Pub Date : 2023-04-17DOI: 10.2174/1574885518666230417085251
P. Shah, Kesha Patel, K. Patel, V. Thakkar, Saloni Dalwadi, T. Gandhi, B. Bhavsar
Glaucoma is widely treated using eye drops, but around 95% of the drug is lost by the ocular barrier resulting in low bioavailability. The incorporation of polymeric nanoparticles into mucoadhesive polymer containing in situ gel is generally helpful in the retention of nanoparticles on the eye and improves the efficacy of the formulation. The objective of the present investigation has to develop polymeric brinzolamide (BRZ) nanoparticles laden with timolol maleate (TM) in situ gel formulation. The optimized BRZ nanoparticles were prepared using PLGA by nanoprecipitation technique utilizing 32 full factorial designs (FFD). Healthy New Zealand White Rabbit (250-300 g) was used for the pharmacokinetic and pharmacodynamic study. Design of the experiment was applied to optimize formulation and validate the model. Some evaluation parameters related to BRZ nanoparticles as well as in-situ gel, have been done. The results of FFD reveal that the optimized condition for drugs to polymer ratio (1:7) containing 0.98 %w/v for poloxamer 188 results in higher entrapment efficiency and drug release with 156.7 nm particle size. The in-situ gel formulation has been prepared using Gelrite (0.5%w/v), and HPMC K4M (0.5%w/v) shows acceptable results with sustained drug release up to 6±0.1 h. The rabbit model's in-vivo pharmacokinetics and pharmacodynamic data showed sustained release of drugs longer than the marketed formulation. The proposed formulation could successfully deliver therapeutic concentrations in the eye with prolonged resident time and serve as a potential alternative for the treatment of glaucoma.
{"title":"Exploring the Advance Data Mining tool for Optimization of Nanoparticles Laden in Situ Gel for Ocular Drug Delivery","authors":"P. Shah, Kesha Patel, K. Patel, V. Thakkar, Saloni Dalwadi, T. Gandhi, B. Bhavsar","doi":"10.2174/1574885518666230417085251","DOIUrl":"https://doi.org/10.2174/1574885518666230417085251","url":null,"abstract":"\u0000\u0000Glaucoma is widely treated using eye drops, but around 95% of the drug is lost by the ocular barrier resulting in low bioavailability. The incorporation of polymeric nanoparticles into mucoadhesive polymer containing in situ gel is generally helpful in the retention of nanoparticles on the eye and improves the efficacy of the formulation.\u0000\u0000\u0000\u0000The objective of the present investigation has to develop polymeric brinzolamide (BRZ) nanoparticles laden with timolol maleate (TM) in situ gel formulation.\u0000\u0000\u0000\u0000The optimized BRZ nanoparticles were prepared using PLGA by nanoprecipitation technique utilizing 32 full factorial designs (FFD). Healthy New Zealand White Rabbit (250-300 g) was used for the pharmacokinetic and pharmacodynamic study. Design of the experiment was applied to optimize formulation and validate the model. Some evaluation parameters related to BRZ nanoparticles as well as in-situ gel, have been done.\u0000\u0000\u0000\u0000The results of FFD reveal that the optimized condition for drugs to polymer ratio (1:7) containing 0.98 %w/v for poloxamer 188 results in higher entrapment efficiency and drug release with 156.7 nm particle size. The in-situ gel formulation has been prepared using Gelrite (0.5%w/v), and HPMC K4M (0.5%w/v) shows acceptable results with sustained drug release up to 6±0.1 h. The rabbit model's in-vivo pharmacokinetics and pharmacodynamic data showed sustained release of drugs longer than the marketed formulation.\u0000\u0000\u0000\u0000The proposed formulation could successfully deliver therapeutic concentrations in the eye with prolonged resident time and serve as a potential alternative for the treatment of glaucoma.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41768885","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 : 2023-04-03DOI: 10.2174/1574885518666230403111528
Y. Garedaghi, Y. Firouzivand, H. Hassanzadeh Khanmiri, A. Shabestari Asl
Fascioliasis is a worldwide parasitic infection caused by a food-borne trematode called Fasciola, and Fasciola infection has been reported in more than 80 countries. Recently, the WHO has presented a roadmap for overlooked diseases from 2021 to 2030, which aims to increase the prevention and control of overlooked different diseases such as Fascioliasis. Our main objective was to conduct a systematic review aiming to summarize recent knowledge on the Antiparasitic Compounds against Human Fascioliasis. A keyword search was performed in PubMed, Web of Science, to gather relevant literature published between the 17th of April 1992 and the 23rd October 2022. A total of 329 records were initially retrieved, with 28 full-text articles retained for the qualitative synthesis. Up to now, various antiparasitic drugs have been used to treat human fascioliasis, the most important of which are: Triclabendazole, Albendazole and Bithionol, Praziquantel, Emetine and Dehydroemetine, Mebendazole in combination with Metronidazole and Nitazoxanide, Chloroquine, Hexylresorcinol. From the past to the present, natural herbal medicines have traditionally been used in most countries to treat various parasitic diseases in humans and animals so that these are known as active anthelmintic phytochemicals such as Artemisinin, Mirazid, Plumbagin, Lycium chinense. Although Triclabendazole is an effective and useful drug of choice for the treatment of human fascioliasis, but due to the gradual resistance of fasciolas to Triclabendazole, further research is needed to find new drugs. Despite many advances in antiparasitic compounds used against human fascioliasis, a number of integrated control measures should be implemented as strong management strategies for fascioliasis.
