RESUMEN
OBJECTIVE: This study was conducted to correlate and compare the immunoexpression of sex-determining region Y-box 2 (SOX-2) in oral leukoplakia (OL) lesions with that in normal buccal mucosa (control). MATERIALS AND METHODS: In this observational study, OL with low-risk (n = 34) and high-risk (n = 33) dysplasia and control samples (n = 25) were subjected to immunohistochemical analysis for SOX-2. In the epithelium, SOX-2 positive and negative cells, as well as semiautomatic segmentation of the immunopositive nuclear area were counted. Statistical tests included chi-square, one-way analysis of variance, Tukey, and Games-Howell. The level of significance was 5%. RESULTS: Groups with OL lesions (low and high-risk) showed higher mean numbers of SOX-2 positive cells (63.47 ± 25.70 and 68.18 ± 21.17) compared to the control group (45.85 ± 27.38) (p = 0.00). Groups with OL lesions (low and high-risk) exhibited higher mean positive nuclear area (0.24 ± 0.47 and 1.09 ± 2.06) compared to the control group (0.00 ± 0.01) (p = 0.01). CONCLUSION: Oral leukoplakia lesions showed a higher expression of SOX-2, suggesting its contribution to the pathogenesis of OL.
Asunto(s)
Leucoplasia Bucal/metabolismo , Factores de Transcripción SOXB1/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Mucosa Bucal/metabolismo , Estudios RetrospectivosRESUMEN
COVID-19 has been considered a vascular disease, and inflammation, intravascular coagulation, and consequent thrombosis may be associated with endothelial dysfunction. These changes, in addition to hypoxia, may be responsible for pathological angiogenesis. This research investigated the impact of COVID-19 on vascular function by analyzing post-mortem lung samples from 24 COVID-19 patients, 10 H1N1pdm09 patients, and 11 controls. We evaluated, through the immunohistochemistry technique, the tissue immunoexpressions of biomarkers involved in endothelial dysfunction, microthrombosis, and angiogenesis (ICAM-1, ANGPT-2, and IL-6, IL-1ß, vWF, PAI-1, CTNNB-1, GJA-1, VEGF, VEGFR-1, NF-kB, TNF-α and HIF-1α), along with the histopathological presence of microthrombosis, endothelial activation, and vascular layer hypertrophy. Clinical data from patients were also observed. The results showed that COVID-19 was associated with increased immunoexpression of biomarkers involved in endothelial dysfunction, microthrombosis, and angiogenesis compared to the H1N1 and CONTROL groups. Microthrombosis and vascular layer hypertrophy were found to be more prevalent in COVID-19 patients. This study concluded that immunothrombosis and angiogenesis might play a key role in COVID-19 progression and outcome, particularly in patients who die from the disease.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Trombosis , Enfermedades Vasculares , Humanos , Pulmón/metabolismo , Hipoxia/metabolismo , HipertrofiaRESUMEN
Uremic toxins, such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS), contribute to endothelial dysfunction in chronic kidney disease (CKD). This process is mediated by several cellular pathways, but it is unclear whether cAMP-responsive element-binding protein (CREB) and activating transcription factor 1 (ATF1) participate in endothelial dysfunction in uremic conditions despite playing roles in inflammatory modulation. This study aimed to evaluate the expression, activation, and transcriptional activity of CREB/ATF1 in endothelial cells exposed to PCS, IS, and uremic serum (US). In vitro, ATF1 protein levels were increased by PCS and IS, whereas CREB levels were enhanced only by IS. Activation through CREB-Ser133 and ATF1-Ser63 phosphorylation was induced by PCS, IS, and US. We evaluated the CREB/ATF1 transcriptional activity by analyzing the expression of their target genes, including ICAM1, PTGS2, NOX1, and SLC22A6, which are related to endothelial dysfunction through their roles in vascular inflammation, oxidative stress, and cellular uptake of PCS and IS. The expression of ICAM1, PTGS2 and NOX1 genes was increased by PCS, IS, and US, whereas that of SLC22A6 was induced only by IS. KG-501, a CREB inhibitor, restored the inductive effects of PCS on ICAM1, PTGS2, and NOX1 expression; IS on ICAM1, PTGS2 and SLC22A6 expression; and US on NOX1 expression. The presence of CREB and ATF1 was observed in healthy arteries and in arteries of patients with CKD, which were structurally damaged. These findings suggest that CREB/ATF1 is activated by uremic toxins and may play a relevant role in endothelial dysfunction in CKD.
