Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs.

BACKGROUND & OBJECTIVES: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. PATIENTS & METHODS: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). RESULTS: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. CONCLUSIONS: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.

New advances in genomics and epigenetics in antiphospholipid syndrome.

APS patients exhibit a wide clinical heterogeneity in terms of the disease's origin and progression. This diversity can be attributed to consistent aPL profiles and other genetic and acquired risk factors. Therefore, understanding the pathophysiology of APS requires the identification of specific molecular signatures that can explain the pro-atherosclerotic, pro-thrombotic and inflammatory states observed in this autoimmune disorder. In recent years, significant progress has been made in uncovering gene profiles and understanding the intricate epigenetic mechanisms and microRNA changes that regulate their expression. These advancements have highlighted the crucial role played by these regulators in influencing various clinical aspects of APS. This review delves into the recent advancements in genomic and epigenetic approaches used to uncover the mechanisms contributing to vascular and obstetric involvement in APS. Furthermore, we discuss the implementation of novel bioinformatics tools that facilitate the investigation of these mechanisms and pave the way for personalized medicine in APS.

Population Genomics Reveals an Emerging Lineage of Xanthomonas perforans on Pepper.

Xanthomonas perforans-the dominant causal agent of bacterial leaf spot of tomato-is an emerging pathogen of pepper, indicative of a potential host expansion across the southeastern United States. However, studies of the genetic diversity and evolution of X. perforans from pepper remain limited. In this study, the whole-genome sequences of 35 X. perforans strains isolated from pepper from four fields and two transplant facilities across southwest Florida between 2019 and 2021 were used to compare genomic divergence, evolution, and variation in type III secreted effectors. Phylogenetic analysis based on core genes revealed that all 35 X. perforans strains formed one genetic cluster with pepper and tomato strains from Alabama and Turkey and were closely related to strains isolated from tomato in Indiana, Mexico, and Louisiana. The in planta population growth of tomato strains isolated from Indiana, Mexico, Louisiana, and Turkey in pepper leaf mesophyll was on par with pepper X. perforans and X. euvesicatoria strains. Molecular clock analysis of the 35 Florida strains dated their emergence to approximately 2017. While strains varied in copper tolerance, all sequenced strains harbored the avrHah1 transcription activation-like effector located on a conjugative plasmid, not previously reported in Florida. Our findings suggest that there is a geographically distributed lineage of X. perforans strains on tomato that has the genetic background to cause disease on pepper. Moreover, this study clarifies potential adaptive variants of X. perforans on pepper that could help forecast the emergence of such strains and enable immediate or preemptive intervention.

Fibronectin-coated polyurethane meniscal scaffolding supplemented with MSCs improves scaffold integration and proteoglycan production in a rabbit model.

PURPOSE: The role of mesenchymal stem cells (MSC) in supporting the formation of new meniscal tissue in a meniscal scaffold is not well understood. The objective of this study was to assess the quality of the meniscal tissue produced in a fibronectin (FN)-coated polyurethane (PU) meniscal scaffold after a meniscal injury was made in an experimental rabbit model. METHODS: Twelve New Zealand white rabbits were divided in two groups after performing a medial meniscectomy of the anterior horn. In group 1, the meniscal defect was reconstructed with a non-MSC supplemented FN-coated PU scaffold. On the other hand, the same scaffold supplemented with MSCs was used in group 2. The animals were sacrificed at 12 week after index surgery. A modified scoring system was used for histological assessment. This new scoring (ranging from 0 to 15) includes a structural evaluation (meniscal scaffold interface and extracellular matrix production) and tissue quality evaluation (proteoglycan and type I-collagen content). RESULTS: The meniscal scaffold was found loose in the joint in three cases, corresponding to two cases in group 1 and 1 case in group 2. No differences were observed between the groups in terms of the total score (7.0 ± 0.9 vs. 9.4 ± 2.6, p = 0.09). However, differences were observed in group 2 in which 2 out of the 5 scored items, scaffold integration (1 ± 0.0 vs. 1.9 ± 0.6, p = 0.03) and proteoglycan production (1.2 ± 0.3 vs. 2.4 ± 0.2, p = 0.001). A trend to a higher production of Type I-Collagen production was also observed in group 2 (1.1 ± 0.4 vs. 1.4 ± 0.7, p = 0.05). CONCLUSION: In a rabbit model at 12 weeks, the adhesion of MSCs to a FN-coated PU scaffold improves scaffold integration, proteoglycan production and the characteristics of the new meniscal-like tissue obtained when compared to a non-supplemented scaffold. This fact could be a major step toward improving the adhesion of the MSCs to meniscal scaffolds and, consequently, the obtention of better quality meniscal tissue.

