion: </strong>The use of probiotic Lactobacillus bifidus along with exercise can neutralize inflammatory damage caused by a high-fat diet in liver tissue. However, further studies are needed in this field.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"215"},"PeriodicalIF":2.6,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}