ABSTRACT
Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely distributed in maize and maized-based products, often occurring together. The implications of co-exposure to aflatoxin and fumonsin for human health are numerous, but a particular concern is the potential of FB1 to modulate AFB1 hepatotoxicity. This study evaluated the toxicity of these mycotoxins, alone or combined, in a human non-tumorigenic liver cell line, HHL-16 cells, and assessed the effects of AFB1 and FB1 on expression of genes involved in immune and growth factor pathways. The results demonstrated that in HHL-16 cells, both AFB1 and FB1 had dose-dependent and time-dependent toxicity, and the combination of them showed a synergistic toxicity in the cells. Moreover, AFB1 caused upregulation of IL6, CCL20, and BMP2, and downregulation of NDP. In combination of AFB1 with FB1, gene expression levels of IL6 and BMP2 were significantly higher compared to individual FB1 treatment, and had a tendency to be higher than individual AFB1 treatment. This study shows that FB1 may increase the hepatoxicity of AFB1 through increasing the inflammatory response and disrupting cell growth pathways.
Subject(s)
Aflatoxin B1 , Fumonisins , Hepatocytes , Fumonisins/toxicity , Humans , Hepatocytes/drug effects , Hepatocytes/metabolism , Aflatoxin B1/toxicity , Cell Line , Inflammation/genetics , Inflammation/chemically induced , Gene Expression Regulation/drug effects , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolismABSTRACT
BACKGROUND: Childhood malnutrition in all forms is a major public health issue worldwide. This review systematically examined the prevalence and determinants and identify the potential interventions and current gap in addressing malnutrition including undernutrition, overnutrition and micronutrient deficiencies (MNDs) in Vietnamese children aged 0-18 years old. METHODS: Embase, Scopus, PubMed, and Web of Science were systematically searched through June 2022 to identify relevant articles published within the past 25 years. Study selection and data extraction were performed by one reviewer and checked for accuracy by the other two reviewers in accordance with PRISMA guideline. Risk of publication bias was assessed using American Dietetic Association Quality Criteria Checklist. RESULTS: Seventy-two studies that met the inclusion criteria were included. Undernutrition has decreased over time but still 22.4%, 5.2% and 12.2% of children under 5 were stunted, wasted and underweight, respectively. Anaemia, iron, zinc, and vitamin D deficiencies were the more common forms of MNDs, the prevalence varied by age, region, and socioeconomic group. Population-based surveys reported that 11% and 48% of children aged 0-11 years old were iron and vitamin D deficient, respectively. Zinc deficiency affected almost one-quarter of the children and adolescents. Retinol deficiency was of less concern (< 20%). However, more evidence on MNDs prevalence is needed. Overweight and obesity is now on the rise, affecting one-third of school-aged children. The key determinants of undernutrition included living in rural areas, children with low birth weight, and poor socio-economic status, whereas living in urban and affluent areas, having an inactive lifestyle and being a boy were associated with increased risk of overweight and obesity. Nutrition specific intervention studies including supplementation and food fortification consistently showed improvements in anthropometric indices and micronutrient biomarkers. National nutrition-sensitive programmes also provided nutritional benefits for children's growth and eating behaviours, but there is a lack of data on childhood obesity. CONCLUSION: This finding highlights the need for effective double duty actions to simultaneously address different forms of childhood malnutrition in Vietnam. However, evidence on the potential intervention strategies, especially on MNDs and overnutrition are still limited to inform policy decision, thus future research is warranted.
Subject(s)
Malnutrition , Overnutrition , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Iron , Malnutrition/epidemiology , Malnutrition/complications , Micronutrients , Nutritional Status , Overnutrition/complications , Overnutrition/epidemiology , Overweight/epidemiology , Pediatric Obesity/epidemiology , Prevalence , Vietnam/epidemiology , ZincABSTRACT
Simultaneous dysregulation of multiple microRNAs (miRs) affects various pathological pathways related to cardiac failure. In addition to being potential cardiac disease-specific markers, miR-23b/27b/24-1 were reported to be responsible for conferring cardiac pathophysiological processes. In this study, we identified a conserved guanine-rich RNA motif within the miR-23b/27b/24-1 cluster that can form an RNA G-quadruplex (rG4) in vitro and in cells. Disruption of this intragenic rG4 significantly increased the production of all three miRs. Conversely, a G4-binding ligand tetrandrine (TET) stabilized the rG4 and suppressed miRs production in human and rodent cardiomyocytes. Our further study showed that the rG4 prevented Drosha-DGCR8 binding and processing of the pri-miR, suppressing the biogenesis of all three miRs. Moreover, CRISPR/Cas9-mediated G4 deletion in the rat genome aberrantly elevated all three miRs in the heart in vivo, leading to cardiac contractile dysfunction. Importantly, loss of the G4 resulted in reduced targets for the aforementioned miRs critical for normal heart function and defects in the L-type Ca2+ channel-ryanodine receptor (LCC-RyR) coupling in cardiomyocytes. Our results reveal a novel mechanism for G4-dependent regulation of miR biogenesis, which is essential for maintaining normal heart function.
Subject(s)
G-Quadruplexes , MicroRNAs/chemistry , MicroRNAs/metabolism , Myocardial Contraction/genetics , Myocytes, Cardiac/metabolism , Animals , Benzylisoquinolines/pharmacology , CRISPR-Cas Systems , Cells, Cultured , G-Quadruplexes/drug effects , Gene Expression Regulation , Myocardium/metabolism , Myocytes, Cardiac/physiology , RNA Processing, Post-Transcriptional , RNA-Binding Proteins/metabolism , Rats , Rats, Sprague-Dawley , Ribonuclease III/metabolism , Ryanodine Receptor Calcium Release Channel/metabolismABSTRACT
Genetic background interacts with dietary components to modulate nutritional health status. This study aimed to review the evidence for gene-diet interactions in all forms of malnutrition. A comprehensive systematic literature search was conducted through April 2021 to identify observational and intervention studies reporting the effects of gene-diet interactions in over-nutrition, under-nutrition and micronutrient status. Risk of publication bias was assessed using the Quality Criteria Checklist and a tool specifically designed for gene-diet interaction research. 167 studies from 27 populations were included. The majority of studies investigated single nucleotide polymorphisms (SNPs) in overnutrition (n = 158). Diets rich in whole grains, vegetables, fruits and low in total and saturated fats, such as Mediterranean and DASH diets, showed promising effects for reducing obesity risk among individuals who had higher genetic risk scores for obesity, particularly the risk alleles carriers of FTO rs9939609, rs1121980 and rs1421085. Other SNPs in MC4R, PPARG and APOA5 genes were also commonly studied for interaction with diet on overnutrition though findings were inconclusive. Only limited data were found related to undernutrition (n = 1) and micronutrient status (n = 9). The findings on gene-diet interactions in this review highlight the importance of personalized nutrition, and more research on undernutrition and micronutrient status is warranted.
ABSTRACT
BACKGROUND: Previous evidence suggests that school garden-based programmes (SGBP) may be a promising yet cost-effective intervention to improve children's knowledge, attitudes and practices (KAP) on healthy eating. This review aimed to summarise and evaluate the evidence available on the impacts of SGBP in addressing diet and nutrition-related KAP among school-aged children. METHODS: Five databases including PubMed, Embase, Cochrane, Web of Science and Scopus were searched until February 2021. Randomised, non-randomised controlled and pre-post intervention studies investigating the impacts of SGBP on at least one of the outcomes of interest including diet and nutrition-related knowledge, attitudes towards fruits and vegetables (F&V), food diversity and dietary practice among school-aged children were included. Study selection and data extraction were performed by one reviewer and checked for accuracy by the other two reviewers in accordance with PRISMA guideline. Quality appraisal for studies included was assessed using American Dietetic Association Quality Criteria Checklist. RESULTS: A total of 10,836 records were identified, and 35 studies that met the inclusion and exclusion criteria were included. This includes 25,726 students from 341 schools and 8 nurseries from 12 countries. Intervention duration ranged from 6 weeks to 4 years with 18 studies involving a varied degree of parental participation. SGBP, which majorly includes school gardening activities, cooking lessons and nutrition education, demonstrated beneficial effects on children's nutritional knowledge, their attitudes and acceptability towards fruits and vegetables and children's dietary practices including the actual F&V consumption and dietary diversity. However, the impacts of SGBP on such outcomes were highly influenced by various social and environmental factors including the activities/components and duration of the intervention, parental involvement, sample size, and the age of children when interventions were first introduced. CONCLUSION: These findings suggest that SGBP may be effective in promoting children's nutritional knowledge, attitudes and acceptability towards vegetables, however, the impacts may vary by the type, the extent, and the length of the programmes, and other factors such as parent involvement. Future SGBP is suggested to implement using a combined multidisciplinary approach targeting the children, parents, and community to effectively promote healthy eating among the children and prevent childhood obesity.
