RESUMEN
Skeletal Class III malocclusion can significantly impact psychological well-being. Although bimaxillary surgery is a well-established corrective intervention, its psychological effects are not fully understood. This study aims to investigate changes in self-esteem, sensitivity to criticism, and social appearance anxiety following surgery to inform targeted nursing interventions for psychological adaptation. This comparative study included 205 participants: 150 patients with skeletal Class III malocclusion who underwent bimaxillary surgery, and a control group of 55 individuals without malocclusion. The malocclusion group had a mean age of 21.99â ±â 2.28 years (96 males, 109 females). The control group consisted of department interns with Class I occlusion, normal overjet and overbite, and typical facial appearance, with a mean age of 21.61â ±â 2.40 years (26 males, 29 females). Psychological assessments, validated for reliability, measured self-esteem, sensitivity to criticism, and social appearance anxiety before and after surgery. Statistical analyses, including independent sample t tests and one-way ANOVA, were performed to compare outcomes between the groups, with a significance level set at Pâ <â .05. Preoperative assessments revealed that patients with skeletal Class III malocclusion had significantly lower self-esteem and higher sensitivity to criticism and social appearance anxiety compared to the control group (Pâ <â .05). Postoperatively, there were modest improvements in self-esteem and significant reductions in sensitivity to criticism and social appearance anxiety, though levels of social appearance anxiety remained higher than those in the control group (Pâ <â .05). No significant differences in self-esteem and sensitivity to criticism were observed between the surgical and control groups postoperatively (Pâ >â .05). Within-group comparisons showed significant improvements in all measures after surgery (Pâ <â .05). Bimaxillary surgery positively affects the psychological well-being of patients with skeletal Class III malocclusion, enhancing self-esteem and reducing sensitivity to criticism and social appearance anxiety. However, some psychological concerns persist, indicating a need for targeted nursing interventions to further support these patients' psychological well-being.
Asunto(s)
Ansiedad , Maloclusión de Angle Clase III , Procedimientos Quirúrgicos Ortognáticos , Autoimagen , Humanos , Maloclusión de Angle Clase III/cirugía , Maloclusión de Angle Clase III/psicología , Femenino , Masculino , Adulto Joven , Procedimientos Quirúrgicos Ortognáticos/psicología , Ansiedad/psicología , Ansiedad/etiología , AdultoRESUMEN
Necroptosis is a form of regulated necrosis involved in various pathological diseases. The process of necroptosis is controlled by receptor-interacting kinase 1 (RIPK1), RIPK3, and pseudokinase mixed lineage kinase domain-like protein (MLKL), and pharmacological inhibition of these kinases has been shown to have therapeutic potentials in a variety of diseases. In this study, using drug repurposing strategy combined with high-throughput screening (HTS), we discovered that AZD4547, a previously reported FGFR inhibitor, is able to interfere with necroptosis through direct targeting of RIPK1 kinase. In both human and mouse cell models, AZD4547 blocked RIPK1-dependent necroptosis. In addition, AZD4547 rescued animals from TNF-induced lethal shock and inflammatory responses. Together, our study demonstrates that AZD4547 is a potent and selective inhibitor of RIPK1 with therapeutic potential for the treatment of inflammatory disorders that involve necroptosis.
Asunto(s)
Necroptosis , Proteínas Quinasas , Ratones , Animales , Humanos , Proteínas Quinasas/metabolismo , Reposicionamiento de Medicamentos , Apoptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Oncogene HER2 is amplified in 20%-25% of human breast cancers and 6.1%-23.0% of gastric cancers, and HER2-directed therapy significantly improves the outcome for patients with HER2-positive cancers. However, drug resistance is still a clinical challenge due to primary or acquired mutations and drug-induced negative regulatory feedback. In this study, we discovered a potent irreversible HER2 kinase inhibitor, CHMFL-26, which covalently targeted cysteine 805 of HER2 and effectively overcame the drug resistance caused by HER2 V777L, HER2 L755S, HER2 exon 20 insertions, and p95-HER2 truncation mutations. CHMFL-26 displayed potent antiproliferation efficacy against HER2-amplified and mutant cells through constant HER2-mediated signaling pathway inhibition and apoptosis induction. In addition, CHMFL-26 suppressed tumor growth in a dose-dependent manner in xenograft mouse models. Together, these results suggest that CHMFL-26 may be a potential novel anti-HER2 agent for overcoming drug resistance in HER2-positive cancer therapy.