Binding Specificity of a Novel Cyclo/Maltodextrin-Binding Protein and Its Role in the Cyclodextrin ABC Importer System from Thermoanaerobacterales.

Extracellular synthesis of functional cyclodextrins (CDs) as intermediates of starch assimilation is a convenient microbial adaptation to sequester substrates, increase the half-life of the carbon source, carry bioactive compounds, and alleviate chemical toxicity through the formation of CD-guest complexes. Bacteria encoding the four steps of the carbohydrate metabolism pathway via cyclodextrins (CM-CD) actively internalize CDs across the microbial membrane via a putative type I ATP-dependent ABC sugar importer system, MdxEFG-(X/MsmX). While the first step of the CM-CD pathway encompasses extracellular starch-active cyclomaltodextrin glucanotransferases (CGTases) to synthesize linear dextrins and CDs, it is the ABC importer system in the second step that is the critical factor in determining which molecules from the CGTase activity will be internalized by the cell. Here, structure-function relationship studies of the cyclo/maltodextrin-binding protein MdxE of the MdxEFG-MsmX importer system from Thermoanaerobacter mathranii subsp. mathranii A3 are presented. Calorimetric and fluorescence studies of recombinant MdxE using linear dextrins and CDs showed that although MdxE binds linear dextrins and CDs with high affinity, the open-to-closed conformational change is solely observed after α- and ß-CD binding, suggesting that the CM-CD pathway from Thermoanaerobacterales is exclusive for cellular internalization of these molecules. Structural analysis of MdxE coupled with docking simulations showed an overall architecture typically found in sugar-binding proteins (SBPs) that comprised two N- and C-domains linked by three small hinge regions, including the conserved aromatic triad Tyr193/Trp269/Trp378 in the C-domain and Phe87 in the N-domain involved in CD recognition and stabilization. Structural bioinformatic analysis of the entire MdxFG-MsmX importer system provided further insights into the binding, internalization, and delivery mechanisms of CDs. Hence, while the MdxE-CD complex couples to the permease subunits MdxFG to deliver the CD into the transmembrane channel, the dimerization of the cytoplasmatic promiscuous ATPase MsmX triggers active transport into the cytoplasm. This research provides the first results on a novel thermofunctional SBP and its role in the internalization of CDs in extremely thermophilic bacteria.

Study of the Early Effects of Chitosan Nanoparticles with Glutathione in Rats with Osteoarthrosis.

Due to cartilage's limited capacity for regeneration, numerous studies have been conducted to find new drugs that modify osteoarthrosis's progression. Some evidence showed the capability of chitosan nanoparticles with glutathione (Np-GSH) to regulate the oxide-redox status in vitro in human chondrocytes. This work aimed to evaluate the capacity of Np-GSH in vivo, using Wistar rats with induced surgical osteoarthritis. Radiographic, biochemical (GSH and TBARS quantification), histopathological, and immunohistochemical (Col-2 and MMP-13) analyses were performed to evaluate the progress of the osteoarthritic lesions after the administration of a single dose of Np-GSH. According to the results obtained, the GSH contained in the NPs could be vectored to chondrocytes and used by the cell to modulate the oxidative state reduction, decreasing the production of ROS and free radicals induced by agents oxidizing xenobiotics, increasing GSH levels, as well as the activity of GPx, and decreasing lipid peroxidation. These results are significant since the synthesis of GSH develops exclusively in the cell cytoplasm, and its quantity under an oxidation-reduction imbalance may be defective. Therefore, the results allow us to consider these nanostructures as a helpful study tool to reduce the damage associated with oxidative stress in various diseases such as osteoarthritis.

