Dr Mohammed Mahmoud Youssif

There is justification for optimism about the potential contribution of alternative medicines to cancer management, which now ranks as the second leading cause of death globally. Primary carcinogens arise from several sources, including agriculture, industry, and dietary intake. Gastric cancer (GC) significantly affects an individual's health due to its classification as a malignant tumor associated with elevated mortality and morbidity rates. Chemotherapy is now widely regarded as the gold standard for treating GC. Chemotherapy, however, exerts significant detrimental effects on human health, including irreversible damage to multiple organs. Consequently, it is essential to employ innovative strategies for cancer prevention. Natural products are now the focus of intensive study due to their efficacy against cancer and low toxicity levels. Natural compounds have shown a diverse range of anti-cancer properties. This review aims to emphasize studies on natural compounds that inhibit metastasis, induce apoptosis in GC, and decrease cellular proliferation. All the natural compounds from different sources were incorporated in this review not only medicinal plants derived compounds. This review aims to examine a comprehensive array of natural therapies that may enhance human health and facilitate GC prevention without inducing discernible negative effects. Moreover, this review aims to discuss the toxic side effects of phytochemicals and shed light on mechanisms underlying the action of potential natural products against GC. This review offers a novel perspective by integrating a broad spectrum of natural compounds from diverse sources, not limited to medicinal plants, to explore their anti-cancer properties against gastric cancer.

5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for solid malignancies. Although it has crucial therapeutic effects, it ranks as the second most cardiotoxic antineoplastic agent. Berberine (BBR) is a quaternary benzylisoquinoline alkaloid with promising antioxidant properties. The current study aimed to assess the palliative effect of BBR on 5-FU-induced cardiotoxicity in rats. Fifty male Sprague Dawley rats were randomly divided into five groups: negative control, which received 2% DMSO orally (PO) for 2 weeks; cardiotoxic, which received a single intraperitoneal (IP) injection of 5-FU (150 mg/kg); groups 3 and 4, which received a single IP injection of 5-FU (150 mg/kg) followed by BBR (50 mg/kg and 100 mg/kg, respectively) PO for 2 weeks; and a BBR-only group, which received BBR (100 mg/kg) PO for 2 weeks. On the 14th day, all groups underwent ECG evaluation. Blood and heart samples were collected 24 h after the last dose for further investigations. 5-FU induced significant alterations in the ECG pattern and caused a significant increase in cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA). Moreover, it led to decreased levels of superoxide dismutase (SOD), reduced glutathione (GSH), and total antioxidant capacity (TAC). Our data suggest that BBR could mitigate 5-FU-induced cardiotoxicity by modulating cardiac injury markers, normalizing cTnI, CK-MB, and LDH levels, reducing oxidative stress by lowering MDA levels, and increasing SOD, GSH, and TAC levels. Additionally, BBR inhibited apoptotic events by suppressing caspase-3 activation and upregulating Bcl-2 expression, reduced the inflammatory response by downregulating cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) expression levels, and decreased the risk of thrombosis by increasing endothelial nitric oxide synthase (eNOS) expression levels. In conclusion, BBR exerts ameliorative effects against 5-FU-induced cardiotoxicity in rats.

BACKGROUND: The purpose of this work was to examine the fundamental mechanisms of reproductive toxicity in rat models following exposure to Fenpropathrin (FNP). Furthermore, our study explores the novel impacts of Date palm kernel extract (DPK) on these detrimental outcomes.

METHODS: Thirty male Wistar rats were used in the investigation. They were split into six groups: one group received corn oil as a control; two groups received DPK at 200 mg/kg and 400 mg/kg; a group received FNP at 4.7 mg/kg; and two combination groups received DPK and FNP at 200 mg/kg and 400 mg/kg, respectively for 60 days.

RESULTS: FNP caused oxidative stress, reduced sperm count, and impaired motility. FNP decreased the expression of the StAR gene and reduced serum testosterone levels. We assessed the histological alterations. In a dose-dependent way, the concurrent administration of DPK extract successfully decreased all the toxicological parameters.

CONCLUSIONS: When taken orally, DPK extract may protect against FNP-induced male reproductive toxicity.

