Accumulating evidence has shown that mesenchymal stem cell (MSC)-derived exosomes (exo) mediate cardiac repair following myocardial infarction (MI). Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, plays critical role in regulating homeostasis. This study aimed to investigate the cardioprotective effects of exo secreted from bone marrow-MSCs (BM-MSCs) overexpressing MIF rat model MI. plasmid was transducted BM-MSCs. Exo were isolated supernatants BM-MSCs and...

Abstract Aging impairs the functions of human mesenchymal stem cells (MSCs), thereby severely reducing their beneficial effects on myocardial infarction (MI). MicroRNAs (miRNAs) play crucial roles in regulating senescence MSCs; however, underlying mechanisms remain unclear. Here, we investigated significance miR‐155‐5p MSC and whether inhibition could rejuvenate aged MSCs (AMSCs) to enhance therapeutic efficacy for MI. Young (YMSCs) AMSCs were isolated from young donors, respectively. The...

Mesenchymal stem cell- (MSC-) based therapy is a novel strategy in regenerative medicine. The functional and capacities of MSCs decline with senescence. Nonetheless, the potential mechanisms that underlie their senescence are not fully understood. This study was aimed at exploring fibroblast growth factor 21 (FGF21) regulation MSC determined by senescence-associated β -galactosidase (SA- -gal) staining. morphology level mitochondrial reactive oxygen species (ROS) were assessed MitoTracker...

The beneficial functions of mesenchymal stem cells (MSCs) decline with age, limiting their therapeutic efficacy for myocardial infarction (MI). Macrophage migration inhibitory factor (MIF) promotes cell proliferation and survival. We investigated whether MIF overexpression could rejuvenate aged MSCs increase in MI. Young were isolated from the bone marrow young donors. MSCs, MIF-overexpressing transplanted into peri-infarct region a rat MI model. Aged exhibited lower proliferative capacity,...

Abstract Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application heavily limited by cardiotoxicity. There accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects EXOs isolated from human induced pluripotent MSCs (iPSC-MSCs) DIC and explore potential mechanisms. were cultural...

Mitochondrial dysfunction in neurons has been implicated hypoxia-ischemia-induced brain injury. Although mesenchymal stem cell therapy emerged as a novel treatment for this pathology, the mechanisms are not fully understood. To address issue, we first co-cultured 1.5 × 105 PC12 cells with that were derived from induced pluripotent at ratio of 1:1, and then intervened cobalt chloride (CoCl2) 24 hours. Reactive oxygen species was measured by Mito-sox. membrane potential (?Ψm) determined JC-1...

Formation of aortic aneurysms as a consequence augmented transforming growth factor β (TGF-β) signaling and vascular smooth muscle cell (VSMC) dysfunction is potentially lethal complication Marfan syndrome (MFS).Here, we examined VSMC senescence in patients with MFS explored the potential mechanisms that link TGF-β.Tissue was harvested from ascending aorta control donors patients, VSMCs were isolated.Senescence-associated β-galactosidase (SA-β-gal) activity expression senescence-related...

High-altitude exposure has been associated with an increased risk of hyperuricemia (HU) and gout, though the underlying mechanisms remain poorly understood. We conducted a comprehensive analysis serum metabolome phenome in both discovery validation cohorts Han Chinese individuals who underwent long-term moderate-altitude (∼12 months), as well independent cohort consisting local Tibetans residing Nyingchi (>5 years). Beta-Alanine intervention was applied hypoxanthine potassium oxonate-induced...

P63 is a p53 family member involved in multiple facets of biology, including embryonic development, cell proliferation, differentiation, survival, apoptosis, senescence and aging. The p63 gene encodes protein isoforms either with (TAp63) or without (ΔNp63) the N-terminal transactivation domain. Amounting evidence suggests that can function as tumor suppressor, yet precise molecular mechanisms, particularly specific roles TAp63 ΔNp63 cancer progression, are still largely unclear. Here, we...

Abstract The cardiac protection of mesenchymal stem cell (MSC) transplantation for myocardial infarction (MI) is largely hampered by low survival. Haem oxygenase 1 (HO‐1) plays a critical role in regulation survival under many stress conditions. This study aimed to investigate whether pre‐treatment with haemin, potent HO‐1 inducer, would promote the MSCs serum deprivation and hypoxia (SD/H) enhance cardioprotective effects MI. Bone marrow (BM)‐MSCs were pretreated or without haemin then...

Abstract Despite promising results in myocardial infarction (MI), mesenchymal stem cell (MSC)‐based therapy is limited by senescence. N6‐methyladenosine (m6A) messenger RNA methylation has been reported to be closely associated with Nonetheless, its role the regulation of MSC senescence remains unclear. We examined ALKB homolog 5 (ALKBH5) regulating and determined whether ALKBH5 downregulation could rejuvenate aged MSCs (AMSCs) improve their therapeutic efficacy for MI. was m6A dot blotting...

