New-onset diabetes after kidney transplantation: Assessing urinary Wilm's tumor-1 protein to predict renal allograft dysfunction.

PURPOSE: New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). MATERIALS AND METHODS: KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. RESULTS: The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 â€‹mL/min/1.73 â€‹m2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. CONCLUSION: The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.

Effect of maternal diet on the frequency of micronuclei in pregnant women and newborns: A protocol for systematic review and meta-analysis.

BACKGROUND: The effects of diet on maternal and child genetic levels have been previously reported. Diet-associated DNA damage, such as the presence of micronuclei (MN), may be related to an increased risk of developing chronic diseases, such as cancer. Such damage is particularly concerning during pregnancy as it can affect the newborn. AIM: This review will aim to summarize the primary evidence of the impact of diet during pregnancy on micronucleus frequency in the maternal-newborn population. METHODS: This protocol was developed based on the Preferred Reporting Items guidelines for Systematic Reviews and Meta-analyses Protocol. The review was registered with the International Register of Prospective Systematic Reviews on February 17, 2022 (registration number: CRD42022302401). We will use PubMed, Embase, Web of Science, Scopus, Science direct, and Google databases to search for observational studies. This review will include studies that investigate the diet consumed by pregnant women and its effect on the frequency of MN in mothers and newborns without any time or language limitations. For data extraction, researchers will independently review the full text and collect information that characterizes the study and its findings. We will analyze the results by calculating the odds ratio for each type of diet evaluated, accompanied by a 95% confidence interval. We will perform a quantitative synthesis of homogeneous studies to perform a meta-analysis. Micronucleus frequency quantifies the effect and will be presented as the mean and standard deviation or median and interquartile range. EXPECTED RESULTS: This review will aim to identify which dietary patterns during pregnancy may be associated with an increase in the frequency of MN in mothers and their newborns. Understanding the impact of diet on the frequency of MN is essential to deepen studies and to propose strategies that aim to protect the health of the public through food.

Unraveling the role of miRNAs as biomarkers in Chagas cardiomyopathy: Insights into molecular pathophysiology.

BACKGROUND: Chagas cardiomyopathy (ChCM) is a severe form of Chagas disease and a major cause of cardiovascular morbidity and mortality. The dysregulation of the immune response leads to cardiac remodeling and functional disruptions, resulting in life-threatening complications. Conventional diagnostic methods have limitations, and therapeutic response evaluation is challenging. MicroRNAs (miRNAs), important regulators of gene expression, show potential as biomarkers for diagnosis and prognosis. AIM: This review aims to summarize experimental findings on miRNA expression in ChCM and explore the potential of these miRNAs as biomarkers of Chagas disease. METHODS: The search was conducted in the US National Library of Medicine MEDLINE/PubMed public database using the terms "Chagas cardiomyopathy" OR "Chagas disease" AND "microRNA" OR "miRNA" OR "miR." Additionally, bioinformatics analysis was performed to investigate miRNA-target interactions and explore enrichment pathways of gene ontology biological processes and molecular functions. RESULTS: The miR-21, miR-146b, miR-146a, and miR-155 consistently exhibited up-regulation, whereas miR-145 was down-regulated in ChCM. These specific miRNAs have been linked to fibrosis, immune response, and inflammatory processes in heart tissue. Moreover, the findings from various studies indicate that these miRNAs have the potential as biomarkers for the disease and could be targeted in therapeutic strategies for ChCM. CONCLUSION: In this review, we point out miR-21, miR-146b, miR-146a, miR-155, and miR-145-5p role in the complex mechanisms of ChCM. These miRNAs have been shown as potential biomarkers for precise diagnosis, reliable prognostic evaluation, and effective treatment strategies in the ChCM.

Unraveling the role of miRNAs as biomarkers in Chagas cardiomyopathy: Insights into molecular pathophysiology

