RESUMEN
Colorectal cancer (CRC) is one of the leading cancers worldwide, with metastasis being a major cause of high mortality rates among patients. In this study, dysregulated gene Tweety homolog 3 (TTYH3) was identified by Gene Expression Omnibus database. Public databases were used to predict potential competing endogenous RNAs (ceRNAs) for TTYH3. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were utilized to analyze TTYH3 and histone deacetylase 7 (HDAC7) levels. Luciferase assays confirmed miR-1271-5p directly targeting the 3' untranslated regions of TTYH3 and HDAC7. In vitro experiments such as transwell and human umbilical vein endothelial cell tube formation, as well as in vivo mouse models, were conducted to assess the biological functions of TTYH3 and HDAC7. We discovered that upregulation of TTYH3 in CRC promotes cell migration by affecting the Epithelial-mesenchymal transition pathway, which was independent of its ion channel activity. Mechanistically, TTYH3 and HDAC7 functioned as ceRNAs, reciprocally regulating each other's expression. TTYH3 competes for binding miR-1271-5p, increasing HDAC7 expression, facilitating CRC metastasis and angiogenesis. This study reveals the critical role of TTYH3 in promoting CRC metastasis through ceRNA crosstalk, offering new insights into potential therapeutic targets for clinical intervention.
RESUMEN
In this study, we investigated the effect of dihydroartemisinin on Echinococcus protoscoleces and explored the role of endoplasmic reticulum stress in this process. Echinococcus protoscoleces were collected and cultured in RPMI 1640 medium. Changes in the expressions of glucose-regulated protein 78 (GRP-78), caspase-12, and C/EBP homologous protein (CHOP) were assessed through confocal immunofluorescence and western blot analysis. Cell viability and morphological changes were observed under a light microscope. The ultrastructure of protoscoleces was observed by scanning electron microscopy and transmission electron microscopy. Caspase-3 activity was detected using an enzyme assay kit. After dihydroartemisinin treatment, the protoscoleces showed loss of viability, and morphological changes including soma contraction, blebs formation, hooks loss, microtrichia destruction, and development of lipid droplets was observed. The levels of caspase-12 and CHOP were increased within 2 days of dihydroartemisinin treatment. However, the levels of GRP-78, caspase-12, and CHOP were decreased in 4 days. Furthermore, caspase-3 activity was increased after treatment with different concentrations of dihydroartemisinin. Dihydroartemisinin can induce apoptosis in protoscoleces via the ER stress-caspase-3 apoptotic pathway in vitro. These results indicate that dihydroartemisinin is a potentially valuable therapeutic agent against echinococcosis.
Asunto(s)
Antihelmínticos/farmacología , Apoptosis/efectos de los fármacos , Artemisininas/farmacología , Echinococcus/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Animales , Caspasa 12/metabolismo , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Duración de la Terapia , Echinococcus/citología , Echinococcus/crecimiento & desarrollo , Echinococcus/ultraestructura , Chaperón BiP del Retículo Endoplásmico , Proteínas de Choque Térmico/metabolismo , Microscopía , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Factor de Transcripción CHOP/metabolismoRESUMEN
OBJECTIVE: The Glasgow Coma Scale (GCS) is widely used in neurosurgery to evaluate the depth of coma in patients with brain injury. The bispectral index (BIS) was developed primarily to monitor the depth of unconsciousness. Recent evidence suggests that BIS may also help in the assessment of brain injury. This study explores the correlation between GCS scores and BIS values in patients with brain injury. METHODS: Fifty patients were divided into 2 groups-moderate (GCS 9-12) and severe (GCS 3-8)-in this prospective, double-blind, observational study. Bispectral index data were recorded when electromyography was less than 40 and signal quality index was greater than 75 for 5 minutes. Linear regression was used to examine the correlation between BIS and GCS, and receiver operating characteristic curves were plotted. Cutoff points were identified to show the feasibility and accuracy of BIS for assessing brain injury. RESULTS: The mean BIS value of the moderate group was 65.62 ± 12.84, and that of the severe group was 46.27 ± 17.35. Bispectral index values were significantly correlated with GCS (R = 0.729, P < .01). The regression line and 95% confidence interval were determined; the regression equation was BIS = 5.46*GCS + 12.72. The receiver operating characteristic curve showed high diagnostic accuracy when GCS is less than 9; the area under the curve was 0.8164, and the cutoff point (BIS value) corresponding to the maximum sensitivity (0.91) and specificity (0.63) was 60.2. CONCLUSION: BIS values and GCS scores were significantly correlated in patients with brain injury. As a continuous and objective measurement, BIS is a viable evaluation and monitoring tool for brain injury.