Pub Date : 2024-04-01Epub Date: 2024-05-06DOI: 10.4103/JAPTR.JAPTR_319_23
Aboutaleb Kousha, Gholamhassan Vaezi, Maryam Haji Ghasem Kashani, Vida Hojati
In this study, we delved into the hippocampal region to understand the effects of adipose stem cells (ADSCs) and rosemary extract (RE). Our main objective was to explore how these substances influence spatial memory, neurotrophins, and changes in antioxidant enzymes. Moreover, we meticulously investigated the impact of dopamine deficiency, a notable characteristic linked with Parkinson's disease (PD), on memory impairment. This study comprised five groups of Wistar rats - all male, all selected randomly. We labeled two of these gatherings "lesion" (L) and "sham" (SH). Each got injections in the bilateral form with 6 μg - one group getting saline, while another got 6-OHDA. From couple weeks before the neurotoxin injection to 8 weeks later on, our lesion cohort was treated with rosemary at a dosage rate of 50 mg/kg body weight - let's call it RE for simplicity sake. Moreover, there is also this other lot, designated as cell-transplanted lesion group or catchy exercise (CE) as we prefer to interpret them; they had cell transplants conducted exactly 7 days after receiving their respective injections. Bringing up the rear, we got a group treated with both cell transplant and rosemary (CE+R). We performed spatial memory tests at 4 weeks, then again at 8. At the end of eighth week, the brains were extracted for q-PCR, enzymatic and immunohistochemical studies. Turning our gaze toward a comparison between the CE+R and CE groups versus the L group, we spot an intriguing drop in escape latency time. There is also more time spent in quadrants. Digging deeper into this matter, the CE+R bunch unveiled a clear surge when it comes to the expression of four genes, namely NGF, BDNF, NT3, and NT4! This was notable especially while comparing with both R and even other fellows from its very own broader group - CE. In a bit complex bit related to enzyme activity now, there is some good news as well for those in favor of potent antioxidants such as GPx or SOD. CE + R group, showed a significant increase of GPX and SOD enzymes, compared to the SH and L groups, and a significant decrease of MDA activity as compared to other treated groups. A significant decrease of escape latency and increase of time in quadrant were observed in the CE+R and CE groups compared to L group. What's more, the levels of MDA in the CE+R group plummeted significantly when set up against the SH group. Wrapping things up, a definite downscale was observed in the density of GFAP-positive cells throughout different regions located within the hippocampus; this decline presented itself not solely in treatment groups but gripped onto those falling under SH as well, especially when compared to its comrade - the L group. Using ADSCs and taking RE orally have shown promising results in improving memory issues linked with PD.
在这项研究中,我们深入海马区,了解脂肪干细胞(ADSCs)和迷迭香提取物(RE)的作用。我们的主要目的是探索这些物质如何影响空间记忆、神经营养素和抗氧化酶的变化。此外,我们还仔细研究了多巴胺缺乏对记忆损伤的影响,多巴胺缺乏是帕金森病(PD)的一个显著特征。这项研究包括五组 Wistar 大鼠,均为雄性,随机挑选。我们将其中两组分别称为 "病变组"(L)和 "假组"(SH)。每组都接受了 6 μg 的双侧注射--一组注射生理盐水,另一组注射 6-OHDA。从注射神经毒素前几周到 8 周后,我们的病变组群接受了迷迭香治疗,剂量为 50 毫克/千克体重,为简单起见,我们称之为 RE。此外,还有另外一批人,我们称他们为细胞移植病变组(CE);他们在接受注射 7 天后进行了细胞移植。最后,我们得到了同时接受细胞移植和迷迭香治疗的一组(CE+R)。在第八周结束时,我们提取大脑进行q-PCR、酶学和免疫组化研究。将目光转向 CE+R 组和 CE 组与 L 组之间的比较,我们发现逃逸潜伏时间有了惊人的下降。在四象限中花费的时间也更长。深入研究发现,CE+R 组在 NGF、BDNF、NT3 和 NT4 这四种基因的表达方面明显激增!这一点在与 "R "和其他更广泛的群体--"CE"--相比时尤为明显。在与酶活性有关的复杂问题上,对于那些支持使用 GPx 或 SOD 等强效抗氧化剂的人来说,也有一些好消息。与 SH 组和 L 组相比,CE + R 组的 GPX 和 SOD 酶活性显著提高,与其他治疗组相比,MDA 活性显著降低。与 L 组相比,CE+R 组和 CE 组的逃逸潜伏期明显缩短,进入象限的时间明显增加。此外,与 SH 组相比,CE+R 组的 MDA 水平明显下降。总之,在海马内的不同区域观察到 GFAP 阳性细胞的密度明显下降;这种下降不仅出现在治疗组中,也出现在 SH 组中,尤其是与 L 组相比。使用 ADSCs 和口服 RE 在改善与帕金森病相关的记忆问题方面取得了可喜的成果。
{"title":"Simultaneous treatment with cells and rosemary extract ameliorates 6-OHDA-induced toxicity in the hippocampus of mice.","authors":"Aboutaleb Kousha, Gholamhassan Vaezi, Maryam Haji Ghasem Kashani, Vida Hojati","doi":"10.4103/JAPTR.JAPTR_319_23","DOIUrl":"10.4103/JAPTR.JAPTR_319_23","url":null,"abstract":"<p><p>In this study, we delved into the hippocampal region to understand the effects of adipose stem cells (ADSCs) and rosemary extract (RE). Our main objective was to explore how these substances influence spatial memory, neurotrophins, and changes in antioxidant enzymes. Moreover, we meticulously investigated the impact of dopamine deficiency, a notable characteristic linked with Parkinson's disease (PD), on memory impairment. This study comprised five groups of Wistar rats - all male, all selected randomly. We labeled two of these gatherings \"lesion\" (L) and \"sham\" (SH). Each got injections in the bilateral form with 6 μg - one group getting saline, while another got 6-OHDA. From couple weeks before the neurotoxin injection to 8 weeks later on, our lesion cohort was treated with rosemary at a dosage rate of 50 