BACKGROUND: Chagas cardiomyopathy (ChCM) is a severe form of Chagas disease and a major cause of cardiovascular morbidity and mortality. The dysregulation of the immune response leads to cardiac remodeling and functional disruptions, resulting in life-threatening complications. Conventional diagnostic methods have limitations, and therapeutic response evaluation is challenging. MicroRNAs (miRNAs), important regulators of gene expression, show potential as biomarkers for diagnosis and prognosis. AIM: This review aims to summarize experimental findings on miRNA expression in ChCM and explore the potential of these miRNAs as biomarkers of Chagas disease. METHODS: The search was conducted in the US National Library of Medicine MEDLINE/PubMed public database using the terms "Chagas cardiomyopathy" OR "Chagas disease" AND "microRNA" OR "miRNA" OR "miR." Additionally, bioinformatics analysis was performed to investigate miRNA-target interactions and explore enrichment pathways of gene ontology biological processes and molecular functions. RESULTS: The miR-21, miR-146b, miR-146a, and miR-155 consistently exhibited up-regulation, whereas miR-145 was down-regulated in ChCM. These specific miRNAs have been linked to fibrosis, immune response, and inflammatory processes in heart tissue. Moreover, the findings from various studies indicate that these miRNAs have the potential as biomarkers for the disease and could be targeted in therapeutic strategies for ChCM. CONCLUSION: In this review, we point out miR-21, miR-146b, miR-146a, miR-155, and miR-145-5p role in the complex mechanisms of ChCM. These miRNAs have been shown as potential biomarkers for precise diagnosis, reliable prognostic evaluation, and effective treatment strategies in the ChCM.

Zinc Status and Autism Spectrum Disorder in Children and Adolescents: A Systematic Review.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the prevalence of which has increased in children and adolescents over the years. Studies point to deficiency of trace elements as one of the factors involved in the etiology of the disorder, with zinc being one of the main trace elements investigated in individuals with ASD. The aim of this review is to summarize scientific evidence about the relationship between zinc status and ASD in children and adolescents. This review has been registered in the International Prospective Register of Systematic Reviews (registration number CRD42020157907). The methodological guidelines adopted were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were selected from an active investigation of the PubMed, Scopus, LILACS, and Google databases to search for observational studies. Fifty-two studies from twenty-two countries were included. The sample sizes ranged from 20 to 2635, and the participants ranged from 2 to 18 years old. Nine types of biological matrices were used, with hair, serum, and plasma being the most frequently used in the evaluation of zinc concentrations. Significant differences in zinc concentrations between the ASD and control groups were observed in 23 studies, of which 19 (36%) showed lower zinc concentrations in the ASD group. The classification of studies according to methodological quality resulted in high, moderate, and low quality in 10, 21, and 21 studies, respectively. In general, we did not observe a significant difference between zinc concentrations of children and adolescents with ASD compared to controls; however, studies point to an occurrence of lower concentrations of Zn in individuals with ASD. This review reveals that more prospective studies with greater methodological rigor should be conducted in order to further characterize this relation.

Impact of overweight and obesity on disease activity and remission in systemic lupus erythematosus: A systematic review and meta-analysis protocol.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease that requires treatment with hydroxychloroquine and glucocorticoids. Glucocorticoids are responsible for adverse effects such as increased weight, which can modify the severity and chronicity of autoimmune pathologies. AIM: To summarize scientific evidence regarding the impact of overweight and obesity on disease activity and remission in SLE. METHODS: The protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol (PRISMA-P) and published in the International Prospective Register of Systematic Reviews database (PROSPERO-CRD42021268217). PubMed, Scopus, Embase, and Google Scholar will be searched for observational studies including adult patients with SLE who were overweight and obese or not, that included disease activity or remission as outcomes. The search is planned for May 2023. Three independent authors will select the eligible articles and extract their data. Subsequently, three authors will independently extract data from each included study using an extraction form created by the researchers. Methodological quality analyses will be performed using the modified Newcastle-Ottawa scale. The results will be presented as a narrative synthesis according to the synthesis without a meta-analysis reporting guideline (SWiM). Meta-analysis will be conducted where appropriate using random-effects models. EXPECTED RESULTS: This review will identify the impact of overweight and obesity on the clinical features of SLE, helping clinicians manage disease activity and remission, both important to optimize disease outcomes and patient quality of life.

Vitamin D status and biomarkers of renal graft function after kidney transplantation: a longitudinal study.

Introduction: Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels occur after kidney transplantation (KTx), and can be associated with increase the risk of graft loss. This longitudinal study aimed to evaluate the vitamin D status and association with biomarkers of the renal graft function after KTx. Methods: this longitudinal study included 42 patients evaluated at baseline, 3 and 6 months after KTx. Biodemographic, clinical, and biochemical parameters such as 25(OH)D and parathyroid hormone (PTH), and biomarkers of renal graft function, such as creatinine, estimated glomerular filtration rate (eGFR), and albumin/creatinine ratio (ACR), were assessed. Sun exposure was also evaluated. Patients were categorized according to their 25(OH)D levels. Results: at baseline, 25(OH)D levels < 30 ng/mL were found in 43 % patients, and 38 % of these patients failed to improve their 25(OH)D levels by 6 months after KTx. Low 25(OH)D levels occurred regardless of sun exposure. Further, 44 % patients developed albuminuria at 6 months. An increased ACR was observed in patients with 25(OH)D levels < 30 ng/mL (p = 0.002) compared to that in patients with 25(OH)D > 30 ng/mL. Additionally, 25(OH)D levels were negatively correlated with ACR at 6 months post-KTx (r = -0.444; p = 0.003). Twelve (28.6 %) patients with 25(OH)D levels < 30 ng/mL showed no eGFR recovery until 6 months after KTx. Conclusion: low vitamin D levels and increased albuminuria were observed at 6 months after KTx, even in a region with high sun exposure. The association between vitamin D status and biomarkers of renal graft function after KTx should be explored in further studies.