Subject(s)
Gardening , Pediatric Obesity , Child , Diet , Gardens , Health Knowledge, Attitudes, Practice , Humans , Pediatric Obesity/prevention & control , Randomized Controlled Trials as Topic , VegetablesABSTRACT
RATIONALE: ßARs (ß-adrenergic receptors) are prototypical GPCRs (G protein-coupled receptors) that play a pivotal role in sympathetic regulation. In heart cells, ß1AR signaling mediates a global response, including both l-type Ca2+ channels in the sarcolemma/T tubules and RyRs (ryanodine receptors) in the SR (sarcoplasmic reticulum). In contrast, ß2AR mediates local signaling with little effect on the function of SR proteins. OBJECTIVE: To investigate the signaling relationship between ß1ARs and ß2ARs. METHOD AND RESULTS: Using whole-cell patch-clamp analyses combined with confocal Ca2+ imaging, we found that the activation of compartmentalized ß2AR signaling was able to convert the ß1AR signaling from global to local mode, preventing ß1ARs from phosphorylating RyRs that were only nanometers away from sarcolemma/T tubules. This offside compartmentalization was eliminated by selective inhibition of ß2AR, GRK2 (GPCR kinase-2), ßarr1 (ß-arrestin-1), and phosphodiesterase-4. A knockin rat model harboring mutations of the last 3 serine residues of the ß1AR C terminus, a component of the putative ßarr1 binding site and GRK2 phosphorylation site, eliminated the offside compartmentalization conferred by ß2AR activation. CONCLUSIONS: ß2AR stimulation compartmentalizes ß1AR signaling into nanoscale local domains in a phosphodiesterase-4-dependent manner by targeting the C terminus of ß1ARs. This finding reveals a fundamental negative feed-forward mechanism that serves to avoid the cytotoxicity of circulating catecholamine and to sharpen the transient ß1AR response of sympathetic excitation.
Subject(s)
Receptors, Adrenergic, beta-1/metabolism , Receptors, Adrenergic, beta-2/metabolism , Ryanodine Receptor Calcium Release Channel/metabolism , Adrenergic Agents/pharmacology , Animals , Cells, Cultured , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Male , Mutation , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Phosphorylation/drug effects , Rats , Rats, Transgenic , Receptors, Adrenergic, beta-1/chemistry , Receptors, Adrenergic, beta-1/genetics , Receptors, Adrenergic, beta-2/genetics , Sarcolemma/drug effects , Sarcolemma/metabolism , Sarcoplasmic Reticulum/drug effects , Sarcoplasmic Reticulum/metabolism , Signal Transduction/drug effectsABSTRACT
Background: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers' blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. Methods: Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population (n = 244), in relation to the child's dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. Results: Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. Conclusions: This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.
Subject(s)
Aflatoxin B1/adverse effects , DNA Methylation/drug effects , Environmental Exposure/adverse effects , Adverse Childhood Experiences , Aflatoxins/adverse effects , Aflatoxins/analysis , Aflatoxins/blood , Albumins/analysis , Child, Preschool , DNA/metabolism , DNA Methylation/genetics , Epigenesis, Genetic/genetics , Epigenomics/methods , Female , Gambia/epidemiology , Humans , Infant , Leukocytes/metabolism , MaleABSTRACT
Contamination of agricultural and food products by some fungi species that produce mycotoxins can result in unsafe food and feed. Mycotoxins have been demonstrated to have disease-causing activities, including carcinogenicity, immune toxicity, teratogenicity, neurotoxicity, nephrotoxicity, and hepatotoxicity. Most of mycotoxins are heat stable and cannot be easily destroyed by conventional thermal food processing or domestic cooking methods. Postharvest approaches to prevent growth of mycotoxin-producing fungi and detoxify mycotoxins from contaminated food are important topics in food safety research. Physical, chemical, and biological methods have been applied to prevent fungal growth or mycotoxin production, or to reduce mycotoxin content in the postharvest period and contribute toward mitigating against the effects of mycotoxins on human health. This literature review aims to evaluate postharvest approaches that have been applied to control both fungi growth and mycotoxin content in food and discuss their potential for upscaling to industrial scale.
