RESUMEN
OBJECTIVE: Nasopharyngeal carcinoma (NPC) remains a challenging cancer to treat. This study investigates the molecular mechanisms of Hedyotis diffusa Willd (HDW) combined with Andrographis paniculata (AP) in treating NPC. METHODS: Key compounds and target genes in HDW and AP were analyzed using network pharmacology. Protein-protein interaction (PPI) networks were constructed with STRING and visualized using Cytoscape. MCODE identified critical clusters, while DAVID facilitated GO and KEGG analyses. In vivo and in vitro experiments evaluated HDW-AP effects on NPC, including tumor volume, weight, Ki-67 expression, cell apoptosis, migration, invasion, cell cycle distribution, and DNA damage. RESULTS: The database identified 495 NPC-related genes and 26 compounds in the HDW-AP pair, targeting 165 genes. Fifty-eight potential therapeutic genes were found, leading to 18 key targets. KEGG analysis revealed a significant impact on 78 pathways, especially cancer pathways. Both in vivo and in vitro tests showed HDW-AP inhibited NPC cell proliferation, migration, invasion, and induced apoptosis. Mechanistically, this was achieved through AKT1 downregulation and VEGFA upregulation. CONCLUSION: The combination of HDW and AP targets 16 key genes to impede the development of NPC, primarily by modulating AKT1 and VEGFA pathways.
Asunto(s)
Hedyotis , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas Proto-Oncogénicas c-akt , Factor A de Crecimiento Endotelial Vascular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Animales , Línea Celular Tumoral , Ratones Desnudos , Apoptosis/efectos de los fármacos , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Andrographis/química , Proliferación Celular/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Ratones Endogámicos BALB C , Movimiento Celular/efectos de los fármacos , Sinergismo Farmacológico , Mapas de Interacción de Proteínas , Carcinogénesis/efectos de los fármacos , Andrographis paniculata , Regulación hacia Abajo , MasculinoRESUMEN
BACKGROUND: Post-stroke fatigue (PSF) was a common complication after stroke. This study aimed to explore the neuroimaging mechanism of PSF, which was rarely studied. METHODS: Patients with the first episode of ischemic stroke were recruited from the First Affiliated Hospital of Wenzhou Medical University between March 2021 and December 2022. The fatigue severity scale (FSS) was used to assess fatigue symptoms. PSF was diagnosed by a neurologist based on the FSS score and PSF diagnostic criteria. All the patients were scanned by resting-state functional MRI (rs-fMRI). Precuneus, the posterior node of default-mode network (pDMN), was related to fatigue. Therefore, imaging data were further analyzed by the seed-based resting-state functional connectivity (FC) approach, with the left (PCUN.L) and right precuneus (PCUN.R) being the seeds. RESULTS: A total of 70 patients with acute ischemic stroke were finally recruited, comprising 40 patients with PSF and 30 patients without PSF. Both the PCUN.L and PCUN.R seeds (pDMN) exhibited decreased FC with the prefrontal lobes located at the anterior part of DMN (aDMN), and the FC values were negatively correlated with FSS scores (both p < 0.001). These two seeds also exhibited increased FC with the right insula, and the FC values were positively correlated with FSS scores (both p < 0.05). CONCLUSION: The abnormal FC between the aDMN and pDMN was associated with PSF. Besides, the insula, related to interoception, might also play an important role in PSF.
