Maryam Hassan Al-Zahrani

Alkaloids have garnered significant interest as potential anticancer agents. Vitamin D receptor (VDR) plays a role in preventing the progression of colorectal cancer (CRC) and may be a crucial mediator of the anticancer effects produced by certain alkaloids. The search for novel anticancer drugs that induce VDR expression and act through the VDR could improve the clinical outcomes of CRC patients. The anticancer and pro-apoptotic effects of coclaurine and reticuline were investigated using CRISPR/Cas9-edited VDR/knockout (KO) and wild-type (WT) CRC HCT116 cell lines. Western blotting, RT-qPCR, confocal microscopy, cell viability, scratch assays, and flow cytometry were employed to assess VDR expression and cellular localization, cell growth, wound-healing, cytotoxicity, apoptotic status, cell cycle progression, and VDR-mediated gene expression. Coclaurine and reticuline dose-dependently inhibited HCT116-WT cell viability, decreased wound-healing, and increased VDR nuclear localization and gene expression while downregulating the oncogenic genes SNAIL1 and SNAIL2. Both alkaloids induced late apoptosis in HCT116-WT cells, increased the cleavage of PARP and caspase-3, and upregulated Bax and TP53 while decreasing BCL-2. Both alkaloids caused HCT116-WT cell growth arrest in the S-phase, which is associated with cyclin A1 overexpression. Coclaurine and reticuline lost their anticancer effects in HCT116-VDR/KO cells. Docking studies revealed that both alkaloids occupied the VDR’s active site. These findings demonstrate that coclaurine and reticuline exert anti-CRC and pro-apoptotic activities via the VDR, suggesting them as natural therapeutic candidates. The use of in vivo CRC models is needed to validate the anticancer activities of coclaurine and reticuline.

Background: Colon cancer progression heavily relies on intricate mechanisms of invasion, metastasis, and migration. Tight junction protein Cldn2 has emerged as a potential regulator of these processes. This study aimed to elucidate the molecular mechanisms linking Clan2 deletion to gene expression changes related to motility, invasion, and metastasis in colon caner. Methods: CRISPR/Cas9-mediated knockout of human Cldn2 in HCT116 cells was conducted, and the resulting cells were compared to the wild-type cells using real-time PCR to analyze the expression of genes associated with invasion and metastasis. Results: Cldn2-KO resulted in a widespread downregulation of genes linked to motility, invasion, and metastasis, including ZONAB, NDRG1, Cldn14, Cldn23, Bcl2, , P53, and BCL-6. These findings suggest a potential regulatory role of Cldn2 in the expression of these genes, influencing colon cancer cell migration and spread. Conclusion: This study identified Claudin-2 as a crucial regulator of genes involved in colorectal cancer metastasis. Downregulation of these genes upon Claudin-2 deletion suggests its inhibitory role in cancer cell motility and invasion. Further investigation into the specific downstream signaling pathways mediated by Claudin-2 could pave the way for novel therapeutic strategies targeting metastasis inhibition.

Nuts are highly valued for their properties and are consumed worldwide owing to their health benefits, particularly, for the prevention and treatment of diseases, as well as a source of essential macro- and micronutrients. This study aimed to evaluate the effects of roasting on the nutritional value of nuts. Three types of nuts, raw and roasted almonds, cashews, and walnuts were selected from three well-known companies in Saudi Arabia. To analyze and evaluate the stability of macro- and micronutrients in nuts, modern separation and quantification methods, including inductively coupled plasma-optical emission spectrometry (ICP-OSE), were used to analyze and evaluate the stability of nutrients and heavy metals in nuts that are widely distributed and consumed. The results of this study indicate that nuts have high nutritional value and an inverse roasting effect. Comparing the nutrient and metal contents of raw and roasted nuts provides useful information on the nutritional science of nuts consumed by well-known manufacturers in the Kingdom of Saudi Arabia. Further investigations of nuts are needed to draw firm conclusions regarding their association with the prevention of many different diseases.

Background/Objective/Methods: Glutathione-S-transferase Mu1 (GSTM1) and glutathione peroxidase 1 (GPX1) are known antioxidant enzymes that help protect cells from the oxidative damage that occurs from smoking. This study explored the correlation between GSTM1 and GPX1 levels between a group of smokers with the GSTM1 and GPX1 genes in the Saudi population and a control group and investigated the genetic risk factors in the group of smokers. Results: The control and smokers’ group (n = 50; aged 22.3 ± 3.1 years; BMI 24.6 ± 5.9 kg/m 2 ) were genotyped using quantitative polymerase chain reaction (qPCR). In comparison with the control group, the smokers’ group displayed a different genotype disruption of GSTM1 and GPX1. Carriers of the homozygous (TT) genotype of GSTM1 had more than a twofold (OR = 2.71, 95% CI = 0.10–70.79, P = 1.000) smoking risk than the carriers of the heterozygous (CT) genotype. Those with the GPX1 gene showed no risk in the control and smokers’ groups. Smokers with the TT/GG combination (homozygous for GPX1 and normal for GPX1) were identified as high risk (OR = 2.58, 95% CI = 0.096–69.341). Conclusion: The main outcomes showed no significant association between genetic polymorphism of the GSTM1 and GPX1 genes and cigarette smoking in the Saudi Arabian population. However, the results showed a slight decrease in the number of GSTM1 and GPX1 gene modifications among smokers.

Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity.Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done.Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin’s therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin’s higher binding affinity than taurine.Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin.