Early-life external exposome in children 2-5 years old in Colombia.

Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.

Cytotoxic Evaluation in HaCaT Cells of the Pa.7 Bacteriophage from Cutibacterium (Propionibacterium) acnes, Free and Encapsulated Within Liposomes.

Introduction: Acne is a multifactorial disease involving the colonization of skin follicles by Cutibacterium (formerly Propionibacterium) acnes. A combination of different retinoid-derived products, antibiotics, and hormonal antiandrogens are used to treat the disease, but these treatments require extended periods, may have secondary effects, are expensive, and not always effective. Owing to antibiotic resistance, the use of bacteriophages has been proposed as an alternative treatment. However, if they are intended for a cosmetic or pharmaceutical use, it is necessary to evaluate the safety of the phages and the preparations containing them. Materials and Methods: In this study, the cytotoxicity of Pa.7 bacteriophage was evaluated in HaCaT cells, along with a liposome suitable for their encapsulation, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays. Results: We found that Pa.7 was not cytotoxic for HaCaT cells. Also, 30 mM of liposomes, or below are considered noncytotoxic concentrations. Conclusion: Phages encapsulated in the liposomes presented in this study can be used safely for skin treatments.

Microbially Synthesized Polymer-Metal Nanoparticles Composites as Promising Wound Dressings to Overcome Methicillin-Resistance Staphylococcus aureus Infections.

Antimicrobial resistance has been declared one of the top 10 global public health threats. Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of recurring skin and soft tissue infections in patients with chronic skin conditions such as diabetic foot infections, making the treatment of the ulcers challenging. Wound dressings combined with metal nanoparticles have been suggested to prevent and treat MRSA-infected wounds. However, these particles are commonly synthesized by chemical approaches. In this study, we developed bio-based silver (Bio-AgNPs) and copper oxide nanoparticles (CuONPs) polymer composites using a microbially produced polyester from the Polyhydroxyalkanoates (PHAs) family. Poly(3-hydroxyoctanoate)-co-(3-hydroxyhexanoate) (PHO) was synthesized by Pseudomonas putida and functionalized in-situ with Bio-AgNPs or ex-situ with CuONPs. PHO-CuONPs films did not inhibit MRSA growth, while a reduction of 6.0 log CFU/mL was achieved with PHO-Bio-AgNPs synthesized from silver nitrate (AgNO3) solution at 3.5 mM. Exposure of human fibroblast cells (HFF-1) to the bioactive films did not induce notable cytotoxicity and genotoxicity, as seen by a viability higher than 79% and no significant changes in basal DNA damage. However, exposure to PHO-Bio-AgNPs induced oxidative DNA damage in HFF-1 cells. No hemolytic potential was observed, while platelet aggregation was promoted and desired for wound healing. Here we demonstrate the biosynthesis of polymer-nanoparticle composites and their potential as bioactive films for MRSA treatment.

Association of buccal micronucleus cytome assay (BMNCyt) biomarkers with inorganic element concentration and genetic polymorphisms in welders.

Welding fumes are classified as carcinogenic to humans. The aim of the present study was to measure buccal micronucleus cytome assay biomarkers and to evaluate their association with inorganic elements and genetic polymorphisms (XRCC1, OGG1, XRCC3, GSTM1, and GSTT1) in welders (n = 98) and control individuals (n = 100). Higher levels of DNA damage and cell death were observed in the exposed group. Also, a significant correlation between the frequency of micronuclei and Na, Si, Cl, Ti, Cr, Zn and Mg concentrations. The formation of micronuclei, binucleated cells, cell death was associated with polymorphisms in repair pathways. The OGG1Ser326Cys and XRCC3 241Thr/Met genotypes were associated with cell death. Individuals with GSTM1 null genotype had a higher frequency of micronuclei. These results demonstrate that the deleterious effects of exposure to welding fumes are exacerbated by lifestyle habits, and genetic polymorphisms can influence DNA damage and cell death.

Novel complexes with ONNO tetradentate coumarin schiff-base donor ligands: x-ray structures, DFT calculations, molecular dynamics and potential anticarcinogenic activity.

The synthesis of eight novel Zn(II), Co(II), Cu(II), Ni(II) and Pt(II) complexes (2-9) derived from the ONNO tetradentate coumarin Schiff-Base donor ligands, L1 and the novel L2, was performed. All compounds were characterized by analytical, spectrometry and spectroscopy techniques. Complexes 2-4 were also characterized by DFT calculations and the structures of 5 and 6 were determined by single-crystal X-ray diffraction analysis. A cytotoxicity study was carried out through an MTT assay in the carcinogenic cell line HeLa and the noncarcinogenic cell lines HFF-1 and HaCaT. The results indicated that among all the evaluated compounds, 2 and 6 presented the best anticarcinogenic potential against HeLa cells with an IC50 of 3.5 and 4.1 µM, respectively. In addition, classical molecular dynamics simulations were performed on the synthesized coordination compounds bound to G4 DNA architectures in the scope of shedding light on their inhibition mode and the most conserved interactions that may lead to the biological activity of the compounds.