Subject(s)
Decontamination/methods , Food Contamination/prevention & control , Fungi , Mycotoxins , Food Handling/methods , Food Microbiology , Food SafetyABSTRACT
There is a global concern regarding the occurrences of harmful algal blooms (HABs) and their effects on human health. Lake Victoria (LV) has been reported to face eutrophication challenges, resulting in an increase of bloom-forming cyanobacteria. This study is aimed at understanding the association of HABs and health risks at Ukerewe Island. A cross-sectional study conducted on 432 study subjects and water samples for cyanobacteria species identification were collected at LV shores. The results reveal that concentrations of cyanobacteria cells are beyond (WHO) acceptable limits; species of Microcystis aeruginosa range from 90,361.63 to 3,032.031.65 cells/mL and Anabaena spp. range from 13,310.00 to 4,814,702 cells/mL. Water usage indicates that 31% use lake water, 53% well water and 16% treated supplied pipe water. Vomiting and throat irritation was highly reported by lake water users as compared to wells and pipe water (P < 0.001). Gastrointestinal illness (GI) was significantly elevated among lake water users as compared to pipe and well water users (P < 0.001). Visible blooms in lake water were associated with GI, skin irritation and vomiting as compared to water without visible blooms (P < 0.001). The concentration of cyanobacteria blooms poses greater risks when water is used without treatment.
Subject(s)
Harmful Algal Bloom , Lakes/microbiology , Microcystis , Cross-Sectional Studies , Humans , TanzaniaABSTRACT
This study was conducted in rural Pakistan to assess the dose-response relationship between skin lesions and arsenic exposure and their variation by demographic characteristics. The study included 398 participants (66 participants with skin lesions and 332 without) residing in six previously unstudied villages exposed to ground water arsenic in the range of <1 to 3090µgL-1. The skin lesions identification process involved interview and physical examinations of participants followed by confirmation by a physician according to UNICEF criteria. Urinary inorganic arsenic (iAs), total arsenic (tAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analysed to determine methylation capacity, methylation efficiency and the dose-response relationship with skin lesions. Study participants with skin lesions were found to be exposed to arsenic >10µgL-1 with a daily arsenic intake of 3.23±3.75mgday-1 from household ground water sources for an exposure duration of 10-20years. The participants with skin lesions compared to those without skin lesions showed higher levels of urinary iAs (133.40±242.48 vs. 44.24±86.48µgg-1Cr), MMA (106.38±135.04 vs. 35.43±39.97µgg-1Cr), MMA% (15.26±6.31 vs.12.11±4.68) and lower levels of DMA% (66.99±13.59 vs. 73.39±10.44) and secondary methylation index (SMI) (0.81±0.11 vs. 0.86±0.07). Study participants carrying a lower methylation capacity characterized by higher MMA% (OR 5.06, 95% CI: 2.09-12.27), lower DMA% (OR 0.64, 95% CI: 0.33-1.26), primary methylation index (PMI) (OR 0.56, 95% CI: 0.28-1.12) and SMI (OR 0.43, 95% CI: 0.21-0.88) had a significantly higher risk of skin lesions compared to their corresponding references after adjusting for occupation categories. The findings confirmed that inefficient arsenic methylation capacity was significantly associated with increased skin lesion risks and the effect might be modified by labour intensive occupations.
