ORCID Profile
0000-0002-6477-9127
Current Organisation
University of South Australia
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Aboriginal and Torres Strait Islander environmental knowledges | Natural products and bioactive compounds | Aboriginal and Torres Strait Islander sciences | Aboriginal and Torres Strait Islander innovation
Publisher: Oxford University Press (OUP)
Date: 02-11-2020
Abstract: APOE ε4 allele is an established risk factor for Alzheimer’s disease and hypercholesterolemia. However, its association with metabolic and genetic risk factors related to glycation is not clear. We tested the hypothesis that, apart from high plasma cholesterol, APOE ε4 carriers may also have higher advanced glycation end products (AGEs) and total soluble extracellular domain of RAGE (sRAGE) and that these biomarkers may be modified by the common Gly82Ser (G82S) polymorphism (rs2070600) in the RAGE gene. To test this, we measured these biomarkers in 172 healthy cognitively normal in iduals, of which 32 were APOE ε4 carriers and 140 noncarriers. APOE ε4 carriers showed higher levels of cholesterol (p & .001), glyoxal (p & .001), fluorescent AGEs (p & .001), Nε-carboxymethyllysine (p & .001) and sRAGE (p = .018) when compared to noncarriers. Furthermore, sRAGE was also higher in those that did not carry the A allele of the RAGE gene that codes for serine instead of glycine (p = .034). Our study indicates that APOE ε4 carriers have a greater propensity to glycation than noncarriers which may further increase their risk for diabetes and dementia. The increased sRAGE levels in APOE ε4 carriers suggests a defensive response against AGEs that may be further influenced by the RAGE G82S polymorphism.
Publisher: MDPI AG
Date: 11-12-2017
Publisher: MDPI AG
Date: 15-09-2023
Publisher: Oxford University Press (OUP)
Date: 02-10-2023
Publisher: Springer Science and Business Media LLC
Date: 27-12-2019
DOI: 10.1038/S41598-019-56248-7
Abstract: There is increasing demand for safe and effective sanitizers for irrigation water disinfection to prevent transmission of foodborne pathogens to fresh produce. Here we compared the efficacy of pH-neutral electrolyzed oxidizing water (EOW), sodium hypochlorite (NaClO) and chlorine dioxide (ClO 2 ) against single and mixed populations of E. coli , Listeria and Salmonella under a range of pH and organic matter content. EOW treatment of the mixed bacterial suspension resulted in a dose-dependent ( mg/L free chlorine), rapid ( min) and effective (4–6 Log 10 ) reduction of the microbial load in water devoid of organic matter under the range of pH conditions tested (pH, 6.0, 7.0, 8.4 and 9.2). The efficacy of EOW containing 5 mg/L free chlorine was unaffected by increasing organic matter, and compared favourably with equivalent concentrations of NaClO and ClO 2 . EOW at 20 mg/L free chlorine was more effective than NaClO and ClO 2 in reducing bacterial populations in the presence of high (20–100 mg/L) dissolved organic carbon, and no regrowth or metabolic activity was observed for EOW-treated bacteria at this concentration upon reculturing in rich media. Thus, EOW is as effective or more effective than other common chlorine-based sanitizers for pathogen reduction in contaminated water. EOW’s other characteristics, such as neutral pH and ease of handling, indicate its suitability for fresh produce sanitation.
Publisher: MDPI AG
Date: 13-01-2021
DOI: 10.3390/APP11020732
Abstract: The effectiveness of sprayed and aerosolised pH-neutral electrochemically activated solutions (ECAS) containing 150 mg/L of free available chlorine in reducing total bacteria load and artificially inoculated Salmonella enterica serotype Enteritidis 11RX on eggs surfaces was investigated. Treatment groups included untreated control, sodium hypochlorite (positive control), sprayed and aerosolised water and sprayed and aerosolised ECAS. Sprayed ECAS (150 mg/L, 45 s) showed a significant reduction in total bacterial load (2.2 log reduction, p 0.0001) and S. Enteritidis (5.4 log reduction, p 0.0001) when compared with the untreated control. Aerosolised ECAS (120 s) was effective in reducing both the total bacterial load (1.4 log reduction, p 0.01) and S. Enteritidis (4.2 log reduction, p = 0.0022). However, aerosolised ECAS (60 s) only significantly reduced S. Enteritidis counts (2.8 log reduction, p 0.0008), indicating that a longer time for bacterial reduction during fogging sanitisation is needed. Tests performed with one egg per oscillating tray were more effective in reducing both the total bacterial load and the S. Enteritidis counts than those with three eggs per oscillating tray. Sprayed ECAS (45 s) and aerosolised ECAS (120 s) did not deteriorate the egg cuticle integrity (ΔEab*), which was evaluated using Cuticle Blue dye solution and colour intensity measurement. Overall, both the reduction in total bacteria counts and S. Enteritidis from the egg surface and retention of cuticle integrity suggest that sprayed and aerosolised ECAS could be used as alternative sanitising approaches to improve the food safety aspect of table eggs.
Publisher: MDPI AG
Date: 04-01-2023
DOI: 10.3390/IJMS24020982
Abstract: The relationship between sleep and micronutrients, including magnesium, is implicated in its regulation. The effects of low magnesium and other micronutrients on sleep disruption and telomere loss are not well understood. The present study was carried out in 172 healthy elderly subjects from South Australia. Plasma micronutrients including magnesium were measured. Each participant provided information about their sleep hours ( h or ≥7 h). Lymphocyte telomere length (TL) was measured by real-time qPCR assay. Plasma magnesium level was significantly low in subjects who sleep less than 7 h (p = 0.0002). TL was significantly shorter in people who are low in magnesium and sleep less than 7 h (p = 0.01). Plasma homocysteine (Hcy) is negatively associated with magnesium (r = −0.299 p 0.0001). There is a significant interaction effect of magnesium and Hcy on sleep duration (p = 0.04) and TL (p = 0.003). Our results suggest that inadequate magnesium levels have an adverse impact on sleep and telomere attrition rate in cognitively normal elderly people, and this may be exacerbated by low levels of vitamin B12 and folate that elevate Hcy concentration.
