Current molecular pharmacology最新文献

{"title":"The Neuropharmacological Effects of Magnolol and Honokiol: A Review of Signal Pathways and Molecular Mechanisms.","authors":"Xiaolin Dai,&nbsp;Long Xie,&nbsp;Kai Liu,&nbsp;Youdan Liang,&nbsp;Yi Cao,&nbsp;Jing Lu,&nbsp;Xian Wang,&nbsp;Xumin Zhang,&nbsp;Xiaofang Li","doi":"10.2174/1874467215666220223141101","DOIUrl":"https://doi.org/10.2174/1874467215666220223141101","url":null,"abstract":"<p><p>Magnolol and honokiol are natural lignans with good physiological effects. As the main active substances derived from Magnolia officinalis, their pharmacological activities have attracted extensive attention. It is reported that both of them can cross the blood-brain barrier (BBB) and exert neuroprotective effects through a variety of mechanisms. This suggests that these two ingredients can be used as effective therapeutic compounds to treat a wide range of neurological diseases. This article provides a review of the mechanisms involved in the therapeutic effects of magnolol and honokiol in combating diseases, such as cerebral ischemia, neuroinflammation, Alzheimer's disease, and brain tumors, as well as psychiatric disorders, such as anxiety and depression. Although magnolol and honokiol have the pharmacological effects described above, their clinical potential remains untapped. More research is needed to improve the bioavailability of magnolol and honokiol and perform experiments to examine the therapeutic potential of magnolol and honokiol.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9509367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review.","authors":"Baljinder Singh, Charan Singh","doi":"10.2174/1874467215666220421130707","DOIUrl":"10.2174/1874467215666220421130707","url":null,"abstract":"<p><p>Mycobacterium tuberculosis causes a contagious pulmonary disease with a high mortality rate in developing countries. However, the recommendation of DOTS (approved by WHO) was effective in treating tuberculosis, but nowadays, resistance from the first line (MDR-TB) and the second line (XDR-TB) drugs is highly common. Whereas, the resistance is a result of factors like poor patient constancy due to the long duration of therapy and co-infection with HIV. The approval of bedaquiline under an accelerated program for the treatment of MDR-TB has revealed its effectiveness in clinical trials as a therapeutic novel molecule. BDQ selectively inhibits the ATP synthase of bacterium and reduces ATP production. Additionally, the poor pharmacokinetic properties raised provocations in the MDR therapy, but the use of targeted drug delivery can solve the hurdles. While the preclinical and clinical studies included in this review are strongly suggesting the usefulness of BDQ in MDR-TB and XDR-TB, the repurposing of different drug classes in resistant TB is opening new opportunities to manage the disease conditions. In this review, we have summarized the examples of pipeline drugs and repurposed molecules with preclinical formulation developments.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9144189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of Beta 1 and Arachidonic Acid Metabolizing Enzymes in the Mouse Hearts and Kidneys after Sub Chronic Administration of Rofecoxib.","authors":"Noor Askar,&nbsp;Yazun Jarrar,&nbsp;Munir Gharaibeh,&nbsp;Mohammad Alqudah","doi":"10.2174/1874467215666220413085316","DOIUrl":"https://doi.org/10.2174/1874467215666220413085316","url":null,"abstract":"<p><strong>Background: </strong>An imbalance in the levels of arachidonic acid (ARA) metabolites in cardiovascular disorders and drug-induced cardiotoxicity have been previously described.</p><p><strong>Aims: </strong>This study aimed to investigate the influence of cyclooxygenase-2 (COX-2) selective inhibitors on the gene expression of ARA-metabolizing genes and beta1 gene in the hearts and kidneys of experimental mice.</p><p><strong>Methods: </strong>Thirty-five balb/c mice were divided into five groups with seven mice per group. The groups were then given two distinct types of COX-2 selective inhibitors, rofecoxib and celecoxib, in two different doses equivalent to those used in human treatment for 30 days. The mRNA expression of beta1, ace2, and ARA-metabolizing genes, coxs, lipoxygenases (aloxs), and cytochrome p450 (cyp450s) in mice heart and kidneys were assessed. Genes were analyzed using real-time polymerase chain reaction analysis. In addition, rofecoxib-induced histological alterations were examined.