The buccal micronucleus cytome assay: New horizons for its implementation in human studies.

In this report we provide a summary of the presentations and discussion of the latest knowledge regarding the buccal micronucleus (MN) cytome assay. This information was presented at the HUMN workshop held in Malaga, Spain, in connection with the 2023 European, Environmental Mutagenesis and Genomics conference. The presentations covered the most salient topics relevant to the buccal MN cytome assay including (i) the biology of the buccal mucosa, (ii) its application in human studies relating to DNA damage caused by environmental exposure to genotoxins, (iii) the association of buccal MN with cancer and a wide range of reproductive, metabolic, immunological, neurodegenerative and other age-related diseases, (iv) the impact of nutrition and lifestyle on buccal MN cytome assay biomarkers; (v) its potential for application to studies of DNA damage in children and obesity, and (vi) the growing prospects of enhancing the clinical utility by automated scoring of the buccal MN cytome assay biomarkers by image recognition software developed using artificial intelligence. The most important knowledge gap is the need of prospective studies to test whether the buccal MN cytome assay biomarkers predict health and disease.

Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men.

Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated with infertility, DNA damage and fragmentation. Oxidative stress has been shown to affect sperm DNA integrity and telomere length. Sirtuins such as SIRT1 and SIRT3 are involved in aging and oxidative stress response. The aim of the present study is to determine the role of SIRT1 and SIRT3 in regulating oxidative stress, telomere shortening, and their association with oligospermia. Therefore, we assessed the protein levels of SIRT1 and SIRT3, total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in the seminal plasma of 272 patients with oligospermia and 251 fertile men. We also measured sperm telomere length (STL) and leukocyte telomere length (LTL) using a standard real-time quantitative PCR assay. Sperm chromatin and protamine deficiency were also measured as per standard methods. Our results for oligospermic patients demonstrate significant reductions in semen parameters, shorter STL and LTL, lower levels of SOD, TAC, CAT, SIRT1 and SIRT3 levels, and also significant protamine deficiency and higher levels of MDA and DNA fragmentation. We conclude that a shorter TL in sperms and leukocytes is associated with increased oxidative stress that also accounts for high levels of DNA fragmentation in sperms. Our results support the hypothesis that various sperm parameters in the state of oligospermia are associated with or caused by reduced levels of SIRT1 and SIRT3 proteins.

Towards prevention of aneuploidy-associated cellular senescence and aging: more questions than answers?

The aim of this review is to discuss how aneuploidy contributes to the aging process, and to identify plausible strategies for its prevention. After an overview of mechanisms leading to aneuploidy and the major features of cellular senescence, we discuss the link between (i) aneuploidy and cellular senescence; (ii) aneuploidy and aging; and (iii) cellular senescence and aging. We also consider (i) interactions between aneuploidy, micronuclei, cellular senescence and aging, (ii) the potential of nutritional treatments to prevent aneuploidy-associated senescence and aging, and (iii) knowledge and technological gaps. Evidence for a causal link between aneuploidy, senescence and aging is emerging. In vitro, aneuploidy accompanies the entry into cellular senescence and can itself induce senescence. How aneuploidy contributes in vivo to cellular senescence is less clear. Several routes depending on aneuploidy and/or senescence converge towards chronic inflammation, the major driver of unhealthy aging. Aneuploidy can induce the pro-inflammatory Senescence Associated Secretory Phenotype (SASP), either directly or as a result of micronucleus (MN) induction leading to leakage of DNA into the cytoplasm and triggering of the cGAS-STING pathway of innate immune response. A major difficulty in understanding the impact of aneuploidy on senescence and aging in vivo, results from the heterogeneity of cellular senescence in different tissues at the cytological and molecular level. Due to this complexity, there is at the present time no biomarker or biomarker combination characteristic for all types of senescent cells. In conclusion, a deeper understanding of the critical role aneuploidy plays in cellular senescence and aging is essential to devise practical strategies to protect human populations from aneuploidy-associated pathologies. We discuss emerging evidence, based on in vitro and in vivo studies, that adequate amounts of specific micronutrients are essential for prevention of aneuploidy in humans and that precise nutritional intervention may be essential to help avoid the scourge of aneuploidy-driven diseases.

Effect of iron and calcium on radiation sensitivity in prostate cancer patients relative to controls.

