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Background: Triple-Negative Breast Cancers (TNBC) are among the most aggressive and therapyresistant breast tumors. Development of new treatment strategies that target pathways involved in cancer cells resistance is an attractive candidate to overcome therapeutic resistance. Objective: To clarify the antitumor activity of [VO (bpy)2 Cl] Cl complex as a new therapeutic agent through studying the interplay between apoptosis, autophagy and notch signaling pathways. Methods: Proliferation of MDA-MB-231 cells and IC50 value of the vanadium complex were assessed by MTT assay. Flow cytometry was utilized to detect cell cycle distribution, apoptosis assay, LC3 levels and Acid Vascular Organelles (AVOs). Caspase 3 levels were detected by ELISA. Changes in Notch1 gene expression were assessed by real-time PCR. AVOs qualitative detection was assessed by a fluorescence microscope. Results: The growth of MDA-MB-231 cells was suppressed after treatment with [VO (bpy)2 Cl] Cl complex, in a dose-dependent manner. The affinity for apoptotic cell death induction was shown through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase 3 levels. The affinity for autophagic cell death induction was observed through the increase in the G0/G1 phase, G2/M arrest, the increase of AVOs red fluorescence and elevated LC3 levels. The affinity for notch pathway inhibition was shown through the suppression of Notch 1 gene expression. Conclusion: [VO (bpy)2 Cl] Cl complex could be a promising candidate as therapeutic agent targeting different therapeutic targets including apoptosis, autophagy and notch signaling pathways.

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The habit of drinking tea is highly prevalent and could be utilized to introduce more health benefits through fortification with medicinal plants. The purpose of this analysis was to assess the nutritional quality and health benefits of fortified Ziziphus tea (ZT) with green tea (GT) against obesity and non‐alcoholic fatty liver disease (NAFLD). Proximate analysis and sensory evaluation were carried out on the fortified tea. In the in vivo study, 15 SD rats were used for each group. Flow cytometry was utilized for caspase 3 analysis. ELISA was used for the detection of tumor necrosis factor‐alpha and adiponectin levels. Real‐time PCR was used to detect Notch‐1 and Hes‐1 gene expression. The composition of fortified (GT+ZT) showed a significant improvement in the nutritional value represented by the increase in overall protein, crude fat, crude fiber, ash, carbohydrate, mineral contents, and antioxidant capacity. Treatment with GT+ZT restored the disturbance in body weight, lipid profile, liver function, glucose, insulin sensitivity index, and oxidative status. It reversed the changes in TNF‐α and adiponectin levels. Their protective effects against NAFLD were indicated by the inhibition of hepatic caspase‐3 activity, suppression of Notch‐1, and Hes‐1 gene expression and amelioration of high‐fat diet (HFD)‐induced histological alterations. Collectively, our findings, elucidate the precise mechanism of fortified ZT+GT for the attenuation of obesity‐induced metabolic disorders and NAFLD via regulating lipolysis, TNF‐α, adiponectin, apoptosis, and Notch‐1 signaling pathways, and provide a foundation for an easily implemented healthy habit of drinking. Practical applications The incorporation of bioactive compounds into functional foods is a growing market. Consumer attention in well‐being has increased rapidly toward a fortified diet that provides additional health effects. The fortified (GT+ZT) tea may potentially serve as an easily implemented healthy drinking habit to prevent and manage obesity and NAFLD and reduce the risk of other diseases. Fortification with ZT improved the health‐promoting functionality of GT through the enhancement of total protein, carbohydrates, antioxidant, and mineral contents. This was reflected by their synergetic therapeutic activity in ameliorating the disturbance in obesity‐related disorders and NAFLD via regulating lipolysis, inflammation, oxidative stress, apoptosis, and Notch‐1 signaling pathways. Therefore, (GT+ZT) could be considered functional foods which attribute to functional improvement and reduction in disease risk.

The focus of consumers in healthy food turned to the possible health benefits of particular foods and food ingredients. This study aimed to evaluate the newly fortified biscuits supplemented with sidr leaves and flaxseed and to highlight their nutritional quality and health benefits against cyclosporine A-induced dexterous effects.Sidr leaves (SL), and flaxseed (FS) were used in the preparation of fortified biscuits.Proximate analysis and sensory evaluation were carried out on the biscuits. In in vivo study, 15 male albino mice were used for each group. Groups were divided into control, CsA, SL, FS, and SL+FS-treated groups. Hematological analysis, kidney function tests, oxidative stress, and anti-oxidant status were estimated. Flow cytometry was utilized to detect apoptosis and autophagy levels. The enzyme-linked immunosorbent assay (ELISA) was used for detection of interleukin-2 (IL-2), interferonγ (IFNγ), and transforming growth factor β1 (TGF-β1) levels. The composition of biscuits complemented by SL and FS demonstrated significant improvement in the nutritional value represented by the increase in overall protein, crude fat, crude fiber, ash, and carbohydrate contents. Treatment with SL and FS restored the disturbance in hematological, kidney function, oxidative, and antioxidant biomarkers. CsA-induced apoptotic and autophagic renal cell death was suppressed. Cytokines and pro-inflammatory markers were ameliorated. The use of SL and FS in dietary products can be recommended as a functional food. Moreover, they showed renal-protective, antioxidant, anti-inflammatory, and immune-enhancing activities. Practical applicationsSidr leaves (SL) and flaxseed (FS) were used in the preparation of fortified biscuits.The composition of biscuits complemented by SL and FS demonstrated a significant improvement in the nutritional values represented by the increase in overall protein, crude fat, crude fiber, ash, and carbohydrate contents. SL and FS showed a potential therapeutic activity in reversing CsA-induced dexterous side effects by acting as an antioxidant, antiapoptotic, antiautophagic, anti-inflammatory, renal-protective, and How to cite this article: El Seedy GM, El-Shafey ES, Elsherbiny ES. Fortification of biscuit with sidr leaf and flaxseed mitigates immunosuppression and nephrotoxicity induced by cyclosporine A.