Introducción: Introducción: los bajos niveles de 25-hidroxivitamina D [25(OH)D] ocurren después del procedimiento de trasplante de riñón (KTx) y pueden estar asociados con un aumento del riesgo de pérdida del injerto. Este estudio longitudinal tuvo como objetivo evaluar el estado de la vitamina D y la asociación con los biomarcadores de función del injerto renal después del KTx. Métodos: este estudio longitudinal incluyó a 42 pacientes que fueron evaluados al inicio del estudio y, 3 y 6 meses después del KTx. Se evaluaron los parámetros biodemográficos, clínicos y bioquímicos, como 25(OH)D y hormona paratiroidea (PTH), y los biomarcadores de función del injerto renal, como creatinina, tasa de filtración glomerular estimada (eGFR) y relación albúmina/creatinina (ACR). También se evaluó la exposición al sol. Los pacientes se clasificaron según sus niveles de 25(OH)D. Resultados: al inicio del estudio se encontraron niveles de 25(OH)D < 30 ng/ml en el 43 % de los pacientes, mientras que el 38 % de estos pacientes no lograron mejorar sus niveles de 25(OH)D a los 6 meses después del KTx. También se produjeron niveles bajos de 25(OH)D independientemente de la exposición al sol. Asimismo, el 44 % de los pacientes desarrollaron albuminuria a los 6 meses. Se observó un aumento de la ACR en los pacientes con niveles de 25(OH)D < 30 ng/mL (p = 0,002) en comparación con los pacientes con 25(OH)D > 30 ng/mL. Además, los niveles de 25(OH)D se correlacionaron negativamente con la ACR a los 6 meses después del KTx (r = -0,444; p = 0,003). Doce (28,6 %) pacientes con niveles de 25(OH)D < 30 ng/ml no mostraron recuperación de la TFGe hasta 6 meses después del KTx. Conclusión: se observaron niveles bajos de vitamina D y un aumento de la albuminuria a los 6 meses después del KTx, incluso en una región con alta exposición solar. La asociación entre el estado de la vitamina D y los biomarcadores de función del injerto renal después del KTx debe explorarse en estudios adicionales.

Effects of selenium supplementation on glycaemic control markers in healthy rodents: a systematic review and meta-analysis.

Overexposure to Se is detrimental to glucose metabolism, mainly because of its pro-oxidant effects and the overexpression of selenoproteins. This systematic review evaluated the effects of Se supplementation on glycaemic control in healthy rodents. The methodology followed the PRISMA. We searched the databases for articles published up to May 2022. The risk of bias and the methodological quality were assessed using the SYRCLE and CAMARADES. The results are presented as meta-analytic estimates of the overall standardised mean difference (SMD) and 95 % CI. Of the 2359 records retrieved, thirteen studies were included, of which eleven used sodium selenite and two used zero-valent Se nanoparticles as supplement. Nine studies were included in the meta-analysis. Generally, the risk of bias was high, and 23·1 % of the studies were of high quality. Supplementation with sodium selenite significantly increased fasting blood glucose (SMD = 2·57 (95 % CI (1·07, 4·07)), I2 = 93·5 % (P = 0·001). Subgroup analyses showed effect size was larger for interventions lasting between 21 and 28 d (SMD = 25·74 (95 % CI (2·29, 9·18)), I2 = 96·1 % (P = 0·001)) and for a dose of 864·7 µg/kg/d of sodium selenite (SMD = 10·26 (95 % CI (2·42, 18·11), I2 = 97·1 % (P = 0·010)). However, it did not affect glutathione peroxidase activity (SMD = 0·60 (95 % CI (-0·71, 1·91)), I2 = 83·2 % (P = 0·37)). The current analysis demonstrated the adverse effects of sodium selenite supplementation on glycaemic control in healthy rodents.