Current limitations in the treatment of hepatocellular carcinoma (HCC) include tumor recurrence, chemoresistance, and severe side effects, all of which call for novel cancer models that better represent the tumor microenvironment (TME). 3D organoids hold promise due to their increased relevance to the TME hallmarks. Herein, we aim to establish an HCC organoid model that mimics the HCC microenvironment and its metabolic interactome. The organoid comprises a decellularized human amniotic membrane (dAM) as a biomimetic matrix, Huh-7 cell line, bone marrow mesenchymal stromal cells (BM-MSC), and human umbilical vein endothelial cell-conditioned medium (HUVEC-CM). The structure integrity of the HCC organoid was monitored using H&E staining at 7, 14, and 21 days and transmission electron microscopy (TEM) and scanning electron microscopy (SEM) at 21 days. The established organoid model maintained its viability over 21 days as tested by propidium iodide (PI) fluorescence staining, MTT, upregulated expression of proliferating cell nuclear antigen (PCNA), and alpha-fetoprotein (AFP). The expression of vascular endothelial growth factor (VEGF) in the HCC organoid induced a neo-angiogenic response in ovo. Metabolic reprogramming in the HCC organoid showed a shift toward glycolysis as indicated by promoted glucose consumption, upregulated lactate production, and reduced cellular pyruvate concentration. Oxidative phosphorylation was suppressed as indicated by reduced reactive oxygen species (ROS), and hydrogen peroxide (HO), and halted urea cycle progression. The dataset shows that the dAM may hold a promise for its use as extracellular matrix (ECM) source for HCC organoid models, by replicating the HCC microenvironment and metabolic signature, thus holding a promise for developing targeted therapeutic strategies.

BACKGROUND: Cryptosporidium parvum, a leading cause of diarrhea, is responsible for millions of food and waterborne illnesses in humans and animals worldwide. Launaea spinosa (Asteraceae family) is a common herb found in the desert of the Mediterranean region, encompassing the peninsula of Sinai. Traditionally, it has been utilized for managing gastrointestinal issues and inflammation.

METHODS AND FINDINGS: The present study aimed to assess Launaea spinosa (LS) extracts viz. ethyl acetate (LS-EtOAc), ethanol (LS-EtOH), and n-butanol (LS-BuOH), of different polarities against C. parvum in experimentally infected mice based on immunological, biochemical, histo- and immunohistochemical assays. Extracts were characterized via UHPLC-ESI-LIT-Orbitrap-MS and metabolite profiles were subjected to correlation modeling with bioactivities via supervised Partial Least Square (PLS) to identify active agents. Most L. spinosa extracts reduced fecal C. parvum oocyst count and mucosal burden (P < 0.05) than untreated infected mice, with LS-BuOH (200 mg/kg) exerting the highest reduction percentage (97%). These extracts increased immunoglobulin G (IgG) levels in infected and treated mice at all examined days post treatment. Also, the highest Interferon-Gamma (IFN-γ) and Interleukin-15 (IL-15) levels were obtained after 10 days of post inoculation (dPI), which were restored to a healthy state after 21 days, concurrent with a decrease in Tumor Necrosis Factor-Alpha (TNF-α) (P < 0.001). The increased liver enzyme (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) levels with infection were likewise reduced with extract administration. The LS extracts caused a significant increase in antioxidant glutathione peroxidase (GSH-Px) and catalase (P < 0.001). Examination of colon tissue revealed that infected-treated mice with LS extracts exhibited a reduction in the expression of cleaved caspase-3, damage score, and degenerative changes. Metabolite profiling of different L. spinosa extracts led to the identification of 86 components, primarily phenolic acids, flavonoids, triterpenoid saponins, and fatty acids, with the first report of sulfated triterpenoid saponins in Launaea genus. PLS regression analysis revealed that bioeffects were significantly positioned close to LS-BuOH extract (R2: 0.9) mostly attributed to triterpenoid saponins and flavonoid glycosides.

CONCLUSIONS: This study demonstrated potential anti-cryptosporidial effects of LS extracts, especially LS-BuOH, suggesting its potential for inclusion in future nutraceuticals aimed at C. parvum treatment.