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1.
Nat Commun ; 15(1): 5694, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972873

RESUMO

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.


Assuntos
Glicoproteínas de Membrana , Células Mieloides , Neoplasias , Receptores Imunológicos , Análise de Célula Única , Microambiente Tumoral , Humanos , Análise de Célula Única/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Células Mieloides/metabolismo , Células Mieloides/patologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Prognóstico , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Feminino , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-30364020

RESUMO

Brazilian ginseng, including Pfaffia townsendii, is used in popular medicine as a natural anti-inflammatory, tonic, analgesic, and antidiabetic agent. In this study, we investigated the chemical composition and evaluated the antioxidant and anti-inflammatory activities of the P. townsendii ethanolic extract as well as the major isolated glycoside flavonoids tiliroside and patuletin 3-O-ß-D-glucopyranoside. Chromatographic techniques and spectroscopic analysis were used for the isolation and identification of the major compounds. The antioxidant potential was determined through DPPH and ORAC-FL assays. The total phenolic content was measured using Folin-Ciocalteu reagent. The anti-inflammatory activity was determined based on a model of paw edema and carrageenan- (Cg-) induced pleurisy. We identified three phenolic acids, one carboxylic acid and two flavonoids, patuletin 3-O-ß-D-glucopyranoside, and tiliroside. The ethanol crude extracts, partitions and isolated flavonoids (4581 µmol of Trolox equivalents/g of extract in ORAC and a SC50 of approximately 31.9 µg/mL in the DPPH assay) demonstrated antioxidant activity, and the ethanolic extract as well as isolated flavonoids inhibited paw edema induced by Cg and leukocyte migration in the Cg-induced pleurisy model. The extract, tiliroside, and patuletin 3-O-ß-D-glucopyranoside obtained from P. townsendii have therapeutic potential against oxidative stress-related and inflammatory disorders.

3.
Nat Prod Res ; 30(9): 1088-92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26586465

RESUMO

The essential oil obtained by hydrodistillation from leaves of Anaxagorea brevipes was analysed by gas chromatography fitted with a flame ionisation detector (GC-FID) and coupled to mass spectrometry (GC-MS). Thirty one components were identified, representing around 75.7% of total oil. The major components were ß-eudesmol (13.16%), α-eudesmol (13.05%), γ-eudesmol (7.54%), guaiol (5.12%), caryophyllene oxide (4.18%) and ß-bisabolene (4.10%). The essential oil showed antimicrobial activity against Gram-positive bacteria and yeast with the MIC values between 25.0 and 100 µg/mL. The highest antiproliferative activity was observed for the oil against MCF-7 (breast, TGI = 12.8 µg/mL), NCI-H460 (lung, TGI = 13.0 µg/mL) and PC-3 (prostate, TGI = 9.6 µg/mL) cell lines, while against no cancer cell line HaCat (keratinocyte) the TGI was 38.8 µg/mL. The oil exhibited a small antioxidant activity assessed through ORAC-FL assay (517 µmol TE/g). This is the first report regarding the chemical composition and bioactivity of A. brevipes essential oil.


Assuntos
Annonaceae/química , Óleos Voláteis/análise , Óleos Voláteis/farmacologia , Folhas de Planta/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Ionização de Chama , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Sesquiterpenos Monocíclicos , Sesquiterpenos Policíclicos , Sesquiterpenos , Sesquiterpenos de Eudesmano , Sesquiterpenos de Guaiano , Leveduras/efeitos dos fármacos
4.
Nat Prod Res ; 29(20): 1966-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25710362

RESUMO

Essential oil from the leaves of Guatteria australis was obtained by hydrodistillation, analyzed by Gas Chromatography coupled to Mass Spectromery (GC-MS) and their antiproliferative, antileishmanial, antibacterial, antifungal and antioxidant activities were also evaluated. Twenty-three compounds were identified among which germacrene B (50.66%), germacrene D (22.22%) and (E)-caryophyllene (8.99%) were the main compounds. The highest antiproliferative activity was observed against NCI-ADR/RES (TGI = 31.08 µg/ml) and HT-29 (TGI = 32.81 µg/ml) cell lines. It also showed good antileishmanial activity against Leishmania infantum (IC50 = 30.71 µg/ml). On the other hand, the oil exhibited a small effect against Staphylococcus aureus ATCC 6538, S. aureus ATCC 14458 and Escherichia coli ATCC 10799 (MIC = 250 µg/ml), as well as small antioxidant activity (457 µmol TE/g) assessed through ORACFL assay. These results represent the first report regarding chemical composition and bioactivity of G. australis essential oil.


Assuntos
Antibacterianos/química , Antineoplásicos Fitogênicos/química , Antiprotozoários/química , Guatteria/química , Óleos Voláteis/química , Óleos de Plantas/química , Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antiprotozoários/isolamento & purificação , Células HT29 , Humanos , Folhas de Planta/química , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação
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