Dr Mohammed Mahmoud Youssif

Drug induced Liver Injury (DILI) is a major problem that usually leads to dose reduction or even drug withdrawal, leading to therapeutic failures. The current study aimed to formulate curcumin (CCM) PEGylated terpesomes and demonstrate its efficacy against carbon tetrachloride (CCl4)- induced liver damage and oxidative stress. A 23 factorial design was employed and a selected formula (SPT), comprising 7.5, 0.25 and 0.5 ratios of Polyethylene glycol 400 (PEG): CCM, fenchone: PEG and phosphatidyl choline: PEG, respectively was obtained. SPT exhibited satisfactory values of percentage entrapment efficiency, vesicular size and zeta potential (84.3 ± 1.9 %, 236.7 ± 5.3 nm and 33.7 ± 0.7 mV, respectively). Transmission Electron Microscopy revealed the spherical morphology of SPT vesicles, with VS like that obtained via zeta sizer. Release of CCM from SPT exhibited a biphasic pattern and obeyed Higuchian diffusion. SPT was stable in the refrigerator for up to three months. The biochemical analysis study revealed the superior hepatoprotective effect of CCM SPT compared to its aqueous suspension against CCl4-induced liver damage and oxidative stress. The decrease in Aspartate transaminase (AST) and Alanine transaminase (ALT) and the increase in Glutathione (GSH) were 76 and 68.1 % and 9-folds vs 19.7 and 9.8 % and 1.6-folds, for CCM SPT and CCM aqueous suspension, respectively. Thus, SPT is considered a promising safe and effective hepatoprotective formula against DILI.

Personalized medicine is an emerging field that provides novel approaches to disease's early diagnosis, prevention, treatment, and prognosis based on the patient's criteria in gene expression, environmental factors, lifestyle, and diet. To date, hepatocellular carcinoma (HCC) is a significant global health burden, with an increasing incidence and significant death rates, despite advancements in surveillance, diagnosis, and therapeutic approaches. The majority of HCC lesions develop in patients with liver cirrhosis, carrying the risks of mortality associated with both the tumor burden and the cirrhosis. New therapeutic agents involving immune checkpoint inhibitors and targeted agents have been developed for sequential or concomitant application for advanced HCC but only a tiny percentage of patients benefit from each approach. Moreover, clinicians encounter difficulties determining the most appropriate regimen for each patient. This emphasizes the need for a personalized treatment approach. In other words, patients should no longer undergo treatment based on their tumor's histology but depending on the distinct molecular targets specific to their tumor biology. However, the utilization of precision medicine in managing HCC is still challenging. This review aims to discuss the role of personalized medicine in diagnosing, managing, and defining the prognosis of HCC. We also discuss the role of liquid biopsy and their clinical applications for immunotherapies in HCC. More clinical studies are still necessary to improve the precision of biomarkers used in the treatment decision for patients with HCC.

The response of neuroblastoma (NB) cells to chemotherapeutics and their influence on NB microenvironment remain incompletely understood. Herein, we examined the underlying molecular mechanism via which Doxorubicin, a chemotherapeutic agent used for NB treatment, promotes proangiogenic response in the SH-SY5Y microenvironment. Doxorubicin treatment at 1 µg/ml reduced SH-SY5Y cell proliferation and primed the apoptosis pathway. Unexpectedly, SH-SY5Y cells treated with doxorubicin upregulated their expression of the pro-angiogenic factors, including vascular endothelial growth factor (VEGF), platelets-derived growth factor (PDGF), and matrix metalloprotease-2 (MMP-2) and secretion of nitric oxide. To assess the functional angiogenesis of SH-SY5Y cells pre-treated with doxorubicin, an indirect co-culture system with human umbilical vein endothelial cells (HUVEC) was established. These HUVECs acquired enhanced proliferation, migration capacity, and tube formation capability and exhibited increased nitric oxide (NO) production, in addition to upregulated α-smooth muscle actin expression, suggesting enhanced contractility. In-ovo studies of the neo-angiogenic response of SH-SY5Y pre-treated with doxorubicin further show their promoted neo-angiogenesis as indicated by the generated blood vessels and histological analysis of CD31 expression. Inhibition of PHD-2 could be a potential target for doxorubicin, as indicated by molecular docking, molecular dynamics (MD) simulation, and MM-GBSA calculations, leading to hypoxia-inducible factor-1 alpha (HIF-1α) stabilization. Bioinformatics analyses and enrichment analyses of RNA-seq data revealed activation of Pi3K pathway which is further validated in-vitro. These results provide evidence of the unexpected pro-angiogenic response of SH-SY5Y cells to doxorubicin treatment and suggest the potential use of multi-modal therapeutic regimens for a more comprehensive approach to NB treatment.

