Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Analgesic and neuroprotective effect of a lipid transfer protein isolated from Morinda citrifolia L. (noni) seeds on oxaliplatin-induced peripheral sensory neuropathy in mice.","authors":"Francisco Rafael Alves Santana Cesário, Jonas Costa de França, Anamaria Falcão Pereira, Diego Bernardo Souza Dias, Amanda Rocha de Oliveira, Andrea Santos Costa, Ana Paula Negreiros Nunes Alves, Nylane Maria Nunes de Alencar, Hermógenes David de Oliveira, Mariana Lima Vale","doi":"10.1007/s00210-025-04216-6","DOIUrl":"10.1007/s00210-025-04216-6","url":null,"abstract":"<p><p>Oxaliplatin, a 3rd-generation platinum compound, has a dose-limiting effect: neurotoxicity manifests as peripheral sensory neuropathy (PNS). Many studies have assessed the different pharmacological properties of a lipid transfer protein isolated from Morinda citrifolia L. (McLTP₁) seeds. This study aimed to evaluate the analgesic and neuroprotective effects of McLTP₁ on oxaliplatin-induced peripheral sensory neuropathy in mice and the mechanisms involved. Male Swiss mice received oxaliplatin twice a week for 28 days. McLTP₁ (1 to 4 mg/kg, p.o.) was administered 60 min before oxaliplatin injection. Mechanical and cold allodynia were assessed once a week via electronic von Frey and acetone tests. TRPA1 and TRPM8 receptor agonists were applied intraplantarly to the hind paw to evaluate their involvement in the antiallodynic mechanism of McLTP₁. ATF3 and c-Fos expression was assessed in the dorsal root ganglia (DRG) or spinal cord (SC) to investigate nociceptive pathway activation and neurotoxic injury. MDA and GSH assays were performed in the sciatic nerve and spinal cord, and histological analysis was performed in the sciatic nerve. Total and differential leukocyte counts were analyzed in the peripheral blood. McLTP₁ prevented the mechanical and cold allodynia and increase in c-Fos and ATF3 expression induced by oxaliplatin in the DRG and SC, possibly involving TRPM8 receptors. McLTP₁ prevented the oxidative stress caused by oxaliplatin in the sciatic nerve and spinal cord and the histological changes associated with oxaliplatin in the sciatic nerve. McLTP₁ inhibited leukopenia, mainly lymphopenia caused by oxaliplatin. McLTP₁ prevents oxaliplatin-induced peripheral sensory neuropathy through its antiallodynic, antioxidant and neuroprotective properties.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"14515-14535"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymeric microneedle advancements in macromolecule drug delivery: current trends, challenges, and future perspectives.","authors":"Madhuchandra Kenchegowda, Mohit Angolkar, Umme Hani, Adel Al Fatease, Farhat Fatima, Sirajunisa Talath, Ayed A Dera, Sharanya Paramshetti, Hosahalli Veerabhadrappa Gangadharappa, Riyaz Ali M Osmani, Heena Shijauddin Kazi","doi":"10.1007/s00210-025-04117-8","DOIUrl":"10.1007/s00210-025-04117-8","url":null,"abstract":"<p><p>Microneedles (MNs) offer a transformative solution for delivering macromolecules, including proteins, RNA, and peptides. These are critical in treating complex diseases but face significant challenges such as immunogenicity, poor stability, high molecular weight, and delivery efficiency. Unlike conventional methods, MNs efficiently bypass biological barriers like the stratum corneum, enabling precise and minimally invasive transdermal drug delivery. This review explores various MN types such as solid, coated, hollow, hydrogel-forming, and dissolving and their therapeutic applications in cancer immunotherapy, diabetes management, and osteoporosis treatment. For instance, dissolving MNs have been employed for transdermal insulin delivery, enhancing patient compliance and therapeutic outcomes. Similarly, hydrogel MNs have shown promise in sustained drug release for immunotherapy applications. By addressing cost and scalability issues, polymeric MNs demonstrate significant potential for clinical translation, paving the way for innovations in macromolecule delivery, diagnostics, and personalised medicine. This review underscores the pivotal role of MNs in redefining drug delivery systems, offering improved efficacy, patient comfort, and accessibility.