The potential of circHIPK3 as a biomarker in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by leukocytosis and left shift. The primary molecular alteration is the BCR::ABL1, chimeric oncoprotein with tyrosine kinase activity, responsible for the initial oncogenesis of the disease. Therapy of CML was revolutionized with the advent of tyrosine kinase inhibitors, but it is still not considered curative and may present resistance and serious adverse effects. Discoveries in CML inaugurated a new era in cancer treatment and despite all the advances, a new biomarker is needed to detect resistance and adverse effects. Circular RNAs (circRNAs) are a special type of non-coding RNA formed through a process called backsplicing. The majority of circRNAs are derived from protein-coding genes. CircHIPK3 is formed from the second exon of the HIPK3 gene and has been found in various pathologies, including different types of cancer. New approaches have demonstrated the potential of circular RNAs in cancer research, and circHIPK3 has shown promising results. It is often associated with cellular regulatory pathways, suggesting an important role in the molecular dynamics of tumors. The identification of biomarkers is an important tool for therapeutic improvement; thus we review the role of circHIPK3 and its potential as a biomarker in CML.

Baccharis anomala DC. extract reduces inflammation and attenuates hepatic fibrosis in vivo by decreasing NF-kB and extracellular matrix compounds.

Baccharis anomala DC. (BA) is a plant species found in the tropical regions of South America and is widely used for its hepatoprotective effects, as well as for the treatment of gastrointestinal diseases. Studies have recently reported its antioxidant and anti-inflammatory potential. BA extract can reverse the activated phenotype of hepatic stellate cells (HSC), which plays a central role in extracellular matrix (ECM) deposition in the development of liver fibrosis. Thus, this study aimed to evaluate the effects of the treatment with BA extract on liver fibrosis in a CCl4-induced liver fibrosis model in BALB/c mice. Methanolic extract was obtained from BA leaves, a gas chromatography/mass spectrometry (GC/MS) to detect the compounds present was performed, and then administered by intraperitoneal injection in Balb/C mice at a concentration of 50 and 100 mg/kg together with the administration of CCl4 for inducing liver fibrosis. After 10 weeks, blood analysis, histopathology, oxidative stress, as well as protein and gene expression in the hepatic tissue were performed. Treatment with BA extract was able to reduce profibrotic markers by reducing the expression of α-SMA and Col-1 proteins, as well as reducing the formation of free radicals and lipid peroxidation. (BA extract showed anti-inflammatory effects in the liver by suppressing NF-kB activation and reducing gene expression of signaling targets (IL-6 and iNOS). The data obtained showed that BA extract has antifibrotic and anti-inflammatory effects.

Medicalização da subjetividade e fetichismo psicofármaco: uma análise dos fundamentos / Medicalization of subjectivity and psychotropic drugs fetishism: an analysis of the fundamentals

Resumo Este trabalho trata dos fundamentos da epidemia das drogas psiquiátricas e tem por objetivo analisar a medicalização da subjetividade e o fetichismo dos psicofármacos em suas bases fundamentais. Trata-se de uma reflexão teórica à luz da análise do discurso inaugurada por Michel Pêcheux, a partir da qual se apresenta um gesto de interpretação, possibilitando identificar a epidemia das drogas psiquiátricas como expressão da medicalização da vida. Com base na crítica dos fundamentos da forma capitalista de consumo e da prescrição dos psicofármacos, esta análise demonstrou como o modelo de metabolismo social do capital impõe aos sujeitos uma terapêutica fetichizada. Espera-se contribuir com práticas que lutam pelo legado do movimento antimanicomial e, com isso, somar aos esforços dos sujeitos envolvidos na produção de práticas terapêuticas efetivamente humanizadas e críticas.

