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1.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255914

RESUMO

Breast cancer is one of the leading causes of death among women worldwide and can be classified into four major distinct molecular subtypes based on the expression of specific receptors. Despite significant advances, the lack of biomarkers for detailed diagnosis and prognosis remains a major challenge in the field of oncology. This study aimed to identify short single-stranded oligonucleotides known as aptamers to improve breast cancer diagnosis. The Cell-SELEX technique was used to select aptamers specific to the MDA-MB-231 tumor cell line. After selection, five aptamers demonstrated specific recognition for tumor breast cell lines and no binding to non-tumor breast cells. Validation of aptamer specificity revealed recognition of primary and metastatic tumors of all subtypes. In particular, AptaB4 and AptaB5 showed greater recognition of primary tumors and metastatic tissue, respectively. Finally, a computational biology approach was used to identify potential aptamer targets, which indicated that CSKP could interact with AptaB4. These results suggest that aptamers are promising in breast cancer diagnosis and treatment due to their specificity and selectivity.


Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , Feminino , Humanos , Animais , Neoplasias da Mama/diagnóstico , Mama , Linhagem Celular Tumoral , Oligonucleotídeos
2.
Front Med (Lausanne) ; 10: 1215916, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928473

RESUMO

Background: In 2019, a highly pathogenic coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced and resulted in the outbreak of coronavirus disease 2019 (COVID-19). With the aim of finding effective drugs to fight against the disease, several trials have been conducted since COVID-19 can only be considered a treatable disease, from a clinical point of view, after the availability of specific and effective antivirals. AZVUDINE (FNC), initially developed for treating HIV, is a potential treatment for COVID-19 as it has the capability to lower the patient's viral load and promote recovery. Methods: Volunteers infected with SARS-CoV-2 confirmed by reverse transcription polymerase chain reaction (RT-PCR), with good kidney and liver function, who were not using other antivirals or monoclonal antibodies were eligible. Samples from patients were assessed for viral load every 48 h during treatment using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and droplet digital polymerase chain reaction (ddPCR). Results: The study's primary outcome measure was the percentage of participants showing an improvement in clinical scores, while the secondary outcome measure was the percentage of participants with a clinical outcome of cure. These measures were used to assess the safety and efficacy of FNC for treating COVID-19. In the analysis of sociodemographic variables, no significant differences were detected between patients in the FNC and the placebo group for race, age group, or sex. The results showed a potential benefit to participants who received FNC during the study, as observed in the shorter hospital stay, shorter negative conversion time of SARS-CoV-2, and a significant reduction in viral load. Furthermore, the reduction in fever and chills were significant at D1, D2, and D3. In this study, a total of 112 adverse events cases were noted, with 105 cases being categorized as non-serious and only 7 cases as serious adverse events. Conclusion: The pandemic is not being effectively controlled and is causing multiple waves of infection that require extensive medical resources. However, FNC has demonstrated potential to reduce the treatment duration of moderate COVID-19 cases, thereby saving significant medical resources. This makes FNC a promising candidate for COVID-19 treatment.Clinical trial registration: [clinicaltrials.gov], identifier [NCT04668235].

3.
Front Public Health ; 11: 1186463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37790714

RESUMO

Introduction: After three years since the beginning of the pandemic, the new coronavirus continues to raise several questions regarding its infectious process and host response. Several mutations occurred in different regions of the SARS-CoV-2 genome, such as in the spike gene, causing the emergence of variants of concern and interest (VOCs and VOIs), of which some present higher transmissibility and virulence, especially among patients with previous comorbidities. It is essential to understand its spread dynamics to prevent and control new biological threats that may occur in the future. In this population_based retrospective observational study, we generated data and used public databases to understand SARS-CoV-2 dynamics. Methods: We sequenced 1,003 SARS-CoV-2 genomes from naso-oropharyngeal swabs and saliva samples from Pará from May 2020 to October 2022. To gather epidemiological data from Brazil and the world, we used FIOCRUZ and GISAID databases. Results: Regarding our samples, 496 (49.45%) were derived from female participants and 507 (50.55%) from male participants, and the average age was 43 years old. The Gamma variant presented the highest number of cases, with 290 (28.91%) cases, followed by delta with 53 (5.28%). Moreover, we found seven (0.69%) Omicron cases and 651 (64.9%) non-VOC cases. A significant association was observed between sex and the clinical condition (female, p = 8.65e-08; male, p = 0.008961) and age (p = 3.6e-10). Discussion: Although gamma had been officially identified only in December 2020/January 2021, we identified a gamma case from Belém (capital of Pará State) dated May 2020 and three other cases in October 2020. This indicates that this variant was circulating in the North region of Brazil several months before its formal identification and that Gamma demonstrated its actual transmission capacity only at the end of 2020. Furthermore, the public data analysis showed that SARS-CoV-2 dispersion dynamics differed in Brazil as Gamma played an important role here, while most other countries reported a new infection caused by the Delta variant. The genetic and epidemiological information of this study reinforces the relevance of having a robust genomic surveillance service that allows better management of the pandemic and that provides efficient solutions to possible new disease-causing agents.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Feminino , Masculino , Adulto , SARS-CoV-2/genética , Brasil/epidemiologia , COVID-19/epidemiologia , Análise de Dados
4.
Mem Inst Oswaldo Cruz ; 118: e230084, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37672426