A systematic literature review on sustainability issues along the value chain in insurance companies and pension funds.

Sustainability is now a priority issue that governments, businesses and society in general must address in the short term. In their role as major global institutional investors and risk managers, insurance companies and pension funds are strategic players in building socio-economic and sustainable development. To gain a comprehensive understanding of the current state of action and research on environmental, social and governance (ESG) factors in the insurance and pension sectors, we conduct a systematic literature review. We rely on the PRISMA protocol and analyze 1 731 academic publications available in the Web of Science database up to the year 2022 and refer to 23 studies outside of scientific research retrieved from the websites of key international and European organizations. To study the corpus of literature, we introduce a classification framework along the insurance value chain including external stakeholders. The main findings reveal that risk, underwriting and investment management are the most researched areas among the nine categories considered in our framework, while claims management and sales tend to be neglected. Regarding ESG factors, climate change, as part of the environmental factor, has received the most attention in the literature. After reviewing the literature, we summarize the main sustainability issues and potential related actions. Given the current nature of the sustainability challenges for the insurance sector, this literature review is relevant to academics and practitioners alike.

Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis.

OBJECTIVE: We analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting. METHODS: Our study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+ -related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti-tumor necrosis factor (anti-TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside. RESULTS: Reduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP-ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti-TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status. CONCLUSION: RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti-TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds.

The thrombus proteome in stroke reveals a key role of the innate immune system and new insights associated with its etiology, severity, and prognosis.

BACKGROUND: Nowadays little is known about the molecular profile of the occluding thrombus of patients with ischemic stroke. OBJECTIVES: To analyze the proteomic profile of thrombi in patients who experienced an ischemic stroke in order to gain insights into disease pathogenesis. METHODS: Thrombi from an exploratory cohort of patients who experienced a stroke were obtained by thrombectomy and analyzed by sequential window acquisition of all theoretical spectra-mass spectrometry. Unsupervised k-means clustering analysis was performed to stratify patients who experienced a stroke. The proteomic profile was associated with both the neurological function (National Institute of Health Stroke Scale [NIHSS]) and the cerebral involvement (Alberta Stroke Program Early CT Score [ASPECTS]) prior to thrombectomy and the clinical status of patients at 3 months using the modified Rankin Scale. In an independent cohort of 210 patients who experienced a stroke, the potential role of neutrophils in stroke severity was interrogated. RESULTS: Proteomic analysis identified 580 proteins in thrombi, which were stratified into 4 groups: hemostasis, proteasome and neurological diseases, structural proteins, and innate immune system and neutrophils. The thrombus proteome identified 3 clusters of patients with distinctive severity, prognosis, and etiology of the stroke. A protein signature clearly distinguished atherothrombotic and cardioembolic strokes. Several proteins were significantly correlated with the severity of the stroke (NIHSS and ASPECTS). Functional proteomic analysis highlighted the prominent role of neutrophils in stroke severity. This was in line with the association of neutrophil activation markers and count with NIHSS, ASPECTS, and the modified Rankin Scale score 90 days after the event. CONCLUSION: The use of sequential window acquisition of all theoretical spectra-mass spectrometry in thrombi from patients who experienced an ischemic stroke has provided new insights into pathways and players involved in its etiology, severity, and prognosis. The prominent role of the innate immune system identified might pave the way for the development of new biomarkers and therapeutic approaches in this disease.

An Overview of PRR- and NLR-Mediated Immunities: Conserved Signaling Components across the Plant Kingdom That Communicate Both Pathways.

