Pharmacology & Therapeutics最新文献

{"title":"G-protein coupled receptors in metabolic reprogramming and cancer","authors":"Songyeon Ahn ,&nbsp;Benny Abraham Kaipparettu","doi":"10.1016/j.pharmthera.2025.108849","DOIUrl":"10.1016/j.pharmthera.2025.108849","url":null,"abstract":"<div><div>G-protein coupled receptors (GPCR) are one of the frequently investigated drug targets. GPCRs are involved in many human pathophysiologies that lead to various disease conditions, such as cancer, diabetes, and obesity. GPCR receptor activates multiple signaling pathways depending on the ligand and tissue type. However, this review will be limited to the GPCR-mediated metabolic modulations and the activation of relevant signaling pathways in cancer therapy. Cancer cells often have reprogrammed cell metabolism to support tumor growth and metastatic plasticity. Many aggressive cancer cells maintain a hybrid metabolic status, using both glycolysis and mitochondrial metabolism for better metabolic plasticity. In addition to glucose and glutamine pathways, fatty acid is a key mitochondrial energy source in some cancer subtypes. Recently, targeting alternative energy pathways like fatty acid beta-oxidation (FAO) has attracted great interest in cancer therapy. Several <em>in vitro</em> and <em>in vivo</em> experiments in different cancer models reported encouraging responses to FAO inhibitors. However, due to the potential liver toxicity of FAO inhibitors in clinical trials, new approaches to indirectly target metabolic reprogramming are necessary for <em>in vivo</em> targeting of cancer cells. This review specifically focused on free fatty acid receptors (FFAR) and β-adrenergic receptors (β-AR) because of their reported significance in mitochondrial metabolism and cancer. Further understanding the pharmacology of GPCRs and their role in cancer metabolism will help repurpose GPCR-targeting drugs for cancer therapy and develop novel drug discovery strategies to combine them with standard cancer therapy to increase anticancer potential and overcome drug resistance.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108849"},"PeriodicalIF":12.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation into biased signaling, glycosylation, and drug vulnerability of acute myeloid leukemia","authors":"Tomasz Pienkowski ,&nbsp;Aleksandra Golonko ,&nbsp;Lukasz Bolkun ,&nbsp;Katarzyna Wawrzak-Pienkowska ,&nbsp;Lukasz Szczerbinski ,&nbsp;Adam Kretowski ,&nbsp;Michal Ciborowski ,&nbsp;Wlodzimierz Lewandowski ,&nbsp;Waldemar Priebe ,&nbsp;Renata Swislocka","doi":"10.1016/j.pharmthera.2025.108848","DOIUrl":"10.1016/j.pharmthera.2025.108848","url":null,"abstract":"<div><div>Understanding and harnessing biased signaling offers significant potential for developing novel therapeutic strategies or enhancing existing treatments. By managing biased signaling, it is possible to minimize adverse effects, including toxicity, and to optimize therapeutic outcomes by selectively targeting beneficial pathways. In the context of acute myeloid leukemia (AML), a highly aggressive blood cancer characterized by the rapid proliferation of abnormal myeloid cells in the bone marrow and blood, the dysregulation of these signaling pathways, particularly those involving G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs), significantly contributes to disease progression and therapeutic resistance. Traditional therapies for AML often struggle with resistance and toxicity, leading to poor patient outcomes. However, by exploiting the concept of biased signaling, researchers may be able to design drugs that selectively activate pathways that inhibit cancer cell growth while avoiding those that contribute to resistance or toxicity. Glycosylation, a key post-translational modification (PTM), plays a crucial role in biased signaling by altering receptor conformation and ligand-binding affinity, thereby affecting the outcome of biased signaling. Chemokine receptors like CXCR4, which are often overexpressed and heavily glycosylated in AML, serve as targets for therapeutic intervention. By externally inducing or inhibiting specific PTMs, it may be possible to further refine therapeutic strategies, unlocking new possibilities for developing more effective and less toxic treatments. This review highlights the importance of understanding the dynamic relationship between glycosylation and biased signaling in AML, which is essential for the development of more effective treatments and overcoming drug resistance, ultimately leading to better patient outcomes.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108848"},"PeriodicalIF":12.