Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry最新文献

{"title":"Synergistic Effect of Polyalthia longifolia Leaf and Antibiotics against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA) by Microscopic Technique.","authors":"Balasupramaniam Kirubakari,&nbsp;Yeng Chen,&nbsp;Sreenivasan Sasidharan","doi":"10.2174/1871523018666190522112902","DOIUrl":"https://doi.org/10.2174/1871523018666190522112902","url":null,"abstract":"<p><strong>Background: </strong>Polyalthia longifolia is a popular medicinal plant and has been widely used as a traditional remedy for centuries in curing of various ailments. The purpose of this study was conducted to determine the in situ antimicrobial synergistic effects between Polyalthia longifolia leaf ethyl acetate fraction (PLEAF) and ampicillin against MRSA local isolate by using modern microscopy technique.</p><p><strong>Methods: </strong>Hence, the evaluation of the synergistic activity of PLEAF and ampicillin against MRSA local isolate was conducted with scanning electron microscopy (SEM).</p><p><strong>Results: </strong>The combinational effect of PLEAF fraction and ampicillin exhibited significant antibacterial activity against MRSA. Bacterial cells observations showed invagination, impaired cell division, extensive wrinkles, cell shrinkage, the appearance of a rougher cell with fibrous matrix and clustered cells which confirmed the synergistic effect of PLEAF and ampicillin against MRSA local isolate by SEM.</p><p><strong>Conclusion: </strong>Conclusively, the in situ SEM observation proved the synergistic antimicrobial activity between PLEAF fraction and ampicillin to destroy the MRSA resistance bacteria which is an important aspect of PLEAF fraction to be used in the future combinational therapy.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37262056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Betulinic Acid-Azaprostanoid Hybrids: Synthesis and Pharmacological Evaluation as Anti-inflammatory Agents.","authors":"Tatyana S Khlebnicova,&nbsp;Yuri A Piven,&nbsp;Fedor A Lakhvich,&nbsp;Iryna V Sorokina,&nbsp;Tatiana S Frolova,&nbsp;Dmitry S Baev,&nbsp;Tatyana G Tolstikova","doi":"10.2174/1871523018666190426152049","DOIUrl":"https://doi.org/10.2174/1871523018666190426152049","url":null,"abstract":"<p><strong>Background: </strong>Prevention and treatment of chronic inflammatory diseases require effective and low-toxic medicines. Molecular hybridization is an effective strategy to enhance the biological activity of new compounds. Triterpenoid scaffolds are in the focus of attention owing to their anti-inflammatory, antiviral, antiproliferative, and immunomodulatory activities. Heteroprostanoids have different pleiotropic effects in acute and chronic inflammatory processes.</p><p><strong>Objective: </strong>The study aimed to develop structurally new and low toxic anti-inflammatory agents via hybridization of betulinic acid with azaprostanoic acids.</p><p><strong>Methods: </strong>A series of betulinic acid-azaprostanoid hybrids was synthesized. The synthetic pathway included the transformation of betulin via Jones' oxidation into betulonic acid, reductive amination of the latter and coupling obtained by 3β-amino-3-deoxybetulinic acid with the 7- or 13-azaprostanoic acids and their homo analogues. The hybrids 1-9 were investigated in vivo on histamine-, formalin- and concanavalin A-induced mouse paw edema models and two models of pain - the acetic acid-induced abdominal writhing and the hotplate test. The hybrids were in vitro evaluated for cytotoxic activity on cancer (MCF7, U- 87 MG) and non-cancer humane cell lines.</p><p><strong>Results: </strong>In the immunogenic inflammation model, the substances showed a pronounced anti-inflammatory effect, which was comparable to that of indomethacin. In the models of the exudative inflammation, none of the compounds displayed a statistically significant effect. The hybrids produced weak or moderate analgesic effects. All the agents revealed low cytotoxicity on human immortalized fibroblasts and cancer cell lines compared with 3β- amino-3-deoxybetulinic acid and doxorubicin.</p><p><strong>Conclusion: </strong>The results indicate that the principal anti-inflammatory effect of hybrids is substantially provided with the triterpenoid scaffold and in some cases with the azaprostanoid scaffold, but the latter makes a significant contribution to reducing the toxicity of hybrids. Hybrid 1 is of interest as a potent low toxic agent against immune-mediated inflammation.