RESUMEN
The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development. The molecular mechanism was confirmed that HA-Cu could downregulate the expression of key proteins in the VEGF/VEGFR2 signaling pathway and the expression of inflammatory cytokines, enhance the advantage of pro-apoptotic protein Bax, and enforce cuproptosis by weakening the expression of FDX1 and enhancing the expression of HSP70. Our research will provide a theoretical and practical reference for the development of metal-sulfamethazine and its derivatives as chemotherapy drugs for cancer treatment.
Asunto(s)
Inhibidores de la Angiogénesis , Antineoplásicos , Apoptosis , Complejos de Coordinación , Fenantrolinas , Neoplasias de la Mama Triple Negativas , Apoptosis/efectos de los fármacos , Humanos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/uso terapéutico , Animales , Fenantrolinas/farmacología , Fenantrolinas/química , Fenantrolinas/síntesis química , Femenino , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/síntesis química , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Ratones , Línea Celular Tumoral , Antiinflamatorios/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Sinergismo Farmacológico , Relación Estructura-Actividad , Ratones Endogámicos BALB C , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
We investigated abnormal functional connectivity (FC) patterns of insular subregions in patients with minimal hepatic encephalopathy (MHE) and examined their relationships with cognitive dysfunction using resting-state functional magnetic resonance imaging (fMRI). We collected resting-state fMRI data in 54 patients with cirrhosis [20 with MHE and 34 without MHE (NHE)] and 25 healthy controls. After defining six subregions of insula, we mapped whole-brain FC of the insular subregions and identified FC differences through three groups. FC of the insular subregions was correlated against clinical parameters (including venous blood ammonia level, Child-Pugh score, and cognitive score). The discrimination performance between the MHE and NHE groups was evaluated by performing a classification analysis using the FC index. Across three groups, the observed FC differences involved four insular subregions, including the left-ventral anterior insula, left-dorsal anterior insula, right-dorsal anterior insula, and left-posterior insula (P < 0.05 with false discovery rate correction). Moreover, the FC of these four insular subregions progressively attenuated from NHE to MHE. In addition, hypoconnectivity of insular subregions was correlated with the poor neuropsychological performance and the evaluated blood ammonia levels in patients (P < 0.05 with Bonferroni correction). The FC of insular subregions yielded moderate discriminative value between the MHE and NHE groups (AUC = 0.696-0.809). FC disruption of insular subregions is related to worse cognitive performance in MHE. This study extended our understanding about the neurophysiology of MHE and may assist for its diagnosis.
RESUMEN
The use of thermoplastic composites (TPCs) as one of the lightweight solutions will inevitably encounter problems in connection. Resistance welding has the characteristics of high strength, simplicity, and high reliability, and is considered a very potential hot-melt connection technology. The resistance welding technology of unidirectional carbon fiber-reinforced polyphenylene sulfide composites (UCF/PPS) was systematically studied. The experimental results show that the 100-mesh brass mesh has the best resin wetting effect and heating efficiency, and the PPS/oxidized 100-mesh brass mesh composite resistance element (Ox-RE/PPS) has the highest welding strength. The welding failure mode changes from interface failure and RE failure to interlayer structure damage and fiber fracture. The single-factor experimental results show that the maximum welding strength is reached at 310 °C, 1.15 MPa, and 120 kW/m2. According to the conclusion of the single-factor experiment, the Box-Behnken method was further used to design a three-factor, three-level experiment, and a quadratic regression model was established according to the test results. The results of variance analysis, fitting curve analysis, and perturbation plot analysis proved that the model had high fitting and prediction abilities. From the 3D surface diagram analysis, the influence of power density is the largest, and the interaction between welding temperature and power density is the most significant. Combined with the analysis of Design Expert 13 software, the optimal range of process parameters was obtained as follows: welding temperature 313-314 °C, welding pressure 1.04-1.2 MPa, and power density 124-128 kW/m2. The average strength of resistance welding joints prepared in the optimal range of process parameters was 13.58 MPa.