Abstract This study deals with the foundations of the psychiatric drug epidemic, aiming to analyze the medicalization of subjectivity and the fetishism of psychotropic drugs in their fundamental bases. It is a theorical reflection in the light of discourse analysis inaugurated by Michel Pêcheux, from which it presents a gesture of interpretation, allowing the identification of the psychiatric drug epidemic as an expression of the medicalization of life. Based on the critique of the foundations of the capitalist form of consumption and prescription of psychotropic drugs, this analysis demonstrated how the social metabolism model of capital imposes a fetishized therapy on the subjects. We hope to contribute to the practices of those who fight for the legacy of the anti-asylum movement and thus add to the efforts of the subjects involved in the production of effectively humanized and critical practices.

Phase angle of bioimpedance as a marker of inflammation in cardiovascular diseases: A systematic review.

OBJECTIVE: The aim of this systematic review was to investigate whether phase angle (PhA) of bioelectrical impedance is associated with inflammatory markers in cardiovascular diseases (CVDs). METHODS: A search was performed in the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American Caribbean Health Sciences Literature (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Scopus; and in the gray literature up to January 2022. Studies with individuals with CVDs were included, to evaluate the association between PhA and the inflammatory markers interleukin (IL)-6, IL-10, IL-18, IL-1ß, IL-33, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), toll-like receptor (TLR) 2, TLR 4, nuclear factor κB, pathogen-associated molecular pattern molecules, lipopolysaccharides, interferon-γ-inducing factor, and JAK STAT. RESULTS: We identified 755 articles and, after an eligibility analysis, 5 studies were included. The inflammatory markers investigated in the studies were CRP, TNF-α, and IL-33. In patients with CVDs, PhA was negatively associated with CRP and TNF-α in 80% and 100% of the studies, respectively. CONCLUSIONS: The present results suggested that PhA is inversely associated with inflammatory markers in individuals with CVDs, and its clinical use is encouraged for better therapeutic planning.

Fructose supplementation shifts rat brain metabolism in experimental migraine.

AIMS: We have previously demonstrated that fructose supplementation (FS), given in a scheme used for inducing metabolic syndrome (MS), elicited pain relief in the nitroglycerin (NTG)-elicited rat migraine model. Herein, we evaluated whether FS could reestablish the impaired metabolic pathways in NTG-injected rats. MAIN METHODS: Male Wistar rats (N = 40) were divided into two groups for receiving 10 % FS or tap water. After 45 days, they were subdivided into NTG-injected (10 mg/kg; 15 days) or controls. After the fourth NTG injection, 18F-fluorodeoxyglucose ([18F] FDG) micro-PET scanning was accomplished. The day after, euthanasia was performed, and blood was collected for glycemia and LDH analysis. The levels of energy molecules, TBARS, PGC-1α, and MCTS1 were evaluated in the brain cortices. The activated satellite glial cells (SGC) were assessed in the trigeminal ganglion (TG). KEY FINDINGS: There were no variations of glycemia or LDH serum levels. NTG-injected rats showed a significant increase in glucose uptake in the hypothalamus (HT) vs. NTG-free rats. The FS-NTG group showed increased metabolism in the superior colliculus (SC) vs. the NTG group. Moreover, the glucose uptake was amplified in the inferior colliculus (IC) of the FS-NTG vs. FS group. The cortical inosine levels were significantly higher in FS-NTG rats vs. NTG or FS groups, with no changes in TBARS or MCTS1 levels, despite a minor decrease of PGC1-α contents in the FS+NTG group. Finally, there was a significant increase of activated SGC around TG in the FS-NTG rats. SIGNIFICANCE: We provide novel evidence linking nutrition and metabolism with migraine.

Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide.

In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H2O2) to induce oxidative stress activation and BZF treatment was administered at the same moment as H2O2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H2O2-induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H2O2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H2O2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis.