mg/kg body weight - let's call it RE for simplicity sake. Moreover, there is also this other lot, designated as cell-transplanted lesion group or catchy exercise (CE) as we prefer to interpret them; they had cell transplants conducted exactly 7 days after receiving their respective injections. Bringing up the rear, we got a group treated with both cell transplant and rosemary (CE+R). We performed spatial memory tests at 4 weeks, then again at 8. At the end of eighth week, the brains were extracted for q-PCR, enzymatic and immunohistochemical studies. Turning our gaze toward a comparison between the CE+R and CE groups versus the L group, we spot an intriguing drop in escape latency time. There is also more time spent in quadrants. Digging deeper into this matter, the CE+R bunch unveiled a clear surge when it comes to the expression of four genes, namely NGF, BDNF, NT3, and NT4! This was notable especially while comparing with both R and even other fellows from its very own broader group - CE. In a bit complex bit related to enzyme activity now, there is some good news as well for those in favor of potent antioxidants such as GPx or SOD. CE + R group, showed a significant increase of GPX and SOD enzymes, compared to the SH and L groups, and a significant decrease of MDA activity as compared to other treated groups. A significant decrease of escape latency and increase of time in quadrant were observed in the CE+R and CE groups compared to L group. What's more, the levels of MDA in the CE+R group plummeted significantly when set up against the SH group. Wrapping things up, a definite downscale was observed in the density of GFAP-positive cells throughout different regions located within the hippocampus; this decline presented itself not solely in treatment groups but gripped onto those falling under SH as well, especially when compared to its comrade - the L group. Using ADSCs and taking RE orally have shown promising results in improving memory issues linked with PD.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We developed innovative self-amplifying mRNA (sa-mRNA) vaccine based on the derivative of S and Nsp3 proteins, which are considered crucial adhering to human host cells. We performed B-cell, Major histocompatibility complex (MHC) I, and II epitope which were merged with the KK and GPGPG linker. We also incorporated 5' cap sequence, Kozak sequence, replicase sequence, 3'/5' UTR, and poly A tail within the vaccine structure. The vaccine structure was subsequently docked and run the molecular dynamic simulation with TLR7 molecules. As the results of immune response simulation, the immune response was accelerated drastically up to >10-fold for immunoglobulin, interferon-γ, interleukin-2, immunoglobulin M (IgM) + immunoglobulin G (IgG) isotype, IgM isotype, and IgG1 isotype in secondary and tertiary dose, whereas natural killer cells, macrophages, and dendritic cells showed relatively high concentrations after the first dose. As our finding, the IgM + IgG, IgG1 + IgG2, and IgM level (induced by sa-mRNA vaccine) ensued three times with two-fold increase in days 25, and 50, then decreased after days 70-150. However, 150-350 days demonstrated constantly in the range of 20,000-21,000.
我们开发了基于 S 和 Nsp3 蛋白衍生物的创新型自扩增 mRNA(sa-mRNA)疫苗。我们将 B 细胞、主要组织相容性复合体(MHC)I 和 II 表位与 KK 和 GPGPG 连接器合并。我们还在疫苗结构中加入了 5' cap 序列、Kozak 序列、复制酶序列、3'/5' UTR 和 poly A 尾部。随后,我们将疫苗结构与 TLR7 分子对接并进行分子动力学模拟。免疫反应模拟结果显示,免疫球蛋白、干扰素-γ、白细胞介素-2、免疫球蛋白M(IgM)+免疫球蛋白G(IgG)同种型、IgM同种型和IgG1同种型的免疫反应在第二和第三剂量时急剧加速,最高可达10倍以上,而自然杀伤细胞、巨噬细胞和树突状细胞在第一剂量后表现出相对较高的浓度。根据我们的研究结果,IgM + IgG、IgG1 + IgG2 和 IgM 水平(由 sa-mRNA 疫苗诱导)随之出现了三次变化,在第 25 和 50 天增加了两倍,然后在第 70-150 天后下降。然而,在 150-350 天内,IgG 水平一直在 20,000-21,000 之间。
{"title":"Immunoinformatic of novel self-amplifying mRNA vaccine lipid nanoparticle against SARS-CoV-2.","authors":"Turmidzi Fath, Endang Winiati Bachtiar, Gulimiran Alitongbieke, Yutian Pan, Yuanqing Hu, Retno Widowati","doi":"10.4103/JAPTR.JAPTR_424_23","DOIUrl":"10.4103/JAPTR.JAPTR_424_23","url":null,"abstract":"<p><p>We developed innovative self-amplifying mRNA (sa-mRNA) vaccine based on the derivative of S and Nsp3 proteins, which are considered crucial adhering to human host cells. We performed B-cell, Major histocompatibility complex (MHC) I, and II epitope which were merged with the KK and GPGPG linker. We also incorporated 5' cap sequence, Kozak sequence, replicase sequence, 3'/5' UTR, and poly A tail within the vaccine structure. The vaccine structure was subsequently docked and run the molecular dynamic simulation with TLR7 molecules. As the results of immune response simulation, the immune response was accelerated drastically up to >10-fold for immunoglobulin, interferon-γ, interleukin-2, immunoglobulin M (IgM) + immunoglobulin G (IgG) isotype, IgM isotype, and IgG1 isotype in secondary and tertiary dose, whereas natural killer cells, macrophages, and dendritic cells showed relatively high concentrations after the first dose. As our finding, the IgM + IgG, IgG1 + IgG2, and IgM level (induced by sa-mRNA vaccine) ensued three times with two-fold increase in days 25, and 50, then decreased after days 70-150. However, 150-350 days demonstrated constantly in the range of 20,000-21,000.