Publisher: Elsevier BV
Date: 02-2021
Publisher: MDPI AG
Date: 03-02-2023
Abstract: Almost half of prostate cancer (PC) patients receive radiation therapy as primary curative treatment. In spite of advances in our understanding of both nutrition and the genomics of prostate cancer, studies on the effects of nutrients on the radiation sensitivity of PC patients are lacking. We tested the hypothesis that low plasma levels of selenium and lycopene have detrimental effects on ionising radiation-induced DNA damage in prostate cancer patients relative to healthy in iduals. The present study was performed in 106 PC patients and 132 age-matched controls. We found that the radiation-induced micronucleus (MN) and nuclear buds (NBuds) frequencies were significantly higher in PC patients with low selenium (p = 0.008 and p = 0.0006 respectively) or low lycopene (p = 0.007 and p = 0.0006 respectively) levels compared to the controls. The frequency of NBuds was significantly higher (p 0.0001) in PC patients who had low levels of both selenium and lycopene compared to (i) controls with low levels of both selenium and lycopene and (ii) PC patients with high levels of both selenium and lycopene (p = 0.0001). Our results support the hypothesis that low selenium and lycopene levels increase the sensitivity to radiation-induced DNA damage and suggest that nutrition-based treatment strategies are important to minimise the DNA-damaging effects in PC patients receiving radiotherapy.
Publisher: Elsevier BV
Date: 12-2017
Abstract: The bacterial species and specific spoilage organisms associated with the Southern Australian King George Whiting (KGW) and Tasmanian Atlantic Salmon (TAS), and the efficacy of a HOCl-containing water-based sanitization product (Electro-Chemically Activated Solution, by ECAS4) in extending the shelf life of KGW and TAS fillets were evaluated. Fillets were washed with an ECAS4 solution containing either 45 ppm or 150 ppm of free chlorine and bacterial species enumerated on selective and non-selective media, followed by identification of pure isolates by 16 S rRNA gene sequencing. The dominant spoilage microbiota in KGW and TAS fillets stored at 4 ± 1 °C were Pseudomonas spp. and Shewanella spp. At either concentration, ECAS4 significantly reduced total bacterial load and specific spoilage organisms on KGW and TAS fillets (approx. 1-2 log colony-forming units) during storage and significantly extended the shelf life of the fillets by 2 and 4 days, respectively. The significant increase in shelf life and quality of fillets was corroborated by raw and cooked sensory evaluation. ECAS4 sanitization could have a significant impact on the overall food industry, translating into health and economic benefits through reduction of food spoilage bacteria and potentially, foodborne pathogens without many of the disadvantages of currently approved biocides.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 03-05-2021
DOI: 10.1038/S41598-021-88786-4
Abstract: To examine if skin autofluorescence (sAF) differed in early adulthood between in iduals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes ( N = 100 20.0 ± 2.8 years M:F 54:46 FBG-11.6 ± 4.9 mmol/mol diabetes duration 10.7 ± 5.2 years BMI 24.5(5.3) kg/m 2 ) and healthy controls ( N = 299 20.3 ± 1.8 years M:F-83:116 FBG 5.2 ± 0.8 mmol/L BMI 22.5(3.3) kg/m 2 ) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFR CKD-EPI CysC and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI ( P model = 1.5 × 10 –12 ). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk ( P model = 2.2 × 10 –9 ), which increased with diabetes duration (51% P model 2.2 × 10 –16 ) and random blood glucose concentrations (56% P model 2.2 × 10 –16 ). HbA 1C and circulating fructosamine albumin were higher in in iduals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.
Publisher: Oxford University Press (OUP)
Date: 23-01-2020
Abstract: This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either with glucose (Glu–BSA) or with fructose (Fru–BSA). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed higher Nε-carboxymethyllysine (CML 26.76 ± 1.09 nmol/mg BSA) levels in the Glu–BSA model. Nε-Carboxyethyllysine (CEL 7.87 ± 0.19 nmol/mg BSA) and methylglyoxal-derived hydroimidazolone-1 (MG-H1 69.77 ± 3.74 nmol/mg BSA) levels were higher in the Fru–BSA model. Genotoxic effects were measured using CBMN-Cyt assay biomarkers [binucleated(BN) cells with micronuclei (MNi), BN with nucleoplasmic bridges (NPBs) and BN with nuclear buds (NBuds)] following 9 days of treatment with either glucose, fructose, Glu–BSA or Fru–BSA. Fructose treatment exerted a significant genotoxic dose–response effect including increases of BN with MNi (R2 = 0.7704 P = 0.0031), BN with NPBs (R2 = 0.9311 P & 0.0001) and BN with NBuds (R2 = 0.7118 P = 0.0091) on cells, whereas the DNA damaging effects of glucose were less evident. High concentrations of AGEs (400–600 µg/ml) induced DNA damage however, there was no effect on cytotoxicity indices (necrosis and apoptosis). In conclusion, this study demonstrates a potential link between physiologically high concentrations of reducing sugars or AGEs with increased chromosomal damage which is an important emerging aspect of the pathology that may be induced by diabetes. Ultimately, loss of genome integrity could accelerate the rate of ageing and increase the risk of age-related diseases over the long term. These findings indicate the need for further research on the effects of glycation on chromosomal instability and to establish whether this effect is replicated in humans in vivo.
Publisher: Springer Science and Business Media LLC
Date: 03-10-2020
Publisher: MDPI AG
Date: 12-06-2020
DOI: 10.3390/NU12061767
Abstract: Dietary advanced glycation end products (AGEs) are believed to contribute to pathogenesis of diabetes and cardiovascular disease. The objective of this study was to determine if a diet high in red and processed meat and refined grains (HMD) would elevate plasma concentrations of protein-bound AGEs compared with an energy-matched diet high in whole grain, dairy, nuts and legumes (HWD). We conducted a randomized crossover trial with two 4-week weight-stable dietary interventions in 51 participants without type 2 diabetes (15 men and 36 women aged 35.1 ± 15.6 y body mass index (BMI), 27.7 ± 6.9 kg/m2). Plasma concentrations of protein-bound Nε-(carboxymethyl) lysine (CML), Nε-(1-carboxyethyl) lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The HMD significantly increased plasma concentrations (nmol/mL) of CEL (1.367, 0.78 vs. 1.096, 0.65 p 0.01 n = 48) compared with the HWD. No differences in CML and MG-H1 between HMD and HWD were observed. HMD increased plasma CEL concentrations compared with HWD in in iduals without type 2 diabetes.
Publisher: Wiley
Date: 30-09-2019
DOI: 10.1111/VDE.12794
Abstract: Multidrug-resistant pathogens present a major global challenge in antimicrobial therapy and frequently complicate otitis externa in dogs. In vitro efficacy of oregano oil, thyme oil and their main phenolic constituents against bacterial and fungal isolates associated with canine otitis externa were investigated. It was hypothesized that the main phenolic components would have greater antimicrobial activity compared to the relative essential oil. Antimicrobial susceptibility testing was performed using broth microdilution with spot-plating technique to determine minimum inhibitory and bactericidal/fungicidal concentrations (MICs, MBCs and MFCs). A time-kill kinetics assay was performed to confirm the bactericidal and fungicidal activity of the oils and their phenolic constituents. One hundred bacterial and fungal isolates, including meticillin-susceptible Staphylococcus pseudintermedius (n = 10), meticillin-resistant S. pseudintermedius (n = 10), β-haemolytic Streptococcus spp. (n = 20), Pseudomonas aeruginosa (n = 20 including 10 isolates resistant to one or two antimicrobials), Proteus mirabilis (n = 20) and Malassezia pachydermatis (n = 20) from dogs with otitis externa were used. Oregano oil, thyme oil, carvacrol and thymol exhibited antibacterial activity against all bacterial and fungal isolates tested. MIC Oregano oil, thyme oil, carvacrol and thymol showed good in vitro bactericidal and fungicidal activity against 100 isolates from dogs with otitis externa, including some highly drug-resistant isolates. These essential oils and their main phenolic constituents have the potential to be further investigated in vivo for the treatment of canine otitis externa.
Publisher: Informa UK Limited
Date: 03-04-2022
Publisher: Elsevier
Date: 2022
Publisher: Informa UK Limited
Date: 19-12-2020
Publisher: MDPI AG
Date: 11-11-2022
DOI: 10.3390/NU14224776
Abstract: Poorer mental health is common in undergraduate students due to academic stress. An interplay between stress and diet exists, with stress influencing food choices. Nutritional interventions may be effective in preventing mental health decline due to complex bidirectional interactions between the brain, the gut and the gut microbiota. Previous studies have shown walnut consumption has a positive effect on mental health. Here, using a randomized clinical trial (Australian New Zealand Clinical Trials Registry, #ACTRN12619000972123), we aimed to investigate the effects of academic stress and daily walnut consumption in university students on mental health, biochemical markers of general health, and the gut microbiota. We found academic stress had a negative impact on self-reported mood and mental health status, while daily walnut consumption improved mental health indicators and protected against some of the negative effects of academic stress on metabolic and stress biomarkers. Academic stress was associated with lower gut microbial ersity in females, which was improved by walnut consumption. The effects of academic stress or walnut consumption in male participants could not be established due to small numbers of participants. Thus, walnut consumption may have a protective effect against some of the negative impacts of academic stress, however sex-dependent mechanisms require further study.
Publisher: Springer Science and Business Media LLC
Date: 21-08-2022
DOI: 10.1007/S00726-021-03069-6
Abstract: Glycation is a non-enzymatic reaction that occurs between the free amino group of proteins and reducing sugars and/or lipids, leading to the formation of advanced glycation end products (AGEs). The reaction also produces reactive oxygen species that have detrimental effects on cellular and extracellular proteins. Aminoguanidine is a known inhibitor of AGEs, and some fatty acids are known to have a beneficial role in vivo by reducing inflammation and oxidative stress. However, the role of fatty acids on AGE formation has not been thoroughly reported. We investigated the role of a range of fatty acids in the formation of AGEs and their reactive intermediates using an in vitro BSA-dicarbonyl model. The model assessed a time-dependent (0-72 h) and dicarbonyl concentration (0-2 mM) -dependent studies for the optimal formation of AGEs. A 72 h time point was found to be optimal for the reaction of BSA with either methylglyoxal (MGO) or glyoxal (GO) to generate AGE-BSA complexes. When arachidonic, eicosapentaenoic or docosahexaenoic acids were included in the reaction, a significant decrease in protein-bound fluorescent AGEs was seen compared to the respective controls. In contrast, saturated and 18 carbon polyunsaturated fatty acids showed no significant activity. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed saturated fatty acids significantly decreased the production of N
Publisher: Elsevier BV
Date: 2021
Publisher: MDPI AG
Date: 08-04-2022
DOI: 10.3390/IJMS23084139
Abstract: The accurate segregation of sister chromatids is complex, and errors that arise throughout this process can drive chromosomal instability and tumorigenesis. We recently showed that methylglyoxal (MGO), a glycolytic by-product, can cause chromosome missegregation events in lymphocytes. However, the underlying mechanisms of this were not explored. Therefore, in this study, we utilised shotgun proteomics to identify MGO-modified proteins, and label-free quantitation to measure changes in protein abundance following exposure to MGO. We identified numerous mitotic proteins that were modified by MGO, including those involved in the separation and cohesion of sister chromatids. Furthermore, the protein abundance of Securin, an inhibitor of sister chromatid separation, was increased following treatment with MGO. Cytological examination of chromosome spreads showed MGO prevented sister chromatid separation, which was associated with the formation of complex nuclear anomalies. Therefore, results from this study suggest MGO may drive chromosomal instability by preventing sister chromatid separation.
