Biology subjects

Co, V. A.

Publications and source records attributed to Co, V. A..

4 recordsLinked to original sources

bioRxiv2025

SARS-CoV-2 Infects Peripheral Sensory Neurons and Promotes Axonal Degeneration via TRPV1 Activation

Common neurological symptoms of COVID-19, such as anosmia, headaches, and cognitive dysfunction, depend on interactions between the peripheral and central nervous systems. However, the molecular mechanisms by which SARS-CoV-2 affects the peripheral nervous system remain poorly understood, with ongoing debate about whether sensory neurons can be directly infected by the virus. In this study, human iPSC-derived sensory neurons were exposed to the SARS-CoV-2 BA.5 variant, a mutant virus, or viral S1 proteins. Under control conditions, sensory neurons exhibited low expression of ACE2. However, exposure to BA.5 or S1 proteins significantly upregulated ACE2 expression in peripherin-positive sensory neurons. Virological analysis confirmed that SARS-CoV-2 directly infects TRPV1-expressing sensory neurons, including olfactory neurons. Moreover, exposure to the live virus or S1 proteins induced TRPV1 upregulation and translocation from the nucleus to the cytosol, resulting in axonal destruction. Single-nucleus transcriptomic analysis revealed that viral exposure enhanced cAMP signaling, virus receptor and transmembrane transporter activities, and inflammatory regulation of TRP channels, which collectively contributed to synaptic and axonal damage. Importantly, treatment with a TRPV1 antagonist demonstrated neuroprotective effects. These findings underscore the need for further research into the interaction between SARS-CoV-2 and TRPV1, as well as its downstream signaling pathways, to develop therapeutic strategies for preventing sensory neuron loss during viral infections. HighlightsO_LIiPSC technology was employed to generate peripheral sensory neurons from human induced pluripotent stem cells (iPSCs), providing a valuable platform for studying the impact of SARS-CoV-2 on peripheral sensory neurons. C_LIO_LIOur findings demonstrated that the SARS-CoV-2 Omicron BA.5 variant exerted both direct and indirect effects on peripheral sensory neurons. Virus exposure upregulated the angiotensin-converting enzyme 2 (ACE2) receptor in peripherin-positive neurons. Additionally, exposure to the virus or its S1 spike protein increased transient receptor potential vanilloid 1 (TRPV1) expression and trafficking, leading to axonal degeneration. C_LIO_LISingle-nucleus RNA sequencing revealed that BA.5 exposure enhanced cAMP signaling pathway, virus receptor and transmembrane transporter activities, and inflammatory regulation of TRP channels that led to the significantly damage on synapses and axon guidance. C_LIO_LIThe TRPV1 antagonist capsazepine inhibited TRPV1 activation and mitigated axonal damage, offering neuroprotective effects for sensory neurons exposed to SARS-CoV-2. C_LI

cell biology↗

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↗