Current molecular medicine最新文献

{"title":"Role of Nrf2 in Epilepsy Treatment.","authors":"Maryam Azadmanesh, Tahereh Farkhondeh, Mohammad Sadra Harifi-Mood, Michael Aschner, Fariborz Samini, Saeed Samarghandian","doi":"10.2174/0115665240305987240918103602","DOIUrl":"https://doi.org/10.2174/0115665240305987240918103602","url":null,"abstract":"<p><p>Oxidative stress is a consequence of the disruption of the balance between the generation of reactive nitrogen and oxygen species and the biological system's ability to neutralize those reactive products. Oxidative stress is involved in the generation of many disorders, including epilepsy, which is a prevalent chronic neurological disease that affects the lives of millions of people around the world. Epilepsy is characterized by unforeseeable and repeated seizures that can be very disturbing. Studies have reported that oxidative stress occurs before and after seizures. A transcription factor named Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) controls genes related to the induction of oxidative stress and defends cells against oxidative stress. The Nrf2 protein has seven different domains, ranging from Neh1 to Neh7. Each domain is responsible for a distinctive function of this protein. Keap1 binds to Nrf2, but during oxidative stress, Nrf2 detaches from the Keap1 protein, moves to the nucleus, and binds to DNA. The result of this translocation and binding is the initiation of transcription of detoxifying genes to control the harmful effects of oxidative stress. There is some evidence of oxidative stress involvement in epilepsy. In this review, we have listed potential Nrf2-related therapeutic targets for treating and controlling epilepsy, such as Berberis alkaloids, pentoxifylline, lovastatin, progesterone, and chrysin nanoparticles. These activators were tested in animals (in vivo) and cells (in vitro), and most of these experiments showed promising results in different epilepsy models. Finally, the results have suggested that the activation of Nrf2 can be an option for controlling epilepsy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343292","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":"Exploring the Neuroprotective Potential of Icariin through Modulation of Neural Pathways in the Treatment of Neurological Diseases.","authors":"Sarthak Sharma, Sidharth Mehan, Zuber Khan, Aarti Tiwari, Aakash Kumar, Ghanshyam Das Gupta, Acharan S Narula, Reni Kalfin","doi":"10.2174/0115665240317650240924041923","DOIUrl":"https://doi.org/10.2174/0115665240317650240924041923","url":null,"abstract":"<p><p>Neuropathological diseases involve the death of neurons and the aggregation of proteins with altered properties in the brain. Proteins are used at the molecular level to categorize neurodegenerative disorders, emphasizing the importance of protein-processing mechanisms in their development. Natural herbal phytoconstituents, such as icariin, have addressed these neurological complications. Icariin, the principal compound in Epimedium, has been studied for its antineuroinflammatory, anti-oxidative, and antiapoptotic properties. Recent scientific investigations have shown that icariin exhibits promising therapeutic and preventive properties for mental and neurodegenerative disorders. In preclinical, icariin has been shown to inhibit amyloid development and reduce the expression of APP and BACE-1. Previous preclinical studies have demonstrated that icariin can regulate proinflammatory responses in neurological conditions like Parkinson's disease, depression, cerebral ischemia, ALS, and multiple sclerosis. Studies have shown that icariin possesses neuroprotective properties by modulating signaling pathways and crossing the blood-brain barrier, suggesting its potential to address various neurocomplications. This review aims to establish a foundation for future clinical investigations by examining the existing literature on icariin and exploring its potential therapeutic implications in treating neurodegenerative disorders and neuropsychiatric conditions. Future research may address numerous concerns and yield captivating findings with far-reaching implications for various aspects of icariin.