Knockdown of FOXO4 protects against OGD/R‑induced cerebral microvascular endothelial cell injury and regulates the AMPK/Nrf2/HO‑1 pathway through transcriptional activation of CTRP6

Experimental and Therapeutic Medicine, Год журнала: 2024, Номер 27(3)

Опубликована: Янв. 9, 2024

Cerebral ischemia is a type of cerebrovascular disease with high disability and mortality rates. The expression forkhead box protein O4 (FOXO4) in the brain increased following traumatic injury. To best our knowledge, however, role FOXO4 as well its mechanism cerebral has not been reported so far. For establishment an in vitro cellular injury model, human microvascular endothelial HCMEC/D3 cells were induced by oxygen‑glucose deprivation/reoxygenation (OGD/R). mRNA expressions C1q/tumor necrosis factor‑related 6 (CTRP6) OGD/R‑induced detected reverse transcription‑quantitative (RT‑q)PCR western blotting. transfection efficacy small interfering (si)‑ overexpression (Ov)‑FOXO4 si‑CTRP6 was assessed using RT‑qPCR Cell Counting Kit‑8 TUNEL assay used to assess viability apoptosis OGD/R, respectively. A FITC‑Dextran kit applied determine permeability immunofluorescence for measurement tight junction zonula occludens‑1. levels oxidative stress markers inflammatory cytokines corresponding kits. binding sites transcription factor, CTRP6 promoter predicted HDOCK SERVER. Luciferase reporter detect activity while chromatin immunoprecipitation evaluate ability promoter. Western blotting detection apoptosis‑ AMPK/Nrf2/heme oxygenase‑1 (HO‑1) pathway‑associated proteins, along proteins. cells. After cells, decreased. Furthermore, interference improved barrier dysfunction but inhibited response OGD/R. knockdown regulated Knockdown protected cell via AMPK/Nrf2/HO‑1 pathway. present study indicated that activated protect against OGD/R

Язык: Английский

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Interaction between SIRT1 and non-coding RNAs in different disorders

Frontiers in Genetics, Год журнала: 2023, Номер 14

Опубликована: Июнь 27, 2023

SIRT1 is a member of the sirtuin family functioning in process removal acetyl groups from different proteins. This protein has several biological functions and involved pathogenesis metabolic diseases, malignancy, aging, neurodegenerative disorders inflammation. Several long non-coding RNAs (lncRNAs), microRNAs (miRNAs) circular (circRNAs) have been found to interact with SIRT1. These interactions assessed contexts sepsis, cardiomyopathy, heart failure, non-alcoholic fatty liver disease, chronic hepatitis, cardiac fibrosis, myocardial ischemia/reperfusion injury, diabetes, ischemic stroke, immune-related cancers. Notably, SIRT1-interacting each other. circRNA/miRNA lncRNA/miRNA pairs that identified. axes are potential targets for design novel therapies disorders. In current review, we summarize between three classes

Язык: Английский

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α‐Pinene inhibits the growth of cervical cancer cells through its proapoptotic activity by regulating the miR‐34a‐5p/Bcl‐2 signaling axis

Drug Development Research, Год журнала: 2022, Номер 83(8), С. 1766 - 1776

Опубликована: Сен. 8, 2022

Among gynecological tumors, cervical cancer (CC) has the second-highest prevalence and mortality rate. α-Pinene is a bicyclic monoterpenoid compound extracted from pine needles that carried promising anticancer properties. Nevertheless, its effect on CC underlying mechanism not yet been elucidated. Therefore, we investigated of apoptosis in via vitro assays flow cytometry (FCW), terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot. Following that, detected proapoptotic function HeLa cells vivo by TUNEL assay immunofluorescence staining. Our results displayed inhibited growth stalled G0/G1 phase. Interestingly, also induced to apoptosis. The along with up-regulating expression Bax, Bid, caspase-9, caspase-3, miR-34a-5p, down-regulating Bcl-2 vitro. At same time, levels target genes were consistent those experiment proved promoted apoptosis, which will be used hopefully maximize therapeutic strategies clinical studies CC.

Язык: Английский

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Composition and regulation of the immune microenvironment of salivary gland in Sjögren’s syndrome

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Сен. 13, 2022

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction and inflammation. Patients often have dry mouth eye symptoms, which seriously affect their lives. Improving symptoms has become common demand from patients. For this reason, researchers conducted many studies on external secretory glands. In paper, we summarize recent the salivary glands of pSS patients perspective immune microenvironment. These showed that hypoxia, senescence, chronic inflammation are essential characteristics SG pSS, genes related to lymphocyte chemotaxis, antigen presentation, activation upregulated. Interferon (IFN)-related genes, DNA methylation, sRNA downregulation, mitochondrial-related differentially expressed also involved in forming microenvironment while multiple signaling pathways regulation. We further elucidated regulation relevant, targeted treatments.

