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当代医学科学(英文)
当代医学科学(英文)

龚菲力；冯敢生

双月刊

2096-5230

jtmu@tjmu.edu.cn

027-83692514

430030

武汉市航空路13号同济医学院学报

当代医学科学(英文)/Journal Current Medical ScienceSCI
正式出版
收录年代

    Kaempferol Improved Rheumatoid Arthritis by Regulating the Immune Imbalance of Treg/Th17

    Nan LIYan-kui YIJie ZHAOQiang WANG...
    1259-1269页
    查看更多>>摘要：Objective:The objective of this study was to explore the therapeutic effects of kaempferol(Kae)on rheumatoid arthritis(RA)and to elucidate the underlying mechanisms.Methods:The collagen-induced arthritis(CIA)model was established using collagen Ⅱ to induce RA.Mice were treated with Kae at a dose of 25 or 50 mg/kg/day via gavage.Pathological changes in the ankle joint were analyzed.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of inflammatory factors.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was used to assess the expression of genes associated with the balance of regulatory T(Treg)/T helper 17(Th 17)cells.Flow cytometry was utilized to determine the Treg/Th17 ratio.Furthermore,these techniques were employed to evaluate the impact of miR-34a and Foxp3 dysregulation on cellular functions in RA under the influence of Kae.Dual luciferase reporter assay was conducted to analyze the binding of miR-34a to Foxp3.Results:Treatment with Kae led to a downregulation of receptor-related orphan receptor gamma t(RORγt)and IL-17 expression,and an upregulation of Foxp3,IL-10,and TGF-β expression in CIA mice.Kae intervention inhibited the production of proinflammatory cytokines and increased the production of anti-inflammatory cytokines.Furthermore,Kae treatment suppressed the expression of miR-34a,which was identified as a target of miR-34a.Finally,Kae regulated Treg/Th 17 balance-related genes and cellular inflammation through the miR-34a/Foxp3 axis.Conclusion:The study demonstrated that Kae effectively ameliorates CIA in mice by modulating the Treg/Th17 balance and related genes via the miR-34a/Foxp3 axis.These findings suggest that Kae may serve as a promising therapeutic agent for the treatment of RA and for restoring immune homeostasis.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    FKBP5 Regulates the Osteogenesis of Human Adipose-derived Mesenchymal Stem Cells

    Xiao-yu TIANBiao ZHUWen-can FANGXiang-bin ZHOU...
    1270-1279页
    查看更多>>摘要：Objective:Human adipose-derived stem cells(ASCs)have shown considerable potential for tissue regeneration.FK506 binding protein(FKBP)5 is a cochaperone of several proteins.The purpose of this work was to explore the function of FKBP5 in ASC osteogenesis.Methods:Lentivirus infection was used to overexpress or knock down FKBP5 in ASCs.To inhibit FKBP5,SAFit2,a specific inhibitor of FKBP5,was used.Next,the osteogenic capacity of ASCs was evaluated via alkaline phosphatase(ALP)staining,and extracellular calcium precipitation was detected via Alizarin red S staining.The binding proteins of FKBP5 were assessed via proteomics and validated via coimmunoprecipitation experiments.Results:Following osteogenic induction,FKBP5 expression increased at both the mRNA and protein levels.Interestingly,FKBP5 upregulation by lentivirus infection increased the ability of ASCs to differentiate into osteoblasts,as revealed by ALP staining,while ALP activity also increased.Moreover,increased extracellular calcium precipitation confirmed that FKBP5 overexpression promoted ASC osteogenesis into osteocytes.On the other hand,FKBP5 knockdown or functional suppression with SAFit2 decreased this process.Furthermore,the proteomics and coimmunoprecipitation data demonstrated that FKBP5 bound to a variety of proteins in ASCs.These proteins serve as the molecular chaperone base upon which the osteogenesis-regulating activity of FKBP5 rests.Conclusion:Our study revealed that FKBP5 enhances the osteogenesis of ASCs,providing a feasible method for clinical bone tissue engineering applications.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    TREM2-mediated Macrophage Glycolysis Promotes Skin Wound Angiogenesis via the Akt/mTOR/HIF-1α Signaling Axis

