Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischemia-reperfusion injury via TXNIP regulation

BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whether the extracellular vesicles(EVs)secreted by adipose mesenchymal stem cells(ADSCs)derived from subcutaneous inguinal adipose tissue(IAT)underγ-aminobutyric acid(GABA)induction(GABA-EVs^(IAT))demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms.METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA.We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays.The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds.To explore the functional RNA diversity between EVs^(IAT)and GABA-EVs^(IAT),we employed microRNA(miR)sequencing.Through a dual-luciferase reporter assay,we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein(TXNIP).Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction.RESULTS Our study demonstrates that,under the influence of GABA,ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs.Consequently,this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention,ultimately resulting in myocardial protection.On a molecular mechanism level,EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes.CONCLUSION Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs,thereby regulating the expression of TXNIP.The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI.

Carney complex: Two case reports and review of literature

Lian Duan, Lin Lu, Carney complex （CNC） is an extremely rare genetic syndrome of pigmented skin lesions, endocrine hyper-function and myxoma. Given its diverse clinical mani-festations, CNC is often misdiagnosed. Recognition of some special clinical manifestations and imaging features may help with the diagnosis. Early diagnosis of CNC would alert ongoing surveillance of tumors and complications; the prognosis of CNC may thus be improved by early treatment. Herein, we report two cases of CNC with bone lesions.

Primary Squamous Cell Carcinoma of the Small Intestine： Pathogenesis and Clinical Features

Relative to the length and surface area of the gastrointestinal tract, malignant tumors of the small intestine are remarkably rare, with a global incidence of〈1 per 100,000 population. Among the forty different histological subtypes of small intestinal cancers, primary squamous cell carcinoma （SCC） is exceptionally rare with only occasional case reports in literature. The present study reported a case of primary SCC of the small intestine and reviewed all cases reported in English literature to provide a systematic overview of this rare disease.