Publisher: Oxford University Press (OUP)
Date: 08-05-2020
Abstract: The cytokinesis-block micronucleus cytome (CBMNcyt) assay is a comprehensive method to measure DNA damage, cytostasis and cytotoxicity caused by nutritional, radiation and chemical factors. A slide imaging technique has been identified as a new method to assist with the visual scoring of cells for the CBMNcyt assay. A NanoZoomer S60 Digital Pathology slide scanner was used to view WIL2-NS cells treated with hydrogen peroxide (H2O2) and measure CBMNcyt assay biomarkers using a high-definition desktop computer screen. The H2O2-treated WIL2-NS cells were also scored visually using a standard light microscope, and the two visual scoring methods were compared. Good agreement was found between the scoring methods for all DNA damage indices (micronuclei, nucleoplasmic bridges and nuclear buds) and nuclear ision index with correlation R values ranging from 0.438 to 0.789, P & 0.05. Apoptotic and necrotic cell frequency was lower for the NanoZoomer scoring method, but necrotic frequency correlated well with the direct visual microscope method (R = 0.703, P & 0.0001). Considerable advantages of the NanoZoomer scoring method compared to direct visual microscopy includes reduced scoring time, improved ergonomics and a reduction in scorer fatigue. This study indicates that a digital slide scanning and viewing technique may assist with visual scoring for the CBMNcyt assay and provides similar results to conventional direct visual scoring.
Publisher: Oxford University Press (OUP)
Date: 22-04-2020
Abstract: This study investigated the effect of dietary sugars and advanced glycation end-products (AGE) on telomere dynamics in WIL2-NS cells. Dietary sugars [glucose (Glu) and fructose (Fru) 0.1 M each] were incubated with bovine serum albumin (BSA) (10 mg/ml) at 60 ± 1°C for 6 weeks to generate AGE-BSA. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed total AGE levels as 87.74 ± 4.46 nmol/mg and 84.94 ± 4.28 nmol/mg respectively in Glu-BSA and Fru-BSA model. Cell treatment studies using WIL2-NS cells were based on either glucose, fructose (each 2.5–40 mM) or AGE-BSA (200–600 µg/ml) in a dose-dependent manner for 9 days. Telomere length (TL) was measured using qPCR. Nitric oxide (NO) production and tumour necrosis factor-α (TNF-α) levels were measured in WIL2-NS culture medium. An increasing trend for TNF-α and NO production was observed with higher concentration of glucose (R2 = 0.358 P = 0.019 R2 = 0.307 P = 0.027) and fructose (R2 = 0.669 P = 0.001 R2 = 0.339 P = 0.006). A decreasing trend for TL (R2 = 0.828 P = 0.000), and an increasing trend for NO production (R2 = 0.352 P = 0.031) were observed with increasing Glu-BSA concentrations. Fru-BSA treatment did not show significant trend on TL (R2 = 0.135 P = 0.352) with increasing concentration, however, a significant reduction was observed at 600 µg/ml (P & 0.01) when compared to BSA treatment. No trends for TNF-α levels and a decreasing trend on NO production (R2 = 0.5201 P = 0.019) was observed with increasing Fru-BSA treatment. In conclusion, this study demonstrates a potential relationship between dietary sugars, AGEs and telomere attrition. AGEs may also exert telomere shortening through the production of pro-inflammatory metabolites, which ultimately increase the risk of diabetes complications and age-related disease throughout lifespan.
Publisher: Informa UK Limited
Date: 09-01-2020
DOI: 10.1080/09637486.2020.1712683
Abstract: This study investigated the role of non-nutritive sweeteners in the formation of advanced glycation end-products (AGEs) and their reactive intermediates using endogenous and exogenous models. In the endogenous model, xylitol and sorbitol formed similar levels of reactive intermediates compared to sucralose. Protein-bound fluorescent AGEs,
Publisher: Oxford University Press (OUP)
Date: 23-07-2021
Abstract: Type 2 diabetes is associated with elevated levels of DNA damage, in particular micronuclei (MNi) which are formed by acentric chromosome fragments caused by double-stranded DNA breaks (DSBs), or whole chromosomes which fail to segregate during mitosis. We investigated if methylglyoxal (MGO), a reactive dicarbonyl known to be elevated in type 2 diabetes is capable of increasing chromosomal instability and DNA damage as measured by the cytokinesis block micronucleus cytome (CBMNcyt) assay in B-lymphoblastoid WIL2-NS cells and primary peripheral blood lymphocytes (PBL). We also investigated the level of various dicarbonyl stress biomarkers, including extracellular and intracellular MGO, protein and MGO modifications of DNA. WIL2-NS cells exposed to either MGO or a glyoxalase 1 inhibitor showed increases in MNi and nuclear buds, which were associated with an increase in intracellular MGO. DNA damage in the form of MNi and nucleoplasmic bridges were observed in primary PBL exposed to 10 µM MGO, suggesting low concentrations of MGO may be genotoxic. Furthermore, we showed, using fluorescent in situ hybridisation, that the majority of MNi caused by MGO in WIL2-NS cells were caused by whole chromosome loss events, rather than DSBs. Our data suggest that MGO, a reactive metabolite elevated in type 2 diabetes and other pathologies, can affect genomic integrity by impairing chromosome segregation during mitosis.