Screening by high-throughput sequencing for pathogenic variants in cystic fibrosis: Benefit of introducing personalized therapies.

This short report documented cystic fibrosis transmembrane conductance regulator (CFTR) variants in 37 patients with cystic fibrosis (CF) in the Rio Grande do Norte region of Northeast Brazil. The high-throughput sequencing technology (HTS) genetic testing provided a definitive molecular diagnosis in 31 patients (83.8%). Among them, 25 patients' carriers of the c.1521_1523delCTT variant, categorized as a class 2 mutation, can be currently treated with CFTR modulator drugs. Five children aged 2-5 years could benefit from double lumacaftor/ivacaftor therapy, and 20 patients aged >6 years could be treated with the triple-combination elexacaftor/tezacaftor/ivacaftor therapy. Thus, the identification of pathogenic variants associated with the development of this disease allows for the introduction of therapy with CFTR modulators that favour better patient management.

Association of CYP2R1 and VDR Polymorphisms with Metabolic Syndrome Components in Non-Diabetic Brazilian Adolescents.

Associations between vitamin D deficiency and metabolic syndrome (MS) have been reported; however, the underlying biological mechanisms remain controversial. The aim of this study was to investigate the associations of CYP2R1 and VDR variants with MS and MS components in non-diabetic Brazilian adolescents. This cross-sectional study included 174 adolescents who were classified as overweight/obese. Three CYP2R1 variants and four VDR variants were identified by allelic discrimination. The CYP2R1 polymorphisms, rs12794714 (GG genotype) (odds ratio [OR] = 3.54, 95% confidence interval [CI] = 1.24-10.14, p = 0.023) and rs10741657 (recessive model-GG genotype) (OR = 3.90, 95%CI = 1.18-12.92, p = 0.026) were significantly associated with an increased risk of MS and hyperglycemia, respectively. The AG + GG genotype (dominant model) of the rs2060793 CYP2R1 polymorphism was associated with hyperglycemia protection (OR = 0.28, 95%CI = 0.08-0.92, p = 0.037). Furthermore, the CC genotype (recessive model) of the rs7975232 VDR polymorphism was significantly associated with a risk of hypertension (OR = 5.91, 95%CI = 1.91-18.32, p = 0.002). In conclusion, the CYP2R1 rs12794714 polymorphism could be considered a possible new molecular marker for predicting the risk of MS; CYP2R1 rs10741657 polymorphism and VDR rs7975232 polymorphism are associated with an increased risk of diabetes and hypertension in adolescents with overweight/obesity.

Antioxidant Effect of Coenzyme Q10 in the Prevention of Oxidative Stress in Arsenic-Treated CHO-K1 Cells and Possible Participation of Zinc as a Pro-Oxidant Agent.

Oxidative stress is an imbalance between levels of reactive oxygen species (ROS) and antioxidant enzymes. Compounds with antioxidant properties, such as coenzyme Q10 (CoQ10), can reduce cellular imbalance caused by an increase in ROS. CoQ10 participates in modulating redox homeostasis due to its antioxidant activity and its preserving mitochondrial functions. Thus, the present study demonstrated the protective effects of CoQ10 against oxidative stress and cytotoxicity induced by arsenic (As). Antioxidant capacity, formation of hydroperoxides, generation of ROS, and the effect on cellular viability of CoQ10, were investigated to determine the protective effect of CoQ10 against As and pro-oxidant compounds, such as zinc. Cell viability assays showed that CoQ10 is cytoprotective under cellular stress conditions, with potent antioxidant activity, regardless of the concentration tested. Zn, when used at higher concentrations, can increase ROS and show a pro-oxidant effect causing cell damage. The cytotoxic effect observed for As, Zn, or the combination of both could be prevented by CoQ10, without any decrease in its activity at cellular levels when combined with Zn.

Effects of an individualized nutritional intervention on kidney function, body composition, and quality of life in kidney transplant recipients: Study protocol for a randomized clinical trial.

