Pub Date : 2021-10-06DOI: 10.5772/intechopen.99705
S. Ben Mansour-Gueddes, Dhouha Saidana-Naija
Oxidation has been related to several diseases in humans. Indeed, to protect the body from high free radical damages, organism requires natural resources of antioxidant compounds, such as phenols, tocopherols (α, β, γ, and σ) which have important roles in the cell antioxidant defense system. In Mediterranean areas, olive oils and pepper fruits are considered among the best foods in a diet, which keeps on attracting the interest of scientists due to the health benefits linked with its consumption. The Olive oil and pepper fruits are among the most consumed nutrients in the Mediterranean diet; their richness in naturally powerful antioxidants, such as alpha-tocopherols, polyphenols, carotenoïds, and capsaicinoïds (specific of capsicum species), and monounsaturated fatty acids in olive and seed pepper oils, constitutes good health protection against oxidative damages and inflammation. Also, these phytochemicals shield and prevent the human body from many diseases such as cardiovascular, coronary, Alzheimer’s diseases, and cancers.
{"title":"Vitamin E: Natural Antioxidant in the Mediterranean Diet","authors":"S. Ben Mansour-Gueddes, Dhouha Saidana-Naija","doi":"10.5772/intechopen.99705","DOIUrl":"https://doi.org/10.5772/intechopen.99705","url":null,"abstract":"Oxidation has been related to several diseases in humans. Indeed, to protect the body from high free radical damages, organism requires natural resources of antioxidant compounds, such as phenols, tocopherols (α, β, γ, and σ) which have important roles in the cell antioxidant defense system. In Mediterranean areas, olive oils and pepper fruits are considered among the best foods in a diet, which keeps on attracting the interest of scientists due to the health benefits linked with its consumption. The Olive oil and pepper fruits are among the most consumed nutrients in the Mediterranean diet; their richness in naturally powerful antioxidants, such as alpha-tocopherols, polyphenols, carotenoïds, and capsaicinoïds (specific of capsicum species), and monounsaturated fatty acids in olive and seed pepper oils, constitutes good health protection against oxidative damages and inflammation. Also, these phytochemicals shield and prevent the human body from many diseases such as cardiovascular, coronary, Alzheimer’s diseases, and cancers.","PeriodicalId":23478,"journal":{"name":"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82684136","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}
Pub Date : 2021-08-30DOI: 10.5772/intechopen.97474
A. M. Jasim, M. Jawad
D-tocopheryl polyethylene glycol succinate (Vitamin E TPGS) has been approved as a safe pharmaceutical adjuvant by FDA, and several drug delivery systems (DDS) based on TPGS have been developed. TPGS properties as a P-gp inhibitor, solubilizer/absorption and permeation enhancer in drug delivery and TPGS-related formulations such as nanocrystals, nanosuspensions, tablets/solid dispersions, vaccine system adjuvant, nutritional supplement, film plasticizer, anticancer reagent, and so on, are discussed in this review. Consequenly, TPGS can inhibit ATP-dependent P-glycoprotein activity and act as a potent excipient that promotes the efficiency of delivery and the therapeutic effect of drugs. Inhibition of P-gp occurs through mitochondria-dependent inhibition of the P-gp pump. Many of the latest studies address the use of TPGS for many poorly water-soluble or permeable drugs in the manufacture of nanodrugs or other formulations. In addition, it has been reported that TPGS shows a robust improvement in chylomicron secretion at low concentrations and improves intestinal lymphatic transport, which would also boost the potential of drug absorption. It also indicates that there are still many problems facing clinical translation of TPGS-based nanomedicines, requiring a more deep evaluation of TPGS properties and a future-based delivery method.
