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all-trans retinoic acid alleviates transmissible gastroenteritis virus-induced intestinal inflammation and barrier dysfunction in weaned piglets

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1131-1144页

作者： Junning Pu Daiwen Chen Gang Tian Jun He Ping Zheng Zhiqing Huang Xiangbing Mao Jie Yu Yuheng Luo Junqiu Luo Hui Yan Aimin Wu Bing Yu Institute of Animal Nutrition Sichuan Agricultural UniversityChengdu 611130SichuanPeople’s Republic of China Key Laboratory of Animal Disease-Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan Province611130 ChengduSichuanPeople’s Republic of China

Background transmissible gastroenteritis virus(TGEV)is one of the main pathogens causing severe diarrhea of *** pathogenesis of TGEV is closely related to intestinal ***-trans retinoic acid(ATRA)is the main active metabolite of vitamin A,which has immunomodulatory and anti-inflammatory ***,it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in *** study aimed to investigate the effects of ATRA on growth performance,diarrhea,intestinal inflammation and intesti-nal barrier integrity of TGEV-challenged *** In a 19-d study,32 weaned piglets were randomly divided into 4 treatments:Control group(basal diet),TGEV group(basal diet+TGEV challenge),TGEV+ATRA5 group(basal diet+5 mg/d ATRA+TGEV challenge)and TGEV+ATRA15 group(basal diet+15 mg/d ATRA+TGEV challenge).On d 14,piglets were orally administered TGEV or the sterile *** Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV(Ptransporter related genes(GLUT2 and SLC7A1)in jejunal mucosa of TGEV-challenged piglets(P<0.05).Furthermore,5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibit-ing the release of interleukin(IL)-1β,IL-8 and tumor necrosis factor-α(TNF-α),and promoting the secretion of IL-10 and secretory immunoglobulin A(sIgA)(P<0.05).Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes(TLR3,TLR4,RIG-I,MyD88,TRIF and MAVS)and the phosphorylation level of nuclear factor-κB-p65(NF-κB p65),and

关键词： all-trans retinoic acid Inflammation Intestinal barrier Piglets transmissible gastroenteritis virus

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all-trans retinoic acid inhibited angiotensin Ⅱ-induced increase in cell growth and collagen secretion of neonatal cardiac fibroblasts

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Acta Pharmacologica Sinica 2006年第4期27卷 423-429页

作者： Yan HE~2 Ying HUANG~2 Li ZHOU~2 Li-min LU~2 Yi-chun ZHU~2 Tai YAO~(2,3,4) ~2Department of Physiology and Pathophysiology,and ~3State Key Laboratory for Medical Neurobiology.Fudan University Shanghai Medical College.Shanghai 200032.China Department of Physiology and Pathophysiology Fudan University Shanghai Medical College Shanghai China State Key Laboratory for Medical Neurobiology Fudan University Shanghai Medical College Shanghai China

Aim:To determine whether all-trans retinoic acid(atRA)acts to modulate angio-tensin Ⅱ(Ang Ⅱ)-induced cardiac fibroblast cell growth and collagen ***:Cultured neonatal rat cardiac fibroblasts(CF)were used in the experiment.A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay wasused to detect cell growth of the CF;and immunocytochemistry and Westernblotting were used to measure the production and secretion of collagen and theexpression of transforming growth factor-β1(TGF-β1)by the ***:atRA(1×10-7to 1×10-5mol/L)inhibited the Ang Ⅱ-induced increase in cell growth of CF(P<0.05).Ang Ⅱ stimulated the secretion of collagen types Ⅰ and Ⅲ by the *** effect was blocked by AT1receptor antagonist losartan(1×10-6mol/L),butnot by AT2receptor antagonist PD 123319 (up to 1×10-6mol/L).Exposure of CF toatRA(1×10-5mol/L)attenuated the Ang Ⅱ-induced increase in the secretion ofcollagen types Ⅰ and Ⅲ(P<0.05).atRA (1×10-5mol/L)also blocked the Ang Ⅱ-induced increase in the expression of TGF-β***:atRA inhibits the AngⅡ-induced increase in cell growth and collagen secretion of neonatal rat *** of atRA is possibly mediated by lowering the TGF-β*** observa-tions support the notion that atRA is a potential candidate for the prevention andtherapy of cardiac remodeling.