BACKGROUND: Proteinuria after kidney transplantation (KTx) has been a frequent problem due to several factors, high protein intake being one of them. Individualized nutritional intervention in the late post-KTx period can promote the improvement or the reduction of risks associated with the parameters of evaluation of kidney function, body composition, and quality of life in individuals submitted to KTx. METHODS: This is a single-center, randomized and stratified clinical trial. The study will be conducted in a university hospital in northeastern Brazil with 174 individuals aged ≥19 years submitted to KTx and followed up for 12 months. Assessments will take place at 3-month intervals (T0, T3, T6, T9, and T12). The patients will be allocated to intervention and control groups by random allocation. The intervention group will receive individualized nutritional interventions with normoproteic diets (1.0 g/kg) after 60 days of KTx whereas the controls will receive the standard nutritional guidance for the post-KTx period. The primary efficacy variable is the change from baseline in log proteinuria assessed with the urinary albumin/creatinine ratio. Secondary efficacy variables include body composition, anthropometry, quality of life assessment and physical activity, lipid profile and glycemic control. Ninety-two subjects per group will afford 70% power to detect a difference of 25% between groups in log proteinuria. Primary efficacy analysis will be on the modified intention-to-treat population with between-groups comparison of the change from baseline in log proteinuria by analysis of covariance. DISCUSSION: The study will assess the effects of an individualized nutritional intervention on proteinuria 12 months after KTx. TRIAL REGISTRATION: REBEC (RBR-8XBQK5).

Effects of selenium supplementation on glycemic control markers in healthy rodents: A systematic review protocol.

BACKGROUND: In vivo and in vitro studies have shown that Se has an insulin-mimetic action associated with its antioxidant activity. Other studies, in turn, suggest that high Se doses and high selenoprotein expression interfere with insulin signaling. This study aims to evaluate the effects of Se supplementation on glycemic control markers in healthy rodents. METHODS: The protocol was developed according to the Preferred Reporting Items for Systematic Review and Metaanalysis Protocol (PRISMA-P) and was published in the International Prospective Register of Systematic Reviews database (PROSPERO; CRD4202121201142019119181). Experimental, randomized, or non-randomized studies of healthy rodents models will be included. All forms of supplemented Se will be considered, including organic, inorganic, and synthetic compounds, selenium-enriched yeasts, zerovalent Se nanoparticles, and selenized polysaccharides. Fasting blood glucose will be considered the primary outcome. Homeostatic model assessment, plasma and erythrocyte Se concentration, GPX activity, SELENOP concentration, and other Se biomarkers will be considered secondary outcomes. EMBASE, Scopus, Pubmed/Medline, Web of Science, and CINAHL will be searched for articles published with no language restrictions. Two reviewers will independently conduct the search and selection of articles, data extraction, and quality analysis. The risk of bias and methodological quality analyses of the included studies will be performed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) and Collaborative Approach to Meta-Analysis and Review (CAMARADES) tools, respectively. The results will be presented as a narrative synthesis according to the Synthesis Without Meta-analysis (SWiM) Reporting Guideline. Meta-analyses will be conducted where appropriate using random-effects models. DISCUSSION: The review may clarify the interaction between different forms of supplemented Se and glycemic control in rodents models. The results will provide evidence that will help select doses and forms of Se to administer in clinical trials while according to impact on the glycemic control while elucidating mechanisms of Se metabolism.

Hyperbaric oxygen therapy mitigates left ventricular remodeling, upregulates MMP-2 and VEGF, and inhibits the induction of MMP-9, TGF-ß1, and TNF-α in streptozotocin-induced diabetic rat heart.

AIMS: Hyperbaric oxygen (HBO) therapy has been widely used for the adjunctive treatment of diabetic wounds, and is currently known to influence left ventricular (LV) function. However, morphological and molecular repercussions of the HBO in the diabetic myocardium remain to be described. We aimed to investigate whether HBO therapy would mitigate adverse LV remodeling caused by streptozotocin (STZ)-induced diabetes. MAIN METHODS: Sixty-day-old Male Wistar rats were divided into four groups: Control (n = 8), HBO (n = 7), STZ (n = 10), and STZ + HBO (n = 8). Diabetes was induced by a single STZ injection (60 mg/kg, i.p.). HBO treatment (100% oxygen at 2.5 atmospheres absolute, 60 min/day, 5 days/week) lasted for 5 weeks. LV morphology was evaluated using histomorphometry. Gene expression analyzes were performed for LV collagens I (Col1a1) and III (Col3a1), matrix metalloproteinases 2 (Mmp2) and 9 (Mmp9), and transforming growth factor-ß1 (Tgfb1). The Immunoexpression of cardiac tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were also quantified. KEY FINDINGS: HBO therapy prevented LV concentric remodeling, heterogeneous myocyte hypertrophy, and fibrosis in diabetic rats associated with attenuation of leukocyte infiltration. HBO therapy also increased Mmp2 gene expression, and inhibited the induction of Tgfb1 and Mmp9 mRNAs caused by diabetes, and normalized TNF-α and VEGF protein expression. SIGNIFICANCE: HBO therapy had protective effects for the LV structure in STZ-diabetic rats and ameliorated expression levels of genes involved in cardiac collagen turnover, as well as pro-inflammatory and pro-angiogenic signaling.

