RESUMEN
Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by wine stains, abnormal tissue and bone growth, and vascular malformations. Genital involvement is uncommon. We report a case of a 12-year-old female with KTS who experienced recurrent profuse vaginal bleeding and provide a comprehensive literature review on KTS cases with genital involvement. The literature reports 7 cases, mainly in individuals aged 25 to 45, presenting with uncontrollable vaginal bleeding and anemia. Endovascular interventions were the primary treatment, although surgery was necessary in some cases. Recent studies have identified a potential association between KTS and the PIK3CA gene mutation, offering insights for pharmacological treatment.
RESUMEN
Abnormal activation of the nuclear factor-kappa B (NF-κB) signaling pathway is closely implicated in triple-negative breast cancer growth, metastasis, and tumor immune escape. In this study, the anti-cancer effects of icariin, a natural flavonol glycoside, toward breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species induction. Importantly, icariin impaired the activation of the NF-κB/EMT pathway, as evidenced by upregulation of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss-128167, an inhibitor of SIRT6, dramatically attenuated anti-migration and anti-invasion effects of icariin. Transcriptomic analysis verified that impairment of NF-κB led to the selective function of icariin in breast cancer cells. Notably, icariin exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MDA-MB-231 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Together, these results showed that icariin could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the SIRT6/NF-κB signaling pathway, suggesting that icariin might serve as a potential candidate drug for the treatment of breast cancer.
Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , FN-kappa B/metabolismo , Oxidación-Reducción/efectos de los fármacos , Sirtuinas/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Femenino , Flavonoides/química , Perfilación de la Expresión Génica , Humanos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Biológicos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Especies Reactivas de Oxígeno/metabolismo , Transcripción Genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/etiología , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The present study aimed to investigate whether 17ßestradiol (E2) exerts protective effects on bone deterioration induced by ovariectomy (OVX) through the ephA2/ephrinA2 signaling pathway in rats. Female rats were subjected to OVX, sham surgeryor OVX+E2 treatment. Levels of biomarkers were measured in serum and urine. Hematoxylin and eosin staining was performed on paraffinembedded bone sections. Expression of genes and proteins was analyzed by reverse transcriptionquantitative polymerase chain reaction and western blotting, respectively. Bone mineral density (BMD) was analyzed by dualenergy Xray absorptiometry. Trabecular bone microarchitecture was also evaluated. Osteoclastogenesis was induced by in vitro culturing with mouse receptor activator of nuclear factor κB ligand (RANKL) and macrophage colonystimulating factor 1. small interfering RNA was designed to knockdown ehpA2 receptor and its ligand ephrinA2. Results of the present study demonstrated that E2 had suppressive effects on OVXinduced body weight gain and bone turnover factors in serum and urine. E2 inhibited the bone resorption function of osteoclasts by inhibiting the production of tartrateresistant acid phosphatase5b and RANKL, and induced bone formation function of osteoblasts by prompting runtrelated transcription factor 2, Sp7 transcription factor and collagen alpha1(I) chain expression in bone marrow cells. E2 treatment significantly increased the tibia BMD and prevented the deterioration of trabecular microarchitecture compared with the OVX group. Moreover, E2 significantly decreased the OVXstimulated expression of ephA2 and ephrinA2. EphA2 or ephrin A2 knockdown significantly suppressed osteoclastogenesis in vitro. In conclusion, E2 can attenuate OVXinduced bone deterioration partially through the suppression of the ephA2/ephrinA2 signaling pathway. Therefore EphA2/ephrinA2 signaling pathway may be a potential target for osteoporosis treatment.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Estradiol/farmacología , Osteoporosis Posmenopáusica/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Densidad Ósea , Regeneración Ósea , Diferenciación Celular , Células Cultivadas , Evaluación Preclínica de Medicamentos , Efrina-A2/genética , Efrina-A2/metabolismo , Femenino , Humanos , Osteoclastos/fisiología , Osteoporosis Posmenopáusica/metabolismo , Ovariectomía , Ratas Sprague-Dawley , Receptor EphA2/genética , Receptor EphA2/metabolismo , Tibia/efectos de los fármacos , Tibia/metabolismo , Tibia/patología , TranscriptomaRESUMEN
Excessive glucocorticoid (GC) in type 2 diabetes mellitus (T2DM) reduces insulin sensitivity, impairs ß-cell function, increases gluconeogenesis and glycogenolysis, impairs glucose uptake and metabolism, and reduces the insulinotropic effects of glucagon-like peptide 1. Melatonin, which serves as a physiological regulator of the hypothalamic-pituitary-adrenal (HPA) axis, has been suggested to have anti-diabetic effects. The objective of the present study was to investigate the effect of the MT1/MT2 melatonin agonist Neu-P11 on glucose and lipid metabolism in T2DM rats induced by a high fat diet combined with low doses of streptozotocin. T2DM rats were intragastrically administered melatonin (20mg/kg), Neu-P11 (20, 10, 5mg/kg), or a vehicle for 4 weeks. The results showed that the increased food intake, water consumption, hyperglycemia, glucose intolerance, and insulin resistance in T2DM rats were all improved by Neu-P11 treatment. Neu-P11 increased GC receptor expression and suppressed 11ß-hydroxysteroid dehydrogenase 1 activity in the hippocampus by enhancing GC sensitivity and HPA feedback, thus decreasing the high GC levels. Transcript levels of the glucose metabolism-related genes peroxisome proliferator-activated receptor-γ, glucose transporter type-4, and adiponectin in adipose tissue were significantly increased after Neu-P11 treatment, while leptin mRNA was significantly decreased. Furthermore, MT1 and MT2 protein levels were enhanced by Neu-P11. These data suggest that normalization of the hyperactivated HPA axis by melatonin and Neu-P11 in T2DM regulates metabolic profiles and insulin sensitivity, which may attenuate insulin resistance and glucose homeostasis. Because Neu-P11 has superior pharmacokinetics and a longer half-life than melatonin, it might be beneficial in treating obesity and T2DM.