No abstract

The aim of this study was to evaluate the expression of USP7, USP15, UBE2O, and UBE2T genes in Myelodysplastic neoplasm (MDS) to identify possible targets of ubiquitination and deubiquitination in MDS pathobiology. To achieve this, eight datasets from the Gene Expression Omnibus (GEO) database were integrated, and the expression relationship of these genes was analyzed in 1092 MDS patients and healthy controls. Our results showed that UBE2O, UBE2T, and USP7 were upregulated in MDS patients compared with healthy individuals, but only in mononucleated cells collected from bone marrow samples (p < 0.001). In contrast, only the USP15 gene showed a downregulated expression compared with healthy individuals (p = 0.03). Additionally, the upregulation of UBE2T expression was identified in MDS patients with chromosomal abnormalities compared with patients with normal karyotypes (p = 0.0321), and the downregulation of UBE2T expression was associated with MDS hypoplastic patients (p = 0.033). Finally, the USP7 and USP15 genes were strongly correlated with MDS (r = 0.82; r2 = 0.67; p < 0.0001). These findings suggest that the differential expression of the USP15-USP7 axis and UBE2T may play an important role in controlling genomic instability and the chromosomal abnormalities that are a striking characteristic of MDS.

Este artigo descreve uma planilha de autopreenchimento completa para o cálculo de Hardy-Weinberg Equilibrium (HWE) para facilitar a compreensão da importância do cálculo de HWE para pesquisa experimental sobre análise de polimorfismo em uma classe remota de biologia molecular durante o período pandêmico do Coronavirus 2019 (COVID-19).

The sirtuins (SIRT) gene family (SIRT1 to SIRT7) contains the targets implicated in cellular and organismal aging. The role of SIRTs expression in the pathogenesis and overall survival of patients diagnosed with solid tumors has been widely discussed. However, studies that seek to explain the role of these pathways in the hematopoietic aging process and the consequences of their instability in the pathogenesis of different onco-hematological diseases are still scarce. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42022310079) and in silico analysis (based on GEPIA database) to discuss the role of SIRTs in the advancement of pathogenesis and/or prognosis for different hematological cancer types. In summary, given recent available scientific evidence and in silico gene expression analysis that supports the role of SIRTs in pathobiology of hematological malignances, such as leukemias, lymphomas and myeloma, it is clear the need for further high-quality research and clinical trials that expands the SIRT inhibition knowledge and its effect on controlling clonal progression caused by genomic instability characteristics of these diseases. Finally, SIRTs represent potential molecular targets in the control of the effects caused by aging on the failures of the hematopoietic system that can lead to the involvement of hematological neoplasms.

Introdução: A relação entre a senescência e o câncer é alvo de estudos, tanto em contexto carcinogênico quanto na supressão tumoral. Considerados importantes marcadores de envelhecimento, as sirtuinas podem auxiliar na medicina preventiva do câncer. Entretanto, estudos com esses marcadores em Síndrome Mielodisplásica ainda são escassos. Objetivo: Investigar o papel das sirtuinas (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 e SIRT7) na patogênese e na evolução prognóstica da Síndrome Mielodisplásica em um estudo do tipo caso-controle retro-prospectivo. Metodologia: Foram selecionados 106 pacientes diagnosticados para SMD e 11 indivíduos saudáveis pareados por sexo e idade cujo as amostras de aspirado de medula óssea serão coletadas e armazenadas em freezer -80°. Análises de citogenética por banda G foram realizadas para todos os pacientes e as expressões das sirtuinas serão realizadas por RT-qPCR. Análises in sílico de predição de expressão gênica das sirtuinas foram realizadas pelo GEPIA (Gene Expression Profilling Interactive Analysis). Os achados citogenéticos e moleculares serão correlacionados com dados clínico-epidemiológicos e laboratoriais coletados via banco RedCap.  Resultados Preliminares: Em análise de dados clínico-epidemiológicos, verificou-se que os pacientes são, predominantemente, do sexo feminino (55,26%) com idade média de 69 anos (70,30%). Os pacientes apresentaram, prioritariamente, cariótipo normal (57,89%) enquanto 25% apresentaram alterações citogenéticas, principalmente relacionadas à del(5q) e +7. Em análise de predição in sílico, foi identificado que, para LMA, SIRT3, SIRT4, SIRT5 e SIRT7 estavam downregulated, enquanto que a expressão de SIRT1 e SIRT2 estavam upregulated quando comparada aos tecidos normais (p<0.05). Conclusão: Este é o primeiro estudo que irá relacionar o papel das sirtuinas na patobiologia da SMD. Atualmente, estamos em fase final de recrutamento dos indivíduos de grupo controle e início das análises de expressão gênica. Assim, a partir da análise in sílico, espera-se que a expressão das sirtuinas possa representar possíveis novos marcadores de diagnóstico e prognóstico para SMD.

An important new biomarker for cancer is the Klotho, an anti-aging target, associated to proliferation and apoptosis of tumor cells. In this study, we hypothesized that the Myelodysplastic syndrome (MDS) pathogenesis, an elderly hematopoietic disease, can be affect by block of the Klotho expression, increasing ROS production in the medullary microenvironment, attenuating the DNA damage in HSCs, and leading to reduced count of blood cell precursors, characterizing the cytopenic profile of MDS patient. The absence or negative regulation of Klotho may be a poor prognostic marker of MDS, especially when patients are stratified by age. We believed that younger adult MDS patients show a higher Klotho expression while compared to old adults MDS patients, demonstrating that its expression is decreased with increasing age, representing a more aggressive disease. To confirm this hypothesis, an extensive clinical case-control study can be performed on bone marrow cell samples of MDS patients to show differential expression of Klotho gene and protein, and as this target can be modulate in this disease (based on promoter region methylation analysis). These approaches may define the Klotho as a new pathologic marker to MDS in elderly and improve future potential therapies.

Based on literature review, the present study aimed to evaluate data on cases of co-infections between tuberculosis and HIV in the period from 2015 to 2018 in the state of Ceará. Between 2015-1018, there were a total of 16,776 new TB cases in the state of Ceará (Figure 1). When we analyzed the first two years (2015 and 2016), there was a minimal difference, at 1%, this figure increased in the following year (2017), from 24.02% to 25.75%, leveraging in 2018, representing a total of 26.28% of the total cases of the last 4 years, that is, there was no change above 2% over the years. However, the number of cases increases gradually. Recognizing the epidemiological status of different regions and locations allows the state to recognize and interpret more efficiently the ways of combating the diseases that so devastate humanity and take the sleep of so many scientists and government leaders. Furthermore, the correct assessment of these data allows us to understand the growth of the disease in the region, and thus help in the process of controlling and informing the population.