Toxicological Research最新文献

{"title":"Toxicity assessment using neural organoids: innovative approaches and challenges.","authors":"Si-Hyung Park, Woong Sun","doi":"10.1007/s43188-025-00279-y","DOIUrl":"10.1007/s43188-025-00279-y","url":null,"abstract":"<p><p>Assessment of toxicity and efficacy in the nervous system is essential to ensure the safety of compounds and the efficacy of neurotherapeutics. Recently, technologies using neural organoids to mimic the structural and functional properties of human brain tissue have been developed to improve our understanding of human-specific brain development and to model neurodevelopmental disorders. This approach offers the potential for standardized toxicity testing and large-scale drug screening at the organ level. Here, we review recent advances in neural organoids and explore the possibility of establishing more accurate and efficient systems for toxicological screening applications. Our review provides insights into toxicity and efficacy assessment research using neural organoids.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"91-103"},"PeriodicalIF":1.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alleviating doxorubicin-induced reproductive toxicity: protective and androgenic effects of drone larvae on sperm morphology and hormonal balance.","authors":"Kağan Ağan, Salih Tunç Kaya, Aydan Fülden Ağan, Pınar Ağyar-Yoldaş, Taner Yoldaş, Ayşe İkinci-Keleş, Tuğçe Çaprazlı, Elif Arıca, Meral Kekeçoglu","doi":"10.1007/s43188-024-00270-z","DOIUrl":"10.1007/s43188-024-00270-z","url":null,"abstract":"<p><p>Male infertility and compromised sperm quality are common side effects of Doxorubicin (DOX), a widely used chemotherapy drug. Its detrimental impact on male reproductive cells underscores the urgent need for effective protective measures. Lyophilized drone larvae (DL) from apitherapy have emerged as a potential solution due to their reported protective properties. By exploring DL's therapeutic potential, this research seeks to address the pressing need for strategies to protect male reproductive health during cancer treatment. The study aims to evaluate the protective effects of lyophilized DL from apitherapy against DOX-induced testicular damage in adult <i>Sprague-Dawley</i> rats. DOX negatively impacts male reproductive cells, leading to infertility and compromised sperm quality. Investigating DL's protective properties is crucial for understanding its therapeutic potential in mitigating such adverse effects. Forty rats were divided into four groups: control, DOX-treated, DL-treated, and DOX + DL-treated. Histopathological assessments, biochemical analyses (TAS, TOS, CAT, SOD, GPX), inflammatory marker measurements (TNF-α, IL-1β, IL-6), and comet assays for DNA damage were conducted on testicular tissue and blood samples. DOX induced histopathological alterations in the testis and epididymis, which DL mitigated. DL increased TAS levels, counteracted DOX-induced decreases in glutathione peroxidase (GPx), total protein, albumin, and increases in total cholesterol. DL also mitigated the rise in Follicle-Stimulating Hormone (FSH) levels caused by DOX, while increasing testosterone levels and lowering Luteinizing Hormone (LH) levels. Inflammatory markers remained unaffected. Tail moment measurements indicated a protective effect against DOX-induced DNA damage in erythrocytes with DL. DL protected sperm morphology, count, and Johnsen's score from DOX-induced reductions, suggesting its potential in mitigating cancer treatment side effects on male reproductive health. The findings suggest that DL, as an apitherapy product, holds significant promise in mitigating DOX's adverse effects on male reproductive systems. However, further investigations into its mechanisms and clinical applications in cancer therapy are warranted, emphasizing the need for continued research to fully understand DL's therapeutic benefits.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"149-165"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the safety parameters of <i>Athenaea velutina</i> ethanolic extract: a step towards harnessing its medicinal potential.","authors":"Jordana Luizi Dos Prazeres, Alisson Andrade Almeida, Renner Philipe Rodrigues Carvalho, Luiz Carlos Maia Ladeira, Luiz Pedro de Souza Costa, Markus Kohlhoff, Leandro Licursi de Oliveira, Mariana Machado-Neves, João Paulo Viana Leite","doi":"10.1007/s43188-024-00276-7","DOIUrl":"10.1007/s43188-024-00276-7","url":null,"abstract":"<p><p><i>Athenaea velutina</i> (Sendtn.) D'Arcy, a native plant of the Brazilian Atlantic Forest, has exhibited potential pharmacological effects due to the presence of withanolides with anti-cancer and anti-inflammatory activities. However, there is a lack of research on the safety and toxicity of this plant