Synthesis and Molecular Modeling Studies of 2-[2-(3-nitrophenyl)-1h-benzimidazol-1-yl]-acetamide Derivatives as Anthelmintic

Benzimidazole derivatives of substituted 2 [2-(3-nitrophenyl)-1H-benzimidazole-1-yl] acetamide analogues were synthesized and studied for antihelminthic activity. Compounds 3a–o were obtained in three steps, starting with the Oxidative Condensation of the appropriate 3-nitrobenzaldeyde, o-phenylenediamine and sodium hydrogen sulfite to form 2-(3-nitrophenyl)-1H-benzimidazole (1a). In second step Nucleophilic substitution, Chlorine atom of ethylchloroacetate will attach on nitrogen of benzimidazole by replacing hydrogen with elimination of hydrochloric acid to form ethyl [2-(3-nitrophenyl)-1H-benzimidazole-1-Yl acetate (2a).In third step amide formation from ester takes place by substitution of electrophilic with loss of ethanol to form substituted 2 [2-(3-nitrophenyl)-1H-benzimidazole-1-yl] acetamide 3a–o The antihelminthic activity showed that compounds 3f, 3h, 3i, 3j and 3k good activity against Indian earthworms (Pheretima posthuma) in comparison to albendazole.

Crosstalk between Sodium–Glucose Cotransporter Inhibitors and Sodium–Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases

Abnormality in glucose homeostasis due to hyperglycemia or insulin resistance is the hallmark of type 2 diabetes mellitus (T2DM). These metabolic abnormalities in T2DM lead to cellular dysfunction and the development of diabetic cardiomyopathy leading to heart failure. New antihyperglycemic agents including glucagon-like peptide-1 receptor agonists and the sodium–glucose cotransporter-2 inhibitors (SGLT2i) have been shown to attenuate endothelial dysfunction at the cellular level. In addition, they improved cardiovascular safety by exhibiting cardioprotective effects. The mechanism by which these drugs exert their cardioprotective effects is unknown, although recent studies have shown that cardiovascular homeostasis occurs through the interplay of the sodium–hydrogen exchangers (NHE), specifically NHE1 and NHE3, with SGLT2i. Another theoretical explanation for the cardioprotective effects of SGLT2i is through natriuresis by the kidney. This theory highlights the possible involvement of renal NHE transporters in the management of heart failure. This review outlines the possible mechanisms responsible for causing diabetic cardiomyopathy and discusses the interaction between NHE and SGLT2i in cardiovascular diseases.

Production of non-ferrous metal concentrate in the processing of pyrite slags

The method of preliminary chemical activation of mineral raw materials was used in the conducted studies for the complex processing of pyritic slags. The influence of preliminary chemical activation of kaolinite clays of Alexeevsky deposit in the solution of sodium hydrogen carbonate on the separation of kaolinite and quartz fractions was studied. The temperature of 150 oC, the duration of 120 minutes, and the concentration of sodium bicarbonate solution of 120 g/dm3 should be considered the optimum mode of activation. As a result of activation, the phase composition of the kaolinite fraction changed: the percentage of kaolinite fraction decreased; new phases of muscovite and sodium aluminosilicate appeared; the amount of quartz increased.

Effects of Disodium Hydrogen Phosphate Addition and Heat Treatment on the Formation of Magnesium Silicate Hydrate Gel

The formation of magnesium silicate hydrate gel is crucial in preventing magnesia aggregates from over hydrated during the construction of refractory castables since the presence of magnesium hydroxide diminish the mechanical properties of the material. This work aimed to investigate the accelerating effects of sodium hydrogen phosphate and heat treatment on the formation of magnesium silicate hydrate gel. Time-dependent pH of magnesia - silica fume slurries with and without sodium hydrogen phosphate addition and heat treatment was measured to verify the dissolution of MgO and magnesium silicate hydrate formation. The effects of sodium hydrogen phosphate were differentiable only at small added amounts, whereas heat treatment at 50 degrees Celsius performed noticeable acceleration. This observation could be applicable in molding to maintain the stability of basic refractory castables.

NHE6-depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load

Apolipoprotein E4 (ApoE4) is the most important and prevalent risk factor for late-onset Alzheimer's disease (AD). The isoelectric point of ApoE4 matches the pH of the early endosome (EE), causing its delayed dissociation from ApoE receptors and hence impaired endolysosomal trafficking, disruption of synaptic homeostasis and reduced amyloid clearance. We have shown that enhancing endosomal acidification by inhibiting the EE-specific sodium-hydrogen exchanger 6 (NHE6) restores vesicular trafficking and normalizes synaptic homeostasis. Remarkably and unexpectedly, loss of NHE6 (encoded by the gene Slc9a6) in mice effectively suppressed amyloid deposition even in the absence of ApoE4, suggesting that accelerated acidification of early endosomes caused by the absence of NHE6 occludes the effect of ApoE on amyloid plaque formation. NHE6 suppression or inhibition may thus be a universal, ApoE-independent approach to prevent amyloid buildup in the brain. These findings suggest a novel therapeutic approach for the prevention of AD by which partial NHE6 inhibition reverses the ApoE4 induced endolysosomal trafficking defect and reduces plaque load.