Contextos de saúde e trabalho de profissionais de enfermagem em tempos de pandemia de COVID-19 / Health and work contexts of nursing professionals during the pandemic of COVID-19 / Contextos de salud y trabajo de profesionales de enfermería en tiempos de pandemia por COVID-19

Introdução: Ao desempenhar e promover práticas que visam a melhoria da saúde, a equipe de enfermagem se assumiu como protagonista e linha de frente em tempos de pandemia de COVID-19. Logo, fica evidente a exposição pessoal-profissional-familiar; a carência de pessoal e a insegurança laboral-emocional, além das consequências que vão recair sobre os contextos de saúde e de trabalho destes profissionais. Objetivo: Analisar os contextos de saúde e trabalho de profissionais de enfermagem durante a pandemia de COVID-19. Metodologia: Estudo de método misto, combinando as abordagens por meio da estratégia de incorporação concomitante - QUAN(qual), realizado em Minas Gerais, Brasil, entre agosto e dezembro de 2020. Aplicou-se, via ligação telefônica, um roteiro de perguntas a 58 profissionais enfermeiros, técnicos e auxiliares de enfermagem. O roteiro continha perguntas abertas e fechadas ligadas a questões sociodemográficas e aos contextos e condições de saúde, trabalho e COVID-19. Realizou-se análise quantitativa descritiva e Análise de Conteúdo Temática. Resultados: A maioria mulheres (93,1%) técnicas de enfermagem (69%). 39,7% trabalhavam em plantão noturno; 58,6% relataram terem sofrido violências no trabalho e 48,3% relataram diagnósticos de transtorno mental. Os contextos de trabalho na pandemia evidenciaram necessidade de estímulos e valorização profissional e relações com fatores institucionais, a dinâmica e organização do trabalho, condições adequadas de trabalho e ao favorável relacionamento interpessoal, enquanto que contextos de saúde evidenciaram relação com interesses, oportunidades, rotina, normalidade, esperança e tenacidade que seriam trazidos pelo fim da COVID-19. Conclusão: A pandemia de COVID-19 fortaleceu um contexto de saúde e de trabalho crítico, amedrontado e inseguro da equipe de Enfermagem brasileira, exacerbando a necessidade de providências, ações e políticas que considerem a Saúde do Trabalhador como estruturantes para a organização dos serviços.

Introducción: Al realizar y promover prácticas que tienen como objetivo la mejora de la salud, el equipo de enfermería asumió el protagonismo en los tiempos de la pandemia por COVID-19. Por tanto, es evidente la exposición personal-profesional-familiar, la falta de personal y la inseguridad laboral-emocional, además de las consecuencias que recaerán sobre la salud y los contextos laborales de este grupo profesional. Objetivo: Analizar el contexto sanitario y laboral de profesionales de enfermería durante la pandemia por COVID-19. Metodología: Estudio de método mixto, combinando los abordajes a través de la estrategia de incorporación concomitante - QUAN(qual), realizado en Minas Gerais, Brasil, entre agosto y diciembre de 2020. Se aplicó un guion de preguntas, mediante llamada telefónica, a 58 profesionales, personal técnico y auxiliares de enfermería. El guion contenía preguntas abiertas y cerradas relacionadas con cuestiones sociodemográficas y los contextos y condiciones de salud, trabajo y COVID-19. Se realizó un análisis cuantitativo descriptivo y un análisis de contenido temático. Resultados: La mayor parte de la muestra estuvo compuesta por mujeres (93.1 %) y personal técnico de enfermería (69 %). El 39.7 % trabajaba en turno de noche, el 58.6 % declaró haber sufrido violencia en el trabajo y el 48.3 % informó de diagnósticos de trastorno mental. Los contextos de trabajo en la pandemia mostraron la necesidad de estímulo y valoración profesional y las relaciones con los factores institucionales, la dinámica y la organización del trabajo, las condiciones adecuadas de trabajo y la relación interpersonal favorable. Los contextos de salud, mientras tanto, mostraron una relación con los intereses, las oportunidades, la rutina, la normalidad, la esperanza y la tenacidad que se produciría al final de la COVID-19. Conclusión: La pandemia de la COVID-19 fortaleció un contexto de salud y trabajo crítico, atemorizado e inseguro del equipo de enfermería brasileño, exacerbando la necesidad de providencias, acciones y políticas que consideren la salud de la persona trabajadora como estructurante para la organización de los servicios.

