Particulate matter 2.5 exposure during pregnancy and birth outcomes: Evidence from Colombia.

Particulate matter is a type of air pollution that consists of fine particles with a diameter <2.5 µm (PM2.5), which can easily penetrate the respiratory system and enter the bloodstream, increasing health risks for pregnant women and their unborn babies. Recent reports have suggested that there is a positive association between PM2.5 exposure and adverse pregnancy outcomes. However, most evidence of this relationship comes from Western countries. Thus, the objective of this study was to evaluate the association between PM2.5 exposure during pregnancy and birth outcomes among pregnant women in Colombia. This study included 542,800 singletons born in 2019 to Colombian women, aged 15+ years, residing in 981 municipalities. Data on parental, child and birth characteristics were extracted from anonymized live birth records. Satellite-based estimates of monthly PM2.5 concentrations at the surface level were extracted for each municipality from the Atmospheric Composition Analysis Group (ACAG). PM2.5 exposure during pregnancy was indicated by the monthly average of PM2.5 concentrations across the pregnancy duration for the municipality where the child was born. The associations of municipality-level PM2.5 concentration during pregnancy with pre-term birth (PTB) and low birth weight (LBW) were tested in separate two-level logistic regression models, with babies nested within municipalities. The prevalence of PTB and LBW were 8.6 % and 8.3 %, respectively. The mean PM2.5 concentration across the 981 municipalities was 18.26 ± 3.30 µg/m3, ranging from 9.11 to 31.44 µg/m3. Greater PM2.5 concentration at municipality level was associated with greater odds of PTB (1.05; 95%CI: 1.04-1.06) and LBW (1.04; 95%CI: 1.03-1.05), after adjustment for confounders. Our findings provide new evidence on the association between PM2.5 on adverse pregnancy outcomes from a middle-income country.

Association of triclosan and human infertility: A systematic review.

Triclosan (TCS) is a chemical compound, which has antibacterial, antiviral, and antifungal properties. TCS is considered an endocrine-disrupting chemical, which has been shown to interfere with developmental, behavioral, and reproductive outcomes in biological models and cell cultures. However, implications about exposure to TCS and human infertility are rare. Thus, the main of this review is summarize the available evidence of the association between triclosan exposure on human infertility. For this, systematic review was conducted following the recommendations established in Report of Systematic Reviews and Meta-Analyses guide (PRISMA). Initially, an electronic search in MEDLINE (via PubMed) and Science direct was performed. The methodological quality of the included studies was verified through the Joanna Briggs Institute (JBI) checklists. All selection and data extraction processes were carried out independently by two reviewers. The evidence was organized and presented using tables and narrative synthesis. There is lacking evidence about the association between triclosan and human infertility. Overall, no association between triclosan and infertility was found. However, semen quality and ovarian reserve are susceptible to triclosan exposure. Thus, future studies are still needed to better elucidate the associations between triclosan and infertility outcomes.

Mercurio y trastornos del neurodesarrollo en niños: una revisión sistemática / Mercury and neurodevelopmental disorders in children: A systematic review

El mercurio es un metal tóxico que puede atravesar la placenta y la barrera hematoencefálica, y causar la interrupción de varios procesos celulares. Estudios han investigado la exposición al mercurio y trastornos en el neurodesarrollo, por lo que se requiere un análisis crítico y riguroso de esta evidencia. El objetivo de esta revisión fue evaluar la evidencia científica disponible sobre los efectos de la exposición al mercurio durante las etapas prenatal y posnatal, y su relación con el desarrollo de trastornos neuroconductuales. Se realizó una búsqueda sistemática en las bases de datos MEDLINE y ScienceDirect; los resultados se presentaron a través de tablas y síntesis narrativa. Solo 31 estudios cumplieron los criterios de elegibilidad. En general, la evidencia es limitada sobre los efectos de la exposición al mercurio y trastornos del neurodesarrollo en niños. Entre los posibles efectos reportados, se hallan problemas en el aprendizaje, autismo y trastorno por déficit de atención e hiperactividad.

Mercury is a toxic metal which can cross the placenta and the blood-brain barrier and cause the disruption of various cellular processes. Studies have investigated mercury exposure and neurodevelopmental disorders; therefore, a critical and rigorous analysis of this evidence is required. The objective of this review was to evaluate the available scientific evidence on the effects of mercury exposure during the prenatal and postnatal periods and its relationship with the development of neurobehavioral disorders. A systematic search of the MEDLINE and ScienceDirect databases was conducted; the results were presented in tables and narrative synthesis. Only 31 studies met the eligibility criteria. Overall, the evidence on the effects of mercury exposure and neurodevelopmental disorders in children is limited. Learning disabilities, autism, and attention deficit hyperactivity disorder were some of the reported potential effects.

Mercury and neurodevelopmental disorders in children: A systematic review. / Mercurio y trastornos del neurodesarrollo en niños: una revisión sistemática.

Mercury is a toxic metal which can cross the placenta and the blood-brain barrier and cause the disruption of various cellular processes. Studies have investigated mercury exposure and neurodevelopmental disorders; therefore, a critical and rigorous analysis of this evidence is required. The objective of this review was to evaluate the available scientific evidence on the effects of mercury exposure during the prenatal and postnatal periods and its relationship with the development of neurobehavioral disorders. A systematic search of the MEDLINE and ScienceDirect databases was conducted; the results were presented in tables and narrative synthesis. Only 31 studies met the eligibility criteria. Overall, the evidence on the effects of mercury exposure and neurodevelopmental disorders in children is limited. Learning disabilities, autism, and attention deficit hyperactivity disorder were some of the reported potential effects.

El mercurio es un metal tóxico que puede atravesar la placenta y la barrera hematoencefálica, y causar la interrupción de varios procesos celulares. Estudios han investigado la exposición al mercurio y trastornos en el neurodesarrollo, por lo que se requiere un análisis crítico y riguroso de esta evidencia. El objetivo de esta revisión fue evaluar la evidencia científica disponible sobre los efectos de la exposición al mercurio durante las etapas prenatal y posnatal, y su relación con el desarrollo de trastornos neuroconductuales. Se realizó una búsqueda sistemática en las bases de datos MEDLINE y ScienceDirect; los resultados se presentaron a través de tablas y síntesis narrativa. Solo 31 estudios cumplieron los criterios de elegibilidad. En general, la evidencia es limitada sobre los efectos de la exposición al mercurio y trastornos del neurodesarrollo en niños. Entre los posibles efectos reportados, se hallan problemas en el aprendizaje, autismo y trastorno por déficit de atención e hiperactividad.

Acoplamiento molecular y modelado tridimensional por homología de flavonoides derivados de amentoflavona con las neuraminidasas H1N1 y H5N1 del virus de gripe aviar / Molecular docking and threedimensional homology modeling of flavonoids derived from amentoflavone with H1N1 and H5N1 neuraminidases of avian influenza virus / Modelagem de homologia tridimensional e de acoplamento molecular de flavonóides derivados de amentoflavona com as neuraminidases H1N1 e H5N1 do vírus da gripe aviária

Resumen El virus de la influenza A es el responsable de la gripe aviar, condición patológica que afecta principalmente aves, caballos y mamíferos marinos, sin embargo, el subtipo H5NI tiene la capacidad de infectar a los humanos de forma rápida, exponiéndolos a un posible evento pandémico. Por tanto, el objetivo de este estudio fue realizar el acoplamiento molecular y modelado tridimensional por homología de flavonoides derivados de amentoflavona con las neuraminidasas H1N1 y H5N1 del virus de gripe aviar. Inicialmente, se obtuvo por homología la estructura 3D de la neuraminidasa H1N1. Seguido, se realizó un acoplamiento molecular de H1N1 con seis ligandos (F36, Ginkgetin, 3S,3R, 5S,5R, 6S y 6R), y más adelante H5N1 y los ligandos F36, Ginkgetin, 5R y 6R. Finalmente, a los complejos obtenidos se les realizó un análisis de interacciones. Los resultados dejaron en evidencia una relación entre la actividad inhibitoria y las interacciones tipo puente de hidrógeno e hidrofóbicas formadas entre el sitio activo de las neuraminidasas y los ligandos. Además, se observó una mejora en la actividad inhibitoria de los ligandos para la estereoquímica tipo R y sustituyentes poco voluminosos. De ahí que se propongan la evaluación experimental de los ligandos 5R y 6R como potenciales inhibidores de H5N1.

Abstract The influenza A virus is responsible for bird flu; a pathological condition that mainly affects birds, horses, and marine mammals, however, the H5N' subtype can infect humans quickly; exposing them to a possible pandemic event. Therefore, the objective of this study was to carry out the molecular docking and three-dimensional homology modeling of flavonoids derived from amentoflavone with H'NI and H5NI neuraminidases of the avian influenza virus. Initially, the 3D structure of H1N1 neuraminidase was obtained by homology. Then, the molecular docking of H1N1 was carried out with six ligands (F36, Ginkgetin, 3S, 3R, 5S, 5R, 6S, and 6R), and subsequently H5N1 and F36, Ginkgetin, 5R, and 6R ligands. Finally, an interaction analysis of the proteinligand complex was performed. The results showed a relationship between the inhibitory activity of ligands and the hydrophobic and hydrogen bridge-type interactions. In addition, an improvement in the inhibitory activity of the ligands for R-type stereochemistry and small bulky substituents was observed. Thus, the experimental evaluation of the 5R and 6R ligands as potential H5N' inhibitors is proposed.

Resumo O vírus influenza A é responsável pela gripe aviária; condição patológica que afeta principalmente pássaros, cavalos e mamíferos marinhos, no entanto, o subtipo H5N' tem a capacidade de infectar humanos rapidamente; assim, expondo-os a um possível evento pandémico. Portanto, o objetivo deste estudo foi realizar o acoplamento e modelagem de homologia tridimensional de flavonóides derivados da amentoflavona com as neuraminidases H1N1 e H5N1 do vírus da influenza aviária. Inicialmente, a estrutura 3D da neuraminidase H1N1 foi obtida por homologia. Em seguida, o acoplamento molecular de H1N1 foi realizado com seis ligantes (F36, Ginkgetin, 3S, 3R, 5S, 5R, 6S e 6R) e, posteriormente, H5NI e os ligantes F36, Ginkgetin, 5R e 6R. Finalmente, uma análise de interação foi realizada nos complexos obtidos. Os resultados mostraram uma relação entre a atividade inibitória e as interações hidrofóbicas e do tipo ponte de hidrogénio formadas entre o sítio ativo das neuraminidases e os ligantes. Além disso, foi observada uma melhoria na atividade inibitória dos ligantes para a estereoquímica do tipo R e pequenos substituintes volumosos. Assim, é proposta a avaliação experimental dos ligantes 5R e 6R como potenciais inibidores do H5NI.

Fluoroquinolone antibiotics and organophosphate pesticides induce carbonylation on Eisenia fetida muscle proteins.

Protein carbonylation is an irreversible oxidative modification that has been associated with a decrease in the quality and nutritional value of products of animal origin. Generally, the carbonylation is attributed to processes of slaughter, processing, and cold storage of products. However, in vitro studies have shown that fluoroquinolone and organophosphate pesticides residues at their maximum residue limits (MRL) can promote carbonylation of animal proteins. Though, this effect on in vivo conditions has not yet been evaluated. Thus, Eisenia fetida was chosen as a model to assay their oxidant effect. For this, adult earthworms were exposed to artificial soil contaminated with ciprofloxacin, danofloxacin, fenthion, and diazinon at three concentrations (0.5, 1.0, and 1.5 MRL) for 28 days. Then, these were purged and sacrificed to obtain the muscle region between the anus and preclitellum. The muscle samples were cold macerated to obtain muscle proteins, which were used for protein quantification, determination of carbonyl levels, and carbonyl protein profiles employing Bradford, Dot-blot, and Western blot assays, respectively. The results showed that at each concentration assayed, all pollutants induced significant carbonylation respect to control (p < 0.05). Additionally, mass spectrometry-based analysis (MALDI-TOF/TOF) identified actin as the protein most susceptible to carbonylation promoted by these substances. Therefore, these findings show for the first time the oxidant power of fluoroquinolones and organophosphates pesticides at MRLs concentrations on muscle proteins under in vivo conditions. Fact causes concern due to the homology of muscle proteins in eukaryotes, which allow to hypothesize that this effect could also be experienced by proteins from food-producing animals in the same way that observed in in vitro studies.