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Herbal products in dentistry have grown significantly. In the current scenario, herbal products are believed to be an effective adjunct to other medications. The present study aims to evaluate Eucalyptus oil and miswak (Salvadora persica) toothpaste for its efficacy in observable reduction in plaque and gingival bleeding. Sixty participants with gingivitis were enrolled in the present study. The study included an interim period (washout) comparing miswak and Eucalyptus toothpaste. Plaque scores were measured at designated time intervals. Both herbal toothpastes significantly decreased plaque index. Nevertheless, with relation to miswak (P = 0.002), Eucalyptus oil-based toothpaste exhibited reduction in bleeding scores. When participants were asked to return to their routine toothpaste, no changes were observed. Results from the study showed that the toothpaste containing Eucalyptus showed a significant decrease in gingival bleeding. More investigations should be looked on the medicinal applications of Eucalyptus toothpaste on commonly seen periodontal parameters.
{"title":"Efficacy of a <i>Eucalyptus</i> oil-based dentifrice in reducing plaque and gingival bleeding scores - A randomized clinical crossover study.","authors":"Fatema Alzahraa Osman, Leen Abdulghani Sarhan, Nirmeen Elhussein Eladl, Vijay Desai, Jayaraj Narayanan, Lakshmi Thangavelu, Sudhir Rama Varma","doi":"10.4103/JAPTR.JAPTR_103_23","DOIUrl":"10.4103/JAPTR.JAPTR_103_23","url":null,"abstract":"<p><p>Herbal products in dentistry have grown significantly. In the current scenario, herbal products are believed to be an effective adjunct to other medications. The present study aims to evaluate <i>Eucalyptus</i> oil and miswak (Salvadora persica) toothpaste for its efficacy in observable reduction in plaque and gingival bleeding. Sixty participants with gingivitis were enrolled in the present study. The study included an interim period (washout) comparing miswak and <i>Eucalyptus</i> toothpaste. Plaque scores were measured at designated time intervals. Both herbal toothpastes significantly decreased plaque index. Nevertheless, with relation to miswak (<i>P</i> = 0.002), <i>Eucalyptus</i> oil-based toothpaste exhibited reduction in bleeding scores. When participants were asked to return to their routine toothpaste, no changes were observed. Results from the study showed that the toothpaste containing <i>Eucalyptus</i> showed a significant decrease in gingival bleeding. More investigations should be looked on the medicinal applications of <i>Eucalyptus</i> toothpaste on commonly seen periodontal parameters.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-15DOI: 10.4103/JAPTR.JAPTR_343_23
Lina AlTamimi, Zainab Z Zakaraya, Mohammad Hailat, Mousa N Ahmad, Nidal A Qinna, Mohammed F Hamad, Wael Abu Dayyih
Type 2 diabetes is common globally. Pioglitazone (PGZ) is an oral TZD antidiabetic, whereas chromium-picolinate (Cr-PL) and Cr-glucose tolerance factor (Cr-GTF) are useful type 2 diabetes mellitus (T2DM) supplements. Cr-PL/GTF antioxidants cure T2DM. They may fail in diabetes with or without insulin-sensitizing medications. It examined how Cr-PL, Cr-GTF, PGZ, and their combination affected glucose, glycosylated hemoglobin, insulin, and HOMA-IR. Sixty-three adult Sprague-Dawley rats (220-300 g) were selected, and nine rats were randomly assigned to a normal nondiabetic group. In contrast, 54 rats were randomly split into 9 rats per each of the 6 major groups and injected intraperitoneally with 40 mg/kg STZ to induce T2DM. Rats were administered PGZ = 0.65 mg/kg (rat weight)/day, Cr-PL = 1 mg/kg, Cr-GTF = 1 mg/kg, and their combinations (PGZ + Cr-PL and Cr-GTF) daily for 6 weeks per intervention. The PGZ + Cr-PL and PGZ + Cr-GTF groups had substantially lower insulin levels than the PGZ group (13.38 ± 0.06, 12.98 ± 0.19 vs. 14.11 ± 0.02, respectively), with the PGZ + Cr-GTF group having the lowest insulin levels (12.98 ± 0.19 vs. 14.11 ± 0.02, 13.38±0.06, respectively). Intervention substantially reduced HOMA-IR in the PZ + Cr-PL and PZ + Cr-GTF groups compared to PGZ (7.49 ± 0.04, 6.69 ± 0.11 vs. 8.37 ± 0.04, respectively). This research found that combining PGZ with Cr-GTF resulted in considerably lower HOMA-IR levels than the PGZ and Cr-PL groups (6.69 ± 0.11 vs. 8.37 ± 0.04, 7.49 ± 0.04, respectively). Both Cr-PL and Cr-GTF may control T2DM. Both Cr complexes improved T2DM biomarkers more than the control diabetic group without medication. PGZ alone and PGZ + Cr-PL had less pharmacological synergy than Cr-GTF and PGZ in altering insulin and HOMA-IR blood levels. These encouraging discoveries need more study.