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factor receptor signaling in metabolic dysfunction-associated fatty liver disease: Pathogenesis and therapeutic targets","authors":"Yi Chu,&nbsp;Su Yang,&nbsp;Xiaodong Chen","doi":"10.1016/j.pharmthera.2025.108844","DOIUrl":"10.1016/j.pharmthera.2025.108844","url":null,"abstract":"<div><div>Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a significant hepatic manifestation of metabolic syndrome, with its prevalence increasing globally alongside the epidemics of obesity and diabetes. MAFLD represents a continuum of liver damage, spanning from uncomplicated steatosis to metabolic dysfunction-associated steatohepatitis (MASH). This condition can advance to more severe outcomes, including fibrosis and cirrhosis. Fibroblast growth factor receptors (FGFRs) are a family of four receptor tyrosine kinases (FGFR1–4) that interact with both paracrine and endocrine fibroblast growth factors (FGFs). This interaction activates the phosphorylation of tyrosine kinase residues, thereby triggering downstream signaling pathways, including RAS-MAPK, JAK-STAT, PI3K-AKT, and PLCγ. In the context of MAFLD, paracrine FGF-FGFR signaling is predominantly biased toward the development of liver fibrosis and carcinogenesis. In contrast, endocrine FGF-FGFR signaling is primarily biased toward regulating the metabolism of bile acids, carbohydrates, lipids, and phosphate, as well as maintaining the overall balance of energy metabolism in the body. The interplay between these biased signaling pathways significantly influences the progression of MAFLD. This review explores the critical functions of FGFR signaling in MAFLD from three perspectives: first, it examines the primary roles of FGFRs relative to their structure; second, it summarizes FGFR signaling in hepatic lipid metabolism, elucidating mechanisms underlying the occurrence and progression of MAFLD; finally, it highlights recent advancements in drug development aimed at targeting FGFR signaling for the treatment of MAFLD and its associated diseases.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108844"},"PeriodicalIF":12.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived nanovesicles and therapeutic application","authors":"Dokyung Jung ,&nbsp;Na-Eun Kim ,&nbsp;Sua Kim ,&nbsp;Ju-Hyun Bae ,&nbsp;Il-Young Jung ,&nbsp;Kyung-Won Doh ,&nbsp;Byungheon Lee ,&nbsp;Do-Kyun Kim ,&nbsp;Young-Eun Cho ,&nbsp;Moon-Chang Baek","doi":"10.1016/j.pharmthera.2025.108832","DOIUrl":"10.1016/j.pharmthera.2025.108832","url":null,"abstract":"<div><div>Plant-derived nanovesicles (PDNVs) are becoming more popular as promising therapeutic tools owing to their diversity, cost-effectiveness, and biocompatibility with very low toxicity. Therefore, this review aims to discuss the methods for isolating and characterizing PDNVs and emphasize their versatile roles in direct therapeutic applications and drug delivery systems. Their ability to effectively encapsulate and deliver large nucleic acids, proteins, and small-molecule drugs was highlighted. Moreover, advanced engineering strategies, such as surface modification and fusion with other vesicles, have been developed to enhance the therapeutic effects of PDNVs. Additionally, we describe key challenges related to this field, encouraging further research to optimize PDNVs for various clinical applications for prevention and therapeutic purposes. The distinctive properties and diverse applications of PDNVs could play a crucial role in the future of personalized medicine, fostering the development of innovative therapeutic strategies.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108832"},"PeriodicalIF":12.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the regulatory landscape of protein phosphatase 2A (PP2A): Pharmacological modulators and potential therapeutics","authors":"David A. Neale ,&nbsp;Jonathan C. Morris ,&nbsp;Nicole M. Verrills ,&nbsp;Alaina J. Ammit","doi":"10.1016/j.pharmthera.2025.108834","DOIUrl":"10.1016/j.pharmthera.2025.108834","url":null,"abstract":"<div><div>Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase with a diverse and integral role in cellular signalling pathways. Consequently, its dysfunction is frequently observed in disease states such as cancer, inflammation and Alzheimer’s disease. A growing understanding of both PP2A and its endogenous regulatory proteins has presented numerous targets for therapeutic intervention. This provides important context for the dynamic control and dysregulation of PP2A function in disease states. Understanding the intricate regulation of PP2A signalling in disease has resulted in the development of novel pharmacological agents aimed at restoring cellular homeostasis. Herein we review the structure and function of PP2A together with pharmacological modulators, both endogenous (proteins) and exogenous (small molecules and peptides), with relevance to targeting PP2A as a future pharmacotherapeutic strategy.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108834"},"PeriodicalIF":12.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor dimers and biased ligands: Novel strategies for targeting G protein-coupled receptors","authors":"Wenkai Liu ,&nbsp;Dexiu Wang ,&nbsp;Luoqi Wang ,&nbsp;Shujuan Hu ,&nbsp;Yunlu Jiang ,&nbsp;Yixiang Wang ,&nbsp;Xin Cai ,&nbsp;Jing Chen","doi":"10.1016/j.pharmthera.2025.108829","DOIUrl":"10.1016/j.pharmthera.2025.108829","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) are the largest superfamily of membrane receptors. They regulate physiological and pathological processes such as metabolic homeostasis, cell proliferation and differentiation, and the immune response, and are one of the most important classes of drug targets, being targeted by 30–40 % of marketed drugs. A growing number of studies continue to reveal the complexity of GPCRs, especially their ability to interact with each other to form higher-order structures such as homodimers and heterodimers, which have different functions than monomers, and are involved in disease development and progression. The existence of GPCR homodimers and heterodimers is opening up new directions in drug discovery and development to harness their therapeutic potential. Particularly striking is the ability of GPCR dimers to trigger unique biased signalling pathways, which exquisitely balance the relationship between therapeutic effects and side effects. By suppressing adverse reactions and enhancing beneficial drug effects, GPCR dimers provide an unprecedented opportunity to minimise side effects, maximise therapeutic efficacy and enhance safety. This review aims to highlight the latest research advances in GPCR dimerization and GPCR-biased signalling, focusing on the development of dimer-targeting and biased ligands as innovative drugs that will likely provide new strategies for treating GPCR-related diseases as well as a better understanding of drug design for compounds that target GPCRs. GPCRs will play an increasingly important role in precision medicine and personalised therapy, leading us towards a safer, more efficient and smarter pharmaceutical future.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108829"},"PeriodicalIF":12.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory bowel disease and neuropsychiatric disorders: Mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis","authors":"Giulia Petracco ,&nbsp;Isabella Faimann ,&nbsp;Florian Reichmann","doi":"10.1016/j.pharmthera.2025.108831","DOIUrl":"10.1016/j.pharmthera.2025.108831","url":null,"abstract":"<div><div>Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108831"},"PeriodicalIF":12.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of chronic metabolic inflammation and regulation of gut homeostasis: Tea as a potential therapy","authors":"Shiyi Yu ,&nbsp;Xuan Zhu ,&nbsp;Xiayu Zhao ,&nbsp;Yan Li ,&nbsp;Xinghe Niu ,&nbsp;Yinghua Chen ,&nbsp;Jian Ying","doi":"10.1016/j.pharmthera.2025.108828","DOIUrl":"10.1016/j.pharmthera.2025.108828","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Chronic metabolic inflammation is a common mechanism linked to the development of metabolic disorders such as obesity, diabetes, and cardiovascular disease (CVD). Chronic metabolic inflammation often related to alterations in gut homeostasis, and pathological processes involve the activation of endotoxin receptors, metabolic reprogramming, mitochondrial dysfunction, and disruption of intestinal nuclear receptor activity. Recent investigations into homeostasis and chronic metabolic inflammation have revealed a novel mechanism which is characterized by a timing interaction involving multiple components and targets. This article explores the positive impact of tea consumption on metabolic health of populations, with a special focus on the improvement of inflammatory indicators and the regulation of gut microbiota. Studies showed that tea consumption is related to the enrichment of gut microbiota. The relative proportion of Firmicutes/Bacteroidetes (F/B) is altered, while the abundance of &lt;em&gt;Lactobacillus&lt;/em&gt;, &lt;em&gt;Bifidobacterium&lt;/em&gt;, and &lt;em&gt;A. muciniphila&lt;/em&gt; increased significantly in most of the studies. Thus, tea consumption could provide potential protection from the development of chronic diseases by improving gut homeostasis and reducing chronic metabolic inflammation. The direct impact of tea on intestinal homeostasis primarily targets lipopolysaccharide (LPS)-related pathways. This