BACKGROUND: Hepatic fibrosis unfolds as a pathological buildup of extracellular matrix triggered by liver injury. Thioacetamide (TAA) plays a versatile role across various fields-from industrial processes and laboratory research to chemical stabilization. Teucrium plants, widely traditional plants, owing to its myriads of pharmacological activities.

METHODS AND FINDINGS: T. oliverianum ethanolic (TO-EtOH) and ethyl acetate (TO-EtOAc) extracts were explored for their bioactive metabolites via UHPLC-ESI-qTOF-MS/MS that yielded 48 compounds, mainly flavonoids and phenylethanoid glycosides, alongside phenolic acids, iridoid glycosides, and limonoids. Both extracts showed notable hepatoprotective effects in a thioacetamide (TAA)-induced liver injury model, supporting their therapeutic potential. The TAA group showed a significant increase in AST, ALT, ALP, MDA and TNF-α levels concurrent with a significant decrease of GSH level versus normal control group. In contrast, TO-EtOAC and TO-EtOH administered rats showed a decrease in liver enzymes, including ALT, AST, ALP, total bilirubin, and MDA, and an increase in GSH as compared to the TAA model group. Furthermore, both extracts considerably decreased the overall liver TNF-α content inferring anti-inflammatory action. The histo- and immunohistochemical assays of liver tissue of rats in TAA revealed prominent pathological alterations with bridging fibroplasia in multiple hepatic lobules. A restorative effect that improved hepatic morphology with apparent normal hepatic cells and nominal fibroplasia was evident in the administration of both extracts. Among both extracts, TO-EtOH appeared more effective than TO-EtOAC as manifested by a significant improvement in liver's biochemical parameters and structural organization.

CONCLUSION: This study provides robust evidence supporting the antifibrotic effects of T. oliverianum in a TAA-induced liver injury model. The anti-proliferative activity and hepatoprotective effects are likely to be mediated by its richness in phenolic acids, flavonoids and phenylethanoids.

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Medicines, food packaging, personal care products, and cosmetics extensively use polyethylene terephthalate nanoplastics (PET-NaPs). However, they also have harmful impacts on several organs. Betaine demonstrates potent antioxidant and anti-inflammatory characteristics. Our goal was to investigate the detrimental impact of PET-NaPs on the mouse brain and evaluate the neuroprotective properties of betaine. We allocated 40 completely mature male Swiss albino mice into four distinct groups: control group, betaine group, PET-NaPs group, and betaine-co-treated group. Following a 30-day duration, euthanasia was performed on the mice, and analyzed tissue samples were obtained from the cerebrum, cerebellum, and hippocampus. PET-NaPs resulted in an elevated level of malondialdehyde and upregulated cyclooxygenase-2 and interleukin-1 beta (IL-1β) expression while significantly reducing the levels of glutathione and downregulating acetylcholinesterase. The PET-NPs also caused significant changes in the histopathology of the brain tissue, and there was a demonstrable rise in the immunostaining of IL-1β and glial fibrillary acidic proteins. Consequently, betaine effectively alleviated the negative consequences of PET-NaPs. Therefore, betaine possesses the capacity to mitigate the neurotoxic consequences induced by PET-NaPs.