{"title":"Vinegar-baked Radix Bupleuri enhances the liver-targeting effect of rhein on liver injury rats by regulating transporters.","authors":"Ya Zhao, Jinqiu Wang, Lijuan Liu, Yayun Wu, Qiaohong Hu, Ruizhi Zhao","doi":"10.1093/jpp/rgac062","DOIUrl":"https://doi.org/10.1093/jpp/rgac062","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore whether the liver-targeting enhancing effect of vinegar-baked Radix Bupleuri (VBRB) on rhein was achieved by affecting transporters, metabolism enzymes as well as hepatocyte nuclear factor 1α/4α (HNF1α/HNF4α) in liver injury.</p><p><strong>Methods: </strong>The effect of VBRB on the efficacy of rhein was performed with the LPS-induced acute liver injury rat model. Aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) levels were determined and histopathological examination was taken. Drug concentrations in tissues were determined by high performance liquid chromatography (HPLC). The protein expressions of drug transporters, metabolic enzymes and hepatic nuclear factors were determined by Western blotting and ELISA assays.</p><p><strong>Key finding: </strong>VBRB improved the liver protecting effect of rhein, which was consistent with its promoting effect on targeted enrichment of rhein in the liver. VBRB or in combination with rhein inhibited P-glycoprotein (Pgp) and multi-resistance related protein 2 (MRP2), while increased organic anion transporting polypeptide 2 (OATP2), which might be the reason why VBRB promoted liver-targeting effect of rhein.</p><p><strong>Conclusion: </strong>VBRB enhances the liver-protecting effect of rhein by down-regulating Pgp, MRP2, and up-regulating OATP2.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1588-1597"},"PeriodicalIF":3.3,"publicationDate":"2022-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40384966","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}
Dimitrios A Lamprou, Dennis Douroumis, Gavin P Andrews, David S Jones
{"title":"3D printing in pharmacological and pharmaceutical sciences.","authors":"Dimitrios A Lamprou, Dennis Douroumis, Gavin P Andrews, David S Jones","doi":"10.1093/jpp/rgac049","DOIUrl":"https://doi.org/10.1093/jpp/rgac049","url":null,"abstract":"","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1365-1366"},"PeriodicalIF":3.3,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40350429","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":"Eleutheroside E functions as anti-cervical cancer drug by inhibiting the phosphatidylinositol 3-kinase pathway and reprogramming the metabolic responses.","authors":"Yipin Cai, Jie Zhang, Tiantian Xin, Songyuan Xu, Xiaoli Liu, Yu Gao, Haiwei Huang","doi":"10.1093/jpp/rgac047","DOIUrl":"https://doi.org/10.1093/jpp/rgac047","url":null,"abstract":"<p><strong>Objectives: </strong>Cervical cancer (CC) is the common female malignant tumour with non-negligible morbidity and mortality. Eleutheroside E (EE) has anti-oxidative stress, anti-inflammatory and anti-proliferation effects in diverse disease models. However, its anti-tumour role remains unclear.</p><p><strong>Methods: </strong>The cell viability, apoptosis rate and protein expressions were detected by CCK-8, flow cytometry and western blot assays, respectively. The metabolic profile was performed by GC/MS analysis. Furthermore, the effect of EE on CC was verified in nude mice.</p><p><strong>Key findings: </strong>EE notably decreased the viability and increased the cell apoptosis, which could be reversed with 740Y-P treatment. EE treatment changed the metabolic categories of SiHa cells. The fatty acids signalling pathway was the most outstanding differential pathway. Myo-inositol prominently enhanced the level of phosphorylated Akt in a dose-dependent way. Moreover, EE declined the tumour volume and weight and the proliferation, but promoted the apoptosis in vivo. EE reduced the relative expression of phosphorylated PI3K and Akt. However, all these in-vivo results were observably antagonized with myo-inositol treatment.</p><p><strong>Conclusions: </strong>EE plays an anti-tumour role in CC via inhibiting the PI3K pathway and reprogramming the metabolic responses.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1251-1260"},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40564024","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":"MTH-3 sensitizes oral cancer cells to cisplatin via regulating TFEB.","authors":"Shih-Chang Tsai, Jai-Sing Yang, Chi-Cheng Lu, Fuu-Jen Tsai, Yu-Jen Chiu, Sheng-Chu Kuo","doi":"10.1093/jpp/rgac056","DOIUrl":"https://doi.org/10.1093/jpp/rgac056","url":null,"abstract":"<p><strong>Objectives: </strong>MTH-3, a curcumin derivative, exhibits improved water solubility. This study aims to elucidate the mechanisms underlying the anticancer effects of MTH-3 on human oral squamous cell carcinoma CAL27 cisplatin-resistant (CAR) cells.</p><p><strong>Methods: </strong>To evaluate the biological functions of MTH-3 in CAR cells, flow cytometry, staining, and western blot analyses were used.