关键词： cardiac fibroblast angiotensin Ⅱ all-trans retinoic acid collagen secretion transforming growth factor-β1

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all-trans retinoic acid(ATRA)inhibits insufficient radiofrequency ablation(IRFA)-induced enrichment of tumor-initiating cells in hepatocellular carcinoma

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Chinese Journal of Cancer Research 2021年第6期33卷 694-707页

作者： Song Wang Jingtao Liu Hao Wu Anna Jiang Kun Zhao Kun Yan Wei Wu Haibo Han Yanhua Zhang Wei Yang Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Department of UltrasoundPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Department of PharmacyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Department of Clinical LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:Local recurrence of hepatocellular carcinoma(HCC)after radiofrequency ablation(RFA)treatment remains a serious ***-initiating cells(TICs)are thought to be responsible for tumor ***,we investigated the effect of the TIC differentiation inducer,all-trans retinoic acid(ATRA),on RFA and explored the potential molecular ***:The proportions of CD133+and epithelial cell adhesion molecule(Ep CAM);TICs in recurrent HCC after RFA and primary HCC were first determined in ***,the effect of heat intervention or insufficient RFA(IRFA)on the malignant potential of HCC cells,including cell migration,sphere formation ability,tumor growth,the proportion of CD133+and Ep CAM+TICs and expression of stem cell-related genes,was evaluated in vitro and in ***,the effect of ATRA on the tumor growth and the proportion of TICs was ***:In clinical data,a higher proportion of CD133+and Ep CAM+TICs was found in recurrent tumors than in primary *** vitro heat intervention promoted the cell migration and sphere formation ***,it increased the proportion of CD133+and Ep CAM+TICs and the expression of stem cell-related *** addition,after IRFA the residual tumors in xenografts grew faster and had more TICs than untreated *** remarkably inhibited residual tumor growth after IRFA by elimination of TICs though the PI3 K/AKT *** treatment with ATRA resulted in longer survival outcomes in mouse xenografts than RFA ***:ATRA,as a TIC differentiation inducer,could help to improve the effect of RFA treatment,which was partially attributed to its effect against *** data indicated its potential as an alternative drug in the development of better therapeutic strategies for use in combination with RFA.

关键词： Radiofrequency ablation hepatocellular carcinoma tumor-initiating cell all-trans retinoic acid tumor differentiation

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all-trans retinoic acid-incorporated Glycol Chitosan Nanoparticles Regulate Macrophage Polarization in Pg-LPS-Induced Inflammation

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Current Medical Science 2022年第5期42卷 974-980页

作者： Tian-rong HE Xiu-yu TANG Qi YAN Xin-yu WU Bin SHI Yi LIN Fujian Provincial Hospital Shengli Clinical College of Fujian Medical UniversityFuzhou350001China The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory for Oral Biomedical Ministry of Education School&Hospital of StomatologyWuhan UniversityWuhan430075China

