Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Medical management of chronic pouch inflammation","authors":"Maia Kayal, Marla C. Dubinsky","doi":"10.1016/j.crphar.2022.100095","DOIUrl":"10.1016/j.crphar.2022.100095","url":null,"abstract":"","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000153/pdfft?md5=f1eacd36b010cbf839d0e193ca6a39a8&pid=1-s2.0-S2590257122000153-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41652691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galantamine tethered hydrogel as a novel therapeutic target for streptozotocin-induced Alzheimer's disease in Wistar rats","authors":"Manickam Rajkumar ,&nbsp;Murugesan Sakthivel ,&nbsp;Kottaisamy Senthilkumar ,&nbsp;Ramasundaram Thangaraj ,&nbsp;Soundarapandian Kannan","doi":"10.1016/j.crphar.2022.100100","DOIUrl":"10.1016/j.crphar.2022.100100","url":null,"abstract":"<div><p>Amyloid-β (Aβ) plaque formation, neuronal cell death, and cognitive impairment are the unique symptoms of Alzheimer's disease (AD). No single step remedy is available to treat AD, so the present study aimed to improve the drugability and minimize the abnormal behavioral and biochemical activities in streptozotocin (STZ) induced AD experimental Wistar rats. In particular, we explored the utilization of methacrylated gelatin (GelMA), which is a biopolymeric hydrogel that mimics the natural tissue environment. The synthesized biopolymeric gel contained the drug galantamine (Gal). Investigations were conducted to evaluate the behavioral activities of STZ-induced AD experimental rats under STZ ​+ ​GelMA ​+ ​Gal treatment. The experimental groups comprised the control and STZ, STZ ​+ ​GelMA, STZ ​+ ​Gal, and STZ ​+ ​GelMA ​+ ​Gal (10 ​mg/kg) treated rats. Intracerebroventricular STZ ensures cognitive decline in terms of an increase in the escape latency period, with a decrease in the spontaneous alteration of behavioral activities. Our results indicated decrease Aβ aggregation in the hydrogel-based drug treatment group and significant decreases in the levels of acetylcholinesterase and lipid peroxidation (<em>p</em> ​&lt; ​0.001). In addition, the glutathione and superoxide dismutase activities appeared to be improved in the STZ ​+ ​GelMA ​+ ​Gal group compared with the other treatment groups. Furthermore, histopathological and immunohistochemical experiments showed that the GelMA ​+ ​Gal treated AD rats exhibited significantly improved behavioral and biochemical activities compared with the STZ treated AD rats. Therefore, STZ ​+ ​GelMA ​+ ​Gal administration from the pre-plaque stage may have a potential clinical application in the prevention of AD. Thus, we conclude that hydrogel-based Gal drugs are efficient at decreasing Aβ aggregation and improving the neuroinflammatory process, antioxidant activity, and neuronal growth.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000207/pdfft?md5=df1ec666f8a8dc260e899bccd6ff055a&pid=1-s2.0-S2590257122000207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45652675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indole: A promising scaffold for the discovery and development of potential anti-tubercular agents","authors":"Nilesh Gajanan Bajad ,&nbsp;Sudhir Kumar Singh ,&nbsp;Sushil Kumar Singh ,&nbsp;Tryambak Deo Singh ,&nbsp;Meenakshi Singh","doi":"10.1016/j.crphar.2022.100119","DOIUrl":"10.1016/j.crphar.2022.100119","url":null,"abstract":"<div><p>Indole-containing small molecules have been reported to have diverse pharmacological activities. The aromatic heterocyclic scaffold, which resembles various protein structures, has received attention from organic and medicinal chemists. Exploration of indole derivatives in drug discovery has rapidly yielded a vast array of biologically active compounds with broad therapeutic potential. Nature is the major source of indole scaffolds, but various classical and advanced synthesis methods for indoles have also been reported. One-pot synthesis is widely considered an efficient approach in synthetic organic chemistry and has been used to synthesize some indole compounds. The rapid emergence of drug-resistant tuberculosis is a major challenge to be addressed. Identifying novel targets and drug candidates for tuberculosis is therefore crucial. Researchers have extensively explored indole derivatives as potential anti-tubercular agents or drugs. Indole scaffolds containing the novel non-covalent (decaprenylphosphoryl-β-D-ribose2′-epimerase) DprE1 inhibitor 1,4-azaindole is currently in clinical trials to treat <em>Mycobacterium tuberculosis</em>. In addition, DG167 indazole sulfonamide with potent anti-tubercular activity is undergoing early-stage development in preclinical studies. Indole bearing cationic