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343290","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":"Multiplex PCR System for the Diagnosis of Plague.","authors":"Wenfang Wang, Xiaoxue Zhang, Hui Yu, Zhanli Wang","doi":"10.2174/0115665240321812240918095931","DOIUrl":"https://doi.org/10.2174/0115665240321812240918095931","url":null,"abstract":"<p><p>The plague caused by Yersinia pestis has a high case fatality rate. It is often transmitted from person to person through mosquito bites, causing serious disease transmission. Due to its clinical symptoms being very similar to influenza, it is difficult to detect by people. Traditional detection methods for Y. pestis mainly include bacterial culture and serological identification, which are cumbersome and require high experimental conditions. Therefore, a fast and effective detection method is very important. At present, polymerase chain reaction (PCR) is one of the methods for rapid detection of Y. pestis. In this review, we focus on the application, advantages, and disadvantages of multiplex PCR technology in clinical detection.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343291","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":"Stem Cells as a Novel Source for Regenerative Medicinal Applications in Alzheimer's Disease: An Update.","authors":"Kratika Pandey, Priyanka Khare, Swaroop Kumar Pandey, Surabhi Johari, Priyanka Bhatnagar, Madhavi Sonane, Anuja Mishra","doi":"10.2174/0115665240334785240913071442","DOIUrl":"https://doi.org/10.2174/0115665240334785240913071442","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by loss of the neurons, excessive accumulation of misfolded Aβ and Tau proteins, and degeneration of neural synapses, primarily occurring in the neocortex and the hippocampus regions of the brain. AD Progression is marked by cognitive deterioration, memory decline, disorientation, and loss of problem-solving skills, as well as language. Due to limited comprehension of the factors contributing to AD and its severity due to neuronal loss, even today, the medications approved by the U.S. Food and Drug Administration (FDA) are not precisely efficient and curative. Stem cells possess great potential in aiding AD due to their self-renewal, proliferation, and differentiation properties. Stem cell therapy can aid by replacing the lost neurons, enhancing neurogenesis, and providing an enriched environment to the pre-existing neural cells. Stem cell therapy has provided us with promising results in regard to the animal AD models, and even pre-clinical studies have shown rather positive results. Cell replacement therapies are potential curative means to treat AD, and there are a number of undergoing human clinical trials to make Stem Cell therapy accessible for AD patients. In this review, we aim to discuss the AD pathophysiology and varied stem cell types and their application.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343293","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":"Fascin Inhibitor NP-G2-044 Decreases Cell Metastasis and Increases Overall Survival of Mice-Bearing Lung Cancers.","authors":"Zhi-Hua Zhang, Xin-Yan Liu, Jun-Peng Feng, Li-Fang Li, Xing-Bing Li, Su-Min Guo, Li-Hua Liu, Shu-Cai Wu","doi":"10.2174/0115665240314325240911063427","DOIUrl":"https://doi.org/10.2174/0115665240314325240911063427","url":null,"abstract":"<p><strong>Aim: </strong>Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model.</p><p><strong>Methods: </strong>The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice.</p><p><strong>Results: </strong>Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/β-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor.</p><p><strong>Conclusion: </strong>Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/β- catenin pathway.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307333","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":"COL12A1 Promotes Osteosarcoma Progression via the FAK/PI3K/AKT/mTOR Pathway.","authors":"Yun-Pu Zhang, Hai-Xia Wang, Zhi-Chao Gao, Li-Zhe Xu, Yu Fu","doi":"10.2174/0115665240322280240903111159","DOIUrl":"https://doi.org/10.2174/0115665240322280240903111159","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is a common malignancy among adolescents and children, characterized by a high propensity for metastasis and resistance to chemotherapy.</p><p><strong>Aims: </strong>This study aimed to investigate the role of COL12A1, a gene often overexpressed in various cancers and associated with poor prognosis, in the progression of OS and explore the underlying mechanisms.</p><p><strong>Methods: </strong>The expression pattern and potential function of COL12A1 in OS were evaluated using bioinformatics analyses, clinical sample examination, and OS cell lines. Various assays, including transwell, CCK-8, flow cytometry, and wound healing, were performed to assess the impact of COL12A1 on OS cell growth, cell cycle progression, apoptosis, invasion, and migration. Western blot analysis was conducted to investigate markers associated with the FAK/PI3K/AKT/mTOR pathway.