Objective The occurrence and development of inflammation are closely correlated to the polarization of ***-trans retinoic acid(ATRA)has been proven to promote the polarization of macrophages from M1 to M2,but this lacks an effective carrier to participate in the biological *** present study aims to determine whether retinoic acid-incorporated glycol chitosan(RA-GC)nanoparticles can regulate macrophage polarization in Porphyromonas gingivalis-lipopolysaccharide(Pg-LPS)-induced *** Mouse 264.7 cell lines were treated with 1µg/mL Pg-LPS to induce *** the effects of ATRA and RA-GC on the activity of macrophages were detected by CCK-8 assay,cells induced with Pg-LPS were assigned to the blank control group(GC)nanoparticles without ATRA,and experimental groups(GC nanoparticles loaded with different concentrations of ATRA:1,10 and 100µg/mL).The effects of RA-GC on inflammatory cytokines tumor necrosis factor-α,interleukin(IL)-10 and IL-12 in macrophages were detected by enzyme-linked immunosorbent assay(ELISA).Subsequently,the effects of GC nanoparticles loaded with/without ATRA on macrophage polarization in an inflammatory environment were detected by RT-PCR and Western *** The results revealed that RA-GC had no significant effect on macrophage ***,RA-GC could effectively inhibit the Pg-LPS-induced inflammatory factor expression in ***,the experimental results confirmed that RA-GC could downregulate the expression of inducible nitric oxide synthase(iNOS)(a marker of M1 macrophages)and upregulate the expression of mannose receptor and Arginase-1(a marker of M2 macrophages)in a dose-dependent *** The present study confirms that RA-GC can promote the M2 polarization of macrophages in an inflammatory environment,and proposes this as a promising target for the clinical treatment of Pg-LPS-related diseases.

关键词： macrophage polarization all-trans retinoic acid lipopolysaccharide inflammation

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all-trans retinoic acid,Arsenic Trioxide,and Anthracycline-based Chemotherapy Improves Outcome in Newly Diagnosed Acute Promyelocytic Leukemia Regardless of FLT3-ITD Mutation Status

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Current Medical Science 2021年第3期41卷 491-497页

作者： Lin-wei XU Yong-zhong SU Hong-fang TAO Department of Hematologyf the First Affiliated Hospital of Shantou University Medical College Shantou 515041China

all-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutations is associated with increased risk of *** aim of this study was to analyze the prognostic impact of FLT3-ITD on APL patients who received remission induction with ATRA,idarubicin(IDA)and/or ATO,followed by ATRA plus ATO along with anthracycline,as consolidation therapy.A total of 72 patients newly diagnosed with APL were included in this study.83.3%of the patients achieved complete remission(CR)after induction ***3-ITD mutations were detected in 16(22.2%)patients and closely related to bcr-3 PML-RARa transcript(Pall survival(OS)rate was 100%in both FLT3-ITDposltlve and FLT3-ITD^(negatlve)groups,and there was no significant difference in 5-year event-free survival(EFS)between the two groups(78.3%vs.83.3%,P=0.85).ATRA plus ATO and anthracycline-based chemotherapy achieved great outcome in newly diagnosed APL regardless of the FLT3-ITD mutation status.

关键词： all-trans retinoic acid acute promyelocytic leukemia arsenic trioxide anthracycline internal tandem duplication of FMS-like tyrosine kinase 3

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all-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members

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Genes & Diseases 2021年第4期8卷 509-520页

作者： Jiejie Cui Mengjia Gong Shuyu Fang Chaoqun Hu Yi Wang Jingfang Zhang Ni Tang Yun He Department of Pediatric Surgery Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of PediatricsChildren’s Hospital of Chongqing Medical UniversityChongqing401122PR China Puyang People’s Hospital PuyangHenan Province457000PR China

As a potential chemo-therapeutic agent,all-trans retinoic acid(ATRA)can signif-icantly reverse epithelial-mesenchymal transition(EMT)of hepal-6 hepatocarcinoma cell line in vitro,but the mechanism is *** expression profile of microRNA-200(miR-200)families is different in hepatocellular *** this study,we found that ATRA trea tment could up-regulate the expression of miR-200a-3p,200c-3p,and 141-3p,which were involved in ATRA regulated proliferation and apoptosis of hepal-6 cell,but not colony ***,miR-200a-3p,200c-3p,and 141-3p could recovery ATRA inhibited migration and invasion abilities of hepal-6 cells at various ***-200a-3p and 200c-3p prevented ATRA from inducing the differentia tion and hepatic functions of hepal-6 ***-tagomir specific for miR-200a-3p and 200c-3p down-regulated the expression of CK18,but only miR-200a-3p anta gomir played prominent role in regula ting the expression of these mesenchymal markers,N-Cadherin,Snail and *** transcriptional activities of 8 tran-scription factors were up-regulated and 35 transcription factors were down-regulated by *** with ATRA group,inhibition of miR-200a-3p,200c-3p,and 141-3p significantly strengthened the expression of Fra1/Jun(AP1),Ets1/PEA3,Brn3,and Zeb1/AREB6 at varying ***,this result suggested that ATRA may suppress EMT through down-regulating miR-200a-3p,200c-3p and 141-3p related transcription ***-200 and their downstream genes might be the potentially specific targets for the treat-ment of hepatocarcinoma.