Cell-surface-localized pattern recognition receptors (PRRs) and intracellular nucleotide-binding domain and leucine-rich repeat receptors (NLRs) are plant immune proteins that trigger an orchestrated downstream signaling in response to molecules of microbial origin or host plant origin. Historically, PRRs have been associated with pattern-triggered immunity (PTI), whereas NLRs have been involved with effector-triggered immunity (ETI). However, recent studies reveal that such binary distinction is far from being applicable to the real world. Although the perception of plant pathogens and the final mounting response are achieved by different means, central hubs involved in signaling are shared between PTI and ETI, blurring the zig-zag model of plant immunity. In this review, we not only summarize our current understanding of PRR- and NLR-mediated immunities in plants, but also highlight those signaling components that are evolutionarily conserved across the plant kingdom. Altogether, we attempt to offer an overview of how plants mediate and integrate the induction of the defense responses that comprise PTI and ETI, emphasizing the need for more evolutionary molecular plant-microbe interactions (EvoMPMI) studies that will pave the way to a better understanding of the emergence of the core molecular machinery involved in the so-called evolutionary arms race between plants and microbes.

Evidence for the Neuronal Expression and Secretion of Adiponectin.

Peripheral adiponectin acts on the hypothalamus to inhibit energy expenditure and increase food intake through its receptors AdipoR1 and adipoR2. The hypothalamic expression of adiponectin is poorly documented. We hypothesize that whether hypothalamic adiponectin is confirmed, its expression and secretion could be regulated as peripheral adiponectin. Thus, in the present work, we aim to determine whether adiponectin is expressed in the hypothalamus and in two neuronal cell lines and investigate the potential mechanisms regulating its neuronal expression. Using immunohistochemistry, we show that adiponectin is expressed in the mediobasal hypothalamic neurons of mice. Adiponectin expression is also evidenced in two neuronal cell lines mHypo POMC (an adult mouse hypothalamic cell line) and SH-SY5Y (human neuroblastoma). The neuronal expression of adiponectin is increased in response to rosiglitazone treatment (a PPARγ agonist) and FGF21 and is decreased in insulin-resistant neurons. Furthermore, we show that adiponectin expressed by mHypo POMC neurons is secreted in a culture medium. Adiponectin also diminished the resistin-induced IL6 expression in SIMA9 cells, a microglia cell line. In conclusion, we evidenced the hypothalamic expression of adiponectin and its regulation at the neuronal level.

Mining for novel cyclomaltodextrin glucanotransferases unravels the carbohydrate metabolism pathway via cyclodextrins in Thermoanaerobacterales.

Carbohydrate metabolism via cyclodextrins (CM-CD) is an uncommon starch-converting pathway that thoroughly depends on extracellular cyclomaltodextrin glucanotransferases (CGTases) to transform the surrounding starch substrate to α-(1,4)-linked oligosaccharides and cyclodextrins (CDs). The CM-CD pathway has emerged as a convenient microbial adaptation to thrive under extreme temperatures, as CDs are functional amphipathic toroids with higher heat-resistant values than linear dextrins. Nevertheless, although the CM-CD pathway has been described in a few mesophilic bacteria and archaea, it remains obscure in extremely thermophilic prokaryotes (Topt ≥ 70 °C). Here, a new monophyletic group of CGTases with an exceptional three-domain ABC architecture was detected by (meta)genome mining of extremely thermophilic Thermoanaerobacterales living in a wide variety of hot starch-poor environments on Earth. Functional studies of a representative member, CldA, showed a maximum activity in a thermoacidophilic range (pH 4.0 and 80 °C) with remarkable product diversification that yielded a mixture of α:ß:γ-CDs (34:62:4) from soluble starch, as well as G3-G7 linear dextrins and fermentable sugars as the primary products. Together, comparative genomics and predictive functional analysis, combined with data of the functionally characterized key proteins of the gene clusters encoding CGTases, revealed the CM-CD pathway in Thermoanaerobacterales and showed that it is involved in the synthesis, transportation, degradation, and metabolic assimilation of CDs.

Precision-cut liver slices as a model for assess hepatic cellular response of chitosan-glutathione nanoparticles on cultures treated with zilpaterol and clenbuterol.

