Biology subjects

El-Nezami, H.

Publications and source records attributed to El-Nezami, H..

6 recordsLinked to original sources

bioRxiv2025

Associations Between Gut Microbiome and 24-Hour Blood Pressure Variability: A Cross-sectional Study Highlighting Sex Differences and Potential Therapeutic Targets

Blood pressure (BP) variability is an independent risk factor for cardiovascular disease (CVD). While gut microbiota (GM) and GM-derived short-chain fatty acids (SCFAs) are recognized to play a key role in BP regulation, their association with BP variability remains poorly understood. This cross-sectional study of 241 community-dwelling individuals from Hong Kong (113 men and 128 women, mean age 54{+/-}6 years) without symptomatic CVD examined the associations of GM, characterized by shotgun sequencing, and plasma SCFAs, with systolic and diastolic blood pressure (SBP/DBP) variability assessed by 24-hour BP monitoring. GM analyses, using covariate-adjusted statistical models, revealed that higher 24-hour SBP CoV associated negatively with GM -diversity (Shannon and Simpsons index, P<0.05) and positively with Firmicutes/Bacteroidetes ratio, driven by the female cohort. Parabacteroides merdae, Bacteroides dorei, Bifidobacterium pseudocatenulatum, Alistipes finegoldii and Bacteroides intestinalis were negatively associated with indices of SBP/DBP variability in a sex-specific manner. Further analysis indicated that B. dorei may mediate SBP CoV via plasma iso-butyric acid in women (bootstrapping 95% CI: -3.6 to -0.19; P<0.05). We demonstrated that higher SBP variability is associated with markers of gut dysbiosis and a reduction in beneficial gut bacteria, particularly in women. Notably, we identified several gut bacterial species with potential therapeutic implications for managing 24-hour SBP/DBP variability, warranting further investigation.

microbiology↗

bioRxiv2024

Deoxynivalenol induced inflammation and increased the adherence of entero-invasive Escherichia coli to intestinal epithelial cells via modulation of mucin and pro-inflammatory cytokine production

Deoxynivalenol (DON) is a mycotoxin that commonly occurs in crops. It was hypothesized that DON could trigger intestinal inflammation and increase the susceptibility of intestinal epithelial cells (IECs) to pathogen infection. Accordingly, the aim of this study was to investigate the effects of DON on intestinal susceptibility to pathogen infection. Semiconfluent Caco-2 cells were exposed to DON followed by acute entero-invasive Escherichia coli (EIEC) infection. The effects of DON and EIEC contamination on mucin, cytokines and related signal transduction pathways were examined as part of the local immune system. Caco-2 cells were able to generate a rapid immune response against DON with or without EIEC post-challenge. An increase in EIEC attachment to DON-exposed cells was observed, probably in part, mediated by modulation of secretory MUC5AC mucins and membrane bound MUC4 and MUC17 mucins. Cells were also able to express and produce important mediators of inflammation, such as cytokines as a result of activation of toll-like receptors signalling cascades, modulation of nuclear factor {kappa}-light chain-enhancer of activated B cells (NK-{kappa}B) and/or mitogen-activated protein kinase (MAPK) pathways. These data indicate that DON may exert immunomodulatory effects on intestinal epithelial cells, which might thereby modify the susceptibility to bacterial infection.

pharmacology and toxicology↗

bioRxiv2023

Schisandrin B suppresses colon cancer growth by inducing cell cycle arrest and apoptosis via the CHOP signalling pathway

Colon cancer is among the most lethal and prevalent malignant tumours in the world, and the lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B (Sch B), a lignan extracted from the fruit Schisandra chinensis, has been reported for its anti-cancer properties. However, no studies to date have been done to characterise the exact molecular mechanisms regarding the anti-tumorigenic effect of Sch B in colon cancer. A comprehensive analysis of the molecular mechanism for the anti-tumorigenic effect of Sch B on human colon cancer cells was performed using combination of Raman spectroscopy, RNA-seq, computational docking and molecular biological experiments. The in vivo efficacy was evaluated by a mouse xenograft model. Sch B reduced cell proliferation and triggered apoptosis in human colon cancer cell lines. Raman spectroscopy, computational, RNA-seq, molecular and cellular studies revealed that Sch B activated unfolded protein responses by interacting with CHOP and upregulating CHOP, which thereby induced apoptosis. CHOP knockdown alleviated the Sch B-induced reduction in cell viability and apoptosis. Sch B reduced colon tumour growth in vivo. Our findings provide essential background for clinical trials examining the effects of Sch B in patients with colon cancer.

pharmacology and toxicology↗

bioRxiv2022

Bioavailability of Schisandrin B and its effect on 5-Fluorouracil metabolism in a xenograft mouse model of colorectal cancer

