RESUMEN
Thousands of years ago, humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both inâ vitro and inâ vivo. Total flavonoids and total phenolic acids content in P30K were 244.6â mg/g and 275.8â mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30â µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11ß-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.
Asunto(s)
Própolis , Humanos , Própolis/farmacología , Simulación del Acoplamiento Molecular , Flavonoides/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , BrasilRESUMEN
OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.
Asunto(s)
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Californio/uso terapéutico , Neoplasias Endometriales/radioterapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia/instrumentación , Carmustina/uso terapéutico , Terapia Combinada , Citarabina/uso terapéutico , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Humanos , Melfalán/uso terapéutico , Persona de Mediana Edad , Podofilotoxina/uso terapéutico , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Adenocarcinoma/radioterapia , Braquiterapia/métodos , Californio/uso terapéutico , Neoplasias Endometriales/radioterapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia/instrumentación , Terapia Combinada , Carmustina/uso terapéutico , Citarabina/uso terapéutico , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Estudios de Seguimiento , Melfalán/uso terapéutico , Podofilotoxina/uso terapéutico , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: To observe the effect of cholecystectomy on the changes of motion pattern of Beagle dogs' sphincter of Oddi (SO), and investigate the modulatory role of nitric oxide (NO) and cholecystokinin (CCK) in the regulation of SO. METHODS: Pressure of common bile duct, SO motility, response to bolus injections of cholecystokinin (CCK, 20 ng/kg and 100 ng/kg), basal pressure (BP) and phasic contraction amplitude (PCA) were measured respectively by manometry in six Beagle dogs before and after cholecystectomy. RESULTS: After cholecystectomy, the pressure and diameter of common bile ducts (CBD) was significantly increased (p<0.01); BP and phasic contraction frequency (PCF) were also increased, however, no significant differences were found between the two groups; the SO motilities was not significantly changed. The relaxation responded to physiological dose of CCK (20ng/kg) was decreased, while bolus-dose of CCK (100ng/kg) induced rapid contractions and decreased PCA after cholecystectomy. The regulation pattern of SO pressure modulated by NO and its inhibitor had changed after cholecystectomy. CONCLUSION: After cholecystectomy in Beagle dogs, no obviously change of motion pattern of SO was observed through self-compensation, but these compensations may lead to some changes of regulation pattern of CCK and NO on SO.
Asunto(s)
Colagogos y Coleréticos/administración & dosificación , Colecistectomía/efectos adversos , Colecistoquinina/administración & dosificación , Motilidad Gastrointestinal/fisiología , Óxido Nítrico/fisiología , Esfínter de la Ampolla Hepatopancreática/fisiología , Animales , Conducto Colédoco/fisiología , Perros , Motilidad Gastrointestinal/efectos de los fármacos , Masculino , Manometría , Óxido Nítrico Sintasa/fisiología , Presión , Valores de Referencia , Esfínter de la Ampolla Hepatopancreática/efectos de los fármacos , Disfunción del Esfínter de la Ampolla Hepatopancreática/etiología , Disfunción del Esfínter de la Ampolla Hepatopancreática/fisiopatología , Factores de TiempoRESUMEN
To observe the effect of cholecystectomy on the changes of motion pattern of Beagle dogs' sphincter of Oddi (SO), and investigate the modulatory role of nitric oxide (NO) and cholecystokinin (CCK) in the regulation of SO. Pressure of common bile duct, SO motility, response to bolus injections of cholecystokinin (CCK, 20 ng/kg and 100 ng/kg), basal pressure (BP) and phasic contraction amplitude (PCA) were measured respectively by manometry in six Beagle dogs before and after cholecystectomy. After cholecystectomy, the pressure and diameter of common bile ducts (CBD) was significantly increased (p<0.01); BP and phasic contraction frequency (PCF) were also increased, however, no significant differences were found between the two groups; the SO motilities was not significantly changed. The relaxation responded to physiological dose of CCK (20ng/kg) was decreased, while bolus-dose of CCK (100ng/kg) induced rapid contractions and decreased PCA after cholecystectomy. The regulation pattern of SO pressure modulated by NO and its inhibitor had changed after cholecystectomy. CONCLUSION: After cholecystectomy in Beagle dogs, no obviously change of motion pattern of SO was observed through self-compensation, but these compensations may lead to some changes of regulation pattern of CCK and NO on SO.
Asunto(s)
Animales , Perros , Cirugía General/métodos , Colecistectomía/métodos , Óxido Nítrico/análisis , Perros/clasificaciónRESUMEN
To observe the effect of cholecystectomy on the changes of motion pattern of Beagle dogs' sphincter of Oddi (SO), and investigate the modulatory role of nitric oxide (NO) and cholecystokinin (CCK) in the regulation of SO. Pressure of common bile duct, SO motility, response to bolus injections of cholecystokinin (CCK, 20 ng/kg and 100 ng/kg), basal pressure (BP) and phasic contraction amplitude (PCA) were measured respectively by manometry in six Beagle dogs before and after cholecystectomy. After cholecystectomy, the pressure and diameter of common bile ducts (CBD) was significantly increased (p<0.01); BP and phasic contraction frequency (PCF) were also increased, however, no significant differences were found between the two groups; the SO motilities was not significantly changed. The relaxation responded to physiological dose of CCK (20ng/kg) was decreased, while bolus-dose of CCK (100ng/kg) induced rapid contractions and decreased PCA after cholecystectomy. The regulation pattern of SO pressure modulated by NO and its inhibitor had changed after cholecystectomy. CONCLUSION: After cholecystectomy in Beagle dogs, no obviously change of motion pattern of SO was observed through self-compensation, but these compensations may lead to some changes of regulation pattern of CCK and NO on SO.(AU)
Asunto(s)
Animales , Perros , Colecistectomía/métodos , Óxido Nítrico/análisis , Cirugía General/métodos , Perros/clasificaciónRESUMEN
PURPOSE: Natural orifice transluminal endoscopic surgery (NOTES) is a new technique. This study describes our initial experience of NOTES and investigates the feasibility of transumbilical endoscopic cholecystectomy (TUEC). METHODS: Eight domestic pigs were submitted to TUEC. After establishment of pneumoperitoneum, a bi-channel endoscope was placed through an infra-umbilical trocar. The gallbladder fundus was lifted by a grasper. The cystic duct and artery was dissected with a flexible hook and clipped by a clip fixing device. The specimen was extracted through the infra-umbilical trocar. RESULTS: The mean operation time was 114 minutes, ranging from 75 to 155 minutes. All the gallbladders were removed successfully. There was one case of subtotal resection, two cases of bleeding and three cases of bile leakage. CONCLUSION: Transumbilical endoscopic cholecystectomy is feasible although it needs more support of experiments and techniques before being applied on human subjects.
Asunto(s)
Colecistectomía Laparoscópica/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Ombligo/cirugía , Animales , Pérdida de Sangre Quirúrgica , Colecistectomía Laparoscópica/instrumentación , Estudios de Factibilidad , Modelos Animales , Cirugía Endoscópica por Orificios Naturales/instrumentación , Tempo Operativo , Reproducibilidad de los Resultados , Porcinos , Factores de TiempoRESUMEN
PURPOSE: Natural orifice transluminal endoscopic surgery (NOTES) is a new technique. This study describes our initial experience of NOTES and investigates the feasibility of transumbilical endoscopic cholecystectomy (TUEC). METHODS: Eight domestic pigs were submitted to TUEC. After establishment of pneumoperitoneum, a bi-channel endoscope was placed through an infra-umbilical trocar. The gallbladder fundus was lifted by a grasper. The cystic duct and artery was dissected with a flexible hook and clipped by a clip fixing device. The specimen was extracted through the infra-umbilical trocar. RESULTS: The mean operation time was 114 minutes, ranging from 75 to 155 minutes. All the gallbladders were removed successfully. There was one case of subtotal resection, two cases of bleeding and three cases of bile leakage. CONCLUSION: Transumbilical endoscopic cholecystectomy is feasible although it needs more support of experiments and techniques before being applied on human subjects.
Asunto(s)
Animales , Colecistectomía Laparoscópica/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Ombligo/cirugía , Pérdida de Sangre Quirúrgica , Colecistectomía Laparoscópica/instrumentación , Estudios de Factibilidad , Modelos Animales , Cirugía Endoscópica por Orificios Naturales/instrumentación , Tempo Operativo , Reproducibilidad de los Resultados , Porcinos , Factores de TiempoRESUMEN
PURPOSE: Natural orifice transluminal endoscopic surgery (NOTES) is a new technique. This study describes our initial experience of NOTES and investigates the feasibility of transumbilical endoscopic cholecystectomy (TUEC). METHODS: Eight domestic pigs were submitted to TUEC. After establishment of pneumoperitoneum, a bi-channel endoscope was placed through an infra-umbilical trocar. The gallbladder fundus was lifted by a grasper. The cystic duct and artery was dissected with a flexible hook and clipped by a clip fixing device. The specimen was extracted through the infra-umbilical trocar. RESULTS: The mean operation time was 114 minutes, ranging from 75 to 155 minutes. All the gallbladders were removed successfully. There was one case of subtotal resection, two cases of bleeding and three cases of bile leakage. CONCLUSION: Transumbilical endoscopic cholecystectomy is feasible although it needs more support of experiments and techniques before being applied on human subjects.(AU)