Язык: Английский

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CTRP family in diseases associated with inflammation and metabolism: molecular mechanisms and clinical implication

Acta Pharmacologica Sinica, Год журнала: 2022, Номер 44(4), С. 710 - 725

Опубликована: Окт. 7, 2022

C1q/tumor necrosis factor (TNF) related proteins (CTRPs) is a newly discovered adipokine family with conservative structure and ubiquitous distribution secreted by adipose tissues. Recently, CTRPs have attracted increasing attention due to the its wide-ranging effects upon inflammation metabolism. To-date, 15 members of (CTRP1-15) characteristic C1q domain been characterized. Earlier in-depth phenotypic analyses mouse models deficiency also unveiled ample function in This review focuses on rise CTRPs, special emphasis latest discoveries regards CTRP metabolism as well diseases. We first introduced polymerization reveal pleiotropic biological functions. Next, intimate association metabolism, involvement nodes complex molecular networks, were elaborated. With expanding membership family, information presented here provides new perspectives for therapeutic strategies improve inflammatory metabolic abnormalities.

Язык: Английский

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High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway

Cells, Год журнала: 2021, Номер 10(11), С. 3230 - 3230

Опубликована: Ноя. 19, 2021

Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells; however, their diabetes-induced salivary gland dysfunction remains unknown. Here, we found that TJ proteins claudin-1 claudin-3 were significantly increased submandibular glands (SMGs) db/db mice high glucose (HG)-treated human SMGs. HG decreased permeability expression SMG-C6 cells. Knockdown or reversed HG-induced decrease permeability. MiR-22-3p was downregulated diabetic SMGs HG-treated A miR-22-3p mimic suppressed abolished increases levels cells, whereas a inhibitor produced opposite effects. Specificity protein-1 (Sp1) enhanced which promoted transcription binding to corresponding promoters. luciferase reporter assay confirmed repressed Sp1 by directly targeting mRNA 3'-untranslated region (3'-UTR). Consistently, suppressed, enhanced, effects on expression. Taken together, our results demonstrate new regulatory decreases SMG cells inhibiting miR-22-3p/Sp1-mediated

Язык: Английский

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C1q/tumor necrosis factor-related protein-6 exerts protective effects on myocardial ischemia–reperfusion injury through the modulation of the Akt-GSK-3β-Nrf2 signaling cascade

International Immunopharmacology, Год журнала: 2023, Номер 115, С. 109678 - 109678

Опубликована: Янв. 10, 2023

Язык: Английский

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Macrophage fatty acid oxidation in atherosclerosis

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 116092 - 116092

Опубликована: Дек. 28, 2023

Atherosclerosis significantly contributes to the development of cardiovascular diseases (CVD) and is characterized by lipid retention inflammation within artery wall. Multiple immune cell types are implicated in pathogenesis atherosclerosis, macrophages play a central role as primary source inflammatory effectors this pathogenic process. The metabolic influences lipids on macrophage function fatty acid β-oxidation (FAO) have similarly drawn attention due its relevance an immunometabolic hub. This review discusses recent findings regarding impact mitochondrial-dependent FAO phenotype macrophages, well transcriptional regulation macrophages. Finally, therapeutic strategy atherosclerosis highlighted.

Язык: Английский

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Advances in the functions of CTRP6 in the development and progression of the malignancy

Frontiers in Genetics, Год журнала: 2022, Номер 13

Опубликована: Окт. 12, 2022

CTRP6, a member of the C1q/TNF-related protein (CTRP) family, has gained increasing scientific interest because its regulatory role in tumor progression. Previous studies have shown that CTRP6 is closely involved regulating various pathophysiological processes, including glucose and lipid metabolism, cell proliferation, apoptosis, inflammation. To date, been identified as related to eight different malignancies, lung cancer, oral gastric colon liver bladder renal ovarian cancer. reported be associated with progression by activating series signal networks. This review article mainly discusses biochemistry pleiotropic functions new molecular mediator carcinogenesis, hoping information summarized herein could make modest contribution development novel cancer treatments future.

Язык: Английский

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Tetrahydroxy stilbene glycoside attenuates endothelial cell premature senescence induced by H2O2 through the microRNA-34a/SIRT1 pathway

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Фев. 1, 2022

Abstract Numerous studies have demonstrated that endothelial cell senescence plays a decisive role in the development and progression of cardiovascular diseases (CVD). Our previous results confirmed Tetrahydroxy stilbene glycoside (TSG) can alleviate human umbilical vein cells (HUVECs) induced by H 2 O through SIRT1. It has been reported miR-34a is translational suppressor In this study, we aimed to explore whether TSG regulates SIRT1 ameliorate HUVECs senescence. was used induce premature HUVECs, mimic or inhibitor were transfected over-express suppress expression level miR-34a. Results revealed apparently decreased -induced HUVECs. When inhibited EX527, attenuation on abolished. knockdown, effect could be enhanced. While reverse conclusion, attenuated targeting miR-34a/SIRT1 pathway.

Язык: Английский

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