d -生育酚基聚乙二醇琥珀酸酯(维生素E TPGS)已被FDA批准为一种安全的药物佐剂，并已开发出几种基于TPGS的给药系统(DDS)。本文综述了TPGS作为P-gp抑制剂、增溶剂/吸收剂和渗透增强剂在药物传递中的性能，以及TPGS在纳米晶体、纳米悬浮液、片剂/固体分散体、疫苗系统佐剂、营养补充剂、薄膜增塑剂、抗癌试剂等相关制剂中的应用。因此，TPGS可以抑制atp依赖性p -糖蛋白活性，并作为一种有效的赋形剂，促进药物的递送效率和治疗效果。P-gp的抑制是通过线粒体依赖性的P-gp泵抑制而发生的。许多最新的研究解决了在纳米药物或其他配方的制造中，将TPGS用于许多水溶性或渗透性差的药物。此外，有报道称，TPGS在低浓度下可显著改善乳糜微粒分泌，改善肠道淋巴运输，从而提高药物吸收潜力。这也表明基于TPGS的纳米药物的临床转化仍面临许多问题，需要更深入地评估TPGS的性质和基于未来的递送方法。
{"title":"Pharmaceutical Applications of Vitamin E TPGS","authors":"A. M. Jasim, M. Jawad","doi":"10.5772/intechopen.97474","DOIUrl":"https://doi.org/10.5772/intechopen.97474","url":null,"abstract":"D-tocopheryl polyethylene glycol succinate (Vitamin E TPGS) has been approved as a safe pharmaceutical adjuvant by FDA, and several drug delivery systems (DDS) based on TPGS have been developed. TPGS properties as a P-gp inhibitor, solubilizer/absorption and permeation enhancer in drug delivery and TPGS-related formulations such as nanocrystals, nanosuspensions, tablets/solid dispersions, vaccine system adjuvant, nutritional supplement, film plasticizer, anticancer reagent, and so on, are discussed in this review. Consequenly, TPGS can inhibit ATP-dependent P-glycoprotein activity and act as a potent excipient that promotes the efficiency of delivery and the therapeutic effect of drugs. Inhibition of P-gp occurs through mitochondria-dependent inhibition of the P-gp pump. Many of the latest studies address the use of TPGS for many poorly water-soluble or permeable drugs in the manufacture of nanodrugs or other formulations. In addition, it has been reported that TPGS shows a robust improvement in chylomicron secretion at low concentrations and improves intestinal lymphatic transport, which would also boost the potential of drug absorption. It also indicates that there are still many problems facing clinical translation of TPGS-based nanomedicines, requiring a more deep evaluation of TPGS properties and a future-based delivery method.","PeriodicalId":23478,"journal":{"name":"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72912733","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}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.78792
A. Rusu
End-stage renal disease patients treated with hemodialysis are characterized by a special diet, increased oxidative stress, cardiovascular morbidity and mortality, as well as many other complications such as inflammation-malnutrition syndrome, muscle cramps, and anemia. Worldwide efforts are focused on reducing hemodialysis complications to increase survival in these patients. In vitro and in vivo studies proved that vitamin E has many beneficial effects such as: decreases reactive oxygen species synthesis, improves antioxidant defense system, inhibits lipids peroxidation and reduces atherosclerosis, and ameliorates anemia treatment. Mechanisms of action are complex and not fully understood. However, there are particularities in regards of vitamin E intake, metabolism, and clearance in patients treated with hemodialysis. Supplementation of vitamin E in these patients has been intensively studied, and it is still under debate. Oral administration and vitamin E-coated membranes for dialysis have been tried. Clinical practice guidelines tried to underline when and how much vitamin E to be given to be safe and costbeneficial. The current chapter aims to synthesize all these issues.