{"title":"Test of insulin resistance in nondiabetic and streptozotocin-induced diabetic rats using glycosylated hemoglobin test and other interventions.","authors":"Lina AlTamimi, Zainab Z Zakaraya, Mohammad Hailat, Mousa N Ahmad, Nidal A Qinna, Mohammed F Hamad, Wael Abu Dayyih","doi":"10.4103/JAPTR.JAPTR_343_23","DOIUrl":"10.4103/JAPTR.JAPTR_343_23","url":null,"abstract":"<p><p>Type 2 diabetes is common globally. Pioglitazone (PGZ) is an oral TZD antidiabetic, whereas chromium-picolinate (Cr-PL) and Cr-glucose tolerance factor (Cr-GTF) are useful type 2 diabetes mellitus (T2DM) supplements. Cr-PL/GTF antioxidants cure T2DM. They may fail in diabetes with or without insulin-sensitizing medications. It examined how Cr-PL, Cr-GTF, PGZ, and their combination affected glucose, glycosylated hemoglobin, insulin, and HOMA-IR. Sixty-three adult Sprague-Dawley rats (220-300 g) were selected, and nine rats were randomly assigned to a normal nondiabetic group. In contrast, 54 rats were randomly split into 9 rats per each of the 6 major groups and injected intraperitoneally with 40 mg/kg STZ to induce T2DM. Rats were administered PGZ = 0.65 mg/kg (rat weight)/day, Cr-PL = 1 mg/kg, Cr-GTF = 1 mg/kg, and their combinations (PGZ + Cr-PL and Cr-GTF) daily for 6 weeks per intervention. The PGZ + Cr-PL and PGZ + Cr-GTF groups had substantially lower insulin levels than the PGZ group (13.38 ± 0.06, 12.98 ± 0.19 vs. 14.11 ± 0.02, respectively), with the PGZ + Cr-GTF group having the lowest insulin levels (12.98 ± 0.19 vs. 14.11 ± 0.02, 13.38±0.06, respectively). Intervention substantially reduced HOMA-IR in the PZ + Cr-PL and PZ + Cr-GTF groups compared to PGZ (7.49 ± 0.04, 6.69 ± 0.11 vs. 8.37 ± 0.04, respectively). This research found that combining PGZ with Cr-GTF resulted in considerably lower HOMA-IR levels than the PGZ and Cr-PL groups (6.69 ± 0.11 vs. 8.37 ± 0.04, 7.49 ± 0.04, respectively). Both Cr-PL and Cr-GTF may control T2DM. Both Cr complexes improved T2DM biomarkers more than the control diabetic group without medication. PGZ alone and PGZ + Cr-PL had less pharmacological synergy than Cr-GTF and PGZ in altering insulin and HOMA-IR blood levels. These encouraging discoveries need more study.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-15DOI: 10.4103/JAPTR.JAPTR_334_23
Roihatul Mutiah, Ermin Rachmawati
Chemotherapy application in lung cancer patients has several side effects and shows lower effectiveness due to chemoresistance. Although Eleutherine bulbosa (Mill.) Urb. (EBE) elicit anticancer properties, yet the exact profile of its active compounds and lung cancer inhibition mechanisms were not fully understood. This study aimed to identify suggestive compounds from EBE extract and explain the molecular mechanisms of EBE against lung cancer. Identification of the compound from the EBE extract was confirmed using liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). The bioavailability profile of three major metabolites was identified using absorption, distribution, metabolism, excretion, toxicity software. The anticancer molecular mechanism prediction of the drugs was ascertained by network pharmacology using Cytoscape 3.9.1 and the protein-protein interaction network technique with STRING 11.0. Interaction between resveratrol and extracellular growth factor receptor (EGFR) was analyzed using site-specific molecular docking with erlotinib as the control using PyRx Autodock Vina 9.0 and BIOVIA Discovery Studio. A total of 16 active compounds were identified from LC-MS/MS. Only resveratrol showed anticancer properties by its interaction with 13 genes and 6 signaling pathways related to lung cancer. The molecular docking result supports the network pharmacology finding. The binding affinity of resveratrol with EGFR, important receptor in lung cancer, was more negative (-6.9 kcal/mol) than erlotinib (-6.2 kcal/mol) as the control. Evidence suggested that resveratrol in EBE exhibits anticancer effects by modulating lung cancer cell proliferation and apoptosis through EGFR binding.