关键词： all-trans retinoic acid Differentiation Epithelial emesenchymal transition Hepatocellular carcinoma cells microRNA 200

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all-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis

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Genes & Diseases 2022年第6期9卷 1742-1756页

作者： Yanting Sun Yun He Jishuang Tong Daijiang Liu Haodong Zhang Tongchuan He Yang Bi Stem Cell Biology and Therapy Laboratory Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014PR China Department of Pediatric Surgery Children’s Hospital of Chongqing Medical UniversityChongqing 400014PR China Department of Gastroenterology Chongqing Emergency Medical CentreChongqing 400014PR China Molecular Oncology Laboratory Department of SurgeryThe University of Chicago Medical CentreChicagoIL 60637USA

all-trans retinoic acid(ATRA)can reverse the malignant behaviors of hepatocellular carcinoma(HCC)cells,thereby exerting anti-HCC effect;however,the underlying mechanism is yet to be *** study aimed to demonstrate that ATRA is vital to ferroptosis in ***-related genes exhibit different expression in patients with HCC compared to that in healthy individuals.A total of 20 amino acid products were detected in HepG2 cells,the expression level of 5 was decreased after ATRA *** improved the levels of lipid ROS,MDA,and NAPDt/NADPH,and reduced the mt-DNA copy number and changed the structure of mitochondria,in HepG2 and Hep3B *** found the expression of genes positively correlated with ferroptosis to increase and those negatively correlated to decrease with ATRA *** of ferroptosis by Ferrostatin-1 reversed ATRA-inhibited proliferation of HCC cells,along with cell migration and *** synthesis was blocked by ATRA,accompanied by decreased cystine content and increased glutamate content,and downregulation of the expression of GSH synthesis-related *** findings suggested that ATRA inhibited the malignancy of HCC cells by improving ferroptosis,and that inhibition of GSH synthesis contributed to ATRA-induced ferroptosis.

关键词： all-trans retinoic acid Ferroptosis Hepatocarcinoma Invasion Migration

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all-trans retinoic acid regulates the expression of MMP-2 and TGF-β2 via RDH5 in retinal pigment epithelium cells

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International Journal of Ophthalmology(English edition) 2023年第6期16卷 849-854页

作者： Yu-Mei Mao Chang-Jun Lan Qing-Qing Tan Gui-Mei Zhou Xiao-Ling Xiang Jia Lin Xuan Liao Department of Ophthalmology Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina Medical School of Ophthalmology and Optometry North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

·AIM: To investigate the effect of all-trans retinoic acid(ATRA) on retinol dehydrogenase 5(RDH5), matrix metalloproteinase-2(MMP-2) and transforming growth factor-β2(TGF-β2) transcription levels, and the effect of RDH5 on MMP-2 and TGF-β2 in retinal pigment epithelium(RPE) cells.·METHODS: After adult RPE cell line-19(ARPE-19 cells) intervened with gradient concentrations of ATRA(0-20 μmol/L) for 24h, flow cytometry was used to detect the proliferation and apoptosis of cells in each group, and quantitative realtime polymerase chain reaction(q RT-PCR) was used to detect RDH5, MMP-2 and TGF-β2 m RNA expression. Then, after ARPE-19 cells transfected with three different si RNA targets for 48h, the RDH5 knockdown efficiency of each group and expression of MMP-2 and TGF-β2 m RNA within them was detected by q RT-PCR. ·RESULTS: Flow cytometry results showed that ATRA could inhibit the proliferation of RPE cells and promote the apoptosis of RPE cells, and the difference of apoptosis was statistically significant when the ATRA concentration exceeded 5 μmol/L and compared with the normal control group(P=0.027 and P=0.031, respectively). q RT-PCR results showed that ATRA could significantly inhibit the expression level of RDH5 m RNA(Pally when treated with 5 μmol/L ATRA. The knockdown efficiency of RDH5 si RNA varies with different targets, among which RDH5 si RNA-435 had the highest knockdown efficiency, i.e., more than 50% lower than that of the negative control group(P=0.02). When RDH5 was knocked down for 48h, the results of q RT-PCR showed that the expressions of MMP-2 and TGF-β2 m RNA were significantly up-regulated(P<0.001).·CONCLUSION: ATRA inhibits the expression of RDH5 and promotes MMP-2 and TGF-β2, and further RDH5 knockdown significantly upregulates MMP-2 and TGF-β2. These findings suggest that RDH5 may be involved in an epithelial-mesen