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"12951-12985"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research mechanism of DBP and DEHP in the development of PCOS based on network toxicology and molecular docking.","authors":"Kang Yi-Fan, Liu Jian-Rong","doi":"10.1007/s00210-025-04173-0","DOIUrl":"10.1007/s00210-025-04173-0","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) constitutes a prevalent endocrine disorder among females, exhibiting a significant incidence rate. The etiology of PCOS predominantly attributes to environmental determinants. Phthalate esters, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), have been demonstrated to exert detrimental effects on reproductive function. However, the effects of these plasticizers on female reproductive health have not been clearly investigated. In the present investigation, we employed network toxicological methodologies to delineate the pivotal genes and associated pathways that are implicated in the pathogenesis of PCOS induced by DBP and DEHP. Molecular docking methodologies were employed to ascertain the interaction between the investigational compound and the designated target protein. The present study delineates pivotal targets, namely AKT1, SRC, PIK3R1, EGFR, ESR1, and STAT3, which are instrumental in the mediation of PCOS. The genes predominantly participate in the EGFR pathway, insulin signaling pathway, and oocyte damage, significantly compromising female ovarian functionality. This investigation underscores the integration of network toxicology, molecular docking, and cell experiment methodologies to elucidate the toxicological properties and underlying molecular mechanisms of plasticizers in the context of PCOS. This study provides a prospective therapeutic target to mitigate the harmful effects of plasticizers on female reproductive health.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"14239-14255"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidrug-resistant gram-negative bacteria in ICU patients of a tertiary care hospital in Saudi Arabia: distribution of carbapenemase genes in clinical and rectal swab samples.","authors":"Amal Daher Alshammari, Alharbi Mohammed Salem, Sumayyah Mohammad Almarshedy, Ehab Rakha, Mohd Saleem","doi":"10.1007/s00210-025-04194-9","DOIUrl":"10.1007/s00210-025-04194-9","url":null,"abstract":"<p><p>Antimicrobial resistance among Gram-negative bacteria is a growing clinical challenge. This study aimed to assess bacterial distribution, antimicrobial susceptibility, and carbapenemase gene prevalence in clinical isolates. A total of 154 patients (mean age: 57.51 ± 18.75 years) were included. Specimens were primarily sputum (42.2%), blood (22.7%), and urine (18.8%). Bacterial isolates included K pneumoniae (43.8%), A. baumannii (24%), and P. aeruginosa (13.5%). Antimicrobial susceptibility testing (AST) was conducted to evaluate resistance patterns. MDR was detected, with alarming resistance to carbapenems, β-lactams, and fluoroquinolones. A. baumannii and P. aeruginosa exhibited near-total resistance to Imipenem (IPM), Meropenem (MRP), and Ertapenem (ETP), indicating extensive drug resistance (XDR). K. pneumoniae demonstrated exceptionally high resistance to carbapenems (IPM: 90.5%, MRP: 92.9%) and β-lactam antibacterial drugs (> 90%). Fluoroquinolone resistance exceeded 90% for Ciprofloxacin and Levofloxacin in A. baumannii, P. aeruginosa, and K. pneumoniae. Aminoglycosides, particularly Gentamicin, showed moderate resistance (A. baumannii: 87%, P. aeruginosa: 69.2%). Tigecycline remained one of the few viable treatment options against K. pneumoniae. Biofilm formation was significant, with 63.6% of isolates producing biofilm, particularly P. aeruginosa (80.9%), K. pneumoniae (67.2%), and A. baumannii (48.6%), increasing their pathogenic potential. Carbapenemase production was detected in 42.9% of isolates. The most prevalent genes were blaOXA- 48 (15.6%), blaNDM (8.4%), and blaVIM (7.1%), with co-expression in 9.7% of isolates. K. pneumoniae exhibited the highest risk for carbapenemase production (OR: 4.23, p < 0.001), whereas A. baumannii had a significantly lower risk (OR: 0.20, p = 0.005). Screening swabs showed more OXA- 48 (42.1%), while clinical isolates had more NDM and VIM. Alternative resistance mechanisms were suggested in 57.3% of clinical cases. The overwhelming prevalence of MDR and Carbapenem resistance among Gram-negative bacteria, particularly K. pneumoniae and A. baumannii, emphasizes an urgent need for strict antimicrobial stewardship, advanced infection control strategies, and novel therapeutic interventions to combat resistance spread.