{"title":"Exploring the anticancer potential of <i>Eleutherine bulbosa</i>: A systematic network pharmacology study on lung cancer.","authors":"Roihatul Mutiah, Ermin Rachmawati","doi":"10.4103/JAPTR.JAPTR_334_23","DOIUrl":"10.4103/JAPTR.JAPTR_334_23","url":null,"abstract":"<p><p>Chemotherapy application in lung cancer patients has several side effects and shows lower effectiveness due to chemoresistance. Although <i>Eleutherine bulbosa</i> (Mill.) Urb. (EBE) elicit anticancer properties, yet the exact profile of its active compounds and lung cancer inhibition mechanisms were not fully understood. This study aimed to identify suggestive compounds from EBE extract and explain the molecular mechanisms of EBE against lung cancer. Identification of the compound from the EBE extract was confirmed using liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). The bioavailability profile of three major metabolites was identified using absorption, distribution, metabolism, excretion, toxicity software. The anticancer molecular mechanism prediction of the drugs was ascertained by network pharmacology using Cytoscape 3.9.1 and the protein-protein interaction network technique with STRING 11.0. Interaction between resveratrol and extracellular growth factor receptor (EGFR) was analyzed using site-specific molecular docking with erlotinib as the control using PyRx Autodock Vina 9.0 and BIOVIA Discovery Studio. A total of 16 active compounds were identified from LC-MS/MS. Only resveratrol showed anticancer properties by its interaction with 13 genes and 6 signaling pathways related to lung cancer. The molecular docking result supports the network pharmacology finding. The binding affinity of resveratrol with EGFR, important receptor in lung cancer, was more negative (-6.9 kcal/mol) than erlotinib (-6.2 kcal/mol) as the control. Evidence suggested that resveratrol in EBE exhibits anticancer effects by modulating lung cancer cell proliferation and apoptosis through EGFR binding.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139935129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-15DOI: 10.4103/japtr.japtr_377_23
Kahtan Jassim Hasson
Sevoflurane, also called fluoromethyl ether, is an inhalation anesthetic agent used to initiate and maintain general anesthesia for adults and pediatric patients during surgical procedures. Several analytical methods have previously been applied to follow the properties and quality of sevoflurane, including mass spectrometry and gas chromatography methods. These methods are practically tedious and need sophisticated apparatus. In the present work, an attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometric method was used for the quantitative determination of sevoflurane which is characterized as a fast, accurate, and available technique for most pharmaceutical laboratories, besides the gas chromatographic method which is the most suitable for the detection of impurities. Sevoflurane is a liquid and it is applied directly on the glass top of the ATR-FTIR either as a concentrated solution or diluted with hexane as a diluent, which did not interfere with sample determination within the specified wavelength range of the IR spectrum, particularly the wavelength of the ethereal group at 1200 cm-1. This method can be applied to the identification test and quantitative assay of sevoflurane since it is validated for the precision, accuracy, reproducibility, and specificity in the analysis of sevoflurane as a pharmaceutical product. However, still, there is a need for a gas chromatographic method to detect the impurities and degradation products during the stability study of sevoflurane.
{"title":"Stability study and development of the validated infrared spectrometric method for quantitative analysis of sevoflurane compared with the gas chromatographic method.","authors":"Kahtan Jassim Hasson","doi":"10.4103/japtr.japtr_377_23","DOIUrl":"10.4103/japtr.japtr_377_23","url":null,"abstract":"<p><p>Sevoflurane, also called fluoromethyl ether, is an inhalation anesthetic agent used to initiate and maintain general anesthesia for adults and pediatric patients during surgical procedures. Several analytical methods have previously been applied to follow the properties and quality of sevoflurane, including mass spectrometry and gas chromatography methods. These methods are practically tedious and need sophisticated apparatus. In the present work, an attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometric method was used for the quantitative determination of sevoflurane which is characterized as a fast, accurate, and available technique for most pharmaceutical laboratories, besides the gas chromatographic method which is the most suitable for the detection of impurities. Sevoflurane is a liquid and it is applied directly on the glass top of the ATR-FTIR either as a concentrated solution or diluted with hexane as a diluent, which did not interfere with sample determination within the specified wavelength range of the IR spectrum, particularly the wavelength of the ethereal group at 1200 cm<sup>-1</sup>. This method can be applied to the identification test and quantitative assay of sevoflurane since it is validated for the precision, accuracy, reproducibility, and specificity in the analysis of sevoflurane as a pharmaceutical product. However, still, there is a need for a gas chromatographic method to detect the impurities and degradation products during the stability study of sevoflurane.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139935130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luteolin exhibited antibacterial activity against Escherichia coli and its chemical structure similar to that of ciprofloxacin (CPF) which works by inhibiting DNA gyrase. Filtrate from passion fruit extract containing luteolin and its derivatives could inhibit extended-spectrum β-lactamase (ESBL)-producing E. coli. Antibacterial compounds that can also inhibit ESBL will be valuable compounds to overcome the problem of resistant bacteria. This study aimed to ensure the potency of luteolin and luteolin derivatives targeting DNA gyrase and ESBL by in silico approach. Docking simulation of ligands L1-L14 was performed using AutoDock Vina, and pharmacokinetics and toxicity (absorption, distribution, metabolism, excretion, and toxicity) profiles were predicted by pKCSM online. The docking result revealed higher binding affinity on DNA gyrase (PDB.1KZN) of 12 luteolin derivatives (energy <-7.6 kcal/mol) compared to CPF and higher affinity (energy <-6.27 kcal/mol) of all compounds than clavulanic acid against ESBL CTX-M-15 (PDB.4HBU). The compounds could be absorbed through the human intestine moderately, which showed low permeability to blood-brain barrier, nontoxic and nonhepatotoxic. The most active luteolin glycoside (L6) is capable to inhibit DNA gyrase and ESBL from E. coli which provided the potential against resistant bacteria and was promoted as lead compounds to be developed further.