Asunto(s)
Neoplasias de la Mama , Receptor ErbB-2 , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Cisteína , Resistencia a Antineoplásicos , Femenino , Humanos , Ratones , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC) worldwide. Protein phosphatase 2A (PP2A) dysfunction has been widely reported in a broad range of malignancies due to its distinctive role in miscellaneous cellular processes. However, it is poorly understood whether aberrant alterations of PP2A are involved in the network of oncogenic events in LSCC. Here, we detected a panel of PP2A-associated proteins using western blot in both laryngeal squamous cell carcinoma tissues and paired adjacent normal tissues from patients (Data S1). We found that phospho-PP2A/C (Y307), α4, cancerous inhibitor of protein phosphatase 2A (CIP2A), Akt, ezrin, phospho-ezrin (T567), 14-3-3, and focal adhesion kinase (FAK) showed increased expression levels in carcinoma tissues relative to normal tissues, while phospho-Akt (T308) showed decreased levels. Our study, thus, provides a rationale for targeting PP2A to develop novel therapies and proposes a combination of interrelated biomarkers for the diagnostic evaluation and prognosis prediction in LSCC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Laríngeas/metabolismo , Laringe/metabolismo , Proteína Fosfatasa 2/metabolismo , Autoantígenos/metabolismo , Carcinoma de Células Escamosas/genética , Estudios de Casos y Controles , Proteínas del Citoesqueleto/metabolismo , Quinasa 1 de Adhesión Focal/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Laríngeas/genética , Proteínas de la Membrana/metabolismo , Fosforilación , Proteína Fosfatasa 2/genéticaRESUMEN
A facile and economical approach was successfully developed to prepare polymeric nanocubes from poly(ε-caprolactone) (PCL). Nanocubes which are rarely achieved with polymer were obtained simply by a proper thermal treatment on PCL thin film on a glass slide or silicon wafer. The results of scanning electron microscopy (SEM) and atomic force microscopy (AFM) observation showed that the nanocubes were as small as â¼70 nm with high yield (up to â¼130 000 nanocubes in 1 cm2 area). The combination of high-resolution transmission electron microscopy (HRTEM) and fast Fourier transform (FFT) demonstrated that these particles were single nanocrystals. We suggest that the formation of these nanocubes is based on a dewetting and crystallization mechanism. In addition, the size and yield of nanocubes could be controlled by the solution concentration and architecture of polymer as well as substrate. This work might not only facilitate gaining further basic knowledge about nucleation and crystalline growth mechanism of PCL but also provide a new way to fabricate nonspherical polymeric nanoparticles.
RESUMEN
The asymmetric Friedel-Crafts amidoalkylation of indoles with aryl aldimines could be efficiently catalyzed by Trost's bis-ProPhenol dinuclear zinc complexes to attain 3-indolyl methanamine derivatives in good to excellent yields (85-98%) with moderate to high enantiomeric ratios (from 70 : 30 up to 95 : 5 er). Remarkably, this approach provides efficient access to enantiomerically enriched 3-indolyl methanamines, which avoids the formation of the undesirable bis- and tris(indolyl)methanes (BIMs and TIMs) byproduct.
RESUMEN
OBJECTIVE: To explore the effects of thyroid hormone on the expression of homeobox gene Nkx2.1 mRNA in child rat by supplying their hypothyroidism pregnant mother with different dose of levothyroxine (L-thyroxine, L-T(4)) in different times. METHODS: 120 female Wistar rats were randomly divided into eight groups according to the body weight: control group, non-treatment hypothyroidism group, hypothyroidism groups supplied with L-T(4) in high, medium and low dosage in early stage (1st-17th day of pregnancy) and in late stage (18th day of pregnancy-20th day after childbirth). According to 100 grams of body weight, the concentrations of L-T(4) were 3.5, 2.0, 0.5 µg/d in high, medium and low dosage group. All the rats were fed with low-iodine food. The control group was given 200 µg/L potassium iodate solution as drinking water and the other groups were given deionized water. After three months, the rats were mated with normal male rats. After the pregnancy was confirmed, hypothyroidism groups were supplied with L-T(4) of different concentrations. Brain samples were taken from the 17-day fetal rats, new-born and 20-day old offsprings