Polymorphisms in TPT1 Pathways in Pediatric Astrocytomas.

Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 (TPT1) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR, MDM2, TP53, and CDKN1A, correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas (p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared (p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma (p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.

Placental Morphologic Similarities Between ZIKV-Positive and HIV-Positive Pregnant Women.

Zika virus (ZIKV) caused global concern due to Brazil's unexpected epidemic, and it was associated with congenital microcephaly and other gestational intercurrences. The study aimed to analyze the placenta morphometric changes of ZIKV-infected pregnant women (ZIKV group; n = 23) compared to placentas of HIV-infected (HIV group; n = 24) and healthy pregnant women (N-control group; n = 22). It also analyzed the relationship between the morphometric results and pathological alterations on conventional microscopy, gestational trimester of infection, and presence of the congenital Zika syndrome (CZS). There was a significant increase in area (p = 0.0172), as well as a higher number of knots (p = 0.0027), sprouts (p < 0.0001), and CD163 +Hofbauer cells (HCs) (p < 0.0001) in the ZIKV group compared to the N-control group, suggesting that villous dysmaturity and HCs hyperplasia could be associated with ZIKV infections. The HIV group had a higher area (p < 0.0001), perimeter (p = 0.0001), sprouts (p < 0.0001), and CD163 + HCs (p < 0.0001) compared to the N-control group, demonstrating that the morphometric abnormalities found in the ZIKV and HIV group are probably similar. However, when ZIKV and HIV groups are compared, it was observed a higher number of sprouts (p = 0.0066) and CD163+ HCs (p < 0.0001) in the first one, suggesting that placental ZIKV congenital changes could be more pronounced.

The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury.

Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.