Potential of semen coicis in enhancing the anti-tumor effects of PD-1 inhibitor on A549 cell lines by blocking the PI3K-AKT-mTOR pathway.

BACKGROUND: The objective of this research was to investigate how the combination of semen coicis extract and PD-1 inhibitors can potentially work together to enhance the anti-tumor effects, with a focus on understanding the underlying mechanism. METHODS: We obtained the active components and specific targets of semen coicis in the treatment of NSCLC from various databases, namely TCMSP, GeneCard, and OMIM. By utilizing the STRING database and Cytoscape software, we established a protein interaction network (PPI) for the active ingredient of semen coicis and the target genes related to NSCLC. To explore the potential pathways involved, we conducted gene ontology (GO) and biological pathway (KEGG) enrichment analyses, which were further supported by molecular docking technology. Additionally, we conducted cyto-inhibition experiments to verify the inhibitory effects of semen coicis alone or in combination with a PD-1 inhibitor on A549 cells, along with examining the associated pathways. Furthermore, we investigated the synergistic mechanism of these two drugs through cytokine release experiments and the PD-L1 expression study on A549 cells. RESULTS: Semen coicis contains two main active components, Omaine and (S)-4-Nonanolide. Its primary targets include PIK3R1, PIK3CD, PIK3CA, AKT2, and mTOR. Molecular docking experiments confirmed that these ingredients and targets form stable bonds. In vitro experiments showed that semen coicis demonstrates inhibitory effects against A549 cells, and this effect was further enhanced when combined with PD-1 inhibitors. PCR and WB analysis confirmed that the inhibition of the PI3K-AKT-mTOR pathway may contribute to this effect. Additionally, semen coicis was observed to decrease the levels of IFN-γ, IL-6, and TNF-α, promoting the recovery of the human anti-tumor immune response. And semen coicis could inhibit the induced expression of PD­L1 of A549 cells stimulated by IFN­Î³ as well. CONCLUSION: Semen coicis not only has the ability to kill tumor cells directly but also alleviates the immunosuppression found in the tumor microenvironment. Additionally, it collaboratively enhances the effectiveness of PD-1 inhibitors against tumors by blocking the activation of PI3K-AKT-mTOR.

Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome.

Activation of the NLRP3 inflammasome by Leishmania parasites is critical for the outcome of leishmaniasis, a disease that affects millions of people worldwide. We investigate the mechanisms involved in NLRP3 activation and demonstrate that caspase-11 (CASP11) is activated in response to infection by Leishmania species and triggers the non-canonical activation of NLRP3. This process accounts for host resistance to infection in macrophages and in vivo. We identify the parasite membrane glycoconjugate lipophosphoglycan (LPG) as the molecule involved in CASP11 activation. Cytosolic delivery of LPG in macrophages triggers CASP11 activation, and infections performed with Lpg1-/- parasites reduce CASP11/NLRP3 activation. Unlike bacterial LPS, purified LPG does not activate mouse CASP11 (or human Casp4) in vitro, suggesting the participation of additional molecules for LPG-mediated CASP11 activation. Our data identify a parasite molecule involved in CASP11 activation, thereby establishing the mechanisms underlying inflammasome activation in response to Leishmania species.

Deslocamento coronário de retalho com tecido conjuntivo interposto para cobertura radicular / Coronally advanced flap wíth connectíve tíssue for the Treatment of Gíngíval Recessíon

Hoje em dia é muito comum nos depararmos com pacientes que apresentam queixas estéticas e álgicas relacionadas a sequelas de uma retração gengival (RG). Dentre as diversas modalidades de tratamento propostos para a correção da RG, a associação da técnica de enxertia de tecido conjuntivo do palato e do deslocamento coronário de retalho tem apresentado resultados satisfatórios. O objetivo deste relato de caso será demostrar uma alternativa para o tratamento da recessão gengival associando a técnica de deslocamento coronário de retalho com o enxerto de tecido conjuntivo interposto. Dentro dos limites deste relato de caso clínico, pode- mos concluir que a cirurgia de recobrimento gengival associando enxerto de tecido conjuntivo e deslocamento coronário de retalho mostrou-se eficaz para o tratamento da recessão gengival

Nowadays it is very common to come across patients who have complaints related to aesthetic and painful sequels of a gingival recession (GR). Among the various treatment modalities proposed for the correction of the RG, the combination of the technique coronally advanced flap with a subepithelial connective tissue graft as shown satisfactory results for the treatment of RG. Objective: to demonstrate, through a case, an alternative for the treatment of gingival recession technique involving coronally advanced flap with subepithelial connective tissue graft interposed. Conclusion: Within the limits of this case report, we conclude that root coverage associating gingival connective tissue graft and coronally advanced flap was effective for the treatment of gingival recession

Microwave-assisted synthesis of a ferrimagnetic dodecanuclear iron(III) complex with a Fe4(OH)4 cubane core.

The microwave-assisted reaction of Fe(ClO(4))(2) with NaN(3), NaO(2)CPh, and 1,3-di(2-pyridyl)-1,3-propanedione gave a ferrimagnetic dodecanuclear iron(III) complex that shows magnetization relaxation behavior.