species. This study aimed to assess the safety of the ethanolic extract of <i>A. velutina</i> leaves (Av-E) through toxicity and phytochemical analysis. Acute [1000 mg kg^-1 body weight (BW)] and subacute (250, 500, and 1000 mg kg^-1 BW) toxicity tests were conducted on female Wistar rats, along with an evaluation of the toxic reversal effect. HPLC-HRMS revealed the presence of withanolide steroids in Av-E. Reduced alanine aminotransferase (ALT), bilirubin levels, and increased calcium concentrations were observed after the acute toxicity test. Subacute toxicity demonstrated lowered ALT (250 and 1000 mg kg^-1 BW) and aspartate aminotransferase (AST) (250 and 500 mg kg^-1 BW) levels and increased sodium concentration (250 mg kg^-1 BW). No fatalities or clinical signs of toxicity occurred, and histological and biochemical analysis revealed no apparent liver or kidney toxicity. In conclusion, Av-E exhibited no toxicity in the experiments, encouraging further research to develop new herbal medicines.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"175-188"},"PeriodicalIF":1.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SRXN1 is a novel protective factor against methylmercury-induced apoptosis in C17.2 mouse neural stem cells.","authors":"Naoya Yamashita, Yukie Yokoyama, Ayano Kumagai, Ryoko Fukushima, Ryota Yamagata, Gi-Wook Hwang","doi":"10.1007/s43188-024-00277-6","DOIUrl":"10.1007/s43188-024-00277-6","url":null,"abstract":"<p><p>Methylmercury is an environmental pollutant that exhibits severe cerebral neurotoxicity and remains a worldwide problem. Motor and mental development disorders have been observed in children born to women who consumed relatively large amounts of methylmercury via contaminated fish during pregnancy. We previously found by RNA-sequencing analysis that treatment of C17.2 mouse neural stem cells with methylmercury induced the expression of SRXN1 (sulfiredoxin-1), a redox regulator. In this study, we examined the effect of methylmercury on SRXN1 expression and the role of SRXN1 in methylmercury-induced cell death. After C17.2 cells were treated with methylmercury, both mRNA and protein expression of SRXN1 increased in a time- and concentration-dependent manner. Because the induction of SRXN1 expression by methylmercury was suppressed by pretreatment with a transcription inhibitor, we searched the upstream region of the SRXN1 gene and found a binding sequence for transcription factor 3 (TCF3). Interestingly, the induction of SRXN1 expression by methylmercury was attenuated in cells in which TCF3 expression was suppressed by siRNA compared with control cells. This suggests that TCF3 is involved in the induction of SRXN1 expression by methylmercury. We previously reported that TCF3 overexpression suppressed methylmercury-induced apoptosis; in the present study, we found that SRXN1 overexpression also suppressed methylmercury-induced apoptosis, as assessed by cleaved caspase-3 expression. In summary, our results indicate that SRXN1 induced by TCF3-mediated expression is a novel protective factor against methylmercury-induced apoptosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-024-00277-6.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"167-173"},"PeriodicalIF":1.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current hPSC-derived liver organoids for toxicity testing: Cytochrome P450 enzymes and drug metabolism.","authors":"Hyemin Kim, Han-Jin Park","doi":"10.1007/s43188-024-00275-8","DOIUrl":"10.1007/s43188-024-00275-8","url":null,"abstract":"<p><p>Drug-induced hepatotoxicity is the leading cause of attrition of drug candidates and withdrawal of marketed drugs owing to safety concerns. In most hepatotoxicity cases, the parent drugs are metabolized by cytochrome P450 (CYP) enzymes, generating reactive metabolites that bind to intracellular organelles and proteins, ultimately causing hepatocellular damage. A major limitation of animal models, which are widely used for toxicity assessment, is the discrepancy in CYP-mediated drug metabolism and toxicological outcomes owing to species differences between humans and animals. Two-dimensional (2D) hepatocytes were first developed as a promising alternative model using human pluripotent stem cells (hPSCs). However, their CYP expression was similar to that of the fetal liver, and they lacked CYP-mediated hepatic metabolism. CYP expression in hPSC-derived hepatic models is closely correlated with liver maturity. Therefore, liver organoids that are more mature than hPSC-derived hepatic models and mimic the structure and physiological functions of the human liver have emerged as new alternatives. In this review, we explored the role and essentiality of CYPs in human hepatotoxicity, their expression, and epigenetic regulation in hPSC-derived hepatocytes and liver organoids, as well as the current state of liver organoid technology in terms of CYP expression and activity, drug metabolism, and toxicity. We also discussed the current challenges and future directions for the practical use of liver organoids. In conclusion, we highlight the importance of methods and metrics for accurately assessing CYP expression and activity in liver organoids to enable the development of feasible models that reproduce hepatotoxicity in humans.