筋膜吸虫病是一种由一种名为筋膜吸虫的食源性吸虫引起的全球性寄生虫感染，80多个国家报告了筋膜吸虫感染。最近，世卫组织提出了2021年至2030年被忽视疾病的路线图，旨在加强对被忽视的不同疾病的预防和控制，如筋膜病。我们的主要目标是进行系统综述，旨在总结抗人类筋膜病寄生虫化合物的最新知识。在PubMed，Web of Science中进行了关键词搜索，以收集1992年4月17日至2022年10月23日期间发表的相关文献。最初共检索到329条记录，保留了28篇全文文章用于定性综合。到目前为止，各种抗寄生虫药物已被用于治疗人筋膜炎，其中最重要的药物是：三氯苯达唑、阿苯达唑和硫醚醇、吡喹酮、埃美汀和脱氢吐梅汀、甲苯达唑联合甲硝唑和硝唑烷、氯喹、己基间苯二酚。从过去到现在，大多数国家传统上都使用天然草药来治疗人类和动物的各种寄生虫病，因此这些药物被称为活性驱虫植物化学物质，如青蒿素、Mirazid、Plumbagin、枸杞。尽管三卡班达唑是治疗人筋膜炎的有效药物，但由于筋膜炎对三卡班达唑的耐药性逐渐增强，还需要进一步研究以寻找新的药物。尽管在对抗人类筋膜炎的抗寄生虫化合物方面取得了许多进展，但应实施一些综合控制措施，作为筋膜炎的有力管理策略。
{"title":"A review of the most important Antiparasitic Compounds effective on Human Fascioliasis from the past until now","authors":"Y. Garedaghi, Y. Firouzivand, H. Hassanzadeh Khanmiri, A. Shabestari Asl","doi":"10.2174/1574885518666230403111528","DOIUrl":"https://doi.org/10.2174/1574885518666230403111528","url":null,"abstract":"\u0000\u0000Fascioliasis is a worldwide parasitic infection caused by a food-borne trematode called Fasciola, and Fasciola infection has been reported in more than 80 countries. Recently, the\u0000WHO has presented a roadmap for overlooked diseases from 2021 to 2030, which aims to increase\u0000the prevention and control of overlooked different diseases such as Fascioliasis.\u0000\u0000\u0000\u0000Our main objective was to conduct a systematic review aiming to summarize recent\u0000knowledge on the Antiparasitic Compounds against Human Fascioliasis. A keyword search was performed in PubMed, Web of Science, to gather relevant literature published between the 17th of April\u00001992 and the 23rd October 2022. A total of 329 records were initially retrieved, with 28 full-text articles retained for the qualitative synthesis.\u0000\u0000\u0000\u0000Up to now, various antiparasitic drugs have been used to treat human fascioliasis, the most\u0000important of which are: Triclabendazole, Albendazole and Bithionol, Praziquantel, Emetine and Dehydroemetine, Mebendazole in combination with Metronidazole and Nitazoxanide, Chloroquine,\u0000Hexylresorcinol. From the past to the present, natural herbal medicines have traditionally been used in\u0000most countries to treat various parasitic diseases in humans and animals so that these are known as active anthelmintic phytochemicals such as Artemisinin, Mirazid, Plumbagin, Lycium chinense.\u0000\u0000\u0000\u0000Although Triclabendazole is an effective and useful drug of choice for the treatment of\u0000human fascioliasis, but due to the gradual resistance of fasciolas to Triclabendazole, further research is\u0000needed to find new drugs. Despite many advances in antiparasitic compounds used against human\u0000fascioliasis, a number of integrated control measures should be implemented as strong management\u0000strategies for fascioliasis.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45745284","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 : 2023-04-03DOI: 10.2174/1574885518666230403111101
Sadegh Zarei, H. Gholami, R. Abbasalipourkabir, N. Ziamajidi, A. Divsalar, M. Saeidifar
The use of nanoparticle drug delivery systems to enhance the therapeutic efficacy and reduce the side effects of anticancer drugs is taken into consideration. Astaxanthin (ATX) is a natural xanthophyll carotenoid with antioxidant, anti-inflammatory, and antiapoptotic properties used to prevent and treat some cancers. The use of nanoparticle drug delivery systems to enhance the therapeutic efficacy and reduce the side effects of anti-cancer drugs is taken into consideration. Astaxanthin (ATX) is a natural xanthophyll carotenoid with antioxidant, anti-inflammatory, and anti-apoptotic properties that has been used in the prevention and treatment of some cancers. In the present study, the antioxidant effect of beta-lactoglobulin (β-LG) nanocapsules containing ATX and 5-fluorouracil (5-FU; the first-line therapy for colorectal cancer) on the antioxidant enzymes activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in HCT116 colorectal cancer cell line was examined. In the present study, the antioxidant effect of beta-lactoglobulin (β-LG) nanocapsules containing ATX and 5-fluorouracil (5-FU; the first-line therapy for colorectal cancer) on the antioxidant enzymes activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in HCT116 colorectal cancer cell line was examined. In this experimental study, HCT116 cells were treated with different treatments of encapsulation of ATX in β-LG, encapsulation 5-FU in β-LG, co-encapsulation of ATX and 5-FU in β-LG, free ATX, free 5-FU, free ATX and free 5-FU, or β-LG nanocapsules without drugs for 24, 48 and 72 hours. There is a control group in which HCT116 cells were not treated with any drug. Then, 50% inhibitory concentration (IC50) and cell viability were determined using an MTT assay. The antioxidant enzyme activity of SOD, CAT, and GPX was measured by a colorimetric method in HCT116 cells. In this experimental study, HCT116 cells were treated with different treatments of encapsulation of ATX in β-LG, encapsulation 5-FU in β-LG, co-encapsulation of ATX and 5-FU in β-LG, free ATX, free 5-FU, free ATX and free 5-FU, or β-LG nanocapsules without drugs for 24, 48 and 72 hours. There is a control group that HCT116 cells not treated with any drug. Then, 50% inhibitory concentration (IC50) and cell viability were determined using an MTT assay. The antioxidant enzyme activity of SOD, CAT and GPX was measured by colorimetric methods in HCT116 cells. Different treatments reduced the cell viability and increased apoptotic cells in a time-dependent manner, which was significant for beta-lactoglobulin nanocapsules treatment (P<0.05). It means receiving more 5-FU or ATX in the encapsulated form by HCT116 cells. The antioxidant enzyme activity of SOD, CAT, and GPX in HCT116 cells treated with beta-lactoglobulin nanocapsule treatment significantly increased compared to the control group (P<0.001). Moreover, the antioxidant activity of these enz
