Advanced pharmaceutical bulletin最新文献

{"title":"Nogapendekin alfa Inbakicept-pmln (Anktiva) with BCG: A Promising Arsenal in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer Intervention.","authors":"ArunSundar MohanaSundaram, Velmurugan Raja, Yeshwanth Kamalakannan, Md Aminul Islam","doi":"10.34172/apb.43870","DOIUrl":"10.34172/apb.43870","url":null,"abstract":"","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 1","pages":"4-6"},"PeriodicalIF":3.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599114","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}

{"title":"Synergistic Enhancement of Osimertinib Efficacy in Non-small Cell Lung Cancer Cells Through Epigallocatechin-3-Gallate: Mechanistic Insights Into YAP/TEAD/CTGF Axis Inhibition.","authors":"Ashwini Somayaji, Chakrakodi Shashidhara Shastry","doi":"10.34172/apb.43809","DOIUrl":"10.34172/apb.43809","url":null,"abstract":"<p><strong>Purpose: </strong>Combinatorial therapies are essential for treating advanced non-small cell lung cancer (NSCLC), particularly overcoming resistance to third-generation epidermal growth factor receptor (EGFR) like osimertinib (OSI). The Hippo signaling pathway, a critical regulator of cell proliferation, apoptosis, and tumor progression, is often dysregulated in NSCLC and contributes to chemo-resistance. This study investigated the potential of epigallocatechin-3-gallate (EGCG), a green tea polyphenol, to overcome OSI resistance by modulating the Hippo signaling pathway, specifically through inhibition of the YAP-1 (Yes-associated protein)-TEAD (TEA domain transcription factor)-CTGF (connective tissue growth factor) axis.</p><p><strong>Methods: </strong>Using stepwise dose escalation, OSI-resistant (OR) clones were developed from EGFR T790M-mutated H460 cells. The anti-proliferative effects of EGCG were assessed, and synergistic interactions between OSI and EGCG were analysed using combination index (CI) values and the median effect concept. Mechanistic studies evaluated the co-treatment's impact on the Hippo signaling pathway, focusing on the inhibition of the YAP/TEAD/CTGF signaling axis.</p><p><strong>Results: </strong>The OR clones exhibited significantly higher IC₅₀ values for OSI (25.12-28.48 µM) compared to parental H460 cells (2.74±0.2µM). EGCG treatment reduced cell viability in a concentration-dependent manner, with IC₅₀ values of 102.54±0.23μM for H460 cells and 225.79-237.36 µM for OR clones. Combination treatment of OSI and EGCG showed strong synergy at a 1:2 molar ratio, with CI values indicating synergism across a range from IC₅₀ to IC₉₅. Mechanistically, co-treatment suppressed the overexpression of the YAP/TEAD/CTGF axis, restoring Hippo pathway activity and reversing OSI resistance.</p><p><strong>Conclusion: </strong>This study provides evidence that EGCG effectively targets the Hippo signaling pathway to overcome OSI resistance in NSCLC. The inclusion of EGCG in combinatorial therapies holds promise as a novel approach to combat therapeutic resistance and improve outcomes for patients with EGFR-mutated NSCLC.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 2","pages":"428-439"},"PeriodicalIF":4.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022668","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}

{"title":"Inhibition of COX-2 and PI3K/AKT Pathways to Prevent Cancer Metastasis.","authors":"Punet Kumar, Sangam Singh","doi":"10.34172/apb.44038","DOIUrl":"10.34172/apb.44038","url":null,"abstract":"","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 2","pages":"230-231"},"PeriodicalIF":4.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022649","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}

