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Biological ageing refers to the gradual decrease in physiological functions, resulting in immune senescence, cellular damage and apoptosis. Telomere length is a biomarker of biological ageing. Limited studies have associated shorter telomere length with HIV and parasite single infections, with no studies reporting the association of HIV and parasite co-infection with telomere length. The study aimed to investigate whether telomere length shortening is accelerated in a South African population co-infected with HIV and helminths compared to participants singly infected with either HIV or helminths. Additionally, telomere length data were compared with participants’ biochemical and full blood count parameters. A total of 200 participants were in groups of uninfected control, HIV single infection, helminth single infection and HIV and helminth co-infection groups. Relative telomere length (RTL) was determined using Real-Time PCR and associated with biochemical and full blood count parameters using multivariate regression analysis models that were adjusted for confounders. The uninfected control group was used as a reference group. The uninfected control group had the highest mean RTL (1.21 ± 0.53) while the HIV-infected (0.96 ± 0.42) and co-infected (0.93 ± 0.41) groups had similar RTLs, and lastly, the helminth-infected group (0.83 ± 0.33) had the lowest RTL (p = 0.0002). When compared to the uninfected control group, a significant association between RTL and biochemical parameters, including blood iron (β = −0.48), ferritin (β = −0.48), transferrin saturation (β = −0.57), transferrin (β = −0.57), phosphate (β = −0.47), vitamin A (β = −0.49) and C-reactive protein (β = −0.52) were noted in the co-infected group (p < 0.05). In addition, a significant association between RTL and full blood count, including (β = −0.47), haematocrit (β = −0.46), mean corpuscular volume (β = −0.47), lymphocytes (β = −0.45), mean corpuscular haemoglobin concentration (β = −0.45), red cell distribution width (β = −0.47), monocytes (β = −0.45), eosinophils (β = −0.45), basophils (β = −0.44) and transferrin saturation (β = −0.57) were also noted in the co-infected group (p < 0.05). Accelerated biological ageing, as indicated by telomere length shortening, is associated with HIV and helminth co-infections.

HIV and parasite infections accelerate biological aging, resulting in immune senescence, apoptosis and cellular damage. Telomere length is considered to be one of the most effective biomarkers of biological aging. HIV and parasite infection have been reported to shorten telomere length in the host. This systematic review aimed to highlight work that explored the influence of HIV and parasite single infections and coinfection on telomere length. Using specific keywords related to the topic of interest, an electronic search of several online databases (Google Scholar, Web of Science, Scopus, Science Direct and PubMed) was conducted to extract eligible articles. The association between HIV infection or parasite infection and telomere length and the association between HIV and parasite coinfection and telomere length were assessed independently. The studies reported were mostly conducted in the European countries. Of the 42 eligible research articles reviewed, HIV and parasite single infections were independently associated with telomere length shortening. Some studies found no association between antiretroviral therapy (ART) and telomere length shortening, while others found an association between ART and telomere length shortening. No studies reported on the association between HIV and parasite coinfection and telomere length. HIV and parasite infections independently accelerate telomere length shortening and biological aging. It is possible that coinfection with HIV and parasites may further accelerate telomere length shortening; however, this is a neglected field of research with no reported studies to date.

IntroductionThe most common soil-transmitted helminthic infection is caused by Ascaris lumbricoides (A. lumbricoides). Approximately 4 billion people are at risk of infection globally. The World Health Organisation recommends the administration of benzimidazole- containing deworming drugs (Albendazole and Mebendazole) to all susceptible populations. Due to this high drug pressure, these parasites may develop resistance to current benzimidazole drugs. The β-tubulin gene family is the target gene for benzimidazole deworming drugs. This systematic review aimed to highlight work that explored the genetic mutations in the β-tubulin gene family of A. lumbricoides that are associated with potential benzimidazole resistance.MethodsAn electronic search of several online databases was used to extract eligible articles using specific keywords related to the topic of interest.ResultsThe majority of ascariasis infections occur in the subtropical and tropical regions of sub-Saharan Africa, the Americas and East Asia, although not enough studies were done to extensively cover this geographical range. In the β-tubulin gene family of A. lumbricoides the mutations at codons F200Y (TTC/Phenylalanine to TAC/Tyrosine), E198A (GAG, GAA/Glutamic acid to GCG, GCA/Alanine) and F167Y (TTC, TTT/Phenylalanine to TAC, TAT/Tyrosine) were associated with potential benzimidazole resistance.DiscussionResistant mutations were found in A. lumbricoides samples at codon F167Y from Haiti, Kenya and Panama. The first evidence of the mutation at codon F200Y was observed in Brazil. The codon E198A mutation was the least prevalent and most undetected.ConclusionThere is a serious shortage of studies investigating the prevalence of β-tubulin gene family mutations in A. lumbricoides populations from endemic areas; this is a serious concern as resistance will negatively impact current mass drug administration programmes.