    Wei WEIZi-lu QULi LEIPing ZHANG...
    1280-1292页
    查看更多>>摘要：Objective:The trigger receptor expressed on myeloid cells-2(TREM2)pathway in myeloid cells is a key disease-inducing immune signaling hub that is essential for detecting tissue damage and limiting its pathological spread.However,the role and potential mechanisms of TREM2 in wound repair remain unclear.The purpose of this study was to determine the role and mechanism of TREM2 in skin wound healing in mice.Methods:Immunofluorescence staining was used to determine the expression and cellular localization of TREM2 and test the effects of TREM2 knockout on angiogenesis,glycolysis,and lactylation in skin tissue.Western blotting was used to analyze the expression of the Akt/mTOR/HIF-1α signaling pathway in the wounded skin tissues of wild-type(WT)and TREM2 knockout mice.A coimmunoprecipitation assay was used to determine whether HIF-1α,which mediates angiogenesis,is modified by lactylation.Results:The number of TREM2+macrophages was increased,and TREM2+macrophages mediated angiogenesis after skin injury.TREM2 promoted glycolysis and lactylation in macrophages during wound healing.Mechanistically,TREM2 promoted macrophage glycolysis and angiogenesis in wounded skin tissues by activating the Akt/mTOR/HIF-lα signaling pathway.HIF-1α colocalized with Klac to mediate lactylation in macrophages,and lactate could stabilize the expression of the HIF-1α protein through lactylation.Lactate treatment ameliorated the impaired angiogenesis and delayed wound healing in wounded skin in TREM2 knockout mice.Conclusion:TREM2+macrophage-mediated glycolysis can promote angiogenesis and wound healing.Our findings provide an effective strategy and target for promoting skin wound healing.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Effects of Exosomes from Menstrual Blood-derived Stem Cells and Ginger on Endometriotic Stem Cells

    Shima AbabzadehFaezeh Davoodi AslHoda FazaeliMohsen Sheykhhasan...
    1293-1302页
    查看更多>>摘要：Objective:Menstrual blood-derived stem cells from endometriosis patients(E-MenSCs)have different gene expression patterns than those from healthy nonendometriotic females(NE-MenSCs).Exosomes extracted from mesenchymal stem cells and plants are considered for the treatment of various diseases.This study aimed to compare the effects of exosomes derived from NE-MenSCs(C-exos)and those from the roots of ginger(P-exos)on E-MenSCs.Methods:E-MenSCs at the third passage were used,and after evaluating the effective dosage with MTT,C-exos(200 μg/mL)or P-exos(100 μg/mL)were added to treat them.Following a 72-h incubation,the cells were analyzed with annexin V/PI test to evaluate the apoptosis rate.Also,genes related to inflammation(IL-6,IL-8,IL-1β,NF-κB,COX2),cell cycle(Cyclin D1),the steroid pathway(ESR1),migration and invasion(MMP-2,MMP-9,VEGF),and the apoptosis pathway(BAX,BCL2)were detected by real-time PCR.Results:Apoptosis was increased in both the P-and C-exos groups.The expression levels of IL-6 and IL-1β were significantly lower in the P-exos group than in the E-MenSCs group.The expression levels of IL-8,NF-κB,COX-2,and MMP-9 were significantly decreased in both the P-exos group and the C-exos group.The expression level of VEGF was significantly lower in the P-exos group than in the E-MenSCs group.The BAX/BCL2 ratio was much lower in the P-exos group than in the E-MenSCs group.Conclusion:In this study,we established the feasibility of using a novel natural nontoxic material to target endometriotic mesenchymal stem cells to modify their gene expression and function toward healthy cells.Both C-exos and P-exos showed positive effects on the gene expression and function of endometriotic cells.Considering that plant exosomes are easier to access and less expensive,they can be considered for clinical use in improving the symptoms of endometriosis patients.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Genome-integrated Human Papilloma Viruses Testing:A Complement to Colposcopy-guided Biopsy for Cervical Cancer Screening

