RESUMO
Desoxyrhapontigenin (DRG), a stilbene compound from Rheum undulatum, has been found to exhibit various pharmacological activities, however, its impact on osteoclast formation has not been investigated. The present study investigated the effect of DRG on receptor activator of nuclear factorκB ligand (RANKL)induced osteoclast differentiation in mouse bone marrow macrophages (BMMs) and inflammationinduced bone loss in vivo. BMMs or RAW264.7 cells were treated with DRG, followed by an evaluation of cell viability, RANKLinduced osteoclast differentiation, actinring formation and resorption pits activity. The effects of DRG on the RANKLinduced phosphorylation of MAPK and the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) and cFos were evaluated using western blot analysis once the BMMs were exposed to RANKL and DRG. The expression levels of osteoclast marker genes were also evaluated using western blot analysis and reverse transcriptionquantitative polymerase chain reaction A lipopolysaccharide (LPS)induced murine bone loss model was used to evaluate the protective effect of DRG on inflammationinduced boneloss. The results demonstrated that DRG suppressed the RANKLinduced differentiation of BMMs into osteoclasts, osteoclast actinring formation and bone resorption activity in a dosedependent manner. Furthermore, DRG significantly inhibited LPSinduced bone loss in a mouse model. At the molecular level, DRG inhibited the RANKLinduced activation of extracellular signalregulated kinase, the expression of cFos, and the induction of NFATc1, a crucial transcription factor for osteoclast formation. DRG decreased the expression levels of osteoclast marker genes, including matrix metalloproteinase9, tartrateresistant acid phosphatase and cathepsin K. In conclusion, these findings suggested that DRG inhibited the differentiation of BMMs into mature osteoclasts by suppressing the RANKLinduced activator protein1 and NFATc1 signaling pathways, and may be a potential candidate for treating and/or preventing osteoclastassociated diseases, including osteoporosis.
Assuntos
Reabsorção Óssea/etiologia , Reabsorção Óssea/prevenção & controle , Inflamação/complicações , Osteoclastos/patologia , Ligante RANK/farmacologia , Estilbenos/uso terapêutico , Actinas/metabolismo , Animais , Células da Medula Óssea/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Estilbenos/química , Estilbenos/isolamento & purificação , Estilbenos/farmacologiaRESUMO
Rabies is an important zoonosis in the public and veterinary healthy arenas. This article provides information on the situation of current rabies outbreak, analyzes the current national rabies control system, reviews the weaknesses of the national rabies control strategy, and identifies an appropriate solution to manage the current situation. Current rabies outbreak was shown to be present from rural areas to urban regions. Moreover, the situation worldwide demonstrates that each nation struggles to prevent or control rabies. Proper application and execution of the rabies control program require the overcoming of existing weaknesses. Bait vaccines and other complex programs are suggested to prevent rabies transmission or infection. Acceleration of the rabies control strategy also requires supplementation of current policy and of public information. In addition, these prevention strategies should be executed over a mid- to long-term period to control rabies.
RESUMO
Entecavir (Baraclude®, Bristol-Myers Squibb) is a potent and selective antiviral agent that has demonstrated efficacy in patients with chronic hepatitis B. The most frequent adverse events attributed to entecavir include increased alanine aminotransferase, upper respiratory tract infection, headache, abdominal pain, cough, pyrexia, fatigue, and diarrhea. Although quite a few randomized double-blind studies including ones investigating adverse events along with these general symptoms have been reported, few cases of cutaneous adverse events have been described in detail. We demonstrate a case of granulomatous drug eruption as a cutaneous adverse event induced by entecavir.