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Insuficiencia Renal Crónica , Enfermedades Vasculares , Ciclooxigenasa 2/metabolismo , Células Endoteliales/metabolismo , Femenino , Humanos , Indicán/metabolismo , Indicán/toxicidad , Masculino , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/metabolismo , Tóxinas Urémicas , Enfermedades Vasculares/metabolismoRESUMEN
The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification. Thus, our goal was to analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-ß), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury. Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-ß, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC). Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages were observed in the COVID-19 group compared to both the H1N1 and the CONTROL groups. A different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-CoV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. Understanding and managing the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.
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Infecciones por Coronavirus/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Pulmón/metabolismo , Neumonía Viral/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , COVID-19 , Infecciones por Coronavirus/patología , Femenino , Humanos , Interleucina-13/genética , Interleucina-4/genética , Pulmón/patología , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología , Esfingosina/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
AIM: Among the several organs affected by perinatal hypoxia, the heart plays a central role, with cell death caused mainly by apoptosis. One of the biomarkers most often linked to hypoxia-derived apoptosis of cardiomyocytes in animals is Gadd45ß. From the published literature, Gadd45ß is proposed as a biomarker of hypoxia-induced lesion in cardiomyocytes, both in vitro, as well as in animal models. Our study suggests that this protein can be used as an early biomarker of cell damage in neonate's cardiomyocytes (humans specimens), a process that can ultimately lead to apoptosis. The aim is to determine levels of tissue immunoexpression of the Gadd45ß biomarker in myocardium samples of newborns affected by hypoxia, and to correlate these results with clinical and anatomopathologic data. METHODS: Myocardium samples from the left ventricle of newborns were used. The samples were collected from 78 autopsies performed in neonates of both genders, with hypoxia (Apgar score at five minutes below 6 and/or pH below 7.2 and/or autopsy with anatomopathological signs of hypoxia), who had died within the first day of life. All samples were organized in Tissue Microarray. Immunohistochemistry analysis, using anti-Gadd45ß as the primary antibody, was performed on 3 multi-sample histological slides. There was no correlation between Gadd45ß tissue immunoexpression and neonatal weight (p=0.93), gestational age (p=0.16), Apgar score at first minute (p=0.914), Apgar score at five minutes (p=0.988) and arterial blood pH (p=0.542). There was a relation between Gadd45ß tissue immunoexpression and survival (p=0.02). The maximum peak of Gadd45ß tissue immunoexpression was 8.43% HPF (high power field) and was observed around of six hours of life. CONCLUSION: Gadd45ß could be a suitable biomarker of cardiomyocytes apoptosis in newborns experiencing hypoxia in the first day of life, as its highest tissue immunoexpression around at the first six hours after birth.
Asunto(s)
Antígenos de Diferenciación/metabolismo , Hipoxia/metabolismo , Miocardio/metabolismo , Apoptosis/fisiología , Biomarcadores/metabolismo , Femenino , Humanos , Hipoxia/patología , Recién Nacido , Masculino , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Análisis de Matrices TisularesRESUMEN
OBJECTIVE: To study the effect of bone marrow derived-mononuclear stem cells transplantation in the growth, VEGF-R and TNF-alpha expression of surgically induced endometriosis in an experimental model. STUDY DESIGN: This is an experimental study conducted in the Center for Health and Biological Sciences at the Pontifical Catholic University of Parana, Brazil. Endometriotic implants were surgically induced in 120 female Wistar rats. The animals with viable endometrial implant (larger than 25 mm(2)) were randomically divided into 3 groups to receive an intraperitoneal injection of 0.2 cc of saline solution (C group; n=30), a subcutaneous injection of 1mg/kg of leuprolide (L group; n=34), or an intraperitoneal injection of 5×10(6) bone marrow derived-mononuclear stem cells (SC group; n=36). They were sacrificed after 21 days to assess the implants' size and the tissue expression of vascular endothelial growth factor receptor (VEGF-R) and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Treatment with leuprolide decreased the surface area of the endometriotic implant compared to the SC group and the C group. The absolute reduction in the surface area of the implant was 16.5mm, 0mm, and 0mm (p=0.007), respectively, and the percent reduction was 40.2%, 0%, and 0% (p=0.001). VEGF-R expression in the endometriotic implant decreased after treatment in the L and SC groups compared to the C group (409.6 µm(2) vs. 465 µm(2) vs. 920.9 µm(2), respectively; p=0.021). TNF-alpha expression also reduced in the L and SC groups compared to the C group (585.7 µm(2) vs. 549.3 µm(2) vs. 2402.1 µm(2), respectively; p<0.001). CONCLUSION: Bone marrow derived-mononuclear stem cells transplantation decreased the expression of VEGF-R and TNF-alpha in the endometriotic implant but did not reduce the surface area of the lesion.