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1.
Biomol Concepts ; 15(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38345545

ABSTRACT

Epigenetic analysis is a fundamental part of understanding pathophysiological processes with potential applications in diagnosis, prognosis, and assessment of disease susceptibility. Epigenetic changes have been widely studied in chronic obstructive pulmonary disease (COPD), but currently, there is no molecular marker used to improve the treatment of patients. Furthermore, this progressive disease is a risk factor for the development of more severe COVID-19. Methylation-specific polymerase chain reaction (MSP-PCR) plays an important role in the analysis of DNA methylation profiles, and it is one of the most widely used techniques. In this context, the combination of MSP-PCR with emerging PCR technologies, such as digital PCR (dPCR), results in more accurate analyses of the DNA methylation profile of the genes under study. In this study, we propose the application of the MSP-dPCR technique to evaluate the methylation profile of the ADAM33 gene from saliva samples and lung tissue biopsies of patients with COPD and COVID-19. MSP-dPCR generated a measurable prediction of gene methylation rate, with the potential application of this combined technology for diagnostic and prognostic purposes. It has also proven to be a powerful tool for liquid biopsy applications.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Humans , DNA Methylation , Polymerase Chain Reaction/methods , Liquid Biopsy , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/genetics , COVID-19/diagnosis , COVID-19/genetics , COVID-19 Testing , ADAM Proteins/genetics
2.
Toxins (Basel) ; 15(12)2023 12 14.
Article in English | MEDLINE | ID: mdl-38133204

ABSTRACT

Podocyte dysfunction plays a crucial role in renal injury and is identified as a key contributor to proteinuria in Fabry disease (FD), primarily impacting glomerular filtration function (GFF). The α3ß1 integrins are important for podocyte adhesion to the glomerular basement membrane, and disturbances in these integrins can lead to podocyte injury. Therefore, this study aimed to assess the effects of chloroquine (CQ) on podocytes, as this drug can be used to obtain an in vitro condition analogous to the FD. Murine podocytes were employed in our experiments. The results revealed a dose-dependent reduction in cell viability. CQ at a sub-lethal concentration (1.0 µg/mL) induced lysosomal accumulation significantly (p < 0.0001). Morphological changes were evident through scanning electron microscopy and immunofluorescence, highlighting alterations in F-actin and nucleus morphology. No significant changes were observed in the gene expression of α3ß1 integrins via RT-qPCR. Protein expression of α3 integrin was evaluated with Western Blotting and immunofluorescence, demonstrating its lower detection in podocytes exposed to CQ. Our findings propose a novel in vitro model for exploring secondary Fabry nephropathy, indicating a modulation of α3ß1 integrin and morphological alterations in podocytes under the influence of CQ.


Subject(s)
Fabry Disease , Integrin alpha3beta1 , Kidney Diseases , Podocytes , Animals , Mice , Fabry Disease/metabolism , Integrin alpha3beta1/genetics , Integrin alpha3beta1/metabolism , Kidney Diseases/metabolism , Podocytes/metabolism , Renal Insufficiency
3.
Chem Biol Interact ; 378: 110480, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37059214

ABSTRACT

Breast cancer is one of the most common types of cancer in the world and current therapeutic strategies present severe drawbacks. l-carvone (CRV), a monoterpene found in Mentha spicata (spearmint), has been reported to have potent anti-inflammatory activity. Here, we examined the role of CRV in breast cancer cell adhesion, migration and invasion in vitro and how this component could suppress the growth of Ehrlich carcinoma-bearing mice. In vivo, treatment with CRV significantly decreased tumor growth, increased tumor necrosis area, and reduced the expression of VEGF and HIF-1α in Ehrlich carcinoma-bearing mice. Furthermore, the anticancer efficacy of CRV was similar to currently used chemotherapy (Methotrexate), and the combination of CRV with MTX potentiated the chemotherapy effects. Further mechanistic investigation in vitro revealed that CRV modulates the interaction of breast cancer cells with the extracellular matrix (ECM) by disrupting focal adhesion, which was shown by scanning electron microscopy (SEM) and immunofluorescence. Moreover, CRV caused a decrease in ß1-integrin expression and inhibited focal adhesion kinase (FAK) activation. FAK is one of the most important downstream activators of several metastatic processes, including MMP-2 mediated invasion and HIF-1α/VEGF angiogenesis stimulus, both of which were found to be reduced in MDA-MB-231 cells exposed to CRV. Our results provide new insight about targeting ß1-integrin/FAK signaling pathway with CRV, which could be a new potential agent in the treatment of breast cancer.


Subject(s)
Carcinoma , Vascular Endothelial Growth Factor A , Animals , Mice , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Vascular Endothelial Growth Factor A/metabolism , Cell Line, Tumor , Cell Movement , Focal Adhesion Kinase 1/metabolism , Integrin beta1/metabolism , Neoplasm Invasiveness , Cell Adhesion
4.
Arch Endocrinol Metab ; 61(3): 238-248, 2017.
Article in English | MEDLINE | ID: mdl-28699988

ABSTRACT

OBJECTIVE: Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. SUBJECTS AND METHODS: 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). RESULTS: All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively. CONCLUSION: The studied polymorphisms were not associated with GDM in a Brazilian population.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Diabetes Mellitus, Type 2/genetics , Diabetes, Gestational/genetics , PPAR gamma/genetics , Polymorphism, Genetic/genetics , Receptors, Leptin/genetics , Transcription Factor 7-Like 2 Protein/genetics , Adult , Analysis of Variance , Anthropometry , Brazil , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 2/ethnology , Diabetes, Gestational/ethnology , Female , Gene Frequency , Genetic Association Studies , Genotype , Humans , Obesity/genetics , Pregnancy , Real-Time Polymerase Chain Reaction , Risk Factors , Statistics, Nonparametric
5.
Arch. endocrinol. metab. (Online) ; 61(3): 238-248, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-887551

ABSTRACT

ABSTRACT Objective Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. Subjects and methods 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). Results All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively. Conclusion The studied polymorphisms were not associated with GDM in a Brazilian population.


Subject(s)
Humans , Female , Adult , Polymorphism, Genetic/genetics , Diabetes, Gestational/genetics , PPAR gamma/genetics , Diabetes Mellitus, Type 2/genetics , Receptors, Leptin/genetics , Transcription Factor 7-Like 2 Protein/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Brazil , Case-Control Studies , Anthropometry , Cross-Sectional Studies , Risk Factors , Analysis of Variance , Diabetes, Gestational/ethnology , Statistics, Nonparametric , Diabetes Mellitus, Type 2/ethnology , Genetic Association Studies , Real-Time Polymerase Chain Reaction , Gene Frequency , Genotype , Obesity/genetics
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