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AbstractPurposeMethodsResultsConclusionMelatonin has promising protective effects for retinopathy. However, its roles in retinopathy of prematurity (ROP) and the underlying mechanisms remain unknown. We aimed to explore its roles and mechanisms in a ROP model.Hematoxylin and eosin staining were used to observe the morphology of the retina. Immunofluorescence was used to detect positive (Nrf2+ and VEGF+) cells. Immunohistochemistry was used to detect the level of nuclear expression of PCNA in retinal tissue. Transmission electron microscope (TEM) was used to observe the morphology and structure of pigment cells. qRT-PCR was used to assay the expression of miR-23a-3p, Nrf2, and HO-1. Western blotting was used to detect the expression of Nrf2, HO-1, β-actin, and Lamin B1.Melatonin or miR-23a-3p antagomir treatment could ameliorate the Oxygen-induced pathological changes, increased the expression of Nrf2 and HO-1, SOD, and GSH-Px, and decreased the expression of VEGF, miR-23a-3p, MDA and the apoptosis in the ROP model. Further target prediction and luciferase reporter assays confirmed the targeted binding relationship between miR-23a-3p and Nrf2.Our study showed that melatonin could ameliorate H2O2-induced apoptosis and oxidative stress injury in RGC cells by mediating miR-23a-3p/Nrf2 signaling pathway, thereby improving retinal degeneration. [ABSTRACT FROM AUTHOR]

Aims: Downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to doxorubicin (DOX)-induced myocardial oxidative stress, and inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) increased Nrf2 protein level in rat heart suffering ischemia/reperfusion, indicating a connection between MALT1 and Nrf2. This study aims to explore the role of MALT1 in DOX-induced myocardial oxidative stress and the underlying mechanisms. Results: The mice received a single injection of DOX (15 mg/kg, i.p.) to induce myocardial oxidative stress, evidenced by increases in the levels of reactive oxidative species as well as decreases in the activities of antioxidative enzymes, concomitant with a downregulation of Nrf2; these phenomena were reversed by MALT1 inhibitor. Similar phenomena were observed in DOX-induced oxidative stress in cardiomyocytes. Mechanistically, knockdown or inhibition of MALT1 notably attenuated the interaction between Nrf2 and MALT1 and decreased the k48-linked ubiquitination of Nrf2. Furthermore, inhibition or knockdown of calcium/calmodulin-dependent protein kinase II (CaMKII-δ) reduced the phosphorylation of caspase recruitment domain-containing protein 11 (CARD11), subsequently disrupted the assembly of CARD11, B cell lymphoma 10 (BCL10), and MALT1 (CBM) complex, and reduced the MALT1-dependent k48-linked ubiquitination of Nrf2 in DOX-treated mice or cardiomyocytes. Innovation and Conclusion: The E3 ubiquitin ligase function of MALT1 accounts for the downregulation of Nrf2 and aggravation of myocardial oxidative stress in DOX-treated mice, and CaMKII-δ-dependent phosphorylation of CARD11 triggered the assembly of CBM complex and the subsequent activation of MALT1.

Background: MicroRNA is anendogenous non-coding single strand RNA which consists of 22 nt. It post-transcriptionally regulates gene expression and development. MicroRNA 21 plays an important role in repairing injured brain tissues. Thus, in this research, we explored the function of miR-21 in learning-memory recovery after brain injury., Method: 3 days old newborn SD rats were separated into three groups: Sham operation group (Sham), inflammation-sensitized hypoxic-ischemic brain injury (LPS+HI) group and miR-21 inhibitor group. 28 days later, the learning and memory capability was assayed by water maze. H&E staining and Nissl's staining were used to assay pathologic changes and TUNEL was used to assay neuron apoptosis in brain tissue., Results: Water maze assay showed that the capability of positioning navigation in the IH-HI group was worse than in the Sham group and miR-21 inhibition group, and the Sham group wass better than miR-21 group. Both of the comparisons had statistical significance (P < 0.05). H&E staining in the sham group showed that the neurons were arranged well in hippocampus. In LPS+HI group, some neurons in hippocampus had vacuolar degeneration and the neurons were not well arranged well. In the hippocampus of miR-21 inhibitor group, the neuron cell layers were decreased but the neurons were arranged better than in the LPS+HI group. Nissl's staining in LPS+HI group showed neuronal edema, neurons decreased, and Nissl's bodies decreased in the cytoplasm compared with the sham group. However, compared with the LPS+HI group, Nissl's staining in miR-21 inhibitor group showed that the neuronal edema was alleviated and neurons were better arranged. TUNEL assay showed that the apoptosis rate of LPS+HI group was higher than in the miR-21 inhibitor group and miR-21 inhibitor group was higher than the sham group., Conclusion: Down-regulated miR-21 can alleviate LPS+HI injury in the brain., Competing Interests: None., (IJCEP Copyright © 2019.)