Publisher: Springer Science and Business Media LLC
Date: 09-2016
Publisher: Public Library of Science (PLoS)
Date: 25-09-2019
Publisher: MDPI AG
Date: 26-06-2023
Abstract: Telomeres are repetitive nucleotide (TTAGGG) sequences that stabilize the chromosome ends and play an important role in the prevention of cancer initiation and progression. Nucleoplasmic bridges (NPBs) are formed when chromatids remain joined together during mitotic anaphase either due to mis-repair of DNA breaks or due to chromatid end fusion as a result of telomere loss or telomere dysfunction. We tested the hypotheses that (i) telomere length (TL) is shorter in prostate cancer (PC) patients relative to healthy age-matched in iduals, (ii) TL differs in different stages of PC and (iii) shorter TL is significantly correlated with NPBs formation in PC cases. TL was measured in whole blood by well-established quantitative PCR method and the frequency of NPBs was measured in lymphocytes using cytokinesis-block micronucleus cytome (CBMNcyt) assay. Our results indicate that TL is shorter and NPBs are increased in PC patients relative to age-matched healthy controls. Furthermore, TL was significantly shorter (p = 0.03) in patients with a Gleason score more than 7 and there was also a significant trend of decreasing TL across all three stages (p trend = 0.01 Gleason score , 7 and ). Furthermore, TL was significantly inversely correlated with NPB frequency in PC patients (r = −0.316 p = 0.001) but not in controls (r = 0.163 p = 0.06) and their relationships became stronger with higher Gleason scores. More studies are required that can confirm our observations and explore mechanistic differences in the role of telomeres in NPB formation in PC cases relative to non-cancer cases.
Publisher: MDPI AG
Date: 28-03-2022
DOI: 10.3390/IJMS23073689
Abstract: Methylglyoxal (MGO) is a highly reactive cellular metabolite that glycates lysine and arginine residues to form post-translational modifications known as advanced glycation end products. Because of their low abundance and low stoichiometry, few studies have reported their occurrence and site-specific locations in proteins. Proteomic analysis of WIL2-NS B lymphoblastoid cells in the absence and presence of exogenous MGO was conducted to investigate the extent of MGO modifications. We found over 500 MGO modified proteins, revealing an over-representation of these modifications on many glycolytic enzymes, as well as ribosomal and spliceosome proteins. Moreover, MGO modifications were observed on the active site residues of glycolytic enzymes that could alter their activity. We similarly observed modification of glycolytic enzymes across several epithelial cell lines and peripheral blood lymphocytes, with modification of fructose bisphosphate aldolase being observed in all s les. These results indicate that glycolytic proteins could be particularly prone to the formation of MGO adducts.
Publisher: MDPI AG
Date: 24-04-2020
DOI: 10.3390/APP10082986
Abstract: Ready-to-eat (RTE) spinach is considered a high-risk food, susceptible to colonization by foodborne pathogens however, other microbial populations present on the vegetable surface may interact with foodborne pathogens by inhibiting/inactivating their growth. In addition, sanitizers applied to minimally processed salad leaves should not disrupt this autochthonous barrier and should be maintained throughout the shelf life of the product. This investigation aimed at comparing the effects of a pH neutral electrochemically activated solution (ECAS), a peroxyacetic acid (PAA)-based commercial sanitizer (Ecolab Tsunami® 100), and tap water wash on the minimally processed spinach leaf microbiome profile for 10 days after washing. The bacterial microbiota composition on spinach s les was assessed by 16S rRNA pyrosequencing and downstream analyses. Predominant phyla observed in decreasing order of abundance were Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes corresponding with the dominant families Micrococcaceae, Clostridiales Family XII, Flavobacteriaceae, Pseudomonadaceae, and Burkholderiaceae. Bacterial species richness and evenness (alpha ersity) and bacterial community composition among all wash types were not significantly different. However, a significant difference was apparent between s ling days, corresponding to a loss of overall heterogeneity over time. Analysis of composition of microbiome (ANCOM) did not identify any licon sequence variants (ASVs) or families having significantly different abundance in wash types however, differences (17 ASVs and five families) were found depending on s ling day. This was the first bacterial microbiome composition study focused on ECAS and PAA-based wash solutions. These wash alternatives do not significantly alter microbial community composition of RTE spinach leaves however, storage at refrigerated temperature reduces bacterial species heterogeneity.
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 04-11-2016
Publisher: Elsevier BV
Date: 02-2019
Publisher: African Journals Online (AJOL)
Date: 30-05-2016
DOI: 10.4314/TJPR.V15I5.3
Publisher: Oxford University Press (OUP)
Date: 2022
Abstract: Type 2 diabetes (T2D) is associated with elevated frequencies of micronuclei (MNi) and other DNA damage biomarkers. Interestingly, in iduals with T2D are more likely to be deficient in micronutrients (folic acid, pyridoxal-phosphate, cobalamin) that play key roles in one-carbon metabolism and maintaining genomic integrity. Furthermore, it has recently been shown that deficiencies in these nutrients, in particular folic acid leaves cells susceptible to glucose-induced DNA damage. Therefore, we sought to investigate if the B lymphoblastoid WIL2-NS cell line cultured under folic acid-deficient conditions was more sensitive to DNA damage induced by glucose, or the reactive glycolytic byproduct methylglyoxal (MGO) and subsequent advanced glycation endproduct formation. Here, we show that only WIL2-NS cultured under folic acid-deficient conditions (23 nmol/l) experience an increase in MNi frequency when exposed to high concentrations of glucose (45 mmol/l) or MGO (100 µmol/l). Furthermore, we showed aminoguanidine, a well-validated MGO and free radical scavenger was able to prevent further MNi formation in folic acid-deficient cells exposed to high glucose, which may be due to a reduction in MGO-induced oxidative stress. Interestingly, we also observed an increase in MGO and other dicarbonyl stress biomarkers in folic acid-deficient cells, irrespective of glucose concentrations. Overall, our evidence shows that folic acid-deficient WIL2-NS cells are more susceptible to glucose and/or MGO-induced MNi formation. These results suggest that in iduals with T2D experiencing hyperglycemia and folic acid deficiency may be at higher risk of chromosomal instability.
