Effects of Bradykinin B2 Receptor Ablation from Tyrosine Hydroxylase Cells on Behavioral and Motor Aspects in Male and Female Mice.

The kallikrein-kinin system is a versatile regulatory network implicated in various biological processes encompassing inflammation, nociception, blood pressure control, and central nervous system functions. Its physiological impact is mediated through G-protein-coupled transmembrane receptors, specifically the B1 and B2 receptors. Dopamine, a key catecholamine neurotransmitter widely distributed in the CNS, plays a crucial role in diverse physiological functions including motricity, reward, anxiety, fear, feeding, sleep, and arousal. Notably, the potential physical interaction between bradykinin and dopaminergic receptors has been previously documented. In this study, we aimed to explore whether B2R modulation in catecholaminergic neurons influences the dopaminergic pathway, impacting behavioral, metabolic, and motor aspects in both male and female mice. B2R ablation in tyrosine hydroxylase cells reduced the body weight and lean mass without affecting body adiposity, substrate oxidation, locomotor activity, glucose tolerance, or insulin sensitivity in mice. Moreover, a B2R deficiency in TH cells did not alter anxiety levels, exercise performance, or motor coordination in female and male mice. The concentrations of monoamines and their metabolites in the substantia nigra and cortex region were not affected in knockout mice. In essence, B2R deletion in TH cells selectively influenced the body weight and composition, leaving the behavioral and motor aspects largely unaffected.

Kinin B1 receptor modulates glucose homeostasis and physical exercise capacity by altering adrenal catecholamine synthesis and secretion.

Our group has shown in several papers that kinin B1 receptor (B1R) is involved in metabolic adaptations, mediating glucose homeostasis and interfering in leptin and insulin signaling. Since catecholamines are involved with metabolism management, we sought to evaluate B1R role in catecholamine synthesis/secretion. Using B1R global knockout mice, we observed increased basal epinephrine content, accompanied by decreased hepatic glycogen content and increased glucosuria. When these mice were challenged with maximal intensity exercise, they showed decreased epinephrine and norepinephrine response, accompanied by disturbed glycemic responses to effort and poor performance. This phenotype was related to alterations in adrenal catecholamine synthesis: increased basal epinephrine concentration and reduced norepinephrine content in response to exercise, as well decreased gene expression and protein content of tyrosine hydroxylase and decreased gene expression of dopamine beta hydroxylase and kinin B2 receptor. We conclude that the global absence of B1R impairs catecholamine synthesis, interfering with glucose metabolism at rest and during maximal exercise.

Kinin B1 receptor controls maternal adiponectin levels and influences offspring weight gain.

Given the importance of the kinin B1 receptor in insulin and leptin hormonal regulation, which in turn is crucial in maternal adaptations to ensure nutrient supply to the fetus, we investigated the role of this receptor in maternal metabolism and fetoplacental development. Wild-type and kinin B1 receptor-deficient (B1KO) female mice were mated with male mice of the opposite genotype. Consequently, the entire litter was heterozygous for kinin B1 receptor, ensuring that there would be no influence of offspring genotype on the maternal phenotype. Maternal kinin B1 receptor blockade reduces adiponectin secretion by adipose tissue ex vivo, consistent with lower adiponectin levels in pregnant B1KO mice. Furthermore, fasting insulinemia also increased, which was associated with placental insulin resistance, reduced placental glycogen accumulation, and heavier offspring. Therefore, we propose the combination of chronic hyperinsulinemia and reduced adiponectin secretion in B1KO female mice create a maternal obesogenic environment that results in heavier pups.

Kinin B1 Receptor Antagonism Prevents Acute Kidney Injury to Chronic Kidney Disease Transition in Renal Ischemia-Reperfusion by Increasing the M2 Macrophages Population in C57BL6J Mice.