The Middle East respiratory syndrome Coronavirus (MERS-CoV) is one of the human coronaviruses that causes severe respiratory infection. Bats are considered to be the natural reservoir, where dromedary camels (DC) are the intermediate hosts of the virus. The current study was undertaken to provide an update on global distribution of the virus in camels, and to investigate the pooled prevalence and camel-associated risk factors of infection. After registration of the review protocol in the Open Science Framework, data searches were conducted on 18 April 2023 through Embase, PubMed, Scopus, and Web of Science. Considering only natural MERS-CoV infection in camels, 94 articles were selected for data curation through blind screening by two authors. Meta-analysis was conducted to estimate the pooled prevalence and to evaluate camel-associated risk factors. Finally, the results were presented in forest plots. The reviewed articles tested 34 countries, of which camels of 24 countries were seropositive and in 15 countries they were positive by molecular method. Viral RNA was detected in DC. Non-DC, such as bactrian camels, alpaca, llama, and hybrid camels were only seropositive. The global estimated pooled seroprevalence and viral RNA prevalence in DC were 77.53% and 23.63%, respectively, with the highest prevalence in West Asia (86.04% and 32.37% respectively). In addition, 41.08% of non-DC were seropositive. The estimated pooled prevalence of MERS-CoV RNA significantly varied by sample types with the highest in oral (45.01%) and lowest in rectal (8.42%) samples; the estimated pooled prevalence in nasal (23.10%) and milk (21.21%) samples were comparable. The estimated pooled seroprevalence in 5 years age groups were 56.32%, 75.31%, and 86.31%, respectively, while viral RNA prevalence was 33.40%, 15.87%, and 13.74%, respectively. Seroprevalence and viral RNA prevalence were generally higher in females (75.28% and 19.70%, respectively) than in males (69.53% and 18.99%, respectively). Local camels had lower estimated pooled seroprevalence (63.34%) and viral RNA prevalence (17.78%) than those of imported camels (89.17% and 29.41%, respectively). The estimated pooled seroprevalence was higher in camels of free-herds (71.70%) than confined herds (47.77%). Furthermore, estimated pooled seroprevalence was higher in samples from livestock markets, followed by abattoirs, quarantine, and farms but viral RNA prevalence was the highest in samples from abattoirs, followed by livestock markets, quarantine, and farms. Risk factors, such as sample type, young age, female sex, imported camels, and camel management must be considered to control and prevent the spread and emergence of MERS-CoV.

Abstract Diagnostic testing for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains a challenge around the world, especially in low-middle-income countries (LMICs) with poor socio-economic backgrounds. From the beginning of the pandemic in December 2019 to August 2021, a total of approximately 3.4 billion tests were performed globally. The majority of these tests were restricted to high income countries. Reagents for diagnostic testing became a premium, LMICs either cannot afford or find manufacturers unwilling to supply them with expensive analytical reagents and equipment. From March to December 2020 obtaining testing kits for SARS-CoV-2 testing was a challenge. As the number of SARS-CoV-2 infection cases increases globally, large-scale testing still remains a challenge in LMICs. The aim of this review paper is to compare the total number and frequencies of SARS-CoV-2 testing in LMICs and high-income countries (HICs) using publicly available data from Worldometer COVID-19, as well as discussing possible interventions and cost-effective measures to increase testing capability in LMICs. In summary, HICs conducted more SARS-CoV-2 testing (USA: 192%, Australia: 146%, Switzerland: 124% and Canada: 113%) compared to middle-income countries (MICs) (Vietnam: 43%, South Africa: 29%, Brazil: 27% and Venezuela: 12%) and low-income countries (LICs) (Bangladesh: 6%, Uganda: 4% and Nigeria: 1%). Some of the cost-effective solutions to counteract the aforementioned problems includes using saliva instead of oropharyngeal or nasopharyngeal swabs, sample pooling, and testing high-priority groups to increase the number of mass testing in LMICs.