木犀草素对大肠杆菌具有抗菌活性,其化学结构与环丙沙星(CPF)相似,后者通过抑制 DNA 回旋酶发挥作用。含有木犀草素及其衍生物的百香果提取物滤液可抑制广谱β-内酰胺酶(ESBL)产生的大肠杆菌。同时能抑制 ESBL 的抗菌化合物将是克服耐药菌问题的重要化合物。本研究旨在通过硅学方法确保木犀草素和木犀草素衍生物针对DNA回旋酶和ESBL的有效性。利用 AutoDock Vina 对配体 L1-L14 进行了对接模拟,并利用 pKCSM 在线预测了药代动力学和毒性(吸收、分布、代谢、排泄和毒性)曲线。对接结果表明,12 种木犀草素衍生物对 DNA 回旋酶(PDB.1KZN)具有更高的结合亲和力,具有抗大肠杆菌的潜力,被作为先导化合物进一步开发。
{"title":"<i>In silico</i> analysis of luteolin derivatives as antibacterial agents targeting DNA gyrase and CTX-M-15 extended-spectrum β-lactamase of <i>Escherichia coli</i>.","authors":"Nuzul Wahyuning Diyah, Dwi Ayu Indriani, Rachma Dessidianti, Siswandono Siswandono","doi":"10.4103/JAPTR.JAPTR_217_23","DOIUrl":"10.4103/JAPTR.JAPTR_217_23","url":null,"abstract":"<p><p>Luteolin exhibited antibacterial activity against <i>Escherichia coli</i> and its chemical structure similar to that of ciprofloxacin (CPF) which works by inhibiting DNA gyrase. Filtrate from passion fruit extract containing luteolin and its derivatives could inhibit extended-spectrum β-lactamase (ESBL)-producing <i>E</i>. <i>coli</i>. Antibacterial compounds that can also inhibit ESBL will be valuable compounds to overcome the problem of resistant bacteria. This study aimed to ensure the potency of luteolin and luteolin derivatives targeting DNA gyrase and ESBL by <i>in silico</i> approach. Docking simulation of ligands L1-L14 was performed using AutoDock Vina, and pharmacokinetics and toxicity (absorption, distribution, metabolism, excretion, and toxicity) profiles were predicted by pKCSM online. The docking result revealed higher binding affinity on DNA gyrase (PDB.1KZN) of 12 luteolin derivatives (energy <-7.6 kcal/mol) compared to CPF and higher affinity (energy <-6.27 kcal/mol) of all compounds than clavulanic acid against ESBL CTX-M-15 (PDB.4HBU). The compounds could be absorbed through the human intestine moderately, which showed low permeability to blood-brain barrier, nontoxic and nonhepatotoxic. The most active luteolin glycoside (L6) is capable to inhibit DNA gyrase and ESBL from <i>E. coli</i> which provided the potential against resistant bacteria and was promoted as lead compounds to be developed further.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-15DOI: 10.4103/japtr.japtr_279_23
Ahmed Mohammed Salman, Esmaeil Babaei, Ahmed Salim Kadhim Al-Khafaji
The major mortality factor for women globally is breast cancer, and current treatments have several adverse effects. Hesperetin (HSP) is a flavone that occurs naturally with anti-tumor capabilities and has been investigated as a potential treatment for cancer. This study aimed to investigate the cytotoxic and anti-malignant potential of HSP on breast cancer cells (BT-474) and normal cells (MCF-10a). The results indicated that HSP has dose-dependent cytotoxicity in BT-474 and MCF-10a cells. The elevated concentration of HSP lowered cell viability and proliferation. The half-maximal inhibitory concentration (IC50) of HSP in BT-474 cancer cells after a 48-h exposure was 279.2 μM/ml, while the IC50 in normal cells was 855.4 μM/ml. The cytotoxicity of HSP was more significant in cancer cell lines than in normal cell lines and this aspect presents a favorable factor in utilizing the drug for the treatment of breast cancer. The apoptotic effect of HSP in BT-474 cells was investigated, and it was found that the higher the concentration of HSP more the cells underwent apoptosis. Furthermore, the highest concentration of HSP led to overexpression of the MLH1 and MSH2 genes in both breast cancer and normal cell lines. Overall, our study suggests that HSP has an anticancer effect on breast cancer cell lines, and the effect is concentration dependent.