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871523018666190426152049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38440429","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 Trinity of Matrix Metalloproteinases, Inflammation, and Cancer: A Literature Review of Recent Updates.","authors":"Erva Ozkan,&nbsp;Filiz Bakar-Ates","doi":"10.2174/1871523018666191023141807","DOIUrl":"https://doi.org/10.2174/1871523018666191023141807","url":null,"abstract":"<p><p>The critical link between cancer and inflammation has been known for many years. This complex network was further complexed by revealing the association of the matrix metalloproteinase family members with inflammatory cytokines, which were previously known to be responsible for the development of metastasis. This article summarizes the current studies which evaluate the relationship between cancer and inflammatory microenvironment as well as the roles of MMPs on invasion and metastasis together.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871523018666191023141807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37742325","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":"Novel Coronavirus Disease and the Current Scenario of the Global Health Emergency.","authors":"Geetanjali Baruah,&nbsp;Jagajjit Sahu","doi":"10.2174/1871523019999200601145931","DOIUrl":"https://doi.org/10.2174/1871523019999200601145931","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871523019999200601145931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37993887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigation of Radiation-induced Pneumonitis and Lung Fibrosis using Alpha-lipoic Acid and Resveratrol.","authors":"Rasoul Azmoonfar,&nbsp;Peyman Amini,&nbsp;Rasoul Yahyapour,&nbsp;Abolhassan Rezaeyan,&nbsp;Alireza Tavassoli,&nbsp;Elahe Motevaseli,&nbsp;Ehsan Khodamoradi,&nbsp;Dheyauldeen Shabeeb,&nbsp;Ahmed E Musa,&nbsp;Masoud Najafi","doi":"10.2174/1871523018666190319144020","DOIUrl":"https://doi.org/10.2174/1871523018666190319144020","url":null,"abstract":"<p><strong>Background: </strong>Lung is a radiosensitive organ. Studies have shown that exposure of the lung to acute and high doses of radiation following inhalation of radioactive agents or an accidental radiological event may lead to pneumonitis and fibrosis, which are associated with a risk of death. So far, some agents have been studied for mitigation of pneumonitis and fibrosis following exposure of murine lung tissues to ionizing radiation. In this study, we aimed to detect the possible mitigatory effect of alpha-lipoic acid, resveratrol and their combination on mice pneumonitis and fibrosis markers following irradiation.</p><p><strong>Methods: </strong>25 mice were divided into 5 groups: control, radiation; radiation plus alpha-lipoic acid; radiation plus resveratrol; and radiation plus both resveratrol and alpha-lipoic acid. Mice chest regions were irradiated with 18 Gy using a cobalt-60 gamma rays source. Treatments started 24 h after irradiation and continued for two weeks. After 100 days, all mice were sacrificed and their lung tissues removed for histopathological evaluation.</p><p><strong>Results: </strong>Pathological study showed that exposure to radiation led to severe pneumonitis and moderate fibrosis after 100 days. Both resveratrol and alpha-lipoic acid, as well as their combination could mitigate pneumonitis and fibrosis markers. Although, resveratrol could not mitigate infiltration of most inflammatory cells as well as inflammation and vascular damage, alpha-lipoic acid and its combination were able to mitigate most damaged markers.</p><p><strong>Conclusion: </strong>Alpha-lipoic acid and its combination with resveratrol were able to mitigate fibrosis and pneumonitis markers in mice lung tissues following lung irradiation. Although resveratrol has a protective effect on some markers, it has a weaker effect on lung injury. In conclusion, our results suggest that the combination of resveratrol and alpha-lipoic acid has a potent mitigatory effect compared to the single forms of these agents.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871523018666190319144020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37072860","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":"Analgesic and Anti-inflammatory Effects of Caryocar brasiliense.","authors":"Armando Jorge Junior,&nbsp;Maicon Matos Leitão,&nbsp;Laura Priscila Toledo Bernal,&nbsp;Elisângela Dos Santos,&nbsp;Ângela Midori Kuraoka-Oliveira,&nbsp;Priscila Justi,&nbsp;Eliana Janet Sanjinez Argandoña,&nbsp;Cândida Aparecida Leite Kassuya","doi":"10.2174/1871523018666190408144320","DOIUrl":"https://doi.org/10.2174/1871523018666190408144320","url":null,"abstract":"<p><strong>Background: </strong>Caryocar brasiliense, popularly known as pequi, is widely distributed in the Amazon rainforest and Brazilian savannah. The fruit obtained from pequi is used in cooking and has folk use as an anti-inflammatory and for the treatment of respiratory disease. Until now, these two properties had not been scientifically demonstrated for Pequi oil in a carrageenan model.</p><p><strong>Objective: </strong>Our group determined the composition and safe use of Pequi oil from the Savannah of Campo Grande, and the anti-inflammatory and anti-nociceptive activities of this pequi oil were investigated in vivo models.</p><p><strong>Materials and methods: </strong>Doses of 300, 700, and 1000 mg/kg of Pequi oil were administered orally (p.o.) to Swiss male mice, and three parameters of inflammation (mechanical hyperalgesia, cold, hyperalgesia, and oedema) were analyzed in a carrageenan model to induce an inflammatory paw state.</p><p><strong>Results and discussion: </strong>The effects of Pequi oil were also carrageenan in pleurisy model, formalin, and acetic acid induced nociception. Oral administration of 1,000 mg/kg orally Pequi oil (p.o.) inhibited (*P<0.05), the migration of total leukocytes, but not alter plasma extravasation, in the pleurisy model when compared to control groups. The paw edema was inhibited with doses of 700 (P <0.05) and 1,000 mg (P<0.001) of pequi oil after 1, 2, and 4 hours after carrageenan. Pequi oil (1,000 mg/kg) also blocked the mechanical hyperalgesy and reduced cold allodynia induced by carrageenan in paw (P <0.05). Pequi oil treatment (1,000 mg/kg) almost blocked (P < 0.001) all parameters of nociception observed in formalin and acid acetic test.</p><p><strong>Conclusion: </strong>This is the first time that the analgesic and anti-inflammatory effects of Pequi oil have been shown.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871523018666190408144320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37132458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis and Pharmacological Evaluation of Gastro- Protective Anti-inflammatory Analgesic Agents based on Dual Oxidative Stress / Cyclooxygenase Inhibition.","authors":"Monika Gaba,&nbsp;Sarbjot Singh,&nbsp;Chander Mohan,&nbsp;Richa Dhingra,&nbsp;Monika Chauhan,&nbsp;Priyanka Rana,&nbsp;Neelima Dhingra","doi":"10.2174/1871523018666190325155244","DOIUrl":"https://doi.org/10.2174/1871523018666190325155244","url":null,"abstract":"<p><strong>Background: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) derived local generation of reactive oxygen species (ROS) plays a crucial role in the formation of gastric ulceration.</p><p><strong>Objective: </strong>Therefore, anti-inflammatory analgesics with potent antioxidant activity could be a potential therapeutic strategy for the treatment of pain and inflammatory disorders without gastrointestinal (GI) side effects.</p><p><strong>Methods: </strong>In an effort to develop gastroprotective analgesic and anti-inflammatory agents, a series of 2-methylamino-substituted-1H-benzo[d] imidazol-1-yl) (phenyl) methanone derivatives were synthesized and evaluated in vitro for cyclooxygenase (COX) inhibition as well as anti-oxidant potential by the FRAP assay. The compounds with significant in vitro COX-1/COX-2 inhibitory activity and antioxidant activity were further screened in vivo for their anti-inflammatory and analgesic activities. Moreover, the ulcerogenic potential of test compounds was also studied. To gain insight into the plausible mode of interaction of compounds within the active sites of COX-1 and COX-2, molecular docking simulations were performed.</p><p><strong>Results: </strong>Among the various synthesized molecules, most of the compounds showed good cyclooxygenase inhibitory activity and efficient antioxidant activity in FRAP assay. After preliminary and indicative in vitro assays, three compounds exhibited most significant antiinflammatory and analgesic activity with better gastric tolerability during their in vivo evaluation. Ligand interaction studies indicated highest dock score -43.05 of 1,2- disubstituted benzimidazole derivatives in comparison to the reference ligand -30.70. Overall studies provided us (2-((4-methoxyphenylamino) methyl) -1h-benzo [d] imidazol- 1-yl) (phenyl) methanone as a lead with potent gastro-protective anti-inflammatory and analgesic activities that can be used for future research.</p><p><strong>Conclusion: </strong>From the above results, it can be concluded that designing of multifunctional molecules with COX-1/COX-2 inhibitory and anti-oxidant activities could hold a great promise for further development of GI-safer NSAIDs.