Chemical Characterization of Flowers and Leaf Extracts Obtained from Turnera subulata and Their Immunomodulatory Effect on LPS-Activated RAW 264.7 Macrophages.

The anti-inflammatory properties of Turnera subulata have been evaluated as an alternative drug approach to treating several inflammatory processes. Accordingly, in this study, aqueous and hydroalcoholic extracts of T. subulata flowers and leaves were analyzed regarding their phytocomposition by ultrafast liquid chromatography coupled to mass spectrometry, and their anti-inflammatory properties were assessed by an in vitro inflammation model, using LPS-stimulated RAW-264.7 macrophages. The phytochemical profile indicated vitexin-2-O-rhamnoside as an important constituent in both extracts, while methoxyisoflavones, some bulky amino acids (e.g., tryptophan, tyrosine, phenylalanine), pheophorbides, and octadecatrienoic, stearidonic, and ferulic acids were detected in hydroalcoholic extracts. The extracts displayed the ability to modulate the in vitro inflammatory response by altering the secretion of proinflammatory (TNF-α, IL-1ß, and IL-6) and anti-inflammatory (IL-10) cytokines and inhibiting the PGE-2 and NO production. Overall, for the first time, putative compounds from T. subulata flowers and leaves were characterized, which can modulate the inflammatory process. Therefore, the data highlight this plant as an option to obtain extracts for phytotherapic formulations to treat and/or prevent chronic diseases.

Cardiovascular Effects Induced by Fruit Peels from Passiflora edulis in Hypertensive Rats and Fingerprint Analysis by HPLC-ESI-MSn spectrometry.

Hypertension is a chronic disease and a global health problem. Due to its high prevalence, it constitutes the most important risk factor for cardiovascular disease. Fruit peels from Passiflora edulis fo. flavicarpa are rich in bioactive natural compounds that may have action in hypertension. This study aimed to perform a fingerprinting analysis of Passiflora edulis fruit peel extract and evaluate its actions on the cardiovascular system in an in vivo model. The extract was obtained from the dried and powdered fruit peels of Passiflora edulis. Glycoside flavonoids were identified in the extract by HPLC-ESI-MSn. The extract showed a significant hypotensive effect after 28 days of treatment and improved vascular function in the mesenteric artery. This effect was verified by decreased vascular hypercontractility and increased vasorelaxant in response to sodium nitroprusside and acetylcholine. There was also a decrease in endothelial dysfunction, which can be attributed to nitric oxide's increased bioavailability. Thus, we hypothesize that all these effects contributed to a reduction in peripheral vascular resistance, leading to a significant hypotensive effect. These results are novel for fruit peels from P. edulis. Also, there was a decrease in plasma and cardiac malondialdehyde levels and an increase in glutathione, suggesting a reduction in oxidative stress, as well as an increase of anti-inflammatory cytokines such as IL-10 in the plasma. This study demonstrated that the extract can be a new source of raw material to be applied as food or medicine adjuvant for treating hypertension.

Cardiometabolic risk factors and hypovitaminosis D in adolescents with overweight from a sunny region in northeast Brazil: a cross-sectional study.

INTRODUCTION: Background: obesity can influence vitamin D levels, which in turn might be associated with cardiometabolic risk factors. Objectives: this study assessed the association between 25-hydroxyvitamin D [25(OH)D] levels and cardiometabolic risk factors in adolescents with overweight living in a region of northeastern Brazil. Material and methods: a cross-sectional study was carried out by non-probabilistic sampling in adolescents diagnosed with overweight or obesity. The subjects were divided according to their 25(OH)D status into two groups: sufficient vitamin D and hypovitaminosis D. Biodemographic, lifestyle, cardiometabolic, and biochemical factors were evaluated. A logistic regression model was applied to determine the predictors of hypovitaminosis D. Results: we found a high frequency of hypovitaminosis D (45.6 %) in adolescents. Weekly sun exposure was negatively associated with hypovitaminosis D (OR = 0.96; 95 % CI: 0.92-0.99), while significant positive associations were observed between hypovitaminosis D and blood pressure above the 95th percentile (OR = 4.00; 95 % CI: 1.19-13.37), body weight (OR = 1.04; 95 % CI: 1.01-1.07), and fasting insulin (OR = 1.13; 95 % CI: 1.05-1.22). Conclusion: hypovitaminosis D showed a high prevalence in adolescents with overweight living in a sunny region of northeastern Brazil, and cardiometabolic risk factors such as systemic arterial hypertension, high body weight, and hyperinsulinemia are predictors of hypovitaminosis D.

