ABSTRACT
Hepatocellular carcinoma is one of the most prevalent malignancies and a leading cause of cancer-related mortality worldwide. However, the therapies to prevent hepatocellular carcinoma are still limited and the emergence of drug resistance leads to the development of new anti-cancer drugs and combinational chemotherapy regimens. Our study was aimed to explore the anticancer effects of the essential oil extract (EEEO) from Euphorbia esula which has been widely used in traditional Chinese folk medicine and possessed potential cytotoxic effects in several human tumor cells. However, the mechanisms of EEEO-induced anti-proliferation and apoptosis have not been completely elucidated. In this study, EEEO was prepared by hydro-distillation and the main chemical component of EEEO was identified by GC-MS. HepG2 cells were treated with EEEO in vitro and then evaluated with respect to proliferation, apoptosis, and levels of reactive oxygen species (ROS) and apoptotic proteins. Our studies showed that EEEO decreased cell viability, elevated ROS levels, and induced apoptosis of HepG2 cells in a concentration- and time-dependent manner. Furthermore, Bcl-2 was down-regulated, while Bax was up-regulated in HepG2 after EEEO treatment. These results suggest that EEEO induced apoptosis of HepG2 cells and indicate that this apoptosis might be mediated by the mitochondrial pathway.
ABSTRACT
Abstract Background and objectives: Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. It is used in the management of chronic pain and is recommended as first line drug in the treatment of postoperative or orthopedic injury induced acute pain. The present work is designed to prepare and evaluate mucoadhesive buccal film of tramadol hydrochloride as a novel form of prolonged analgesia for patients with orthopedic injuries. Methods: Buccal films of tramadol hydrochloride were prepared by solvent casting method. The prepared films were evaluated for the various evaluation parameters like thickness, surface pH, weight uniformity, content uniformity, folding endurance, swelling index, in vitro drug release study, in vitro test for mucoadhesion and in vivo studies (primary mucosal irritancy test and analgesic activity). Results: All the formulations exhibited good results for physicochemical characterizations. In in vitro drug release study the films exhibited controlled release more than 12 hours. The formulation BFT2 (containing chitosan and PVP K-90) showed no irritant effect on buccal mucosa and elicit the significant in vivo analgesic activity with 57.14% analgesia against that of standard (61.04%). It was concluded that the mucoadhesive films of tramadol hydrochloride can be effectively used to alleviate the severe pain of orthopedic injuries with prompt onset and prolonged action.
Resumo Justificativa e objetivos: O cloridrato de tramadol é um analgésico opioide de ação central que se liga a receptores opioides específicos. É usado no tratamento de dor crônica e recomendado como fármaco de primeira linha para o tratamento no pós-operatório ou em dor aguda induzida por lesão ortopédica. O presente estudo visa a preparar e avaliar o filme bucal mucoadesivo de cloridrato de tramadol como uma nova forma de analgesia prolongada para pacientes com lesões ortopédicas. Método: Filmes bucais de cloridrato de tramadol foram preparados pelo método de evaporação de solvente. Os filmes preparados foram avaliados para os vários parâmetros de avaliação, como espessura, pH da superfície, uniformidade do peso, uniformidade do conteúdo, resistência a dobras, índice de intumescimento, estudo de liberação da droga in vitro, teste in vitro para mucoadesão e estudos in vivo (teste de irritação da mucosa primária e atividade analgésica). Resultados: Todas as formulações apresentaram bons resultados para caracterizações físico-químicas. Em estudo de libertação de droga in vitro, os filmes exibiram liberação controlada por mais de 12 horas. A formulação de BFT2 (com quitosana e PVP K-90) não mostrou efeito irritante sobre a mucosa bucal e provocou uma atividade analgésica significativa in vivo com 57,14% de analgesia versus a do padrão (61,04%). Concluiu-se que os filmes mucoadesivos de cloridrato de tramadol podem ser usados eficazmente para aliviar a dor intensa de lesões ortopédicas com início rápido e ação prolongada.
Subject(s)
Animals , Male , Rats , Tramadol/administration & dosage , Adhesives , Drug Delivery Systems , Pain Management/methods , Analgesics, Opioid/administration & dosage , Treatment Outcome , Rats, Wistar , Dosage Forms , Mouth MucosaABSTRACT
In the era of genome-wide association study (GWAS), a large number of drug response-related loci have been identified in the non-coding sequences. The interpretation of these loci in mechanism is concerned with the effects on the mRNA expression level of these genes. Expression quantitative trait loci (eQTL) studies indicate the relationship of genome variants and the level of mRNA. Its elucidation of the relationship between genetic variation and gene expression, gene interaction and gene regulatory network provides an efficacious mean for pharmacogenomics. The effects of gene polymorphism on drug responses have been unraveled thoroughly in studies which combined pharmacogenomics with eQTL and GWAS.
ABSTRACT
Objective:To study and investigate the expression effects of interleukin-8 (IL-8)in interstitial fibroblast cells of breast cancer before and after the application of docetaxel chemotherapy.Methods:46 cases of breast cancer without chemotherapy surgical resection in patients with resected tissue specimens from August 2014 to February 2016 in our hospital were selected,all specimens were cultured to form stable breast cancer stromal fibroblast cells,each cell line after raising Daipei were divided into the observation group and control group,the control group cells without any treatment,the observation group of 24h cells treated with docetaxel(20ng/mL),two groups of cells were extracted from the mRNA and analyzed the gene expression and differential gene expression analysis,and then to PCR and protein to detected the expression level of electrophoresis detection of interleukin two interleukin-8 cells,the expression of interleukin-8 in two groups of breast cancer cells was observed and compared.Results:After docetaxel chemotherapy,the breast cancer stromal fibroblast gene expression changed,and compared to the control group,the observation group were given docetaxel chemotherapy after breast cancer between matter into fiber cell interleukin-6 serum IL-8 mRNA and protein expression levels were significantly higher than that of the control group,the difference had statistical significance (P＜0.05).Conclusions:Interleukin IL-8 in the breast cancer matter into fiber cells were significantly up-regulated after docetaxel chemotherapy,indicating that the expression changes of breast cancer may be related with the effect of chemotherapy and chemotherapy drug resistance related.