Zilpaterol and clenbuterol are two ß-adrenergic agonist drugs used in animal production. Both drugs have anabolic effects with advantages on carcass yield. Meanwhile, zilpaterol is approved for animal feed in authorized countries. Clenbuterol is a banned substance due to the risk of toxicity; however, it is still being used in unknown dose levels in many farm species. Therefore, the use and abuse of these substances should be closely monitored, considering the clenbuterol ability and the not proved yet of zilpaterol to produce reactive oxygen and nitrogen species. Regarding glutathione which is the main intracellular antioxidant plays detoxification functions on liver metabolism; in this work, it is our interest to know the capacity of chitosan-glutathione nanoparticles (CS/GSH-NP) as a complementary source of exogenous GSH to modify the oxide-reduction status on bovine precision-cut liver slice cultures (PCLS) exposed to clenbuterol and zilpaterol. A single drug assay was performed in first instance by adding clenbuterol, zilpaterol, chitosan nanoparticles (CS-NP), and CS/GSH-NP. Then combinate drug assay was carried out by testing clenbuterol and zilpaterol combined with CS-NP or CS/GSH-NP. The results showed that both ß-adrenergic agonists modify in a dose-dependent manner in oxide-reduction response through ROS generation. The activity or content of glutathione peroxidase activity, intracellular GSH, gamma glutamyl-transpeptidase, aspartate aminotrasnferase and alanine aminotrasnferase were modified. The exogenous GSH delivered by nanoparticles could be used to modulate these markers.

Instrumentos de evaluación del riesgo psicosocial en trabajadores de diferentes sectores laborales. Revisión narrativa descriptiva / Instruments for assessing psychosocial risk in workers in different occupational sectors. Descriptive narrative review / Instrumentos de avaliação de riscos psicossociais para trabalhadores de diferentes sectores de trabalho. Revisão narrativa descritiva

Introducción: Los factores psicosociales son condiciones presentes en el medio laboral y fuera de este que, al no ser identificados y controlados, afectan la integridad física y psicológica de los trabajadores, así como el rendimiento y la satisfacción laboral. Objetivo: Analizar y sintetizar información reportada en literatura científica sobre la aplicabilidad de diversos instrumentos que evalúan el riesgo psicosocial en trabajadores de diferentes sectores laborales. Metodología: Se desarrolló a través de revisión narrativa descriptiva con investigaciones originales, publicadas en las bases de datos Pubmed, Proquest, Scopus, Science Direct, Redalyc, SciELO, Dialnet, VirtualPro, escritas en idioma español, inglés y portugués, publicados entre 2007 y 2021, tomando como referente la fecha de implementación de la Batería de Riesgo Psicosocial en Colombia. Resultados: Se identificaron 27 investigaciones que emplearon instrumentos de medición y valoración de los factores de riesgo psicosocial. En el ámbito internacional se encontró la batería Unipsico, el Cuestionario Psicosocial de Conpenhagen, el Cuestionario de Evaluación de Factores Psicosociales, el Psychosocial Risk Management-Excellence Framework, el Cuestionario Naqre y la Batería MCMutual-UB; mientras que en Colombia se encontró la Batería de Instrumentos para la Evaluación de Factores de Riesgo Psicosocial, el Cuestionario Psicosocial de Conpenhagen, un instrumento de medición de riesgos psicosociales y cuestionarios elaborados. Conclusiones: Los instrumentos han sido adaptados transculturalmente y proporcionan una perspectiva abreviada de las herramientas de evaluación de los factores de riesgo psicosocial empleadas en personas que se encuentran activas laboralmente para identificar riesgos presentes en los ámbitos intralaboral y extralaboral.

Introduction: Psychosocial factors are conditions present in the work environment and outside it, which, when not identified and controlled, affect the physical and psychological integrity of workers, as well as performance and job satisfaction. Objective: To analyze and synthesize information reported in the literature on the applicability of various instruments that evaluate psychosocial risk in workers in different occupational sectors. Methodology: It was developed through a descriptive narrative review with original research published in the databases Pubmed, Proquest, Scopus, Science Direct, Redalyc, SciELO, Dialnet, VirtualPro, written in Spanish, English and Portuguese, published between 2007 and 2021, taking as reference the date of implementation of the Psycho Risk Battery. Social in Colombia. Results: 27 research projects were identified which used instruments to measure and assess psychosocial risk factors. The Unipsico battery, the Conpenhagen psychosocial questionnaire, the Psychoso- cial Factors Assessment Questionnaire, the Psychosocial Risk Management-Excellence Framework, the Naqre Questionnaire and the MCMutual Battery were found internationally. UB and at the national level the Toolkit for the Assessment of Psychosocial Risk Factors, the Conpenhagen Psychosocial Questionnaire, a psychosocial risk measurement tool and questionnaires developed. Conclusions: The instruments have been adapted cross-culturally and provide a shortened perspective of the tools for assessing psychosocial risk factors used in people who are active at work to identify risks present in the workplace and outside of the workplace.