High intake of red meat and/or dairy products may increase the concentration of iron and calcium in plasma-a risk factor for prostate cancer (PC). Despite our understandings of nutrients and their effects on the genome, studies on the effects of iron and calcium on radiation sensitivity of PC patients are lacking. Therefore, we tested the hypothesis that high plasma levels of iron and calcium could increase baseline or radiation-induced DNA damage in PC patients relative to healthy controls. The present study was performed on 106 PC patients and 132 age-matched healthy individuals. CBMN assay was performed to measure mi-cronuclei (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBuds) in lymphocytes. Plasma concentrations of iron and calcium were measured using inductively coupled plasma atomic emission spectroscopy. MN, NPBs, and NBuds induced by radiation ex vivo were significantly higher in PC patients with high plasma iron (P = .004, P = .047, and P = .0003, respectively) compared to healthy controls. Radiation-induced MN and NBuds frequency were also significantly higher in PC patients (P = .001 and P = .0001, respectively) with high plasma calcium levels relative to controls. Furthermore, radiation-induced frequency of NBuds was significantly higher in PC patients (P < .0001) with high plasma levels of both iron and calcium relative to controls. Our results support the hypothesis that high iron and calcium levels in plasma increases the sensitivity to radiation-induced DNA damage and point to the need of developing nutrition-based strategies to minimize DNA damage in normal tissue of PC patients undergoing radiotherapy.

Red Blood Cell Fatty Acid Profiles Are Significantly Altered in South Australian Mild Cognitive Impairment and Alzheimer's Disease Cases Compared to Matched Controls.

Nutritional imbalances have been associated with a higher risk for cognitive impairment. This study determined the red blood cell (RBC) fatty acid profile of newly diagnosed mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients compared to age and gender-matched controls. There was a significant increase in palmitic acid (p < 0.00001) for both MCI and AD groups. Saturated fatty acids were significantly elevated in the MCI group, including stearic acid (p = 0.0001), arachidic acid (p = 0.003), behenic acid (p = 0.0002), tricosanoic acid (p = 0.007) and lignoceric acid (p = 0.001). n-6 polyunsaturated fatty acids (PUFAs) were significantly reduced in MCI, including linoleic acid (p = 0.001), γ-linolenic acid (p = 0.03), eicosatrienoic acid (p = 0.009) and arachidonic acid (p < 0.00004). The n-3 PUFAs, α-linolenic acid and docosahexaenoic acid, were both significantly reduced in MCI and AD (p = 0.0005 and p = 0.00003). A positive correlation was evident between the Mini-Mental State Examination score and nervonic acid in MCI (r = 0.54, p = 0.01) and a negative correlation with γ-linolenic acid in AD (r = -0.43, p = 0.05). Differences in fatty acid profiles may prove useful as potential biomarkers reflecting increased risk for dementia.

Protective Effects of Micronutrient Supplements, Phytochemicals and Phytochemical-Rich Beverages and Foods Against DNA Damage in Humans: A Systematic Review of Randomized Controlled Trials and Prospective Studies.

Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor ß-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B12, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.

The Relationship between Telomere Length and Nucleoplasmic Bridges and Severity of Disease in Prostate Cancer Patients.

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 individuals, (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, 7 and >7). 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.

Association between the use of muscle-building supplements and DNA damage in resistance training practitioners.

OBJECTIVES: Little is known about the relationship between the supplements used for sport and safety, especially regarding the induction of genotoxicity. Therefore, more knowledge about a DNA damage possibly caused using sport supplements is necessary. The aim of this study was to investigate the potential association between the use of muscle-building supplements and DNA damage in resistance training practitioners. METHODS: Muscle-building supplements were classified into three categories based on evidence of efficacy and safety: Strong Evidence to Support Efficacy and Apparently Safe (SESEAS); Limited or Mixed Evidence to Support Efficacy (LMESE), and Little to No Evidence to Support Efficacy and/or Safety (LNESES). DNA damage was evaluated by the comet assay (DNA damage index and frequency) and buccal micronucleus by the cytome assay (micronuclei and nuclear buds). In the sequence, the adjusted analysis of covariance was performed. This study included 307 individuals ages 37.99 ± 13.95 y (52.1% men), of which 157 consumed supplements. RESULTS: The results of the comet assay revealed that participants who used supplements had higher DNA damage indexes (P = 0.018) and damage frequency (P = 0.045) than those who reported using no supplements. Moreover, the comet assay also indicated that the participants who used supplements classified into the SESEAS category presented the highest DNA damage index (P = 0.025) and frequency (P = 0.044) compared with those who used no supplements. However, we found no significant difference in the micronuclei and nuclear buds in the evaluated groups (P > 0.05). CONCLUSION: Supplement use is not associated with permanent damage, suggesting that SESEAS supplements are safe for consumption.