Introduction: By performing and promoting practices that aim to improve health, the nursing team has assumed itself as a protagonist during the COVID-19 pandemic. Therefore, the personal, professional, and family exposure is evident; the lack of personnel and occupational security, in addition to the consequences on the health and work contexts of these professionals. Objective: To analyze the health and work contexts of nursing professionals during the pandemic of COVID-19. Methodology: This is a mixed-method study that combines approaches through the concurrent incorporation strategy - QUAN(qual), conducted in Minas Gerais, Brazil, between August and December 2020. A script of questions was applied over the phone to 58 professional nurses, nursing technicians, and nursing assistants. The script included open and closed questions related to sociodemographic issues and health, work, and COVID-19 contexts and conditions. A descriptive quantitative analysis and thematic content analysis were performed. Results: The majority were women (93.1%) nursing technicians (69%). The 39.7% of the participants worked the night shift; the 58.6% reported experiencing violence at work and the 48.3% was diagnosed with mental disorders. The work contexts during the pandemic showed that there was a need for encouragement and professional evaluation; they also portrayed the relationships with the institutional factors, the work dynamics and the organization, the appropriate working conditions and the favorable interpersonal relationships. On the other hand, health contexts showed the relationship between interests, opportunities, routine, normality, hope and tenacity that would occur at the end of COVID-19. Conclusion: The pandemic of COVID-19 strengthened a critical, fearful, and insecure health and work context of the Brazilian nursing team, exacerbating the need for provisions, actions and policies that consider worker's health crucial for the organization of services.

Consequences of post-weaning sleep deprivation on behaviour and oxidative stress parameters in rat plasma and brain.

Sleep is essential for health: Adequate sleep is essential for healthy development and sleep deprivation results in several consequences. Indeed, sleep deprivation early in life is associated with poor behaviour and cognition, as well as impaired mental and physical health. Preclinical studies have shown that sleep deprivation alters several physiological functions later in life such as the cardiovascular, immune and endocrine systems, resulting in altered oxidative states. Most of the preclinical literature is focused on adult animals, and little is known about oxidative alterations during development, especially in the context of sleep deprivation. Hence, we adapted a classic and well-documented model of sleep deprivation, paradoxical sleep deprivation using multiple platforms, for juvenile rats and explored central and peripheral oxidative parameters, as well as the behavioural consequences of sleep deprivation post-weaning. We showed that 96 h of paradoxical sleep deprivation induced a significant reduction in body weight, decreased sucrose preference-a behaviour suggestive of anhedonia-and increased glucose and decreased cholesterol in the plasma. In the brain, we observed a decrease in reduced glutathione levels in the medial prefrontal cortex and an increase in thiobarbituric acid reactive substance levels in the hypothalamus, indicating oxidative damage in these regions. Taken together, our findings suggest that paradoxical sleep deprivation during development induces anhedonic behaviour and promotes central and peripheral alterations in oxidative parameters.

Moquiniastrum polymorphum subsp. polymorphum extract inhibits the proliferation of an activated hepatic stellate cell line (GRX) by regulating the p27 pathway to generate cell cycle arrest.

ETHNOPHARMACOLOGICAL RELEVANCE: The chosen plant and its extracts have been an alternative in the treatment of several inflammatory and oxidant diseases, and is therefore a viable option for the treatment of hepatic fibrosis. AIM OF THE STUDY: This study aimed to use Moquiniastrum polymorphum subsp. polymorphum, mainly the ethanolic extract and fractions, in the treatment of hepatic fibrosis. MATERIALS AND METHODS: Extracts were prepared from dried leaves in 100% ethanol (ET) and fractionated with an increased polarity solvent (dichloromethane to methanol). The quantification of compounds in the extracts was characterized by GCMS. The decrease in cell proliferation and the cytotoxicity of the extracts were evaluated together with the mechanisms of apoptosis and autophagy. The expression of genes associated with decreased fibrosis and cell cycle control was assessed and the production of lipid droplets was quantified by Oil Red O staining. RESULTS: The experiments showed that treatment with ET and fraction 1 (F1) inhibited the expression of CDKIs (CCDN1, CDK2, CDK4 and CDK6) through an increase in p27, related to an increase in autophagic vesicles. The extract and F1 were able to decrease proliferation and revert the activated state of GRX cells to their quiescent state. CONCLUSION: Our results suggest that extracts obtained from Moquiniastrum polymorphum subsp. polymorphum have a potential therapeutic effect against liver fibrosis.