</p><p><strong>Key findings: </strong>MTH-3 reduced CAR cell viability and significantly induced autophagy in the presence of 10 and 20 μM MTH-3. Transcription factor EB was identified as the potential target of MTH-3. Autophagy-related proteins were upregulated after 24 h of MTH-3 incubation. MTH-3 treatment increased caspase-3 and caspase-9 enzyme activities. Mitochondrial membrane potential was decreased after MTH-3 treatment. MTH-3 triggered the intrinsic apoptotic pathway.</p><p><strong>Conclusions: </strong>MTH-3 induces autophagy and apoptosis of CAR cells via TFEB. MTH-3 might be an effective pharmacological agent for treating oral cancer cells.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1261-1273"},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40539601","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}
Nidhi Gupta, Sana Nafees, Aziz Ur Rahman, Jamal Akhtar, Asim Ali Khan, Alpana Sharma
{"title":"Itrifal-e-Aftimoon potentiates imatinib-induced anti-leukemic effect by influencing FAK/STAT/Akt/ERK signalling pathways against chronic myeloid leukaemia in vitro.","authors":"Nidhi Gupta, Sana Nafees, Aziz Ur Rahman, Jamal Akhtar, Asim Ali Khan, Alpana Sharma","doi":"10.1093/jpp/rgac045","DOIUrl":"https://doi.org/10.1093/jpp/rgac045","url":null,"abstract":"<p><strong>Objectives: </strong>Limited treatment options are available for advanced stages of chronic myeloid leukaemia (CML). Moreover, patients' relapse after a short remission period, which prompts them to identify a potent drug with the least toxicity. An Unani herbal formulation, Itrifal-e-Aftimoon (IEA) is used for certain neurological disorders, however, its antitumor potential has not been reported yet in any malignancy, including CML.</p><p><strong>Methods: </strong>The aqueous extract of IEA was characterized by HPLC/LC-MS and used alone or in combination with standard drug, imatinib in CML cell lines (K562, KU812) in vitro to assess its effect on cancer-associated parameters such as cytotoxicity, cell cycle, apoptosis, oxidative stress, inflammation, angiogenesis, and certain signalling pathways.</p><p><strong>Results: </strong>LC-MS characterization of IEA showed the presence of antitumor compounds including catechin and caffeic acid. Treatment with IEA caused cytotoxicity and arrested cells in the sub-G0/G1 phase. Subsequent assays confirmed apoptosis-mediated cell death with mitochondrial membrane depolarization and alleviation of oxidative stress. IEA abrogates IL-6, VEGF, angiopoietin-2, and alters Th1/Th2 cytokines. IEA potentiated the effect of imatinib even at lower doses by affecting FAK/STAT/Akt/ERK pathways.</p><p><strong>Conclusion: </strong>IEA possesses antitumor potential against CML and increases the efficacy of imatinib when used in combination, suggesting utilization of IEA as an adjuvant therapy for better management of CML in the future.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1330-1341"},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40487406","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":"Phytochemical profile and protective effects on myocardial ischaemia-reperfusion injury of sweated and non-sweated Salvia miltiorrhiza. Bge alcoholic extracts.","authors":"Xiaoxiao Shan, Yaoyao Xiao, Bangzhen Hong, Ling Li, Yueting Chen, Guokai Wang, Nianjun Yu, Daiyin Peng, Caiyun Zhang, Lei Wang, Weidong Chen","doi":"10.1093/jpp/rgac012","DOIUrl":"https://doi.org/10.1093/jpp/rgac012","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to compare the fingerprint and the content of the three components of sweated and non-sweated Salvia miltiorrhiza alcoholic extracts (SSAE and NSAE). It also aims to investigate the difference in protective effects of SSAE and NSAE on myocardial ischaemia-reperfusion injury (MIRI).</p><p><strong>Methods: </strong>The fingerprints of SSAE and NSAE were established by HPLC with a UV detector to identify the common peaks and detect the content of the three major components (cryptotanshinone, tanshinone I and tanshinone IIA). The protective effects of SSAE and NSAE were compared with MIRI rat model after orally administered SSAE and NSAE (2 g/kg of raw drug) for 7 days. The ST segment, PR and QT interval changes and the infarct size were assessed in the rat hearts. Moreover, the activity of aspartate transaminase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and the level of cardiac troponin I (cTn I) in serum as well as the cardiac H&E staining were evaluated.</p><p><strong>Key findings: </strong>The results showed that the fingerprints of SSAE and NSAE were similar, and cluster analysis showed that the sweating methods had effects on the alcoholic extracts. The content determination showed that sweating could increase the total content of cryptotanshinone, tanshinone I and tanshinone IIA of S. miltiorrhiza. The results of electrocardiograms (ECG) showed that SSAE could make the ST segment drop more obviously, PR and QT intervals become shorter, and the size of the infarct much smaller. Compared with NSAE, SSAE had more significant effects on the enzymatic activity of AST, LDH and the level of cTn I in serum. The H&E staining showed that both SSAE and NSAE could reduce the degree of heart damage.</p><p><strong>Conclusions: </strong>The present investigation results demonstrated that sweating increased the content of tanshinone components in S. miltiorrhiza alcoholic extracts, and SSAE had a better protective effect on MIRI.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1230-1240"},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504526","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-histamine effects of dipotassium glycyrrhizinate on lung fibroblasts, implicating its therapeutic mechanism for pulmonary fibrosis.","authors":"Wenwen Huang, Xiaoying Zhou","doi":"10.1093/jpp/rgac030","DOIUrl":"https://doi.org/10.1093/jpp/rgac030","url":null,"abstract":"<p><strong>Objectives: </strong>To examine the possible anti-histamine effects of dipotassium glycyrrhizinate (DG), a dipotassium salt of glycyrrhizic acid, on histamine-mediated lung fibroblast activation, differentiation and proliferation; to investigate the potential and underlying mechanisms for pulmonary fibrosis (PF) treatment.</p><p><strong>Methods: </strong>Rat primary lung fibroblasts were extracted to establish cell models; histamine, DG and loratadine (LTD, a histamine receptor antagonist) were applied. Cell proliferation, migration and cell cycle were explored; intracellular signal proteins were detected; mitochondrial membrane potential was examined.</p><p><strong>Key findings: </strong>The anti-histamine effects of DG were found in a similar pattern of LTD on lung fibroblasts. DG inhibited histamine-induced cell activation, proliferation and migration; DG altered histamine-mediated mitochondrial membrane potentials. DG reduced the histamine-induced PAR-2 (a tryptase receptor) expression to impair mast cell tryptase co-working. Histamine-induced expressions of MMP-2, FAK, TNF-α, P38, iNOS were decreased by DG, while Bax and caspase-3, P53 were increased by DG against histamine effects. Histamine drove cells from G0/G1 to S phases, whereas DG rested cells by inhibiting G0/G1 and G2/M phases.</p><p><strong>Conclusions: </strong>This study provided the evidences that DG can inhibit histamine-induced effects on lung fibroblasts and promote apoptosis of abnormally activated lung fibroblasts, implicating its potential therapeutic mechanisms against PF development, also for those histamine-related diseases.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1241-1250"},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40471177","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":"Docetaxel in combination with metformin enhances antitumour efficacy in metastatic breast carcinoma models: a promising cancer targeting based on PEGylated liposomes.","authors":"Roghayyeh Vakili-Ghartavol, Amin Mehrabian, Farshad Mirzavi, Seyed Mahdi Rezayat, Mohammad Mashreghi, Leila Farhoudi, Sharmin Kharrazi, Kayvan Sadri, Mahmoud Reza Jaafari","doi":"10.1093/jpp/rgac048","DOIUrl":"https://doi.org/10.1093/jpp/rgac048","url":null,"abstract":"<p><strong>Objectives: </strong>Metformin has been shown to kill cancer stem-like cells in genetically various types of breast carcinoma. With the aim to simultaneously eradicate the bulk population of tumour cells and the rare population of cancer stem-like cells in breast cancer tissues, we used the combination chemotherapy of docetaxel (DTX) with metformin (MET). Furthermore, we introduce an active loading method based on ammonium sulphate 250 mM (SA) for encapsulating docetaxel into liposomes.</p><p><strong>Methods: </strong>Docetaxel and metformin encapsulated into PEGylated liposomes with two different methods based on remote or passive loading methods, respectively. The size and surface charge of the liposomes were characterized. DTX content in the nanoliposomes was measured by the high-performance liquid chromatography method. The drug release profiles were evaluated in phosphate-buffered dextrose 5% with the pH of 6.5 and 7.4. We examined the antitumour activity of Taxotere (TAX), and liposomal formulation of DTX and MET as a monotherapy or combination therapy. The biodistribution of liposomes was also investigated using 99mTc hexamethyl propylene amine oxime method in BALB/c mice bearing 4T1 breast carcinoma tumours.