{"title":"The effect of beta-lactoglobulin nanocapsules containing astaxanthin and 5-fluorouracil on the antioxidant enzymes activity of superoxide dismutase, catalase and glutathione peroxidase in HCT116 colorectal cancer cell line","authors":"Sadegh Zarei, H. Gholami, R. Abbasalipourkabir, N. Ziamajidi, A. Divsalar, M. Saeidifar","doi":"10.2174/1574885518666230403111101","DOIUrl":"https://doi.org/10.2174/1574885518666230403111101","url":null,"abstract":"\u0000\u0000The use of nanoparticle drug delivery systems to enhance the therapeutic efficacy and reduce the side effects of anticancer drugs is taken into consideration. Astaxanthin (ATX) is a natural xanthophyll carotenoid with antioxidant, anti-inflammatory, and antiapoptotic properties used to prevent and treat some cancers.\u0000\u0000\u0000\u0000The use of nanoparticle drug delivery systems to enhance the therapeutic efficacy and reduce the side effects of anti-cancer drugs is taken into consideration. Astaxanthin (ATX) is a natural xanthophyll carotenoid with antioxidant, anti-inflammatory, and anti-apoptotic properties that has been used in the prevention and treatment of some cancers.\u0000\u0000\u0000\u0000In the present study, the antioxidant effect of beta-lactoglobulin (β-LG) nanocapsules containing ATX and 5-fluorouracil (5-FU; the first-line therapy for colorectal cancer) on the antioxidant enzymes activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in HCT116 colorectal cancer cell line was examined.\u0000\u0000\u0000\u0000In the present study, the antioxidant effect of beta-lactoglobulin (β-LG) nanocapsules containing ATX and 5-fluorouracil (5-FU; the first-line therapy for colorectal cancer) on the antioxidant enzymes activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in HCT116 colorectal cancer cell line was examined.\u0000\u0000\u0000\u0000In this experimental study, HCT116 cells were treated with different treatments of encapsulation of ATX in β-LG, encapsulation 5-FU in β-LG, co-encapsulation of ATX and 5-FU in β-LG, free ATX, free 5-FU, free ATX and free 5-FU, or β-LG nanocapsules without drugs for 24, 48 and 72 hours. There is a control group in which HCT116 cells were not treated with any drug. Then, 50% inhibitory concentration (IC50) and cell viability were determined using an MTT assay. The antioxidant enzyme activity of SOD, CAT, and GPX was measured by a colorimetric method in HCT116 cells.\u0000\u0000\u0000\u0000In this experimental study, HCT116 cells were treated with different treatments of encapsulation of ATX in β-LG, encapsulation 5-FU in β-LG, co-encapsulation of ATX and 5-FU in β-LG, free ATX, free 5-FU, free ATX and free 5-FU, or β-LG nanocapsules without drugs for 24, 48 and 72 hours. There is a control group that HCT116 cells not treated with any drug. Then, 50% inhibitory concentration (IC50) and cell viability were determined using an MTT assay. The antioxidant enzyme activity of SOD, CAT and GPX was measured by colorimetric methods in HCT116 cells.\u0000\u0000\u0000\u0000Different treatments reduced the cell viability and increased apoptotic cells in a time-dependent manner, which was significant for beta-lactoglobulin nanocapsules treatment (P<0.05). It means receiving more 5-FU or ATX in the encapsulated form by HCT116 cells. The antioxidant enzyme activity of SOD, CAT, and GPX in HCT116 cells treated with beta-lactoglobulin nanocapsule treatment significantly increased compared to the control group (P<0.001). Moreover, the antioxidant activity of these enz","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42431176","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 : 2023-03-31DOI: 10.2174/1574885518666230331084428
Chetna Modi, Ravina Kathota, Ayushi G. Patel, V. Thakkar, Hardik B. Rana
Febuxostat is a BCS class-II drug, used in the treatment of gout. However, because of its lower solubility, a higher and more frequent dose of the drug is required in the treatment. Febuxostat is a BCS class-II drug, used in the treatment of gout. Therapeutic window of Febuxostat is at site of stomach. But because of its lower solubility, higher and frequent dose of drug is required in the treatment. The objective of this research was to develop and evaluate febuxostat-loaded floating beads as a gastro-retentive drug delivery system (GRDDS) to target drug release up to 24hr in order to enhance bioavailability. The objective of this research was to develop and evaluate febuxostat loaded floating beads as Gastro-retentive drug delivery system (GRDDS) to target drug release up to 24hr in order of enhancement of bioavailability. Gastro-retentive floating beads were formulated using the ionotropic gelation method. Screening of lipids was carried out based on the shape and texture of floating beads. Drug-excipient compatibility study was done using DSC analysis. Further optimization of gastro-retentive floating beads of febuxostat was performed by Box-Behnken design using gelucire 43/01, lactose, and soluplus as independent variables and %drug entrapment and %drug release after 24 hr as dependent variables. Evaluation of the optimized batch was performed for in vitro buoyancy, %drug entrapment, %drug release, FTIR, and