Wajd Y. Al-Asiri, Ebtesam S. Al-Sheddi, Nida N. Farshori, Mai M. Al-Oqail, Shaza M. Al-Massarani, Tabarak Malik, Javed Ahmad, Abdulaziz A. Al-Khedhairy, Maqsood A. Siddiqui
{"title":"Cytotoxic and Apoptotic Effects of Green Synthesized Silver Nanoparticles via Reactive Oxygen Species–Mediated Mitochondrial Pathway in Human Breast Cancer Cells","authors":"Wajd Y. Al-Asiri, Ebtesam S. Al-Sheddi, Nida N. Farshori, Mai M. Al-Oqail, Shaza M. Al-Massarani, Tabarak Malik, Javed Ahmad, Abdulaziz A. Al-Khedhairy, Maqsood A. Siddiqui","doi":"10.1002/cbf.4113","DOIUrl":"10.1002/cbf.4113","url":null,"abstract":"<div>\u0000 \u0000 <p>Due to their exceptional physicochemical features, green synthesized silver nanoparticles (AgNPs) have been of considerable interest in cancer treatment. In the present study, for the first time, we aimed to green synthesize AgNPs from <i>Euphorbia retusa</i> and explore their anticancer potential on human breast cancer (MCF-7) cells. First, the green synthesized AgNPs (EU-AgNPs) were well characterized by UV–visible spectroscopy, Fourier transmission infrared (FTIR) spectrum, XRD, scanning and transmission electron microscopy (SEM and TEM), and EDX techniques. The characterization data exhibited that EU-AgNPs were spherical in shape and crystalline in nature with an average size of 17.8 nm. FTIR results established the presence of active metabolites in EU-AgNPs. Second, the anticancer effect of EU-AgNPs was evaluated against MCF-7 cells by MTT and neutral red uptake (NRU) assays. Moreover, morphological changes, ROS production, MMP, and apoptotic marker genes were also studied upon exposure to cytotoxic doses of EU-AgNPs. Our results showed that EU-AgNPs induce cytotoxicity in a concentration-dependent manner, with an IC<sub>50</sub> value of 40 μg/mL. Morphological changes in MCF-7 cells exposed to EU-AgNPs also confirm their cytotoxic effects. Increased ROS and decreased MMP levels revealed that EU-AgNPs induced oxidative stress and mitochondrial membrane dysfunction. Moreover, ROS–mediated apoptosis was confirmed by elevated levels of proapoptotic marker genes (p53, Bax, caspase-3, and caspase-9) and reduced levels of an antiapoptotic gene (Bcl-2). Altogether, these findings suggested that EU-AgNPs could induce potential anticancer effects through ROS–mediated apoptosis in MCF-7 cells.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanlin Ding, Tingye Wang, Zhenyu Xu, Yuxuan Fu, Yanqing Liu, Li Tao
{"title":"A Novel 3-Benzyloxychromone From Celastrus orbiculatus Thunb. Exhibits Anticancer Effects on Non–Small Cell Lung Cancer Cells via GSK-3β–Dependent c-Jun/ATF2 Pathway","authors":"Yanlin Ding, Tingye Wang, Zhenyu Xu, Yuxuan Fu, Yanqing Liu, Li Tao","doi":"10.1002/cbf.4120","DOIUrl":"https://doi.org/10.1002/cbf.4120","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Celastrus orbiculatus</i> Thunb. is a vine used as a traditional Chinese medicinal herb. In this study, we focused on the anticancer cytotoxicity and underlying mechanism of previously unreported 3-oxygen–substituted isoflavone analogue (3-benzyloxychromone, 3-Boc) from the herb. Initially, we established cell line–derived xenograft mouse model using H1299 non–small cell lung cancer (NSCLC) cells and found that the ethanol crude extracts of the stem part of <i>C. orbiculatus</i> (200 mg/kg) could substantially suppress the growth of xenograft tumors in athymic nu/nu mice. We compared 3-Boc with three other flavonoid analogues isolated from the stem part of <i>C. orbiculatus.</i> Among these, 3-Boc showed the most potent cytotoxicity against H1299 and H1975 NSCLC cells. Colony formation, EdU incorporation and Annexin V-FITC/PI apoptosis assays demonstrated that 3-Boc induced growth inhibition primarily by inhibiting DNA replication and inducing apoptotic death of NSCLC cells. Structure-based target prediction and MD simulation suggested that 3-Boc potentially suppressed the activity of glycogen synthase kinase-3β (GSK-3β) by interacting with the ATP–binding site. Western blot analysis indicated that 3-Boc triggered the phosphorylation of Serine 21 of GSK-3α or Serine 9 of GSK-3β in a time- and dose-dependent manner. To investigate the dependency of GSK-3β, we established GSK-3β knockout in H1299 cells. Depletion of GSK-3β enhanced 3-Boc–induced cytotoxicity compared with wild-type counterparts through activated c-Jun/ATF2 signaling pathway. Altogether, our study highlights the anticancer potential of <i>C. orbiculatus</i> and the discovery of novel 3-oxygen–substituted chromone from the herb, which may have important implications for screening promising modulators of GSK-3β and related signaling pathways in the treatment of cancer.