BACKGROUND: Chronic kidney disease (CKD) is a multifactorial, world public health problem that often develops as a consequence of acute kidney injury (AKI) and inflammation. Strategies are constantly sought to avoid and mitigate the irreversibility of this disease. One of these strategies is to decrease the inflammation features of AKI and, consequently, the transition to CKD. METHODS: C57Bl6J mice were anesthetized, and surgery was performed to induce unilateral ischemia/reperfusion as a model of AKI to CKD transition. For acute studies, the animals received the Kinin B1 receptor (B1R) antagonist before the surgery, and for the chronic model, the animals received one additional dose after the surgery. In addition, B1R genetically deficient mice were also challenged with ischemia/reperfusion. RESULTS: The absence and antagonism of B1R improved the kidney function following AKI and prevented CKD transition, as evidenced by the preserved renal function and prevention of fibrosis. The protective effect of B1R antagonism or deficiency was associated with increased levels of macrophage type 2 markers in the kidney. CONCLUSIONS: The B1R is pivotal to the evolution of AKI to CKD, and its antagonism shows potential as a therapeutic tool in the prevention of CKD following AKI.

Kinin receptors regulate skeletal muscle regeneration: differential effects for B1 and B2 receptors.

OBJECTIVE AND DESIGN: After traumatic skeletal muscle injury, muscle healing is often incomplete and produces extensive fibrosis. Bradykinin (BK) reduces fibrosis in renal and cardiac damage models through the B2 receptor. The B1 receptor expression is induced by damage, and blocking of the kallikrein-kinin system seems to affect the progression of muscular dystrophy. We hypothesized that both kinin B1 and B2 receptors could play a differential role after traumatic muscle injury, and the lack of the B1 receptor could produce more cellular and molecular substrates for myogenesis and fewer substrates for fibrosis, leading to better muscle healing. MATERIAL AND METHODS: To test this hypothesis, tibialis anterior muscles of kinin receptor knockout animals were subjected to traumatic injury. Myogenesis, angiogenesis, fibrosis, and muscle functioning were evaluated. RESULTS: Injured B1KO mice showed a faster healing progression of the injured area with a larger amount of central nucleated fiber post-injury when compared to control mice. In addition, they exhibited higher neovasculogenic capacity, maintaining optimal tissue perfusion for the post-injury phase; had higher amounts of myogenic markers with less inflammatory infiltrate and tissue destruction. This was followed by higher amounts of SMAD7 and lower amounts of p-SMAD2/3, which resulted in less fibrosis. In contrast, B2KO and B1B2KO mice showed more severe tissue destruction and excessive fibrosis. B1KO animals had better results in post-injury functional tests compared to control animals. CONCLUSIONS: We demonstrate that injured skeletal muscle tissues have a better repair capacity with less fibrosis in the presence of B2 receptor and absence of B1 receptor, including better performances in functional tests.

Incentivos eleitorais e o gerenciamento de resultados orçamentários por meio de restos a pagar / Incentivos electorales y gestión de resultados presupuestarios a través de saldos a pagar / Electoral incentives and the management of budgetary results through unpaid commitment

Resumo O objetivo desta pesquisa é analisar o efeito dos ciclos políticos eleitorais sobre o gerenciamento de resultados orçamentários por meio de restos a pagar nos municípios brasileiros. Ao assinalar como lacuna empírico-teórica as incipientes métricas de qualidade da informação contábil no ambiente governamental, embasado na teoria da agência, da legitimidade e do gerenciamento de impressão, propõe-se um modelo de estimativa de accruals orçamentários discricionários, captados por meio do carry-over do tipo restos a pagar. Para isso, valemo-nos da teoria dos ciclos políticos para justificar o comportamento cíclico oportunista do gestor, em razão do calendário eleitoral. A partir de uma amostra contemplando 62,1% dos municípios brasileiros, foram testadas três hipóteses embasadas na literatura. Os resultados evidenciaram accruals orçamentários discricionários positivos nos anos imediatamente anteriores aos pleitos democráticos e sua reversão - accruals orçamentários discricionários negativos - em anos eleitorais, perfazendo o ciclo eleitoral orçamentário. Além disso, demonstra-se que os gestores em primeiro mandato estão mais inclinados a ingressar nesse tipo de prática, motivados pelas chances de sua recondução ao cargo, a despeito do sucesso no pleito, denotando que os prefeitos estão mais dispostos a adotar tais práticas durante o primeiro mandato. Essa evidência é ratificada, tendo em vista a não observância de níveis significativos dessa prática no segundo mandato. Em caráter incremental às pesquisas no setor público, esta propõe uma proxy de qualidade da informação contábil governamental e comprova que o gerenciamento de resultados, mensurados pelos accruals orçamentários discricionários, tem comportamentos cíclicos em razão do calendário eleitoral previamente estabelecido.

Resumen El objetivo de esta investigación es analizar el efecto de los ciclos políticos electorales en la gestión de los resultados presupuestarios a través de los saldos a pagar en los municipios brasileños. Al señalar como un vacío empírico-teórico las incipientes métricas de calidad de la información contable en el ámbito gubernamental, basadas en la teoría de agencia, legitimidad y gestión de impresiones, se propone un modelo de estimación de devengos presupuestarios discrecionales, capturados a través del arrastre del tipo remanentes a pagar. Para ello, utilizamos la teoría de los ciclos políticos para justificar el comportamiento cíclico oportunista del gestor, debido al calendario electoral. A partir de una muestra que cubre el 62,1% de los municipios brasileños, se probaron tres hipótesis basadas en la literatura. Los resultados mostraron devengos presupuestarios discrecionales positivos en los años inmediatamente anteriores a las elecciones democráticas y su reversión (devengos presupuestarios discrecionales negativos) en los años electorales, completando el ciclo electoral presupuestario. Asimismo, se demuestra que los gestores en su primer mandato son más proclives a incursionar en este tipo de práctica, motivados por las posibilidades de ser reelegidos en el cargo, a pesar de su éxito en las elecciones, denotando que los alcaldes están más dispuestos a adoptar este tipo de prácticas durante el primer mandato. Esta evidencia se ratifica al constatar la ausencia de niveles significativos de esta práctica en el segundo mandato. Además de la investigación en el sector público, propone una proxy de calidad de la información contable gubernamental y demuestra que la gestión de resultados, medida por los devengos presupuestarios discrecionales, tiene un comportamiento cíclico debido al calendario electoral previamente establecido.

Abstract This research aims to analyze the effect of electoral political cycles on the management of budgetary results by observing the unpaid commitments of Brazilian local governments. The study proposes a model to estimate discretionary budgetary accruals based on unpaid commitments, addressing an empirical-theoretical gap regarding incipient quality metrics of accounting information in public administration, considering the theory of agency, legitimacy, and impression management. The theory of political cycles was adopted to justify the managers' opportunistic cyclical behavior aligned with the electoral calendar. Three hypotheses based on the literature were tested from a sample covering 62.1% of Brazilian municipalities. The results showed positive discretionary budgetary accruals in the years immediately preceding the elections and the opposite in election years (i.e., negative discretionary budgetary accruals), completing the budgetary electoral cycle. Furthermore, it is demonstrated that managers in their first term are more inclined to enter into this type of practice, motivated by the chances of being re-elected. This evidence is ratified by the absence of this practice at significant levels during the managers' second term. This research incrementally contributes to public administration research, proposing a proxy for the quality of government accounting information. It proves that earnings management, measured by discretionary budgetary accruals, has cyclical behavior aligned with the electoral calendar.

Kinin B1 receptor modulates mitochondrial activity responsivity in fasting and voluntary exercise.