Introdução: Os fatores psicossociais são condições presentes dentro e fora do ambiente de trabalho que, quando não identificadas e controladas, afetam a integridade física e psicológica dos trabalha- dores, bem como o desempenho e a satisfação no trabalho. Objetivo: Analisar e sintetizar a informação relatada na literatura científica sobre a aplicabilidade de vários instrumentos que avaliam o risco psicossocial em trabalhadores de diferentes sectores de trabalho. Metodologia: Foi desenvolvida através de uma revisão narrativa descritiva com pesquisas originais, publicada nas bases de dados Pubmed, Proquest, Scopus, Science Direct, Redalyc, SciELO, Dialnet, VirtualPro, escrita em espanhol, inglês e português, publicada entre 2007 e 2021, tomando como referência a data de implementação do questionário de Risco Psicossocial na Colômbia. Resultados: Foram identificados 27 estudos de investigação que utilizaram instrumentos para medir e avaliar fatores de risco psicossocial. A nível internacional, foram encontrados o Questionário Unip- sico, o Questionário Psicossocial Conpenhagen, o Questionário de Avaliação de Fatores Psicossociais, o Quadro de Gestão de Risco Psicossocial-Excelência, o Questionário Naqre e o Questionário MCMutual-UB; enquanto na Colômbia foram encontrados os Instrumentos para a Avaliação de Fatores de Risco Psicossociais, o Questionário Psicossocial Conpenhagen, um instrumento de medição de risco psicossocial e questionários elaborados. Conclusões: Os instrumentos foram adaptados de forma inter-cultural e fornecem uma visão geral abreviada dos instrumentos de avaliação do fator de risco psicossocial utilizados em pessoas ativas no trabalho para identificar riscos presentes nos domínios intra e extra-ocupacionais.

Modification of Proliferation and Apoptosis in Breast Cancer Cells by Exposure of Antioxidant Nanoparticles Due to Modulation of the Cellular Redox State Induced by Doxorubicin Exposure.

In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (CH-GSH NPs) can modify proliferation and apoptosis, and reduce cell damage induced by doxorubicin on breast cancer cells. Doxorubicin is a widely used antineoplasic agent for the treatment of various types of cancer. However, it is also a highly toxic drug because it induces oxidative stress. Thus, the use of antioxidant molecules has been considered to reduce the toxicity of doxorubicin. CH-GSH NPs were characterized in size, zeta potential, concentration, and shape. When breast cancer cells were treated with CH-GSH nanoparticles, they were localized in the cellular cytoplasm. Combined doxorubicin exposure with nanoparticles increased intracellular GSH levels. At the same time, decreasing levels of reactive oxygen species and malondialdehyde were observed and modified antioxidant enzyme activity. Levels of the Ki67 protein were evaluated as a marker of cell proliferation and the activity of the Casp-3 protein related to cell apoptosis was measured. Our data suggests that CH-GSH NPs can modify cell proliferation by decreasing Ki67 levels, induce apoptosis by increasing caspase-3 activity, and reduce the oxidative stress induced by doxorubicin in breast cancer cells by modulating molecules associated with the cellular redox state. CH-GSH NPs could be used to reduce the toxic effects of this antineoplastic. Considering these results, CH-GSH NPs represent a novel delivery system offering new opportunities in pharmacy, material science, and biomedicine.

Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility.

OBJECTIVES: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes. METHODS: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed. RESULTS: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development. CONCLUSION: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS.

