Biology subjects

Vander Wyk, B.

Publications and source records attributed to Vander Wyk, B..

4 recordsLinked to original sources

bioRxiv2025

Effect of prescribing and deprescribing oxycodone on pain and function in a mouse model of osteoarthritis: impact of polypharmacy and sex on response

Osteoarthritis and polypharmacy are common in older adults. While not consistent with guidelines, opioid analgesia is commonly prescribed to older adults with osteoarthritis and other causes of chronic non-cancer pain. Long term use of opioids is associated with tolerance, addiction, loss of efficacy and adverse events. Thus, deprescribing (reducing or ceasing) opioids is often required. The effect of polypharmacy on the efficacy and safety of opioid prescribing and deprescribing in this setting is poorly understood. Here we aimed to assess the effects of chronic oxycodone, as monotherapy and in polypharmacy (oxycodone, citalopram, simvastatin, oxybutynin, and metoprolol), and of deprescribing oxycodone, on allodynia, physical and cognitive function, and daily activities in middle-aged, osteoarthritic male and female C57BL/6J mice (n=11-15/ group). Only oxycodone monotherapy reduced mechanical allodynia after 6 weeks of treatment. Chronic polypharmacy with oxycodone transiently increased mechanical allodynia in the injured limb and caused marked reductions in mobility, maximum walking speed, activities of daily living, and increased anxiety. Polypharmacy also altered daily activities detected by an automated animal behaviour recognition cage. Sex differences in treatment response were observed in frailty measurements and activity over 23 hours. Deprescribing oxycodone was well tolerated and did not alter physical or cognitive function but did reverse some of the daily activity changes and mechanical allodynia in polypharmacy treated animals only. This clinically relevant preclinical model provides an opportunity to understand the effects of prescribing and deprescribing opioids in older adults with osteoarthritis, including the impact of comedications and sex.

pharmacology and toxicology↗

bioRxiv2023

Early cellular and molecular signatures correlate with severity of West Nile Virus infection

Infection with West Nile Virus (WNV) can drive a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence at 3 months and 1 year employing multiplexed single cell protein and transcriptional profiling (CyTOF and Seq-Well) complemented with matched serum proteomics and metabolomics. At the acute time point, we detected both an elevated proportion of pro-inflammatory markers in innate immune cell types and reduced frequency of regulatory T cell activity in participants with severe infection compared to those with asymptomatic infection. Single-cell transcriptomics of paired samples revealed that asymptomatic donors had higher expression of genes associated with innate immune pathways, in particular anti-inflammatory CD16+ monocytes at the acute time point. A multi-omics analysis identified factors--beyond those from individual analyses--that distinguished immune state trajectory between severity groups. Here we highlighted the potential of systems immunology using multiple cell-type and cell-state-specific analyses to identify correlates of infection severity and host cellular activity contributing to an effective anti-viral response.

immunology↗

bioRxiv2022

Dectin-1 Stimulation Promotes a Distinct Inflammatory Signature in the Setting of HIV-infection and Aging

Dectin-1 is an innate immune receptor that recognizes and binds {beta}-1,3/1,6 glucans on fungi. We evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. Stimulation of monocytes with {beta}-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN- production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF- and coagulation response (increased at baseline), a persistent IFN- and IFN-{gamma} response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). Overall, our study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and Aging.

immunology↗

bioRxiv2022

Platelet response to influenza vaccination reflects effects of aging

Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity, but how age and alterations in functional status such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome in younger (age 21-35) and older (age [≥] 65) adults (including frail and non-frail individuals) following influenza vaccination. Prior to vaccination, we identified an age- and frailty-associated increase in expression of platelet activation and mitochondrial RNAs and decrease in RNAs encoding proteins mediating translation. Using tensor decomposition analysis, we also elucidated dynamic post-vaccination platelet activation and translation signatures associated with age and frailty. At the protein level, enhanced platelet activation was found in non-frail older adults, compared to young individuals both prior to and post-vaccine; but frail adults showed decreased platelet activation compared to non-frail that could reflect the influence of decreased translation RNA expression. Our results reveal an age-dependent alteration in platelet function prior to and post-vaccination that may contribute to age-associated chronic inflammation.

immunology↗