The Kallikrein-Kinin System (KKS) plays an important role in energy metabolism. We have previously described the importance of the kinin B1 receptor (B1R) in metabolism regulation. Considering that the liver manages the different energy demands of different body tissues, we combined two stressful conditions - fasting and voluntary exercise - to address how B1R may affect liver metabolism, focusing on mitochondrial function. AIMS: To investigate how the kinin B1 receptor (B1R) modulates mitochondrial activity under stress conditions, focusing on the rate of energy expenditure and shift in metabolism. MAIN METHODS: Wild-type and B1R-knockout (B1KO) male mice remained in a calorimetric cage with a wheel for 7 days; 48 h before euthanasia, half of the animals from both groups were submitted to fasting conditions. Mitochondrial activity, ketone bodies, and gene expression involving mitochondrial activity were evaluated. KEY FINDINGS: B1R modulates the mitochondrial activity under fasting and voluntary exercise, reducing the VO2 expenditure and HEAT. B1KO animals who exercised and underwent fasting did not have increased glucose levels, suggesting a preference for lipids as an energy source. Moreover, these animals displayed RER around 0.8, which indicates a ß-oxidation increment. Interestingly, the lack of B1R did not induce mitochondrial activity and biogenesis, suggesting interference in metabolism responsivity, a condition modulated by sirtuins under PGC-1α control. SIGNIFICANCE: B1R modulates mitochondrial respiratory control ratios, which suggests metabolic suppression, influencing hepatic metabolism and, consequently, energy homeostasis.

Perspectivas multidisciplinares sobre 'desinformação' em ciência e saúde / Multidisciplinary perspectives on 'disinformation' in science and health / Perspectivas multidisciplinares sobre 'desinformación' en ciencia y salud

Este dossiê possa contribuir para o esclarecimento de diferentes perspectivas sobre um problema comum, porém não menos complexo e que, portanto, exige uma compreensão a partir de diferentes olhares disciplinares: a desinformação relacionada à ciência e à saúde e seus impactos junto à sociedade

Kinin B1 receptor deficiency protects mice fed by cafeteria diet from abnormal glucose homeostasis.

The kallikrein-kinin system has been implicated in body weight and glucose homeostasis. Their major effectors act by binding to the kinin B2 and B1 receptors. It was assessed the role of the kinin B1 receptor in weight and glucose homeostasis in B1 receptor knockout mice (B1RKO) subjected to a cafeteria diet (CAF). Wild-type (WT) and B1RKO male mice (C57BL/6 background; 8 weeks old) were fed a standard diet (SD) or CAF for 14 weeks, ad libitum, and four groups were formed: WT-SD; B1RKO-SD; WT-CAF; B1RKO-CAF. Body weight and food intake were assessed weekly. It was performed glucose tolerance (GTT) and insulin tolerance tests (ITT), and HOMA-IR, HOMA-ß and HOMA-ß* 1/HOMA-IR were calculated. Islets from WT and B1RKO were isolated in order to measure the insulin secretion. Western blot was used to assess the hepatic AKT phosphorylation and qPCR to assess gene expression. CAF induced a higher body mass gain in B1RKO compared to WT mice. CAF diet increased epididymal fat depot mass, hepatic fat infiltration and hepatic AKT phosphorylation in both genotypes. However, B1RKO mice presented lower glycemic response during GTT when fed with CAF, and a lower glucose decrease in the ITT. This higher resistance was overcomed with higher insulin secretion when stimulated by high glucose, resulting in higher glucose uptake in the GTT when submitted to CAF, despite lower insulin sensitivity. Islets from B1RKO delivered 4 times more insulin in 3-month-old mice than islets from WT. The higher insulin disposition index and high insulin delivery of B1RKO can explain the decreased glucose excursion during GTT. In conclusion, CAF increased the ß-cell function in B1RKO mice, compensated by the diet-induced insulin resistance and resulting in a healthier glycemic response despite the higher weight gain.

Metabolic fasting stress is ameliorated in Kinin B1 receptor-deficient mice.

