Expression patterns of serum miR-27a-3p and activating transcription factor 3 in children with bronchial asthma and their correlations with airway inflammation.

INTRODUCTION: Bronchial asthma (BA) is a heterogeneous disease characterized by chronic airway inflammation. This study investigated the serum miR-27a-3p/activating transcription factor 3 (ATF3) expression in children with BA and their correlations with airway inflammation. METHODS: Children with BA (N = 120) and healthy children (N = 108) were enrolled. Serum levels of interleukin (IL)-17, IL-6, tumor necrosis factor (TNF)-α, immunoglobulin E (IgE), miR-27a-3p, ATF3, and the number of eosinophils (EOS) were measured using enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT-qPCR), and an automatic hematology analyzer. The correlations between miR-27a-3p and ATF3 and between miR-27a-3p/ATF3 and inflammation-related factors were analyzed by the Pearson method. The diagnostic values of miR-27a-3p and ATF3 in BA were evaluated using receiver operating characteristic (ROC) curves. The influencing factors of BA were assessed using multivariate logistic regression. Finally, the targeting relation between miR-27a-3p and ATF3 was predicted and analyzed by TargetScan and Starbase databases, and dual-luciferase assay. RESULTS: There were significant differences in forced expiratory volume in 1 s (FEV1)% predicted and FEV1/forced vital capacity (FVC)%, serum levels of IgE, IL-17, IL-6, and TNF-α, and EOS numbers between healthy children and BA children. Serum miR-27a-3p was negatively correlated with ATF3 and positively correlated with inflammation-related factors in BA children. Serum ATF3 mRNA levels were negatively correlated with inflammatory factors in BA children. miR-27a-3p and ATF3 had good diagnostic values in BA children. FEV% predicted, IL-6, TNF-α, miR-27a-3p, and ATF3 were independent risk factors for BA. miR-27a-3p targeted ATF3. CONCLUSION: Serum miR-27a-3p was highly expressed, whereas ATF3 was poorly expressed in BA children, and they were significantly correlated with airway inflammation, had good diagnostic values in BA children, and were independent risk factors for asthma.

Targeting ferroptosis as novel therapeutic approaches for epilepsy.

Epilepsy is a chronic disorder of the central nervous system characterized by recurrent unprovoked seizures resulting from excessive synchronous discharge of neurons in the brain. As one of the most common complications of many neurological diseases, epilepsy is an expensive and complex global public health issue that is often accompanied by neurobehavioral comorbidities, such as abnormalities in cognition, psychiatric status, and social-adaptive behaviors. Recurrent or prolonged seizures can result in neuronal damage and cell death; however, the molecular mechanisms underlying the epilepsy-induced damage to neurons remain unclear. Ferroptosis, a novel type of regulated cell death characterized by iron-dependent lipid peroxidation, is involved in the pathophysiological progression of epilepsy. Emerging studies have demonstrated pharmacologically inhibiting ferroptosis can mitigate neuronal damage in epilepsy. In this review, we briefly describe the core molecular mechanisms of ferroptosis and the roles they play in contributing to epilepsy, highlight emerging compounds that can inhibit ferroptosis to treat epilepsy and associated neurobehavioral comorbidities, and outline their pharmacological beneficial effects. The current review suggests inhibiting ferroptosis as a therapeutic target for epilepsy and associated neurobehavioral comorbidities.

The Oncogenic Effects, Pathways, and Target Molecules of JC Polyoma Virus T Antigen in Cancer Cells.

JC polyoma virus (JCPyV) is a ubiquitous polyoma virus that infects the individual to cause progressive multifocal leukoencephalopathy and malignancies. Here, we found that T-antigen knockdown suppressed proliferation, glycolysis, mitochondrial respiration, migration, and invasion, and induced apoptosis and G2 arrest. The reverse was true for T-antigen overexpression, with overexpression of Akt, survivin, retinoblastoma protein, ß-catenin, ß-transducin repeat-containing protein (TRCP), and inhibitor of growth (ING)1, and the underexpression of mammalian target of rapamycin (mTOR), phosphorylated (p)-mTOR, p-p38, Cyclin D1, p21, vascular endothelial growth factor (VEGF), ING2, and ING4 in hepatocellular and pancreatic cancer cells and tissues. In lens tumor cells, T antigen transcriptionally targeted viral carcinogenesis, microRNAs in cancer, focal adhesion, p53, VEGF, phosphoinositide 3 kinase-Akt, and Forkhead box O signaling pathways, fructose and mannose metabolism, ribosome biosynthesis, and choline and pyrimidine metabolism. At a metabolomics level, it targeted protein digestion and absorption, aminoacryl-tRNA biosynthesis, biosynthesis of amino acids, and the AMPK signal pathway. At a proteomic level, it targeted ribosome biogenesis in eukaryotes, citrate cycle, carbon metabolism, protein digestion and absorption, aminoacryl-tRNA biosynthesis, extracellular-matrix-receptor interaction, and biosynthesis of amino acids. In lens tumor cells, T antigen might interact with various keratins, ribosomal proteins, apolipoproteins, G proteins, ubiquitin-related proteins, RPL19, ß-catenin, ß-TRCP, p53, and CCAAT-enhancer-binding proteins in lens tumor cells. T antigen induced a more aggressive phenotype in mouse and human cancer cells due to oncogene activation, inactivation of tumor suppressors, and disruption of metabolism, cell adhesion, and long noncoding RNA-microRNA-target axes.

Naringenin Inhibit the Hydrogen Peroxide-Induced SH-SY5Y Cells Injury Through Nrf2/HO-1 Pathway.

Naringenin (NGN), a flavonoid, abundantly present in citrus fruits, has been established as a neuroprotective agent. However, the precise protective mechanisms remain worthy of further investigation. The present study was designed to explore the protective effects of NGN against hydrogen peroxide (H2O2)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. Exposure of cells to 400 µM H2O2 for 2 h caused viability loss, apoptotic increase, and reactive oxygen species (ROS) increase, pre-treatment with NGN for 12 h significantly reduced the viability loss, apoptotic rate, and attenuated H2O2-mediated ROS production. In addition, NGN inhibited H2O2-induced mitochondrial dysfunctions, including lowered membrane potential, decreased Bcl-2/Bax ratio, cytochrome c release, and the cleavage of caspase-3. We also showed that NGN increased HO-1 expression. NGN treatment caused nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2). NGN activated both ERK and PI3 K/Akt, and treatments with the specific ERK inhibitor PD98059, the PI3 K inhibitor LY294002, and the specific Nrf2 shRNA suppressed the NGN-induced HO-1 expression. The HO-1 inhibitor ZnPP abolished the neuroprotective effect of NGN against H2O2-induced neurotoxicity. Taken together, the present study demonstrates that regulation of Nrf2/HO-1 pathway through activation of ERK and PI3 K/Akt, and the inhibition of mitochondria-dependent apoptosis together may render NGN protect SH-SY5Y cells from H2O2-induced neurotoxicity.