Subject(s)
Arsenic/metabolism , Drinking Water/adverse effects , Environmental Exposure/adverse effects , Skin Diseases/chemically induced , Skin Diseases/metabolism , Water Pollutants, Chemical/metabolism , Adolescent , Adult , Arsenic/toxicity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pakistan/epidemiology , Risk Factors , Rural Population/trends , Skin Diseases/epidemiology , Water Pollutants, Chemical/toxicity , Young AdultABSTRACT
PURPOSE: To determine levels of urinary aflatoxin M1 (AFM1) in children and correlate the concentrations with previously reported aflatoxin albumin adduct (AF-alb) levels in these children. MATERIALS AND METHODS: Matched urine and blood samples were collected from 84 Tanzanian children aged 6-14 months old. From 31 children in one village (Kigwa), samples were collected at three time points six months apart. Samples were collected from 31 and 22 children from two different regions at the second time point only. Urinary AFM1 was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit with a modified protocol to improve sensitivity. AF-alb was measured using an established ELISA method. RESULTS: The relative ranking of the three villages for exposure to aflatoxin based on either AFM1 or AF-alb biomarker measurements was the same. In Kigwa village, both AFM1 and AF-alb levels were higher at six months post-harvest compared to baseline. However, at the next visit, the AFM1 levels dropped from a GM (interquartile range) of 71.0 (44.7, 112.6) at visit two to 49.3 (31.5, 77.3) pg/ml urine, whereas AF-alb levels increased from 47.3 (29.7, 75.2) to 52.7 (35.4, 78.3) pg/mg albumin between these two visits, reflecting the fact that AFM1 measures short-term exposure, whereas AF-alb measures longer term exposure. There was a correlation between AFB1 intake and AFM1 excretion (r= 0.442, p ≤ 0.001). CONCLUSIONS: Urinary AFM1 is a good biomarker for AFB1 exposure in Tanzanian children, reflecting geographical and temporal variations in exposure to this foodborne toxin.
Subject(s)
Aflatoxin M1/urine , Aflatoxins/urine , Biomarkers/urine , Food Contamination/analysis , Aflatoxin M1/blood , Aflatoxins/blood , Albumins , Biomarkers/blood , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Humans , Infant , Tanzania , Zea maysABSTRACT
Biomarker-based strategies to assess human exposure to mycotoxins have gained increased acceptance in recent years. In this study, an improved method based on UPLC-MS/MS following 96-well µElution solid-phase extraction was developed and validated for the sensitive and high-throughput determination of zearalenone (ZEN) and its five metabolites α-zearalenol (α-ZEL), ß-zearalenol (ß-ZEL), α-zearalanol (α-ZAL), ß-zearalanol (ß-ZAL), and zearalanone (ZAN) in human urine samples, using 13C-ZEN as an internal standard for accurate quantification. Two plates of samples (n = 192) could be processed within 2 h, and baseline separation of all the analytes was achieved in a total runtime of 6 min. The proposed method allowed ZEN and its metabolites to be sensitively determined in a high-throughput way for the first time, and with significantly improved efficiency and accuracy with respect to existing methods. The limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.02 to 0.06 ng mL-1 and from 0.05 to 0.2 ng mL-1, respectively. The recoveries for the spiked samples were from 87.9 to 100%, with relative standard deviations (RSDs) of less than 7%. 301 urine samples collected from healthy volunteers aged 0-84 years in China were analyzed with and without enzyme hydrolysis to determine total and free ZEN biomarkers, respectively. ZEN, ZAN, α-ZEL, and ß-ZEL were detected in 71.4% of the samples at levels of 0.02-3.7 ng mL-1 after enzyme hydrolysis. The estimated mean probable daily intake (PDI) was much lower than the tolerable daily intake (TDI). Adolescents had higher exposure than children, adults, and the elderly. Graphical abstract á .
