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Wanas, H., Z. El Shereef, L. Rashed, and B. E. Aboulhoda, "Ticagrelor Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Inhibition of TGF-β1/Smad3 and PI3K/AKT/mTOR Pathways.", Current molecular pharmacology, 2021. Abstract

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious disease with high mortality rate. Activation of transforming growth factor (TGF)-β1 production and signalling is considered the corner stone in the epithelial-mesenchymal transition (EMT) process. EMT plays a central role in development of fibrosis in many organs including the lungs. Activated platelets are an important source of TGF-β1 and play a pivotal role in EMT and fibrosis process. The antiplatelet, ticagrelor was previously found to inhibit the EMT in different types of cancer cells, but its ability to serve as an anti-pulmonary fibrosis (PF) agent was not previously investigated.

OBJECTIVE: In this study, we aim to investigate the potential ability of ticagrelor to ameliorate bleomycin-induced fibrosis in rats.

METHODS: PF was induced in rats by intratracheal BLM at a dose of 3 mg/kg. The effect of daily daily 20 mg/kg oral ticagrelor on different histological and biochemical parameters of fibrosis was investigated.

RESULTS: Our results revealed that ticagrelor can alleviate lung fibrosis. We found that ticagrelor inhibited TGF-β1 production and suppressed Smad3 activation and signaling pathway with subsequent inhibition of Slug and Snail. In addition, ticagrelor antagonized PI3K/AKT/mTOR pathway signaling. Moreover, ticagrelor inhibited the EMT that revealed by its ability to up-regulate the epithelial markers as E-cadherin (E-cad) and to decrease the expression of the mesenchymal markers as vimentin (VIM) and alpha-smooth muscle actin (α-SMA).

CONCLUSION: Our results suggest that the P2Y12 inhibitor, ticagrelor may have a therapeutic potential in reducing the progression of PF.

Barsoum, R., H. Wanas, and T. Shehab, Anticoagulation in Patients with Renal Insufficiency, , pp. 203 - 238, 2020/01/01. Abstract

The retained metabolic products in kidney insufficiency are toxic to two main cells connected with blood coagulation, namely, the endothelial cells and the blood platelets. These interact with each other, with leukocytes and with a complex metabolic network involving inflammation, complement activation, coagulation, fibrinolysis, and others. Owing to the unstable nature of kidney insufficiency, the associated coagulation disorders vary from a procoagulant state where endothelial cell injury predominates, to a bleeding disorder where platelet dysfunction supervenes. Amid all that, patients with kidney insufficiency may need anticoagulation either for the commonly associated heart disease, venous thrombosis, antiphospholipid syndrome, etc., for the treatment of certain intrinsic renal disease, or for extracorporeal therapy. This requires a careful benefit/risk balance that can be quantitated by validated scores. As the decision to anticoagulate is made, several practical issues emerge, including the choice of pharmacokinetically compatible agents, their dose in relation to the degree of impairment of kidney function, and potential drug-drug interactions. The decision is confounded by the plethora of currently available anticoagulants, often with superior efficacy, less bleeding tendency, and limited need for monitoring and frequent dose tailoring compared to the traditional heparin and warfarin.

Fadl, H. O., N. M. Amin, H. Wanas, S. Saad El-Din, H. A. Ibrahim, B. E. Aboulhoda, and N. Z. Bocktor, "The impact of l-arginine supplementation on the enteral phase of experimental infection in treated and untreated mice.", Journal of parasitic diseases : official organ of the Indian Society for Parasitology, vol. 44, issue 4, pp. 737-747, 2020. Abstract

The role of nitric oxide (NO) in the immunopathological response during () infection remains controversial. The amino acid, l-arginine is a NO precursor commonly used by athletes and bodybuilders as a protein supplement. As to our knowledge, there are no published studies which have tested the effect of l-arginine on the intestinal phase of experimental trichinellosis. The present work aims to investigate the effect of l-arginine on the enteral phase of experimental infection in albendazole-treated and untreated mice. Forty BALB/C mice infected orally with larvae were divided into 4 groups as follows: Group A were infected and untreated (control) mice, Group B received albendazole alone, Group C received l-arginine alone, and Group D received both l-arginine and albendazole. Compared to the control group, l-arginine supplementation showed; a significant increase in the intestinal adult worm burden, a significantly high inducible NO synthase (iNOS) expression, elevated immune markers; tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and enhanced apoptosis. Albendazole treated-group had a significant reduction in the adult worm number (90.9%), while combined albendazole-arginine regimen showed a lower percentage of worm reduction (72.7%). During the enteral phase of infection, l-arginine supplementation should be taken cautiously, as it may modulate the proinflammatory immune response and subsequently affect the outcome of the infection and/or treatment.

Elamin, A. A., S. Steinicke, W. Oehlmann, Y. Braun, H. Wanas, E. A. Shuralev, and C. Huck, "Novel drug targets in cell wall biosynthesis exploited by gene disruption in Pseudomonas aeruginosa", plos one, 2017.
Singh, M., H. Wanas, W. Oehlmann, C. Vilaplana, P. J. Cardona, and undefined, Combination of ethambutol with at least one additional anti-bacterial agent for use in the treatment of bacterial infections, , 2014.