Browsing by Author "Pearce, Keenau"

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    Effects of xhosa specific solute carrier family 22-member 2 haplotypes on the cellular uptake of metformin and cimetidine
    (Elsevier B.V., 2025) Abrahams-October, Zainonesa; Kippie, Yunus; Pearce, Keenau; Benjeddou, Mongi
    Background: Studies have shown that solute carrier transporters play an important role in the transport and distribution of metformin, and that genetic variation(s) in solute carrier genes have play a role in the variation of metformin efficacy and disposition observed in populations. This study aimed to determine the cellular uptake efficiency of metformin in SLC22A2 coding haplotypes of an indigenous South African population. Methods and results: To determine metformin and cimetidine cellular uptake in transfected HEK-293 cells, ultra high-performance liquid chromatography was used to quantitate substrate concentration(s). Haplotypes 3 and 4 showed decreased metformin uptake, and haplotypes 2 and 5 displayed increased metformin uptake in comparison to haplotype 1 (i.e. wildtype haplotype). Haplotypes 2–5 showed decreased uptake of cimetidine in comparison to haplotype 1, implying a reduced sensitivity to the inhibition of cimetidine. In all haplotypes, no significant transport was observed for metformin and cimetidine. Passive permeability of metformin was favoured in haplotypes 3 and 5, whilst the remaining haplotypes demonstrate higher passive permeability ratios in favour of cimetidine. Conclusion: Haplotype 4, which is characterised by the non-synonymous single nucleotide polymorphisms rs316019 and rs8177517, demonstrates potential impaired metformin transport.
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    Green nanotechnology as an innovative drug delivery approach for typha capensis and naringenin—new class of phytochemical embedded biocompatible gold nanoparticles in prostate cancer therap
    (Journal of Drug Delivery Science and Technology, 2022) Henkel, Ralf; Pearce, Keenau
    Naringenin, a flavone with a growing body of evidence as an anti-cancer agent, is found in Typha capensis, an indigenous South African plant commonly used in traditional medicine. However, despite favourable in vitro results, clinical usage of naringenin remains restricted due to notoriously poor oral bioavailability, rapid metabolism and poor tumour site availability. This study aimed to investigate a simple, easily reproduced, reliable and effective drug delivery method of mitigating these issues using green nanotechnology principles, and assess their biomedical applications in the treatment of prostate cancer. Gold nanoparticles (AuNPs) were synthesized using green nanotechnology principles and characterized by spectrophotometry, dynamic light scattering, zeta potential, transmission electron microscopy, and Folin-ciocalteu phenol assay.
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    Intervertebral disc degenerative disease in South Africa: a case-control analysis of selected gene variants
    (Springer Nature, 2024) Pearce, Keenau; Less, Stephanie; Benjeddou, Mongi
    Intervertebral disc (IVD) degenerative disease is a multifactorial disease for which genetics plays an integral role. Several genes, and their variants, associated with the development and progression of IVD degenerative disease have been identified. While several studies have investigated these genes in Asian and European populations, no available evidence exists for the South African population. Therefore, this study aimed to investigate these parameters.
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    Intervertebral disc degenerative disease in South Africa: a case-control analysis of selected gene variants
    (Springer Science and Business Media B.V., 2024) Pearce, Keenau; Less, Stephanie; Benjeddou, Mongi
    Background: Intervertebral disc (IVD) degenerative disease is a multifactorial disease for which genetics plays an integral role. Several genes, and their variants, associated with the development and progression of IVD degenerative disease have been identified. While several studies have investigated these genes in Asian and European populations, no available evidence exists for the South African population. Therefore, this study aimed to investigate these parameters. Methods and results: Biological samples were collected in the form of buccal swabs from patients and DNA was extracted using a standard salt-lysis protocol. DNA purity and quantity was assessed by spectrophotometry, and subsequent genotyping was performed using the MassARRAY®System IPLEX extension reaction. For associations between variants and the presence of IVD degenerative disease, odds ratios (OR), confidence intervals (CI), chi-squared analysis and logistic regression was calculated. Age and sex were adjusted for, and Bonferroni’s correction was applied. This study found statistically significant associations for five of the evaluated single nucleotide polymorphisms (SNPs) with IVD degenerative disease, whereby IL-1α rs1304037 and rs1800587, ADAMTs-5 rs162509, and MMP-3 rs632478 demonstrated increased odds of a positive diagnosis for IVD degenerative disease, while decreased odds of IVD degenerative disease were seen for GDF-5 rs143383. Conclusion: To the best of our knowledge, this study represents the first of its kind to investigate the association of gene variants associated with IVD degenerative disease within the South African population. This study has shown that 5 of these gene variants were significantly associated with the presence of IVD degenerative disease, reflecting their integral roles in development and possible progression of the disease.
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    Liposomal-naringenin radiosensitizes triple-negative breast cancer mda-mb-231 cells in vitro
    (John Wiley and Sons Inc, 2024) Pearce, Keenau; Cairncross, Samantha; Benjeddou, Mongi
    Naringenin has shown great promise in the realm of cancer therapeutics, demonstrating excellent cytotoxic action toward cancer cells and the enhanced effects of radiation therapy in vitro. However, the medicinal value of naringenin is severely limited clinically by poor bioavailability. Thus, multiple drug-delivery strategies for overcoming this limitation have been developed, of which liposomes are considered the most suitable due to their amphiphilic, modifiable, and biocompatible characteristics. In this study, we investigated the role of naringenin and liposomal-delivered naringenin as adjuncts to radiotherapy in the MDA-MB-231 triple-negative breast cancer cell line in vitro. Liposomal-naringenin was synthesized by thin-film hydration and extrusion and was characterized by spectrophotometry, dynamic light scattering, and zeta potential. The effects of free-from naringenin and liposomal-naringenin were evaluated toward MDA-MB-231 cell viability when combined with varying doses of radiation. Additionally, cell growth patterns, morphology, and colony formation were evaluated. The analysis demonstrated IC50 values of 387.5 and 546.6 µg/ml for naringenin and liposomal-naringenin, respectively. Naringenin and liposomal-naringenin significantly lowered cell viability, proliferation, and colony formation dose-dependently, as compared to radiation in isolation. The findings presented herein concur with previous accounts of the radiosensitizing potential of naringenin and further highlight the considerable biomedical application of liposomal-naringenin within the realm of radiotherapy.