Estudio fitoquímico de hojas de Cavendishia compacta (Ericaceae) y evaluación de su actividad antiinflamatoria / Phytochemical study of leaves of Cavendishia compacta (Ericaceae) and evaluation of its anti-inflammatory activity

RESUMEN Se realizó el estudio fitoquímico de hojas de Cavendishia compacta. La separación de extractos y fracciones por cromatografías en columna, capa delgada y capa delgada preparativa, permitieron obtener una mezcla de diterpenos conformada por kaurano, rimuneno y biformeno; una mezcla de compuestos aromáticos constituida por acetofenona y benzaldehído; una mezcla de triterpenos constituida por α-amirina y β-amirina y el aislamiento de morina y miricetina. La actividad antiinflamatoria se evaluó al extracto etanólico y las fracciones de hexano, dicolorometano y acetato de etilo, utilizando el modelo de edema auricular inducido por TPA, siendo el extracto etanólico y la fracción de dicolorometano los que presentaron un efecto antiinflamatorio moderado de 49,3% y 39,8% respectivamente.

Summary The phytochemical study of leaves of Cavendishia compacta was carried out. The separation of extracts and fractions by column chromatography, thin layer and preparative thin layer allowed to obtain a mixture of diterpenes consisting of kaurane, rimunene and biformene; a mixture of aromatic compounds constituted by acetophenone and benzaldehyde; a mixture of triterpenes constituted by α -amirine and β-amirin and the isolation of morine and myricetin. The anti-inflammatory activity was evaluated to the ethanolic extract and fractions of hexane, dichloromethane and ethyl acetate using the model of atrial edema induced by TPA, being the etha-nolic extract and the fraction of dicholoromethane those that presented a moderate anti-inflammatory effect of 49.3 % and 39.8% respectivel.

Biomasa y carbono en Guadua angustifolia y Bambusa oldhamii en dos comunidades de la sierra Nororiental de Puebla, México / Biomass and carbon of Guadua angustifolia and Bambusa oldhamii in two communities of the Nororiental Sierra of Puebla, México

Resumen El incremento de CO2 en la atmósfera puede disminuir mediante su captura por plantas a través del proceso fotosintético, con especial énfasis en especies perennes de rápido crecimiento como los bambús. El objetivo fue evaluar cuantitativamente la biomasa aérea y estimar el contenido de carbono para las especies Guadua angustifolia y Bambusa oldhamii, en plantaciones comerciales establecidas en dos comunidades de la Sierra Nororiental de Puebla, México. La estimación de población y biomasa aérea para ambas especies se obtuvo mediante una selección del 10 % de plantas en una hectárea. Los muestreos se realizaron de junio 2016 a septiembre 2017. Para la plantación de B. oldhamii, el número de culmos por planta aumentó gradualmente hacia las generaciones más recientes, de 3.6 tallos en la cohorte más adulta a 4.5 en la más joven. El diámetro de los tallos y su altura promedio presenta aumento gradual de las cohortes de mayor edad a las más recientes. La biomasa aérea total estimada en la plantación de B. oldhamii fue de 103 403 48 Mg.ha-1 distribuida en los culmos de los cuatro años. La biomasa aérea total estimada en la plantación de G. angustifolia es 47 665 11 Mg.ha-1.(AU)

Abstract The increase of CO2 in the atmosphere can be reduced by capturing them through the photosynthetic process, with special emphasis on fast growing perennial species such as bamboo. The objective of the present study was to quantitatively evaluate the aerial biomass and estimate the carbon content for the species Guadua angustifolia Kunth and Bambusa oldhamii Munro, in commercial plantations established in communities of the Northeast Sierra of Puebla, Mexico. The estimation of population and aerial biomass for both species is tended by a selection of 10 % of plants in one hectare. The samplings were carried out from June 2016 to September 2017. For the plantation of B. Oldhamii Munro, the number of culms per plant gradually increased towards the most recent generations, from 3.6 stems in the most adult cohort to 4.5 in the youngest. The diameter of the stems and their average height show a gradual increase from the older cohorts to the recent cohorts. The total aerial biomass estimated in the plantation of B. oldhamii Munro was 103 403 48 Mgha-1 distributed in the asses of the four years. The total aerial biomass estimated in the plantation of G. angustifolia Kunth is 47 665 11 Mgha-1.(AU)

