Metabolomics applied to maternal and perinatal health: a review of new frontiers with a translation potential

The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and "omics" sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent "boom" in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies.74CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESSem informação88881.134095/2016-01; 8881.134512/2016-0

A Mycobacterium leprae Hsp65 Mutant as a Candidate for Mitigating Lupus Aggravation in Mice

Hsp60 is an abundant and highly conserved family of intracellular molecules. Increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. Administration of M. leprae Hsp65 [WT] in [NZBxNZW]F1 mice accelerates the Systemic Lupus Erythematosus [SLE] progression whereas the point mutated K409A Hsp65 protein delays the disease. Here, the biological effects of M. leprae Hsp65 Leader pep and K409A pep synthetic peptides, which cover residues 352–371, are presented. Peptides had immunomodulatory effects similar to that observed with their respective proteins on survival and the combined administration of K409A+Leader pep or K409A pep+WT showed that the mutant forms were able to inhibit the deleterious effect of WT on mortality, indicating the neutralizing potential of the mutant molecules in SLE progression. Molecular modeling showed that replacing Lysine by Alanine affects the electrostatic potential of the 352–371 region. The number of interactions observed for WT is much higher than for Hsp65 K409A and mouse Hsp60. The immunomodulatory effects of the point-mutated protein and peptide occurred regardless of the catalytic activity. These findings may be related to the lack of effect on survival when F1 mice were inoculated with Hsp60 or K409A pep. Our findings indicate the use of point-mutated Hsp65 molecules, such as the K409A protein and its corresponding peptide, that may minimize or delay the onset of SLE, representing a new approach to the treatment of autoimmune diseases

Metabolomics applied to maternal and perinatal health: a review of new frontiers with a translation potential

Made available in DSpace on 2019-10-06T16:24:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01. Added 1 bitstream(s) on 2019-10-09T18:35:21Z : No. of bitstreams: 1 S1807-59322019000100303.pdf: 766293 bytes, checksum: d3694a392a2120b7b8d5e91ffe93d3f0 (MD5)The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and “omics” sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent “boom” in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies.Departamento de Ginecologia e Obstetricia Faculdade de Ciencias Medicas Universidade Estadual de CampinasDepartamento Materno Infantil Faculdade de Medicina Universidade Federal de PernambucoDepartamento de Ginecologia e Obstetricia Faculdade de Medicina de Botucatu Universidade Estadual de Sao Paulo (UNESP)Departamento de Ginecologia e Obstetricia Faculdade de Medicina Universidade Federal do Rio Grande do SulDepartamento de Ginecologia e Obstetricia Faculdade de Medicina Universidade Federal do CearaUniversity of LeicesterUniversity of CorkGravida: National Center for Growth & Development Liggins Institute University of AucklandSchool of Medical Sciences University of CampinasLNBioDepartment of Mother and Child Health School of Medicine Federal University of PernambucoSchool of Medicine of Botucatu UNESPHospital de Clínicas de Porto Alegre and School of Medicine Federal University of Rio Grande do SulSchool of Medicine Federal University of CearaDepartamento de Ginecologia e Obstetricia Faculdade de Medicina de Botucatu Universidade Estadual de Sao Paulo (UNESP)School of Medicine of Botucatu UNES

Biochar: pyrogenic carbon for agricultural use: a critical review.

O biocarvão (biomassa carbonizada para uso agrícola) tem sido usado como condicionador do solo em todo o mundo, e essa tecnologia é de especial interesse para o Brasil, uma vez que tanto a ?inspiração?, que veio das Terras Pretas de Índios da Amazônia, como o fato de o Brasil ser o maior produtor mundial de carvão vegetal, com a geração de importante quantidade de resíduos na forma de finos de carvão e diversas biomassas residuais, principalmente da agroindústria, como bagaço de cana, resíduos das indústrias de madeira, papel e celulose, biocombustíveis, lodo de esgoto etc. Na última década, diversos estudos com biocarvão têm sido realizados e atualmente uma vasta literatura e excelentes revisões estão disponíveis. Objetivou-se aqui não fazer uma revisão bibliográfica exaustiva, mas sim uma revisão crítica para apontar alguns destaques na pesquisa sobre biochar. Para isso, foram selecionados alguns temaschave considerados críticos e relevantes e fez-se um ?condensado? da literatura pertinente, mais para orientar as pesquisas e tendências do que um mero olhar para o passad

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta