RESUMEN
Abstract Diabetic Neuropathy (DN) is one of the prevailing micro vascular complications of diabetes which can be characterized by neuropathic pain. Streptozotocin (STZ) induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy. STZ injection leads to neurotoxicity of peripheral nerves that leads to development of Peripheral Diabetic Neuropathy in rat model. The present study was aimed at exploring the protective role of Tinospora cordifolia extract in STZ induced neurotoxicity and evaluating mechanisms responsible for attenuating neuropathic pain. Neuropathic pain markers like hyperalgesia, allodynia and motor deficits were assessed before STZ injection and after the treatment with 250 mg/kg and 500 mg/kg dose of Tinospora cordifolia. Oxidative stress markers, NGF expression in sciatic nerve were observed after seven weeks treatment. Our results demonstrated that seven weeks treatment with Tinospora cordifolia leaf extract significantly relieved thermal hyperalgesia and allodynia by increasing the antioxidant enzyme levels, decreasing the lipid peroxidation and by increasing the Nerve growth factor (NGF) expression in diabetic rat sciatic nerves. Our findings highlighted the beneficial effects of oral administration of Tinospora cordifolia extract in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and by inducing NGF m RNA in sciatic nerves.
Asunto(s)
Animales , Masculino , Ratas , Plantas Medicinales/efectos adversos , Extractos Vegetales/análisis , Menispermaceae/clasificación , Hiperalgesia/dietoterapiaRESUMEN
Ovarian cancer is the most lethal gynecological neoplasm, and epithelial ovarian cancer (EOC) accounts for 90% of ovarian malignancies. The 5-year survival is less than 45%, and, unlike other types of cancer, the proportion of women who die from this disease has not improved in recent decades. Nerve growth factor (NGF) and tropomyosin kinase A (TRKA), its high-affinity receptor, play a crucial role in pathogenesis through cell proliferation, angiogenesis, invasion, and migration. NGF/TRKA increase their expression during the progression of EOC by upregulation of oncogenic proteins as vascular endothelial growth factor (VEGF) and c-Myc. Otherwise, the expression of most oncoproteins is regulated by microRNAs (miRs). Our laboratory group reported that the tumoral effect of NGF/TRKA depends on the regulation of miR-145 levels in EOC. Currently, mitochondria have been proposed as new therapeutic targets to activate the apoptotic pathway in the cancer cell. The mitochondria are involved in a myriad of functions as energy production, redox control, homeostasis of Ca+2, and cell death. We demonstrated that NGF stimulation produces an augment in the Bcl-2/BAX ratio, which supports the anti-apoptotic effects of NGF in EOC cells. The review aimed to discuss the role of mitochondria in the interplay between NGF/TRKA and miR-145 and possible therapeutic strategies that may decrease mortality due to EOC.
RESUMEN
AIMS: To investigate the effects of moderate aerobic physical training on cardiac function and morphology as well as on the levels of glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) of animals infected with the Y strain of Trypanosoma cruzi. MAIN METHODS: Twenty-eight male C57BL/6 mice were distributed into 4 groups: sedentary control (SC), trained control (TC), sedentary infected (CHC) and trained infected (CHT). The infection was performed by intraperitoneal injection of trypomastigote forms and the animals were adapted to treadmill in the week before the beginning of the training protocol, initiated 45â¯days post infection. Maximal exercise test (TEM) was performed at the baseline as well as at the end of the 4th, 8th and 12th weeks of training. At the end of the 12th week, all animals were evaluated for cardiac morphology and function by echocardiography. KEY FINDINGS: CHC group showed a larger area of right ventricle (RVA), increased end-systolic volume and reduction in ejection fraction (EF), stroke volume (SV), cardiac output (CO) and fractional area change (FAC). The training reduced the RVA and improved the FAC of chagasic animals. GDNF level was higher in TC and CHC groups compared to SC in heart and BDNF levels were higher in CHC compared to SC in heart and serum. SIGNIFICANCE: Physical training ameliorated the cardiac function of infected animals and promoted adjusts in BDNF and GDNF levels. These findings evidenced these neurotrophins as possible biomarkers of cardiac function responsive to exercise stimulus.
Asunto(s)
Tolerancia al Ejercicio/fisiología , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/fisiología , Animales , Biomarcadores/sangre , Factor Neurotrófico Derivado del Encéfalo/análisis , Factor Neurotrófico Derivado del Encéfalo/fisiología , Gasto Cardíaco , Enfermedad de Chagas/metabolismo , Modelos Animales de Enfermedad , Ecocardiografía , Prueba de Esfuerzo , Factor Neurotrófico Derivado de la Línea Celular Glial/análisis , Factor Neurotrófico Derivado de la Línea Celular Glial/fisiología , Corazón/fisiología , Pruebas de Función Cardíaca , Ventrículos Cardíacos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Factor de Crecimiento Nervioso/análisis , Factor de Crecimiento Nervioso/fisiología , Factores de Crecimiento Nervioso/metabolismo , Factores de Crecimiento Nervioso/fisiología , Volumen Sistólico/fisiología , Trypanosoma cruzi/patogenicidadRESUMEN
Ovarian cancer is the eighth most common cancer in women worldwide, and epithelial ovarian cancer (EOC) represents 90% of cases. Nerve growth factor (NGF) and its high affinity receptor tyrosine kinase A receptor (TRKA) have been associated with the development of several types of cancer, including EOC; both NGF and TRKA levels are elevated in this pathology. EOC presents high angiogenesis and several molecules have been reported to induce this process. NGF increases angiogenesis through its TRKA receptor on endothelial cells, and by indirectly inducing vascular endothelial growth factor expression. Other molecules controlled by NGF include ciclooxigenase-2, disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) and calreticulin (CRT), proteins involved in crucial processes needed for EOC progression. These molecules could be modified through microRNA regulation, which could be regulated by NGF. MicroRNAs are the widest family of non-coding RNAs; they bind to 3'-UTR of mRNAs to inhibit their translation, to deadenilate or to degraded them. In EOC, a deregulation in microRNA expression has been described, including alterations of miR-200 family, cluster-17-92, and miR-23b, among others. Since the NGF-microRNA relationship in pathologies has not been studied, this review proposes that some microRNAs could be associated with NGF/TRKA activation, modifying protein levels needed for EOC progression.