Plantas medicinales con propiedades frías y calientes en la cultura Zoque de Ayapa, Tabasco, México / Medicinal plants with hot-cold properties in the Zoque culture of Ayapa, Tabasco, México

El objetivo del trabajo fue realizar un registro de plantas medicinales presentes en los solares-huertos familiares de la localidad zoque de Ayapa, Tabasco, México, considerando las cualidades frías y calientes asignadas a las plantas por los habitantes de la comunidad y utilizadas en el tratamiento de enfermedades. A partir de las investigaciones etnobotánicas realizadas mediante 24 entrevistas e información de 5 informantes clave se identificaron 140 especies de uso medicinal correspondientes a 65 familias botánicas diferentes, de las cuales 25 especies medicinales son consideradas de carácter caliente, 98 de carácter frío y 17 especies presentan características tanto frías como calientes. Las plantas medicinales presentes en la zona son utilizadas en el tratamiento de 70 padecimientos. 104 plantas son especies de origen americano y 36 introducidas. Este trabajo representa una primera aproximación al uso de la flora medicinal zoque de Tabasco siendo el primer reporte sobre plantas medicinales en la localidad, lo cual contribuirá a preservar su uso en la región.

The aim of this research was to record plants with medicinal value cultivated in solares or home gardens from Ayapa, a Zoque Village in Tabasco, México. We consider the analysis of the hot-cold qualities assigned by people of the community to the medicinal plants used in the treatment of illnesses. The research has an ethnobotanical perspective. Through 24 interviews and information provided by 5 key informants, we identified 140 medicinal plant species, corresponding to 69 botanical families. 25 species are considered to have a hot quality, whilst 98 are considered cold. 17 species have both cold and hot qualities. 70 ailments are treated using medicinal plants found in the area of study. 104 plants have American origin and 36 are introduced. This first approach to the analysis of the medicinal plants from the Zoque of Tabasco constitutes a first report and a contribution on medicinal lore in this community. This will help to preserve the medical knowledge of this ethnic group.

Síndrome de Sotos diagnosticado por hibridación genómica comparativa / Sotos syndrome diagnosed by comparative genomic hybridisation

El síndrome de Sotos (SS) es una enfermedad genética con un patrón de herencia autosómico dominante, causado por haploinsuficiencia del gen NSD1 secundaria a mutaciones puntuales o microdeleciones del locus 5q35 en el que está ubicado el gen. Es un síndrome poco frecuente, presentándose en 7 de cada 100.000 nacimientos. El objetivo de este reporte es presentar el caso de una paciente de 4 años con retardo global del desarrollo, y hallazgos físicos especiales que sugerían un sindrome genético. Caso clínico: Paciente de 4 años, género femenino, cabello ralo, fascie triangular, fisura palpebral alargada, papadar ojival, mandíbula prominente, escápula alada y clinodactilia del quinto dedo de ambas manos. La prueba molecular de hibridación genómica comparativa por microarreglos, mostró microdeleción de la región 5q35.2 q35.3 de 2.082 MB, que incluye el gen NSD1. Conclusión: Proponemos realizar la prueba de hibridación genómica comparativa en pacientes con retraso global del desarrollo y hallazgos fenotípicos menores.

Sotos Syndrome (SS) is a genetic disease with an autosomal dominant pattern caused by haplo-insufficiency of NSD1 gene secondary to point mutations or microdeletion of the 5q35 locus where the gene is located. It is a rare syndrome, occurring in 7 out of every 100,000 births. The objective of this report is to present the case of a 4 year-old patient with a global developmental delay, as well as specific physical findings suggesting a syndrome of genetic origin. Clinical case: Female patient, 4 years of age, thinning hair, triangular facie, long palpebral fissure, arched palate, prominent jaw, winged scapula and clinodactilia of the fifth finger both hands. The molecular test comparative genomic hybridisation test by microarray was subsequently performed, with the result showing 5q35.2 q35.3 region microdeletion of 2,082 MB, including the NSD1 gene. Conclusion: Finally, this article also proposes the performing of comparative genomic hybridisation as the first diagnostic option in cases where clinical findings are suggestive of SS.