Diabetic cardiomyopathy(DCM)is a prevalent cardiovascular complication associated with diabe-tes,which is characterized by abnormalities in heart structure and function.Chronic inflammation,which is mediated by the nuclear factor-κB(NF-κB)signaling pathway,is pivotal in the onset and progression of DCM.NF-κB can be activated by diabetes-related factors,including hyperglycemia,oxidative stress,and endoplasmic reticulum stress,which in turn promote the expression of inflammatory cytokines,chemokines,and adhesion molecules.This cascade leads to cardiac in-flammation,fibrosis,and apoptosis.Therefore,we summarized the role of the NF-κB signaling pathway in DCM,particu-larly its activation mechanisms and downstream reactions.The regulatory effects of cytokines,receptors,reactive oxygen species,and other factors involved in NF-κB activation were also analyzed.In addition,potential therapeutic strategies to modulate NF-κB activity,including natural compounds,synthetic inhibitors,gene therapy,and monoclonal antibodies,were summarized in this study.Targeting the NF-κB signaling pathway can mitigate the inflammatory response and en-hance cardiac function in patients with DCM.However,the development of selective and effective NF-κB inhibitors,along with the validation of their safety and efficacy through clinical trials,remains a critical focus for future research.

Aim To investigate the biological function and molecular mechanisms of piRNA-823 in the phenotypic transformation of human umbilical vein endothelial cells(HUVEC)induced by high glucose.Methods HUVEC were incubated in high glucose(33.3 mmol/L)culture medium for 72 h.The relative expression levels of piR-NA-823 were detected by RT-qPCR,the expression changes of endothelial cell markers,mesenchymal cell markers and proteins related to transforming growth factor-β1(TGF-β1)signaling pathway were detected by Western blot,the changes of cell migration ability were evaluated by scratch and Transwell assays,the formation of new angiogenesis were assessed through angiogenesis experiments.piRNA-823 mimic(overexpression of piRNA-823)were transfected into HUVEC to analyze their effects on high glucose induced endothelial-mesenchymal transition(EndMT)and angiogenesis.Further in-tervention was performed using TGF-β1 activator(SRI011381)and inhibitor(SB525334)to verify whether piRNA-823 ex-erts its effect by regulating the TGF-β1/Smad2/3 signaling pathway.Results piRNA-823 mimic significantly inhibited the viability,proliferation,migration and angiogenesis of HUVEC induced by high glucose.The piRNA-823 mimic inhibited high glucose induced EndMT in HUVEC,characterized by upregulation of endothelial cell markers and downregulation of mesenchymal cell markers.Scratch experiments,Transwell experiments and angiogenesis experiments further confirmed that piRNA-823 mimic could effectively reverse high glucose induced HUVEC proliferation,migration a-bility enhancement,and increase in the number of new angiogenesis.Mechanistic studies revealed that the TGF-β1 acti-vator partially reversed the protective effect of piRNA-823 mimic,whereas the TGF-β1 inhibitor enhanced its effect,sug-gesting that piRNA-823 exerts its regulatory role by suppressing the activation of the TGF-β1/Smad2/3 signaling pathway.Conclusion piRNA-823 significantly inhibits high glucose induced EndMT,proliferation,migration and angiogenesis in HUVEC by suppressing the activation of TGF-β1/Smad2/3 signaling pathway.

Aim To investigate the biological function and molecular mechanisms of piRNA-823 in the phenotypic transformation of human umbilical vein endothelial cells(HUVEC)induced by high glucose.Methods HUVEC were incubated in high glucose(33.3 mmol/L)culture medium for 72 h.The relative expression levels of piR-NA-823 were detected by RT-qPCR,the expression changes of endothelial cell markers,mesenchymal cell markers and proteins related to transforming growth factor-β1(TGF-β1)signaling pathway were detected by Western blot,the changes of cell migration ability were evaluated by scratch and Transwell assays,the formation of new angiogenesis were assessed through angiogenesis experiments.piRNA-823 mimic(overexpression of piRNA-823)were transfected into HUVEC to analyze their effects on high glucose induced endothelial-mesenchymal transition(EndMT)and angiogenesis.Further in-tervention was performed using TGF-β1 activator(SRI011381)and inhibitor(SB525334)to verify whether piRNA-823 ex-erts its effect by regulating the TGF-β1/Smad2/3 signaling pathway.Results piRNA-823 mimic significantly inhibited the viability,proliferation,migration and angiogenesis of HUVEC induced by high glucose.The piRNA-823 mimic inhibited high glucose induced EndMT in HUVEC,characterized by upregulation of endothelial cell markers and downregulation of mesenchymal cell markers.Scratch experiments,Transwell experiments and angiogenesis experiments further confirmed that piRNA-823 mimic could effectively reverse high glucose induced HUVEC proliferation,migration a-bility enhancement,and increase in the number of new angiogenesis.Mechanistic studies revealed that the TGF-β1 acti-vator partially reversed the protective effect of piRNA-823 mimic,whereas the TGF-β1 inhibitor enhanced its effect,sug-gesting that piRNA-823 exerts its regulatory role by suppressing the activation of the TGF-β1/Smad2/3 signaling pathway.Conclusion piRNA-823 significantly inhibits high glucose induced EndMT,proliferation,migration and angiogenesis in HUVEC by suppressing the activation of TGF-β1/Smad2/3 signaling pathway.

Diabetic cardiomyopathy(DCM)is a prevalent cardiovascular complication associated with diabe-tes,which is characterized by abnormalities in heart structure and function.Chronic inflammation,which is mediated by the nuclear factor-κB(NF-κB)signaling pathway,is pivotal in the onset and progression of DCM.NF-κB can be activated by diabetes-related factors,including hyperglycemia,oxidative stress,and endoplasmic reticulum stress,which in turn promote the expression of inflammatory cytokines,chemokines,and adhesion molecules.This cascade leads to cardiac in-flammation,fibrosis,and apoptosis.Therefore,we summarized the role of the NF-κB signaling pathway in DCM,particu-larly its activation mechanisms and downstream reactions.The regulatory effects of cytokines,receptors,reactive oxygen species,and other factors involved in NF-κB activation were also analyzed.In addition,potential therapeutic strategies to modulate NF-κB activity,including natural compounds,synthetic inhibitors,gene therapy,and monoclonal antibodies,were summarized in this study.Targeting the NF-κB signaling pathway can mitigate the inflammatory response and en-hance cardiac function in patients with DCM.However,the development of selective and effective NF-κB inhibitors,along with the validation of their safety and efficacy through clinical trials,remains a critical focus for future research.

Aim To explore the role of the ten-eleven translocation 2(TET2)/ubiquinol-cytochrome C reductase hinge protein(UQCRH)axis in the inhibition of vascular smooth muscle cell(VSMC)apoptosis by fibroblast growth fac-tor-2(FGF-2).Methods Cultured VSMCs were divided into control group,FGF-2 group,and FGF-2+fibroblast growth factor receptor(FGFR)pan-inhibitor LY2874455 group.VSMCs overexpressing TET2(OETET2)or UQCRH(OEUQCRH)were divided into control group,FGF-2 group,and OETET2+FGF-2 or OEUQCRH+FGF-2 group.Ho-echst33342 and PI staining were used to detect cell apoptosis,CCK-8 assay was employed to measure cell proliferation,and Western blot was used to examine the expression levels of apoptosis-related proteins pro-Caspase-3,cleaved Caspase-3,Bax,Bcl-2,as well as TET2 and UQCRH.The NCBI and methprimer websites were utilized for predicting and analyzing CpG island sites in the UQCRH gene promoter.Results FGF-2 could inhibit VSMC apoptosis,promote proliferation,downregulate apoptosis-related proteins cleaved Caspase-3,Bax,TET2,and UQCRH expression,and upregulate anti-ap-optotic protein Bcl-2 expression(compared with control group,P＜0.05).However,it did not affect pro-Caspase-3 ex-pression(compared with control group,P＞0.05).LY2874455 could counteract the effects of FGF-2(compared with FGF-2 group,P＜0.05).Overexpression of TET2 or UQCRH could reverse the anti-apoptotic and pro-proliferative effects of FGF-2 on VSMC,with upregulation of apoptosis-related protein expression and downregulation of anti-apoptotic protein expression(compared with FGF-2 group,P＜0.05).The UQCRH gene promoter region contained three CpG islands.Overexpression of TET2 could upregulate UQCRH expression in VSMC treated with FGF-2(compared with FGF-2 group,P＜0.05).Conclusion FGF-2,by inhibiting TET2 expression and UQCRH expression,reduces VSMC apoptosis and promotes its proliferation.