Abstract Vascular smooth muscle cells (VSMCs) senescence contributes to abdominal aortic aneurysm (AAA) formation although the underlying mechanisms remain unclear. This study aimed investigate role of miR‐199a‐5p in regulating VSMC AAA. was determined by a senescence‐associated β‐galactosidase (SA‐β‐gal) assay. RT‐PCR and Western blotting were performed measure miRNA protein level, respectively. The generation reactive oxygen species (ROS) evaluated H2DCFDA staining. Dual‐luciferase...

Moderate altitude exposure has shown beneficial effects on diabetes incidence but the underlying mechanisms are not understood. Our study aimed to investigate how human gut microbiome impacted serum metabolome and associated with glucose homeostasis in healthy Chinese individuals upon moderate-altitude exposure. Faecal composition was assessed using shotgun metagenomic sequencing. Serum acquired by untargeted metabolomics technology, amino acids (AAs) propionic acid were quantified targeted...

In endometrial carcinoma, the clinical outcome directly correlates with TNM stage, but lack of sufficient information prevents accurate prediction. The molecular mechanism underlying competing endogenous RNA (ceRNA) hypothesis has not been investigated in cancer. Multi-bioinformatic analyses, including differentially expressed gene analysis, ceRNA network construction, Cox regression function enrichment and protein-protein were performed on sequence data acquired from Cancer Genome Atlas...

Mesenchymal stem cells (MSCs) have shown beneficial effects in the treatment of abdominal aortic aneurysm (AAA). Nonetheless, biological properties adipose-derived MSCs (ASCs) from patients with AAA (AAA-ASCs) remain unclear. This study is aimed at investigating cell phenotype and function AAA-ASCs compared ASCs age-matched healthy donors (H-ASCs). H-ASCs were studied for phenotype, differentiation capacity, senescence, mitochondrial autophagic functions. Cellular senescence was examined by...

Female-specific cancers seriously affect physical and psychological health of women worldwide.We aimed to elucidate trends in the age-standardized mortality rates (ASMRs) breast cancer, cervical uterine ovarian cancer female populations with different socioeconomic statuses China countries Human Development Index (HDI).A longitudinal study was performed using data death other 39 countries. The were standardized Segi's world population. Trends mortalities exhibited by estimated annual...

Abstract Vascular progenitor cells (VPCs) present in the adventitia of vessel wall play a critical role regulation vascular repair following injury. This study aimed to assess function VPCs isolated from patients with Marfan syndrome (MFS). were control and MFS donors characterized. Compared control‐VPCs, MFS‐VPCs exhibited cellular senescence as demonstrated by increased cell size, higher SA‐β‐gal activity elevated levels p53 p21. RNA sequencing showed that several process‐related pathways...

ABSTRACT Aortic dissection (AD) represents a critical condition characterised by tear in the inner lining of aorta, leading to leakage blood into layers aortic wall, posing significant risk life. However, pathogenesis is unclear. In this study, scRNA‐seq was applied cells derived from aortas both AD and non‐AD donors (control) unveil cellular landscape. ScRNA‐seq data uncover heterogeneity aortas. Specifically, we observed an accumulation CD4 + T cells, which contributed inflammation cell...

Breast invasive carcinoma (BRCA) is a complex polygenic disease characterized by molecular and histological heterogeneity. An effort underway to explore investigate multiple reliable prognostic markers improve management of BRCA patients provide novel therapeutic targets. The aim the study identify miRNA signature in patients.The miRNA-sequencing data clinical information were downloaded from Cancer Genome Atlas (TCGA) database.A total 106 differentially expressed miRNAs identified between...

Soluble Nogo66 receptor-Fc protein (sNgR-Fc) enhances axonal regeneration following central nervous system injury. However, the underlying mechanisms remain unclear. In this study, we investigated effects of sNgR-Fc on proliferation and differentiation neural progenitor cells. The photothrombotic cortical injury model ischemic stroke was produced in parietal cortex Sprague-Dawley rats. rats with were randomized to receive infusion 400 μg/kg (sNgR-Fc group) or an equal volume...

To explore whether the differentiation of vascular stem cells (VSC) into smooth muscle (SMC) in aortic dissection (AD) is dysregulated, and to verify role Notch3 pathway this process.Aortic tissues were obtained from AD patients undergoing replacement heart transplant donors at Department Cardiovascular Surgery, Guangdong Provincial People's Hospital Affiliated Southern Medical University. VSC isolated by enzymatic digestion c-kit immunomagnetic beads. The divided normal donor-derived group...

OBJECTIVE Evidence from previous studies has demonstrated that NRF2 can protect cardiovascular progression,which prompted us to study if is involved in AAA development. APPROACH AND RESULTS The difference and function of were verified on human aortic tissues combined with scRNA-seq samples.We then used angiotensin II (Ang II) infusion mouse model VSMCs-specific knockout the role formation.Primary cultured VSMCs how regulates contractile phenotype.Patient specimens obtained investigate...

Abstract Background Intestinal epithelial barrier dysfunction is a major pathological feature of inflammatory bowel disease (IBD). Stability and accuracy intestinal cells (IECs) self-renew are the fundament mucosal regeneration repair. Fermentable dietary fibre short-chain fatty acid (SCFA) play role in cell proliferation, histone acetylation immune responses. However, results about SCFA modulating IECs proliferation not coincided. There several reason that can have an impact on through...