Coumaric acid from M. polymorphum extracts reverses the activated state of hepatic stellate cells (GRX) and inhibits their proliferation by decreasing the p53/p21 pathway.

Coumaric acid is a phenolic compound found in medicinal plants. Its use has been reported in the treatment of inflammatory diseases, prevention of alterations induced by oxidative stress, as well as acetaminophen-induced hepatotoxicity. Thus, this study evaluated coumaric acid as a potential treatment for liver fibrosis. Cell proliferation was assessed by the trypan blue exclusion technique and the cytotoxicity of coumaric acid was performed using an LDH assay. Mechanisms of cell apoptosis were evaluated by flow cytometry. The expression of genes associated with apoptosis, cell cycle control, and fibrosis was assessed by qPCR. The production of lipid droplets was quantified by oil red staining. The experiments performed showed that the treatment with coumaric acid was able to reduce cell proliferation without causing cell cytotoxicity or apoptosis. Coumaric acid was able to inhibit the expression of cyclin D1 and CDK's (CDK2, CDK4, and CDK6), increasing p53 and p21, which could lead to cell cycle arrest. Treatment with coumaric acid was also able to revert the activated phenotype of GRX cells to their quiescent state. Thus, our results suggest that coumaric acid has a potential therapeutic effect against liver fibrosis.

Simvastatin attenuates inflammatory process on LPS-induced acute lung injury in mice.

Acute lung injury (ALI) is a disease of high prevalence and is characterized by the excessive production of inflammatory mediators in the lungs of people sick. Inflammation is the major characteristic of ALI and studies report that inhibition of inflammatory cytokines could be an alternative treatment. Statins such as Simvastatin (SV) are known to their use for cholesterol reduction but also for inflammatory and immunoregulatory processes. In this study, we evaluated the effects of SV on LPS-induced alveolar macrophages and in ALI mice model. Our study has demonstrated the protective effects of SV on LPS-activated alveolar macrophages RAW 264.7 and LPS-induced ALI in mice. SV treatment significantly inhibited the alveolar macrophages activation by decreasing the iNOS, IL-1ß, and IL-6 gene expression in vitro and in vivo. The treatment also decreased the inflammatory cells migration and the cytokines gene expression. Our findings suggest that SV can act as an anti-inflammatory agent for acute lung injury.

Impact of maternal physical exercise on inflammatory and hypothalamic-pituitary-adrenal axis markers in the brain and lungs of prenatally stressed neonatal mice.

This study aimed to evaluate the effects of maternal exercise on alterations induced by prenatal stress in markers of the inflammatory process and the hypothalamic-pituitary-adrenal axis in the brain and lungs of neonatal mice. Female Balb/c mice were divided into three groups: control, prenatal restraint stress, prenatal restraint stress and physical exercise before and during the gestational period. On day 0 (PND0) and 10 (PND10), mice were euthanized for brain and lung analyses. The gene expression of GR, MR, IL-6, IL-10, and TNF in the brain and lungs and the protein expression of MMP-2 in the lungs were analyzed. Maternal exercise reduced IL-6 and IL-10 gene expression in the brain of PND0 mice. Prenatal stress and maternal exercise decreased GR, MR, IL-6, and TNF gene expression in the lungs of PND0 mice. In the hippocampus of PND10 females, exercise inhibited the effects of prenatal stress on the expression of MR, IL-6, and IL-10. In the lungs of PND10 females, exercise prevented the decrease in GR expression caused by prenatal stress. In the hippocampus and lungs of PND10 males, prenatal stress decreased GR gene expression. Our findings confirm the effects induced by prenatal stress and demonstrate that physical exercise before and during the gestational period may have a protective role on inflammatory changes.

