Toxicology in Vitro最新文献

{"title":"Tripartite motif 22 interacts with protein phosphatase magnesium-dependent 1 A to aggravate radiation-induced epithelial-mesenchymal transition and fibrogenesis in lung epithelial cells","authors":"Jinhua Lu ,&nbsp;Menglei Wang ,&nbsp;Yeyue Zhou ,&nbsp;Yazhen Zhong ,&nbsp;Shengyou Lin","doi":"10.1016/j.tiv.2024.105972","DOIUrl":"10.1016/j.tiv.2024.105972","url":null,"abstract":"<div><div>Radiation-induced lung injury (RILI) is the damage to lung tissue caused by radiation. Epithelial-mesenchymal transition (EMT) and fibrogenesis in radiated lung epithelial cells play critical roles in RILI. Tripartite motif-containing (TRIM) family proteins have been shown to be involved in fibrotic diseases, but whether TRIM22 plays a role in RILI and relative underlying mechanism remain unexplored. Here, we reported a unique comprehensive analysis of the impact of TRIM22 on radiation-induced EMT and fibrogenesis in A549 and BEAS-2B cells. Cell viability and proliferation were measured by Cell-Counting Kit (CCK)-8 and colony formation assays. The interaction between TRIM22 and protein phosphatase magnesium-dependent 1 A (PPM1A) was validated using co-immunoprecipitation. A chromatin immunoprecipitation assay was used to verify the interaction between SMAD3 and TRIM22 promoter. Cell viability and proliferation were decreased by 8 Gy raddition. TRIM22 was elevated in a dose- and time-dependent manner after radiation, and its knockdown reduced EMT and fibrogenesis. TRIM22 could interact with PPM1A and promote its ubiquitination to activate the TGF-β1/Smad pathway. The overexpression of PPM1A abolished TRIM22-mediated EMT and fibrogenesis. Meanwhile, SMAD3 could bind to the TRIM22 promoter to elevate its expression. This study revealed a novel TRIM22/PPM1A/Smad3 signaling pathway that contributes to the raddition-induced EMT and fibrogenesis, which would provide novel targets and strategies for treating RILI.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105972"},"PeriodicalIF":2.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conditioned medium of human umbilical cord-mesenchymal stem cells cultivated with human cord blood serum enhances stem cell stemness and secretome profiles","authors":"Palakorn Kaokaen,&nbsp;Amorn Pangjantuk,&nbsp;Phongsakorn Kunhorm,&nbsp;Wilasinee Promjantuek,&nbsp;Nipha Chaicharoenaudomrung,&nbsp;Parinya Noisa","doi":"10.1016/j.tiv.2024.105973","DOIUrl":"10.1016/j.tiv.2024.105973","url":null,"abstract":"<div><div>The proteins secreted by human umbilical cord mesenchymal stem cells (hUC-MSCs) may enhance tissue regeneration and wound healing. Traditional hUC-MSC cultures may not be enough since they undergo recurrent cellular senescence during large-scale production. This decreases the therapeutic ability of hUC-MSCs by altering genes and proteins that control stemness, proliferation, and protein release. Human cord blood serum (CBS) and the middle-density technique were used to evaluate hUC-MSC regeneration ability. To evaluate early-passage hMSCs for secretome-based therapies, they were expanded and secreted in vitro. After 4 days, hUC-MSCs cultivated at 3000 cells/cm² and supplemented with 1 ng/ml CBS showed increased growth, cell proliferation, and a much lower population doubling time. CBS treatment reduced CD34, CD45, and HLA-DR levels in human umbilical cord mesenchymal stem cells (hUC-MSCs) by less than 2 %. Positive markers such CD73, CD90, and CD105 were found at &gt;97 %, like control hUC-MSCs. Over extended culture, this combination culture can increase survival, proliferation, and stemness and postpone cell death and hUC-MSC senescence. The protein profile and hUC-MSC secretion were improved to make MSC secretion protein therapeutic. This improves cell-free treatment, proliferation, and wound healing in human skin cells. To improve cell-based transplantation or cosmeceutical manufacturing, this technique can boost hUC-MSC regeneration capacity.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105973"},"PeriodicalIF":2.