and the levels of Nkx2.1 mRNA in brain tissue were analyzed by real-time fluorescence quantitative PCR techniques. RESULTS: The levels of TT(3) in hypothyroidism groups supplied with L-T(4) in high, medium and low dosages in early and late pregnant stages, non-treatment hypothyroidism group and control group were (0.85 ± 0.17), (0.81 ± 0.18), (0.86 ± 0.21), (0.85 ± 0.20), (0.89 ± 0.18), (0.85 ± 0.20), (0.86 ± 0.20), (1.08 ± 0.07) nmol/L (F = 4.08, P < 0.01); the levels of TT(4) in each group were (0.43 ± 0.16), (0.39 ± 0.11), (0.39 ± 0.13), (0.43 ± 0.17), (0.51 ± 0.19), (0.43 ± 0.16), (0.41 ± 0.15), (39.43 ± 14.16) nmol/L (F = 31.99, P < 0.01); the levels of FT(3) in each group were (3.29 ± 0.61), (3.29 ± 0.61), (3.24 ± 0.61), (3.28 ± 0.63), (3.31 ± 0.59), (3.28 ± 0.50), (3.24 ± 0.49), (4.93 ± 0.46) pmol/L (F = 5.79, P < 0.01); the levels of FT(4) in each group were (3.38 ± 0.80), (3.31 ± 0.67), (3.29 ± 0.73), (3.27 ± 0.71), (3.48 ± 0.81), (3.56 ± 0.66), (3.29 ± 0.61), (27.29 ± 4.53) pmol/L (F = 26.34, P < 0.01). The expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (9.15 × 10(-5) ± 9.17 × 10(-5)) was lower than control group (65.1 × 10(-5) ± 40.90 × 10(-5)) in 17th day of pregnancy (t = 66.224, P < 0.05); the expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (3.16 × 10(-5) ± 0.142 × 10(-5)) was lower than control group (55.6 × 10(-5) ± 51.05 × 10(-5)) in new-born (t = 102.225, P < 0.05); the expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (8.09 × 10(-5) ± 8.21 × 10(-5)) was lower than control group (13.9 × 10(-5) ± 7.43 × 10(-5)) in 20th day after birth (t = 9.235, P < 0.05). The trend of Nkx2.1 mRNA in hypothyroidism groups was decreased in group supplied with L-T(4) in medium dosage in early stage descends in 17th day of pregnancy, new-born and 20th day after birth (57.1 × 10(-5) ± 22.90 × 10(-5)), (30.8 × 10(-5) ± 27.20 × 10(-5)), (17.1 × 10(-5) ± 0.623 × 10(-5)) (F = 13.394, P < 0.01). The expression of Nkx2.1 mRNA in hypothyroidism groups supplied with L-T(4) in medium dosage in early stage in 17th day of pregnancy, new-born and 20th day after childbirth was closest to the control group in every period (t values were 0.225, 0.336, 0.345, all P values > 0.05). CONCLUSION: The difference in the expression of homeobox gene Nkx2.1 mRNA is highly related to the level of thyroid hormone.
Asunto(s)
Encéfalo/metabolismo , Hipotiroidismo/tratamiento farmacológico , Proteínas Nucleares/genética , ARN Mensajero/genética , Tiroxina/farmacología , Factores de Transcripción/genética , Animales , Animales Recién Nacidos/genética , Animales Recién Nacidos/metabolismo , Femenino , Embarazo , Preñez , Ratas , Ratas Wistar , Factor Nuclear Tiroideo 1RESUMEN
OBJECTIVE: To investigate the effects of "Neiguan" (PC 6)-electroacupunture (EA) preconditioning on the myocardium and its mast cells in myocardial ischemia/reperfusion (MI/R) rats. METHODS: Eighteen male SD rats were randomly assigned to sham group, model (IR) group and EA group (n=6/ group). MI/R model was established by occlusion of the descending anterior branch of the coronary artery. Blood samples were taken from the femoral vein before MI (T0), EA for 30 min (T1), 30 min after MI (T2), 30 min after MI/R (T3) and 120 min after MI/R (T4) for assaying serum tumor necrosis factor (TNF)-alpha and histamine contents by using ELISA. Serum lactate dehydrogenase (LDH) and creatinkinase isoenzyme (CK-MB) levels were measured at T0, T3 and T4 by using an automatic biochemistry analyzer. The infarct size was detected by Evan's blue and tetrazolium chloride (TTC) staining. Myocardial TNF-alpha and histamine contents were detected by ELISA. The percentage of mast cell degranulation was determined by toluidine blue staining. RESULTS: Following MI/R, serum LDH and CK-MB levels at phase T3 and T4, serum TNF-alpha and histamine contents at phase T2 and T3, and myocardial mast cell degranulation rate increased significantly, and myocardial TNF-alpha and histamine contents decreased in model group in comparison with pre-MI/R (P < 0.05). Compared with IR model group, serum LDH and CK-MB levels at phase T3 and T4, myocardial TNF-alpha and histamine contents all decreased significantly (P < 0.05), but serum TNF-al infarct size was remarkably smaller in EA group than that in IR model group (P < 0.05). CONCLUSION: "Neiguan" (PC 6)-EA preconditioning has a cardioprotective effect on the ischemia-reperfusion myocardium by promoting mast cell degranulation.