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"105-121"},"PeriodicalIF":1.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro study of silver nanoparticles-induced embryotoxicity using a rat whole embryo culture model.","authors":"Woong-Il Kim, So-Won Pak, Se-Jin Lee, Sin-Hyang Park, In-Sik Shin, Changjong Moon, Wook-Jun Yu, Sung-Hwan Kim, Jong-Choon Kim","doi":"10.1007/s43188-024-00274-9","DOIUrl":"10.1007/s43188-024-00274-9","url":null,"abstract":"<p><p>Recently, our in vivo experiment showed that silver nanoparticles (AgNPs) did not cause developmental toxicity. However, the putative influences of direct exposure of AgNPs on the embryo-fetuses could not be elucidated because the embryo-fetus was exposed to AgNPs through their dams. In this study, the potential impact of AgNPs on embryonic development during the critical phase of organogenesis was examined utilizing a rat whole embryo culture model. This system could separate the direct effects of AgNPs from those that are maternally mediated. To evaluate the embryotoxic potential of AgNPs, embryos were exposed to 1.67, 5, and 15 μg/mL of AgNPs for 48 h. At the conclusion of the culture period, embryonic growth and development were assessed, and morphological abnormalities were systematically evaluated. Also, apoptosis induced by AgNPs was evaluated by TUNEL and immunohistochemistry for caspase-3. At 15 μg/mL, a retardation in embryonic growth and differentiation, accompanied by a heightened frequency of morphological abnormalities, including abnormal axial rotation, open neural tube, absent optic vesicle, and growth retarded were observed in a dose-dependent manner. At this concentration, caspase-3-positive cells appeared in the treated embryonic tissues compared to controls. At 5 μg/mL, AgNPs also caused a decrease in the embryonic otic system, somite number, and total morphological score. No adverse effects on embryonic growth and development associated with the treatment were observed at 1.67 μg/mL. The findings demonstrated that the direct exposure of AgNPs to rat embryos induces developmental delays and morphological abnormalities, and that AgNPs can induce a direct developmental toxicity and caspase-dependent apoptosis in rat embryos.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"189-197"},"PeriodicalIF":1.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress and NRF2 signaling in kidney injury.","authors":"Cherry Ng, Maxine Kim, Yanti, Mi-Kyoung Kwak","doi":"10.1007/s43188-024-00272-x","DOIUrl":"10.1007/s43188-024-00272-x","url":null,"abstract":"<p><p>Oxidative stress plays a crucial role in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and the AKI-to-CKD transition. This review examines the intricate relationship between oxidative stress and kidney pathophysiology, emphasizing the potential therapeutic role of nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of cellular redox homeostasis. In diverse AKI and CKD models, diminished NRF2 activity exacerbates oxidative stress, whereas genetic and pharmacological NRF2 activation alleviates kidney damage induced by nephrotoxic agents, ischemia-reperfusion injury, fibrotic stimuli, and diabetic nephropathy. The renoprotective effects of NRF2 extend beyond antioxidant defense, encompassing its anti-inflammatory and anti-fibrotic properties. The significance of NRF2 in renal fibrosis is further underscored by its interaction with the transforming growth factor-β signaling cascade. Clinical trials using bardoxolone methyl, a potent NRF2 activator, have yielded both encouraging and challenging outcomes, illustrating the intricacy of modulating NRF2 in human subjects. In summary, this overview suggests the therapeutic potential of targeting NRF2 in kidney disorders and highlights the necessity for continued research to refine treatment approaches.