</p><p><strong>Results: </strong>It was found that only the high dose of rofecoxib (5 mg/kg) caused toxicological alterations, a finding that was indicated by a significant increase (P < 0.05) in the relative weight of the mouse hearts and increase in the ventricle wall thickness as observed through pathohistological examination. This increase was associated with a significant increase in the mRNA expression level of the beta1 receptor in both the heart and kidneys of the mice (53- and 12-fold, respectively). The expression of both cox1 and 2 genes was increased 4-fold in the kidneys. In addition, the expression of the alox12 gene increased significantly (by 67-fold in the heart and by 21-fold in the kidney), while alox15 gene expression was upregulated in the heart by 8-fold and 5-fold in the kidney. The genes responsible for synthesizing 20- Hydroxyeicosatetraenoic acid (cyp4a12 and cyp1a1) were significantly upregulated (P < 0.05) in the hearts of high-dose rofecoxib-treated mice by 7- and 17 -fold, respectively. In addition, the expression of epoxyeicosatrienoic acid-synthesizing genes, cyp2c29 and cyp2j5, was increased significantly (P < 0.05) in the hearts of high-dose rofecoxib-treated mice by 4- and 16-fold, respectively.</p><p><strong>Conclusion: </strong>Rofecoxib caused upregulation of the mRNA expression of the beta 1 gene in association with increased expression of ARA-metabolizing genes in mouse hearts and kidneys. These findings may help us understand the molecular cardiotoxic mechanism of rofecoxib.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9493604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive and Therapeutic Aspects of Migraine for Patient Care: An Insight.","authors":"Ruchi Tiwari,&nbsp;Gaurav Tiwari,&nbsp;Sonam Mishra,&nbsp;Vadivelan Ramachandran","doi":"10.2174/1874467215666220211100256","DOIUrl":"https://doi.org/10.2174/1874467215666220211100256","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a common neurological condition marked by frequent mild to extreme headaches that last 4 to 72 hours. A migraine headache may cause a pulsing or concentrated throbbing pain in one part of the brain. Nausea, vomiting, excessive sensitivity to light and sound, smell, feeling sick, vomiting, painful headache, and blurred vision are all symptoms of migraine disorder. Females are more affected by migraines in comparison to males.</p><p><strong>Objective: </strong>The present review article summarizes preventive and therapeutic measures, including allopathic and herbal remedies for the treatment of migraine.</p><p><strong>Results: </strong>This review highlights the current aspects of migraine pathophysiology and covers an understanding of the complex workings of the migraine state. Therapeutic agents that could provide an effective treatment have also been discussed.</p><p><strong>Conclusion: </strong>It can be concluded that different migraines could be treated based on their type and severity.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9141290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of Genotoxicity of Carbamazepine to Human Lymphocytes by Pre-treatment with Vitamin B12.","authors":"Eman K Hendawi,&nbsp;Omar F Khabour,&nbsp;Laith N Al-Eitan,&nbsp;Karem H Alzoubi","doi":"10.2174/1874467215666220420135924","DOIUrl":"https://doi.org/10.2174/1874467215666220420135924","url":null,"abstract":"<p><strong>Background: </strong>Carbamazepine (CBZ) is widely used as an anti-epileptic drug. Vitamin B12 has been shown to protect against DNA damage caused by several mutagenic agents.</p><p><strong>Objective: </strong>This study aimed to investigate the effect of vitamin B12 on CBZ-induced genotoxicity in cultured human lymphocytes.</p><p><strong>Methods: </strong>Sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) genotoxic assays were utilized to achieve the study objective.</p><p><strong>Results: </strong>The results showed significantly higher frequencies of CAs and SCEs in the CBZ-treated cultures (12 μg/mL) compared to the control group (P<0.01). The genotoxic effects of CBZ were reduced by pre-treatment of cultures with vitamin B12 (13.5μg/ml, P<0.05). Neither CBZ nor vitamin B-12 showed any effects on mitotic and proliferative indices.</p><p><strong>Conclusion: </strong>CBZ is genotoxic to lymphocyte cells, and this genotoxicity can be reduced by vitamin B12.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9141303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Acute and Chronic Sleep Deprivation on the Immune Profile in the Rat.","authors":"Alaa Fahmawi,&nbsp;Mohammad Khalifeh,&nbsp;Karem H Alzoubi,&nbsp;Abeer M Rababa'h","doi":"10.2174/1874467215666220316104321","DOIUrl":"https://doi.org/10.2174/1874467215666220316104321","url":null,"abstract":"<p><strong>Background: </strong>Acute and chronic sleep deprivation present many health-related problems in modern societies, mainly concerning the immune system. Immune factors, particularly the interleukins, regulate sleep and, therefore, may be altered by sleep deprivation (SD).