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tannic acid modulates SARS-CoV-2 pathogenesis by curbing key host receptors and oxidative stress","authors":"Akshaya Rani Augustus ,&nbsp;Yashwanth Radhakrishnan ,&nbsp;James Prabhanand Bhaskar ,&nbsp;Suresh Ramamurthi ,&nbsp;Karutha Pandian Shunmugiah","doi":"10.1016/j.tiv.2024.105971","DOIUrl":"10.1016/j.tiv.2024.105971","url":null,"abstract":"<div><div>The novel coronavirus SARS-CoV-2, which wrecked havoc around the world in the recent years through COVID-19, gains entry into the host cell through various receptors. Development of therapies targeting host–pathogen interaction will be a key to curb the infection as it potentially suppresses viral attachment and entry into the host. Boundless bioactives abundant in natural resources are the important source of new as well as safer alternatives. Tannic acid, a polyphenolic compound found abundantly in various plant sources, has gained much attention owing to its multifaceted pharmacological properties. This research paper presents a comprehensive investigation on antioxidant, anti-inflammatory and anti-viral abilities of tannic acid, substantiated through a triad of methodologies: <em>in silico</em>, <em>in vitro</em> and <em>in vivo</em> approaches. <em>In vitro</em> experiments, confirmed the antioxidant and anti-inflammatory efficacy as well as the host receptor modulating potential of tannic acid. <em>In silico</em> docking analyses elucidated the molecular interactions between tannic acid and key host receptors involved in inflammation and viral pathogenesis. Furthermore, the <em>in vivo</em> studies involving <em>Danio rerio</em> provided a holistic understanding of the systemic impact of tannic acid, including its antioxidant effects by mitigating the oxidative stress.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105971"},"PeriodicalIF":2.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclosporin A toxicity on endothelial cells differentiated from induced pluripotent stem cells: Assembling an adverse outcome pathway","authors":"Zahra Mazidi ,&nbsp;Matthias Wieser ,&nbsp;Nicoleta Spinu ,&nbsp;Adelheid Weidinger ,&nbsp;Andrey V. Kozlov ,&nbsp;Kristijan Vukovic ,&nbsp;Sara Wellens ,&nbsp;Cormac Murphy ,&nbsp;Pranika Singh ,&nbsp;Liadys Mora Lagares ,&nbsp;Madhusudhan Reddy Bobbili ,&nbsp;Lisa Liendl ,&nbsp;Markus Schosserer ,&nbsp;Andreas Diendorfer ,&nbsp;Bruno Bettelheim ,&nbsp;Wolf Eilenberg ,&nbsp;Thomas Exner ,&nbsp;Maxime Culot ,&nbsp;Paul Jennings ,&nbsp;Anja Wilmes ,&nbsp;Johannes Grillari","doi":"10.1016/j.tiv.2024.105954","DOIUrl":"10.1016/j.tiv.2024.105954","url":null,"abstract":"<div><div>Cyclosporin A (CSA) is a potent immunosuppressive agent in pharmacologic studies. However, there is evidence for side effects, specifically regarding vascular dysfunction. Its mode of action inducing endothelial cell toxicity is partially unclear, and a connection with an adverse outcome pathway (AOP) is not established yet. Therefore, we designed this study to get deeper insights into the mechanistic toxicology of CSA on angiogenesis. Stem cells, especially induced pluripotent stem cells (iPSCs) with the ability of differentiation to all organs of the body, are considered a promising <em>in vitro</em> model to reduce animal experimentation. In this study, we differentiated iPSCs to endothelial cells (ECs) as one cell type that in other studies would allow to generate multi-cell type organoids from single donors. Flow cytometry and immunostaining confirmed our scalable differentiation protocol. Then dose and time course experiments assessing CSA cytotoxicity on iPS derived endothelial cells were performed. Transcriptomic data suggested CSA dependent induction of reactive oxygen species (ROS), mitochondrial dysfunction, and impaired angiogenesis <em>via</em> ROS induction which was confirmed by <em>in vitro</em> experiments. In order to put these data into a potential adverse outcome pathway (AOP) context, we performed a literature review for CSA-mediated endothelial cell toxicity and combined our experimental data with the publicly available knowledge. Such an AOP will help to design <em>in vitro</em> test batteries and to model events observed in human toxicity studies, as well in predictive toxicology.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105954"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro toxicity of two functionalized reduced graphene oxide materials with potential application in food packaging","authors":"Óscar Cebadero-Domínguez ,&nbsp;Leticia Diez-Quijada ,&nbsp;Sergio López ,&nbsp;Alejandro Prieto ,&nbsp;María Puerto ,&nbsp;Ana M. Cameán ,&nbsp;Angeles Jos","doi":"10.1016/j.tiv.2024.105970","DOIUrl":"10.1016/j.tiv.2024.105970","url":null,"abstract":"<div><div>Functionalized graphene materials have been proposed as nanofillers in food packaging applications as they improve the characteristics of the resulting nanocomposites. But food contact materials require a toxicity evaluation previous their authorization and use. In this sense, reduced graphene oxide functionalized with dodecyl amine (DA-rGO), and [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MTAC-rGO) were characterized and their internalization and cytotoxicity in Caco-2 and HepG2 cultures evaluated. Cell viability decreased from 100 μg/mL in all experimental trials, and oxidative stress by means of a reduction in glutathione levels was evidenced as one of the potential toxicity mechanisms involved. Moreover, both materials were subjected to an <em>in vitro</em> digestion process to investigate their potential changes along the gastrointestinal tract. Digested samples were characterized, and the cytotoxicity also evaluated showing an exacerbation. These results raise concerns about the impact of these materials after oral exposure, and therefore further research is necessary.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105970"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Exploring the combined impact of cisplatin and copper-cysteamine nanoparticles through Chemoradiation: An in-vitro study” [Toxicology in vitro 99 (2024) 105878].","authors":"Mahsa Ejtema ,&nbsp;Nahid Chegeni ,&nbsp;Amanollah Zarei-Ahmady ,&nbsp;Zeinab Salehnia ,&nbsp;Masoumeh Shamsi ,&nbsp;Sasan Razmjoo","doi":"10.1016/j.tiv.2024.105968","DOIUrl":"10.1016/j.tiv.2024.105968","url":null,"abstract":"","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105968"},"PeriodicalIF":2.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer activity of EMD37 against human head and neck cancer: Impact on apoptotic and inflammatory machineries","authors":"Marwa Sharaky ,&nbsp;Eman M.E. Dokla ,&nbsp;Amal Kamal Abdel-Aziz","doi":"10.1016/j.tiv.2024.105967","DOIUrl":"10.1016/j.tiv.2024.105967","url":null,"abstract":"<div><div>Accumulating evidence emphasizes the tumorigenic role of epidermal growth factor receptor (EGFR) in head and neck cancer (HNC). Although cetuximab is the sole anti-EGFR approved by the Food and Drug Administration for treating HNC patients.its response rates are modest. Thus, novel effective and tolerable therapeutic strategies are urged. We previously reported the capability of oxadiazole derivatives to degrade tyrosine kinase receptors including EGFR and exhibit potent anticancer activities against NCI-60 panel which does not include HNC. The aim of this study was to investigate the potential anticancer activity of EMD37, a novel 1,2,4-oxadiazole derivative, against human HNC cells and if effective, to examine the effect of EMD37 on apoptotic and inflammation mediators. Indeed, EMD37 exhibited potent cytotoxicity against patient-derived HNC cell lines (HNO-97, HN-9 and FaDu). Delving deeper, EMD37 triggered intrinsic and extrinsic apoptosis in HNC cells as evidenced by increased levels of caspase-8, caspase-9, caspase-3, caspase-7, caspase-6, TP53BP1 tumor suppressor and Bax, and downregulated anti-apoptotic Bcl-2 protein. EMD37 also significantly abrogated the levels of pro-inflammatory interleukin-1β, interleukin-6, cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MMP-9) which are heightened in HNC. Bioinformatic analysis revealed that BCL2^low, IL6^low and MMP9^low HNC biospecimens are enriched with epithelial cell differentiation gene set, and CASP8^high cohort is enriched with extrinsic apoptosis. Altogether, this study emphasizes the therapeutic potential of targeting the apoptotic and inflammatory machineries in HNC using EMD37.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105967"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat shock protein HSPA8 impedes hemin-induced cellular-toxicity in liver","authors":"Alok Kumar Pandey,&nbsp;Vishal Trivedi","doi":"10.1016/j.tiv.2024.105959","DOIUrl":"10.1016/j.tiv.2024.105959","url":null,"abstract":"<div><div>Accumulation of hemin in cells, tissues, and organs is one of the major pathological conditions linked to hemolytic diseases like malaria. Pro-oxidant hemin confers high toxicity following its accumulation. We tested the cellular toxicity of hemin on HepG2 cells by exploring modulation in various cellular characteristics. Hemin reduces the viability of HepG2 cells and brings about visible morphological changes. Hemin causes perforations on the surface of HepG2 cells observed through SEM. Hemin leads to the extracellular release of liver enzymes and reduces the wound-healing potential of HepG2 cells. Hemin leads to the fragmentation of HepG2 DNA, arrests the cell cycle progression in the S-phase and induces apoptosis in these cells. Western blot analysis revealed that hemin triggers both the extrinsic and intrinsic pathways of apoptosis in HepG2 cells. We have already shown that the cytoprotective protein HSPA8 can polymerize hemin and minimize its toxicity. Similar experiments with hemin in the presence and absence of HSPA8 showed that HSPA8 reverses all the tested toxic effects of hemin on HepG2 cells. The protection from hemin toxicity in HepG2 cells appeared to be due to the extracellular polymerization of hemin by HSPA8.