</p><p><strong>Results: </strong>COL12A1 expression was significantly elevated in OS tissues and cells. Upregulation of COL12A1 promoted cell growth, accelerated cell cycle progression, and enhanced migration and invasion while inhibiting apoptosis. Conversely, the knockdown of COL12A1 had the opposite effect. Additionally, COL12A1 overexpression increased the phosphorylation of components in the FAK/PI3K/AKT/mTOR pathway. The FAK inhibitor Y15 mitigated the effects of COL12A1 overexpression on cell apoptosis, invasion, proliferation, and the FAK/PI3K/AKT/mTOR pathway in OS.</p><p><strong>Conclusion: </strong>Our findings indicated that COL12A1 enhanced OS development by activating the FAK/PI3K/AKT/mTOR pathway, suggesting that COL12A1 could serve as a valuable biomarker for the prediction and identification of OS patients.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281627","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":"Extracorporeal Shock Wave and Melatonin Alleviate Joint Capsule Fibrosis after Knee Trauma in Rats by Regulating Autophagy.","authors":"Jing Mao, Jin Niu Zhang, Quan Bing Zhang, De Ting Zhu, Xue Ming Li, Han Xiao, Xiu Li Kan, Run Zhang, Yun Zhou","doi":"10.2174/0115665240339436240909100847","DOIUrl":"https://doi.org/10.2174/0115665240339436240909100847","url":null,"abstract":"<p><strong>Background: </strong>Joint contracture is a common clinical problem affecting joint function. Capsule fibrosis plays a pivotal role in the progression of Joint contracture. Previous studies have reported that autophagy plays a regulatory role in visceral fibrosis.</p><p><strong>Objective: </strong>This study aimed to investigate whether extracorporeal shock wave therapy (ESWT) and melatonin alleviate joint capsule fibrosis in rats with extended knee joint contracture by regulating autophagy.</p><p><strong>Methods: </strong>A rat knee joint extension contracture model was made. Then, the rats were treated with ESWT, melatonin, ESWT + melatonin, or ESWT + melatonin + mTOR agonist for 4 weeks. The range of motion (ROM) of the knee joints was measured. Joint capsules were collected and observed for pathological changes by H&E and Masson staining. LC3B protein expression was evaluated by immunofluorescence staining. TGF-β1, MMP-1, Col-Ⅰ, Col-Ⅲ, LC3, ATG7, Beclin1, p-AMPK, p-mTOR and p-ULK1 protein expressions were measured by Western blot assay.</p><p><strong>Results: </strong>The intervention groups had significantly improved ROM of knee joint (P < 0.05), significantly improved pathological changes on HE and Masson staining, significantly decreased protein expressions of TGF-β1, MMP-1, Col-Ⅰ, Col-Ⅲ and pmTOR (P < 0.05), and significantly increased protein expressions of LC3B, LC3II/LC3I ratio, ATG7, Beclin1, p-AMPK, and p-ULK1 (P < 0.05). Among these groups, the effects demonstrated by the ESWT + melatonin group were the best. With the mTOR agonist supplement, the therapeutic effects of extracorporeal shock waves and melatonin were significantly reduced.</p><p><strong>Conclusion: </strong>ESWT plus melatonin alleviated knee joint capsule fibrosis in rats by regulating autophagy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281628","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":"The AMPK/cAMP Metabolic Signaling Axis as a Possible Therapeutic Target for Diabetes","authors":"José Augusto Nogueira-Machado, Nathália Augusta Gomes, Fabiana Rocha-Silva","doi":"10.2174/0115665240298668240528110159","DOIUrl":"https://doi.org/10.2174/0115665240298668240528110159","url":null,"abstract":"&lt;p&gt;Diabetes is a complex disease, despite the availability of numerous treatments, its progression and complications can only be mitigated and managed to a certain extent. After the onset, diabetes cannot be reversed. Its global expansion makes it challenging for governments to control the considerable costs of treating people with diabetes. Many studies have been carried out by widely recognized pharmaceutical companies that are considering the development of new drugs for diabetic treatments. Diets, sedentary habits, and lifestyles that are currently prevalent have an enormous influence on the global spread of diabetes. The tools available to clinicians for therapy do not solve the problem. It is known that a patient, when diagnosed, would already have had diabetes for more than three years. Studies on diabetes signaling consider the effects of hyperglycemia but also highlight the roles of insulin receptor activation and resistance. &lt;/p&gt;&lt;p&gt; Understanding the intricate signaling network and its interactions with hyperglycemiainduced pathways is crucial. In this context, the cyclic AMP/AMPK axis emerges as a promising therapeutic target for diabetes. However, there is a noticeable lack of literature exploring the metabolic network induced by hyperglycemia and its interconnected pathways. Therefore, investigating the cyclic cAMP/AMPK axis could provide valuable insights, given its complex connections with various metabolic pathways. This mini-review aims to delve into the metabolic signaling of the AMPK/cAMP axis in the context of diabetes, highlighting its metabolic interactions and potential implications.&lt;/p&gt;","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195372","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":"Targeting the Molecules in EMT: A Potential Therapeutic Opportunity in Breast Cancer.","authors":"Siri Chandana Gampa, Sireesha Garimella","doi":"10.2174/0115665240310780240805114133","DOIUrl":"https://doi.org/10.2174/0115665240310780240805114133","url":null,"abstract":"<p><p>Breast Cancer (BC) is one of the most frequently occurring diseases in women, accounting for 90% of cancer-related deaths in women. Tumor cells can invade nearby tissues and spread to distant organs by metastasis. The epithelialmesenchymal transition or EMT, which involves a number of transcription factors and signaling pathways, is a mechanism by which cells of the epithelium change into mesenchymal type capable of motility, invasion, and metastasis. EMT has grown to be a more intriguing target for developing cutting-edge treatment approaches since it is involved in diverse malignant transformation-related activities. Besides preventing tumor cell invasion and spread and the development of metastatic lesions, anti-EMT treatment methods also lessen cancer stemness and improve the efficacy of more traditional chemotherapeutics. EMT is, therefore, a desirable target in oncology. This review gives an overview of EMT, various markers of EMT, and different inhibitors used in therapies targeting EMT in BC.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003825","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":"Caffeic Acid Reduces Ferroptosis to Dampen Inflammation of Keratinocytes in Psoriasis by Inhibiting EGR1-induced Transcription Activation of CHAC1.","authors":"Yadi Li, Xiaoqian Zhou, Zhusheng Yang, Lichao Zhang, Xiumin Yang, Aihua Wei","doi":"10.2174/0115665240296144240419063309","DOIUrl":"https://doi.org/10.2174/0115665240296144240419063309","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis of keratinocytes is closely associated with amplification of skin inflammation in psoriasis. This study focuses on unlocking the role of caffeic acid (CA), a polyphenol compound, in keratinocyte ferroptosis and understanding the underlying mechanistic basis.</p><p><strong>Methods: </strong>The interaction between early growth response protein 1 (EGR1) and chac glutathione specific γ‑glutamylcyclotransferase 1 (CHAC1) was predicted by bioinformatics and validated via chromatin immunoprecipitation and dual-luciferase reported assays. Their expressions in primary human epidermal keratinocytes were altered by transfection of EGR1/CHAC1 overexpression or knockdown plasmids, and then keratinocytes were followed by CA treatment and Erastin (ferroptosis inducer). Keratinocyte viability was determined by CCK-8 assay, and the ferroptotic effect was evaluated using colorimetric assay and flow cytometry. Proinflammatory cytokine secretion by keratinocytes was detected via ELISA. Expressions of EGR1 and CHAC1 in keratinocytes were analyzed by qRT-PCR or Western blot.</p><p><strong>Results: </strong>Increased expressions of EGR1 and CHAC1 were detected in keratinocytes with Erastin treatment. CA (100 μM) antagonized Erastin (10 μM)-induced decrease in viability, increases in EGR1 and CHAC1 expressions, upregulation of MDA, ROS, and Fe2+, downregulation of GSH and SOD, and secretion of proinflammatory cytokines from keratinocytes. EGR1 overexpression potentiated Erastin-induced effects. Moreover, EGR1 overexpression and CA mutually counteracted their effects on Erastin-induced keratinocytes. EGR1 transcriptionally activated and positively regulated CHAC1. The above Erastin-induced effects were neutralized by EGR1 knockdown but potentiated by CHAC1 overexpression. Moreover, EGR1 knockdown and CHAC1 overexpression reversed each other's effects.</p><p><strong>Conclusion: </strong>CA reduces ferroptosis by inhibiting EGR1-induced activation of CHAC1 to dampen inflammation of keratinocytes in psoriasis. This study providing new compounds and candidate targets for the clinical treatment of psoriasis.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916302","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}