</p><p><strong>Objectives: </strong>We aimed to investigate the possible effects of acute and chronic sleep deprivation on selected cytokines, including interleukins (IL-1β, IL-9, IL-17, and IL-23) and tumor necrosis factor- alpha (TNF-α).</p><p><strong>Methods: </strong>The animals were grouped into acute sleep-deprived (SD; for 24 hours) and chronic sleep-deprived (8 hours a day for 10, 20, and 30-days). The SD was induced using the multipleplatforms model. The serum levels of cytokines were measured using commercially available ELISA.</p><p><strong>Results: </strong>The serum levels of IL-1β were significantly reduced after acute SD, whereas they were increased after 20-days of chronic SD. The IL-9 levels were reduced after acute SD, increased after 10-days of SD, and reduced again after 30-days of SD. Conversely, the levels of IL-23 were not changed after acute SD, reduced after 10 days of SD, and increased after 30-days of SD. Levels of TNF-α were not changed after acute SD, whereas they were increased after 20 and 30- days of SD.</p><p><strong>Conclusion: </strong>In conclusion, both acute and chronic SD distinctly disturb the immune profile, which might result in the emergence of various pathologies presented during sleep deprivation.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Protective Effect of Bajijiasu on the Treatment of Hypertensive Nephropathy in Rats.","authors":"Minyi Li,&nbsp;Beifeng Lie,&nbsp;Tingting Duan,&nbsp;Deqi Chen,&nbsp;Tao Xia,&nbsp;Heng Xie,&nbsp;Guixuan Lin,&nbsp;Junzheng Yang,&nbsp;Zhenghai Li","doi":"10.2174/1874467215666221005141210","DOIUrl":"https://doi.org/10.2174/1874467215666221005141210","url":null,"abstract":"<p><strong>Backgrounds: </strong>Hypertensive nephropathy (HN) is a kind of renal disease caused by essential hypertension that eventually worsens into end-stage renal disease (ESRD). HN could damage the renal tubules, induce kidney damage and renal failure, and increase the risk of stroke, heart disease or death, but there are few ideal drugs for HN treatment.</p><p><strong>Methods: </strong>In this study, we explored the therapeutic effect of bajijiasu (a compound from Morinda officinalis how and a common traditional Chinese medicine for tonifying the kidney) on the HN rat model. Biochemical analysis, HE staining, and PAS staining were used to assess the effects of bajijiasu on HN rat model. Western blotting was used to analyze the potential mechanisms.</p><p><strong>Results: </strong>The results of HE staining and PAS staining showed that bajijiasu could alleviate the pathological changes in HN rat models; biochemical analysis found that the concentration of Malondialdehyde (MDA), total protein (TP), albumin (ALB), microalbuminuria (MALB), blood urea nitrogen (BUN), creatinine (Cr), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) were significantly decreased compared with the model group after bajijiasu treatment; and bajijiasu could regulate the expression of TNF-α, IL-6, MDA, SOD1 and AGEs in HN rats; the result of western blotting demonstrated that bajijiasu could down-regulate the expression of TGFβ1, NOX4, JNK, p- JNK and up-regulate the expression PPARγ and SOD 1 in HN rats.</p><p><strong>Conclusion: </strong>Those results demonstrated that bajijiasu could alleviate the pathological changes and physiological and biochemical symptoms of HN rat models by regulating the expression of TGFβ1, PPARγ, JNK, p-JNK, NOX4 and SOD1 but could not lower the blood pressure of HN rats. Those pieces of evidence may provide a new therapeutic method for HN treatment.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity, Genotoxicity, and Carcinogenicity of Isotretinoin.","authors":"Serkan Yilmaz","doi":"10.2174/1874467215666220520143124","DOIUrl":"https://doi.org/10.2174/1874467215666220520143124","url":null,"abstract":"<p><strong>Background: </strong>Acne is a chronic inflammatory disease mainly observed in adolescence, but it can also be seen during the neonatal, infantile, pre-pubertal, and adult periods. Isotretinoin (13-cis-retinoic acid) is a first-generation retinoid and is the most effective treatment for acne vulgaris.</p><p><strong>Objective: </strong>The present study has been systematically designed to figure out the toxic, genotoxic, and carcinogenic activities of isotretinoin.</p><p><strong>Methods: </strong>In this study, a systematic approach was followed by focusing on the possible links between these topics. The search of the databases was carried out author in accordance with the guidelines of the Centre for Reviews and Dissemination (2009) developed by York University National Institute of Health Research. The search was concentrated on the Web of Science, PubMed, Science Direct, Scopus, EBSCO Host, and Google Scholar databases.