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acyl-CoA Synthetase Long-Chain Isoenzymes in Kidney Diseases: Mechanistic Insights and Therapeutic Implications","authors":"Swati Mishra, Vishwadeep Shelke, Anil Bhanudas Gaikwad","doi":"10.1002/cbf.4114","DOIUrl":"https://doi.org/10.1002/cbf.4114","url":null,"abstract":"<div>\u0000 \u0000 <p>Long-chain acyl-CoA synthetases (ACSLs) are pivotal enzymes in fatty acid metabolism, essential for maintaining cellular homeostasis and energy production. Recent research has uncovered their significant involvement in the pathophysiology of various kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), and renal cell carcinoma (RCC). While ACSL1, ACSL3, ACSL4, and ACSL5 have been extensively studied for their roles in processes such as ferroptosis, lipid peroxidation, renal fibrosis, epithelial-mesenchymal transition, and tumor progression, the role of ACSL6 in kidney diseases remain largely unexplored. Notably, these isoenzymes exhibit distinct functions in different kidney diseases. Therefore, to provide a comprehensive understanding of their involvement, this review highlights the molecular pathways influenced by ACSLs and their roles in modulating cell death, inflammation, and fibrosis during kidney disease progression. By examining these mechanisms in detail, this review underscores the potential of ACSLs as biomarkers and therapeutic targets, advocating for further research to elucidate the precise roles of individual ACSL isoenzymes in kidney disease progression. Understanding these mechanisms opens new avenues for developing targeted interventions and improving therapeutic outcomes for patients with kidney diseases.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Levilactobacillus brevis IBARAKI-TS3 Isolated From Pickles Promotes Production of Interleukin-10 via Toll-Like Receptor 2 in Human M2 Macrophages","authors":"Keisuke Tobita, Satoru Iwasa","doi":"10.1002/cbf.4110","DOIUrl":"https://doi.org/10.1002/cbf.4110","url":null,"abstract":"<div>\u0000 \u0000 <p>M2 macrophages play an important role in food allergy. Several studies have reported that lactic acid bacteria isolated from pickles exert antiallergic effects. We investigated the effects of several strains of lactic acid bacteria on the immune function of M2 macrophages. M2 macrophages differentiated from THP-1 cell line by interleukin-4 (IL-4) and IL-13 strongly expressed CD163, CD206, and HMOX1 mRNA. <i>Levilactobacillus brevis</i> IBARAKI-TS3 (IBARAKI-TS3) isolated from pickles was identified as a lactic acid bacterium that enhances the expressions of IL-10 and EBI3 mRNA in M2 macrophages. IBARAKI-TS3 induced the expression of genes involved in Toll-like receptor (TLR) signaling, such as IRAK, mitogen-activated protein kinases (MAPKs), and NF-κB mRNA. IBARAKI-TS3–induced IL-10 production was suppressed by anti-TLR2–neutralizing antibodies. Furthermore, the IBARAKI-TS3–induced increase in IL-10 levels was significantly reduced in TLR2–knockdown M2 macrophages compared to M2 macrophages. These results suggest that IBARAKI-TS3 promotes of IL-10 production via TLR2 in M2 macrophages.