RESUMO
Osteoporosis is a common metabolic disease of elderly and postmenopausal women, with no obvious symptoms during its early stages. In the latter stages of this condition, the patients are prone to fractures, and this can seriously affect their health and quality of life. The worldwide increase in life expectancy has made osteoporosis a global concern. The Xiaoyao pills were previously used in the treatment of depression. In addition, the drug appeared to have estrogen-like activity, which affected the expression of ALP, an early osteoblast-specific marker, and COL-1, a major component of bone extracellular matrix. Xiaoyao pills were assessed for their effects on postmenopausal osteoporosis (PMOM) in mice. The target information of each herbal component of Xiaoyao pills was accessed through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Information from GeneCards, OMIM, PharmGkb, TTD, DrugBank, and other websites was used to construct the regulatory network of the herbal complex through Cytoscape and String network to assess the protein interactions. Mice were ovariectomized, and treated with high and low doses of Xiaoyao pills and these were compared to controls. Their symptoms were assessed by immunocytochemistry of bone tissues. The results suggested that Xiaoyao pills had the ability to alleviate the symptoms of PMOM in ovariectomized mice through the IL-17 signaling pathway. This drug has the potential to become a novel therapeutic agent for the treatment of osteoporosis.
Assuntos
Medicamentos de Ervas Chinesas , Osteoporose Pós-Menopausa , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Camundongos , Feminino , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ovariectomia , HumanosRESUMO
The oncolytic measles virus Edmonston (MV-Edm) strain shows considerable oncolytic activity against a variety of human tumors. In this study, we report MV-Edm is able to trigger apoptosis pathways in infected tumor cells and elucidate the roles of cellular apoptosis in the whole oncolytic process. We also show that activated caspase 3, a key executioner of apoptosis, plays key roles in the oncolytic virotherapy. Activated caspase 3 can accelerate viral replication in cervical cancer cells and enhance the killing effects of the virus. Deficiency of caspase 3 either in tumor cells or in tumor xenograft significantly desensitized tumor to oncolysis with MV-Edm. In the infected cells, caspase 3 regulates interferon α release, which can inhibit viral replication in neighboring tumor cells. We propose that caspase-3 activation enhances the oncolytic effects of MV-Edm, thus inhibiting tumor growth in mice.
Assuntos
Apoptose , Caspase 3/metabolismo , Vírus do Sarampo/genética , Terapia Viral Oncolítica , RNA Interferente Pequeno/genética , Neoplasias do Colo do Útero/prevenção & controle , Animais , Western Blotting , Caspase 3/química , Caspase 3/genética , Proliferação de Células , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Replicação Viral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Resveratrol (RES), a natural plant polyphenol, is an effective inducer of cell cycle arrest and apoptosis in a variety of carcinoma cell types. In addition, RES has been reported to inhibit tumorigenesis in several animal models suggesting that it functions as a chemopreventive and anti-tumor agent in vivo. The chemopreventive and chemotherapeutic properties associated with resveratrol offer promise for the design of new chemotherapeutic agents. However, the mechanisms by which RES mediates its effects are not yet fully understood. In this study, we showed that RES caused cell cycle arrest and proliferation inhibition via induction of unfolded protein response (UPR) in human leukemia K562 cell line. Treatment of K562 cells with RES induced a number of signature UPR markers, including transcriptional induction of GRP78 and CHOP, phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), ER stress-specific XBP-1 splicing, suggesting the induction of UPR by RES. RES inhibited proliferation of K562 in a concentration-dependent manner. Flow cytometric analyses revealed that K562 cells were arrested in G1 phase upon RES treatment. Salubrinal, an eIF2alpha inhibitor, or overexpression of dominant negative mutants of PERK or eIF2alpha, effectively restored RES-induced cell cycle arrest, underscoring the important role of PERK/eIF2alpha branch of UPR in RES-induced inhibition of cell proliferation.
Assuntos
Antineoplásicos/farmacologia , Apoptose , Proliferação de Células/efeitos dos fármacos , Dobramento de Proteína , Estilbenos/farmacologia , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Chaperona BiP do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Processamento de Proteína , Fatores de Transcrição de Fator Regulador X , Resveratrol , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína 1 de Ligação a X-Box , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismoRESUMO
OBJECTIVE: To investigate the quality of life (QOL) and its influence factors in epilepsy patients in Zhuang population in Guangxi Guixi area. METHODS: Totally 78 epilepsy patients in Zhuang populations and 60 healthy controls were enrolled, and their QOL was assessed with Quality of Life in Epilepsy Inventory-31 (QOLIE-31). The QOLIE-31 scores of patients between different sexes, anti-epileptic drugs (AEDs) usage, duration of seizure, and seizure types were compared. RESULTS: QOL score was significantly lower in epileptic group (53.9 +/- 8.0) compared with control group (77.0 +/- 7.1) (P < 0.01). No difference was found in QOLIE-31 scores of patients between men and women (P > 0.05). Patients with single AED, shorter duration of seizure, and tonic-clonic seizure had higher QOLIE-31 scores than those with multiple AEDs, longer duration of seizure, and other seizure types (P < 0.01, P < 0.05, P < 0.01, respectively). CONCLUSIONS: QOL is lower in epilepsy patients than normal people in Zhuang populations in Guangxi Guixi area. Medication and seizure type affects the QOL in patients with epilepsy.