Background: Helminth and HIV infections are endemic among poor populations. Studies investigating the socio-demographic and economic risk factors associated with dual HIV and helminth coinfection are scarce. Objectives: This study aimed to describe risk factors associated with HIV and helminth coinfections among peri-urban South African adults residing in poorly developed areas with high poverty levels, lack of sanitation and a clean water supply. Method: Adult participants (n = 414) were recruited from clinics in the south of Durban, KwaZulu-Natal, South Africa. Participants’ demographic, socio-economic, sanitation and household information, anthropometric measurements and HIV status were collected. Stool samples were donated for coproscopy to detect helminths using the Kato-Katz and Mini Parasep techniques. Blood was collected to confirm participants’ HIV status and to determine Ascaris lumbricoides-specific immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) levels to improve microscopy sensitivity. Results: Overall coinfection was 15%, and single helminth and HIV prevalence were 33% and 52%, respectively. Ascaris lumbricoides was predominant (18%). Univariate analysis of variance (ANOVA) showed that coinfection was 11.9% and 19.8%, respectively, among the 18–34 years and 35–59 years age groups (p = 0.0006), 16.4% and 19.9%, respectively, for the no income and R1000.00 groups (p = 0.0358) and 22.8% and 17.1%, respectively, for the pit or public toilets and toilets not connected to sewage groups (p = 0.0007). Conclusion: Findings suggest that the dual infection with HIV and helminth infections among adults residing in under-resourced areas with poor sanitary conditions is frequent. Older age, poor toilet use and low income are associated with coinfection. More attention is required to break the cycle of coinfections and possible disease interactions. Contribution: The study highlights the importance of determining and treating helminth infections among adult population during HIV and helminth coinfection and the influence of poor sanitation and socioeconomic status on disease transmission.

Background: Intestinal helminth parasites are potent stimulators of T helper type 2 (Th2) and regulatory Th3 anti-inflammatory immune responses, while human immunodeficiency virus (HIV) infections are activators of predominantly T helper type 1(Th1) pro-inflammatory responses. Studies investigating the immune profiles of individuals coinfected with helminths and HIV are scarce. Although it is well known that helminths cause a type 2 immune response during the chronic stage of infection that is characterised by Th2 cell differentiation, eosinophil recruitment, and alternative macrophage activation, the immune mechanisms that regulate tissue damage at the time of parasite invasion are poorly understood. Aim: The aim of the study was to determine the cytokine gene expression profiles during HIV and helminth coinfection in underprivileged South African adults living in a peri-urban area with poor sanitary conditions and a lack of clean water supply. Method: Study participants (n = 164) were subdivided into uninfected controls, HIV-infected, helminth-infected, and HIV and helminth-coinfected groups. The Kato–Katz and Mini Parasep techniques and Ascaris lumbricoides-specific Immunoglobulin E (IgE) and Immunoglobulin G4 (IgG4) levels were used to detect helminth infections. Participants’ HIV status was determined using two HIV1/2 antibody test kits. RNA was isolated from white blood cells for cytokine (Th1-, Th2-, and Th17-related) and transcription factor gene expression profiling using real-time PCR. Results: Multivariate regression data were adjusted for age, gender, BMI, antiretroviral treatment (ART), and nutritional supplement intake. The HIV and helminth-coinfected group had significantly higher tumour necrosis factor alpha (TNF-α) (adjusted β = 0.53, p = 0.036), interleukin 2 (IL-2) (adjusted β = 6.48, p = 0.008), and interleukin 17 (IL-17) (adjusted β = 1.16, p = 0.001) levels and lower GATA binding protein 3 (GATA3) levels (adjusted β = −0.77, p = 0.018) compared to the uninfected controls. No statistical significance was noted for Th2-related cytokines. Conclusion: The coinfected group had higher proinflammatory Th1- and Th17-related cytokine gene expression profiles compared to the uninfected controls. The findings suggest that pro-inflammatory responses are elevated during coinfection, which supports the hypothesis that helminths have a deleterious effect on HIV immune responses.

