GDF11 ameliorated myocardial ischemia reperfusion injury by antioxidant stress and up-regulating autophagy in STZ-induced type 1 diabetic rats

Abstract Purpose: To investigate whether GDF11 ameliorates myocardial ischemia reperfusion (MIR) injury in diabetic rats and explore the underlying mechanisms. Methods: Diabetic and non-diabetic rats subjected to MIR (30 min of coronary artery occlusion followed by 120 min of reperfusion) with/without GDF11 pretreatment. Cardiac function, myocardial infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) 15-F2tisoprostane, autophagosome, LC3II/I ratio and Belcin-1 level were determined to reflect myocardial injury, oxidative stress and autophagy, respectively. In in vitro study, H9c2 cells cultured in high glucose (HG, 30mM) suffered hypoxia reoxygenation (HR) with/without GDF11, hydrogen peroxide (H2O2) and autophagy inhibitor 3-methyladenine (3-MA) treatment, cell injury; oxidative stress and autophagy were assessed. Results: Pretreatment with GDF11 significantly improved cardiac morphology and function in diabetes, concomitant with decreased arrhythmia severity, infarct size, CK-MB, LDH and 15-F2tisoprostane release, increased SOD activity and autophagy level. In addition, GDF11 notably reduced HR injury in H9c2 cells with HG exposure, accompanied by oxidative stress reduction and autophagy up-regulation. However, those effects were completely reversed by H2O2 and 3-MA. Conclusion: GDF11 can provide protection against MIR injury in diabetic rats, and is implicated in antioxidant stress and autophagy up-regulation.

Substitutos ósseos sintéticos na Implantodontia / Synthetic bone substitutes for Implant Dentistry ­ a literature review

Objetivo: analisar sistematicamente, na literatura científica, o uso de substitutos ósseos sintéticos na regeneração óssea para Implantodontia. Material e métodos: uma busca foi realizadas nas bases de dados PubMed, Cochrane, LILACS e SciELO, nos últimos quinze anos, combinando as palavras-chave "regeneração óssea", "materiais biocompatíveis", "implantes dentários", e "materiais aloplásticos". Resultados: Dos 199 artigos inicialmente recuperados, apenas 27 foram selecionados, incluindo revisões sistemáticas/ metanálises (n=2), revisões da literatura (n=1), estudos clínicos (n=9) e pré-clínicos (n=12), relato de caso (n=1) e tese (n=1). Nos modelos animais, o vidro bioativo é capaz de provocar formação óssea à distância, inibir a migração apical do epitélio juncional, e gerar maior deposição de cemento na superfície radicular. Partículas esféricas geram melhor dissolução e integração com o novo osso circundante, e bons resultados são vistos nas técnicas de ROG e RTG. Em um estudo clínico randomizado, o vidro bioativo misturado ao osso autógeno para regeneração de defeitos intraósseos reduziu significativamente a profundidade de sondagem, com ganho de nível clínico de inserção, e resolução dos defeitos já aos seis meses. Nos modelos animais, a tríade hidroxiapatita (HA), beta-fosfato tricálcio (ß-TCP), e fosfato de cálcio bifásico (HA+ ß-TCP) tem se mostrado biocompatível, biorreabsorvível e osteocondutora. Um estudo clínico controlado com HA+ ß-TCP/ membrana revelou melhor preservação óssea vertical e horizontal comparado ao coágulo/membrana, nas TCFCs de seis meses. Regenerações ósseas verticais significativas com estes materiais sintéticos são potencializadas pelo uso dos fatores de crescimento. Conclusão: substitutos ósseos sintéticos demonstram uso promissor para regeneração. Entretanto, a evidência clínica deve ser substancialmente aumentada.

Objective: to systematically analyze in the scientifi c literature the use of synthetic bone substitutes for bone regeneration in implant dentistry. Material and methods: a search was conducted at the PubMed, Cochrane, LILACS and SciELO databases considering the last fi fteen years, and combining the keywords "bone regeneration", "biocompatible materials", "dental implants", and "alloplastic materials". Results: of the 199 articles initially retrieved, only 27 were selected, including systematic reviews/meta-analysis (n=2), literature reviews (n=1), clinical (n=9) and pre-clinical (n=12) studies, case report (n=1) and thesis (n=1). In animal models, the bioactive glass can cause bone formation at distance, inhibit apical migration of the junctional epithelium, and generate greater deposition of cementum over the root surface. Spherical particles generate better dissolution and integration with the new surrounding bone, and good results are seen in the ROG and RTG techniques. In a randomized study, the bioactive glass mixed with autogenous bone to regenerate intra-osseous defects signifi cantly reduced probing depths, with clinical attachment level gains, and defect resolution as early as 6 months. In animal models, the triad hydroxyapatite (HA), beta-tricalcium phosphate (ß-TCP), and biphasic calcium phosphate (HA + ß-TCP) has been shown to be biocompatible, bioresorbable, and osteoconductive. A controlled clinical study with (HA + ß-TCP/membrane) showed better vertical and horizontal bone preservation compared to clot / membrane at the 6 month CBCT images. Also, signifi cant vertical bone regeneration with these synthetic materials is enhanced by the use of growth factors. Conclusion: the synthetic bone substitutes are good candidates for regeneration. However, the level of clinical evidence must be substantially increased.

Orientações para uso clínico da BMP / Orientations for clinical use of BMP

Qual é a origem das BMPs e qual a vasta sinonímia empregada para identificá-las?As proteínas morfogenéticas ósseas são as responsáveis pela sinalização para a indução da formação óssea. As BMPs (bone morphogenetic proteins) representam uma família com mais de vinte proteínas relatadas, as quais fazem parte da família dos fatores ß de crescimento e transformação (TGF-ß), ativando e inibindo os fatores de diferenciação e crescimento (GDFs).

What is the origin of BMPs and how extensive is the synonymy employed to identify them?The morphogenetic proteins of the bone are responsible for signaling to induce bone formation. BMPs (bone morphogenetic proteins) represent a family with more than 20 reported proteins, which are part of the transforming growth ß factor family (TGF-ß), activating and inhibiting the differentiation and growth factors (GDF).