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"131-147"},"PeriodicalIF":1.6,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal smoking and its short- or long-term impact on offspring liver pathologies: a review of experimental and clinical studies.","authors":"Daram Yang, Yu Ji Kim, Jong-Won Kim","doi":"10.1007/s43188-024-00271-y","DOIUrl":"10.1007/s43188-024-00271-y","url":null,"abstract":"<p><p>This review investigates the correlation between prenatal tobacco exposure and the risk of liver diseases in offspring. By synthesizing data from clinical trials and animal studies, it provides a comprehensive overview of the potential mechanisms underlying this association. This review begins by analyzing the prevalence of maternal smoking and its impact on fetal development. It then discusses specific liver diseases observed in offspring exposed prenatally to tobacco, such as acute liver injuries and metabolic dysfunction-associated fatty liver disease, and discusses the underlying pathophysiological pathways. Current evidence indicates that altered fetal liver development, oxidative stress, and genetic modifications may predispose offspring to liver diseases. Furthermore, this review highlights the gaps in current research and the need for longitudinal studies to better understand the long-term effects of prenatal tobacco exposure on the liver. The review concludes with recommendations for public health policies aimed at enhancing our understanding of maternal smoking and mitigating its adverse effects on offspring, emphasizing the importance of smoking cessation during pregnancy.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"123-129"},"PeriodicalIF":1.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinine inhibits myogenic differentiation by disrupting AKT signaling pathway.","authors":"Mi Ran Byun, Sou Hyun Kim, RanJu Woo, Seung Jun Noh, Sang Hoon Joo, Young-Suk Jung, Joon-Seok Choi","doi":"10.1007/s43188-024-00273-w","DOIUrl":"10.1007/s43188-024-00273-w","url":null,"abstract":"<p><p>Sarcopenia is a disease characterized by decreased muscle fibers and mass. Although it mainly affects the older adults, it can also occur in various age groups as a secondary effect of medications used for treating certain diseases, such as cancer and diabetes. With population aging, sarcopenia has drawn significant attention owing to its increasing prevalence. However, its pathogenesis remains unclear, and no specific treatment is available. Natural products containing bioactive compounds have long been used as therapeutic agents and are crucial sources for drug development. However, the use of drugs derived from natural extracts is limited because of their ambiguous mechanisms of action and potential side effects. Therefore, a systematic analysis of the potential effects of using natural products is required. In this study, we investigated the effects of the antimalarial drug quinine on myogenic differentiation. Our findings revealed that quinine significantly inhibited the expression of marker genes and proteins associated with myogenic differentiation and markedly impaired muscle regeneration following injury. Furthermore, this reduction occurred when quinine selectively decreased the AKT signaling activity. Quinine reduced muscle protein and gene expression by modulating AKT signaling and inhibiting myogenic differentiation and muscle regeneration. Therefore, quinine may cause sarcopenia, and this risk should be considered when using quinine for treatment.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"81-90"},"PeriodicalIF":1.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of renal fibrosis in PHF20 transgenic mice.","authors":"Uijin Juang, Soohyeon Lee, Suhwan Gwon, Woohyeong Jung, Huonggiang Nguyen, Qingzhi Huang, Beomwoo Lee, So Hee Kwon, Seon-Hwan Kim, In Soo Kim, Jongsun Park","doi":"10.1007/s43188-024-00268-7","DOIUrl":"10.1007/s43188-024-00268-7","url":null,"abstract":"<p><p>Plant homeodomain finger protein 20 (PHF20) plays a crucial role in various biological processes, but its involvement in renal fibrosis remains unclear. This study investigated the role of PHF20 in renal fibrosis using a unilateral ureteral obstruction (UUO) mouse model, a widely accepted model for chronic kidney disease. PHF20 transgenic (PHF20-TG) and wild-type (WT) mice were utilized to explore how PHF20 influences renal inflammation and fibrosis. After UUO surgery, serum analysis revealed elevated creatinine levels and increased inflammatory markers, indicating worsened renal function in PHF20-TG mice. Histological analyses, including H&E, PAS, and Sirius Red staining, confirmed significant tissue damage and fibrosis in the PHF20-TG group. Molecular investigations demonstrated enhanced activation of the TGF-β/SMAD2/3 and NF-κB signaling pathways, both of which are crucial in the progression of renal fibrosis. Our findings suggest that PHF20 overexpression accelerates early-stage renal fibrosis by amplifying inflammatory responses and promoting collagen deposition. This indicates that PHF20 expression could serve as an early marker for renal fibrosis progression.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 1","pages":"71-80"},"PeriodicalIF":1.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}