Background: Helminth infections are widespread in tuberculosis-endemic areas and are associated with an increased risk of active tuberculosis. In contrast to the pro-inflammatory Th1 responses elicited by Mycobacterium tuberculosis (Mtb) infection, helminth infections induce anti-inflammatory Th2/Treg responses. A robust Th2 response has been linked to reduced tuberculosis protection. Several studies show the effect of helminth infection on BCG vaccination and TB, but the mechanisms remain unclear. Aim: To determine the cytokine response profiles during tuberculosis and intestinal helminth coinfection. Methods: For the in vitro study, lymphocytic Jurkat and monocytic THP-1 cell lines were stimulated with Mtb H37Rv and Ascaris lumbricoides (A. lumbricoides) excretory-secretory protein extracts for 24 and 48 h. The pilot human ex vivo study consisted of participants infected with Mtb, helminths, or coinfected with both Mtb and helminths. Thereafter, the gene transcription levels of IFN-γ, TNF-α, granzyme B, perforin, IL-2, IL-17, NFATC2, Eomesodermin, IL-4, IL-5, IL-10, TGF-β and FoxP3 in the unstimulated/uninfected controls, singly stimulated/infected and costimulated/coinfected groups were determined using RT-qPCR. Results: TB-stimulated Jurkat cells had significantly higher levels of IFN-γ, TNF-α, granzyme B, and perforin compared to unstimulated controls, LPS- and A. lumbricoides-stimulated cells, and A. lumbricoides plus TB-costimulated cells (p < 0.0001). IL-2, IL-17, Eomes, and NFATC2 levels were also higher in TB-stimulated Jurkat cells (p < 0.0001). Jurkat and THP-1 cells singly stimulated with TB had lower IL-5 and IL-4 levels compared to those singly stimulated with A. lumbricoides and those costimulated with TB plus A. lumbricoides (p < 0.0001). A. lumbricoides-singly stimulated cells had higher IL-4 levels compared to TB plus A. lumbricoides-costimulated Jurkat and THP-1 cells (p < 0.0001). TGF-β levels were also lower in TB-singly stimulated cells compared to TB plus A. lumbricoides-costimulated cells (p < 0.0001). IL-10 levels were lower in TB-stimulated Jurkat and THP-1 cells compared to TB plus A. lumbricoides-costimulated cells (p < 0.0001). Similar results were noted for the human ex vivo study, albeit with a smaller sample size. Conclusions: Data suggest that helminths induce a predominant Th2/Treg response which may downregulate critical Th1 responses that are crucial for tuberculosis protection.

Abstract Background Low birthweight (LBW) and preterm birth (PB) remain the leading cause of morbidity and mortality in neonates worldwide. The aim of this study was to identify maternal demographic and antenatal factors associated with PB and LBW among low socio-economic communities. Methods Pregnant women (n = 1099) were recruited in the first trimester into the Mother and Child in the Environment (MACE) birth cohort in Durban, South Africa. Maternal factors such as demographic information, health status, residential area, occupational, personal and environmental smoking and biomass fuel use were obtained through standardised interviews, while clinical status was obtained in each trimester and antenatal information on HIV status and treatment, syphilis and conditions such as pregnancy induced hypertension, diabetes etc. was extracted from the antenatal assessments. Key outcomes of interest were preterm birth and low birthweight. The latter data was obtained from the clinical assessments performed by midwives at delivery. Logistic regression models identified factors associated with PB and LBW. Results Of the 760 live births, 16.4 and 13.5% were preterm and LBW, respectively. Mothers who delivered by caesarean section had an increased odds of having LBW babies (Adjusted odds ratio (AOR): 1.7; 95% CI: 1.1–2.7) and PB (AOR: 1.7, 95% CI: 1.1–2.7) versus normal vaginal deliveries. Mothers > 30 years (AOR: 1.8, 95% CI: 1.1–2.9) and current smokers (AOR: 2.7, 95% CI: 1.3–5.8) had an increased odds of having PB babies. Compared to younger mothers and non-smokers respectively. An effect of PB and LBW was seen among mothers with high BMI (25.0–29.9 kg/m2) (PB: AOR: 0.5, 95% CI: 0.3–0.9 and LBW: AOR: 0.5, 0.5, CI: 0.3–0.8), and obese BMI (> 30 kg/m2) (PB: AOR: 0.5, 95% CI: 0.3–0.9 and LBW: AOR: 0.4, CI: 0.2–0.7). Maternal HIV (PB AOR: 1.4 and LBW AOR: 1.2) and history of sexually transmitted infections (PB AOR: 2.7 and LBW AOR: 4.2) were not statistically significant. Conclusion Maternal age, cigarette smoking and caesarean delivery were associated with LBW and PB. Findings highlight the need of maternal health interventions to improve new-born health outcomes.