Peptidomics and proteomics data of oxidised peptides from in vitro gastrointestinal digestion of chicken breast exposed to chlorpyrifos.

Chlorpyrifos (CPF) is an organophosphorus pesticide used in poultry to prevent and/or kill insects and such as preserving agents of poultry feed. Exposure continues to CPF can promote its accumulation at trace concentrations in animal tissue. The toxicological effects of these residues (carcinogenicity, genotoxicity, and neurological disorders) have been related to oxidative stress. Nevertheless, it is still unknown if these trace concentrations might promote oxidative stress in muscle proteins since chicken meat proteins are susceptible to undergo oxidation reactions. Moreover, protein oxidation has been related to a decrease in the nutritional value in of meat. To investigate the oxidative effect of CPF on chicken breast proteins, peptidomics and proteomics analysis were used. For this, chicken breast samples were exposed to CPF and subjected to simulated gastrointestinal digestion. The identification of oxidized peptides from digested and undigested proteins were performed by LC MS/MS (nanoESI qQTOF). Prior to mass analyses undigested proteins were trypsinated. Data were analysed using MASCOT and ProteinPilot v 4.5 software. In this study, 90 and 107 oxidized peptides from digested proteins of control and exposed samples were identified, respectively. These peptides corresponding to 12 oxidized proteins. Meanwhile, 260 and 324 oxidized peptides from undigested proteins (control and exposed samples) were identified, which corresponding to 19 and 17 proteins, respectively. Collagen was protein more susceptible to oxidation promoted by chlorpyrifos in digested and undigested proteins. Identification of these oxidized proteins from simulated digestion provides an important insight about the impact of substances like certain veterinary drugs at trace concentrations on the nutritional value of chicken breast meat.

In vitro oxidation promoted by chlorpyrifos residues on myosin and chicken breast proteins.

Organophosphate pesticides are frequently used to eliminate or prevent insects in poultry. However, their residues may continue in meat after slaughtering. In this study, proteomics and peptidomics approaches were used to evaluate their oxidative impact on myosin and chicken breast proteins under in vitro conditions. Myosin protein was exposed to diazinon and chlorpyrifos showing an increase in its oxidation by increasing times, especially with chlorpyrifos. Then, chicken breast was contaminated with chlorpyrifos to evaluate carbonylation and the effect of simulated gastrointestinal digestion. Proteins were isolated using size-exclusion-chromatography and identified by mass spectrometry in tandem. Myosin, ß-enolase, CK-M-type and actin were identified as main proteins susceptible to oxidation. Also, oxidised peptides obtained before and after simulated gastrointestinal digestion were identified. Collagen peptides the most susceptible to oxidation. These results suggest that the presence of chlorpyrifos residues on meat could have a negative effect on its final quality and nutritional value.

Residues of Fluoroquinolone Antibiotics Induce Carbonylation and Reduce In Vitro Digestion of Sarcoplasmic and Myofibrillar Beef Proteins.

Although the impact of oxidation on human health has been of growing interest, the oxidation of proteins, major component of meat, has received little attention. This paper describes the in vitro effect of five fluoroquinolones (FQs) on carbonylation of sarcoplasmic and myofibrillar proteins of beef when found at concentrations close to the maximum residue limit (MRL). Samples were treated individually with the FQs, determining in each protein fraction the carbonyl index, protein content and oxidized proteins identification, using 2,4-dinitrophenyhydrazine (DNPH) alkaline assay, Western blot and Bradford methods, and mass spectrometry, respectively. Besides, the in vitro effect of these residues on gastric and duodenal digestion of proteins was evaluated. The carbonylation induced by FQs affected both protein fractions being significant with respect to the blank in 73.3% of cases. This damage was correlated with loss of solubility and digestibility, with sarcoplasmic proteins the most affected. Danofloxacin and enrofloxacin were the FQs with greatest oxidant effects, especially affecting glycolysis and glycogen proteins. Our results suggest that these residues induce irreversible oxidative damage on the main beef proteins and could affect their nutritional value.