Publisher: Wiley
Date: 09-2009
DOI: 10.1002/JBT.20301
Abstract: The extent of absorption of dietary advanced glycation end products (AGEs) is not fully known. The possible physiological impact of these absorbed components on inflammatory processes has been studied little and was the aim of this investigation. Aqueous solutions of bovine casein and glucose were heated at 95 degrees C for 5 h to give AGE-casein (AGE-Cas). Simulated stomach and small intestine digestion of AGE-Cas and dialysis (molecular mass cutoff of membrane = 1 kDa) resulted in a low molecular mass (LMM) fraction of digestion products, which was used to prepare bovine serum albumin (BSA)-LMM-AGE-Cas complexes. Stimulation of human microvascular endothelial cells with BSA-LMM-AGE-Cas complexes significantly increased mRNA expression of the receptor of AGE (RAGE), galectin-3 (AGE-R3), tumor necrosis factor alpha, and a marker of the mitogen-activated protein kinase pathway (MAPK-1), as well as p65NF-kappaB activation. Cells treated with LMM digestion products of AGE-Cas significantly increased AGE-R3 mRNA expression. Intracellular reactive oxygen species production increased significantly in cells challenged with BSA-LMM-AGE-Cas and LMM-AGE-Cas. In conclusion, in an in vitro cell system, digested dietary AGEs complexed with serum albumin play a role in the regulation of RAGE and downstream inflammatory pathways. AGE-R3 may protect against these effects.
Publisher: Oxford University Press (OUP)
Date: 21-09-2020
Abstract: Apolipoprotein-ε4 (APOE-ε4)—common variant is a major genetic risk factor for cognitive decline and Alzheimer's disease (AD). An accelerated rate of biological aging could contribute to this increased risk. Glycation of serum proteins due to excessive glucose and reactive oxygen species leads to the formation of advanced glycation end products (AGEs)—a risk factor for diabetes and AD, and decline in motor functioning in elderly adults. Aim of present study was to investigate impact of APOE-ε4 allele containing genotype and accumulation of AGEs in plasma on telomere length (TL). Results showed that TL is significantly shorter in APOE-ε4 carriers compared with non-APOE-ε4 carriers (p = .0003). Higher plasma glucose level was associated with shorter TL irrespective of APOE-ε4 allele containing genotype (r = −.26 p = .0004). With regard to AGEs, higher plasma glyoxal and fluorescent AGEs concentrations were inversely related to TL (r = −.16 p = .03 r = −.28 p = .0001), however, plasma Nε-(carboxymethyl)lysine levels didn't correlate with TL (r = −.04 p = .57). Results support the hypotheses that APOE-ε4 carriers have shorter telomeres than noncarriers and telomere erosion is increased with higher concentration of glucose, fluorescent AGEs, and glyoxal.
Publisher: Informa UK Limited
Date: 15-06-2022
Publisher: Oxford University Press (OUP)
Date: 06-10-2021
Abstract: Advanced glycation end products (AGEs) are formed via non-enzymatic reactions between amino groups of proteins and the carbonyl groups of reducing sugars. Previous studies have shown that highly glycated albumin prepared using a glucose-bovine serum albumin (Glu-BSA) model system incubated at 60°C for 6 weeks induces genotoxicity in WIL2-NS cells at 9 days of exposure measured by the cytokinesis-block micronucleus cytome (CBMNcyt) assay. However, this AGE model system is not physiologically relevant as normal body temperature is 37°C and the degree of glycation may exceed the extent of albumin modification in vivo. We hypothesised that the incubation temperature and purification method used in these studies may cause changes to the chemical profile of the glycated albumin and may influence the extent of genotoxicity observed at 3, 6 and 9 days of exposure. We prepared AGEs generated using Glu-BSA model systems incubated at 60°C or 37°C purified using trichloroacetic acid (TCA) precipitation or ultrafiltration (UF) and compared their chemical profile (glycation, oxidation, and aggregation) and genotoxicity in WIL2-NS cells using the CBMNcyt assay after 3, 6 and 9 days of exposure. The number of micronuclei (MNi) was significantly higher for cells treated with Glu-BSA incubated at 60°C and purified via TCA (12 ± 1 MNi/1000 binucleated cells) compared to Glu-BSA incubated at 37°C and purified using UF (6 ± 1 MNi/1000 binucleated cells) after 9 days (P & 0.0001). The increase in genotoxicity observed could be explained by a higher level of protein glycation, oxidation, and aggregation of the Glu-BSA model system incubated at 60°C relative to 37°C. This study highlighted that the incubation temperature, purification method and cell exposure time are important variables to consider when generating AGEs in vitro and will enable future studies to better reflect in vivo situations of albumin glycation.