SEM study. Gastro-retentive floating beads were formulated using ionotropic gelation method. Screening of lipids was carried out on the basis of shape and texture of floating beads. Drug-excipient compatibility study was done using DSC analysis. Further optimization of gastro-retentive floating beads of febuxostat was done by Box-Behnken Design using Gelucire 43/01, lactose, soluplus as independent variables and %Drug entrapment and %drug release after 24 hr as dependent variables. Evaluation of optimized batch was performed for in vitro buoyancy, %drug entrapment, %drug release, FTIR and SEM study. In the ANOVA, contour plots, and 3D surface plots, the optimized batch showed 93.95±0.29 % drug entrapment and 88.14±0.58 % drug release after 24 hr with 98%±1% in-vitro buoyancy. Overlay plots and checkpoint batches were accompanied to confirm the optimization. Polynomial equations proved the positive effect of lipids on drug entrapment and drug release. SEM images explained porous and microstructures on beads. From the ANOVA table, Contour plots and 3D surface plots, Optimized batch showed 93.95±0.29 %drug entrapment, 88.14±0.58 % drug release after 24 hr, with 98%±1% in-vitro buoyancy. Overlay plot and check point batches were accompanied to confirm the optimization. Polynomial equations prove positive effect of lipid on drug entrapment and drug release. SEM images explained porous and micro structure on beads. In conclusion, gastro-retentive febuxostat floating beads were successfully developed and characterized
{"title":"Development and Characterization of Febuxostat loaded floating beads as Gastro-Retentive Drug Delivery System in the treatment of Gout: A Statistical Approach","authors":"Chetna Modi, Ravina Kathota, Ayushi G. Patel, V. Thakkar, Hardik B. Rana","doi":"10.2174/1574885518666230331084428","DOIUrl":"https://doi.org/10.2174/1574885518666230331084428","url":null,"abstract":"\u0000\u0000Febuxostat is a BCS class-II drug, used in the treatment of gout. However, because of its lower solubility, a higher and more frequent dose of the drug is required in the treatment.\u0000\u0000\u0000\u0000Febuxostat is a BCS class-II drug, used in the treatment of gout. Therapeutic window of Febuxostat is at site of stomach. But because of its lower solubility, higher and frequent dose of drug is required in the treatment.\u0000\u0000\u0000\u0000The objective of this research was to develop and evaluate febuxostat-loaded floating beads as a gastro-retentive drug delivery system (GRDDS) to target drug release up to 24hr in order to enhance bioavailability.\u0000\u0000\u0000\u0000The objective of this research was to develop and evaluate febuxostat loaded floating beads as Gastro-retentive drug delivery system (GRDDS) to target drug release up to 24hr in order of enhancement of bioavailability.\u0000\u0000\u0000\u0000Gastro-retentive floating beads were formulated using the ionotropic gelation method. Screening of lipids was carried out based on the shape and texture of floating beads. Drug-excipient compatibility study was done using DSC analysis. Further optimization of gastro-retentive floating beads of febuxostat was performed by Box-Behnken design using gelucire 43/01, lactose, and soluplus as independent variables and %drug entrapment and %drug release after 24 hr as dependent variables. Evaluation of the optimized batch was performed for in vitro buoyancy, %drug entrapment, %drug release, FTIR, and SEM study.\u0000\u0000\u0000\u0000Gastro-retentive floating beads were formulated using ionotropic gelation method. Screening of lipids was carried out on the basis of shape and texture of floating beads. Drug-excipient compatibility study was done using DSC analysis. Further optimization of gastro-retentive floating beads of febuxostat was done by Box-Behnken Design using Gelucire 43/01, lactose, soluplus as independent variables and %Drug entrapment and %drug release after 24 hr as dependent variables. Evaluation of optimized batch was performed for in vitro buoyancy, %drug entrapment, %drug release, FTIR and SEM study.\u0000\u0000\u0000\u0000In the ANOVA, contour plots, and 3D surface plots, the optimized batch showed 93.95±0.29 % drug entrapment and 88.14±0.58 % drug release after 24 hr with 98%±1% in-vitro buoyancy. Overlay plots and checkpoint batches were accompanied to confirm the optimization. Polynomial equations proved the positive effect of lipids on drug entrapment and drug release. SEM images explained porous and microstructures on beads.\u0000\u0000\u0000\u0000From the ANOVA table, Contour plots and 3D surface plots, Optimized batch showed 93.95±0.29 %drug entrapment, 88.14±0.58 % drug release after 24 hr, with 98%±1% in-vitro buoyancy. Overlay plot and check point batches were accompanied to confirm the optimization. Polynomial equations prove positive effect of lipid on drug entrapment and drug release. SEM images explained porous and micro structure on beads.\u0000\u0000\u0000\u0000In conclusion, gastro-retentive febuxostat floating beads were successfully developed and characterized ","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42598619","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 : 2023-03-30DOI: 10.2174/1574885518666230330162748
Rashmi Saxena Pal, Saranya Punniyakotti, K. Khera, Deepti Katiyar