{"title":"Exploring the modulation of MLH1 and MSH2 gene expression in hesperetin-treated breast cancer cells (BT-474).","authors":"Ahmed Mohammed Salman, Esmaeil Babaei, Ahmed Salim Kadhim Al-Khafaji","doi":"10.4103/japtr.japtr_279_23","DOIUrl":"10.4103/japtr.japtr_279_23","url":null,"abstract":"<p><p>The major mortality factor for women globally is breast cancer, and current treatments have several adverse effects. Hesperetin (HSP) is a flavone that occurs naturally with anti-tumor capabilities and has been investigated as a potential treatment for cancer. This study aimed to investigate the cytotoxic and anti-malignant potential of HSP on breast cancer cells (BT-474) and normal cells (MCF-10a). The results indicated that HSP has dose-dependent cytotoxicity in BT-474 and MCF-10a cells. The elevated concentration of HSP lowered cell viability and proliferation. The half-maximal inhibitory concentration (IC<sub>50</sub>) of HSP in BT-474 cancer cells after a 48-h exposure was 279.2 μM/ml, while the IC<sub>50</sub> in normal cells was 855.4 μM/ml. The cytotoxicity of HSP was more significant in cancer cell lines than in normal cell lines and this aspect presents a favorable factor in utilizing the drug for the treatment of breast cancer. The apoptotic effect of HSP in BT-474 cells was investigated, and it was found that the higher the concentration of HSP more the cells underwent apoptosis. Furthermore, the highest concentration of HSP led to overexpression of the MLH1 and MSH2 genes in both breast cancer and normal cell lines. Overall, our study suggests that HSP has an anticancer effect on breast cancer cell lines, and the effect is concentration dependent.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-15DOI: 10.4103/JAPTR.JAPTR_267_23
Sugiyartono, Widji Soeratri, Arini Permatasari, Ayun Dewi Rahayu, Dwi Setyawan, Dewi Isadiartuti
Lactobacillus casei (LC) is a type of lactic acid bacterium that is known for its beneficial probiotic properties. However, it is not typically found in the human intestine because it lacks acid resistance. LC thrives in an optimal pH environment of 6.8 and can be initiated in a more acidic environment at a pH of 3.5. This study purposed to compare the effect of L-type methacrylic acid copolymer (MAC) as a matrix (0.50%, 0.75%, and 1.00%) on the physical characteristics of LC probiotic microparticles made by the spray drying process. Probiotic microparticles were also made from a dry suspension of LC FNCC 0090 bacteria and dispersed in a solution of L-type MAC. The results showed that a rise in matrix content by 1.00% increased particle size (4.47 ± 0.19 µm) and reduced moisture content (7.45 ± 0.11%). The analysis of microparticle morphology also indicated a positive correlation between the level of L-type MAC and the production of smooth, nonporous, and almost spherical shapes. In addition, it was observed that encapsulation efficiency (92.46 ± 0.17%) and protection against stomach acid (98.17% ±1.17%) increased with the level of the matrix.
干酪乳杆菌(LC)是一种乳酸菌,因其有益的益生特性而闻名。然而,由于缺乏耐酸性,人类肠道中通常找不到这种细菌。乳酸菌在最佳 pH 值为 6.8 的环境中茁壮成长,并可在 pH 值为 3.5 的较酸性环境中开始生长。本研究旨在比较以 L 型甲基丙烯酸共聚物(MAC)为基质(0.50%、0.75% 和 1.00%)对喷雾干燥工艺制作的 LC 益生菌微颗粒物理特性的影响。益生菌微颗粒也是由 LC FNCC 0090 细菌的干悬浮液制成,并分散在 L 型 MAC 溶液中。结果表明,基质含量增加 1.00%,颗粒尺寸(4.47 ± 0.19 µm)增大,水分含量(7.45 ± 0.11%)降低。对微粒形态的分析还表明,L 型 MAC 的含量与产生光滑、无孔和近似球形的微粒之间存在正相关。此外,还观察到封装效率(92.46 ± 0.17%)和对胃酸的保护(98.17% ± 1.17%)随着基质水平的提高而增加。
{"title":"Characteristics of <i>Lactobacillus casei</i> probiotic microparticles in L-type methacrylic acid copolymer matrix.","authors":"Sugiyartono, Widji Soeratri, Arini Permatasari, Ayun Dewi Rahayu, Dwi Setyawan, Dewi Isadiartuti","doi":"10.4103/JAPTR.JAPTR_267_23","DOIUrl":"10.4103/JAPTR.JAPTR_267_23","url":null,"abstract":"<p><p><i>Lactobacillus casei</i> (LC) is a type of lactic acid bacterium that is known for its beneficial probiotic properties. However, it is not typically found in the human intestine because it lacks acid resistance. LC thrives in an optimal pH environment of 6.8 and can be initiated in a more acidic environment at a pH of 3.5. This study purposed to compare the effect of L-type methacrylic acid copolymer (MAC) as a matrix (0.50%, 0.75%, and 1.00%) on the physical characteristics of LC probiotic microparticles made by the spray drying process. Probiotic microparticles were also made from a dry suspension of LC FNCC 0090 bacteria and dispersed in a solution of L-type MAC. The results showed that a rise in matrix content by 1.00% increased particle size (4.47 ± 0.19 µm) and reduced moisture content (7.45 ± 0.11%). The analysis of microparticle morphology also indicated a positive correlation between the level of L-type MAC and the production of smooth, nonporous, and almost spherical shapes. In addition, it was observed that encapsulation efficiency (92.46 ± 0.17%) and protection against stomach acid (98.17% ±1.17%) increased with the level of the matrix.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-15DOI: 10.4103/japtr.japtr_344_23
