Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy.

Among sickle cell anemia (SCA) complications, proliferative sickle cell retinopathy (PSCR) is one of the most important, being responsible for visual impairment in 10-20% of affected eyes. The aim of this study was to identify differentially expressed genes (DEGs) present in pathways that may be implicated in the pathophysiology of PSCR from the transcriptome profile analysis of endothelial progenitor cells. RNA-Seq was used to compare gene expression profile of circulating endothelial colony-forming cells (ECFCs) from HbSS patients with and without PSCR. Furthermore, functional enrichment analysis and protein-protein interaction (PPI) networks were performed to gain further insights into biological functions. The differential expression analysis identified 501 DEGs, when comparing the groups with and without PSCR. Furthermore, functional enrichment analysis showed associations of the DEGs in 200 biological processes. Among these, regulation of mitogen-activated protein (MAP) kinase activity, positive regulation of phosphatidylinositol 3-kinase (PI3K), and positive regulation of Signal Transducer and Activator of Transcription (STAT) receptor signaling pathway were observed. These pathways are associated with angiogenesis, cell migration, adhesion, differentiation, and proliferation, important processes involved in PSCR pathophysiology. Moreover, our results showed an over-expression of VEGFC (vascular endothelial growth factor-C) and FLT1 (Fms-Related Receptor Tyrosine Kinase 1) genes, when comparing HbSS patients with and without PSCR. These results may indicate a possible association between VEGFC and FLT1 receptor, which may activate signaling pathways such as PI3K/AKT and MAPK/ERK and contribute to the mechanisms implicated in neovascularization. Thus, our findings contain preliminary results that may guide future studies in the field, since the molecular mechanisms of PSCR are still poorly understood.

Placental transcriptome profile of women with sickle cell disease reveals differentially expressed genes involved in migration, trophoblast differentiation and inflammation.

Sickle cell disease (SCD) is a group of disorders whose common characteristic is the presence of hemoglobin (Hb) S in erythrocytes. The main consequence of this abnormality is vaso-occlusion, which can affect almost all organs including the placenta. This study aimed to evaluate the gene expression profile in placentas of women with SCD by means of total RNA sequencing. For this, we proposed a case-control study, with three groups of pregnant women: HbSS (n = 10), HbSC (n = 14) and HbAA (n = 21). The results showed differences in expression in a number of genes such as NOS2 (fold change, FC = 4.52), HLAG (FC = 5.56), ASCL2 (FC = 3.61), CXCL10 (FC = -3.66) and IL1R2 (FC = 3.92) for the HbSC group and S100A8 (FC = -3.82), CPXM2 (FC = 4.57), CXCL10 (FC = -4.59), CXCL11 (FC = -3.72) and CAMP (FC = -4.55) for the HbSS group. Differentially expressed genes are mainly associated with migration, trophoblast differentiation and inflammation. The causes leading to altered gene expression in placentas of sickle cell patients are not fully understood, but the presence of intravascular hemolysis and vaso-occlusion, with cycles of ischemia and reperfusion, may contribute to the emergence of an environment which can be very harmful for placental physiology, altering the nutrient supply and metabolic exchange for fetal growth.

Mechanisms and biomarker candidates in pterygium development / Mecanismos e candidatos a biomarcadores no desenvolvimento do pterígio

ABSTRACT Pterygium pathogenesis has been mainly asso ciated with UV light exposure; however, this association remains quite controversial. The complete mechanism of pterygium also remains to be clarified. Factors such as inflammation, viral infection, oxidative stress, DNA methylation, inflammatory mediators, extracellular matrix modulators, apoptotic and oncogenic proteins, loss of heterozygosity, microsatellite instability, lymphangiogenesis, epithelial-mesenchymal cell transition, and alterations in cholesterol metabolism have been identified as causes. Several studies aimed to clarify the molecular mechanisms underlying the growth and proliferation of pterygium. Understanding its molecular basis provides new potential therapeutic targets for its prevention and treatment. A comprehensive search of the databases, namely, MedLine, EMBASE, and LILACS, was conducted with the following key words: pterygium, epidemiology, pathogenesis, biomarkers, and review. This review describes the epidemiology, clinical presentation, and current investigation of biological mediators involved in pterygium development.