The role of maternal exercise on placental, behavioral and genetic alterations induced by prenatal stress.

The present study aimed to evaluate the effects of treadmill maternal exercise on alterations induced by prenatal stress in neonatal mice. Female and male Balb/c mice were divided into five groups: control (CON), prenatal restraint stress (PNS), prenatal restraint stress and physical exercise before pregnancy (PNS + EX1), prenatal restraint stress and physical exercise during pregnancy (PNS + EX2), and prenatal restraint stress and physical exercise before and during pregnancy (PNS + EX3). Exercise was performed using a treadmill, at a speed of 10 m/min, for 60 min, 5 days a week. Maternal behavior was assessed on days 3, 4 and 5 postpartum (PPD). Placental gene expression of glucocorticoid receptor (GR), 11-ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2), 5-hydroxytryptamine receptor 1A (5HT1AR), and corticotropin releasing hormone receptor 1 (CRHR1) were analyzed. In neonatal mice, the gene expression of GR, mineralocorticoid receptor (MR), CRHR1, 5HTr1, oxytocin Receptor 1 (OXTr1), tropomyosin related kinase B (TRκB), brain-derived neurotrophic factor exon I (BDNF I), and BDNF IV was analyzed in the brain (PND0) and hippocampus (PND10). Maternal exercise improved (p < 0.05) maternal care. In the placenta, maternal exercise prevented (p < 0.01) the increase in GR expression caused by PNS. In the brain from PND0, exercise before pregnancy prevented (p = 0.002) the decreased CRHR1 expression promoted by PNS. In the hippocampus of PND10 males, PNS decreased (p = 0.0005) GR expression, and exercise before pregnancy prevented (p = 0.003) this effect. In PND10 females, maternal exercise prevented (p < 0.05) the PNS-induced increase in MR expression. PNS + EX2 males showed increased (p < 0.01) BDNF I gene expression and PNS + EX1 females demonstrated increased (p = 0.03) BDNF IV expression. In conclusion, maternal physical exercise may play a role in modulating maternal-fetal health and may contribute to preventing neurodevelopmental changes induced by prenatal stress.

The genetics of hereditary cancer risk syndromes in Brazil: a comprehensive analysis of 1682 patients.

Hereditary cancer risk syndromes are caused by germline variants, commonly in tumor suppressor genes. Most studies on hereditary cancer have been conducted in white populations. We report the largest study in Brazilian individuals with multiple ethnicities. We genotyped 1682 individuals from all country regions with Next-generation sequencing (NGS) panels. Most were women with a personal/family history of cancer, mostly breast and ovarian. We identified 321 pathogenic/likely pathogenic (P/LP) variants in 305 people (18.1%) distributed among 32 genes. Most were on BRCA1 and BRCA2 (129 patients, 26.2% and 14.3% of all P/LP, respectively), MUTYH (42 monoallelic patients, 13.1%), PALB2 (25, 7.8%), Lynch syndrome genes (17, 5.3%), and TP53 (17, 5.3%). Transheterozygosity prevalence in our sample was 0.89% (15/1682). BRCA1/BRCA2 double heterozygosity rate was 0.78% (1/129) for BRCA variants carriers and 0.06% (1/1682) overall. We evaluated the performance of the genetic testing criteria by NCCN and the Brazilian National Health Agency (ANS). The inclusion criteria currently used in Brazil fail to identify 17%-25% of carriers of P/LP variants in hereditary cancer genes. Our results add knowledge on the Brazilian spectrum of cancer risk germline variants, demonstrate that large multigene panels have high positivity rates, and indicate that Brazilian inclusion criteria for genetic testing should be improved.

Methoxyeugenol Protects Against Lung Inflammation and Suppresses Neutrophil Extracellular Trap Formation in an LPS-Induced Acute Lung Injury Model.

