Development of a refined ex vivo model of peritoneal adhesion formation,and a role for connexin 43 in their development

Molecular and Cellular Biochemistry - Despite many advances across the surgical sciences, post-surgical peritoneal adhesions still pose a considerable risk in modern-day procedures and are highly...     

Long Non-coding RNA Peg13 Alleviates Hypoxic-Ischemic Brain Damage in Neonatal Mice via miR-20a-5p/XIAP Axis

Neurochemical Research - Long noncoding RNA (LncRNA) Peg13 has been demonstrated to protect against neurological diseases. However, its underlying mechanism in the progression of hypoxic-ischemic...     

Ferritinophagy is Involved in Experimental Subarachnoid Hemorrhage-Induced Neuronal Ferroptosis

Ferroptosis is a novel form of regulated cell death involved in the pathophysiological process of experimental subarachnoid hemorrhage (SAH), but how neuronal ferroptosis occurs remains unknown. In this study, we report that SAH-induced ferroptosis is macroautophagy/autophagy dependent because the inhibition of autophagy by knocking out autophagy-related gene 5 (ATG5) apparently mitigated SAH-induced ferroptosis. We created an experimental SAH model in Sprague–Dawley rats to determine the possible mechanism. We found that SAH can trigger neuronal ferroptosis, as evidenced by the disruption of iron homeostasis, elevation of intracellular lipid peroxidation (LPO) and decreased expression of ferroptosis–protective proteins. Then, we inhibited autophagy by ATG5 gene knockout, showing that autophagy inhibition can reduce the intracellular iron level and LPO, improve the expression of ferroptosis–protective proteins, and subsequently alleviate SAH-induced cell death. Additionally, autophagy inhibition also attenuated SAH prognostic indicators, such as brain edema, blood–brain barrier permeability, and neurological deficits. These findings not only present an opinion that SAH triggers neuronal ferroptosis via activation of ferritinophagy but also indicate that regulating ferritinophagy and maintaining iron homeostasis could provide clues for the prevention of early brain injury.

     

Alteration of Glycerophospholipid Metabolism in Hippocampus of Post-stroke Depression Rats

Post-stroke depression (PSD) is the most common mental disorder in stroke survivors. However, its specific pathophysiology remains largely unknown. Previous studies suggested a role of hippocampus in PSD. Therefore, we conducted this study to investigate the lipid metabolic signatures in hippocampus of PSD rats. Here, the liquid chromatography mass spectrometry was used to identify the lipid metabolic signatures in the hippocampus of PSD, control and stroke rats. Then, correlations between behavior indices and differential lipid metabolites in PSD rats were explored. Pathway and enrichment analysis were further conducted to uncover the crucial metabolic pathways related to PSD. Finally, we found that the lipid metabolic phenotype in hippocampus of PSD rats was substantially different from that in control and stroke rats, and identified 50 key lipid metabolites that were significantly decreased in PSD rats. These differential metabolites were mainly involved in glycerophospholipid metabolism. Meanwhile, the sucrose preference and immobility time were found to be significantly positively and negatively, respectively, correlated with glycerophospholipid metabolites. The pathway and enrichment analysis showed that the glycerophospholipid metabolism, especially cardiolipin metabolism, was significantly disturbed in PSD rats. These results suggested that the down-regulated glycerophospholipids in hippocampus, especially cardiolipin, might participate in the pathophysiology of PSD. Our findings would be helpful for future exploring the pathophysiology of PSD.

     

Identification of miR-200a as a novel suppressor of connexin 43?in breast cancer cells

Both miRNAs (miRs) and connexin 43 (Cx43) were important regulators of the metastasis of breast cancer, whereas the miRs regulating Cx43 expression in breast cancer cells were still obscure. In the present study, we scanned and found miR-1, miR-206, miR-200a, miR-381, miR-23a/b and miR-186 were functional suppressors of human Cx43 mRNA and protein expression. Specially, we demonstrated that only miR-200a could directly target the 3′-untranslated region (3′-UTR) of human Cx43 gene. Functionally, overexpression of Cx43 in MCF cells potentiated the migration activity, whereas additional miR-200a treatment notably prevented this effect. Finally, we demonstrated that decreased levels of miR-200a and elevated expression of Cx43 in the metastatic breast cancer tissues compared with the primary ones. Thus, we are the first to identify miR-200a as a novel and direct suppressor of human Cx43, indicating that miR200a/Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer.