Publications by authors named "Caitlin W Lehman"

Early growth response 1 (EGR1) is an immediate early gene and transcription factor previously found to be significantly upregulated in human astrocytoma cells infected with Venezuelan equine encephalitis virus (VEEV). The loss of EGR1 resulted in decreased cell death but had no significant impact on viral replication. Here, we extend these studies to determine the impacts of EGR1 on gene expression following viral infection.

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Venezuelan equine encephalitis virus (VEEV) is an Alphavirus in the Togaviridae family of positive-strand RNA viruses. The viral genome of positive-strand RNA viruses is infectious, as it produces infectious virus upon introduction into a cell. VEEV is a select agent and samples containing viral RNA are subject to additional regulations due to their infectious nature.

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Article Synopsis
  • SARS-CoV-2 is the virus responsible for COVID-19, leading to severe cases that can cause serious lung damage, often requiring mechanical ventilation due to conditions like acute lung injury and ARDS.
  • The study highlighted that infection with SARS-CoV-2 results in an inflammatory response marked by elevated levels of specific chemokines (CXCL9, CXCL10, CXCL11) and cytokines (IL-6, TNFα, IFN-γ) in lung cells and infected mouse models.
  • It found that blocking certain signaling pathways, particularly the AKT pathway, significantly reduces the expression of these harmful chemokines, suggesting potential therapeutic targets to mitigate inflammation and improve outcomes in COVID-19 patients.
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Numerous natural phytochemicals such as resveratrol are acknowledged as potent botanical agents in regulating immune responses. However, it is less understood whether such immunomodulatory phytochemicals are appropriate for use as direct treatments in veterinary viral diseases. In the present study, we investigated the efficacy of resveratrol in suppressing vesicular stomatitis virus (VSV) infection.

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  • Venezuelan equine encephalitis virus (VEEV) infection leads to cell death through the early growth response 1 (EGR1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway.
  • Inhibition of PERK in human astrocytes significantly decreased VEEV and eastern equine encephalitis virus (EEEV) replication, while showing no effect on replication in certain transformed cell lines.
  • This research suggests that targeting PERK could be a promising strategy for developing antiviral therapies against various RNA viruses, including VEEV, Rift Valley fever virus, and Zika virus.
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Marine microorganisms have been a resource for novel therapeutic drugs for decades. In addition to anticancer drugs, the drug acyclovir, derived from a marine sponge, is FDA-approved for the treatment of human herpes simplex virus-1 infections. Most alphaviruses that are infectious to terrestrial animals and humans, such as Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV), lack efficient antiviral drugs and it is imperative to develop these remedies.

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The host proteins Protein Kinase B (AKT) and glycogen synthase kinase-3 (GSK-3) are associated with multiple neurodegenerative disorders. They are also important for the replication of Venezuelan equine encephalitis virus (VEEV), thereby making the AKT/GSK-3 pathway an attractive target for developing anti-VEEV therapeutics. Resveratrol, a natural phytochemical, has been shown to substantially inhibit the AKT pathway.

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  • - Crotonoside, a guanosine analog, is known for its strong inhibition of tyrosine kinases and ability to suppress immune cell activity, prompting research into its anti-arthritic effects.
  • - In studies on collagen-induced arthritic (CIA) DBA/1 mice, crotonoside treatment improved arthritis symptoms by reducing inflammatory cytokine levels and down-regulating co-stimulatory molecules on dendritic cells (DCs).
  • - The research suggests that crotonoside may serve as a promising immunosuppressive agent by modifying pathogenic DC activity, indicating potential future applications for treating autoimmune conditions.
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Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), became a pandemic in early 2020. Lateral flow immunoassays for antibody testing have been viewed as a cheap and rapidly deployable method for determining previous infection with SARS-CoV-2; however, these assays have shown unacceptably low sensitivity. We report on nine lateral flow immunoassays currently available and compare their titer sensitivity in serum to a best-practice enzyme-linked immunosorbent assay (ELISA) and viral neutralization assay.

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Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that substantially affects a patient's quality of life. While steroids are the most common therapy used to temporally alleviate the symptoms of AD, effective and nontoxic alternatives are urgently needed. In this study, we utilized a natural, plant-derived phenolic compound, phloretin, to treat allergic contact dermatitis (ACD) on the dorsal skin of mice.

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  • Protein phosphorylation is crucial for the Venezuelan equine encephalitis virus (VEEV), specifically regarding its capsid protein which has four phosphorylation sites.
  • Research indicates that Protein Kinase C (PKC) is responsible for this phosphorylation, with evidence that knocking down PKCδ reduces both capsid phosphorylation and viral replication.
  • A mutated version of the virus that cannot be phosphorylated showed improved assembly and infectivity, and also resulted in better survival rates in mice compared to the original virus, highlighting the importance of capsid phosphorylation in viral pathogenesis.
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The aim of this study was to evaluate the immunomodulatory effects of atractylodin, a polyethylene alkyne, on the maturation of bone marrow-derived dendritic cells (BM-DC) as well as its antirheumatic effect on collagen-induced arthritis (CIA) in DBA/1 mice. Our results indicate that atractylodin effectively suppressed the secretion of pro-inflammatory cytokines, expression of costimulatory molecules, and p38 MAPK, ERK, and NF-κBp65 signaling pathways in LPS-incubated dendritic cells (DCs). Additionally, the proliferation and cytokine secretion (IFN-γ and IL-17A) of CD8 and CD4 T cells were reduced.

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Zika virus (ZIKV) is a re-emerging Flavivirus that has been linked to microcephaly and other neurological pathologies. In this study, phloretin, a glucose transporter inhibitor naturally derived from plants, was used to investigate the glucose dependence of ZIKV replication in host cells. The results showed that phloretin significantly decreased infectious titres of two ZIKV strains, namely MR766 (African genotype) and PRVABC59 (Puerto Rico genotype).

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Objective: Influenza is an acute respiratory disease caused by the influenza virus which circulates annually in populations of different species. Madin-Darby Canine Kidney (MDCK) is the most widely utilized cell-line for conducting influenza research. However, the infectivity of various influenza strains in MDCK cells is not equivalent and the productivity of viral propagation is also limited.

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Atopic dermatitis is a common chronic inflammatory skin disease affecting up to 20% of children and 1% of adults worldwide. Treatment of atopic dermatitis include corticosteroids and immunosuppressants, such as calcineurin inhibitors and methotrexate. However, these treatments often bring about adverse effects including skin atrophy, osteoporosis, skin cancer, and metabolic syndrome.

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Objective: To compare the healing results between platelet-rich plasma (PRP) and platelet-derived patches versus traditional advanced wound dressings in patients with chronic wounds.

Method: Patients with and without diabetes were divided into two groups, each of which received either PRP patch treatments or the advanced wound dressings. All wounds were cleaned, debrided and assessed by physicians.

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Previous studies have shown that the natural diterpene compound, sclareol, potentially inhibits inflammation, but it has not yet been determined whether sclareol can alleviate inflammation associated with rheumatoid arthritis (RA). Here, we utilized human synovial cell line, SW982, and an experimental murine model of rheumatoid arthritis, collagen-induced arthritis (CIA), to evaluate the therapeutic effects of sclareol in RA. Arthritic DBA/1J mice were dosed with 5 and 10 mg/kg sclareol intraperitoneally every other day over 21 days.

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