</p><p><strong>Results: </strong>Isotretinoin was found as a toxic agent in all studies. All researchers proposed that apoptosis is the only pathway of adverse effects of isotretinoin. However, genotoxicity, teratogenicity, and carcinogenicity information of isotretinoin is very limited and controversial.</p><p><strong>Conclusion: </strong>More detailed studies need to clarify the genotoxic and carcinogenic potential of isotretinoin. Patients should be informed correctly, the risks of treatment should be explained, and awareness should be raised.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9134450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Bazedoxifene and Genistein Ameliorate Ovariectomy-Induced Hippocampal Neuro-Alterations via Activating CREB/BDNF/TrkB Signaling Pathway.","authors":"Mai A Samak,&nbsp;Abeer A Abdelrahman,&nbsp;Walaa Samy,&nbsp;Shaimaa A Abdelrahman","doi":"10.2174/1874467215666220902112939","DOIUrl":"https://doi.org/10.2174/1874467215666220902112939","url":null,"abstract":"<p><strong>Objectives: </strong>The scientific research community devotes stupendous efforts to control the arguable counterbalance between the undesirable effects of hormone replacement therapy (HRT) and post-menopausal syndrome. The recent emergence of 3rd generation selective estrogen receptor modulators and phytoestrogens has provided a promising alternative to HRT. Hence, we assessed the potential effects of combined Bazedoxifene and Genistein on hippocampal neuro-alterations induced by experimental ovariectomy.</p><p><strong>Methods: </strong>For this purpose, we utilized forty-eight healthy sexually mature female Wistar rats assorted to control, ovariectomy (OVX), Genistein-treated ovariectomized (OVX+GEN) and Bazedoxifene and Genistein-treated ovariectomized (OVX+BZA+GEN) groups. Hippocampi samples from various groups were examined by H&E, silver stains and immunohistochemical examination for calbindin-D28k, GFAP, and BAX proteins. We also assessed hippocampal mRNA expression of ERK, CREB, BDNF and TrkB.</p><p><strong>Results: </strong>Our histopathological results confirmed that combined BZA+GEN induced restoration of hippocampal neuronal architecture, significant reduction of GFAP and BAX mean area % and significant upregulation of calbindin-D28k immunoexpression. Furthermore, we observed significant upregulation of ERK, CREB, BDNF and TrkB mRNA expression in the BZA+GEN group compared to the OVX group.</p><p><strong>Conclusion: </strong>Taken together, our findings have provided a comprehensive assessment of histological, immunohistochemical and cyto-molecular basis of combined Genistein and Bazedoxifene ameliorative impacts on hippocampal neuro-alterations of OVX rats via upregulation of Calbindin, CERB, BDNF, Trk-B and ERK neuronal expression.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9859455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of Dravet Syndrome and its Targeted Therapy by Nanomedicine: A Roadmap for Future Treatment of Drug Resistant Seizures.","authors":"Muhammad Ikram,&nbsp;Sufian Rasheed","doi":"10.2174/1874467215666220819143105","DOIUrl":"https://doi.org/10.2174/1874467215666220819143105","url":null,"abstract":"<p><p>According to the World Health Organization (WHO), epilepsy is the 4th most prevalent neurological disorder after migraine, stroke, and Alzheimer's disease. There are numerous types of epileptic syndrome that are reported in children; one of them is Dravet syndrome. It is a neurological disorder of infants' outset during the first year of life. Dravet syndrome is a genetically determined syndrome and the most studied form of genetic epilepsy. Nearly 70-80% of its cases are due to genetic alterations in the SCN1A gene, and almost 16% of cases are due to variations in the PCDH19 gene. Besides that, mutations in SCN1B, SCN2A, and GABRG2, including some novel genes, STXBP1, HCN1, and CDH2 have been observed in DS patients. It is a drug-resistant epileptic syndrome and its complete removal is still challenging. So, novel therapeutic techniques are being used to treat drug-resistant seizures. Recently, new strategies have been made to improve the neuron-specific targeting of AEDs encapsulated by nanocarriers. The nanocarriers will have a major contribution to nano-neuro medicines such as drug delivery, neuroimaging, neuroprotection, neurosurgery, and neuroregeneration. The nanotechnology-mediated techniques also have a fantastic success rate in gene therapy, as reported in recent years. The anti- epileptic drug delivery with the help of nanoparticles, at the targeted position, makes them applicable for the possible treatment of drug-resistant seizures and gives new hope to patients affected with it.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9361520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}