The liver has an essential role in responding to metabolic demands under stress conditions. The organ stores, releases, and recycles metabolism-related substrates. However, it is not clear how the Kallikrein-Kinin System modulates metabolic flexibility shift between energetic sources. AIMS: To analyze the hepatic metabolism in kinin B1 receptor deficient mice (B1KO mice) under fasting conditions. MAIN METHODS: WT and B1KO male mice were allocated in a calorimetric cage for 7 days and 48 h before the euthanasia, half of the animals of both groups were under fasting conditions. Biochemical parameters, ketone bodies (KB), and gene expression involving the liver energetic metabolism genes were evaluated. KEY FINDINGS: Kinin B1 receptor (B1R) modulates the metabolic shift under fasting conditions, reducing the VO2 expenditure. A preference for carbohydrates as an energetic source is suggested, as the B1KO group did not display an increase in KB in the serum. Moreover, the B1KO animals displayed higher serum triglycerides concentration compared to WT fasting mice. Interestingly, the lack of B1R induces the increase expression of enzymes from the glycolysis and lipolysis pathways under the fed. However, under fasting, the enzymatic expression of gluconeogenesis, glyceroneogenesis, and ketogenesis of these pathways does not occur, suggesting an absence of the shift metabolism responsivity, and this condition is modulated by PDK4 under FOXO1 control. SIGNIFICANCE: B1R has an important role in the hepatic glucose metabolism, which in turn influences the energetic metabolism, and in long-term outcomes, such as in the decrease in hepatic glycogen stores and in the enhancement of hepatic metabolism.

Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice.

Anemia is a common feature of chronic kidney disease (CKD). It is a process related to erythropoietin deficiency, shortened erythrocyte survival, uremic erythropoiesis inhibitors, and disordered iron homeostasis. Animal models of CKD-induced anemia are missing and would be desirable in order to study anemia mechanisms and facilitate the development of novel therapeutic tools. We induced three different models of CKD in mice and evaluated the development of anemia characteristics. Mice were subjected to unilateral ischemia-reperfusion or received repeated low doses of cisplatin or folic acid to induce nephropathy. Renal function, kidney injury and fibrotic markers were measured to confirm CKD. Moreover, serum hemoglobin, ferritin and erythropoietin were analyzed. Renal mRNA levels of HIF-2α, erythropoietin, hepcidin, GATA-2, and GATA-2 target genes were also determined. All three CKD models presented increased levels of creatinine, urea, and proteinuria. Renal up-regulation of NGAL, KIM-1, and TNF-α mRNA levels was observed. Moreover, the three CKD models developed fibrosis and presented increased fibrotic markers and α-SMA protein levels. CKD induced decreased hemoglobin and ferritin levels and increased erythropoietin levels in the serum. Renal tissue showed decreased erythropoietin and HIF-2α mRNA levels, while an increase in the iron metabolism regulator hepcidin was observed. GATA-2 transcription factor (erythropoietin repressor) mRNA levels were increased in all CKD models, as well as its target genes. We established three models of CKD-induced anemia, regardless of the mechanism and severity of kidney injury.

Cortisol Dose-Dependently Impairs Migration and Tube-like Formation in a Trophoblast Cell Line and Modulates Inflammatory and Angiogenic Genes.

Several stimuli can change maternal hormone levels during pregnancy. These changes may affect trophoblastic cells and modulate the development of the embryo and the placental tissue itself. Changes in cortisol levels are associated with impaired trophoblast implantation and function, in addition to other pregnancy complications. This study aims to analyze the effects of low and high doses of cortisol on an extravillous trophoblast cell line, and the effects of various exposures to this hormone. SGHPL-4 cells were treated with cortisol at five doses (0-1000 nM) and two exposures (continuous: 24 h/day; and intermittent: 2 h/day). In intermittent treatment, cortisol acted mainly as an anti-inflammatory hormone, repressing gene expression of kinin B1 receptors, interleukin-6, and interleukin-1ß. Continuous treatment modulated inflammatory and angiogenic pathways, significantly repressing angiogenic factors and their receptors. Cortisol affected cell migration and tube-like structures formation. In conclusion, both continuous and intermittent exposure to cortisol repressed the expression of inflammatory genes, while only continuous exposure repressed the expression of angiogenic genes, suggesting that a sustained increase in the levels of this hormone is more harmful than a high short-term increase. Cortisol also impaired tube-like structures formation, and kinin receptors may be involved in this response.