Publisher: MDPI AG
Date: 19-06-2023
Abstract: Background: The soluble form of receptor for advanced glycation end products (sRAGE) have been implicated in the prevention of numerous pathologic states, and highlights as an attractive therapeutic target. Because diets rich in monounsaturated fatty acids (MUFA) reduce postprandial oxidative stress and inflammation that is related to better health during aging, we investigated the association between red blood cell (RBC) fatty acids with circulatory AGE biomarkers and further stratified this correlation based on GG and GA + AA genotype. Methods: A total of 172 healthy participants (median age = 53.74 ± 0.61 years) were recruited for the study. RBC fatty acid was analysed using gas chromatography and sRAGE was measured using a commercial ELISA kit. Results: The result showed a non-significant correlation between total MUFA with sRAGE however oleic acid (C18:1) exhibited a positive correlation (r = 0.178, p = 0.01) that remained statistically significant (β = 0.178, p = 0.02) after a stepwise multivariate regression analysis after adjusting for age, BMI and gender. In a univariate analysis, a positive significant correlation between C18:1 and sRAGE in GG genotype (r = 0.169, p = 0.02) and a non-significant correlation with GA + AA genotype (r = 0.192, p = 0.21) was evident. When C18:1 was stratified, a significant difference was observed for oleic acid and G82S polymorphism: low C18:1/GA + AA versus high C18:1/GG (p = 0.015) and high C18:1/GA + AA versus high C18:1/GG (p = 0.02). Conclusion: Our study suggests that increased levels of C18:1 may be a potential therapeutic approach in increasing sRAGE in those with GG genotype and play a role in modulating AGE metabolism.
Publisher: Oxford University Press (OUP)
Date: 21-05-2019
DOI: 10.1111/JAM.14298
Abstract: The antimicrobial activity of cinnamon essential oil and cinnamaldehyde against bacterial and fungal pathogens associated with canine otitis externa, as well as the effect of their combination with EDTA were investigated. Antimicrobial susceptibility testing was performed using the broth microdilution method while spot-plating technique was used to determine their bactericidal activity. Time-kill kinetics and checkerboard assays were performed to confirm the bactericidal activity and combination effects of the compounds. Cinnamon oil and cinnamaldehyde exhibited antimicrobial activity against Gram-positive and Gram-negative pathogens, as well as Malassezia pachydermatis. Synergistic interaction was shown when EDTA (672 μg ml Cinnamon essential oil and cinnamaldehyde, either used alone or in combination with EDTA, were effective against the causative micro-organisms of canine otitis externa. The data suggest that cinnamaldehyde could be a promising antimicrobial agent against canine otitis externa. This study shows that cinnamon essential oil and cinnamaldehyde, especially the latter, could be used in combination with EDTA as novel treatment for sensitive and resistant bacterial and fungal pathogens involved in canine otitis externa.
Publisher: Oxford University Press (OUP)
Date: 10-10-2022
Abstract: Red blood cell (RBC) fatty acid status is used as a biomarker of dietary intake of fats however, there is still a paucity of evidence regarding in idual fatty acids and modulation of endogenous advanced glycation end product (AGE) levels. Due to membrane polyunsaturated fatty acid (PUFA) being a well-known target for peroxidation, we hypothesized that cellular PUFAs are positively associated with circulatory Nε-carboxymethyllysine (CML) that is also influenced by glyoxal levels in healthy cohorts. To test this, we investigated the association between RBC fatty acids and circulatory AGE biomarkers in healthy in iduals. The results showed a negative association between saturated fatty acids (SFA) and CML, and stepwise multivariate regression analysis indicated that stearic acid was negatively associated with CML levels (β = -0.200, p = .008) after adjusting for age, body mass index (BMI), and gender. In addition, stearic acid:palmitic acid ratio was also negatively correlated with plasma concentrations of CML (rp = -.191, p = .012) and glucose (rp = -.288, p = .0001). PUFAs showed a positive association with CML levels, particularly docosapentaenoic acid, γ-linolenic acid, arachidonic acid, and docosadienoic acid. However, these associations were not evident after the multiple regression analysis adjusted for age, BMI, and gender. A strong negative correlation (rp = -.98, p < .0001) between total PUFA and total SFA was observed. Furthermore, the SFA:PUFA ratio was inversely correlated with CML (rp = -.227, p < .003). Overall, this study indicates that different fats and their combinations may influence the formation of AGEs and that carefully controlled interventions are required to further test this hypothesis.
Publisher: Oxford University Press (OUP)
Date: 07-09-2021
Abstract: Lymphocyte telomere length (LTL) is a biomarker of aging that may be modified by dietary factors including fat. Red blood cell fatty acid status is a well-validated indicator of long-term dietary intake of fat from various sources. Recent findings from epidemiological studies of LTL in relation to fatty acids in red blood cells are not conclusive. The present study was carried out to investigate if red blood cell fatty acid status in 174 healthy older South Australians is associated with LTL. Lymphocyte telomere length was measured by real-time qPCR and fatty acid content in red blood cells was measured by gas chromatography. Our results indicate that the majority of saturated fatty acids and monounsaturated fatty acids are negatively associated with LTL, whereas polyunsaturated fatty acids are positively associated with LTL. Multiple regression analysis revealed that arachidonic acid (C20:4n-6) is significantly, independently, positively correlated with LTL (β = 0.262 p = .000). The significant association of fatty acids, particularly C20:4n-6, with telomere length warrants further research.