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The humoral immune landscape in Parkinson's disease: Unraveling antibody and B cell changes","authors":"Zahra Baridjavadi, Mahmoud Mahmoudi, Narges Abdollahi, Negar Ebadpour, Samaneh mollazadeh, Dariush Haghmorad, Seyed-Alireza Esmaeili","doi":"10.1002/cbf.4109","DOIUrl":"10.1002/cbf.4109","url":null,"abstract":"<p>Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) in the brain and progressive loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Although the role of neuroinflammation and cellular immunity in PD has been extensively studied, the involvement of humoral immunity mediated by antibodies and B cells has received less attention. This article provides a comprehensive review of the current understanding of humoral immunity in PD. Here, we discuss alterations in B cells in PD, including changes in their number and phenotype. Evidence mostly indicates a decrease in the quantity of B cells in PD, accompanied by a shift in the population from naïve to memory cells. Furthermore, the existence of autoantibodies that target several antigens in PD has been investigated (i.e., anti-α-syn autoantibodies, anti-glial-derived antigen antibodies, anti-Tau antibodies, antineuromelanin antibodies, and antibodies against the renin-angiotensin system). Several autoantibodies are generated in PD, which may either provide protection or have harmful effects on disease progression. Furthermore, we have reviewed studies focusing on the utilization of antibodies as a potential treatment for PD, both in animal and clinical trials. This review sheds light on the intricate interplay between antibodies and the pathological processes in PD, including complement system activation.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi-Fan Liu, Yuan Tian, Xiao-Fang Chen, Chi Zhang, Liang Huang
{"title":"Role of osteokines in atherosclerosis","authors":"Yi-Fan Liu, Yuan Tian, Xiao-Fang Chen, Chi Zhang, Liang Huang","doi":"10.1002/cbf.4107","DOIUrl":"10.1002/cbf.4107","url":null,"abstract":"<p>Despite their diverse physiologies and roles, the heart, skeletal muscles, and smooth muscles all derive from a common embryonic source as bones. Moreover, bone tissue, skeletal and smooth muscles, and the heart share conserved signaling pathways. The maintenance of skeletal health is precisely regulated by osteocytes, osteoblasts, and osteoclasts through coordinated secretion of bone-derived factors known as osteokines. Increasing evidence suggests the involvement of osteokines in regulating atherosclerotic vascular disease. Therefore, this review aims to examine the evidence for the role of osteokines in atherosclerosis development and progression comprehensively. Specifically discussed are extensively studied osteokines in atherosclerosis such as osteocalcin, osteopontin, osteoprotegerin, and fibroblast growth factor 23. Additionally, we highlighted the effects of exercise on modulating these key regulators derived from bone tissue metabolism. We believe that gaining an enhanced understanding of how osteocalcin contributes to the process of atherosclerosis will enable us to develop targeted and comprehensive therapeutic strategies against diseases associated with its progression.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myostatin's marvels: From muscle regulator to diverse implications in health and disease","authors":"Sonakshi Sharma, Amol S. Patil","doi":"10.1002/cbf.4106","DOIUrl":"10.1002/cbf.4106","url":null,"abstract":"<p>Myostatin, a member of the transforming growth factor-β superfamily, is a pivotal regulator of skeletal muscle growth in mammals. Its discovery has sparked significant interest due to its multifaceted roles in various physiological processes and its potential therapeutic implications. This review explores the diverse functions of myostatin in skeletal muscle development, maintenance and pathology. We delve into its regulatory mechanisms, including its interaction with other signalling pathways and its modulation by various factors such as microRNAs and mechanical loading. Furthermore, we discuss the therapeutic strategies aimed at targeting myostatin for the treatment of muscle-related disorders, including cachexia, muscular dystrophy and heart failure. Additionally, we examine the impact of myostatin deficiency on craniofacial morphology and bone development, shedding light on its broader implications beyond muscle biology. Through a comprehensive analysis of the literature, this review underscores the importance of further research into myostatin's intricate roles and therapeutic potential in human health and disease.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microfluidic device: A versatile biosensor platform to multiplex aptamer-based detection of malaria biomarkers","authors":"Adewoyin M. Ogunmolasuyi, Mary A. Adewoyin","doi":"10.1002/cbf.4104","DOIUrl":"10.1002/cbf.4104","url":null,"abstract":"<p><i>Plasmodium falciparum</i> malaria remains a dominant infectious disease that affects Africa than the rest of the world, considering its associated cases and death rates. It's a febrile illness that produces several reliable biomarkers, for example, <i>P. falciparum</i> lactate dehydrogenase (<i>Pf</i>LDH), <i>P. falciparum Plasmodium</i> glutamate dehydrogenase (PfGDH), and <i>P. falciparum</i> histidine-rich proteins (HRP-II) in blood circulatory system that can easily be employed as targets in rapid diagnostic tests (RDTs). In recent times, several DNA aptamers have been developed via SELEX technology to detect some specific malaria biomarkers (<i>Pf</i>LDH, <i>Pv</i>LDH, HRP-II, PfGDH) in a biosensor mode with good binding affinity properties to overcome the trend of cross-reactivity, limited sensitivity and stability problems that have been observed with immunodiagnostics. In this review, we summarized existing diagnostic methods and relevant biomarkers to suggest promising approaches to develop sensitive and species-specific multiplexed diagnostic devices enabling effective detection of malaria in complex biological matrices and surveillance in the endemic region.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anion exchanger1 (AE1/SLC4A1) function is impaired in red blood cells from prediabetic subjects: Potential benefits of finger lime (Citrus australasica, Faustrime cultivar) juice extract","authors":"Alessia Remigante, Sara Spinelli, Lucrezia Gambardella, Elisabetta Straface, Giovanna Cafeo, Marina Russo, Daniele Caruso, Paola Dugo, Silvia Dossena, Angela Marino, Rossana Morabito","doi":"10.1002/cbf.4105","DOIUrl":"10.1002/cbf.4105","url":null,"abstract":"<p>Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia-induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (<i>SLC4A1</i>), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (<i>Citrus australasica</i>, Faustrime cultivar) in counteracting oxidative stress-related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/β-spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.4105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The interaction between cannabinoids and long-term synaptic plasticity: A survey on memory formation and underlying mechanisms","authors":"Maryam Azarfarin, Tahereh Ghadiri, Masoomeh Dadkhah, Sajad Sahab-Negah","doi":"10.1002/cbf.4100","DOIUrl":"10.1002/cbf.4100","url":null,"abstract":"<p>Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is an essential phenomenon in memory formation as well as maintenance along with many other cognitive functions, such as those needed for coping with external stimuli. Synaptic plasticity consists of gradual changes in the biochemistry and morphology of pre- and postsynaptic neurons, particularly in the hippocampus. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory-related tasks. Evidence regarding the effects of cannabinoids on LTP and memory is contradictory. While cannabinoids can affect a variety of specific cannabinoid receptors (CBRs) and nonspecific receptors throughout the body and brain, they exert miscellaneous systemic and local cerebral effects. Given the increasing use of cannabis, mainly among the young population, plus its potential adverse long-term effects on learning and memory processes, it could be a future global health challenge. Indeed, the impact of cannabinoids on memory is multifactorial and depends on the dosage, timing, formula, and route of consumption, plus the background complex interaction of the endocannabinoids system with other cerebral networks. Herein, we review how exogenously administrated organic cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}