    Han XIELi LITao ZHUHu ZHOU...
    1303-1311页
    查看更多>>摘要：Objective:Our research aims to evaluate the diagnostic accuracy of colposcopy-guided biopsy(CGB)in detecting high-grade cervical lesions and explore how human papilloma virus(HPV)integration status and other factors affect its performance.Methods:A retrospective cohort analysis involving 550 patients was conducted to evaluate whether the HPV integration plays a role in identifying high-grade cervical lesions and cervical cancer.Logistic regression models and area under the curve(AUC)calculations were employed.Results:Our findings revealed that 53.5％of CGB/surgery pairs demonstrated congruent diagnoses,whereas 17.1％showed underestimation and 29.5％overestimation.Furthermore,multivariate logistic regression analysis identified several key predictors for cervical intraepithelial neoplasia(CIN)2+and CIN3+according to surgical pathology.Notably,a CGB confirming CIN2+[odds ratio(OR)=6.0,95％confidence interval(CI):3.9-9.1,P＜0.001],high-grade cytology(OR=2.6,95％CI:1.4-4.9,P=0.003),and HPV integration positivity(OR=2.2,95％CI:1.3-3.5,P＜0.001)emerged as significant factors for CIN2+.Similarly,for CIN3+identification,CGB confirming CIN2+(OR=5.3,95％CI:3.4-8.3,P＜0.001),high-grade cytology(OR=2.6,95％CI:1.5-4.7,P=0.001),and HPV integration positivity(OR=2.0,95％CI:1.3-3.1,P=0.003)were independent predictors.Conclusion:Our study highlights the innovative role of HPV integration testing as a pivotal adjunct to CGB and cytology,offering a comprehensive approach that may enhance the diagnostic precision for high-grade cervical lesions,ultimately achieving more precise management strategies.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Causal Link between Gut Microbiota and Infertility:A Two-sample Bidirectional Mendelian Randomization Study

    Jia-xin ZHANGQin-lan LIXiao-yan WANGCheng-chang ZHANG...
    1312-1324页
    查看更多>>摘要：Objective:To investigate the associations of the gut microbiota with reproductive system diseases,including female infertility,male infertility,polycystic ovary syndrome(PCOS),primary ovarian failure,endometriosis,uterine fibroids,uterine polyps,sexual dysfunction,orchitis,and epididymitis.Methods:A two-sample bidirectional Mendelian randomization(MR)analysis was performed to evaluate the potential causal relationship between the composition of gut microbiota and infertility,along with associated diseases.Results:Sixteen strong causal associations between gut microbes and reproductive system diseases were identified.Sixty-one causal associations between gut microbes and reproductive system diseases were determined.The genus Eubacterium hallii was a protective factor against premature ovarian failure and a pathogenic factor of endometriosis.The genus Erysipelatoclostridium was the pathogenic factor of many diseases,such as PCOS,endometriosis,epididymitis,and orchitis.The genus Intestinibacter is a pathogenic factor of male infertility and sexual dysfunction.The family Clostridiaceae 1 was a protective factor against uterine polyps and a pathogenic factor of orchitis and epididymitis.The results of reverse causal association analysis revealed that endometriosis,orchitis,and epididymitis all led to a decrease in the abundance of bifidobacteria and that female infertility-related diseases had a greater impact on gut microbes than male infertility-related diseases did.Conclusions:The findings from the MR analysis indicate that there is a bidirectional causal relationship between the gut microbiota and infertility as well as associated ailments.Compared with ovarian diseases,uterine diseases are more likely to lead to changes in women's gut microbiota.The findings of this research offer valuable perspectives on the mechanism and clinical investigation of reproductive system diseases caused by microorganisms.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Regulation of Alternative Splicing by PARP1 in HTR-8/Svneo Cells:Implications for Placental Development and Spontaneous Abortion

    Jing ZHAODe-hua YANGYeerdeng QIEQIEKENing-ning HAN...
    1325-1336页
    查看更多>>摘要：Objective:Alternative splicing affects gene expression during placental development.The present study aimed to identify poly(ADP-ribose)polymerase 1(PARP1)-regulated alternative splicing events in HTR-8/Svneo cells.Methods:Decidual tissues were collected from women with induced abortion and spontaneous abortion.PARP1 transcription was quantified by RT-qPCR.Small interfering RNA(siRNA)was used to knock down the PARP1 expression in HTR-8/Svneo cells.The transfection efficiency was verified by RT-qPCR and Western blotting.Total RNA was extracted,and the RNA-sequencing approach was used to identify alternative splicing events and transcriptomes.The PARP1 knockdown-induced differentially expressed genes with changes in alternative splicing events were quantified by RT-qPCR.Functional analysis,which included the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways,was performed.Results:The PARP1 mRNA expression increased in decidual tissues in the spontaneous abortion group,when compared to the induced abortion group.However,the PARP1 knockdown significantly downregulated 1491 genes and upregulated 881 genes in HTR-8/Svneo cells.Furthermore,227 genes that underwent alternative splicing were identified,and these were differentially expressed in siPARP1 cells,when compared to siNC cells.Conclusion:The functional analysis revealed that these alternative splicing genes affected the functional phenotypes of extravillous cytotrophoblasts.Furthermore,the PARP1 knockdown led to alterations in gene expression and specific alternative splicing patterns in extravillous trophoblasts.
      原文链接:
    • NETL
    • NSTL
    • 万方数据