Oleic Acid Status Positively Correlates with the Soluble Receptor for Advanced Glycation End-Products (sRAGE) in Healthy Adults Who Are Homozygous for G Allele of RAGE G82S Polymorphism.

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 (ß = 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.

Effect of Selenium and Lycopene on Radiation Sensitivity in Prostate Cancer Patients Relative to Controls.

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 individuals. 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.

Low Magnesium in Conjunction with High Homocysteine and Less Sleep Accelerates Telomere Attrition in Healthy Elderly Australian.

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 (<7 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.

Current Evidence on the Association of Micronutrient Malnutrition with Mild Cognitive Impairment, Frailty, and Cognitive Frailty among Older Adults: A Scoping Review.

Micronutrient malnutrition is thought to play an important role in the cause of cognitive impairment and physical frailty. The purpose of this scoping review was to map current evidence on the association between micronutrient deficiency in blood and mild cognitive impairment, frailty, and cognitive frailty among older adults. The scoping review was conducted based on the 2005 methodological framework by Arksey and O'Malley. The search strategy for potential literature on micronutrient concentration in blood and cognitive frailty was retrieved based on the keywords using electronic databases (PubMed, Cochrane Library, Google Scholar, Ovid, and Science Direct) from January 2010 to December 2021. Gray literature was also included in the searches. A total of 4310 articles were retrieved and 43 articles were incorporated in the review. Findings revealed a trend of significant association between low levels of B vitamins (folate and vitamin B12), vitamin D, vitamin A, vitamin E, omega 3 fatty acid, and albumin, and high homocysteine levels in blood with an increased risk of mild cognitive impairment among older adults. The results also indicated that low vitamin D levels, albumin, and antioxidants (lutein and zeaxanthin) in blood were significantly associated with frailty among older adults, while ß-cryptoxanthin and zeaxanthin in blood were inversely associated with the risk of cognitive frailty. Vitamin D and antioxidants seemed to be targeted nutrients for the prevention of cognitive frailty. In conclusion, a wide range of micronutrient deficiency was associated with either mild cognitive impairment or frailty; however, little evidence exists on the dual impairment, i.e., cognitive frailty. This scoping review can serve as preliminary evidence for the association between micronutrient deficiency in blood and mild cognitive impairment, frailty, and cognitive frailty among older adults and prove the relevancy of the topic for future systematic reviews.

Incidence and Predictors of Mortality among Community-Dwelling Older Adults in Malaysia: A 5 Years Longitudinal Study.

With older adults accounting for 10.7% of the Malaysian population, determining the predictors of mortality has now become crucial. Thus, this community-based longitudinal study aimed to investigate the predictors for mortality among community-dwelling older adults using a wide range of factors, including clinical or subclinical. A total of 2322 older adults were interviewed and assessed by trained fieldworkers using validated structured questionnaires. The questionnaire consisted of information on socio-demographic characteristics, health status, neuropsychological and psychosocial functions, lifestyle, dietary intake and biophysical measures. The incidence rate of mortality was 2.9 per 100 person-years. Cox regression analysis indicated that advancing age (Adjusted Hazard Ratio, Adj HR = 1.044, 95% CI: 1.024-1.064), male (Adj HR = 1.937, 95% CI: 1.402-2.675), non-married status (Adj HR = 1.410, 95% CI: 1.078-1.843), smoking (Adj HR = 1.314, 95% CI: 1.004-1.721), a higher fasting blood sugar (Adj HR = 1.075, 95% CI: 1.029-1.166), a lower serum albumin (Adj HR = 0.947, 95% CI: 0.905-0.990), a longer time to complete the TUG test (Adj HR = 1.059, 95% CI: 1.022-1.098), and a lower intake of total dietary fibre (Adj HR = 0.911, 95% CI: 0.873-0.980) were the predictors of mortality in this study. These findings provide an estimated rate of multiethnic mortality in middle-income countries and diet is one of the predictors. These predictors of mortality could be a reference in identifying new public health strategies to ensure longer healthier life spans with lower disability rate among community-dwelling older adults in Malaysia.