Neneng Siti Silfi Ambarwati, Nurnisya Tiara Sukma, Yesi Desmiaty, Annisa Auliya, Setia Budi, M Arifuddin, Islamudin Ahmad
Garcinia dulcis and Garcinia forbesii King are native plants from Indonesia and have tremendous potential as a source of raw medicines based on local wisdom. However, scientific data for strengthening pharmaceuticals are still limited. Therefore, it is necessary to conduct a study to strengthen and develop the potential of both plants using the approach of traditional medicine. This study aimed to explore the secondary metabolite composition and biological activity (antioxidant and antielastase) of both plants. Both samples were extracted using 70% ethanol and microwave-assisted extraction with a microwave power of 120 watts for 15 min. The extract obtained was then screened for phytochemicals using specific reagents. The total phenolic content (TPC) was determined using spectrophotometry with a 96-well microplate reader method. The total flavonoid content (TFC) was determined using the colorimetric method, whereas metabolite profiling analysis was conducted using the UPLC-QToF-MS/MS system. Meanwhile, biological activity was tested for antioxidant activity and antielastase as measured by a microplate reader 96-well spectrophotometry method at specific wavelengths. According to the results, G. dulcis and G. forbesii fruit peel extracts showed positive detection of particular secondary metabolites. TPC and TFC values were 13.98 ± 1.90 mg GAE/g and 10.33 ± 1.90 mg QE/g for G. dulcis and 11.98 ± 2.04 mgGAE/g and 1.96 ± 0.36 mgQE/g for G. forbesii. Metabolite profiling detected some compounds from G. dulcis, including ephedrannin B, hinokiflavone, mahuannin J, and candidate mass C9H12O8, and G. forbesii, including 5-Hydroxy-7,8,2'- trimethoxyflavone, lucialdehyde B, candidate mass C21H39NO4, candidate mass C14H10O6, and candidate mass C14H12O6. Meanwhile, the biological activities (antioxidant and antielastase) were 137.721 μg/mL and 108.893 μg/mL for G. dulcis and 481.948 μg/mL and 250.611 μg/mL for G. forbesii, respectively. Both plants showed different profiles of secondary metabolites and biological activities (antioxidant and antielastase) according to their respective characteristics.
{"title":"<i>Garcinia dulcis</i> and <i>Garcinia forbesii</i> King fruit peel extract: Secondary metabolite composition, antioxidant, and elastase inhibitory activity evaluation.","authors":"Neneng Siti Silfi Ambarwati, Nurnisya Tiara Sukma, Yesi Desmiaty, Annisa Auliya, Setia Budi, M Arifuddin, Islamudin Ahmad","doi":"10.4103/japtr.japtr_344_23","DOIUrl":"10.4103/japtr.japtr_344_23","url":null,"abstract":"<p><p><i>Garcinia dulcis</i> and <i>Garcinia forbesii</i> King are native plants from Indonesia and have tremendous potential as a source of raw medicines based on local wisdom. However, scientific data for strengthening pharmaceuticals are still limited. Therefore, it is necessary to conduct a study to strengthen and develop the potential of both plants using the approach of traditional medicine. This study aimed to explore the secondary metabolite composition and biological activity (antioxidant and antielastase) of both plants. Both samples were extracted using 70% ethanol and microwave-assisted extraction with a microwave power of 120 watts for 15 min. The extract obtained was then screened for phytochemicals using specific reagents. The total phenolic content (TPC) was determined using spectrophotometry with a 96-well microplate reader method. The total flavonoid content (TFC) was determined using the colorimetric method, whereas metabolite profiling analysis was conducted using the UPLC-QToF-MS/MS system. Meanwhile, biological activity was tested for antioxidant activity and antielastase as measured by a microplate reader 96-well spectrophotometry method at specific wavelengths. According to the results, <i>G. dulcis</i> and <i>G. forbesii</i> fruit peel extracts showed positive detection of particular secondary metabolites. TPC and TFC values were 13.98 ± 1.90 mg GAE/g and 10.33 ± 1.90 mg QE/g for <i>G. dulcis</i> and 11.98 ± 2.04 mgGAE/g and 1.96 ± 0.36 mgQE/g for <i>G. forbesii</i>. Metabolite profiling detected some compounds from <i>G. dulcis</i>, including ephedrannin B, hinokiflavone, mahuannin J, and candidate mass C<sub>9</sub>H<sub>12</sub>O<sub>8</sub>, and <i>G. forbesii</i>, including 5-Hydroxy-7,8,2'- trimethoxyflavone, lucialdehyde B, candidate mass C<sub>21</sub>H<sub>39</sub>NO<sub>4</sub>, candidate mass C<sub>14</sub>H<sub>10</sub>O<sub>6</sub>, and candidate mass C<sub>14</sub>H<sub>12</sub>O<sub>6</sub>. Meanwhile, the biological activities (antioxidant and antielastase) were 137.721 μg/mL and 108.893 μg/mL for <i>G. dulcis</i> and 481.948 μg/mL and 250.611 μg/mL for <i>G. forbesii</i>, respectively. Both plants showed different profiles of secondary metabolites and biological activities (antioxidant and antielastase) according to their respective characteristics.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}