Subject(s)
Chromatography, High Pressure Liquid/methods , Estrogens, Non-Steroidal/urine , Tandem Mass Spectrometry/methods , Zearalenone/urine , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Estrogens, Non-Steroidal/metabolism , Female , High-Throughput Screening Assays/methods , Humans , Infant , Limit of Detection , Male , Middle Aged , Solid Phase Extraction/methods , Young Adult , Zearalenone/metabolismABSTRACT
BACKGROUND: Exposure to aflatoxin, a mycotoxin produced by fungi that commonly contaminates cereal crops across sub-Saharan Africa, has been associated with impaired child growth. We investigated the impact of aflatoxin exposure on the growth of Gambian infants from birth to two years of age, and the impact on insulin-like growth factor (IGF)-axis proteins. METHODS: A subsample (N = 374) of infants from the Early Nutrition and Immune Development (ENID) trial (ISRCTN49285450) were included in this study. Aflatoxin-albumin adducts (AF-alb) were measured in blood collected from infants at 6, 12 and 18 months of age. IGF-1 and IGFBP-3 were measured in blood collected at 12 and 18 months. Anthropometric measurements taken at 6, 12, 18 and 24 months of age were converted to z-scores against the WHO reference. The relationship between aflatoxin exposure and growth was analysed using multi-level modelling. RESULTS: Inverse relationships were observed between lnAF-alb and length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores from 6 to 18 months of age (ß = - 0·04, P = 0·015; ß = - 0·05, P = 0.003; ß = - 0·06, P = 0·007; respectively). There was an inverse relationship between lnAF-alb at 6 months and change in WLZ between 6 and 12 months (ß = - 0·01; P = 0·013). LnAF-alb at 12 months was associated with changes in LAZ and infant length between 12 and 18 months of age (ß = - 0·01, P = 0·003; ß = - 0·003, P = 0·02; respectively). LnAF-alb at 6 months was associated with IGFBP-3 at 12 months (r = - 0·12; P = 0·043). CONCLUSIONS: This study found a small but significant effect of aflatoxin exposure on the growth of Gambian infants. This relationship is not apparently explained by aflatoxin induced changes in the IGF-axis.
Subject(s)
Aflatoxins/toxicity , Environmental Exposure/adverse effects , Growth Disorders/epidemiology , Rural Population , Aflatoxins/blood , Albumins , Child, Preschool , Female , Gambia/epidemiology , Growth Disorders/chemically induced , Humans , Infant , Infant, Newborn , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/analysis , Male , Prospective Studies , Rural Population/statistics & numerical dataABSTRACT
Child undernutrition, a form of malnutrition, is a major public health burden in developing countries. Supplementation interventions targeting the major micronutrient deficiencies have only reduced the burden of child undernutrition to a certain extent, indicating that there are other underlying determinants that need to be addressed. Aflatoxin exposure, which is also highly prevalent in developing countries, may be considered an aggravating factor for child undernutrition. Increasing evidence suggests that aflatoxin exposure can occur in any stage of life, including in utero through a trans-placental pathway and in early childhood (through contaminated weaning food and family food). Early life exposure to aflatoxin is associated with adverse effects on low birth weight, stunting, immune suppression, and the liver function damage. The mechanisms underlying impaired growth and aflatoxin exposure are still unclear but intestinal function damage, reduced immune function, and alteration in the insulin-like growth factor axis caused by the liver damage are the suggested hypotheses. Given the fact that both aflatoxin and child undernutrition are common in sub-Saharan Africa, effective interventions aimed at reducing undernutrition cannot be satisfactorily achieved until the interactive relationship between aflatoxin and child undernutrition is clearly understood, and an aflatoxin mitigation strategy takes effect in those vulnerable mothers and children.
Subject(s)
Aflatoxins/toxicity , Child Nutrition Disorders/etiology , Malnutrition/etiology , Child , Child Nutrition Disorders/epidemiology , Developing Countries , Humans , Malnutrition/epidemiologyABSTRACT
OBJECTIVE: Aflatoxin is known to cross the placental barrier and exposures in utero could influence genomic programming, foetal growth and development, resulting in long-term health effects. We aimed to determine aflatoxin exposure in Gambian women at two stages of pregnancy and during the rainy and dry seasons. METHODS: We examined aflatoxin exposure in pregnant Gambian women at early (<16 weeks) and later (16 weeks onward) stages of pregnancy and at different times of the year, during the rainy (June to October 2009) or dry (November to May 2010) season, using aflatoxin-albumin adducts (AF-alb). RESULTS: Mean AF-alb was higher during the dry season than in the rainy season, in both early and later pregnancy although the difference was strongest in later pregnancy. There was a modest increase in AF-alb in later than early pregnancy (geometric mean 41.8 vs. 34.5 pg/mg, P < 0.05), but this was restricted to the dry season when exposures were generally higher. CONCLUSIONS: The study confirmed that Gambian pregnant women were exposed to aflatoxin throughout the pregnancy, with higher levels in the dry season. There was some evidence in the dry season that women in later pregnancy had higher AF-alb levels than those in earlier pregnancy. Further research on the effects of exposure to this potent mutagen and carcinogen throughout pregnancy, including the epigenetic modification of foetal gene expression and impact on pre- and post-natal growth and development, are merited.
Subject(s)
Aflatoxins/metabolism , Maternal Exposure/statistics & numerical data , Poisons/metabolism , Pregnancy Trimesters/blood , Seasons , Adolescent , Adult , Aflatoxins/blood , Albumins , Analysis of Variance , Biomarkers/blood , Enzyme-Linked Immunosorbent Assay , Female , Fetal Development/drug effects , Food Contamination , Gambia/epidemiology , Gestational Age , Humans , Middle Aged , Pregnancy , Prenatal Exposure Delayed Effects , Statistics, Nonparametric , Young AdultABSTRACT
OBJECTIVES: The fungal metabolite aflatoxin is a common contaminant of foodstuffs, especially when stored in damp conditions. In humans, high levels can result in acute hepatic necrosis and death, while chronic exposure is carcinogenic. We conducted a pilot study nested within an existing population cohort (the General Population Cohort), to assess exposure to aflatoxin, among people living in rural south-western Uganda. METHODS: Sera from 100 adults and 96 children under 3 years of age (85 male, 111 female) were tested for aflatoxin-albumin adduct (AF-alb), using an ELISA assay. Socio-demographic and dietary data were obtained for all participants; HIV serostatus was available for 90 adults and liver function tests (LFTs) for 99. RESULTS: Every adult and all but four children had detectable AF-alb adduct, including five babies reported to be exclusively breastfed. Levels ranged from 0 to 237.7 pg/mg albumin and did not differ significantly between men and women, by age or by HIV serostatus; 25% had levels above 15.1 pg/mg albumin. There was evidence of heterogeneity between villages (P = 0.003); those closest to trading centres had higher levels. Adults who consumed more Matooke (bananas) had lower levels of AF-alb adduct (P = 0.02) than adults who did not, possibly because their diet contained fewer aflatoxin-contaminated foods such as posho (made from maize). Children who consumed soya, which is not grown locally, had levels of AF-alb adduct that were almost twice as high as those who did not eat soya (P = 0.04). CONCLUSIONS: Exposure to aflatoxin is ubiquitous among the rural Ugandans studied, with a significant number of people having relatively high levels. Sources of exposure need to be better understood to instigate practical and sustainable interventions.
Subject(s)
Aflatoxins/blood , Environmental Exposure/analysis , Environmental Monitoring/statistics & numerical data , Food Contamination/statistics & numerical data , Rural Population/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Albumins , Biomarkers/blood , Breast Feeding , Child, Preschool , Cohort Studies , Cross-Sectional Studies , Diet/methods , Diet/statistics & numerical data , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Infant , Infant, Newborn , Liver Function Tests/methods , Liver Function Tests/statistics & numerical data , Male , Middle Aged , Pilot Projects , Sex Distribution , Uganda , Young AdultABSTRACT
The association between aflatoxin intake from maize-based weaning food and aflatoxin albumin adducts (AF-alb) was investigated in 148 Tanzanian children aged between 12 and 22 months, at 2 visits 6 months apart. At the first visit (storage season) there was a significant correlation at the individual level between AF-alb (geometric mean 43.2 pg/mg albumin) and aflatoxin intake (geometric mean 81.7 ng/kg b.w./d) through maize-based weaning food (r = 0.51, p < 0.01). Overall, this correlation was r = 0.43 (p < 0.01). The AF-alb level in weaning-age children in Tanzania closely reflects aflatoxin intake from maize in weaning food. Exposure levels suggest children may be at risk from aflatoxin associated health effects.