Proteomic Analysis of Methylglyoxal Modifications Reveals Susceptibility of Glycolytic Enzymes to Dicarbonyl Stress.

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 samples. These results indicate that glycolytic proteins could be particularly prone to the formation of MGO adducts.

Methylglyoxal Impairs Sister Chromatid Separation in Lymphocytes.

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.

Aneuploidy, inflammation and diseases.

This review discusses how numerical aneuploidy may trigger inflammation in somatic cells and its consequences. Therefore we: i) summarized current knowledge on the cellular and molecular pathological effects of aneuploidy; ii) considered which of these aspects are able to trigger inflammation; iii) determined the genetic and environmental factors which may modulate the link between aneuploidy and inflammation; iv) explored the rôle of diet in prevention of aneuploidy and inflammation; v) examined whether aneuploidy and inflammation are causes and/or consequences of diseases; vi) identified the knowledge gaps and research needed to translate these observations into improved health care and disease prevention. The relationships between aneuploidy, inflammation and diseases are complex, because they depend on which chromosomes are involved, the proportion of cells affected and which organs are aneuploid in the case of mosaic aneuploidy. Therefore, a systemic approach is recommended to understand the emergence of aneuploidy-driven diseases and to take preventive measures to protect individuals from exposure to aneugenic conditions.

Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability.

Idiopathic pulmonary fibrosis (IPF) is associated with several hallmarks of aging including telomere shortening, which can result from germline mutations in telomere related genes (TRGs). Here, we assessed the length and stability of telomeres as well as the integrity of chromosomes in primary lung fibroblasts from 13 IPF patients (including seven patients with pathogenic variants in TRGs) and seven controls. Automatized high-throughput detection of telomeric FISH signals highlighted lower signal intensity in lung fibroblasts from IPF patients, suggesting a telomere length defect in these cells. The increased detection of telomere loss and terminal deletion in IPF cells, particularly in TRG-mutated cells (IPF-TRG), supports the notion that these cells have unstable telomeres. Furthermore, fibroblasts from IPF patients with TRGs mutations exhibited dicentric chromosomes and anaphase bridges. Collectively, our study indicates that fibroblasts from IPF patients exhibit telomere and chromosome instability that likely contribute to the physiopathology.

Folic acid deficiency increases sensitivity to DNA damage by glucose and methylglyoxal.

Type 2 diabetes (T2D) is associated with elevated frequencies of micronuclei (MNi) and other DNA damage biomarkers. Interestingly, individuals 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 individuals with T2D experiencing hyperglycemia and folic acid deficiency may be at higher risk of chromosomal instability.

Plasma Micronutrient Profile of Prostate Cancer Cases Is Altered Relative to Healthy Controls-Results of a Pilot Study in South Australia.

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 samples 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 ß-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, <0.0001, <0.0001 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), ß-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.

Association between Diet-related Behaviour and Risk of Colorectal Cancer: A Scoping Review.

Individual dietary patterns may be influenced by diet-related behaviours, which may eventually play a significant role in contributing to colorectal cancer risk. As nearly half of colorectal cancer cases can be prevented through diet and lifestyle modification, in this study, we aimed to present an overview of the literature on diet-related behaviour and its effect on colorectal cancer risk among adults. Articles published from 2011 until July 2021 were selected. Out of the 1,198 articles retrieved, 25 were analyzed. There were 16 case-control studies, and nine of them were cohort studies. As a finding, the instruments used in this review were food frequency questionnaires (n = 23), followed by a semi-structured interview (n = 1), and diet records (n = 1). We demonstrated that unhealthy diet-related behaviours are linked to an increased risk of colorectal cancer in adults and those food frequency questionnaires or food records are common instruments used to collect diet-related behaviours. This article imparts the research trends and directions of colorectal cancer risk factors and shows that diet-related behaviour varies and changes over time.