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"14175-14188"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory phenotypes of immune cells after myocardial infarction and prospects of therapeutic strategy.","authors":"Jiacheng Zhang, Shuai Feng, Yannan Geng, Xiaoli Wang, Zhen Wang, Yang Liu","doi":"10.1007/s00210-025-04167-y","DOIUrl":"10.1007/s00210-025-04167-y","url":null,"abstract":"<p><p>Often causing negative cardiac remodeling and heart failure, a major threat to human life and health, myocardial infarction (MI) is a cardiovascular disease with a high morbidity and fatality rate worldwide. Maintaining ordinary heart function depends significantly on the immune system. Necrotic cardiomyocyte signals promote specific immunity and activate general immunity as the disease progresses in MI. Complex immune cells play a key role in all stages of MI progression by removing necrotic cardiomyocytes and tissue and promoting the healing of damaged tissue cells. Immune cells can help to regrow injured heart muscle as well as enable both inflammation and cardiomyocyte death. Immune cells are essential elements that help the immune system carry out its protective function. There are two types of immunity: nonspecific immunity and specific immunity. Developed throughout the long-term evolution of species, nonspecific immunity (including macrophages, myeloid-derived suppressor cells MDSC, natural killer cells NK, neutrophils, and dendritic cells DC) offers immediate and conservative host defense that might destroy healthy tissues because of its nonspecific nature. Precisely acquired immunity, specific immunity helps humoral and cellular immunity mediated through B and T cells correspondingly. These findings offer crucial information needed for the creation of effective immunomodulatory treatment, as discussed in this article.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"13225-13247"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: The selective 5-LOX inhibitor 11-keto-β-boswellic acid protects against myocardial ischemia reperfusion injury in rats: involvement of redox and inflammatory cascades.","authors":"Shimaa M Elshazly, Dalia M Abd El Motteleb, Noha N Nassar","doi":"10.1007/s00210-025-04602-0","DOIUrl":"10.1007/s00210-025-04602-0","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"14555"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirzepatide increased force of contraction in the isolated human atrium.","authors":"Joachim Neumann, Britt Hofmann, Uwe Kirchhefer, Ulrich Gergs","doi":"10.1007/s00210-025-04214-8","DOIUrl":"10.1007/s00210-025-04214-8","url":null,"abstract":"<p><p>Tirzepatide is an approved drug that is used to treat type 2 diabetes. Tirzepatide is a peptide comprised of 39 amino acids and activates glucose-dependent insulinotropic polypeptide receptors (GIPR) and glucagon-like peptide-1 receptors (GLP-1R). Via GIPR and GLP-1R, tirzepatide stimulated in cell culture adenylyl cyclases (AC) and thereby elevated the cellular content of 3':5' cyclic adenosine monophosphate (cAMP). We tested the hypothesis that tirzepatide augmented the force of contraction (FOC) in isolated electrically driven (1 Hz) human right atrial preparations (HAP) obtained during open heart surgery from adult patients. Cumulatively applied tirzepatide, starting at nanomolar concentrations, raised FOC in a concentration-dependent manner and a time-dependent manner (p < 0.05). The positive inotropic effects (PIE) of tirzepatide were attenuated by about a quarter by a GIPR antagonist (100 nM, Pro3-GIP) and by about three quarters by a GLP-1R antagonist (100 nM, exendin9-39) in HAP. Tirzepatide (1 µM) was less effective than 1 µM isoprenaline in raising FOC in HAP. The inhibitor of the cAMP-dependent protein kinase called H89 reversed the PIE of tirzepatide. We suggest that tirzepatide probably acts via stimulation of GIPR and GLP-1R to exert a PIE in HAP.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"14451-14459"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002056","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":"Anti-neoplastic activity of celastrol in experimentally-induced mammary adenocarcinoma in mice: targeting wnt/β-catenin signaling pathway.","authors":"Mohamed M Salama, Randa A Zaghloul, Rania M Khalil, Mamdouh M El-Shishtawy","doi":"10.1007/s00210-025-04148-1","DOIUrl":"10.1007/s00210-025-04148-1","url":null,"abstract":"<p><p>Natural bioactive compounds with anti-neoplastic effects, such as celastrol (CLS), have attracted considerable interest in recent years. The present study aimed to investigate the effect of CLS on wnt/β-catenin signaling, and its potential combination with doxorubicin (Dox) to enhance chemotherapeutic effects. After intramuscular inoculation of Ehrlich tumor cells, tumor-bearing mice received CLS (2 mg/kg, i.p), Dox (5 mg/kg, once/week, i.p), and their combination for 21 days. Treatment with CLS showed showing antioxidant and anti-inflammatory, as evidenced by a significant increase in glutathione content and a significant decrease in the malondialdehyde, interleukin 6, and interleukin 1β concentrations. CLS also inhibited VEGF-mediated angiogenesis. The current study revealed that CLS downregulated β-catenin gene expression with subsequent downstream target genes, such as cyclin-D1, and survivin, which dampens tumor cell proliferation and triggers cell cycle arrest as well as induces apoptosis as indicated by the increased expression of p53, caspase-3. The current study concludes that CLS exerted its anti-neoplastic activity by suppressing the wnt/β-catenin signaling pathway, and opens a new perspective for combining CLS with Dox to enhance its chemotherapeutic effects and reduce the oxidative imbalance and inflammatory responses associated with Dox treatment.