{"title":"Vitamin E in Hemodialysis Patients","authors":"A. Rusu","doi":"10.5772/INTECHOPEN.78792","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78792","url":null,"abstract":"End-stage renal disease patients treated with hemodialysis are characterized by a special diet, increased oxidative stress, cardiovascular morbidity and mortality, as well as many other complications such as inflammation-malnutrition syndrome, muscle cramps, and anemia. Worldwide efforts are focused on reducing hemodialysis complications to increase survival in these patients. In vitro and in vivo studies proved that vitamin E has many beneficial effects such as: decreases reactive oxygen species synthesis, improves antioxidant defense system, inhibits lipids peroxidation and reduces atherosclerosis, and ameliorates anemia treatment. Mechanisms of action are complex and not fully understood. However, there are particularities in regards of vitamin E intake, metabolism, and clearance in patients treated with hemodialysis. Supplementation of vitamin E in these patients has been intensively studied, and it is still under debate. Oral administration and vitamin E-coated membranes for dialysis have been tried. Clinical practice guidelines tried to underline when and how much vitamin E to be given to be safe and costbeneficial. The current chapter aims to synthesize all these issues.","PeriodicalId":23478,"journal":{"name":"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87372281","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}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.79445
Lisa Schmölz, Martin Schubert, S. Kluge, M. Birringer, MariaWallert, S. Lorkowski
Vitamin E is a lipophilic vitamin and thus is naturally occurring mainly in high-fat plant products such as oils, nuts, germs, seeds, and in lower amounts in vegetables and some fruits. The term “vitamin E” comprises different structures that are classified as tocopherols, tocotrienols, and “vitamin E-related structures.” Vitamin E follows the same route in the body like other lipophilic substances. In brief, vitamin E is absorbed in the intestine, packaged into chylomicrons together with other lipophilic molecules, and distributed via lymph and blood in the body. As the liver is the central organ in lipoprotein metabolism, it is also essential for the uptake, distribution, metabolism, and storage of vitamin E. Based on the current knowledge on that field, the physiological, nonphysiological, and pathophysiological factors influencing the hepatic handling of vitamin E, verifying the crucial role of the liver in vitamin E homeostasis, are described.
{"title":"The Hepatic Fate of Vitamin E","authors":"Lisa Schmölz, Martin Schubert, S. Kluge, M. Birringer, MariaWallert, S. Lorkowski","doi":"10.5772/INTECHOPEN.79445","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79445","url":null,"abstract":"Vitamin E is a lipophilic vitamin and thus is naturally occurring mainly in high-fat plant products such as oils, nuts, germs, seeds, and in lower amounts in vegetables and some fruits. The term “vitamin E” comprises different structures that are classified as tocopherols, tocotrienols, and “vitamin E-related structures.” Vitamin E follows the same route in the body like other lipophilic substances. In brief, vitamin E is absorbed in the intestine, packaged into chylomicrons together with other lipophilic molecules, and distributed via lymph and blood in the body. As the liver is the central organ in lipoprotein metabolism, it is also essential for the uptake, distribution, metabolism, and storage of vitamin E. Based on the current knowledge on that field, the physiological, nonphysiological, and pathophysiological factors influencing the hepatic handling of vitamin E, verifying the crucial role of the liver in vitamin E homeostasis, are described.","PeriodicalId":23478,"journal":{"name":"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects","volume":"219 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76602074","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}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.80954
M. Mileva, A. Galabov
Influenza is an infectious disease causing huge medical and economic losses. Influenza pathogenesis is associated with two processes in the human body: (i) lung damage due to viral replication in the columnar ciliary epithelium of bronchi and bronchioles and (ii) inflammatory burst inducing an increase in reactive oxygen species generation that causes extensive damage in cellular membranes of the small vessels. The oxidative stress in influenza virus-infected organism provokes free-radical oxidation of unsaturated lipid chains in the cell membranes. As vitamin E is a lipid-soluble substance and possesses a hydrophobic tail, it tends to accumulate within lipid membranes. There, it acts as the most important chain breaker, reacting with lipid peroxyl radicals much faster than they can react with adjacent fatty acid side chains. Among the antioxidants tested in influenza virus infections in mice, vitamin E occupies the leading position because of its efficacy in preventing oxidative damage through its free-radical scavenging activity. Although vitamin E is not possessing specific antiviral action, its antioxidant effect probably plays important role in lung and liver protection. Attention should be paid to the synergistic character of antiviral effect of the combination vitamin E and oseltamivir. Vitamin E could be recommended as a component in multitarget influenza therapy.