{"title":"Exosome-Like Nanoparticles from Indonesian Red and Emprit Ginger Varieties Suppress LPS-Induced IL-6 Production in RAW 264.7 Macrophages.","authors":"Daisy Ramadhani Muhammad, Natasya Emmanuela, Iriawati Iriawati, Christofora Hanny Wijaya, Ika Dewi Ana, Triarti Dewi Kencana Wungu, Diah Ratnadewi, Hiroshi Takemori, Anggraini Barlian","doi":"10.34172/apb.42675","DOIUrl":"10.34172/apb.42675","url":null,"abstract":"<p><strong>Purpose: </strong>Studies have shown the potential of exosomes as therapeutic agents with anti-inflammatory properties. However, the clinical application of mammalian-derived exosomes is hindered by mass production challenges and strict regulations. Plant-derived exosome-like nanoparticles (PELNs) are a more economical alternative possessing a similar therapeutic potential. Ginger is a readily available plant with components that are clinically proven to inhibit inflammation. Therefore, it is interesting to investigate the potential of red ginger and emprit ginger, cultivated varieties in Indonesia possessing the most potent anti-inflammatory activities, as a PELN source for anti-inflammatory therapy.</p><p><strong>Methods: </strong>In this work, PELNs from the rhizomes of red ginger (RG-ELN) and emprit ginger (EG-ELN) were obtained through differential centrifugation and polymer precipitation using PEG6000. The PELNs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and bicinchoninic acid assay. Their internalization and effect on RAW 246.7 cell viability were also assessed. The anti-inflammatory potential of PELNs was investigated by assessing interleukin 6 (IL-6) expression of lipopolysaccharide (LPS)-stimulated macrophages treated with RG-ELN and EG-ELN.</p><p><strong>Results: </strong>Both RG-ELN and EG-ELN exhibited cup-shaped morphologies with average sizes of 195.83±1.35 and 194.40±8.40 nm, respectively. Both PELNs can be internalized within 2 h and did not significantly affect RAW 264.7 cell viability after 24 h. The reverse transcription quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay results indicated a significantly lower expression and secretion of IL-6 in the macrophage cells pre-treated with RG-ELN and EG-ELN.</p><p><strong>Conclusion: </strong>The RG-ELN and EG-ELN samples were successfully obtained through the polymer precipitation method, as confirmed by the TEM and DLS results which aligned with typical PELN characteristics. The pre-treatment of RG-ELN and EG-ELN to activated RAW 264.7 cells decreased the pro-inflammatory cytokine IL-6 expression relative to activated controls.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 1","pages":"60-69"},"PeriodicalIF":4.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599108","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}

{"title":"Inhibitory Effects of Citrus-Derived Flavonoids Hesperidin and Hesperetin on SARS-CoV-2 Spike-Mediated Syncytia Formation Using In Vitro Cell Model.","authors":"Dennaya Kumara, Hayfa Salsabila Harsan, Endah Puji Septisetyani, Pekik Wiji Prasetyaningrum, Komang Alit Paramitasari, Mukh Syaifudin, Okid Parama Astirin, Muthi Ikawati, Edy Meiyanto","doi":"10.34172/apb.44060","DOIUrl":"10.34172/apb.44060","url":null,"abstract":"<p><strong>Purpose: </strong>SARS-CoV-2 infection may lead to a worse prognosis in COVID-19 patients by inducing syncytia formation which implies intercellular transmission and immune evasion. Hesperidin (HSD) and hesperetin (HST) are two citrus flavonoids that demonstrate the potential to interfere with spike/human angiotensin-converting enzyme-2 (hACE2) binding and show an inhibitory effect in the SARS-CoV-2 pseudovirus internalization model. Here, we determined the effects of HSD and HST to inhibit syncytia formation using in vitro cell models.</p><p><strong>Methods: </strong>We confirmed spike, hACE2, and transmembrane protease, serine 2 (TMPRSS2) ectopic expressions by immunofluorescence staining (IF) after transfection using polyethylene imine (PEI) in 293T cells. Then, the cells were transfected with a set of plasmids encoding spike/hACE2/TMPRSS2 or spike/hACE2 to induce syncytia formation. Cell treatment with HSD/HST was performed 4-5 h after transfection and then incubated for another 16-18 h. Syncytia were observed using an inverted microscope or a high content screening (HCS) platform. The data obtained from syncytia formation assays were statistically analyzed using ANOVA (Bonferroni).</p><p><strong>Results: </strong>We successfully observed spike, hACE2, and TMPRSS2 expression in 293T cells by IF staining. Furthermore, we showed that HSD 10 and 100 µM significantly inhibited the formation of small-to-medium-sized syncytia compared to the control cells by manual syncytia observation. In the HCS assay, 10 µM HSD showed an inhibitory effect of syncytia induced by spike WT. In contrast, 100 µM HSD, 10 and 100 µM HST, and 10 µg/mL citrus peel extract containing HSD prepared by the hydrodynamic cavitation method (HCV) inhibited syncytia formation induced by spike Omicron.</p><p><strong>Conclusion: </strong>HSD and HST show the potential inhibitory activity of SARS-CoV-2 intercellular transmission. Further study is needed to confirm the mechanism of action of the antiviral activity.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 2","pages":"416-427"},"PeriodicalIF":4.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022646","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}