Abstract Environmental factors such as pollution, pesticide exposure and socio-demographic location have been implicated as a pressure capable of altering genetic make-up. Altered genetic sequence of genes encoding enzymes may result in single nucleotide polymorphism (SNP). Of peculiar interest is the genetic variance on the paraoxonase-1 gene induced by pre- and postnatal exposure to pesticides. SNP have been reported on the paraoxonase-1 gene and post-xenobiotic exposure and are presumed to alter gene sequence and ultimately enzymatic activity. The altered enzymatic activity may facilitate neurodevelopment disorders. Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are among the neurodevelopment disorders of which prevalence is concurrently associated with increasing environmental xenobiotic exposure. The variance on xenobiotic metabolising genes is associated with altered neurodevelopment outcome and ultimately altered neurobehavioural outcome. Prime interests of this systematic review were to establish an understanding of the sequences on the paraoxonase-1 gene associated with adverse neurobehavioural outcome. An in-depth literature search was conducted using the term combination “pesticide exposure, pre- and postnatal exposure, organophosphates/organophosphorus, single nucleotide polymorphism, paraoxonase-1 (PON-1), neurodevelopment/neurobehavioural outcome in child/infant”. Articles published from the year 2000 to 2018 were considered for review. The result showed that variance on the PON1-108 and 192 alleles could be implicated in the development of altered neurobehavioural outcomes.

Female sex, high estrogen levels, aging, obesity, and dyslipidemia are some of the risk factors associated with gallstone formation. HIV-infected patients on combination antiretroviral therapy (cART) are more prone to hypercholesterolemia. Bile acid synthesis is initiated by cholesterol 7-alpha hydroxylase (CYP7A1) and regulated by hepatocyte nuclear factors (HNF1α, HNF4α, and LXRb). The aim of this study was to evaluate the expression of HNF1α, HNF4α, LXRb, and miRNAs (HNF4α specific: miR-194-5p and miR-122*_1) that regulate CYP7A1 transcription in HIV-infected Black South African women on cART and presenting with gallstones relative to HIV-negative patients with gallstone disease. Females (n = 96) presenting with gallstone disease were stratified based on HIV status. The gene expression of CYP7A1, HNF1α, HNF4α, LXRb, miR-194-5p, and miR-122*_1 was determined using RT-qPCR. Messenger RNA and miRNA levels were reported as fold change expressed as 2−ΔΔCt (RQ min; RQ max). Fold changes >2 and p = 0.0267) and displayed higher low-density lipoprotein cholesterol (LDL-c) (p = 0.0419), CYP7A1 [2.078-fold (RQ min: 1.278; RQ max: 3.381)], LXRb [2.595-fold (RQ min: 2.001; RQ max: 3.000)], and HNF1α [3.428 (RQ min: 1.806; RQ max: 6.507] levels. HNF4α [0.642-fold (RQ min: 0.266; RQ max: 1.55)], miR-194-5p [0.527-fold (RQ min: 0.37; RQ max: 0.752)], and miR-122*_1 [0.595-fold (RQ min: 0.332; RQ max: 1.066)] levels were lower in HIV-infected females. In conclusion, HIV-infected women with gallstone disease displayed higher LDL-c levels and increased bile acid synthesis, which was evidenced by the elevated expression of CYP7A1, HNF1α, and LXRb. This could have been further influenced by cART and aging.