RESUMO

BACKGROUND: Few studies have focused on microbial diversity in indoor environments of ships, as well as the role of the microbiome and its ecological interconnections. In this study, we investigated the microbiome and virome present on the internal surfaces of a polar ship in different stages (beginning, during, and at the end) of the Brazilian Antarctic expedition in order to evaluate abundance of microorganisms in different periods. OBJECTIVES AND METHODS: We used shotgun metagenomic analysis on pooled samples from sampling surfaces in the ship's interior to track the microbial diversity. FINDINGS: Considering the total fraction of the microbiome, the relative abundance of bacteria, eukaryotes, viruses, and archaea was 83.7%, 16.2%, 0.04%, and 0.002%, respectively. Proteobacteria was the most abundant bacterial phyla, followed by Firmicutes, Actinobacteria, and Bacteroidetes. Concerning the virome, the greatest richness of viral species was identified during the middle of the trip, including ten viral families after de novo assembly: Autographiviridae, Chrysoviridae, Genomoviridae, Herelleviridae, Myoviridae, Partitiviridae, Podoviridae, Potyviridae, Siphoviridae, and Virgaviridae. MAIN CONCLUSIONS: This study contributed to the knowledge of microbial diversity in naval transportation facilities, and variations in the abundance of microorganisms probably occurred due to factors such as the number of passengers and activities on the ship.


Assuntos
Microbiota , Viroma , Humanos , Navios , Regiões Antárticas , Archaea/genética
5.
Int J Mol Sci ; 24(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37047289

RESUMO

Ovarian cancer is among the seven most common types of cancer in women, being the most fatal gynecological tumor, due to the difficulty of detection in early stages. Aptamers are important tools to improve tumor diagnosis through the recognition of specific molecules produced by tumors. Here, aptamers and their potential targets in ovarian cancer cells were analyzed by in silico approaches. Specific aptamers were selected by the Cell-SELEX method using Caov-3 and OvCar-3 cells. The five most frequent aptamers obtained from the last round of selection were computationally modeled. The potential targets for those aptamers in cells were proposed by analyzing proteomic data available for the Caov-3 and OvCar-3 cell lines. Overexpressed proteins for each cell were characterized as to their three-dimensional model, cell location, and electrostatic potential. As a result, four specific aptamers for ovarian tumors were selected: AptaC2, AptaC4, AptaO1, and AptaO2. Potential targets were identified for each aptamer through Molecular Docking, and the best complexes were AptaC2-FXYD3, AptaC4-ALPP, AptaO1-TSPAN15, and AptaO2-TSPAN15. In addition, AptaC2 and AptaO1 could detect different stages and subtypes of ovarian cancer tissue samples. The application of this technology makes it possible to propose new molecular biomarkers for the differential diagnosis of epithelial ovarian cancer.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Apoptose , Simulação de Acoplamento Molecular , Proteômica , Aptâmeros de Nucleotídeos/metabolismo , Técnica de Seleção de Aptâmeros/métodos , Proteínas de Membrana , Proteínas de Neoplasias
6.
Mem. Inst. Oswaldo Cruz ; 118: e230084, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1506733

RESUMO

BACKGROUND Few studies have focused on microbial diversity in indoor environments of ships, as well as the role of the microbiome and its ecological interconnections. In this study, we investigated the microbiome and virome present on the internal surfaces of a polar ship in different stages (beginning, during, and at the end) of the Brazilian Antarctic expedition in order to evaluate abundance of microorganisms in different periods. OBJECTIVES AND METHODS We used shotgun metagenomic analysis on pooled samples from sampling surfaces in the ship's interior to track the microbial diversity. FINDINGS Considering the total fraction of the microbiome, the relative abundance of bacteria, eukaryotes, viruses, and archaea was 83.7%, 16.2%, 0.04%, and 0.002%, respectively. Proteobacteria was the most abundant bacterial phyla, followed by Firmicutes, Actinobacteria, and Bacteroidetes. Concerning the virome, the greatest richness of viral species was identified during the middle of the trip, including ten viral families after de novo assembly: Autographiviridae, Chrysoviridae, Genomoviridae, Herelleviridae, Myoviridae, Partitiviridae, Podoviridae, Potyviridae, Siphoviridae, and Virgaviridae. MAIN CONCLUSIONS This study contributed to the knowledge of microbial diversity in naval transportation facilities, and variations in the abundance of microorganisms probably occurred due to factors such as the number of passengers and activities on the ship.

7.
Sci Total Environ ; 852: 158537, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36075413

RESUMO

Polar freshwater ecosystems are characterized by a distinct microbiota. However, little is known about viral diversity and abundance, especially regarding the ecology of RNA viruses. We used shotgun metagenomic analysis on samples from Antarctic ecosystems, and report here the characterization of the virome fraction, from different lakes located in the South Shetland Islands (Penguin, Ardley, Deception and King George Island) in the Peninsula Antarctica, in the summer season 2020. DNA viruses (99.4 %) prevailed over RNA viruses (0.6 %) in the lake samples. Six viral orders were identified in the metagenomic libraries: Caudovirales (dsDNA), which was prevalent in most lakes; Picornavirales (ssRNA+); Sobelivirales (ssRNA+); Tolivirales (ssRNA+); Petitvirales (ssDNA) and Baphyvirales (ssDNA), including eight viral families (Herelleviridae, Siphoviridae, Myoviridae, Microviridae, Marnaviridae, Bacilladnaviridae, Barnaviridae and Tombusviridae) and several other, mainly non-classified ssRNA(+) viruses in the lakes of Ardley Island. Bacteriophages (dsDNA) (Herelleviridae family) infecting the phylum Firmicutes and Siphoviridae were predominant in most lakes evaluated. Functional analysis demonstrated a prevalence of unknown proteins (68 %) in the virome. Our prospective study provides virome analysis data from different lakes in the South Shetland Islands, Antarctica, opening exploratory lines for future research related to the biodiversity and viral ecology in this extreme ecosystem.


Assuntos
Microbiota , Vírus de RNA , Vírus , Humanos , Lagos , Regiões Antárticas , Viroma , Estudos Prospectivos , Vírus/genética , Ilhas
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