Acute lung injury (ALI) is a life-threatening acute inflammatory disease with high rates of morbidity and mortality worldwide. 4-Allyl-2,6-dimethoxyphenol (methoxyeugenol), a phenylpropanoid from a synthetic source, exhibits strong anti-inflammatory activity, but its effects on the inflammation of ALI have not yet been reported. In our study, the anti-inflammatory effects of methoxyeugenol were investigated on RAW 264.7 cells and a mice model of ALI. Our results showed that methoxyeugenol (7.5 and 30 µM) attenuated the proliferation and gene expression of interleukin (IL)-6 in LPS-stimulated RAW 264.7 cells. In a mice model of ALI induced with LPS, methoxyeugenol exhibited a significant protective effect, based on influx reduction of macrophages and neutrophils into the lungs; reduction in release of the cytokines IL-6, TNF-α, and IL-10; and in reactive oxygen species (ROS) formation. We show that the anti-inflammatory effects of methoxyeugenol are associated with the suppression of the NFκB signaling pathway. Moreover, we demonstrated for the first time that a phenolic compound, from a synthetic source, protects against lung tissue inflammation and promotes a reduction of NET formation. These findings provided evidence for the use of methoxyeugenol as a new strategy to control inflammation in ALI disease.

Gestational stress alters maternal behavior and inflammatory markers in the olfactory bulb of lactating mice.

Inflammatory markers represent important candidates responsible for the altered behavior and physiology observed after stressful experiences. In the maternal brain, the olfactory bulb (OB) is a key constituent of the neural circuit that mediates the reciprocal interaction between mother and infant. This study aimed to investigate the effects of stress during pregnancy on maternal behavior and inflammatory changes in the olfactory bulb of lactating mice. Female Balb/c mice were divided into two groups: control (CT) and restraint stress (RS). Maternal behavior was performed during the first 8 days of life of the offspring. On the 10th day after parturition, corticosterone, gene, and protein expression were assessed. Stress during pregnancy decreased the maternal index at postnatal day 4 and the nuclear factor-κB 1 (NFκB1) gene expression in the OB. Moreover, females from the RS group showed increased interleukin (IL-1ß) protein expression. In contrast, stressed females exhibited a decreased tumor necrosis factor (TNF-α) protein expression in the OB. In conclusion, exposure to stress during pregnancy was able to induce specific postnatal effects on maternal behavior and balance of inflammatory mediators in the OB.

Octyl gallate decrease lymphocyte activation and regulates neutrophil extracellular traps release.

BACKGROUND: Inflammation is a complex mechanism with an objective to destroy and eliminate the invading microorganisms. During acute inflammation, the neutrophils are the major cells involved in this process and, although they defend the organism, must die to not generate damage. The two major mechanisms that drive neutrophils to death are: apoptosis and a novel mechanism recently discovered denominated NETosis. This process is a "suicidal mechanism", in which the cells release "neutrophil extracellular traps" (NETs) during the inflammatory response. Octyl gallate (OG) is one of the gallic acid derivates, with several protective effects, such as antioxidant and anti-inflammatory in cancer models. Thus, this study aimed to investigate the action of OG on the proliferation of lymphocytes, neutrophils activation, and its effectiveness in an experimental sepsis model. METHODS: Lymphocytes and neutrophils were obtained from healthy donors. Cell viability, apoptosis, NETs release and antioxidant capacity of OG were observed. In addition, survival was evaluated in an experimental model of sepsis in C57BL/6 mice. RESULTS: Our study demonstrated, for the first time, that the OG can act as an inhibitor of reactive oxygen species (ROS) release, NETs formation in primary human neutrophils and, modulates the lipopolysaccharide (LPS) effect in neutrophil apoptosis. The OG also inhibited peripheral blood mononuclear cells (PBMCs) proliferation in vitro. Despite the positive results, we did not observe an increase in the survival of septic animals. CONCLUSIONS: The pharmacological potential of OG, modulating activation of neutrophils and lymphocytes, suggests the use as an adjuvant therapeutic strategy in inflammatory diseases.