关键词： KEYWORDS:retinol dehydrogenase 5 matrix metalloproteinase-2 transforming growth factor-β2 all-trans retinoic acid ARPE-19

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all-trans retinoic acid Induced the Differentiation of Human Glioma Cells

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Clinical oncology and cancer researeh 2011年第1期8卷 42-46页

作者： Qing-xi LIU Nan WANG Xing-hua LIAO Guang-da REN Tao QIN Ru-fa YU Cai-lian CHENG Guang-cun LIU Tong-cun ZHANG Key Laboratory of Industrial Microbiology Ministry of Education and Tianjin City College of Biotechnology Tianjin University of Science and Technology Tianjin 300457 China Department of Biochemistry College of Medicine Wuhan University of Science and Technology Wuhan 430081 Hubei ProvinceChina Department of Neurological Surgery Qianfoshan Hospital of Shandong Province Jinan 250014 Shandong Province China

OBJECTIVE To observe the effect of all-trans retinoic acid （ATRA） on inducing human glioma MO59K cells differentiation and further explore the underlying molecular *** The expression of glial fibrillary acidic protein （GFAP） was detected by immunocytochemistry staining. The mRNA levels of GFAP, retinoid X receptor α（RXRα）, p21 were examined by semi-quantitative RT-PCR analysis. Luciferase activity assay was performed in the COS-7, MO59K cells to measure p21 promoter transcription *** ATRA could significantly enhance the expression and mRNA level of GFAP by immunostaining and RT-PCR （P〈0.05）. Simultaneously, the mRNA levels of RXRα and p21 were remarkably increased in dose-dependent manner by RT-PCR （P〈0.05）. Furthermore, luciferase assay confirmed that ATRA and RXRα could transactivate p21 promoter in COS-7 and glioma cells （P〈0.05）.CONCLUSION ATRA can induce differentiation of human glioma cells. The RXRα and p21 were activated during ATRAinduced differentiation process. This effect may be caused by directly RXRα-induced p21 gene transactivation. Our findings provide novel evidence for the future studies to explore the molecular mechanism of transcriptional regulation for glioma cell differentiation and cellular therapeutic approaches for glioblastoma.

关键词： glioma cells all-trans retinoic acid Retinoid X receptor α,P21

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Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid

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International Journal of Oral Science 2014年第3期6卷 150-153页

作者： Jin Man Kim Sang Wook Kang Su-Mi Shin Duck Su Kim Kyong-Kyu Choi Eun-Cheol Kim Sun-Young Kim Department of Conservative Dentistry School of Dentistry Kyung Hee University Department of Maxillofacial Tissue Regeneration School of Dentistry Kyung Hee University

all-trans retinoic acid（ATRA） inhibits matrix metalloproteinase（MMP）-2 and MMP-9 in synovial fibroblasts, skin fibroblasts,bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells（HDPCs）. The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and-9 in HDPCs. The productions and messenger RNA（mRNA） expressions of MMP-2 and-9 were accessed by gelatin zymography and real-time polymerase chain reaction（PCR）, respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 mmol？L21ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs,which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.

关键词： all-trans retinoic acid human dental pulp cell matrix metalloproteinase zymography

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