Secondary metabolites of natural origin exhibit numerous pharmacological activities like anti-inflammatory and anti-oxidant effects. Lipid peroxidation is observed to be prevented by terminating free radical chains and chelating redox active metal ions. These properties of the secondary products can also aid in preventing carcinoma. Many traditional and emerging plants are blessed with plenty of unexplored phytometabolites, which contain the probability to carry huge anti-neoplastic potential. Acetogenins are anticancer compounds that kill tumor cells through a variety and series of developmental methods. They are very powerful apoptosis inducers and can regulate the exclusion of chemotherapy medicines from cancer cells. Chalcone is a pharmacologically active molecule that can be found in both natural and manufactured products. Marine species, which are also examples of naturally derived drug sources such as algae, sponges, tunicates, and bryozoans have emerged as important components of choice for the separation of novel anticancer drugs obtained from marine sources. Bacteria of marine origin are the source of new drug discoveries and therapeutic targets, which are being explored to unprecedented heights and they have proven to be sources of various medicinal agents such as antibiotics etc. Numerous secondary metabolites have been isolated from marine fungi, that were active biologically and unique structural and also therapeutically beneficial. So far, almost 1000 secondary metabolites have been found, the majority of which are exclusive to lichens. This mini-review aims for the discussion of different aspects related to the natural derivatives obtained from various sources, which play a pivotal role as anti-neoplastic agents.
{"title":"Miscellaneous naturally derived anticancer agents","authors":"Rashmi Saxena Pal, Saranya Punniyakotti, K. Khera, Deepti Katiyar","doi":"10.2174/1574885518666230330162748","DOIUrl":"https://doi.org/10.2174/1574885518666230330162748","url":null,"abstract":"\u0000\u0000Secondary metabolites of natural origin exhibit numerous pharmacological activities like anti-inflammatory and anti-oxidant effects. Lipid peroxidation is observed to be prevented by terminating free radical chains and chelating redox active metal ions. These properties of the secondary products can also aid in preventing carcinoma. Many traditional and emerging plants are blessed with plenty of unexplored phytometabolites, which contain the probability to carry huge anti-neoplastic potential. Acetogenins are anticancer compounds that kill tumor cells through a variety and series of developmental methods. They are very powerful apoptosis inducers and can regulate the exclusion of chemotherapy medicines from cancer cells. Chalcone is a pharmacologically active molecule that can be found in both natural and manufactured products. Marine species, which are also examples of naturally derived drug sources such as algae, sponges, tunicates, and bryozoans have emerged as important components of choice for the separation of novel anticancer drugs obtained from marine sources. Bacteria of marine origin are the source of new drug discoveries and therapeutic targets, which are being explored to unprecedented heights and they have proven to be sources of various medicinal agents such as antibiotics etc. Numerous secondary metabolites have been isolated from marine fungi, that were active biologically and unique structural and also therapeutically beneficial. So far, almost 1000 secondary metabolites have been found, the majority of which are exclusive to lichens. This mini-review aims for the discussion of different aspects related to the natural derivatives obtained from various sources, which play a pivotal role as anti-neoplastic agents.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46353388","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 : 2023-03-30DOI: 10.2174/1574885518666230330114431
L. Kothapalli, Komal Bhosale, Asha B. Thomas, Pooja Sawant
Skin pigmentation is one of the most serious problems in the adult population of all races. The underlying factors of skin pigmentation are excessive exposure to UV radiation, oxidative stress, and other provocative causes that cause melasma, black spots, and post-inflammatory hyperpigmentation. Hence, treating hyperpigmentation disorders is challenging. Skin pigmentation occurs as a process of melanin biosynthesis triggered by UV exposure. Tyrosinase, an enzyme that catalyzes the rate-confining step in melanogenesis, if inhibited, can cause skin hypopigmentation. This has evoked an interest in reviewing plant extracts/ phytoconstituents, which can serve the purpose of sun protection and treat hyperpigmentation, ensuring skin glow for a better quality of life. A literature search on Medline, PubMed, Embase, and Scopus databases was done using various keywords like hyperpigmentation, melasma, skin-lightening agents, and sunscreen. Sun protection products for canopy with photo-aging and skin pigmentation are recommended. Tyrosinase inhibitors are first-line topical medicines available as single or combined topical formulations. Hydroquinone, retinoids, corticosteroids, and kojic acid are clinically proven as exceptionally powerful. However, the adverse effects reported with these small molecules largely impact skin appearance, dermatitis, and exogenous ochronosis. Currently, there is a rising trend towards comfortable, fascinating, and well-endured skin depigmenting agents from natural products that might be utilized by a wide populace. This present study aimed at exploring plant and fruit extracts together with their active ingredients as potential multitargeted anti-hyperpigmentation agents with sunscreen properties, tyrosinase inhibition, and skin whitening effects.