INTRODUCCIÓN: Introducción: la obesidad puede influir en los niveles de vitamina D, lo que a su vez podría estar asociado con factores de riesgo cardiometabólico. Objetivos: este estudio evaluó la asociación entre los niveles de 25-hidroxivitamina D [25(OH)D] y los factores de riesgo cardiometabólico en adolescentes con sobrepeso que viven en una región del noreste de Brasil. Material y métodos: se realizó un estudio transversal mediante muestreo no probabilístico con adolescentes diagnosticados de sobrepeso u obesidad. Los sujetos se dividieron según su estado de 25(OH)D en dos grupos: suficiente vitamina D e hipovitaminosis D. Se evaluaron factores biodemográficos, de estilo de vida, cardiometabólicos y bioquímicos. Se aplicó un modelo de regresión logística para determinar los predictores de la hipovitaminosis D. Resultados: encontramos una alta frecuencia de hipovitaminosis D (45,6 %) en los adolescentes. La exposición semanal al sol se asoció negativamente a la hipovitaminosis D (OR = 0,96; IC 95 %: 0,92-0,99), mientras que se observaron asociaciones positivas significativas entre hipovitaminosis D y presión arterial por encima del percentil 95 (OR = 4,00; IC 95 %: 1,19-13,37), peso corporal (OR = 1,04; IC del 95 %: 1,01-1,07) e insulina en ayunas (OR = 1,13; IC del 95 %: 1,05-1,22). Conclusión: la hipovitaminosis D mostró una alta prevalencia entre los adolescentes con sobrepeso que viven en una región soleada del noreste de Brasil, y los factores de riesgo cardiometabólico, como hipertensión arterial sistémica, peso corporal elevado e hiperinsulinemia, son predictores de hipovitaminosis D.

Hypoglycemic and Vasorelaxant Effect of Passiflora edulis Fruit Peel By-Product.

Passiflora edulis fo. flavicarpa (Passifloraceae) is popularly known as yellow passion fruit and its fruit peels are considered a rich by-product in bioactive compounds which has greatly beneficial health properties. The objective of this study was to evaluate the effects of P. edulis fruit peel extracts in a type 1 diabetes model and the potential vasorelaxant effect. The aqueous and hydroethanolic extracts were obtained from P. edulis fruit peels and orientin and isorientin flavonoids were identified in both extracts through ultra-high performance liquid chromatography. Pectin was only identified in the aqueous extract by high-performance steric exclusion chromatography and nuclear magnetic resonance. Regarding the vascular system, the hydroethanolic extract showed better vasorelaxant effects in the mesenteric artery rings when compared to the aqueous extract. These effects mainly occur by opening the potassium channels. In the type 1 diabetes model, extracts at doses of 400 and 600 mg/kg were able to restore the effect of insulin in diabetic rats which were not responding to its action. The antidiabetic effect was more significant for the aqueous extract. Thus, the results suggest that the hydroethanolic and aqueous extracts have greater potential to be used to treat cardiovascular diseases such as hypertension and as a hypoglycemic agent, respectively. Taken together, P. edulis fruit peel extracts proved to be a source of valuable bioactive raw material to produce nutraceuticals or pharmaceutical products.

IRF6 polymorphisms in Brazilian patients with non-syndromic cleft lip with or without palate / Polimorfismos do gene IRF6 em pacientes brasileiros com fenda labial não sindrômica com ou sem fenda palatina

Abstract Introduction: Non-syndromic orofacial clefts have a complex etiology due to the contribution from both genetic and environmental risk factors, as well as the interaction between them. Among the more than 15 susceptibility loci for non-syndromic orofacial clefts with considerable statistical and biological support, the IRF6 is the most validated gene by the majority of studies. Nonetheless, in genetically heterogeneous populations such as Brazilian, the confirmation of association between non-syndromic orofacial clefts and IRF6 common variants is not a consolidated fact and unrecognized IRF6 variants are poorly investigated. Objective: The aim of this study was to investigate the association of IRF6 polymorphisms with non-syndromic orofacial clefts development in a population from northeast Brazil. Methods: Blood samples of 186 non-syndromic orofacial clefts patients and 182 controls from Rio Grande do Norte, Brazil, were obtained to analyze IRF6 polymorphisms (rs2235371, rs642961, rs2236907, rs861019, and rs1044516) by real-time polymerase chain reaction. Non-syndromic orofacial clefts patients were classified in cleft lip and palate, cleft palate only and cleft lip only groups. Results: The genotype and allele frequencies of single nucleotide polymorphism rs2235371 in IRF6 showed significant differences in patients with cleft palate when compared to the controls, whereas no association was shown between rs642961, rs2236907, rs861019, and rs1044516 and non-syndromic orofacial clefts. Conclusion: The association found between rs2235371 and isolated cleft palate should be interpreted with caution due to the low number of individuals investigated, and more studies with larger sample size are needed to confirm these association. In addition, there is a lack of association of the rs642961, rs2236907 and rs861019 polymorphisms with non-syndromic orofacial clefts susceptibility.