includes reducing the synthesis of intestinal LPS, inhibiting LPS translocation, and preventing the binding of LPS to TLR4 receptors to block downstream inflammatory pathways. The TLR4/MyD88/NF-κB p65 pathway is crucial for anti-metaflammatory responses. The antioxidant properties of tea are linked to enhancing mitochondrial function and mitigating mitochondria-related inflammation by eliminating free radicals, inhibiting NLRP3 inflammasomes, and modulating Nrf2/ARE activity. Tea also contributes to safeguarding the intestinal barrier through various mechanisms, such as promoting the synthesis of short-chain fatty acids in the intestine, activating intestinal aryl hydrocarbon receptor (AhR) and farnesoid X receptor (FXR), and improving enteritis. Functional components that improve chronic metabolic inflammation include tea polyphenols, tea pigments, TPS, etc. Tea metabolites such as 4-Hydroxyphenylacetic acid and 3,4-Dihydroxyflavan derivatives, etc., also contribute to anti-chronic metabolic inflammation effects of tea consumption. The raw materials and processing technologies affect the functional component compositions of tea; therefore, consuming different types of tea may result in varying action characteristics and mechanisms. However, there is currently limited elaboration on this aspect. Future research should conduct in-depth studies on the mechanism of tea and its functional components in improving chronic metabolic inflammation. Researchers should pay attention to whether there are interactions between tea and other foods or drugs, explor","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108828"},"PeriodicalIF":12.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in target identification technology of natural products","authors":"Ting-Ting Liu ,&nbsp;Ke-Wu Zeng","doi":"10.1016/j.pharmthera.2025.108833","DOIUrl":"10.1016/j.pharmthera.2025.108833","url":null,"abstract":"<div><div>Natural products, characterized by their structural diversity, broad spectrum of biological activities, and safe yet effective therapeutic potential, have become pivotal resources in drug research and development. However, the target proteins of many natural products remain unidentified, a significant challenge that impedes their development into viable drug candidates. Therefore, the target identification is crucial for elucidating the pharmacological mechanisms of natural products and facilitating their therapeutic applications. In this review, we present a comprehensive overview of recent advancements in methodologies for target identification of natural products. Additionally, we predict future developments in new technologies for target discovery. Collectively, this review establishes a methodological framework for uncovering the cellular targets and pharmacological mechanisms of natural products, thereby advancing the development of innovative natural product-based drugs.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108833"},"PeriodicalIF":12.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimmune modulators derived from natural products: Mechanisms and potential therapies","authors":"Wan-Di Feng,&nbsp;Dong-Ni Liu,&nbsp;Yu-Fu Shang,&nbsp;Wen-Fang Zhang,&nbsp;Shuang Xu,&nbsp;Dan-Hong Feng,&nbsp;Yue-Hua Wang","doi":"10.1016/j.pharmthera.2025.108830","DOIUrl":"10.1016/j.pharmthera.2025.108830","url":null,"abstract":"<div><div>Neuroimmunology is a multidisciplinary field that investigates the interactions between the nervous and immune systems. Neuroimmune interactions persist throughout the entire lifespan, and their dysregulation can lead to the onset and development of multiple diseases. Despite significant progress over the past decades in elucidating the interaction between neuroscience and immunology, the exact mechanism underlying neuroimmune crosstalk has not yet been fully elucidated. In recent years, natural products have emerged as a promising avenue for the therapeutic implications of neuroimmune diseases. Naturally derived anti-neuroimmune disease agents, such as polyphenols, flavonoids, alkaloids, and saponins, have been extensively studied for their potential neuroimmune modulatory effects. This comprehensive review delves into the specific molecular mechanisms of bidirectional neuro-immune interactions, with particular emphasis on the role of neuro-immune units. The review synthesizes a substantial body of evidence from in vitro and in vivo experiments as well as clinical studies, highlighting the therapeutic potential of various natural products in intervening in neuroimmune disorders.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108830"},"PeriodicalIF":12.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}