Tissue engineering chambers (TECs) represent a new and attractive in vivo tissue engineering model that can successfully generate mature adipose tissue. However, the newly formed adipose tissue is not able to fill the...Tissue engineering chambers (TECs) represent a new and attractive in vivo tissue engineering model that can successfully generate mature adipose tissue. However, the newly formed adipose tissue is not able to fill the volume of the chamber as expected. To investigate whether the capsule surrounding the newly formed adipose tissue limits the adipose tissue volume in the chamber, we detected fibrotic parameters two months after these chambers were implanted into rats. The results showed that the newly formed adipose tissue was surrounded by a thick layer of capsule, and the protein levels of transforming growth factor-<em>β</em>1 (TGF-<em>β</em>1), phosphorylated Smad2 (p-Smad2), connective tissue growth factor (CTGF), collagen type I (COL-I) and α-smooth muscle actin (<em>α</em>-SMA) in the capsule were increased. The levels of these proteins decreased following systemic administration of P144 (a peptide inhibitor of TGF-<em>β</em>1). Furthermore, the capsule thickness was significantly reduced, and the adipose tissue volume was markedly greater when using P144. These findings indicate that capsule formation, which is mediated through a TGF-<em>β</em>1 signaling pathway, restricted the volume of the engineered adipose tissue that was formed. This study may provide a new approach to regenerate amounts of adipose tissue for the reconstruction of large soft tissue defects.展开更多
Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics anal...Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure.DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability,apoptosis,and lipid peroxidation.The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays.Cardiac function was assessed by echocardiography,and biochemical markers of heart failure were measured using ELISA.The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.Results miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts.Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis,lipid peroxidation,and cardiac dysfunction.ACSM1 was identified as a direct target of miR-144-5p,and its expression was downregulated by DOX.Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability,apoptosis,and lipid peroxidation of cardiomyocytes.Furthermore,miR-144-5p inhibition improved cardiac function in DOX-treated mice,as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers(BNP,LDH,Ang II,and ALD).Conclusions Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation.The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure.Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.展开更多
Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the...Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the human endometrial epithelial cells(HEECs)was explored.Methods HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device(Cu-IUD)implantation.Reverse transcription quantitative PCR(RT-qPCR)was used to detect the differential expression of miR-144-3p in HEECs after Cu^(2+)treatment.MiRNAs,siRNAs and related inhibitors were used to treat HEECs.The expression levels of related downstream genes were then analyzed by RT-qPCR,Western blotting and immunofluorescence to explore the specific mechanism involved.Results MiR-144-3p was significantly upregulated in the Cu^(2+)-treated HEECs.The expression of P-NF-κB,MMP9,TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10μg/mL Cu^(2+).MiR-144-3p regulated the expression of metallothionein 1A(MT1A)and thrombospondin-1(THBS-1)in Cu^(2+)-treated HEECs.The expression of P-NF-κB can be regulated by MT1A,and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu^(2+)-treated HEECs.The expression of TGF-β3 can be regulated by THBS-1,and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu^(2+)-treated HEECs.The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.Conclusions The increased Cu^(2+)concentration led to the upregulation of miR-144-3p,further reducing the expression levels of its target genes(MT1A and THBS-1),which in turn downregulated the expression of NF-κB,MMP9,TGF-β3 and SMAD3,ultimately leading to increased endometrial cell damage and decreased cell proliferation.展开更多
文摘Tissue engineering chambers (TECs) represent a new and attractive in vivo tissue engineering model that can successfully generate mature adipose tissue. However, the newly formed adipose tissue is not able to fill the volume of the chamber as expected. To investigate whether the capsule surrounding the newly formed adipose tissue limits the adipose tissue volume in the chamber, we detected fibrotic parameters two months after these chambers were implanted into rats. The results showed that the newly formed adipose tissue was surrounded by a thick layer of capsule, and the protein levels of transforming growth factor-<em>β</em>1 (TGF-<em>β</em>1), phosphorylated Smad2 (p-Smad2), connective tissue growth factor (CTGF), collagen type I (COL-I) and α-smooth muscle actin (<em>α</em>-SMA) in the capsule were increased. The levels of these proteins decreased following systemic administration of P144 (a peptide inhibitor of TGF-<em>β</em>1). Furthermore, the capsule thickness was significantly reduced, and the adipose tissue volume was markedly greater when using P144. These findings indicate that capsule formation, which is mediated through a TGF-<em>β</em>1 signaling pathway, restricted the volume of the engineered adipose tissue that was formed. This study may provide a new approach to regenerate amounts of adipose tissue for the reconstruction of large soft tissue defects.
基金supported by Chongqing Science and Health Joint Medical Research Project(No.2023MSXM081)2023 Key Disciplines on Public Health Construction in Chongqing.
文摘Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure.DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability,apoptosis,and lipid peroxidation.The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays.Cardiac function was assessed by echocardiography,and biochemical markers of heart failure were measured using ELISA.The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.Results miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts.Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis,lipid peroxidation,and cardiac dysfunction.ACSM1 was identified as a direct target of miR-144-5p,and its expression was downregulated by DOX.Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability,apoptosis,and lipid peroxidation of cardiomyocytes.Furthermore,miR-144-5p inhibition improved cardiac function in DOX-treated mice,as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers(BNP,LDH,Ang II,and ALD).Conclusions Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation.The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure.Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.
文摘Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the human endometrial epithelial cells(HEECs)was explored.Methods HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device(Cu-IUD)implantation.Reverse transcription quantitative PCR(RT-qPCR)was used to detect the differential expression of miR-144-3p in HEECs after Cu^(2+)treatment.MiRNAs,siRNAs and related inhibitors were used to treat HEECs.The expression levels of related downstream genes were then analyzed by RT-qPCR,Western blotting and immunofluorescence to explore the specific mechanism involved.Results MiR-144-3p was significantly upregulated in the Cu^(2+)-treated HEECs.The expression of P-NF-κB,MMP9,TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10μg/mL Cu^(2+).MiR-144-3p regulated the expression of metallothionein 1A(MT1A)and thrombospondin-1(THBS-1)in Cu^(2+)-treated HEECs.The expression of P-NF-κB can be regulated by MT1A,and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu^(2+)-treated HEECs.The expression of TGF-β3 can be regulated by THBS-1,and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu^(2+)-treated HEECs.The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.Conclusions The increased Cu^(2+)concentration led to the upregulation of miR-144-3p,further reducing the expression levels of its target genes(MT1A and THBS-1),which in turn downregulated the expression of NF-κB,MMP9,TGF-β3 and SMAD3,ultimately leading to increased endometrial cell damage and decreased cell proliferation.