Resumo Introdução: As fendas orofaciais não sindrômicas possuem uma etiologia complexa devido à contribuição de fatores de risco genéticos e ambientais, assim como a interação entre eles. Dentre os mais de 15loci de susceptibilidade para as fendas orofaciais não sindrômicas com considerável suporte estatístico e biológico, o IRF6 é o gene mais validado pela maioria dos estudos. Apesar disso, em populações geneticamente heterogêneas como a brasileira, a confirmação da associação entre as fendas orofaciais não sindrômicas e as variantes mais comuns do IRF6 ainda não é um fato consolidado e outras variantes não tão conhecidas IRF6 são pouco investigadas. Objetivo: O objetivo deste estudo foi investigar a associação de variados polimorfismos do IRF6 com o desenvolvimento das fendas orofaciais não sindrômicas em uma população do nordeste do Brasil. Método: Amostras de sangue de 186 pacientes com fendas orofaciais não sindrômicas e 182 controles do estado do Rio Grande do Norte, Brasil, foram obtidas para analisar os polimorfismos do IRF6 (rs2235371, rs642961, rs2236907, rs861019 e rs1044516) por reação em cadeia da polimerase em tempo real. Os pacientes com fendas orofaciais não sindrômicas foram classificados em fenda labiopalatina, fenda palatina isolada e fenda labial isolada. Resultados: As frequências genotípica e alélica do polimorfismo de único nucleotídeo rs2235371 no IRF6 mostraram-se significativamente diferentes em pacientes com fenda palatina isolada quando comparadas às dos controles, enquanto que nenhuma associação foi encontrada entre rs642961, rs2236907, rs861019 e rs1044516 e risco para o desenvolvimento das fendas orofaciais não sindrômicas. Conclusão: A associação encontrada entre rs2235371 e fenda palatina isolada deve ser interpretada com cautela devido ao baixo número de indivíduos investigados, sendo necessários mais estudos com um tamanho amostral maior para confirmar essa associação. Além disso, não foram encontradas associações significativas entre os demais polimorfismos do IRF6 rs642961, rs2236907, rs861019 e rs1044516 e a susceptibilidade às fendas orofaciais não sindrômicas.

Chloroquine as a promising adjuvant therapy for type 1 Diabetes Mellitus.

Chloroquine (CQ) and hydroxychloroquine, are promising anti-inflammatory drugs for the treatment of Diabetes mellitus (DM) to prevent associated complications. Therefore, this study evaluated the anti-inflammatory effects of CQ-free and CQ-incorporated polylactic acid nanoparticles (NPs) in the peripheral blood mononuclear cells (PBMCs) of patients with type 1 Diabetes mellitus (T1DM). In total, 25 normoglycemic individuals and 25 patients with T1DM aged 10-16 years were selected and glycemic controls evaluated. After cell viability assessed by MTT assay, T1DM PBMCs were subjected to a CQ concentration of 10 µM in three different conditions: not treated (NT), treated with CQ, and treated with CQ NPs. The cells were incubated for 48 h, and the mRNA expressions of cytokines IL1B, IFNG, TNFA, IL12, and IL10 were determined by relative quantification through real-time PCR at 24 h intervals. IL1B expression decreased in CQ and CQ NP-treated cells after 48 h (p < 0.001) and 24 h (p < 0.05) of treatment, respectively. IFNG and IL12 expressions significantly decreased (p < 0.001) in cells treated with CQ and CQ NPs at 24 and 48 h compared to NT. TNFA and IL10 expressions significantly decreased after 48 h (p < 0.001) and 24 h (p < 0.002), respectively, by both CQ and CQ NPs treatment. Despite being a preliminary in vitro study, CQ has anti-inflammatory activity in the primary cells of T1DM patients and could represent an alternative and adjuvant anti-inflammatory therapy to prevent diabetes complications.