{"title":"Small T Oncoprotein of Merkel Cell Polyomavirus Attenuates Cisplatin-Induced Apoptosis and Enhances E1, E6/E7, MMP-1, and Ki-67 Expression in HeLa Cervical Cancer Cells.","authors":"Fatemeh Pakdel, Seyed Masoud Hosseini, Neda Soleimani, Ali Farhadi","doi":"10.34172/apb.43882","DOIUrl":"10.34172/apb.43882","url":null,"abstract":"<p><strong>Purpose: </strong>Cervical cancer (CxCa) is primarily caused by high-risk human papillomaviruses (hrHPV), which disrupt p53 and pRb regulation, leading to uncontrolled growth and progression. Co-infection with polyomaviruses like MCPyV in some HPV-positive cases suggests a potential combined effect on tumor development. Cisplatin is commonly used for advanced CxCa, but resistance remains a challenge. This study examines whether MCPyV sT oncoprotein and HPV-18 oncoproteins affect key gene transcription, influencing proliferation and cisplatin resistance in CxCa.</p><p><strong>Methods: </strong>The sT gene was cloned into the pCMV6 vector, and HeLa cells were transfected with pCMV6-sT using Lipofectamine 3000. Transfection efficiency was assessed via fluorescence microscopy and flow cytometry. Protein expression was analyzed using SDS-PAGE and Western blotting. Cytotoxicity was measured with the MTT assay, gene expression was analyzed by RT-qPCR, Ki-67 staining was performed on cell blocks, and cisplatin-induced effects on proliferation and apoptosis were examined.</p><p><strong>Results: </strong>Cytotoxicity assays showed a significant increase in cell viability at 0.2 μg of sT plasmid after 72 hours (13.76%, <i>P</i><0.05). MCPyV sT expression significantly upregulated E1 (4.22-fold), E6/E7 (3.80-fold), and MMP1 (6-fold) mRNA levels (<i>P</i><0.001). Increased Ki-67 positivity indicated enhanced proliferation. Additionally, sT expression reduced cisplatin-induced apoptosis, with fewer apoptotic cells observed in the sT+cisplatin group than in the cisplatin-only group (25.9% vs. 38.3%, <i>P</i><0.05).</p><p><strong>Conclusion: </strong>The presence of MCPyV sT and HPV oncoproteins together enhances resistance to cisplatin-induced apoptosis in CxCa cells, highlighting the need for further investigation into viral oncoprotein interactions to overcome therapeutic resistance.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 1","pages":"194-205"},"PeriodicalIF":4.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599120","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}

{"title":"Well-regulated Dermal Regeneration Using Amnion-containing Scaffold in a Preclinical Study.","authors":"Masumeh Staji, Arezoo Karamivandishi, Roya Fattahi, Masoud Soleimani, Hamidreza Moosavian, Simzar Hosseinzadeh","doi":"10.34172/apb.43476","DOIUrl":"10.34172/apb.43476","url":null,"abstract":"<p><strong>Purpose: </strong>we investigated the synergistic influence of amnion and keratinocytes on dermal regeneration in mice.</p><p><strong>Methods: </strong>A scaffold derived from amnion and gelatin via electrospinning was used to synthesize a polyurethane-based scaffold. polyurethane/gelatin/amnion (PU/G/A) scaffold was characterized by scanning electron microscopy (SEM), FTIR, and tensile test. biocompatibility of the corresponding scaffold was investigated using the MTT method in the culture of keratinocytes.</p><p><strong>Results: </strong>The SEM images showed sufficient cell adhesion on the PU/G/A scaffold. The tensile test results indicated that the scaffold containing PU/G/A with the lowest Young's modulus (12 MPa±2.1) displayed higher elasticity than the scaffold without amnion. Furthermore, the MTT assay revealed that the amniotic scaffold contributed to 100% cell viability (<i>P</i>≤0.0001 compared to control) and proliferation. Moreover, an in vivo study conducted on mice showed that the PU/G/A/ keratinocytes scaffold results in increased granulation, tissue formation and wound closure (<i>P</i><0.001 compared to control).</p><p><strong>Conclusion: </strong>This innovative nanofiber device not only addresses the limitations of traditional dressings but also offers additional functionalities such as wound compatibility, gas exchange, promotion of angiogenesis in the injured area and a substrate that amplifies the biological functions of stem cells.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 1","pages":"206-216"},"PeriodicalIF":4.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599133","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}