{"title":"Potential of Herbal Extracts as Sunscreens and Antihyperpigmentation Treatment","authors":"L. Kothapalli, Komal Bhosale, Asha B. Thomas, Pooja Sawant","doi":"10.2174/1574885518666230330114431","DOIUrl":"https://doi.org/10.2174/1574885518666230330114431","url":null,"abstract":"\u0000\u0000Skin pigmentation is one of the most serious problems in the adult population of all races. The underlying factors of skin pigmentation are excessive exposure to UV radiation, oxidative stress, and other provocative causes that cause melasma, black spots, and post-inflammatory hyperpigmentation. Hence, treating hyperpigmentation disorders is challenging.\u0000\u0000\u0000\u0000Skin pigmentation occurs as a process of melanin biosynthesis triggered by UV exposure. Tyrosinase, an enzyme that catalyzes the rate-confining step in melanogenesis, if inhibited, can cause skin hypopigmentation. This has evoked an interest in reviewing plant extracts/ phytoconstituents, which can serve the purpose of sun protection and treat hyperpigmentation, ensuring skin glow for a better quality of life.\u0000\u0000\u0000\u0000A literature search on Medline, PubMed, Embase, and Scopus databases was done using various keywords like hyperpigmentation, melasma, skin-lightening agents, and sunscreen.\u0000\u0000\u0000\u0000Sun protection products for canopy with photo-aging and skin pigmentation are recommended. Tyrosinase inhibitors are first-line topical medicines available as single or combined topical formulations. Hydroquinone, retinoids, corticosteroids, and kojic acid are clinically proven as exceptionally powerful. However, the adverse effects reported with these small molecules largely impact skin appearance, dermatitis, and exogenous ochronosis. Currently, there is a rising trend towards comfortable, fascinating, and well-endured skin depigmenting agents from natural products that might be utilized by a wide populace.\u0000\u0000\u0000\u0000This present study aimed at exploring plant and fruit extracts together with their active ingredients as potential multitargeted anti-hyperpigmentation agents with sunscreen properties, tyrosinase inhibition, and skin whitening effects.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46267775","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 : 2023-03-28DOI: 10.2174/1574885518666230328150208
S. Dhir, R. Verma, S. Bhatt, Vandana Garg, R. Dutt
The green synthesis approach using plants for the formation of metal/metal oxide nanoparticles is biologically safe and environment-friendly as compared to various physical and chemical methods. Various phytoconstituents present in the plants such as phenols, flavonoids, alkaloids, tannins, and proteins act as a potential bioresource for the formation of metal/metal oxide nanoparticles. The most common metals/metal oxides used are silver (Ag), copper (Cu), zinc, iron and gold. Amongst the above, copper is a comparably cheap metal as compared to gold and silver. Copper oxide nanoparticles have diverse applications in various fields of therapeutics. This review provides insights regarding the bio-mediated synthesis of copper/copper oxide nanoparticles, factors affecting the synthesis, their characterization, and the biomedical applications mainly the antibacterial, antifungal, and anticancer activity. Still, more research is needed focusing on different ways to minimize toxicity and improve biological efficacy. Although many trials and research have already been conducted and it seems that the potential for developing copper and copper oxide nanoparticles as a future drug is very bright.
{"title":"Green Synthesis, Characterization, and Biomedical Applications of Copper and Copper Oxide Nanoparticles of Plant Origin","authors":"S. Dhir, R. Verma, S. Bhatt, Vandana Garg, R. Dutt","doi":"10.2174/1574885518666230328150208","DOIUrl":"https://doi.org/10.2174/1574885518666230328150208","url":null,"abstract":"\u0000\u0000The green synthesis approach using plants for the formation of metal/metal oxide nanoparticles is biologically safe and environment-friendly as compared to various physical and chemical methods. Various phytoconstituents present in the plants such as phenols, flavonoids, alkaloids, tannins, and proteins act as a potential bioresource for the formation of metal/metal oxide nanoparticles. The most common metals/metal oxides used are silver (Ag), copper (Cu), zinc, iron and gold. Amongst the above, copper is a comparably cheap metal as compared to gold and silver. Copper oxide nanoparticles have diverse applications in various fields of therapeutics. This review provides insights regarding the bio-mediated synthesis of copper/copper oxide nanoparticles, factors affecting the synthesis, their characterization, and the biomedical applications mainly the antibacterial, antifungal, and anticancer activity. Still, more research is needed focusing on different ways to minimize toxicity and improve biological efficacy. Although many trials and research have already been conducted and it seems that the potential for developing copper and copper oxide nanoparticles as a future drug is very bright.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49498052","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 : 2023-03-16DOI: 10.2174/1574885518666230316111902
S. Husain, Faiza Fathima, R. Parveen, M. Khan, Z. Malik, S. Mustafa, Sheersh Massey, Sayeed Ahmad
Saraca asoca (Ashoka, family; Caesalpiniaceae) is an indigenous sacred tree, native to India. It has been used in various traditional medicinal systems and is one such plant that is highly therapeutic but its use in disease management is underrated in today’s era and has lost its importance. This narrative review is written to provide the information on medicinal importance of S. asoca and the significance of S. asoca in various traditional medicinal systems Different databases were searched to gather information. Research articles, abstracts, and reviews are included in this review. Saraca asoca is known for its unique pharmacological role in treating various uterine complications, menstrual disorders, and bacterial infections, bleeding hemorrhoids, urinary and dermatological problems. The stem bark of the tree is the principal constituent for treating menorrhagia and genito-urinary disorders. The stem bark, leaves, and seeds of S. asoca are known to contain flavonoids, tannins, alkaloids, glycosides, polyphenolics, fatty acids, and saponins. The reported major phytoconstituents responsible for its therapeutic uses are epicatechin, procyanidin B2, lyoniside, nudiposide, catechin, leucocyanidin, and leucopelargonidin. Various pharmacological activities of this plant are discussed in this review. It has been proved that Saraca asoca possesses several pharmacological properties and is useful in treating various diseases. More studies on quality control, standardization, and clinical trials on S. asoca should be performed, so that this plant could be utilized as an effective anti-cancer drug which could be a promising source for the herbal and pharmaceutical industry
{"title":"Saraca Asoca: From Traditional Herb To Modern Drug As A Cure For Various Diseases","authors":"S. Husain, Faiza Fathima, R. Parveen, M. Khan, Z. Malik, S. Mustafa, Sheersh Massey, Sayeed Ahmad","doi":"10.2174/1574885518666230316111902","DOIUrl":"https://doi.org/10.2174/1574885518666230316111902","url":null,"abstract":"\u0000\u0000Saraca asoca (Ashoka, family; Caesalpiniaceae) is an indigenous sacred tree, native to India. It has been used in various traditional medicinal systems and is one such plant that is highly therapeutic but its use in disease management is underrated in today’s era and has lost its importance.\u0000\u0000\u0000\u0000This narrative review is written to provide the information on medicinal importance of S. asoca and the significance of S. asoca in various traditional medicinal systems\u0000\u0000\u0000\u0000Different databases were searched to gather information. Research articles, abstracts, and reviews are included in this review.\u0000\u0000\u0000\u0000Saraca asoca is known for its unique pharmacological role in treating various uterine complications, menstrual disorders, and bacterial infections, bleeding hemorrhoids, urinary and dermatological problems. The stem bark of the tree is the principal constituent for treating menorrhagia and genito-urinary disorders. The stem bark, leaves, and seeds of S. asoca are known to contain flavonoids, tannins, alkaloids, glycosides, polyphenolics, fatty acids, and saponins. The reported major phytoconstituents responsible for its therapeutic uses are epicatechin, procyanidin B2, lyoniside, nudiposide, catechin, leucocyanidin, and leucopelargonidin. Various pharmacological activities of this plant are discussed in this review.\u0000\u0000\u0000\u0000It has been proved that Saraca asoca possesses several pharmacological properties and is useful in treating various diseases. More studies on quality control, standardization, and clinical trials on S. asoca should be performed, so that this plant could be utilized as an effective anti-cancer drug which could be a promising source for the herbal and pharmaceutical industry\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44176750","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 : 2023-03-13DOI: 10.2174/1574885518666230313145936
Mohd Ashif Khan, Haya Majid, M. Masoom, Aakriti Garg
Sanfilippo syndrome, commonly known as mucopolysaccharidosis type III (MPS III), is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and spinal cord. It is caused by a deficiency of enzymes involved in the catabolism of glycosaminoglycan (GAG) and heparin sulfate (HS). Although Genistein has been presented as a potential therapeutic, its safety and efficacy for the treatment of Sanfilippo syndrome are not well established. This systematic review aims to evaluate the safety and efficacy of Genistein with a primary endpoint of providing an inference whether the medication is producing any improvements when administered in patients suffering from Sanfilippo syndrome. An intensive computerized literature search was performed according to PRISMA guidelines in major databases such as PubMed, ScienceDirect, Embase, Science Citation Index Expanded, The Cochrane Library, and Web of Science until 30 April 2022. Studies evaluating the efficacy and safety of genistein in patients with Sanfilippo Syndrome were included. The quality of the included studies was assessed using the New Castle Ottawa Scale. A total of 558 studies were identified in the initial search. After removing duplicates, 25 studies were screened based on title and abstract, of which 06 studies were included in this systematic review. Among them, 02 studies were of high quality and 04 studies were of moderate quality. After administration of genistein, a decrease in urinary GAG levels and HS levels was observed. Based on the limited evidence present in the literature, this systematic review suggests that genistein can be safely used to treat Sanfilippo syndrome as it lowers GAG levels. However, data on the long-term benefit profile of genistein and high-quality evidence are still needed as a conclusive result could not be withdrawn.