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105959"},"PeriodicalIF":2.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Food grade titanium dioxide induced endoplasmic reticulum stress in colon cells: Comparison between normal and colorectal carcinoma cells","authors":"Alina Uribe-García ,&nbsp;Estefany I. Medina-Reyes ,&nbsp;Carlos A. Flores-Reyes ,&nbsp;Alejandro A. Zagal-Salinas ,&nbsp;Octavio Ispanixtlahuatl-Meraz ,&nbsp;Eduardo Delgado-Armenta ,&nbsp;Miguel Santibáñez-Andrade ,&nbsp;Cesar M. Flores ,&nbsp;Yesennia Sánchez-Pérez ,&nbsp;Claudia M. García-Cuéllar ,&nbsp;Yolanda I. Chirino","doi":"10.1016/j.tiv.2024.105957","DOIUrl":"10.1016/j.tiv.2024.105957","url":null,"abstract":"<div><h3>Background</h3><div>Food-grade titanium dioxide (E171) has been under scrutiny in the last decade since its possible adverse effects; however, the cellular mechanisms underlying E171 toxicity have not been thoroughly described.</div></div><div><h3>Aim</h3><div>We aimed to compare the effects of E171 on endoplasmic reticulum (ER) homeostasis in normal and cancer colon cells.</div></div><div><h3>Experimental design</h3><div>We exposed normal, carcinoma, and adenocarcinoma cells to 0.1, 1, 10, 50 and 100 μg/cm² of E171 for 24, 48 and 72 h, and we evaluated ER stress, cell viability, titanium uptake, intracellular calcium concentration, and gene expression related to unfolded protein response (UPR) and chaperone pathways.</div></div><div><h3>Results</h3><div>Cell viability decreased only after 72 h of exposure to 100 μg/cm² of E171. Adenocarcinoma cells internalized higher titanium amounts than normal and carcinoma cells, but the effects in ER distribution, intracellular calcium concentration, and gene expression were similar among the three cell lines. The expression of UPR and chaperone pathways were downregulated at the lowest concentrations but upregulated at the highest concentrations in the three cell lines.</div></div><div><h3>Conclusion</h3><div>E171 induces ER stress through alterations in ER distribution, intracellular calcium, and UPR and chaperone protein pathways.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105957"},"PeriodicalIF":2.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin-loaded emulsome nanoparticles induces apoptosis through p53 signaling pathway in pancreatic cancer cell line PANC-1","authors":"Zuleyha Demirci ,&nbsp;Zeynep Islek ,&nbsp;Halime Ilhan Siginc ,&nbsp;Fikrettin Sahin ,&nbsp;Mehmet H. Ucisik ,&nbsp;Zeynep Busra Bolat","doi":"10.1016/j.tiv.2024.105958","DOIUrl":"10.1016/j.tiv.2024.105958","url":null,"abstract":"<div><div>Pancreatic cancer is a global health problem with a poor prognosis, limited treatment options and low survival rates of patients. Thus, the exploration of novel treatment approaches is crucial. Curcumin shows promise in pancreatic cancer. Curcumin has anticancer properties promoting apoptosis through the p53 pathway. However, adverse effects and low bioavailability are curcumin's main drawbacks and its delivery by nanoparticles could improve its effectiveness as a treatment option. Curcumin-loaded emulsome nanoparticles (CurEm) have shown promise in colorectal, hepatocellular, and prostate cancers. This study aims to evaluate the anticancer potential of CurEm in pancreatic cancer cell line PANC-1. The cytotoxic effects of CurEm on PANC-1 cells show cytotoxicity in dose and time-dependent manner. The selected dose 30 μM CurEm resulted spheroidal morphology in PANC-1 cells and colony forming and scratch assay conducted demonstrated significant growth inhibition and decrease in migration ability, respectively. Cell cycle analysis shows that CurEm induces G2/M arrest in PANC-1 cells. CurEm-treated PANC-1 cells showed a significant increase in p53 and Caspase 3 genes, while a significant decrease in Bcl-2 genes compared to untreated group. Western blot results showed parallel results to qPCR analysis for Bcl-2 protein levels. Interestingly, we saw low p53 protein levels in CurEm-treated PANC-1 cells. These findings shed light on the potential of CurEm as an effective and stable therapeutic approach for pancreatic cancer.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105958"},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}