Suporte ético-emocional à profissionais de enfermagem frente à pandemia de COVID-19: relato de experiência / Ethical-emotional support for nursing professionals facing the COVID-19 pandemic: An experience report / Soporte ético-emocional a profesionales de enfermería ante la pandemia COVID-19: relato de experiencia

Objetivo: Descrever a experiência de planejamento, execução e avaliação de um serviço de suporte ético-emocional para profissionais de enfermagem frente à pandemia de COVID-19. Método: Relato de experiência no âmbito da Comissão de Suporte Ético-Emocional do Conselho Regional de Minas Gerais, Brasil, desenvolvido entre os meses de abril e dezembro de 2020 e operacionalizado através de ligações telefônicas e mensagens via aplicativo de comunicação. Resultados: Foram atendidos 241 profissionais. Foram revelados e declarados sentimentos, emoções, vivências e problemas oriundos do cotidiano de trabalho da enfermagem diante do contexto pandêmico. Tais problemas reforçam a eminência, a urgência e o valor que o suporte teve para a vida, trabalho e saúde dos profissionais atendidos, configurando-se como uma estratégia de saúde e de intervenção indispensável à promoção, prevenção, segurança e proteção da saúde mental frente à pandemia. Os atendimentos culminaram na redução de sentimentos negativos; na percepção aumentada (identificação de potenciais ameaças e contextos de "gatilhos"); na valorização pessoal; no autoconhecimento e autocuidado. Considerações finais e implicações para a prática: O suporte fez-se inovador para área da saúde e da enfermagem ao constituir-se como uma estratégia multidisciplinar promotora, aconselhadora e facilitadora do cuidado em tempos de COVID-19. Encoraja-se a manutenção desta estratégia após a pandemia

Objective: To describe the experience of planning, implementing and evaluating an ethical-emotional support service for Nursing professionals facing the COVID-19 pandemic. Method: An experience report in the scope of the Ethical-Emotional Support Commission of the Regional Council of Minas Gerais, Brazil, developed between April and December 2020 and operationalized through phone calls and messages via a communication application. Results: A total of 241 professionals were assisted. Feelings, emotions, experiences and problems arising from the daily Nursing work in the pandemic context were revealed and stated. Such problems reinforce the prominence, urgency and value that the support service had for the life, work and health of the professionals assisted, configuring itself as a health and intervention strategy, indispensable for mental health promotion, prevention, safety and protection in the face of the pandemic. The consultations culminated in the reduction of negative feelings; in increased perception (identification of potential threats and "trigger" contexts); in personal appreciation; and in self-knowledge and self-care. Final considerations and implications for the practice: The support service was innovative for the Health and Nursing areas by constituting a multidisciplinary strategy that promotes, counsels, and facilitates care in times of COVID-19. We encourage the maintenance of this strategy after the pandemic

Objetivo: Describir la experiencia de planificación, implementación y evaluación de un servicio de soporte ético-emocional para los profesionales de enfermería ante la pandemia de COVID-19. Método: Relato de experiencia en el ámbito de la Comisión de Soporte Ético-Emocional del Consejo Regional de Minas Gerais, Brasil, desarrollado entre los meses de abril y diciembre de 2020 y operacionalizado a través de enlaces telefónicos y mensajes vía la aplicación de comunicación. Resultados: Se atendió a 241 profesionales. Se revelaron y declararon los sentimientos, las emociones, las experiencias y los problemas derivados del trabajo diario de las enfermeras ante el contexto de la pandemia. Estos problemas refuerzan la eminencia, la urgencia y el valor que el soporte tiene para la vida, el trabajo y la salud de los profesionales atendidos, configurándose como una estrategia de salud y de intervención indispensable para la promoción, prevención, seguridad y protección de la salud mental frente a la pandemia. Las consultas culminaron en la reducción de los sentimientos negativos; en el aumento de la percepción (identificación de posibles amenazas y contextos "desencadenantes"); en la valoración personal; en el autoconocimiento y el autocuidado. Consideraciones finales e implicaciones para la práctica: El soporte fue innovador en el ámbito de la salud y la enfermería como estrategia multidisciplinaria para promover, asesorar y facilitar la asistencia en tiempos de COVID-19. Se fomenta el mantenimiento de esta estrategia después de la pandemia