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871523018666190325155244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37268186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Chitosan, Pectin Based Mesalamine Colon Targeted Drug Delivery Systems on TNBS-induced IBD Model Rats.","authors":"Amaldoss M J Newton,&nbsp;Prabakaran Lakshmanan","doi":"10.2174/1871523018666190118112230","DOIUrl":"https://doi.org/10.2174/1871523018666190118112230","url":null,"abstract":"<p><strong>Objective: </strong>A number of natural polymer-based drug delivery systems targeting the colon are reported for different applications. Most of the research is based on the class of natural polymers such as polysaccharides. This study compares the anti-inflammatory effect of different polysaccharide based tablets on IBD when a drug carrier is targeted to the colon as matrix and coated systems.</p><p><strong>Methods: </strong>The TNBS induced IBD Wistar rats were used as a model for the study. The microscopic and macroscopic parameters were studied in detail. Almost all the important IBD parameters were reported in this work.</p><p><strong>Results: </strong>The results demonstrated that the polysaccharides are efficient in carrying the drugs to the colon. Reduction in the level of ulcer index (UI), Myeloperoxidase (MPO), and Malondialdehyde MDA, confirmed the inhibitory activity on the development of Reactive oxygen species (ROS). The increased level of Tumor necrosis factor (TNFα) an expression of colonic inducible nitric oxide synthase (iNOS) was lowered in treatments as compared to TNBS control.</p><p><strong>Conclusion: </strong>The different polymer-based mesalamine (DPBM) confirmed the efficient anti- inflammatory activity on IBD induced rats. The increased level of glutathione (GSH), and superoxide dismutase (SOD) also confirmed the effective anti-inflammatory effect. A significant decrease in the ulcer score and ulcer area was reported. The investigation revealed that chitosan is superior to pectin in IBD treatment likewise polysaccharide-based matrix systems are superior to the coated system.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36919580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory Effect of <i>Woodfordia fructicosa</i> Leaves Ethanolic Extract on Adjuvant and Carragenan Treated Rats.","authors":"Hem Raj,&nbsp;Avneet Gupta,&nbsp;Neeraj Upmanyu","doi":"10.2174/1871523018666190222120127","DOIUrl":"https://doi.org/10.2174/1871523018666190222120127","url":null,"abstract":"<p><strong>Background: </strong>Woodfordia fructicosa is used traditionally for the treatment of inflammation associated with arthritis.</p><p><strong>Methods: </strong>In the present study, the anti-inflammatory activity of W. fructicosa (WFE) leaves ethanolic extract was assessed in Sprague Dawley rats by giving 200 mg/kg dose orally. Inflammation was studied by using carrageenan induced paw edema, Freund's adjuvant (FA) and monosodium iodo acetate (MIA) induced arthritis as animal models. Serum tumor necrosis factor-alpha (TNF-α) was estimated in blood sample of animals treated with FA. The one way ANOVA followed by Bonferroni's test was used for statistical analysis.</p><p><strong>Results: </strong>WFE significantly decreased (P<0.05, P<0.001) paw thickness in carrageenan induced paw edema and FA induced arthritis. The significant decrease in knee diameter (P<0.001) in MIA induced arthritis as well as inhibitory effect (P<0.001) on elevated TNF- α was observed.</p><p><strong>Conclusion: </strong>These results showed that the WFEexerted an inhibitory effect on TNF-α and carrageenan paw edema which may justify its traditional use in inflammatory conditions. Thus, the study shows that leaves of W. fruticose afford anti-inflammatory activity by preventing the inflammation in different animal models.</p>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/0f/AIAAMC-19-103.PMC7475893.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37169557","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":"Are there any Therapeutic Options Currently Available for Wuhan Coronavirus?","authors":"Simone Carradori","doi":"10.2174/1871523019999200228100917","DOIUrl":"https://doi.org/10.2174/1871523019999200228100917","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":35423,"journal":{"name":"Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871523019999200228100917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37771868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}