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Effects of ketamine in methicillin-resistant Staphylococcus aureus and in silico interaction with sortase A

Fri, 01 Jan 2021 00:00:00 GMT

Título: Effects of ketamine in methicillin-resistant Staphylococcus aureus and in silico interaction with sortase A Autor(es): Coutinho, Tatiana do Nascimento Paiva; Barroso, Fátima Daiana Dias; Silva, Cecília Rocha da; Silva, Anderson Ramos da; Cabral, Vitória Pessoa de Farias; Sá, Lívia Gurgel do Amaral Valente; Cândido, Thiago Mesquita; Silva, Lisandra Juvencio da; Ferreira, Thais Lima; Silva, Wildson Max Barbosa da; Marinho, Emmanuel Silva; Cavalcanti, Bruno Coelho; Moraes, Manoel Odorico de; Andrade Neto, João Batista de; Silva, Jacilene Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main human pathogens and is responsible for many diseases, ranging from skin infections to more invasive infections. These infections are dangerous and expensive to treat because these strains are resistant to a large number of conventional antibiotics. Thus, the antibacterial effect of ketamine against MRSA strains, its mechanism of action, and in silico interaction with sortase A were evaluated. The antibacterial effect of ketamine was assessed using the broth microdilution method. Subsequently, the mechanism of action was assessed using flow cytometry and molecular docking assays with sortase A. Our results showed that ketamine has a significant antibacterial activity against MRSA strains in the range of 2.49–3.73 mM. Their mechanism of action involves alterations in membrane integrity and DNA damage, reducing cell viability, and inducing apoptosis. In addition, ketamine had an affinity for S. aureus sortase A. These results indicate that this compound can be used as an alternative to develop new strategies to combat infections caused by MRSA. Tipo: Artigo de Periódico

Telomerase (hTERT) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia

Fri, 01 Jan 2021 00:00:00 GMT

Título: Telomerase (hTERT) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia Autor(es): Nogueira, Beatriz Maria Dias; Pantoja, Laudreísa da Costa; Silva, Emerson Lucena da; Mello Júnior, Fernando Augusto Rodrigues; Teixeira, Eliel Barbosa; Wanderley, Alayde Vieira; Maués, Jersey Heitor da Silva; Moraes Filho, Manoel Odorico de; Moraes, Maria Elisabete Amaral de; Montenegro, Raquel Carvalho; Khayat, André Salim; Nunes, Caroline Aquino Moreira Abstract: Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system defined as a clonal expansion of an abnormal lymphoid precursor cell. It mostly affects children under five years of age and is the most common tumor to afflict pediatric patients. The expression of the human telomerase gene (hTERT) in patients with ALL has been studied as a biomarker and could become a new therapeutic target. We evaluate the role of hTERT gene expression in ALL pediatric patients, through quantitative real-time PCR technique, and the possible correlation between hTERT expression and clinical variables: gender, age, white blood cells (WBC), gene fusions, and immunophenotyping. The analysis between healthy controls and ALL patients (N = 244) was statistically significant (p < 0.001), demonstrating hTERT overexpression in these patients. In comparison with the usual set of clinical variables, the data were not statistically significant (p > 0.05), indicating that hTERT is equally overexpressed among patients regardless of gender, age, gene fusions, and immunophenotyping. Moreover, patients who presented a higher hTERT expression level had a significant (p < 0.0001) lower overall survival rate. In summary, hTERT expression emerges as an important molecular pathway in leukemogenesis regardless patient’s clinical variables, thus, the data here presented pointed it as a valuable biomarker in pediatric acute lymphoblastic leukemia and a promising target for new therapeutic and prognostic measures. Tipo: Artigo de Periódico

Diferenças clínicas entre gêmeas idênticas com anemia falciforme

Tue, 01 Jan 2019 00:00:00 GMT

Título: Diferenças clínicas entre gêmeas idênticas com anemia falciforme Autor(es): Laurentino, Marilia Rocha; Almeida Filho, Tarcísio Paulo de; Maia Filho, Pedro A.; Nascimento, Francisco O. F.; Advincula, Adlene F.; Machado, Clarissa Maria G.; Lemes, Romélia Pinheiro Gonçalves Abstract: Sickle cell anemia (SCA) is a genetic disease that causes important clinical manifestations due to chronic hemolysis and vascular occlusion. The aim of this study was to report a rare case of monozygotic twins diagnosed with SCA, presenting a different clinical characteristic. An interview with the patients was carried out and the medical records were consulted. One patient has a history of malleolar ulcer in the left back, while the other does not. Both patients used hydroxyurea at the same dosage. This study shows that SCA presents, in addition to genetic factors, non-genetic factors involved in the severity of the disease and its clinical manifestations. Studies are needed that may contribute to the understanding of the clinical heterogeneity of SCA. Tipo: Artigo de Periódico

Molecular fractionation with conjugate caps study of the interaction of the anacardic acid with the active site of Trypanosoma cruzi gapdh enzyme: a quantum investigation

Sun, 01 Dec 2019 00:00:00 GMT

Título: Molecular fractionation with conjugate caps study of the interaction of the anacardic acid with the active site of Trypanosoma cruzi gapdh enzyme: a quantum investigation Autor(es): Marinho, Márcia Machado; Santos, Ricardo Pires dos; Bezerra, Eveline Matias; Costa, Roner Ferreira; Figueira, Ciro Siqueira; Martins, Alice Maria Costa; Lima Neto, Pedro; Marinho, Emmanuel Silva; Freire, Valder Nogueira; Albuquerque, Eudenilson Lins de Abstract: Objective: The objective of this study was to use the molecular fractionation with conjugate caps (MFCC) method to elucidate the possible interaction mechanism of anacardic acid (AA) with the saturated alkyl chain (AA0) in the Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPHD) enzyme. Methods: Initially, the geometry optimization of the AA three-dimensional structure (with the pentadecyl chain) was performed using density functional theory (B3LYP) calculations. With the AA0 optimization data, it was possible to plot the molecular electrostatic potential (MESP) surface. Molecular docking simulation was performed using automated coupling with the AutoDock Vina program. The best-fit conformation in the docking simulation of AA0 is the binding site used for the construction of the TcGAPHD-AA0 complex. Interaction energies between the AA0 molecule and the amino acid residues of the TcGAPHD enzyme were estimated using the MFCC strategy. Results: To obtain more reliable quantitative information on the interaction of AA with the active site of the TcGAPHD enzyme, the fragmentation method was combined with conjugated layers (MFCC) and molecular docking. It can be observed that the AA0 molecule occupies a region near the active site of the chalepin molecule in the TcGAPHD enzyme, and the Ile13 residue has the strongest binding energy of approximately 25 kcal/mol with AA0, through a strong Van der Waals interaction. Conclusion: The paper presents an improved quantitative analysis approach for assessing the contribution of individual amino acids to the free energy of interaction between AA and TcGAPHD. Specifically, the paper illustrates the advantageous approach of combining molecular docking with the MFCC method. Tipo: Artigo de Periódico