Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC₅₀ 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC₅₀ 476.0 µg/mL) and HepG2 (CC₅₀ 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum, as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer.

GSCs play an important role in GBM recurrence. Understanding the resistance mechanisms in these cells is therefore crucial for radiation therapy optimization. In this study, using patient-derived GSCs, we demonstrate that GDF15, a cytokine belonging to the TGF-β superfamily, is regulated by irradiation (IR) and the transcription factor WWTR1/TAZ. Blocking WWTR1/TAZ using specific siRNAs significantly reduces GDF15 basal expression and reverses the upregulation of this cytokine induced by IR. Furthermore, we demonstrate that GDF15 plays an important role in GSC radioresistance. Targeting GDF15 expression by siRNA in GSCs expressing high levels of GDF15 sensitizes the cells to IR. In addition, we also found that GDF15 expression is critical for GSC spheroid formation, as GDF15 knockdown significantly reduces the number of GSC neurospheres. This study suggests that GDF15 targeting in combination with radiotherapy may be a feasible approach in patients with GBM.

This study aimed to evaluate the anti-leishmania activity of extracts and fractions from stem and leaf of Montrichardia linifera against Leishmania amazonensis. The stem (EES) and leaf (EEL) extracts were obtained by maceration of powders with 96º GL alcohol. The extracts were subjected to exhaustive extraction using a reflux system and solvents of increasing polarity, obtaining 4 fractions for each extract: hexane, dichloromethane, ethyl acetate and methanol. The extracts and fractions were submitted to a phytochemical prospecting study. The antipromastigote activity and cytotoxicity in macrophages (J774) were performed using the cell viability test (MTT). In the extract and fractions of the stem, alkaloids, steroids, terpenes, flavonic heterosides, tannins, polyphenols and saponins were detected. In the extract and fractions of the leaves, coumarins, steroids, terpenes, flavonic heterosides, tannins, polyphenols and saponins were detected. In the anti-leishmania evaluation, the hexane fraction of the leaf (HFL) showed promising activity (IC50=38.56 µg/mL), and the hexane fraction of the stem (HFS) showed moderate activity (CI50=179.3 µg/mL), the extracts and the other fractions were inactive (IC50>200 µg/mL). In the cytotoxicity test, EES and HFS were cytotoxic (CC50 54.82 µg/mL and 26.95 µg/mL, respectively). EEF and HFL showed moderate cytotoxicity (CC50 of 162.7 µg/mL and 347.1 µg/mL). As for the selectivity index, the HFL showed high selectivity (SI=90). In summary, fractionation contributed to increase anti-leishmania activity and the selectivity of HFS, such activity may be related to steroids or terpenes.

O presente estudo objetivou caracterizar o perfil clinico-epidemiológico de pessoas vivendo com HIV (PVHIV) residentes no estado do Pará. Foram incluídos todos os indivíduos, independente de idade ou sexo, cujas amostras, de 2013 a 2015, foram encaminhadas ao Laboratório Central do Pará (LACEN-PA) para a realização do teste de genotipagem do HIV. Os dados foram obtidos por meio da coleta de informações nos laudos do teste de genotipagem guardados no LACEN. Foram coletadas informações como sexo, idade, nível de escolaridade, raça, ano de diagnóstico, motivos relacionados a mudança de esquema terapêutico e presença de mutações. O gênero masculino foi predominante, com faixa etária entre 40 e 50 anos ou mais, pardos e com ensino fundamental. A maioria teve o diagnóstico para o HIV entre os anos 2000 e 2009, tendo a maior parte apresentado mudanças de esquema terapêutico. Tal fato se deu em grande parte pela presença de falha terapêutica e intolerância, corroborando assim com a presença de mutações. No presente estudo observamos um perfil epidemiológico de PVHIV condizente com a literatura, caracterizado pela prevalência do gênero masculino, com faixa etária entre 40 e 50 anos ou mais, pardo e escolaridade em nível fundamental. Foi possível observar também um alto índice de mudanças nos regimes terapêuticos, de falha terapêutica, além de elevadas taxas de mutações. Demonstrando assim, a importância do exame de genotipagem não só para a escolha da terapia mais adequada como também para a adoção de estratégias que busquem melhorar a adesão de PVHIV ao tratamento com antirretrovirais. Novos estudos que possam contribuir com a compreensão e identificação das mudanças dos regimes terapêuticos assim como a contribuição destes para o aparecimento de mutações e consequente falha terapêutica são necessários.