Schisandrin B (Sch-B) is a predominant bioactive lignan in the fruit of a traditional Chinese medicinal plant Schisandra Chinensis with widely reported anti-cancer properties. Using a xenograft mouse model of colorectal cancer (CRC), we showed potent anti-tumor effects of Sch-B and synergistic effects when co-treated with the chemotherapy drug, fluorouracil (5-FU). To explore the underlying anti-tumor mechanism of Sch-B, we first compared the bioavailability, metabolism and tissue distribution of Sch-B and its metabolites among healthy and tumor-bearing mice. To understand the drug-phytochemical interactions associated with the synergy between Sch-B and 5-FU, we examined their reciprocal influence on drug metabolism, tissue distribution, and multidrug resistance (MDR) gene expression in tumor-bearing mice. Using a targeted metabolomics approach, three Sch-B metabolites and two bioactive 5-FU metabolites were quantified and found to reach tumor tissue. Generally, Sch-B metabolites were present at higher levels in tumor-bearing than healthy mice, whereas 5-FU metabolite accumulation was remarkably higher in the co-treatment than 5-FU alone group. Moreover, MDR genes were significantly downregulated upon co-treatment, demonstrating the capacity of Sch-B to reverse MDR in chemotherapy. This study showed that Sch-B may serve as a promising adjuvant to chemotherapy drugs via favorably modulating drug metabolism and bioavailability, and attenuating MDR.

pharmacology and toxicology↗

bioRxiv2022

Mechanistic insights into zearalenone-accelerated colorectal cancer in mice using integrative multi-omics approaches

Zearalenone (ZEA), a secondary metabolite of Fusarium fungi found in cereal-based foods, promotes the growth of colon, breast, and prostate cancer cells in vitro. However, the lack of animal studies hinders a deeper mechanistic understanding of the cancer-promoting effects of ZEA. This study aimed to determine the effect of ZEA on colon cancer progression and its underlying mechanisms. Through integrative analyses of transcriptomics, metabolomics, metagenomics, and host phenotypes, we investigated the impact of a 4-week ZEA intervention on colorectal cancer in xenograft mice. Our results showed a twofold increase in tumor weight with the 4-week ZEA intervention. ZEA exposure significantly increased the mRNA and protein levels of BEST4, DGKB, and Ki67 and the phosphorylation levels of ERK1/2 and AKT. Serum metabolomic analysis revealed that the levels of amino acids, including histidine, arginine, citrulline, and glycine, decreased significantly in the ZEA group. Furthermore, ZEA lowered the alpha diversity of the gut microbiota and reduced the abundance of nine genera, including Tuzzerella and Rikenella. Further association analysis indicated that Tuzzerella was negatively associated with the expression of BEST4 and DGKB genes, serum uric acid levels, and tumor weight. Additionally, circulatory hippuric acid levels positively correlated with tumor weight and the expression of oncogenic genes, including ROBO3, JAK3, and BEST4. Altogether, our results indicated that ZEA promotes colon cancer progression by enhancing the BEST4/AKT/ERK1/2 pathway, lowering circulatory amino acid concentrations, altering gut microbiota composition, and suppressing short chain fatty acids production.

cancer biology↗

bioRxiv2019

A Clostridia-rich microbiota contributes to increased excretion of bile acids in diarrhea-predominant irritable bowel syndrome

ObjectiveAn excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remains unclear. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D.\n\nDesignMetabolomic and metagenomic analyses were performed of specimens from 290 IBS-D patients and 89 healthy volunteers. By transplanting human microbiota and manipulating specific microbiome species in mice, the effects of microbiota on host BA metabolism were assessed at metabolic, genetic and protein levels. Effects of individual and mixed BAs on enterohepatic feedback pathways were also tested in vitro and in vivo.\n\nResultsTotal fecal BAs were excessively excreted in 24.5% of IBS-D patients. Their fecal metagenomes showed increased abundances of Clostridia and BA-transforming genes (hdhA and bais). The increases of Clostridia bacteria (e.g. C. scindens) were positively associated with the levels of fecal BAs and serum 7-hydroxy-4-cholesten-3-one (C4), while being negatively correlated with serum fibroblast growth factor 19 (FGF19). Both Clostridia-rich human microbiota and C. scindens enhanced levels of serum C4 and hepatic conjugated BAs in mice recipients and reduced ileal FGF19 expression. Inhibition of Clostridium species by vancomycin yielded opposite findings. Clostridia-derived BAs (e.g. conjugated and free ursodeoxycholic acid) significantly suppressed intestinal FGF19 expression.\n\nConclusionThe Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients. This study provided the basis for more precise clinical diagnosis and management for IBS-D.

microbiology↗