</p><p><strong>Key findings: </strong>The final formulations were prepared according to the best physicochemical characteristics which were HSPC/mPEG2000-DSPE/Chol (DTX liposomes) and HSPC/DPPG/mPEG2000-DSPE/Chol (MET liposomes), at molar ratios of 85/5/10 and (55/5/5/35), respectively. In vivo experiments showed that when free or liposomal metformin used in combination with liposomal docetaxel, they prolonged median survival time (MST) from 31 in the control group to 46 days, which demonstrates their promising effects on the survival of the 4T1 breast carcinoma mice models. Moreover, combination therapies could significantly increase life span in comparison with phosphate-buffered saline (PBS) and Taxotere groups at the same dose. Furthermore, in the combination therapy study, treatment with DTX liposomes prepared by ammonium sulphate 250 mM buffer alone resulted in similar therapeutic efficacy to combination therapy. The biodistribution study exhibited significant accumulation of DTX liposomes in the tumours due to the Enhanced Permeability and Retention effect.</p><p><strong>Conclusions: </strong>This study also showed that metformin-based combinatorial chemotherapies have superior efficacy versus their corresponding monotherapy counterparts at same doses. The findings confirm that liposomes based on ammonium sulphate 250 mM could be as a promising formulation for efficient DTX delivering and cancer targeting and therefore merit further investigations.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1307-1319"},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40521374","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}
Chinyere Aloke, Ikenna C Ohanenye, Patrick M Aja, Chukwunonso E C C Ejike
{"title":"Phytochemicals from medicinal plants from African forests with potentials in rheumatoid arthritis management.","authors":"Chinyere Aloke, Ikenna C Ohanenye, Patrick M Aja, Chukwunonso E C C Ejike","doi":"10.1093/jpp/rgac043","DOIUrl":"https://doi.org/10.1093/jpp/rgac043","url":null,"abstract":"<p><strong>Objectives: </strong>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation, pain, and cartilage and bone damage. There is currently no cure for RA. It is however managed using nonsteroidal anti-inflammatory drugs, corticosteroids and disease-modifying anti-rheumatic drugs, often with severe side effects. Hidden within Africa's lush vegetation are plants with diverse medicinal properties including anti-RA potentials. This paper reviews the scientific literature for medicinal plants, growing in Africa, with reported anti-RA activities and identifies the most abundant phytochemicals deserving research attention. A search of relevant published scientific literature, using the major search engines, such as Pubmed/Medline, Scopus, Google Scholar, etc. was conducted to identify medicinal plants, growing in Africa, with anti-RA potentials.</p><p><strong>Key findings: </strong>Twenty plants belonging to 17 families were identified. The plants are rich in phytochemicals, predominantly quercetin, rutin, catechin, kaempferol, etc., known to affect some pathways relevant in RA initiation and progression, and therefore useful in its management.</p><p><strong>Summary: </strong>Targeted research is needed to unlock the potentials of medicinal plants by developing easy-to-use technologies for preparing medicines from them. Research attention should focus on how best to exploit the major phytochemicals identified in this review for the development of anti-RA 'green pharmaceuticals'.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1205-1219"},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40572184","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":"Comparison of three in vitro keratinocytes-fibroblasts wound healing models commonly used in pharmaceutical research.","authors":"Hui Xin Wong, Chin Chiat Lee, Paul Chi-Lui Ho","doi":"10.1093/jpp/rgac046","DOIUrl":"https://doi.org/10.1093/jpp/rgac046","url":null,"abstract":"<p><strong>Objectives: </strong>Several common wound healing models have been used to evaluate wound healing agents and formulations, namely: conditioned media (CM), transwell co-cultures (TWCC) and co-cultures (CC) in a monolayer. However, no study has been conducted to compare the relevance of these models in the keratinocytes and fibroblasts interaction physiologically. Therefore, this study aimed to compare these models based on cell migration and proliferation, and matrix metalloproteinase (MMP) expression.</p><p><strong>Methods: </strong>Cell migration was analysed by scratch assay and MMP-7, while cell proliferation was analysed by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay.</p><p><strong>Key findings: </strong>Increased cell migration was observed in CM and TWCC models, while varied results were obtained in CC. Cell migration was increased due to upregulation of MMP-7 in CM and TWCC models, while it was downregulated in CC, which might have hindered migration of both cells in monolayers.</p><p><strong>Conclusions: </strong>CM and TWCC are more suitable than CC for wound healing research and for evaluating wound healing agents or formulations, as they can better simulate the layered tissue constructs and paracrine interactions in the physiological environment.</p>","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":" ","pages":"1220-1229"},"PeriodicalIF":3.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40561620","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}