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"14327-14339"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010536","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":"Alternative medicines in oncology: a focus on natural products against gastric cancer.","authors":"Ahmed S Doghish, Mohamed Bakr Zaki, Abdulrahman Hatawsh, Nourhan Elfar, Nora A A Alhamshry, Mai A Abd-Elmawla, Nora M Aborehab, Abdullah F Radwan, Rewan Moussa, Sherif S Abdel Mageed, Mustafa Ahmed Abdel-Reheim, Osama A Mohammed, Hanan Elimam","doi":"10.1007/s00210-025-04058-2","DOIUrl":"10.1007/s00210-025-04058-2","url":null,"abstract":"<p><p>There is justification for optimism about the potential contribution of alternative medicines to cancer management, which now ranks as the second leading cause of death globally. Primary carcinogens arise from several sources, including agriculture, industry, and dietary intake. Gastric cancer (GC) significantly affects an individual's health due to its classification as a malignant tumor associated with elevated mortality and morbidity rates. Chemotherapy is now widely regarded as the gold standard for treating GC. Chemotherapy, however, exerts significant detrimental effects on human health, including irreversible damage to multiple organs. Consequently, it is essential to employ innovative strategies for cancer prevention. Natural products are now the focus of intensive study due to their efficacy against cancer and low toxicity levels. Natural compounds have shown a diverse range of anti-cancer properties. This review aims to emphasize studies on natural compounds that inhibit metastasis, induce apoptosis in GC, and decrease cellular proliferation. All the natural compounds from different sources were incorporated in this review not only medicinal plants derived compounds. This review aims to examine a comprehensive array of natural therapies that may enhance human health and facilitate GC prevention without inducing discernible negative effects. Moreover, this review aims to discuss the toxic side effects of phytochemicals and shed light on mechanisms underlying the action of potential natural products against GC. This review offers a novel perspective by integrating a broad spectrum of natural compounds from diverse sources, not limited to medicinal plants, to explore their anti-cancer properties against gastric cancer.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"13065-13086"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing lead toxicity with advanced nanotechnology methods.","authors":"Alireza Ghassemi Toussi, Sadaf Sadat Rafati, Elham Einafshar","doi":"10.1007/s00210-025-04170-3","DOIUrl":"10.1007/s00210-025-04170-3","url":null,"abstract":"<p><p>Lead exposure remains a pressing global health concern, particularly due to its pervasive nature in our environment and the associated toxicological risks. This review article explores the multifaceted aspects of lead, including its physical and chemical properties, the epidemiological prevalence of lead poisoning, and the pathophysiological mechanisms underlying its toxicity. Clinical manifestations, particularly in occupational settings, highlight the significant health impacts on vulnerable populations. We will discuss current methodologies for the identification and detection of lead, emphasizing the importance of prevention and treatment strategies to mitigate exposure. Given the growing interest in sustainable remediation approaches, microbial remediation techniques are evaluated for their effectiveness in addressing lead contamination. Furthermore, this review underscores the potential of nanoparticles in modifying lead toxicity. Focusing on their role in both in vitro and in vivo conditions, we examine how nanoparticles can influence lead bioavailability and toxicity in various environments, including wastewater, soil, and plants. Our findings suggest that nanoparticles offer innovative solutions for reducing lead's harmful effects, thus providing a pathway for enhanced environmental and public health protection. This comprehensive review aims to inform researchers, healthcare professionals, and policymakers about the potential of cutting-edge nanotechnology methods in combating lead toxicity and improving health outcomes.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"13205-13224"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}