Sanfilippo综合征，通常被称为粘多糖病III型（MPS III），是一种罕见的常染色体隐性溶酶体储存病，主要影响大脑和脊髓。它是由参与糖胺聚糖（GAG）和硫酸肝素（HS）分解代谢的酶缺乏引起的。尽管Genistein已被认为是一种潜在的治疗方法，但其治疗Sanfilippo综合征的安全性和有效性尚不明确。这项系统综述旨在评估染料木黄酮的安全性和有效性，主要终点是推断该药物在桑菲利波综合征患者中使用时是否有任何改善。在2022年4月30日之前，根据PRISMA指南，在PubMed、ScienceDirect、Embase、Science Citation Index Expanded、The Cochrane Library和Web of Science等主要数据库中进行了密集的计算机化文献搜索。包括评价染料木黄酮治疗Sanfilippo综合征患者的疗效和安全性的研究。纳入研究的质量使用渥太华新城量表进行评估。在最初的搜索中，共确定了558项研究。删除重复项后，根据标题和摘要筛选了25项研究，其中06项研究被纳入本系统综述。其中，02项研究质量较高，04项研究质量中等。染料木素给药后，观察到尿GAG水平和HS水平下降。基于文献中有限的证据，这项系统综述表明，染料木黄酮可以安全地用于治疗Sanfilippo综合征，因为它可以降低GAG水平。然而，仍然需要关于染料木黄酮的长期效益状况的数据和高质量的证据，因为结论性的结果无法撤回。
{"title":"Safety and Efficacy of Genistein in Sanfilippo Syndrome - A Systematic Review","authors":"Mohd Ashif Khan, Haya Majid, M. Masoom, Aakriti Garg","doi":"10.2174/1574885518666230313145936","DOIUrl":"https://doi.org/10.2174/1574885518666230313145936","url":null,"abstract":"\u0000\u0000Sanfilippo syndrome, commonly known as mucopolysaccharidosis type III (MPS III), is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and spinal cord. It is caused by a deficiency of enzymes involved in the catabolism of glycosaminoglycan (GAG) and heparin sulfate (HS). Although Genistein has been presented as a potential therapeutic, its safety and efficacy for the treatment of Sanfilippo syndrome are not well established.\u0000\u0000\u0000\u0000This systematic review aims to evaluate the safety and efficacy of Genistein with a primary endpoint of providing an inference whether the medication is producing any improvements when administered in patients suffering from Sanfilippo syndrome.\u0000\u0000\u0000\u0000An intensive computerized literature search was performed according to PRISMA guidelines in major databases such as PubMed, ScienceDirect, Embase, Science Citation Index Expanded, The Cochrane Library, and Web of Science until 30 April 2022. Studies evaluating the efficacy and safety of genistein in patients with Sanfilippo Syndrome were included. The quality of the included studies was assessed using the New Castle Ottawa Scale.\u0000\u0000\u0000\u0000A total of 558 studies were identified in the initial search. After removing duplicates, 25 studies were screened based on title and abstract, of which 06 studies were included in this systematic review. Among them, 02 studies were of high quality and 04 studies were of moderate quality. After administration of genistein, a decrease in urinary GAG levels and HS levels was observed.\u0000\u0000\u0000\u0000Based on the limited evidence present in the literature, this systematic review suggests that genistein can be safely used to treat Sanfilippo syndrome as it lowers GAG levels. However, data on the long-term benefit profile of genistein and high-quality evidence are still needed as a conclusive result could not be withdrawn.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45386541","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 : 2023-02-28DOI: 10.2174/1574885518666230228120343
A. Asghari, Seyed Yaser Foroughi Ghomi, A. Mohammadbeigi, A. Ahmadi, S. Ahmadpour, M. Shakeri, S. Adeli, Jamshid Vafaei Manesh, Reihane Tabaraii, R. Shajari, M. Vahedian
The outbreak of acute respiratory syndrome with novel coronavirus 2019 (COVID-19) in December 2019 in Wuhan, China, caused a worldwide outbreak of the disease. To treat the disease, some drugs were identified and introduced that did not show a significant effect on the recovery of the disease. Due to the need to manage inpatient beds, this study was conducted to evaluate the effectiveness of Remdesivir in the treatment of outpatients with moderate to severe COVID-19. The present study was a retrospective cohort with a convenience sampling method. It was conducted by referring to the records of COVID-19 patients who were referred to the respiratory clinic of Shahid Beheshti Hospital as outpatients in the period from April to August 2021. This study was conducted on 263 COVID-19 patients with a mean age of 51.16±14.39 years from 19 and 90 years old. Data were collected through a researcher-made checklist and analyzed using SPSS 20. Kolmogorov-Smirnov test, paired t-test, and Mc Nemar's test were used to evaluate the data. The significance level was considered at the level of 0.05. Findings revealed that no clear correlation was found between hospitalization and death rate compared to other patients. In our study, the risk factors for severe COVID-19 did not affect the rate of hospitalization or death of patients.
{"title":"Evaluation of the Effectiveness of Remdesivir in the Treatment of COVID-19 Outpatients: A retrospective cohort study","authors":"A. Asghari, Seyed Yaser Foroughi Ghomi, A. Mohammadbeigi, A. Ahmadi, S. Ahmadpour, M. Shakeri, S. Adeli, Jamshid Vafaei Manesh, Reihane Tabaraii, R. Shajari, M. Vahedian","doi":"10.2174/1574885518666230228120343","DOIUrl":"https://doi.org/10.2174/1574885518666230228120343","url":null,"abstract":"\u0000\u0000The outbreak of acute respiratory syndrome with novel coronavirus 2019 (COVID-19) in December 2019 in Wuhan, China, caused a worldwide outbreak of the disease. To treat the disease, some drugs were identified and introduced that did not show a significant effect on the recovery of the disease. Due to the need to manage inpatient beds, this study was conducted to evaluate the effectiveness of Remdesivir in the treatment of outpatients with moderate to severe COVID-19.\u0000\u0000\u0000\u0000The present study was a retrospective cohort with a convenience sampling method. It was conducted by referring to the records of COVID-19 patients who were referred to the respiratory clinic of Shahid Beheshti Hospital as outpatients in the period from April to August 2021.\u0000\u0000\u0000\u0000This study was conducted on 263 COVID-19 patients with a mean age of 51.16±14.39 years from 19 and 90 years old. Data were collected through a researcher-made checklist and analyzed using SPSS 20. Kolmogorov-Smirnov test, paired t-test, and Mc Nemar's test were used to evaluate the data. The significance level was considered at the level of 0.05.\u0000\u0000\u0000\u0000Findings revealed that no clear correlation was found between hospitalization and death rate compared to other patients. In our study, the risk factors for severe COVID-19 did not affect the rate of hospitalization or death of patients.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46318273","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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