Potencial de nitrificação/desnitrificação de tanque séptico e wetland construído com recirculação no tratamento descentralizado de esgoto de empreendimento habitacional / Nitrification/denitrification potential of a septic tank and a constructed wetland with recirculation in the decentralized wastewater treatment from a housing development

RESUMO Os wetlands construídos (WC) são uma ecotecnologia aplicável para o tratamento descentralizado de esgotos notadamente em pequenas comunidades, em razão de sua simplicidade operacional. Existem vários arranjos e combinações de WC possíveis, destacando-se o arranjo tanque séptico (TS), seguido da modalidade de WC de escoamento vertical (WCV) com recirculação do efluente do WCV de volta para o TS, como proposta para possibilitar a remoção de nitrogênio presente no esgoto afluente. Entretanto, no Brasil, essa configuração e suas implicações operacionais e de desempenho são pouco exploradas. Diante disso, o objetivo deste trabalho foi avaliar o desempenho de um sistema de TS seguido de um WCV com recirculação no tratamento descentralizado de esgoto doméstico. O sistema empregado no tratamento de esgoto de um equivalente populacional de dez habitantes é composto de um TS (4,7 m3 de volume útil), seguido de um WCV (24,5 m2 de área superficial) preenchido com brita e plantado com Canna spp. O monitoramento, que compreendeu um período de nove meses, teve início após um ano e cinco meses de operação do sistema. Utilizando taxa de 50% de recirculação, taxa de aplicação hidráulica no WCV de 85 mm d-1 e carga de 47 g DQO m-2.d-1, foram obtidas boas eficiências para remoção conjunta de demanda química de oxigênio — DQO (80%), sólidos em suspensão totais — SST (85%) e nitrogênio total —NT (42%), mesmo com elevadas cargas orgânicas. Além das boas eficiências apresentadas, o sistema demonstrou ser robusto e de operação simples e representa uma alternativa tecnológica com potencial para o tratamento descentralizado de esgotos de empreendimentos habitacionais.

ABSTRACT Constructed wetland (CW) is an applicable eco-technology for decentralized wastewater treatment, notably in small communities, due to its operational simplicity. CW has several possible arrangements and combinations, among which the septic tank (ST) stands out, followed by the vertical flow constructed wetland (VFCW), with treated effluent recirculation back to the ST to enable nitrogen removal. However, in Brazil, this configuration and its operational and performance implications are little explored. Therefore, this study aimed to evaluate the performance of an ST system, followed by a VFCW with recirculation in the decentralized treatment of domestic wastewater. The wastewater treatment system for 10 inhabitants consists of an ST (4.7 m3 of useful volume), followed by a VFCW (24.5 m2 of surface area) planted with Canna spp. The monitoring, which covered a period of nine months, started after one year and five months of system operation. Using a 50% recirculation rate, VFCW hydraulic loading rate of 85 mm d-1, and organic load of 47 g COD m-2 d-1, good efficiencies were obtained for the joint removal of chemical oxygen demand — COD (80%), total suspended solids — TSS (85%), and total nitrogen — TN (42%), even with high organic loads. In addition to the good efficiencies presented, the system proved to be robust and easy to operate, representing a technological alternative with potential for the decentralized wastewater treatment of housing developments.

The Effects of High-Protein Diet and Resistance Training on Glucose Control and Inflammatory Profile of Visceral Adipose Tissue in Rats.

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-ß levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.

Effects of 12†weeks of resistance training on rat gut microbiota composition.

In addition to its health benefits, exercise training has been noted as a modulator of the gut microbiota. However, the effects of resistance training (RT) on gut microbiota composition remain unknown. Wistar rats underwent 12 weeks of RT. Body mass, glucose tolerance, visceral body fat, triglyceride concentration and food consumption were evaluated. The gut microbiota was analyzed by 16S rRNA gene sequencing. Rats that underwent RT showed lower body mass (P=0.0005), lower fat content (P=0.02) and better glucose kinetics (P=0.047) when compared with the control. Improvements in the diversity and composition of the gut microbiota were identified in the RT group. The relative abundance of Pseudomonas, Serratia and Comamonas decreased significantly after 12 weeks of RT (P<0.001). These results suggest that RT has the potential to enhance the diversity of the gut microbiota and improve its biological functions.

