RESUMEN
Patchouli alcohol (PA) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine, and the related mechanism remains to be fully understood. Our previous study has indicated that PA significantly reduced visceral sensitivity and defecation area in IBS-D rats. In this study, we prepared an IBS-D rat model and observed the dynamic intestinal motility and colonic longitudinal muscle and myenteric plexus (LMMP) neurons, as well as their subtypes at D14, D21, and D28. After PA administration, we observed the effects on the changes in intestinal motility, colonic LMMP neurons, and LMMP Myosin Va in IBS-D rats and their co-localization with inhibitory neurotransmitter-related proteins. The results indicated that PA treatment could alleviate IBS-D symptoms, regulate the abnormal expression of LMMP neurons, increase Myosin Va expression, up-regulate co-localization levels of Myosin Va with neuronal nitric oxide synthase (nNOS), and promote co-localization levels of Myosin Va with vasoactive intestinal polypeptide (VIP). In conclusion, this study demonstrated the neuropathic alterations in the colon of chronic restraint stress-induced IBS-D rat model. PA reversed the neuropathological alteration by affecting the transport process of nNOS and VIP vesicles via Myosin Va and the function of LMMP inhibitory neurons, and these effects were related to the mechanism of enteric nervous system (ENS) remodeling.
Asunto(s)
Síndrome del Colon Irritable , Ratas , Animales , Síndrome del Colon Irritable/tratamiento farmacológico , Modelos Animales de Enfermedad , Diarrea/tratamiento farmacológico , Diarrea/etiología , Diarrea/metabolismo , Neuronas/metabolismo , Adaptación Fisiológica , MiosinasRESUMEN
Resistance to cancer therapy is a challenge because of innate tumor heterogeneity and constant tumor evolution. Since the pathway of resistance cannot be predicted, combination therapies may address this progression. We discovered that in addition to IGF1 and IGF2, IGFBP-3 binds bFGF, HGF, neuregulin, and PDGF AB with nanomolar affinity. Because growth factors drive resistance, simultaneous inhibition of multiple growth factor pathways may improve the efficacy of precision therapy. Growth factor sequestration by IGFBP-3-Fc enhances the activity of EGFR inhibitors by decreasing cell survival and inhibiting bFGF, HGF, and IGF1 growth factor rescue and also potentiates the activity of other cancer drugs. Inhibition of tumor growth in vivo with adjuvant IGFBP-3-Fc with erlotinib versus erlotinib after treatment cessation supports that the combination reduces cell survival. Inhibition of multiple growth factor pathways may postpone resistance and extend progression-free survival in many cancer indications.
Asunto(s)
Receptores ErbB/genética , Clorhidrato de Erlotinib/farmacología , Regulación Neoplásica de la Expresión Génica , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Carga Tumoral/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Células HEK293 , Células HT29 , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Fragmentos Fc de Inmunoglobulinas/farmacología , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/antagonistas & inhibidores , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Células MCF-7 , Masculino , Ratones , Ratones Endogámicos NOD , Neurregulina-1/genética , Neurregulina-1/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Sleep disorders are common in hemodialysis (HD) patients. This study examined the relationship between quality of sleep (QoS) and religious/spiritual activity in HD patients. METHODS: The study subjects were 861 HD patients from 14 dialysis clinics in Taiwan. QoS and religious/spiritual activity were evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and the Royal Free Questionnaire respectively. RESULTS: There was no difference in clinical parameters between the good and poor sleepers. Although total scores of religious and spiritual activity did not correlate with global PSQI score, patients who held strong 'spiritual' beliefs reported more problems in 'sleep disturbances', while those who exercised religious beliefs more strongly reported less trouble in 'daytime dysfunction'. CONCLUSION: There is no significant correlation between QoS and religious/spiritual activity globally. However, the spiritual and religious activity did associate with different components of QoS.