RESUMO
Breast cancer (BC) is the most common cancer in women, with incidence rates increasing globally in recent years. Therefore, it is important to find new molecules with prognostic and therapeutic value to improve therapeutic response and quality of life. The polyunsaturated fatty acids (PUFAs) metabolic pathway participates in various physiological processes, as well as in the development of malignancies. Although aberrancies in the PUFAs metabolic pathway have been implicated in carcinogenesis, the functional and clinical relevance of this pathway has not been well explored in BC. To evaluate the clinical significance of soluble epoxide hydrolase (EPHX2) expression in Mexican patients with BC using tissue microarrays (TMAs) and digital pathology (DP). Immunohistochemical analyses were performed on 11 TMAs with 267 BC samples to quantify this enzyme. Using DP, EPHX2 protein expression was evaluated solely in tumor areas. The association of EPHX2 with overall survival (OS) was detected through bioinformatic analysis in public databases and confirmed in our cohort via Cox regression analysis. Clear nuclear expression of EPHX2 was identified. Receiver operating characteristics (ROC) curves revealed the optimal cutoff point at 2.847062 × 10-3 pixels, with sensitivity of 69.2% and specificity of 67%. Stratification based on this cutoff value showed elevated EPHX2 expression in multiple clinicopathological features, including older age and nuclear grade, human epidermal growth factor receptor 2 (HER2) and triple negative breast cancer (TNBC) subtypes, and recurrence. Kaplan-Meier curves demonstrated how higher nuclear expression of EPHX2 predicts shorter OS. Consistently, multivariate analysis confirmed EPHX2 as an independent predictor of OS, with a hazard ratio (HR) of 3.483 and a 95% confidence interval of 1.804-6.724 (p < 0.001). Our study demonstrates for the first time that nuclear overexpression of EPHX2 is a predictor of poor prognosis in BC patients. The DP approach was instrumental in identifying this significant association. Our study provides valuable insights into the potential clinical utility of EPHX2 as a prognostic biomarker and therapeutic target in BC.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Epóxido Hidrolases , Humanos , Epóxido Hidrolases/metabolismo , Epóxido Hidrolases/genética , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/genética , Pessoa de Meia-Idade , Prognóstico , Biomarcadores Tumorais/metabolismo , Idoso , Adulto , Núcleo Celular/metabolismo , Regulação para Cima , Regulação Neoplásica da Expressão Gênica , Curva ROC , Idoso de 80 Anos ou mais , Estimativa de Kaplan-MeierRESUMO
BACKGROUND: There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables. MATERIAL AND METHODS: A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16-65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed. RESULTS: Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8⯱â¯18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (pâ¯=â¯0.035). A significant correlation was found between percentage of C4d expression in CG with SA (pâ¯=â¯0.012) and SA with tubular atrophy and interstitial fibrosis (pâ¯<â¯0.05). CONCLUSIONS: C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS.
Assuntos
Complemento C4b , Glomerulosclerose Segmentar e Focal , Humanos , Masculino , Glomerulosclerose Segmentar e Focal/patologia , Adulto , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Idoso , Complemento C4b/análise , Fragmentos de Peptídeos/análiseRESUMO
This study aimed to investigate the immunomodulatory behavior of soluble immune checkpoints (sICPs) and other biomarkers in the pathophysiology of SARS-CoV-2 infection. The study included 59 adult participants, 43 of whom tested positive for SARS-CoV-2. Patients were divided into three cohorts: those with moderate disease (n = 16), recovered patients with severe disease (n = 13), and deceased patients with severe disease (n = 16). In addition, 16 participants were pre-pandemic subjects negative for SARS-CoV-2. The relative activity of neutralizing antibodies (rNAbs) against SARS-CoV-2 and the values of 14 sICPs in peripheral blood were compared between the four groups. Because the increase of markers values of inflammation [NLR > 12; CRP > 150 mg/L] and venous thromboembolism [D-dimer > 0.5 mg/L] has been associated with mortality from COVID-19, the total and differential leukocyte counts, the NLR, and CRP and D-dimer values were obtained in patients with severe disease. No differences in rNAbs were observed between the cohorts. Only the levels of five sICPs, sCD27, sHVEM sTIM-3, sPD-1, and sPDL-1, were significantly higher in patients with severe rather than moderate disease. The sPDL-2 level and NLR were higher in deceased patients than in recovered patients. However, there was no difference in CRP and D-dimer values between the two groups. Of the five soluble biomarkers compared among patients with severe disease, only sPDL-2 was higher in deceased patients than in recovered patients. This suggests that immuno-inhibitory sICPs might be used as indicators for severe COVID-19, with sPDL-2 used to assess individual risk for fatality.IMPORTANCECOVID-19, the disease caused by a SARS-CoV-2 infection, generates a broad spectrum of clinical symptoms, progressing to multiorgan failure in the most severe cases. As activation of the immune system is pivotal to eradicating the virus, future research should focus on identifying reliable biomarkers to efficiently predict the outcome in severe COVID-19 cases. Soluble immune checkpoints represent the function of the immune system and are easily determined in peripheral blood. This research could lead to implementing more effective severity biomarkers for COVID-19, which could increase patients' survival rate and quality of life.