Interleukin-6 deficiency modulates testicular function by increasing the expression of suppressor of cytokine signaling 3 (SOCS3) in mice.

Several cytokines have been reported to participate in spermatogenesis, including interleukin-6 (IL6). However, not many studies have been conducted on the loss of Il6 on the male reproductive tract. Nonetheless, there is considerable knowledge regarding the pathological and physiological role of IL6 on spermatogenesis. In this way, this study evaluated the impact of Il6 deficiency on mice testicles in the absence of infection or inflammation. We showed that Il6 deficiency increases daily sperm production, the number of spermatids, and the testicular testosterone and dihydrotestosterone levels. Besides that, mice with a deleted Il6 (IL6KO) showed increased testicular SOCS3 levels, with no changes in pJAK/JAK and pSTAT3/STAT3 ratios. It is worth noting that the aforementioned pathway is not the only pathway to up-regulate SOCS3, nor is it the only SOCS3 target, thus proposing that the increase of SOCS3 in the testis occurs independently of the JAK-STAT signaling in IL6KO mice. Therefore, we suggest that the lack of Il6 drives androgenic production by increasing SOCS3 in the testis, thus leading to an increase in spermatogenesis.

Eletrocoagulação como pós-tratamento do efluente de um wetland construído de escoamento vertical / Electrocoagulation as post-treatment of the effluent from a vertical flow constructed wetland

RESUMO A eletrocoagulação (EC) foi aplicada como tratamento terciário para o efluente de wetland construído de escoamento vertical (WCV). O sistema de EC compreendeu um reator cilíndrico de vidro (1 L) e eletrodos de alumínio conectados a uma fonte de alimentação de corrente contínua. O estudo foi desenvolvido em duas etapas. Na primeira, as condições operacionais do reator foram delimitadas por meio de um experimento bifatorial 32 (3×3) de natureza quantitativa × quantitativa, analisando intensidade de corrente e tempo. Com base nos resultados obtidos, a regressão linear resultou na combinação de 1,3 A e 18 min, com custo operacional elétrico de 2,71 R$.m−3. Em seguida, realizou-se a etapa de monitoramento durante quatro meses, aplicando a EC sob essas condições fixas estabelecidas. As eficiências médias de remoção alcançadas foram de 99,7% para P-PO43-, 20,6% para N-NO3−, 2,37 log de coliformes totais, 2,35 log de Escherichia coli, 84,9% para demanda química de oxigênio, 95% para turbidez, 95,1% para cor aparente, aumento de 19% no pH, de 18,6% na temperatura e diminuição de 15,8% na condutividade elétrica. O tratamento demonstrou elevadas e homogêneas eficiências de remoção dos poluentes, principalmente para P-PO43-, indicando que a EC produz efluente com menor potencial poluidor e é indicada para tratamento de efluente doméstico em nível terciário.

ABSTRACT Electrocoagulation (EC) was applied as a tertiary treatment for the effluent of a vertical flow constructed wetland (VFCW). The EC system was composed of a cylindrical glass reactor (1 L) and aluminum electrodes connected to a DC power supply. The study was developed in two stages. In the first, the reactor operating conditions were set by a 32 (3×3) two-factor experiment, quantitative × quantitative, analyzing current intensity and time (current × time). Based on the results, the linear regression resulted in the combination of 1.3 A and 18 min, with an electric operation cost of 2.71 $.m−3. Next, the monitoring stage was conducted for four months, applying the EC under the established conditions. The mean removal efficiencies were 99.6% for P-PO43-, 20.6% for N-NO3−, 2.37 log of total coliforms, 2.35 log of Escherichia coli, 84.8% for chemical oxygen demand, 94.9% for turbidity, 95% for apparent color, an increase of 18.9% in pH and of 18.6% in temperature, and a decrease of 15.8% in electrical conductivity. The treatment showed high and homogeneous pollutant removal efficiencies, mainly for P-PO43-, indicating that the EC produces an effluent with lower polluting potential and it is recommended in the tertiary treatment of domestic wastewater.

