Dynamics of Early Establishment of SARS-CoV-2 VOC Omicron Lineages in Minas Gerais, Brazil.

Brazil is one of the nations most affected by Coronavirus disease 2019 (COVID-19). The introduction and establishment of new virus variants can be related to an increase in cases and fatalities. The emergence of Omicron, the most modified SARS-CoV-2 variant, caused alarm for the public health of Brazil. In this study, we examined the effects of the Omicron introduction in Minas Gerais (MG), the second-most populous state of Brazil. A total of 430 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples from November 2021 to June 2022 from Belo Horizonte (BH) city were sequenced. These newly sequenced genomes comprise 72% of all previously available SARS-CoV-2 genomes for the city. Evolutionary analysis of novel viral genomes reveals that a great diversity of Omicron sublineages have circulated in BH, a pattern in-keeping with observations across Brazil more generally. Bayesian phylogeographic reconstructions indicate that this diversity is a product of a large number of international and national importations. As observed previously, São Paulo state is shown as a significant hub for viral spread throughout the country, contributing to around 70% of all viral Omicron introductions detected in MG.

Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the lack of chemoresistance biomarkers contributes to the poor prognosis. Cancer stem cells (CSC) have been investigated in EOC to understand its relationship with chemoresistance and recurrence. In this context, in vitro cultivation-models are important tools for CSC studies. MicroRNAs (miRNAs) play key roles in cancer, CSC regulation and apoptosis. Thus, this study aims to evaluate the tumorsphere model as CSC-enrichment method in EOC studies and investigate apoptosis-related miRNAs in tumorspheres-derived EOC cell lines. TOV-21G and SKOV-3 were cultured in monolayer and tumorspheres. Genetic profiles of cell lines were obtained using COSMIC database. CD24/CD44/CD146/CD177 and ALDH1 markers were evaluated in cell lines and tumorspheres-derived by flow cytometry. Eleven miRNAs were selected by in silico analysis for qPCR analysis. According to COSMIC, TOV-21G and SKOV-3 have eight and nine cancer-related mutations, respectively. TOV-21G showed a CD44+/high/CD24-/low/CD117-/low/CD146-/low/ALDH1low profile in both culture models; thus, no significant difference between cultivation models was identified. SKOV-3 showed a CD44+/high/CD24+/high/ CD117-/low/CD146-/low/ALDH1low profile in both culture models, although the tumorsphere model showed a significant increase in CD24+/high subpopulation (ovarian CSC-like). Among eleven miRNAs, we observed differences in miRNA expression between culture models. MiR-26a was overexpressed in TOV-21G tumorspheres, albeit downregulated in SKOV-3 tumorspheres. MiR-125b-5p, miR-17-5p and miR-221 was downregulated in tumorsphere model in both cell lines. Given that tumorsphere-derived SKOV-3 had a higher ratio of CD24+/high cells, we suggest that miR-26a, miR-125b-5p, miR-17-5p and miR-221 downregulation could be related to poor EOC prognosis.

New 3-alkylpyridine marine alkaloid analogues as promising antitumor agents against the CD44+/high /CD24-/low subset of triple-negative breast cancer cell line.

Triple-negative breast cancer (TNBC) is one of the most aggressive cancers in women. Additionally, presence of residual cancer stem cells (CSC) in TNBC has challenged the efficacy of chemotherapy. Thus, the development of new molecules with potential action against CSC is fundamental. In this study, six synthetic analogues of theonelladin C, a 3-alkylpyridine marine alkaloid, were tested for cytotoxic activity against human TNBC cell line (BT-549) and tumorspheres derived from BT-549. Cytotoxicity assay was performed by sulforhodamine B (SRB). BT-549 and tumorspheres were examined for CD44+/high /CD24-/low markers, indicative of CSC profile, by flow cytometry. Clonogenic assay was performed to verify inhibiting growth of tumorspheres by the synthetic analogues. Cell death by apoptosis was investigated employing annexin V assay. SRB assay on BT-549 cells revealed that compounds 1c and 2c were the most active of the series, with IC50 values of 18.66 and 9.8 µm, respectively. Compounds 1c and 2c were able to reduce both CSC-like population (CD44+/high /CD24-/low ) and non-CSC population (CD44+/high /CD24+/high ) in tumorsphere model. Clonogenic and annexin V assays confirmed the ability of 1c and 2c to induce growth inhibition and apoptosis in BT-549 cells and tumorspheres. These preliminary data indicate that these compounds are a promising class for development of anticancer agents.

Synthesis and biological evaluation of novel 3-alkylpyridine marine alkaloid analogs with promising anticancer activity.

Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA) analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c) were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.