Antimicrobial and Biocompatible Polycaprolactone and Copper Oxide Nanoparticle Wound Dressings against Methicillin-Resistant Staphylococcus aureus.

One of the major health problems linked to methicillin-resistant Staphylococcus aureus (MRSA) is severe diabetic foot ulcers (DFU), which are associated with hospital-acquired infections, lower limb amputations and emerging resistance to the current antibiotics. As an alternative, this work aims to develop a biodegradable and biocompatible material with antimicrobial capacity to prevent DFU. This was achieved by producing active polymeric films with metallic nanoparticles dispersed through a polycaprolactone (PCL) dressing. First, the antimicrobial activity of copper oxide nanoparticles (CuONPs) was tested by the microdilution method, selecting the lowest concentration that has an inhibitory effect on MRSA. Then, active PCL films were prepared and characterized in terms of their physicochemical properties, antimicrobial performance, cytotoxicity, genotoxicity and hemocompatibility. Active films had chemical and thermal properties like the ones without the antimicrobial agents, which was confirmed through FTIR, Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) analysis. In relation to antimicrobial activity, active PCL films inhibited MRSA growth when treated with CuONPs at a concentration of 0.07% (w/w). After exposure to the active film extracts, human foreskin fibroblast cells (ATCC® SCRC1041™) (HFF-1) exhibited a cell viability average above 80% for all treatments and no DNA damage was found. Finally, PCL films with 0.07% (w/w) CuONPs proved to be hemocompatible, and none of the films evaluated had red blood cell breakage greater than 5%, being within the acceptable limits established by the International Organization for Standardization ISO 10993-4:2002.

Efficacy and Molecular Effects of a Reduced Graphene Oxide/Fe3O4 Nanocomposite in Photothermal Therapy Against Cancer.

PURPOSE: Expanded research on the biomedical applications of graphene has shown promising results, although interactions between cells and graphene are still unclear. The current study aims to dissect the cellular and molecular effects of graphene nanocomposite in photothermal therapy against cancer, and to evaluate its efficacy. METHODS: In this study, a reduced graphene oxide and iron oxide (rGO-Fe3O4) nanocomposite was obtained by chemical synthesis. The nanocomposite was fully characterized by Raman spectroscopy, TEM, VSM and thermal profiling. Cell-nanocomposite interaction was evaluated by confocal microscopy and viability assays on cancer cell line HeLa. The efficacy of the thermal therapy and changes in gene expression of Bcl-2 and Hsp70 was assessed. RESULTS: The resulting rGO-Fe3O4 nanocomposite exhibited superparamagnetic properties and the capacity to increase the surrounding temperature by 18-20°C with respect to the initial temperature. The studies of cell-nanocomposite interaction showed that rGO-Fe3O4 attaches to cell membrane but there is a range of concentration at which the nanomaterial preserves cell viability. Photothermal therapy reduced cell viability to 32.6% and 23.7% with 50 and 100 µg/mL of nanomaterial, respectively. The effect of treatment on the molecular mechanism of cell death demonstrated an overexpression of anti-apoptotic proteins Hsp70 and Bcl-2 as an initial response to the therapy and depending on the aggressiveness of the treatment. CONCLUSION: The results of this study contribute to understanding the interactions between cell and graphene and support its application in photothermal therapy against cancer due to its promising results.

Tridimensional alginate disks of tunable topologies for mammalian cell encapsulation.

We have developed a protocol to produce three-dimensional matrices based on alginate hydrogels for mammalian cell encapsulation. Based on the gelation properties of this polysaccharide, we implemented a calcium ion-based diffusion method where the designed hydrogels can be obtained with well-defined mechanical properties and replicable 3D topologies. The developed protocol can be extended to different types of alginates and an ample range of concentrations. This makes it very attractive for various biomedical applications where strict control over structure-function relationships is desirable.

Oxidative stress and repetitive element methylation changes in artisanal gold miners occupationally exposed to mercury.

