Transforming growth factor beta (TGF‐β) is a cytokine with important involvement in biological processes related to the pathogenesis of sickle cell disease (SCD), including endothelial and vascular dysfunction, inflammation, and hematopoietic homeostasis. This study is aimed at investigating associations between levels of TGF‐β1 and classical laboratory biomarkers and inflammatory mediators, as well as the tissue inhibitor of metalloproteases‐1 (TIMP‐1) and matrix metalloproteinase‐9 (MMP‐9), in pediatric patients (n = 123) with SCD in steady state: 84 with sickle cell anemia (HbSS) and 39 with hemoglobin SC disease (HbSC). A healthy control (HC) group of 59 individuals was also included. Hematological and biochemical analyses were carried out using electronic methods. TGF‐β1, TIMP‐1, and MMP‐9 plasma quantifications were performed by ELISA. TGF‐β1 plasma levels were higher in HbSS individuals than in HbSC and HC. In individuals with HbSS, TGF‐β1 levels were positively correlated with red blood cells, hemoglobin, hematocrit, platelets, and TIMP‐1. In addition, HbSS individuals with TGF‐β1 levels above the median (≥72.29 ng/mL) also presented increased monocyte counts and decreased albumin levels. In patients with HbSC, TGF‐β1 levels were positively correlated with leukocytes, eosinophils, lymphocytes, monocytes, and platelets, as well as levels of TIMP‐1, VLDL‐C, triglycerides, heme, and AST. Additionally, HbSC individuals with TGF‐β1 levels above the median (≥47.80 ng/mL) presented increased leukocyte and platelet counts, as well as increased levels of triglycerides, VLDL‐C, MMP‐9, and TIMP‐1, and decreased HDL‐C. Our findings suggest that TGF‐β1 may play important roles in vascular remodeling, vasculopathy, angiogenesis, and inflammation in pediatric patients with SCD.

Osteosarcoma (OS) is a fast-progressing bone tumor with high incidence in children and adolescents. The main diagnostic methods for OS are imaging exams and biopsies. In spite of the several resources available for detecting the disease, establishing an early diagnosis is still difficult, resulting in worse prognosis and lower survival rates for patients with OS. The identification of novel biomarkers would be helpful, and recently, circulating microRNAs (miRNAs) have been pointed to as possible non-invasive biomarkers. In order to assess the effectiveness of miRNA research, we performed a systematic review to assess the potential role of circulating miRNAs as biomarkers for OS diagnosis. We performed a search in various databases—PubMed, LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde), VHL (Virtual Health Library), Elsevier, Web of Science, Gale Academic One File—using the terms: “Circulating microRNAs” OR “plasma microRNAs” OR “serum microRNAs” OR “blood microRNAs” OR “cell-free microRNAs” OR “exosome microRNAs” OR “extracellular vesicles microRNAs” OR “liquid biopsy” AND “osteosarcoma” AND “diagnostic”. We found 35 eligible studies that were independently identified and had had their quality assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Despite the useful number of publications on this subject and the fact that several microRNAs showed excellent diagnostic performance for OS, the lack of consistency in results suggests that additional prospective studies are needed to confirm the role of circulating miRNAs as non-invasive biomarkers in OS.

Individuals with sickle cell disease (SCD) present both chronic and acute inflammatory events. The TGF-β pathway is known to play a role in immune response, angiogenesis, inflammation, hematopoiesis, vascular inflammation, and cell proliferation. Polymorphisms in the transforming growth factor-beta receptor 3 (TGFBR3) gene have been linked to several inflammatory diseases. This study investigated associations between two TGFBR3 haplotypes and classical laboratory parameters, as well as clinical manifestations, in SCD. We found that individuals with the GG haplotype presented higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, non-HDL cholesterol, total proteins, and globulin than individuals with non-GG haplotypes. In addition, the GG haplotype was associated with a previous history of pneumonia. Individuals with the CGG haplotype presented increased plateletcrit, TC, LDL-C levels, and non-HDL cholesterol. The CCG haplotype was also associated with a previous history of pneumonia. Our findings suggest that individuals with the GG and CGG haplotypes of TGFBR3 present important alterations in lipid profile.

Introduction: The clarification of etiopathology, the improvement of chemotherapy regimens and their risk stratifications, and the improvement in treatment support have increased the survival of children and adolescents affected by Acute Lymphoblastic Leukemia (ALL) past few years. This study aimed to estimate overall survival (OS) and event-free survival (EFS) in an onco-hematology treatment center in Brazil, reports the main clinical-laboratory characteristics of patients at diagnosis, verify the frequency of treatment-related adverse effects and the main causes of death.Material and methods: Retrospective analysis involving patients diagnosed with ALL, treated with the protocol of the Brazilian Group for Treatment of Leukemias in Childhood (GBTLI), between 2010 and 2020 was carried out; the outcomes (relapse, deaths, development of new neoplasms) were analyzed SPSS® software was used for the statistical analyses, and the p-value was considered significant when less than 0.05 for all analyses.Results: 109 patients were included in the study; the median age was 5 years, with a slight predominance of males. Sixty-six patients were classified as high-risk (HR) group and 43 patients were classified as low-risk (LR) group. After 5 years of diagnosis, the OS was 71.5%, and the EFS was 65%. No statistical difference was found between the HR and LR groups for OS and EFS, while leukocyte counts were statistically associated with the outcome of death (p = 0.028). Among the patients, 28 (25.6%) died due to infection accounting 46.4% of death causes. Among the 34 patients with unfavorable outcomes (death and/or relapse), 32 had no research for the minimal residual disease at the end of remission induction, and 25 were not investigated for the presence of chromosomal abnormalities. The most reported complications and treatment-related adverse effects were increased liver transaminases (85.9%), airway infection (79.4%), oral mucositis (67.2%), febrile neutropenia (64.4%), and diarrhea (36.4%).Conclusions: The rates of OS and EFS obtained in this cohort are similar to those obtained in the few previous similar studies in Brazil and lower than those carried out in developed countries. The unavailability of prognostic tests may have hindered risk stratification and influenced the results obtained.

Sickle leg ulcers (SLU) are malleoli lesions with exuberant hemolytic pathophysiology. The microRNAs are potential genetic biomarkers for several pathologies. Thereby, we aimed to assess the expression of circulating miR-199a-5p, miR-144, and miR-126 in association with hemolytic biomarkers in SLU. This cross-sectional study included 69 patients with sickle cell disease, 52 patients without SLU (SLU-) and 17 patients with active SLU or previous history (SLU+). The results demonstrated elevated expression of circulating miR-199a-5p and miR-144 in SLU+ patients while miR-126 expression was reduced. Circulating miR-199a-5p and miR-144 were associated with hemolytic biomarkers such as LDH, indirect bilirubin, AST, GGT, iron, ferritin, RBC, hemoglobin, and NOm, in addition to association with impaired clinical profile of SLU. Furthermore, in silico analyses indicated interactions of miR-199a-5p with HIF1A, Ets-1, and TGFB2 genes, which are associated with vasculopathy and reduced NO. In contrast, miR-126 was associated with an attenuating clinical profile of SLU, in addition to not characterizing hemolysis. In summary, this study demonstrates, for the first time, that hemolytic mechanism in SLU can be characterized by circulating miR-199a-5p and miR-144. The circulating miR-126 may play a protective role in SLU. Thus, these microRNAs can support to establish prognosis and therapeutic strategy in SLU.