Aim The effect of miR-223-3p on H9c2 cells in high glucose environments was investigated through bioinformatics and its role in the mechanism of development of diabetic cardiomyopathy was analyzed in conjunction with transcriptomic sequencing results.The objective was to identify novel therapeutic targets at the molecular level and explore the specific mechanisms of action of miR-223-3p.Methods In high glucose-cultivated H9c2 cells,miR-223-3p inhibition and control were transfected,respectively.RT-qPCR was used to detect the differences in miR-222-3p expression between the two cell groups.Differential mRNA was identified through high-throughput sequen-cing.GO functional analysis was conducted using TopGO software.DESeq2 software(v1.16.1)filtered differentially expressed genes and analyzed them using a miR-223-3p target gene database.This process predicted the target genes of miR-223-3p and validated the changes in their expression through RT-qPCR.Results The activity of H9c2 cells trea-ted with high glucose decreased significantly.Significant differences in gene expression between the control group and the inhibitor group had been indicated by transcriptomic sequencing results.GO function enrichment analysis showed that the predicted target gene set was significantly enriched in G protein-coupled receptor activity,glycerol ether monooxygenase ac-tivity,cellular anion homeostasis,and chloride ion homeostasis,among others.KEGG pathway enrichment analysis fur-ther showed that these genes were mainly involved in the TNF signaling pathway and the IL-17 signaling pathway.In ad-dition,they were related to type 1 diabetes,cytochrome P450 metabolism of exogenous drugs,and other diseases and phys-iological processes.Target gene prediction suggested that miR-223-3p may be associated with the expression changes of Cxcl10,Creb313,Mmp3,and Bc13,among others.Conclusion The prediction of miR-223-3p and its downstream target genes in high glucose induced H9c2 cell injury may provide new targets for the treatment of diabetic cardiomyopa-thy,which is of great significance for revealing the pathogenesis of diabetic cardiomyopathy and developing new treatment strategies.

As the fourth member of the globin family, cytoglobin ( CYGB) is a hypoxia-induced gene, and its expression is upregulated under hypoxia.CYGB is widely distributed in the living body and has a variety of physiological functions, such as anti-oxi-dative stress, anti-fibrosis, and neuroprotection.It also plays a protective role in cardiovascular disease, cancer, and other hypoxia-re-lated diseases.This article presents an overview on the structure and distribution of CYGB, its physiological functions of anti-fibrosis, anti-cancer and muscle regeneration, and the regulation and the mechanism of its expression under hypoxia.

Aim To study the effect of proteasome inhibitor MG132 on expression of Caspase-3 and UPP associated genes in the apoptosis of human hepatocelluar cancer cells.Methods HepG2 cells were treated with MG132 (2,5,10 ?mol?L -1) for 24 h. The apoptotic cells were determined with flow cytometric analysis. The levels of E1, E2, E3 and Caspase-3 mRNA expression were detected with RT-PCR. Caspase-3 protein expression was detected with immunohistochemistry. Results The results showed that the increase of the degree of HepG2 cell apoptosis was concentrationly dependent. RT-PCR showed that E1, E2 and E3 gene expressions were decreased in the treatment group. MG132 down-regulated the gene expression of E1, E2, E3 and up-regulated the gene/protein expression of Caspase-3. Conclusion Proteasome inhibitor MG132 may induce HepG2 cells apoptosis by inhibitting UPP activity,up-regulating the gene/protein expression of Caspase-3.

Objective:To analyze a novel epitope of Homo sapiens synapse associated protein and synthesize polyclonal antibody.Methods:FRG4 full-length sequence was obtained by PCR from human fetal liver library;by bioinformatics to detect the second structure of amino acids encoded by FRG4 and its epitope and motifs;by solid-phase peptide synthesis method to synthesize FRG4 peptides,then peptides were immunized to rabbits;by immunohistory to detect the expression of FRG4 in HepG_2 cells.Results:Select 13-peptides PKLVKEEVFWRNY by bioinformatics to synthesize rabbit anti-human FRG4 polyclonal antibody.Antibody purity was 82.79% and antibody dilution was 1∶16 000 detected by ELISA.The antibody had a good reaction and speciality in Western blot,it was mainly expressed in cytoplasm of HepG_2 cells.Conclusion:A novel Homo sapiens synapse associated protein(FRG4) antibody was synthesized successfully.

0. 05); The long-term effective rate was 84. 21% in the treatment group and 54. 55% in the control group with a significant difference between the two groups (P