{"title":"Preparation and Anti-cancer Evaluation of Methotrexate-loaded Inositol-6 Phosphate Cross-linked Chitosan Nanoparticles on Breast Cancer.","authors":"Masoud Farshbaf, Nasrin Gobakhlou, Muhammad Sarfraz, Javid Shahbazi-Mojarrad, Mohammad Feyzizadeh, Hamed Hamishehkar, Parvin Zakeri-Milani, Hadi Valizadeh","doi":"10.34172/apb.43661","DOIUrl":"10.34172/apb.43661","url":null,"abstract":"<p><strong>Purpose: </strong>Chitosan nanoparticles (CNs) have directed considerable research efforts towards developing biocompatible, biodegradable, inexpensive and efficient particulate drug delivery systems.</p><p><strong>Methods: </strong>In the present investigation, we utilized green and safe inositol hexaphosphate (InsP6) as a physical cross-linker to obtain CNs (^InsP6CNs) and compared their size, zeta potential and cell uptake ability with the CNs cross-linked with tripolyphosphate (TPP) as a commonly used cross-linker (^TPPCNs). Methotrexate (MTX) as the model drug was physically incorporated within the both types of CNs (^InsP6CNs_MTX and ^TPPCNs_MTX) and their time-dependent anti-cancer behavior was evaluated on MCF-7 cell line.</p><p><strong>Results: </strong>Compared to ^TPPCNs, ^InsP6CNs were bigger in hydrodynamic diameter and showed far different zeta potential value. The MTX encapsulation efficiency was much higher for ^InsP6CNs_MTX than that of ^TPPCNs_MTX. ^InsP6CNs and ^TPPCNs showed similar <i>in vitro</i> cell uptake behavior, examined on MCF-7 cell line. Furthermore, after 24 h, ^InsP6CNs_MTX had the most <i>in vitro</i> antitumor effect on the MCF-7 cells, compared to free MTX and ^TPPCNs_MTX.</p><p><strong>Conclusion: </strong>Consequently, InsP6 can be presented as an accessible and cost-effective member of physical cross-linkers to prepare efficient CNs as drug delivery systems.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 1","pages":"217-222"},"PeriodicalIF":4.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599116","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}

{"title":"Nanovaccines against Cervical Cancer: Reliable Strategies to Circumvent Limitations of Traditional Therapeutic Vaccines.","authors":"Enwa Felix Oghenemaro, Safia Obaidur Rab, Ebraheem Abdu Musad Saleh, Asmaa F Kassem, Jasur Rizaev, Deepak Nathiya, Parjinder Kaur, M Ravi Kumar, Karam Kadhim, Ahmed M Hashim","doi":"10.34172/apb.43712","DOIUrl":"10.34172/apb.43712","url":null,"abstract":"<p><p>Cervical cancer ranks fourth in terms of diagnosis and cancer-related deaths in women worldwide. Despite the approval of prophylactic vaccines against cervical cancers, these vaccines are not able to eradicate the existing ones. Therefore, various platforms have been developed to design therapeutic vaccines against cervical cancers, including DNA/RNA-based, protein/peptide-based, vector-based, and cell-based platforms. Despite the advantages of each platform, therapeutic vaccines have displayed limited clinical benefit in patients with cervical cancer, which is partially associated with inefficient delivery of vaccine components. To address these issues, different nanoplatforms have been developed to carry cellular or molecular components of vaccines to target cells and lymphoid tissues, thus promoting the durability and potency of immune responses against tumor cells and antigens besides decreasing side effects. Moreover, nanoparticles (NPs), as adjuvants and/or carriers, provide other advantages, including sufficient antigen loading and uptake by antigen-presenting cells (APCs), adaptable antigen presentation, high immunogenicity, high stability, increased lymph node retention, and precise targeting. Thus, nanovaccines also lead us to design and develop personalized vaccines against cervical cancer. Here, we discuss platforms that have been used in clinical trials for the treatment of cervical cancer, their advantages and disadvantages, platforms for developing nanovaccines, and how they improve the therapeutic efficacy of vaccines.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 1","pages":"46-59"},"PeriodicalIF":4.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599113","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}

{"title":"GATA3 and Aging Raise the Susceptibility of Metastasis to High-Grade Serous Ovarian Carcinoma.","authors":"Mohnad Abdalla, Amr Ahmed El-Arabey, Zhongtao Gai","doi":"10.34172/apb.43915","DOIUrl":"10.34172/apb.43915","url":null,"abstract":"","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 1","pages":"1-3"},"PeriodicalIF":4.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599110","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}