Soil-transmitted helminths infect billions of people globally, particularly those residing in low- and middle-income regions with poor environmental sanitation and high levels of air and water pollution. Helminths display potent immunomodulatory activity by activating T helper type 2 (Th2) anti-inflammatory and Th3 regulatory immune responses. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes Coronavirus disease 2019 (COVID-19), can exacerbate Th1/Th17 pro-inflammatory cytokine production in humans, leading to a cytokine storm. Air pollutants (particulate matter, oxygen radicals, hydrocarbons and volatile organic compounds) and water pollutants (metals and organic chemicals) can also intensify Th1/Th17 immune response and could exacerbate SARS-CoV-2 related respiratory distress and failure. The present review focused on the epidemiology of SARS-CoV-2, helminths and fine particulate matter 2.5 µm or less in diameter (PM2.5) air pollution exposure in helminth endemic regions, the possible immunomodulatory activity of helminths against SARS-CoV-2 hyper-inflammatory immune response, and whether air and water pollutants can further exacerbate SARS-CoV-2 related cytokine storm and in the process hinder helminths immunomodulatory functionality. Helminth Th2/Th3 immune response is associated with reductions in lung inflammation and damage, and decreased expression levels of angiotensin-converting enzyme 2 (ACE2) receptors (SARS-CoV-2 uses the ACE2 receptors to infect cells and associated with extensive lung damage). However, air pollutants are associated with overexpression of ACE2 receptors in the epithelial cell surface of the respiratory tract and exhaustion of Th2 immune response. Helminth-induced immunosuppression activity reduces vaccination efficacy, and diminishes vital Th1 cytokine production immune responses that are crucial for combating early stage infections. This could be reversed by continuous air pollution exposure which is known to intensify Th1 pro-inflammatory cytokine production to a point where the immunosuppressive activities of helminths could be hindered. Again, suppressed activities of helminths can also be disadvantageous against SARS-CoV-2 inflammatory response. This “yin and yang” approach seems complex and requires more understanding. Further studies are warranted in a cohort of SARS-CoV-2 infected individuals residing in helminths and air pollution endemic regions to offer more insights, and to impact mass periodic deworming programmes and environmental health policies.

Helminth infections are among the neglected tropical diseases affecting billions of people globally, predominantly in developing countries. Helminths’ effects are augmented by coincident tuberculosis disease, which infects a third of the world’s population. The role of helminth infections on the pathogenesis and pathology of active tuberculosis (T.B.) remains controversial. Parasite-induced suppression of the efficacy of Bacille Calmette-Guerin (BCG) has been widely reported in helminth-endemic areas worldwide. T.B. immune response is predominantly proinflammatory T-helper type 1 (Th1)-dependent. On the other hand, helminth infections induce an opposing anti-inflammatory Th2 and Th3 immune-regulatory response. This review summarizes the literature focusing on host immune response profiles during single-helminth, T.B. and dual infections. It also aims to necessitate investigations into the complexity of immunity in helminth/T.B. coinfected patients since the research data are limited and contradictory. Helminths overlap geographically with T.B., particularly in Sub-Saharan Africa. Each disease elicits a response which may skew the immune responses. However, these effects are helminth species-dependent, where some parasites have no impact on the immune responses to concurrent T.B. The implications for the complex immunological interactions that occur during coinfection are highlighted to inform government treatment policies and encourage the development of high-efficacy T.B. vaccines in areas where helminths are prevalent.

Fusaric acid (FA), a mycotoxin contaminant of maize, displays toxicity in plants and animals; however, its epigenetic mechanism is unknown. DNA methylation, an epigenetic modification that regulates gene expression, is mediated by DNA methyltransferases (DNMTs; DNMT1, DNMT3A, and DNMT3B) and demethylases (MBD2). The expression of DNMTs and demethylases are regulated by promoter methylation, microRNAs (miR-29b) and post-translational modifications (ubiquitination). Alterations in these DNA methylation modifying enzymes affect DNA methylation patterns and offer novel mechanisms of FA toxicity. We determined the effect of FA on global DNA methylation as well as a mechanism of FA-induced changes in DNA methylation by transcriptional (promoter methylation), post-transcriptional (miR-29b) and post-translational (ubiquitination) regulation of DNMTs and MBD2 in the human hepatocellular carcinoma (HepG2) cell line. FA induced global DNA hypomethylation (p < 0.0001) in HepG2 cells. FA decreased the mRNA and protein expression of DNMT1 (p < 0.0001), DNMT3A (p < 0.0001), and DNMT3B (p < 0.0001) by upregulating miR-29b (p < 0.0001) and inducing promoter hypermethylation of DNMT1 (p < 0.0001) and DNMT3B (p < 0.0001). FA decreased the ubiquitination of DNMT1 (p = 0.0753), DNMT3A (p = 0.0008), and DNMT3B (p < 0.0001) by decreasing UHRF1 (p < 0.0001) and USP7 (p < 0.0001). FA also induced MBD2 promoter hypomethylation (p < 0.0001) and increased MBD2 expression (p < 0.0001). Together these results indicate that FA induces global DNA hypomethylation by altering DNMT promoter methylation, upregulating miR-29b, and increasing MBD2 in HepG2 cells.