RESUMO A patogênese do pterígio tem sido relacionada, prin cipalmente, à exposição à luz ultravioleta, mas esta asso ciação permanece bastante controversa. O mecanismo completo do pte rígio também permanece por esclarecer. Fatores como inflamação, infecção viral, estresse oxidativo, metilação do DNA, mediadores inflamatórios, moduladores de matriz extracelular, proteínas apoptóticas e oncogênicas, perda de heterozigose, instabilidade de microssatélites, linfangiogênese, transição celular epitelial-mesenquimal e alterações no metabolismo do colesterol tem sido identificados como causas. Diversos estudos visam esclarecer os mecanismos moleculares subjacentes ao crescimento e proliferação do pterígio. Entender sua base mo lecular fornece novos alvos terapêuticos potenciais para sua prevenção e tratamento. Uma busca abrangente nas bases de dados, a saber, MedLine, EMBASE e LILACS, foi realizada com as seguintes palavras-chave: pterígio; epidemiologia; patogênese; biomarcadores e revisão. Esta revisão descreve a epidemiologia, apresentação clínica e a atual investigação de mediadores biológicos envolvidos no desenvolvimento do pterígio.

Mechanisms and biomarker candidates in pterygium development.

Pterygium pathogenesis has been mainly asso ciated with UV light exposure; however, this association remains quite controversial. The complete mechanism of pterygium also remains to be clarified. Factors such as inflammation, viral infection, oxidative stress, DNA methylation, inflammatory mediators, extracellular matrix modulators, apoptotic and oncogenic proteins, loss of heterozygosity, microsatellite instability, lymphangiogenesis, epithelial-mesenchymal cell transition, and alterations in cholesterol metabolism have been identified as causes. Several studies aimed to clarify the molecular mechanisms underlying the growth and proliferation of pterygium. Understanding its molecular basis provides new potential therapeutic targets for its prevention and treatment. A comprehensive search of the databases, namely, MedLine, EMBASE, and LILACS, was conducted with the following key words: pterygium, epidemiology, pathogenesis, biomarkers, and review. This review describes the epidemiology, clinical presentation, and current investigation of biological mediators involved in pterygium development.

Abnormal expression of inflammatory genes in placentas of women with sickle cell anemia and sickle hemoglobin C disease.

Sickle cell disease (SCD) is a complex disease that is characterized by the polymerization of deoxyhemoglobin S, altered red blood cell membrane biology, endothelial activation, hemolysis, a procoagulant state, acute and chronic inflammation, and vaso-occlusion. Among the physiological changes that occur during pregnancy, oxygen is consumed by fetal growth, and pregnant women with SCD are more frequently exposed to low oxygen levels. This might lead to red blood cells sickling, and, consequently, to vaso-occlusion. The mechanisms by which SCD affects placental physiology are largely unknown, and chronic inflammation might be involved in this process. This study aimed to evaluate the gene expression profile of inflammatory response mediators in the placentas of pregnant women with sickle cell cell anemia (HbSS) and hemoglobinopathy SC (HbSC). Our results show differences in a number of these genes. For the HbSS group, when compared to the control group, the following genes showed differential expression: IL1RAP (2.76-fold), BCL6 (4.49-fold), CXCL10 (-2.12-fold), CXCR1 (-3.66-fold), and C3 (-2.0-fold). On the other hand, the HbSC group presented differential expressions of the following genes, when compared to the control group: IL1RAP (4.33-fold), CXCL1 (3.05-fold), BCL6 (4.13-fold), CXCL10 (-3.32-fold), C3 (-2.0-fold), and TLR3 (2.38-fold). Taken together, these data strongly suggest a differential expression of several inflammatory genes in both SCD (HbSS and HbSC), indicating that the placenta might become an environment with hypoxia, and increased inflammation, which could lead to improper placental development.

Keeping an eye on myocilin: a complex molecule associated with primary open-angle glaucoma susceptibility.

MYOC encodes a secretary glycoprotein of 504 amino acids named myocilin. MYOC is the first gene to be linked to juvenile open-angle glaucoma (JOAG) and some forms of adult-onset primary open-angle glaucoma (POAG). The gene was identified as an up-regulated molecule in cultured trabecular meshwork (TM) cells after treatment with dexamethasone and was originally referred to as trabecular meshwork-inducible glucocorticoid response (TIGR). Elevated intraocular pressure (IOP), due to decreased aqueous outflow, is the strongest known risk factor for POAG. Increasing evidence showed that the modulation of the wild-type (wt) myocilin protein expression is not causative of glaucoma while some misfolded and self-assembly aggregates of mutated myocilin may be associated with POAG in related or unrelated populations. The etiology of the disease remains unclear. Consequently, a better understanding of the molecular mechanisms underlying POAG is required to obtain early diagnosis, avoid potential disease progression, and develop new therapeutic strategies. In the present study, we review and discuss the most relevant studies regarding structural characterizations, expressions, molecular interactions, putative functions of MYOC gene and/or its corresponding protein in POAG etiology.