amphiphiles with high chemical diversity have been reported to depolarize and disrupt the mycobacterial membrane. Some indole-based compounds have potential inhibitory activities against distinct anti-tubercular targets, including the inhibition of cell wall synthesis, replication, transcription, and translation, as summarized in the graphical abstract. The success of computer-aided drug design in the fields of cancer and anti-viral drugs has accelerated <em>in silico</em> studies in antibacterial drug development. This review describes the sources of indole scaffolds, the potential for novel indole derivatives to serve as anti-tubercular agents, <em>in silico</em> findings, and proposed actions to facilitate the design of novel compounds with anti-tubercular activity.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100119"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/c3/main.PMC9389259.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inonotus obliquus aqueous extract prevents histopathological alterations in liver induced by environmental toxicant Microcystin","authors":"Pir Mohammad Ishfaq ,&nbsp;Shivani Mishra ,&nbsp;Anjali Mishra ,&nbsp;Zaved Ahmad ,&nbsp;Shovanlal Gayen ,&nbsp;Subodh Kumar Jain ,&nbsp;Swati Tripathi ,&nbsp;Siddhartha Kumar Mishra","doi":"10.1016/j.crphar.2022.100118","DOIUrl":"10.1016/j.crphar.2022.100118","url":null,"abstract":"<div><p>Environmental toxicants like microcystins are known to adversely impact liver physiology and lead to the increased risk for abnormal liver function and even liver carcinoma. Chaga mushroom (<em>Inonotus obliquus</em>) is reported for various properties mainly antibacterial, antiallergic, anti-inflammatory, antioxidant, and anticancer properties. This study was aimed to assess the effect microcystin (MC-LR) on histopathology of liver in mice and a preventive measure by using aqueous extract of <em>Inonotus obliquus</em> (IOAE). Adult Balb/c mice were administered with MC-LR at 20 ​μg/kg body weight, per day, intraperitoneal (i.p.) for 4 weeks. IOAE was treated to one group of MC-LR mice at 200 ​mg/kg body weight, per oral, for 4 weeks. Histological staining for liver structural details and biochemical assays for functions were assessed. The results of the study showed that MC-LR drastically reduced the body weight of mice which were restored close to the range of control by IOAE treatment. MC-LR exposed mice showed 1.9, 1.7 and 2.2-fold increase in the levels of SGOT, SGPT and LDH which were restored by IOAE treatment as compared to control (one-fold). MC-LR exposed mice showed reduced level of GSH (19.83 ​± ​3.3 ​μM) which were regained by IOAE treatment (50.83 ​± ​3.0 ​μM). Similar observations were noted for catalase activity. Histological examinations show that MC-LR exposed degenerative changes in the liver sections which were restored by IOAE supplementation. The immunofluorescence analysis of caspase-3 counterstained with DAPI showed that MC-LR led to the increased expression of caspase-3 which were comparatively reduced by IOAE treatment. The cell viability decreased on increasing the concentration of MC-LR with 5% cell viability at concentration of 10 ​μg MC-LR/mL as that of control 100% Cell viability. The IC₅₀ was calculated to be 3.6 ​μg/ml, indicating that MC-LR is chronic toxic to AML12 mouse hepatocytes. The molecular docking interaction of NF-κB-NIK with ergosterol peroxidase showed binding interaction between the two and showed the plausible molecular basis for the effects of IOAE in MC-LR induced liver injury. Collectively, this study revealed the deleterious effects of MC-LR on liver through generation of oxidative stress and activation of caspase-3, which were prevented by treatment with IOAE.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c7/6c/main.PMC9389225.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The future of inhalation therapy in chronic obstructive pulmonary disease","authors":"Mario Cazzola ,&nbsp;Josuel Ora ,&nbsp;Luigino Calzetta ,&nbsp;Paola Rogliani ,&nbsp;Maria Gabriella Matera","doi":"10.1016/j.crphar.2022.100092","DOIUrl":"10.1016/j.crphar.2022.100092","url":null,"abstract":"<div><p>The inhaled route is critical for the administration of drugs to treat patients suffering from COPD, but there is still an unmet need for new and innovative inhalers to address some limitations of existing products that do not make them suitable for many COPD patients. The treatment of COPD, currently limited to the use of bronchodilators, corticosteroids, and antibiotics, requires a significant expansion of the therapeutic armamentarium that is closely linked to the widening of knowledge on the pathogenesis and evolution of COPD. The great interest in the development of new drugs that may be able to interfere in the natural history of the disease is leading to the synthesis of numerous new molecules, of which however only a few have entered the stages of clinical development. On the other hand, further improvement of inhaled drug delivery could be an interesting possibility because it targets the organ of interest directly, requires significantly less drug to exert the pharmacological effect and, by lowering the amount of drug needed, reduces the cost of therapy. Unfortunately, however, the development of new inhaled drugs for use in COPD is currently too slow.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000128/pdfft?md5=714138333bf52b7adc079b29050b2c77&pid=1-s2.0-S2590257122000128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48716939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose melittin is safe for intravitreal administration and ameliorates inflammation in an experimental model of uveitis","authors":"Brenda Fernanda Moreira Castro ,&nbsp;Carolina Nunes da Silva ,&nbsp;Lídia Pereira Barbosa Cordeiro ,&nbsp;Sarah Pereira de Freitas Cenachi ,&nbsp;Daniel Vitor Vasconcelos-Santos ,&nbsp;Renes Resende Machado ,&nbsp;Luiz Guilherme Dias Heneine ,&nbsp;Luciana Maria Silva ,&nbsp;Armando Silva-Cunha ,&nbsp;Silvia Ligório Fialho","doi":"10.1016/j.crphar.2022.100107","DOIUrl":"10.1016/j.crphar.2022.100107","url":null,"abstract":"<div><p>Uveitis is a group of sight-threatening ocular inflammatory disorders, whose mainstay of therapy is associated with severe adverse events, prompting the investigation of alternative treatments. The peptide melittin (MEL) is the major component of <em>Apis mellifera</em> bee venom and presents anti-inflammatory and antiangiogenic activities, with possible application in ophthalmology. This work aims to investigate the potential of intravitreal MEL in the treatment of ocular diseases involving inflammatory processes, especially uveitis. Safety of MEL was assessed in retinal cells, chick embryo chorioallantoic membranes, and rats. MEL at concentrations safe for intravitreal administration showed an antiangiogenic activity in the chorioallantoic membrane model comparable to bevacizumab, used as positive control. A protective anti-inflammatory effect in retinal cells stimulated with lipopolysaccharide (LPS) was also observed, without toxic effects. Finally, rats with bacille Calmette-Guerin- <strong>(</strong>BCG) induced uveitis treated with intravitreal MEL showed attenuated disease progression and improvement of clinical, morphological, and functional parameters, in addition to decreased levels of proinflammatory mediators in the posterior segment of the eye. These effects were comparable to the response observed with corticosteroid treatment. Therefore, MEL presents adequate safety profile for intraocular administration and has therapeutic potential as an anti-inflammatory and antiangiogenic agent for ocular diseases.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259025712200027X/pdfft?md5=f643e5c5dfb49192bcdbf7ff51f5b383&pid=1-s2.0-S259025712200027X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49449982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial/introduction to special issue","authors":"Joana Torres,&nbsp;Ryan C. Ungaro","doi":"10.1016/j.crphar.2022.100125","DOIUrl":"10.1016/j.crphar.2022.100125","url":null,"abstract":"","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100125"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/9c/main.PMC9780059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies for drug repurposing against coronavirus targets","authors":"Poppy O. Smith,&nbsp;Peiqin Jin,&nbsp;Khondaker Miraz Rahman","doi":"10.1016/j.crphar.2021.100072","DOIUrl":"10.1016/j.crphar.2021.100072","url":null,"abstract":"<div><p>Repurposing regulatory agency approved drugs and investigational compounds with known safety profiles can significantly fast track the drug development timeline over <em>de novo</em> drug discovery, with lower investment requirements and improved attrition rate. These advantages are vital in any epidemic or pandemic situation, where hospital beds are occupied by patients for whom there is no known treatment. Here we examine drug repurposing in the context of human coronaviruses, SARS-CoV, MERS-CoV, and, in particular, SARS-CoV-2, the virus currently causing a continued widespread pandemic with substantial impacts on public health and economy. The key druggable targets explored were those involved in viral entry, viral replication, and viral-induced ARDS, as well as viral proteases, with a focus on the strategy by which the drugs were repurposed.