Polymorphism of the bradykinin type 2 receptor gene modulates blood pressure profile and microvascular function in prepubescent children.

Previous reports reveal that +9/-9 polymorphism of the bradykinin B2 receptor (BDKRB2) is suggestive of cardiometabolic diseases. The aim of this study was to examine the impact of BDKRB2 + 9/-9 polymorphism genotypes on the blood pressure parameters and microvascular function in prepubescent children. We screened for BDKRB2 + 9/-9 polymorphism in the DNA of 145 children (86 boys and 59 girls), and its association with body composition, blood pressure levels, biochemical parameters, and endothelial function was determined. No significant association of the BDKRB2 genotypes with gender (P=0.377), race (P=0.949) or family history of cardiovascular disease (CVD) (P=0.858) was observed. Moreover, we did not identify any interaction between BDKRB2 genotypes with a phenotype of obesity (P=0.144). Children carrying the +9/+9 genotype exhibited a significant linear trend with higher levels of systolic blood pressure and pulse pressure (P<0.001). Moreover, the presence of +9 allele resulted in a decrease of reactive hyperemia index, showing a decreasing linear trend from -9/-9 to +9/+9, wherein this parameter of endothelial function was the lowest in the +9/+9 children, intermediate in the +9/-9 children, and the highest in the -9/-9 children (P<0.001). There was a significant inverse correlation between reactive hyperemia index and systolic blood pressure (r= - 0.348, P< 0.001) and pulse pressure (r= - 0.399, P< 0.001). Our findings indicate that the +9/+9 BDKRB2 genotype was associated with high blood pressure and microvascular dysfunction in prepubescent Brazilian children.

Interleukin-6 and the Gut Microbiota Influence Melanoma Progression in Obese Mice.

There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin (ob/ob) or adiponectin (AdpKO) and in wild-type mice (WT, C57BL/6J) fed a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. The survival rates of ob/ob and HFD-fed mice were lower than those of their respective controls. AdpKO mice also died earlier than WT control mice. We then verified the involvement of IL-6 signaling in obese mice that were inoculated with melanoma cells. Both ob/ob and AdpKO mice had higher circulating IL-6 levels than wild-type mice. Melanoma tumor volumes in IL-6 KO mice fed an HFD were reduced compared to those of WT mice subjected to the same diet. Also evaluated the effect of microbiota in tumor development. Cohousing and fecal matter transfer experiments revealed that microbiota from ob/ob mice can stimulate tumor development in lean WT mice. Taken together, our data show that in some conditions IL-6 and the gut microbiota are key mediators that link obesity and melanoma.

Combination of ACTN3 R577X and ACE I/D polymorphisms as a tool for prediction of obesity risk in children.

The genetic influence in obesity prevalence is well described, but the role of genetic markers related to athletic strength/ endurance performance remains controversial. We investigated associations between obesity and the genetic polymorphisms alpha-actinin-3 (ACTN3) R577X and angiotensin-converting enzyme (ACE) I/D in schoolchildren aged 4-13 years from Southern Brazil. We collected sociodemographic data from parents through a questionnaire and conducted an anthropometric assessment. DNA was extracted from buccal cells and genotyping was performed by PCR. We found that 1.9% of the individuals were classified as low weight-for-age, 57.6% as normal weight and 40.5% as overweight/ obesity. Regarding allelic distribution, we found that 52.5% of individuals were DD, 30.8% ID, and 16.7% II for ACE; and 38.8% of individuals were RR, 40.2% RX and 21.0% XX for ACTN3. When both polymorphisms were combined, we observed a clear association between the composed genetic profile of these alleles and severe obesity in schoolchildren. Our data suggest that the combined analysis of ACTN3 R577X and ACE I/D polymorphisms may serve as a predictor for the risk of severe obesity in children. These data can contribute to a better understanding of the relationship between these polymorphisms and the body weight development of school-age children.