{"title":"Vitamin E and Influenza Virus Infection","authors":"M. Mileva, A. Galabov","doi":"10.5772/INTECHOPEN.80954","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.80954","url":null,"abstract":"Influenza is an infectious disease causing huge medical and economic losses. Influenza pathogenesis is associated with two processes in the human body: (i) lung damage due to viral replication in the columnar ciliary epithelium of bronchi and bronchioles and (ii) inflammatory burst inducing an increase in reactive oxygen species generation that causes extensive damage in cellular membranes of the small vessels. The oxidative stress in influenza virus-infected organism provokes free-radical oxidation of unsaturated lipid chains in the cell membranes. As vitamin E is a lipid-soluble substance and possesses a hydrophobic tail, it tends to accumulate within lipid membranes. There, it acts as the most important chain breaker, reacting with lipid peroxyl radicals much faster than they can react with adjacent fatty acid side chains. Among the antioxidants tested in influenza virus infections in mice, vitamin E occupies the leading position because of its efficacy in preventing oxidative damage through its free-radical scavenging activity. Although vitamin E is not possessing specific antiviral action, its antioxidant effect probably plays important role in lung and liver protection. Attention should be paid to the synergistic character of antiviral effect of the combination vitamin E and oseltamivir. Vitamin E could be recommended as a component in multitarget influenza therapy.","PeriodicalId":23478,"journal":{"name":"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects","volume":"111 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87035321","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}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.78273
R. Ahmed, P. Sylvester
γ-Tocotrienol, a natural isoform within the vitamin E family of compounds, displays potent antiproliferative, apoptotic and reversal of epithelial-to-mesenchymal transition (EMT) activity against breast cancer using treatment doses that have little or no effect on normal cell viability. EMT is a route by which epithelial cells undergo various biochemical alterations leading to the acquisition of mesenchymal traits. Several aberrant signaling pathways are involved in EMT-dependent cancer metastasis. Specifically, dysregulation of the canonical Wnt and Hedgehog pathways are intimately involved in promoting breast cancer EMT and metastasis. Therefore, studies were conducted to examine effects of γ-tocotrienol on Wnt and Hedgehog signaling. Results from these studies demon- strate that γ-tocotrienol significantly inhibits canonical Wnt and Hedgehog signaling by inhibiting receptors, co-receptors and ligand expression, as well as inhibiting expression of cytosolic and nuclear signaling proteins within these pathways. Additional studies showed that γ-tocotrienol treatment increased the expression of negative regulators of both the Wnt and Hedgehog pathways. These findings demonstrate that γ-tocotrienol reversal of EMT is mediated, at least in part, through the inhibition of canonical Wnt and Hedgehog signaling, and strongly suggest that this form of vitamin E may provide significant benefit in the prevention and treatment of metastatic breast cancer. and signal transduction. These findings provide evidence to explanation the wide range of inhibitory ligand, FZD7/LRP6 complex activation, DVL2 and cyclin D1 and a corresponding increase in Naked 1 level. Additionally, γ-tocotrienol inhibits Hedgehog signaling by decreasing the expression of Shh ligand, PTCH2, Smo, GSK3β, and Gli1 associated with a corresponding increase in SUFU levels. Several other cytosolic and nuclear proteins were minimized which can ultimately lead to a suppression in gene expression associated with EMT.