Publisher: Oxford University Press (OUP)
Date: 11-09-2021
Abstract: Significant alterations in sleep duration and/or quality of sleep become more pronounced as people get older. Poor sleep in elderly people is associated with adverse health outcomes and cellular aging. We examined the relationship between telomere length (TL) and sleep duration, Health Promotion Index (HPI), and tested whether the presence of Apolipoprotein-E4 (ApoE-ε4) allele affects both sleep and TL. The present study was carried out in 174 healthy participants (21% male mean age 53.79 years) from South Australia. Lymphocyte TL was measured by real-time quantitative PCR (qPCR) and ApoE genotype was determined by TaqMan assay. HPI was calculated from a questionnaire regarding 8 lifestyle habits, including sleeping hours. Multivariate regression analysis was used to establish these associations adjusted for specified confounders. TL was found to be inversely associated with age (r = −0.199 p = .008) and body mass index (r = −0.121 p = .11), and was significantly shorter in participants who slept for less than 7 hours (p = .001) relative to those sleeping ≥7 hours. TL was positively correlated with HPI (r = 0.195 p = .009). ApoE-ε4 allele carriers who slept for less than 7 hours had shortest TL (p = .01) compared to noncarriers. Plasma soluble receptor for advanced glycation end product (sRAGE) level was significantly (p = .001) lower in in iduals who sleep less than 7 hours and ApoE-ε4 carriers. Our results suggest that inadequate sleep duration or poor HPI is associated with shorter TL in cognitively normal people and that carriage of APOE-ε4 genotype may influence the extent of these effects.
Publisher: Wiley
Date: 22-02-2023
DOI: 10.1111/IJFS.16341
Abstract: In this study, sea cucumber ( Holothuria scabra Jaegar 1833) extracts and collagens were evaluated for inhibitory properties of protein‐bound advanced glycation end products (AGEs). Processed dried sea cucumber with salt extract showed a significant lower IC 50 value for fluorescent AGEs (9.19 ± 7.68 μg mL −1 , P 0.05) and fructosamine (503.47 ± 46.37 μg mL −1 , P 0.05), respectively. Processed dried with and without salt extracts significantly reduced the N ε ‐carboxymethyllysine (CML) and methylglyoxal‐derived hydroimidazolone‐1 (MG‐H1) levels tested at 250 μg mL −1 . Smoked dried and fresh‐dried extracts significantly reduced the N ε ‐carboxyethyllysine (CEL) levels tested at 250 μg mL −1 . Pepsin‐solubilised collagen and the crude collagen fibrils significantly reduced CML and MG‐H1 levels whereas CEL levels were unchanged. Pearson's correlation analysis showed that protein‐bound AGE and CML inhibition significantly correlated with the total phenolic and antioxidant activities, respectively. This study provides a strong rationale for further investigation aimed at identifying the active compounds responsible for the observed effects on biomarkers relevant to diabetes.
Publisher: Elsevier BV
Date: 07-2021
DOI: 10.1016/J.MRREV.2021.108384
Abstract: The purpose of the "Micronuclei and Disease" special issue (SI) is to: (i) Determine the level of evidence for association of micronuclei (MN), a biomarker of numerical and structural chromosomal aberrations, with risk of specific diseases in humans (ii) Define plausible mechanisms that explain association of MN with each disease (iii) Identify knowledge gaps and research needed to translate MN assays into clinical practice. The "MN and Disease" SI includes 14 papers. The first is a review of mechanisms of MN formation and their consequences in humans. 11 papers are systematic reviews and/or meta-analyses of the association of MN with reproduction, child health, inflammation, auto-immune disease, glycation, metabolic diseases, chronic kidney disease, cardiovascular disease, eleven common cancers, ageing and frailty. The penultimate paper focuses on effect of interventions on MN frequency in the elderly. A road map for translation of MN data into clinical practice is the topic of the final paper. The majority of reviewed studies were case-control studies in which the ratio of mean MN frequency in disease cases relative to controls, i.e. the mean ratio (MR), was calculated. The mean of these MR values, estimated by meta-analyses, for lymphocyte and buccal cell MN in non-cancer diseases were 2.3 and 3.6 respectively, and for cancers they were 1.7 and 2.6 respectively. The highest MR values were observed in studies of cancer cases in which MN were measured in the same tissue as the tumour (MR = 4.9-10.8). This special issue is an important milestone in the evidence supporting MN as a reliable genomic biomarker of developmental and degenerative disease risk. These advances, together with results from prospective cohort studies, are helping to identify diseases in which MN assays can be practically employed in the clinical setting to better identify high risk patients and to prioritise them for preventive therapy.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 02-04-2021
Abstract: This study shows how highly processed foods can cause innate immune inflammation that promotes chronic microvascular disease.
Publisher: ACM
Date: 30-04-2023
Publisher: Elsevier BV
Date: 09-2018
Publisher: MDPI AG
Date: 23-12-2022
Abstract: Emerging evidence suggests possible roles of micronutrients in cancer prevention. The study was designed to test the hypothesis that the concentration profile of plasma micronutrients (i.e., the nutriome) in prostate cancer patients is different from that of healthy controls. Plasma s les from 116 Caucasian men diagnosed with late onset of prostate cancer and 132 matched controls from the South Australian population were collected and analysed for their concentration of micronutrients. Plasma concentrations of lutein, lycopene, α-carotene and β-carotene were found to be significantly lower in prostate cancer patients (p = 0.03, 0.008, 0.002 and 0.002, respectively). Plasma levels of elements such as iron, copper, calcium and sulphur were significantly higher (p 0.0001, .0001, .0001 and p = 0.0003, respectively) while that of selenium was significantly lower (p = 0.002) in prostate cancer patients. Higher prostate cancer risk is significantly associated with plasma levels below the median of lycopene (OR: 2.24), α-carotene (OR: 2.13), β-carotene (OR: 1.97) and high levels above the median of iron (OR: 2.31), calcium (OR: 4.35) and sulphur (OR: 2.39). The results of this study suggest that the plasma nutriome could be a useful diagnostic of prostate cancer risk.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 07-2023
End Date: 06-2026
Amount: $380,833.00
Funder: Australian Research Council
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