Mercury (Hg) exposure is a public health concern due to its persistence in the environment and its high toxicity. Such toxicity has been associated with the generation of oxidative stress in occupationally exposed subjects, such as artisanal gold miners. In this study, we characterize occupational exposure to Hg by measuring blood, urine and hair levels, and investigate oxidative stress and DNA methylation associated with gold mining. To do this, samples from 53 miners and 36 controls were assessed. We show higher levels of oxidative stress marker 8-OHdG in the miners. Differences in LINE1 and Alu(Yb8) DNA methylation between gold miners and control group are present in peripheral blood leukocytes. LINE1 methylation is positively correlated with 8-OHdG levels, while XRCC1 and LINE1 methylation are positively correlated with Hg levels. These results suggest an effect of Hg on oxidative stress and DNA methylation in gold miners that may have an impact on miners' health.

HLA-DRB1*14 is a protective allele for multiple sclerosis in an admixed Colombian population.

OBJECTIVE: The aim of this study was to determine ancestry informative markers, mitochondrial DNA haplogroups, and the association between HLA-DRB1 alleles and multiple sclerosis (MS) in a group of patients from Bogotá, Colombia. METHODS: In this case-control study, genomic DNA was isolated and purified from blood samples. HLA-DRB1 allele genotyping was done using PCR. Mitochondrial hypervariable region 1 was amplified and haplogroups were determined using HaploGrep software. Genomic ancestry was estimated by genotyping a panel of ancestry informative markers. To test the association of HLA polymorphisms and MS, we ran separate multivariate logistic regression models. Bonferroni correction was used to account for multiple regression tests. RESULTS: A total of 100 patients with MS (mean age 40.4 ± 12 years; 70% females) and 200 healthy controls (mean age 37.6 ± 11 years; 83.5% females) were included in the analysis. Ancestry proportions and haplogroup frequencies did not differ between patients and controls. HLA-DRB1*15 was present in 31% of cases and 13.5% of controls, whereas HLA-DRB1*14 was present in 5% of cases and 15.5% of controls. In the multivariate model, HLA-DRB1*15 was significantly associated with MS (odds ratio [OR] = 3.05, p < 0.001), whereas HLA-DRB1*14 was confirmed as a protective factor in our population (OR = 0.16, p = 0.001). CONCLUSIONS: This study provides evidence indicating that HLA-DRB1*15 allele confers susceptibility to MS and HLA-DRB1*14 allele exerts resistance to MS in a highly admixed population. This latter finding could partially explain the low prevalence of MS in Bogotá, Colombia.

Antibacterial, antifungal and cytotoxic activities of eight Asteraceae and two Rubiaceae plants from colombian biodiversity

Thirty crude extracts of eight plants belonging to Asteraceae and two to Rubiaceae families collected at different places from the Regional Natural Park Ucumarí (RNPU), Colombia, were tested for their antibacterial activity against two Gram-positive and two Gram-negative bacteria and three fungi. Both the antibacterial and the antimycotic activities were tested by the agar well diffusion method. The cytotoxic activity on the same plant extracts was determined through the brine shrimp lethality bioassay. The extracts from the Asteraceae family were more bioactive against Bacillus subtilis and Staphylococcus aureus. The extracts of both families studied were bioactive against the fungi Candida albicans and Fusarium solani. In addition, the extracts of Asteraceae species displayed the greatest cytotoxic activities. However, the most important specie in this research was Gonzalagunia rosea Standl (Rubiaceae) because of the strong and moderate activities of the methanol and dichloromethane extracts against C. albicans and F. solani, respectively; as well as the strong cytotoxic activity of the methanol extract. None of these ten plants has previously been reported for their biological activities.

Trinta extratos crus de oito plantas da família Asteraceae e a duas plantas da família Rubiaceae, coletadas em diferentes lugares do Parque Natural Regional Ucumarí (PNRU), Colombia, foram avaliadas quanto à atividade contra duas bactérias Gram-positivas, duas Gram-negativas e três fungos. As atividades antibacteriana e antimicótica foram determinadas pelo método de difusão em agar. A atividade citotóxica dos mesmos extratos foi determinada através do bioensaio de Artemia salina. Os extratos da família Asteraceae foram os mais bioativos contra Bacillus subtilis e Staphylococcus aureus. Os extratos de ambas famílias estudadas foram bioativos contra os fungos Candida albicans e Fusarium solani. Os extratos da família Asteraceae exibiram maior atividade citotóxica. A espécie mais importante desta pesquisa foi Gonzalagunia rosea Standl (Rubiaceae) devido à atividade intensa e moderada dos extratos de metanol e diclorometano contra F. solani e C. albicans, respectivamente, bem como a intensa atividade citotóxica do extrato metanólico. Não se encontraram estudos prévios acerca das atividades biológicas das dez plantas avaliadas nesse estudo.