Subject(s)
Aflatoxins/administration & dosage , Biomarkers/blood , Food Contamination/analysis , Aflatoxins/blood , Albumins , Eating , Female , Food Contamination/prevention & control , Humans , Infant , Linear Models , Male , Multivariate Analysis , Tanzania , Weaning , Zea maysABSTRACT
High-risk HPVs were detected in both breast cancer tissues and cervical cells from 56 breast cancer patients. The results suggested that HPV infection did not coexist in breast and cervical tissues. HPV infection of the breast cancer tissue is more likely to happen in patients without cervical infection.
Subject(s)
Breast Neoplasms/virology , Cervix Uteri/virology , Papillomaviridae/isolation & purification , Female , HumansABSTRACT
Background: The global burden of liver cirrhosis is increasing, with 2.1 million incident cases and nearly 1.5 million deaths in 2019. Despite the enormous progress in our understanding of the etiology of liver cirrhosis, significant cases of the disease have been reported in Eastern Ethiopia due to unidentified causes. Hence, this study aimed to identify predictors of liver cirrhosis of unknown etiology in Eastern Ethiopia. Methods: A score of 7 out of 11 possible points on the ultrasound-based cirrhosis scale was used as a diagnostic criterion to include 127 liver cirrhosis patients. The study participants' demographic, dietary, lifestyle, and clinical data were gathered using a structured questionnaire and standardized reporting forms. The associations between the outcome (known and unknown etiology) and independent variables were modeled using binary logistic regression analysis. Results: The etiology of liver cirrhosis was known in only 23% of patients and attributed to hepatitis B virus (21%), hepatitis C virus (0.8%), and alcohol abuse (0.8%). Sorghum consumption as a staple food (adjusted odds ratio (AOR) =3.8; 95% CI: 1.2, 12.5), splenomegaly (AOR = 4.0; 95% CI: 1.1, 14.4), and a family history of liver disease (AOR = 0.24; 95% CI: 0.06, 0.91) were significantly associated with liver cirrhosis of unknown etiology. Conclusion: Sorghum consumption was found to be the determinant factor of liver cirrhosis of unknown etiology, suggesting it as a possible source of exposure to aflatoxin B1.
ABSTRACT
INTRODUCTION: Traditionally associated with undernutrition, increasing evidence suggests micronutrient deficiencies can coexist with overnutrition. Therefore, this work aimed to systematically review the associations between iron, zinc and vitamin A (VA) status and weight status (both underweight and overweight) in children and young people. METHODS: Ovid Medline, Ovid Embase, Scopus and Cochrane databases were systematically searched for observational studies assessing micronutrient status (blood, serum or plasma levels of iron, zinc or VA biomarkers) and weight status (body mass index or other anthropometric measurement) in humans under 25 years of any ethnicity and gender. Risk of bias assessment was conducted using the American Dietetic Association Quality Criteria Checklist. Where possible, random effects restricted maximum likelihood meta-analyses were performed. RESULTS: After screening, 83 observational studies involving 190 443 participants from 44 countries were identified, with many studies having reported on more than one micronutrient and/or weight status indicator. Iron was the most investigated micronutrient, with 46, 28 and 27 studies reporting data for iron, zinc and VA status, respectively. Synthesising 16 records of OR from seven eligible studies, overnutrition (overweight and obesity) increased odds of iron deficiency (ID) (OR (95% CI): 1.51 (1.20 to 1.82), p<0.0001, I2=40.7%). Odds appeared to be higher for children living with obesity (1.88 (1.33 to 2.43), p<0.0001, I2=20.6%) in comparison to those with overweight (1.31 (0.98 to 1.64), p<0.0001, I2=40.5%), although between group differences were not significant (p=0.08). CONCLUSIONS: Overnutrition is associated with increased risk of ID, but not zinc or VA deficiencies, with an inverted U-shaped relationship observed between iron status and bodyweight. Our results highlight significant heterogeneity in the reporting of micronutrient biomarkers and how deficiencies were defined. Inflammation status was rarely adequately accounted for, and the burden of ID may well be under-recognised, particularly in children and young people living with overnutrition. PROSPERO REGISTRATION NUMBER: CRD42020221523.