Assuntos
Biomarcadores , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , SARS-CoV-2/imunologia , Idoso , Adulto , Índice de Gravidade de Doença , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Proteínas de Checkpoint Imunológico/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Idoso de 80 Anos ou maisRESUMO
Stenotrophomonas is a bacterial genus that can be found in various environments, such as water, soil, and clinical samples. Due to their high genetic and phenotypic diversity, it is difficult to properly identify and classify all isolates. The COVID-19 pandemic caused an increase in nosocomial infections, which played a major role in the high mortality rate among patients in intensive care. This is the first report of the identification of S. geniculata as a nosocomial opportunistic pathogen isolated from a patient with COVID-19. Their genome was isolated, sequenced, and assembled, and it consists of 4,488,090 bp in 24 contigs, 4,103 coding sequences, and a G+C content of 66.58%.
RESUMO
Knowledge about the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly regarding the function of eosinophils, has been steadily emerging recently. There exists controversy regarding the implications of eosinophils in the coronavirus disease 2019 (COVID-19)'s pathology. We report a retrospective cohort study including the comparison of leukocyte counts in COVID-19 patients, considering the outcomes of recovery (n = 59) and death (n = 60). Among the different types of leukocytes, the eosinophil counts were those that showed the greatest difference between recovered and deceased patients. Eosinopenia (eosinophil count < 0.01 × 109/L) was more frequently observed in deceased than recovered patients (p = 0.0012). The eosinophil counts more rapidly increased and showed a greater proportion over the course of the disease in the recovered than deceased patients. Furthermore, the estimated survival rate was greater in patients without eosinopenia than in patients with eosinopenia (p = 0.0070) during hospitalization. Importantly, recovered but not deceased patients showed high negative correlations of the eosinophils with the neutrophil-to-lymphocyte ratio (NLR) and neutrophil counts at Day 9 of the onset of clinical symptoms (p ≤ 0.0220). Our analysis suggests that eosinopenia may be associated with unfavorable disease outcomes and that the eosinophils have a beneficial function in COVID-19 patients, probably contributing by controlling the exacerbated inflammation induced by neutrophils.
Assuntos
COVID-19/sangue , COVID-19/virologia , Eosinófilos , Interações Hospedeiro-Patógeno , Contagem de Leucócitos , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , COVID-19/diagnóstico , COVID-19/imunologia , Comorbidade , Progressão da Doença , Eosinófilos/imunologia , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Leucócitos , Contagem de Linfócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Prognóstico , Estudos Retrospectivos , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
Knowledge of glycogen synthase kinase 3ß (GSK3ß) activity and the molecules identified that regulate its function in infections caused by pathogenic microorganisms is crucial to understanding how the intensity of the inflammatory response can be controlled in the course of infections. In recent years many reports have described small molecular weight synthetic and natural compounds, proteins, and interference RNA with the potential to regulate the GSK3ß activity and reduce the deleterious effects of the inflammatory response. Our goal in this review is to summarize the most recent advances on the role of GSK3ß in the inflammatory response caused by bacteria, bacterial virulence factors (i.e. LPS and others), viruses, and parasites and how the regulation of its activity, mainly its inhibition by different type of molecules, modulates the inflammation.