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipotálamo/efectos de los fármacos , Indoles/farmacología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Piranos/farmacología , Receptor de Melatonina MT1/agonistas , Receptor de Melatonina MT2/agonistas , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , Adiponectina/genética , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Corticosterona/sangre , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Ingestión de Líquidos/efectos de los fármacos , Ayuno/sangre , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 4/genética , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Indoles/uso terapéutico , Resistencia a la Insulina , Leptina/genética , PPAR gamma/genética , Piranos/uso terapéutico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
Three new pyrones, solanapyrones P-R (1-3), were afforded by the extracts of the endophytic fungus Alternaria tenuissima SP-07 isolated from the fresh root of Chinese herbal medicine Salvia przewalskii, along with the known solanapyrones (4-6) and benzopyrones (7-9). Solanapyrones P (1) and Q (2) possess an unprecedented nor-solanapyrone skeleton as natural products. Their structures were determined on the basis of NMR and HR-ESI-MS analysis. The plausible biosynthetic pathways to those unknown compounds were discussed. All the isolated compounds were evaluated for their antibacterial activities against six bacteria.
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Alternaria/química , Antibacterianos/química , Pironas/química , Salvia/microbiología , Antibacterianos/aislamiento & purificación , Medicamentos Herbarios Chinos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Raíces de Plantas/microbiología , Pironas/aislamiento & purificaciónRESUMEN
The aim of this study was to determine whether the Rehmannia glutinosa oligosaccharides (ROS) ameliorate the impaired glucose metabolism and the potential mechanism in chronic stress rats fed with high-fat diet. The rats were fed by a high-fat diet and simultaneously stimulated by chronic stress over 5 weeks. Body weight, fasting plasma glucose, intraperitoneal glucose tolerance test (IPGTT), plasma lipids, gluconeogenesis test (GGT), glycogen content, and corticosterone, insulin and leptin levels were measured. The results showed that ROS administration (100, 200 mg/kg, i.g.) for 5 weeks exerted the effects of increasing the organ weights of thymus and spleen, lowering the fasting plasma glucose level, improving impaired glucose tolerance, increasing the contents of liver and muscle glycogen, decreasing the gluconeogenesis ability, plasma-free fatty acid's level, as well as plasma triglyceride and total cholesterol levels in chronic stress and high-fat fed rats, especially in the group of 200mg/kg; while the plasma corticosterone level was decreased, and plasma leptin level was increased. These results suggest that ROS exert an ameliorating effect of impaired glucose metabolism in chronic stress rats fed with high-fat diet, and the potential mechanism may be mediated through rebuilding the glucose homeostasis in the neuroendocrine immuno-modulation (NIM) network through multilinks and multitargets.
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Trastornos del Metabolismo de la Glucosa/tratamiento farmacológico , Oligosacáridos/uso terapéutico , Fitoterapia , Especies Reactivas de Oxígeno/metabolismo , Rehmannia , Animales , Glucemia/metabolismo , Corticosterona/sangre , Dieta Alta en Grasa/efectos adversos , Evaluación Preclínica de Medicamentos , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Glucógeno/metabolismo , Insulina/sangre , Leptina/sangre , Lípidos/sangre , Hígado/metabolismo , Masculino , Músculos/metabolismo , Oligosacáridos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Plantas Medicinales , Distribución Aleatoria , Ratas Wistar , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismoRESUMEN
Two new isocoumarins (1 and 2), a new alkaloid (3), and a known N-acetyldopamine dimer (4) were isolated from the ethyl acetate extract of Chinese insect medicine Eupolyphaga sinensis. Their structures were elucidated on the basis of detailed spectroscopic investigations, such as 1D- and 2D NMR spectroscopy, as well as by means of HR-MS. The structure of 1 was firmly confirmed by X-ray crystallography, and the absolute configuration was revealed by experimental and computational optical rotation analyses. Cytotoxicities of 1-4 were measured in vitro against 10 selected cancer cell lines.
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Alcaloides/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Cucarachas/química , Isocumarinas/aislamiento & purificación , Neoplasias/tratamiento farmacológico , Alcaloides/farmacología , Alcaloides/uso terapéutico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Humanos , Isocumarinas/farmacología , Isocumarinas/uso terapéutico , Medicina Tradicional China , Ratones , Estructura MolecularRESUMEN
A new oxazole (1) was obtained from Chinese insect medicine Aspongopus chinensis, along with three known N-acetyldopamine derivatives (2-4). Their structures were determined on the basis of NMR and ESI-MS analyses. The possible biosynthetic pathways of the isolated compounds are discussed. Cytotoxicities of those compounds against 10 selected cancer cells were measured in vitro.