Study of interaction energies between residues of the active site of Hsp90 and geldanamycin analogues using quantum mechanics/molecular mechanics methods.

Background: Heat shock protein (Hsp90KDa) is a molecular chaperone involved in the process of cellular oncogenesis, hence its importance as a therapeutic target. Geldanamycin is an inhibitor of Hsp90 chaperone activity, which binds to the ATP binding site in the N-terminal domain of Hsp90. However, geldanamycin has shown hepatotoxic damage in clinical trials; for this reason, its use is not recommended. Taking advantage that geldanamycin binds successfully to Hsp90, many efforts have focused on the search for similar analogues, which have the same or better biological response and reduce the side effects of its predecessor; 17-AAG and 17-DMAG are examples of these analogues. Methods: In order to know the chemical factors influencing the growth or decay of the biological activity of geldanamycin analogues, different computational techniques such as docking, 3DQSAR and quantum similarity were used.  Moreover, the study quantified the interaction energy between amino acids residues of active side and geldanamycin analogues, through hybrid methodology (Autodock-PM6) and DFT indexes. Results: The evaluation of interaction energies showed that the interaction with Lys58 residue is essential for the union of the analogues to the active site of Hsp90, and improves its biological activity. This union is formed through a substituent on C-11 of the geldanamycin macrocycle. A small and attractor group was found as the main steric and electrostatic characteristic that substituents on C11 need in order to interact with Lys 58; behavior was observed with hydroxy and methoxy series of geldanamycin analogues, under study. Conclusion: This study contributes with new hybrid methodology (Autodock-PM6) for the generation of 3DQSAR models, which to consider the interactions between compounds and amino acids residues of Hsp90´s active site in the alignment generation. Additionally, quantum similarity and reactivity indices calculations using DFT were performed to know the non-covalent stabilization in the active site of these compounds.

Asociación entre endometriosis pélvica y estrés oxidativo / Association between pelvic endometriosis and oxidative stress

Objetivo: precisar el estado actual del conocimiento referente a la asociación entre endometriosis pélvica y estrés oxidativo. Materiales y métodos: se realizó búsqueda temática en las bases de datos Sciencedirect y Medline vía Pubmed. Se seleccionaron estudios publicados en lengua inglesa entre enero de 1990 y junio del 2012, que hubieran evaluado la asociación entre estrés oxidativo y endometriosis pélvica. Resultados: de 984 resúmenes identificados, 201 fueron escogidos por tener información relacionada; 110 artículos completos fueron evaluados, 45 que tenían información relevante acorde con el objetivo de la revisión fueron tenidos en cuenta. Existen estudios en humanos y en modelos experimentales que proponen que el estrés oxidativo puede estar involucrado en la fisiopatología de la endometriosis pélvica. Distintos estudios señalan que las mujeres con infertilidad asociada a endometriosis presentan niveles más altos de prooxidantes y más bajos de antioxidantes, con respecto al control sano, en mediciones en líquido peritoneal o tejido endometrial, sin consistencia con los hallazgos en plasma o suero. Conclusiones: no es claro el papel que desempeñan las especies reactivas de oxígeno en la endometriosis pélvica. Este campo se presenta como un atractivo ámbito de investigación en ciencias básicas y aplicadas.

Objective: To determine the current state of knowledge regarding the association between pelvic endometriosis and oxidative stress. Materials and methods: A search on the topic was conducted in the Sciencedirect and Medline databases through Pubmed. Studies published in the English language between January 1990 and June 2012 assessing the association between oxidative stress and pelvic endometriosis were selected. Results: Of a total of 984 abstracts identified, 201 were selected because they contained related information. Overall, 110 complete articles were assessed and, of them, 45 that contained relevant information consistent with the objective of the review were taken into account. There are studies in experimental models and in humans suggesting the potential involvement of oxidative stress in the pathophysiology of pelvic endometriosis. Different studies point to the fact that women with endometriosis-associated infertility have higher levels of pro-oxidants and lower levels of anti-oxidants when compared with healthy controls, as measured in peritoneal fluid or endometrial tissue; these levels are not consistent plasma or serum levels. Conclusions: The role of reactive oxygen species in pelvic endometriosis is yet unclear. This field opens an interesting possibility for research in basic and applied science.