The investigation of therapeutic potential of oxytocin and liraglutide on vincristine-induced neuropathy in rats.

The aim of this study was to assess the therapeutic potential of oxytocin and liraglutide (LIR), a GLP-1 analogue, in a rat model of vincristine-induced neuropathy. Rats were injected with vincristine (VCR) at a dose of 4 mg/kg twice a week for 5 weeks. The VCR-administered rats were divided into three groups and received saline, oxytocin, or liraglutide simultaneously with VCR. After the treatment period, electrophysiological, biochemical, histological, and immunohistochemical investigations were performed. Electromyography (EMG) recordings demonstrated significant alterations in the VCR + saline group (p < .001). Also, motor performance was decreased in the VCR + saline group (p < .05). Histologically, the axonal diameter was decreased in all groups. VCR + saline group showed significantly increased lipid peroxidation and decreased nerve growth factor (NGF) expression. However, the administration of oxytocin and liraglutide significantly prevented the EMG alterations, lipid peroxidation, and reduction in neuronal NGF expression. On the basis of these findings, oxytocin and liraglutide may be considered as potential agents for the prevention of VCR-induced neuropathy.

Multifunctional cholinesterase inhibitors for Alzheimer's disease: Synthesis, biological evaluations, and docking studies of o/p-propoxyphenylsubstituted-1H-benzimidazole derivatives.

This study indicates the synthesis, cholinesterase (ChE) inhibitory activity, and molecular modeling studies of 48 compounds as o- and p-(3-substitutedethoxyphenyl)-1H-benzimidazole derivatives. According to the ChE inhibitor activity results, generally, para series are more active against acetylcholinesterase (AChE) whereas ortho series are more active against butyrylcholinesterase (BuChE). The most active compounds against AChE and BuChE are compounds A12 and B14 with IC50 values of 0.14 and 0.22 µM, respectively. Additionally, the most active 16 compounds against AChE/BuChE were chosen to investigate the neuroprotective effects, and the results indicated that most of the compounds have free radical scavenging properties and show their effects by reducing free radical production; moreover, some of the compounds significantly increased the viability of SH-SY5Y cells exposed to H2 O2 . Overall, compounds A12 and B14 with potential AChE and BuChE inhibitory activities, high neuroprotection against H2 O2 -induced toxicity, free radical scavenging properties, and metal chelating abilities may be considered as lead molecules for the development of multi-target-directed ligands against Alzheimer's disease.

Mice with diet-induced obesity demonstrate a relative prothrombotic factor profile and a thicker aorta with reduced ex-vivo function.

: Classical risk factors such as cholesterol and lipoproteins are currently not sufficient to explain all physiopathological processes of obesity-related vascular dysfunction as well as atherosclerosis and arteriosclerosis. Therefore, the discovery of potential markers involved in vascular dysfunction in the obese state is still needed. Disturbances in hemostatic factors may be involved in the developmental processes associated with obesity-related cardiovascular disorders. We hypothesized that alterations of several hemostatic factors in the obese state could correlate with the function and morphology of the aorta and it could play an important role in the development of vascular dysfunction. To test this, we fed mice with a high-fat diet for 18 weeks and investigated the relationships between selected hemostatic factors (in either plasma or in the liver), metabolic hormones and morphology, and ex-vivo function of the aorta. Here, we show that 18-week exposure to a high-fat diet results in a higher plasma fibrinogen and prolonged prothrombin time in diet-induced obese mice compared to the controls. In addition, liver levels or activities of FII, FX, activated protein C, AT-III, and protein S are significantly different in diet-induced obese mice as compared to the controls. Curiously, FII, FVIII, FX, activated protein C, PTT, and protein S are correlated with both the aorta histology (aortic thickness and diameter) and ex-vivo aortic function. Notably, ex-vivo studies revealed that diet-induced obese mice show a marked attenuation in the functions of the aorta. Taken together, aforementioned hemostatic factors may be considered as critical markers for obesity-related vascular dysfunction and they could play important roles in diagnosing of the dysfunction.