{"title":"γ-Tocotrienol Reversal of Epithelial-to-Mesenchymal Transition in Human Breast Cancer Cells is Mediated through a Suppression of Canonical Wnt and Hedgehog Signaling","authors":"R. Ahmed, P. Sylvester","doi":"10.5772/INTECHOPEN.78273","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78273","url":null,"abstract":"γ-Tocotrienol, a natural isoform within the vitamin E family of compounds, displays potent antiproliferative, apoptotic and reversal of epithelial-to-mesenchymal transition (EMT) activity against breast cancer using treatment doses that have little or no effect on normal cell viability. EMT is a route by which epithelial cells undergo various biochemical alterations leading to the acquisition of mesenchymal traits. Several aberrant signaling pathways are involved in EMT-dependent cancer metastasis. Specifically, dysregulation of the canonical Wnt and Hedgehog pathways are intimately involved in promoting breast cancer EMT and metastasis. Therefore, studies were conducted to examine effects of γ-tocotrienol on Wnt and Hedgehog signaling. Results from these studies demon- strate that γ-tocotrienol significantly inhibits canonical Wnt and Hedgehog signaling by inhibiting receptors, co-receptors and ligand expression, as well as inhibiting expression of cytosolic and nuclear signaling proteins within these pathways. Additional studies showed that γ-tocotrienol treatment increased the expression of negative regulators of both the Wnt and Hedgehog pathways. These findings demonstrate that γ-tocotrienol reversal of EMT is mediated, at least in part, through the inhibition of canonical Wnt and Hedgehog signaling, and strongly suggest that this form of vitamin E may provide significant benefit in the prevention and treatment of metastatic breast cancer. and signal transduction. These findings provide evidence to explanation the wide range of inhibitory ligand, FZD7/LRP6 complex activation, DVL2 and cyclin D1 and a corresponding increase in Naked 1 level. Additionally, γ-tocotrienol inhibits Hedgehog signaling by decreasing the expression of Shh ligand, PTCH2, Smo, GSK3β, and Gli1 associated with a corresponding increase in SUFU levels. Several other cytosolic and nuclear proteins were minimized which can ultimately lead to a suppression in gene expression associated with EMT.","PeriodicalId":23478,"journal":{"name":"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88930648","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}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.78642
J. J. G. Nava, P. Ambrósio, D. Dominguez
Carcinogenesis induced chemically produces mutations affecting standard cells ’ behavior. An electrophilicattackonDNA result as the primarycharacteristic.Once xenobiotics are adminis- trated to mammals they suffer a metabolic activation in the liver through cytochrome P450 (CYP450)enzymes,convertingthemtotoxiccompounds,generatingoxidativestress(OS),andburstingelectrophilesnearthesiteofoxidation.CYP450areelectroncarrierproteinsthat generate spin-correlated radical pair (RP) intermediaries. An extremely low-frequencyelectro- magnetic field (ELF-EMF) can modulate the spin-flip conversion between singlet and triplet spinstatesoftheRPpopulations,modifyingtheproductformationduringtheirmetabolization. Experimentally,weinducehepaticcancerchemically;wefoundthatELF-EMFinhibitsboththe number and area of preneoplastic lesions by more than 50%. Furthermore, theoretically, we develop a quantum mechanical model based on the RP mechanism (RPM) in the Haberkorn approximation to explain the cytoprotective effects of ELF-EMF. Here, we review the status of theaction ’ smechanismofELF-EMFonourresearchonearlyhepatocarcinogenesis.
{"title":"Cytoprotective Effect of 120 Hz Electromagnetic Fields on Early Hepatocarcinogenesis: Experimental and Theoretical Findings","authors":"J. J. G. Nava, P. Ambrósio, D. Dominguez","doi":"10.5772/INTECHOPEN.78642","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78642","url":null,"abstract":"Carcinogenesis induced chemically produces mutations affecting standard cells ’ behavior. An electrophilicattackonDNA result as the primarycharacteristic.Once xenobiotics are adminis- trated to mammals they suffer a metabolic activation in the liver through cytochrome P450 (CYP450)enzymes,convertingthemtotoxiccompounds,generatingoxidativestress(OS),andburstingelectrophilesnearthesiteofoxidation.CYP450areelectroncarrierproteinsthat generate spin-correlated radical pair (RP) intermediaries. An extremely low-frequencyelectro- magnetic field (ELF-EMF) can modulate the spin-flip conversion between singlet and triplet spinstatesoftheRPpopulations,modifyingtheproductformationduringtheirmetabolization. Experimentally,weinducehepaticcancerchemically;wefoundthatELF-EMFinhibitsboththe number and area of preneoplastic lesions by more than 50%. Furthermore, theoretically, we develop a quantum mechanical model based on the RP mechanism (RPM) in the Haberkorn approximation to explain the cytoprotective effects of ELF-EMF. Here, we review the status of theaction ’ smechanismofELF-EMFonourresearchonearlyhepatocarcinogenesis.","PeriodicalId":23478,"journal":{"name":"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83708901","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}
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