Harmine prevents 3-nitropropionic acid-induced neurotoxicity in rats via enhancing NRF2-mediated signaling: Involvement of p21 and AMPK.

Oxidative stress induced neurotoxicity is increasingly perceived as an important neuropathologic mechanism underlying the motor and behavioral phenotypes associated with Huntington's disease (HD). Repeated exposure to 3-nitropropionic acid (3-NP) induces neurotoxic changes which closely simulate the neuropathological and behavioral characteristics of HD. This study aimed at evaluating the prophylactic effects of the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) inhibitor "harmine" against 3-NP-indued neurotoxicity and HD-like symptoms. The potential prophylactic effect of harmine (10 mg/kg/day; intraperitoneal) was investigated on 3-NP-induced motor and cognitive HD-like deficits, nuclear factor erythroid 2 like 2 (NRF2), AMP kinase (AMPK) and p21 protein levels and the gene expression of haem oxygenase-1 (Ho-1), NAD(P)H: quinone oxidoreductase-1 (Nqo-1) and p62 in addition to redox imbalance and histological neurotoxic changes in the striatum, prefrontal cortex, and hippocampus of male Wistar rats. Harmine successfully increased the protein levels of NRF2, AMPK and p21 and the gene expression of Ho-1, Nqo-1 and p62, restored redox homeostasis, and reduced CASPASE-3 level. This was reflected in attenuation of 3-NP-induced neurodegenerative changes and improvement of rats' motor and cognitive performance. This study draws attention to the protective role of harmine against 3-NP-induced motor and cognitive dysfunction that could be mediated via enhancing NRF2-mediated signaling with subsequent amelioration of oxidative stress injury via NRF2 activators, p21 and AMPK, in the striatum, prefrontal cortex, and hippocampus which could offer a promising therapeutic tool to slow the progression of HD.

Electrochemical and quantum chemical studies on the corrosion inhibition of 1037 carbon steel by different types of surfactants.

In this work, three different types of surfactants, namely, dodecyl trimethyl ammonium chloride (DTAC, C12H25N (CH3)3Cl)-, octyl phenol poly(ethylene glycol ether) x (TX-100, C34H62O11 for x = 10) and dioctyl sodium sulfosuccinate (AOT-100, C20H37O7NaS) with corrosion restraint were utilized as corrosion inhibitors for 1037 CS in 0.5 M HCl. The protection efficacy (% IE) was indicated by weight loss and electrochemical measurements. Polarization curves showed that the investigated compounds are mixed-type inhibitors. The protection efficacy (% IE) increases with the increase in the surfactant concentration and reached 64.42-86.46% at 8 × 10-4 M and 30 °C. Adsorption of these utilized surfactants (DTAC, TX-100, and AOT) onto the CS surface concurred with the Langmuir adsorption isotherm. Impedance data revealed that by increasing the surfactant concentration, the charge transfer resistance (R ct) increases and vice versa for the capacitance of double layer (C dl). Surface morphological investigations such as scanning electron microscopy (SEM) combined with EDX and atomic force microscopy (AFM) were used to further investigate the inhibitors' protective abilities. Monte Carlo simulations showed the great interaction between the tested surfactants and the metal surface of the CS. The theoretical results (density functional theory, DFT) were in good agreement with experimental measurements. The restraint efficiencies of anionic, neutral, and cationic surfactants regarded a certain dating to HSAB precept and Fukui indices.

Pioglitazone improves skeletal muscle functions in reserpine-induced fibromyalgia rat model.

BACKGROUND: Fibromyalgia (FM) is characterized by musculoskeletal pain, fatigue, sleep and memory disturbance. There is no definitive cure yet for FM-related health problems. Peroxisome proliferator-activated receptor's (PPAR's) activation is associated with insulin sensitisation and improved glucose metabolism. PPAR-γ was reported to alleviate FM allodynia. Limited data are discussing its effect on motor disorders. OBJECTIVE: To investigate the potential effect of PPAR-γ agonists (pioglitazone, as one member of thiazolidinediones (TZD)) on motor dysfunction in reserpine-induced FM in a rat model. MATERIALS AND METHODS: Thirty-six male Wistar rats were divided into negative control (n = 9) and reserpine-induced FM (n = 27) groups. The latter was subdivided into three equal subgroups (n = 9), positive control (untreated FM model), pioglitazone-treated and GW9662-treated. We evaluated muscle functions and activity of chloramphenicol acetyltransferase, superoxide dismutase, malondialdehyde, and serum levels of interleukin-8 and monocyte chemoattractant protein-1. RESULTS: Pioglitazone significantly relieved fatigue, improved muscle performance, reduced inflammatory cytokines and enhanced antioxidant's activity, while GW9662, a known PPAR-γ antagonist, aggravated the FM manifestations in the rat model. CONCLUSION: PPAR-γ agonists show a promising role against FM-associated motor dysfunctions.

Thrombosis in children with acute lymphoblastic leukemia treated at a tertiary care center in Lebanon: revisiting the role of predictive models.

The incidence of symptomatic venous thromboembolism (VTE) in children receiving therapy for acute lymphoblastic leukemia (ALL) varies widely and is protocol dependent. The authors herein report the incidence and potential risk factors for VTE in children with ALL while being treated on a uniform protocol at a single tertiary care center in Lebanon. The authors also examine necessary modifications in a recently published model before it could predict VTE in their patients.