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39833603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative differential cytotoxicity of clinically used SERMs in human cancer lines of different origin and its predictive molecular docking studies of key target genes involved in cancer progression and treatment responses","authors":"Lakshmi S ,&nbsp;Shanitha A ,&nbsp;Shiny Dv ,&nbsp;Rahul Bs ,&nbsp;Saikant R ,&nbsp;Shehna Sharaf ,&nbsp;Abi Sa ,&nbsp;Rajmohan G","doi":"10.1016/j.crphar.2021.100080","DOIUrl":"10.1016/j.crphar.2021.100080","url":null,"abstract":"<div><p>SERMS like Tamoxifene, 5-hydroxy tamoxifene, raloxifene and endoxifene has been used for the treatment of hormonal imbalances and dependent cancers owing to their action via Estrogen receptors as in the treatment of estrogen sensitive breast cancers. Due to the adverse side effects, modifications and development of the existing or newer SERMS has always been of immense interest. Ormeloxifene, a SERM molecule manufactured by HLL Lifecare Ltd, India as birth control under the trade names Saheli, Novex, and Novex-DS which is also investigated against mastalgia, fibro-adenoma and abnormal uterine bleeding. Anti-cancer effects have been reported in estrogen dependent and independent cancers which shows its wide scope to be implemented in cancer therapy. Current investigation is a comprehensive effort to find the cytotoxic potential of Ormeloxifene in comparison with clinically used four SERMS in twenty six cancer cell lines of different origin using Adriamycin as positive control. Also the computational studies pertaining to selected target/ligand with respect to tumor progression, development, treatment responses and apoptosis. The studies proved effective cytotoxicity of Ormeloxifene on cancer cell lines with lower TGI, GI50 and LC₅₀ values which are significantly comparable. Also the <em>in silico</em> studies proved that the docking score of the compound suggests the interaction of the compound which could tightly regulate key target genes controlling cancer like ER, EGFR kinase, EGFR-cSRC, HDAC-2, PARP-1 and BRAF. This study brings out the superior efficacy of Ormeloxifene compared to other SERMS with proven safety profile to be repositioned as an anti-cancer drug to treat diverse cancer types.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39934515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of synergism in drug combinations and reference models for future orientations in oncology","authors":"Diana Duarte ,&nbsp;Nuno Vale","doi":"10.1016/j.crphar.2022.100110","DOIUrl":"10.1016/j.crphar.2022.100110","url":null,"abstract":"<div><p>Current cancer therapy includes a variety of strategies that can comprise only one type of treatment or a combination of multiple treatments. Chemotherapy is still the gold standard for cancer therapy, though sometimes associated with undesired side effects and the development of drug resistance. For this reason, drug combination is an approach that has been proposed to overcome the problems related to monotherapy and several studies have already demonstrated the superiority of combined therapies compared to monotherapy. The main goal when designing and evaluating drug combinations is to achieve synergistic effects by demonstrating that the combined effects are greatly superior to the expected from the additive effects of the single drugs, allowing for dosage reduction and therefore decreasing toxicity. Nevertheless, synergism quantification is not a simple task due to the different definitions of additivity and over the years several reference models have been proposed based on different assumptions and with different mathematical frameworks. In this review, we begin to cover the available treatment options for cancer therapy, with emphasis on the importance of drug combinations in cancer therapy. We next describe the classical reference models that have been proposed for synergism evaluation, usually classified as effect-based and dose-effect based methods, with a brief analysis of the current limitations of these models. We also describe here the novel methods for the accurate quantification of drug interactions in combined treatments. At the end of this manuscript, we covered some of the most recent preclinical and clinical combination studies that reflect the importance of the appropriate, accurate and precise application of the concepts and methodologies here described for the evaluation of synergism.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259025712200030X/pdfft?md5=93da5dfe339f8268a344b44c2ba420dc&pid=1-s2.0-S259025712200030X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42990267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}