Rehab Mamdouh Abdel-Megeed

Targeting macro-autophagy (MAut) through Nano-medicine can be more prospective than traditional medicine subjected to resistance in atrophic arthritis (RA). MAut is a degenerative process that restores healthy chondrocytes it plays a vital role in RA onset and cell homeostasis this opened Novel Avenue in targeting RA via liposomal drug delivery system. The insufficient response to existing therapies or systemic toxicity and poor bioavailability, are quiet unsettled problems lying across the full retardation of RA treatment. Various Nano-carriers with sustained drug release, improved physicochemical properties, and active targeting were designed to promote the drug delivery efficiency. Single subcutaneous dose of Norphytane (200 μL) induced Atrophic arthritis in rat model then rats were treated with Liposomal loaded-Isethione or Isethione. Liposomal-Isethione ameliorated autophagy biomarkers including Beclin-1, P62, and X-box binding protein-1 (XBP-1), cell survival, and oncogenic biomarkers including Signal transducer and activator of transcription (STAT-3A), Phosphoinisitol kinase-3 (PI3K), AKT Serine/Threonine Kinase-1 (AKT), and Phosphatase and tensin homolog (PTEN) post elevation via Norphytane. Moreover, rheumatoid factor biomarkers including Cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP-9), tumor necrosis factor (TNF-α). Liposomal-Isethione significantly targeted MAut signaling pathways, including Beclin-1/XBP/COMP/STAT-3A/PI3K/AKT/PTEN via increased bioavailability and targeting inflamed tissues, thus decreased drug resistance.

Autophagy is balanced machinery that supports anti-malignant mechanism via the removal of dysfunctional proteins, ROS and DNA abnormalities. Appropriate autophagic machinery is fundamental for mutant eradication and suitable genomic constancy thus it prevents the genetic faults aggregation which contributes to malignant conversion. This article focuses on the application of liposomal-formulated Nano-medicine as prospective therapy for colon carcinoma and the complemented autophagic deviation. Colon carcinoma was induced experimentally in rat model via 3-Methyl cholantherene (3-MCA) for 6 months proceeded with liposomal Isethione, Turmeric and Adriamycin treatment for 1 month and was further compared with their non-liposomal analogue. Concomitant supplementation with the aforementioned liposomal-formulated Nano-medicine influence on the gene expression of autophagy biomarkers including X-box binding protein 1 (XBP), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF-4) and Beclin in addition to, angiogenic biomarker (NOX) and oxidative stress biomarker (Butryl cholinesterase) was investigated. Liposomal-formulated Nano-medicine modulated the deviated autophagy biomarkers and oxidative and nitosative stress biomarkers in addition to, modulating histomorphological changes induced post 3-MCA colorectal cancer induction. Autophagy was involved in all steps of colon cancer progression and apoptosis. liposomal-formulated Nano-medicine might be a prospective candidate for colorectal carcinoma treatment via modulating autophagy XBP/ATF4/Beclin/CHOP.

Aim: Endoplasmic reticulum stress triggers neuronal unfolded protein accumulation, contributing to the pathophysiology of depression psychiatric illnesses.Materials & methods: The brain-derived neurotrophic factor (BDNF), metabotropic glutamate receptor type 7 (GRM7), phosphoinisitol kinase-3 (PIK3), serine/threonine kinase 1 (AKT) and Homer1 may afford an important signaling pathways in LPS induced depression rat model. Herein, thioctic acid, Burdock and propolis therapeutic index on lipopolysaccharide (LPS)-induced depression was monitored. BDNF/PI3K/GR7M/ATF6/CHOP/XBP/AKT/Homer-1 signaling pathways also opened a novel avenue in the integration of synaptic neurotransmission.Results: The aforementioned treatments elevated GR7M/BDNF/GABA gene expression meanwhile decreased reactive oxygen species generation (Malondialdehyde/glutathione reductase/Total antioxidant capacity) and reduced the expression of ATF6/CHOP/PI3K/AKT/XBP/Homer-1 post LPS elevation.Conclusion: Thioctic acid, propolis and Burdock are prospective therapeutic agents via GRM7/BDNF/AKT/PI3K/ATF6/XBP/homer -1 signaling pathways in LPS-induced depression.

Aim: Drug resistance is still a significant barrier to effective hepatocellular carcinoma therapy. Address the issue of doxorubicin resistance and inter-receptor crosstalk various doxorubicin formulations were investigated. Methods: Hepatocellular carcinoma was carried out using 3-methylechloroanthrene. Animals were then treated with doxorubicin, liposomal doxorubicin, titanium-loaded doxorubicin (TiO2-Dox), lactoferrin-doxorubicin and PEGylated doxorubicin. Biochemical and molecular analyses were assessed. Results: Results have declared a significant alternation of both sodium and potassium concentrations upon 3-methylechloroanthrene administration. Arginase-I and α-L-Fucodinase tumor biomarkers were significantly elevated. C-myc, Hprt-1 and EGFR gene expression were over-expressed. Treatment with the aforementioned treatment regimens significantly modulated all measured parameters. Conclusion: TiO2-Dox, doxorubicin-lactoferrin and PEGylated doxorubicin could be a promising regimen in hepatocellular carcinoma and overcoming the problem of drug resistance.

Aim: To clarify the alternation of gene expression responsible for resistance of Adriamycin (ADR) in rats, in addition to investigation of a novel promising drug-delivery system using titanium diox... Plain language summary The current study aimed to investigate a novel and promising drug-delivery system to overcome the resistance problem by loading Adriamycin (ADR) into titanium dioxide nanopar... Graphical abstract

Cancer of the blood-generating tissues, such as the bone marrow and lymphatic system, is recognized as leukemia (T-ALL). There are several forms of leukemia. Leukemia often affects white blood cell...