Abstract Background Psoriasis and psoriatic arthritis (PsA) are inflammatory associated autoimmune disorders. MicroRNA (miR)-146a plays a crucial role in regulating inflammation. A single nucleotide polymorphism in the miR-146a gene (rs2910164), aberrantly alters its gene expression and linked with the pathogenesis of several disorders, including psoriasis and PsA. In South Africa, psoriasis and PsA are extremely rare in the indigenous African population and most common in both the Indian and Caucasian population. The aim of this study was to investigate whether the miR-146a rs2910164 contributes towards psoriasis and PsA development in South African Indian and Caucasian patients. Methods South African Indian (n = 84) and Caucasian (n = 32) PsA patients (total n = 116) and healthy control subjects (Indian: n = 62 and Caucasian: n = 38; total n = 100) were recruited in the study. DNA was extracted from whole blood taken from all subjects, and genotyped for the miR-146a rs2910164 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data for laboratory parameters were obtained from pathology reports. The consulting rheumatologist collected all other clinical data. Results Unstratified data (Caucasians + Indians) : A significant decrease in C-reactive protein (CRP) levels in PsA patients was observed (CRP monitored at inclusion vs. after 6 months of treatment) (18.95 ± 2.81 mg/L vs. 9.68 ± 1.32 mg/L, p = 0.0011). The miR-146a rs2910164 variant C-allele frequency in PsA patients was significantly higher vs. healthy controls (35.78% vs. 26% respectively, p = 0.0295, OR = 1.59 95% CI 1.05–2.40). Stratified data (Indians) : The variant C-allele frequency in Indian PsA patients was significantly higher vs. healthy Indian controls (35.71% vs. 22.58%, p = 0.0200, OR = 1.91 95% CI 1.13–3.22). Stratified data (Caucasians) : The variant C-allele frequency distribution between Caucasian PsA patients and healthy Caucasian controls was similar. Conclusion The rs2910164 variant C-allele may play a role in the progression of PsA in the South African Indian population. The main limitation in this study was the small sample size in the case-control cohorts, with a low overall statistical power (post-hoc power analysis = 19%).

The Developmental Origins of Health and Disease (DOHaD) concept postulates that in utero exposures influence fetal programming and health in later life. Throughout pregnancy, the placenta plays a central role in fetal programming; it regulates the in utero environment and acts as a gatekeeper for nutrient and waste exchange between the mother and the fetus. Maternal exposure to air pollution, including heavy metals, can reach the placenta, where they alter DNA methylation patterns, leading to changes in placental function and fetal reprogramming. This review explores the current knowledge on placental DNA methylation changes associated with prenatal air pollution (including heavy metals) exposure and highlights its effects on fetal development and disease susceptibility. Prenatal exposure to air pollution and heavy metals was associated with altered placental DNA methylation at the global and promoter regions of genes involved in biological processes such as energy metabolism, circadian rhythm, DNA repair, inflammation, cell differentiation, and organ development. The altered placental methylation of these genes was, in some studies, associated with adverse birth outcomes such as low birth weight, small for gestational age, and decreased head circumference. Moreover, few studies indicate that DNA methylation changes in the placenta were sex-specific, and infants born with altered placental DNA methylation patterns were predisposed to developing neurobehavioral abnormalities, cancer, and atopic dermatitis. These findings highlight the importance of more effective and stricter environmental and public health policies to reduce air pollution and protect human health.