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[PMID]:29348072
[Au] Autor:Liu C; Chen X; Zhi X; Weng W; Li Q; Li X; Zou Y; Su J; Hu HG
[Ad] Endereço:Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
[Ti] Título:Structure-based development of an osteoprotegerin-like glycopeptide that blocks RANKL/RANK interactions and reduces ovariectomy-induced bone loss in mice.
[So] Source:Eur J Med Chem;145:661-672, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone, for which the underlying mechanism is an imbalance between bone resorption and bone remodeling. The protein-protein interactions between receptor activator of nuclear factor-κB ligand (RANKL), RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the development and activation of osteoclasts in bone remodeling, and are regarded as a pivotal therapeutic target for the treatment of osteoporosis. Herein, we disclose the successful development of a novel glycopeptide (OM-2), the structure of which is based on the key interacting sites of the reported RANKL and OPG crystal structure. OM-2 exhibited potent binding affinity with RANKL and resistance to degradation by protease enzymes. It also blocked RANKL/RANK interactions, and inhibited osteoclastogenesis in vitro. In vivo studies confirmed that OM-2 could effectively reduce bone loss and inhibit osteoclast activation in ovariectomized (OVX) mice at a dosage of 20.0 mg/kg/day. Accordingly, OM-2 is suggested as a therapeutic candidate for postmenopausal osteoporosis (PMOP) and osteoclastogenesis-related diseases like rheumatoid arthritis (RA). More importantly, its identification validates our structure-based strategy for the development of drugs that target the RANKL/RANK/OPG system.
[Mh] Termos MeSH primário: Glicopeptídeos/farmacologia
Osteoporose/tratamento farmacológico
Osteoprotegerina/farmacologia
Ovariectomia
Ligante RANK/antagonistas & inibidores
Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Osso e Ossos/efeitos dos fármacos
Osso e Ossos/metabolismo
Osso e Ossos/patologia
Relação Dose-Resposta a Droga
Feminino
Glicopeptídeos/síntese química
Glicopeptídeos/química
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Simulação de Acoplamento Molecular
Estrutura Molecular
Osteoporose/metabolismo
Osteoprotegerina/química
Ligação Proteica/efeitos dos fármacos
Ligante RANK/metabolismo
Receptores Citoplasmáticos e Nucleares/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycopeptides); 0 (Osteoprotegerin); 0 (RANK Ligand); 0 (Receptors, Cytoplasmic and Nuclear)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE


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[PMID]:28450653
[Au] Autor:Soewondo P; Suyono S; Sastrosuwignyo MK; Harahap AR; Sutrisna B; Makmun LH
[Ad] Endereço:Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia. soewondops@yahoo.com.
[Ti] Título:Prediction of Wound Healing in Diabetic Foot Ulcers: an Observational Study in Tertiary Hospital in Indonesia.
[So] Source:Acta Med Indones;49(1):41-51, 2017 Jan.
[Is] ISSN:0125-9326
[Cp] País de publicação:Indonesia
[La] Idioma:eng
[Ab] Resumo:AIM: to evaluate the role of clinical characteristics, functional markers of vasodilation, inflammatory response, and atherosclerosis in predicting wound healing in diabetic foot ulcer. METHODS: a cohort study (February - October 2010) was conducted from 40 subjects with acute diabetic foot ulcer at clinical ward of Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia. Each subject underwent at least two variable measurements, i.e. during inflammatory phase and proliferation phase. The studied variables were clinical characteristics, complete peripheral blood count (CBC) and differential count, levels of HbA1c, ureum, creatinine, lipid profile, fasting blood glucose (FBG), marker of endothelial dysfunction (asymmetric dimethylarginine/ADMA, endothelin-1/ET-1, and flow-mediated dilation/FMD of brachial artery), and marker of vascular calcification (osteoprotegerin/OPG). RESULTS: median of time achieving 50% granulation tissue in our study was 21 days. There were nine factors that contribute in the development of 50% granulation tissue, i.e. family history of diabetes mellitus (DM), previous history of wound, wound area, duration of existing wound, captopril and simvastatin medications, levels of ADMA, ET-1, and OPG. There were three out of the nine factors that significantly correlated with wound healing, i.e. wound area, OPG levels, and simvastatin medications. CONCLUSION: in acute diabetic foot ulcers, wound area and OPG levels had positive correlation with wound healing, whereas simvastatin medications had negative correlation with wound healing.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/complicações
Pé Diabético/sangue
Osteoprotegerina/sangue
Calcificação Vascular/sangue
Cicatrização
[Mh] Termos MeSH secundário: Idoso
Biomarcadores/sangue
Estudos de Coortes
Endotelina-1/sangue
Feminino
Seres Humanos
Indonésia
Estimativa de Kaplan-Meier
Modelos Lineares
Masculino
Meia-Idade
Análise Multivariada
Centros de Atenção Terciária
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers); 0 (Endothelin-1); 0 (Osteoprotegerin); 0 (TNFRSF11B protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29441931
[Au] Autor:Li N; Tu Y; Shen Y; Qin Y; Lei C; Liu X
[Ti] Título:Calycosin attenuates osteoporosis and regulates the expression of OPG/RANKL in ovariectomized rats MAPK signaling.
[So] Source:Pharmazie;71(10):607-612, 2016 Oct 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:We aimed at exploring the effect of calycosin (CA) on osteoporosis in ovariectomized (OVX) rats. Sprague-Dawley (SD) rats were divided into five groups: Sham group, OVX group, OVX group treated with estradiol valerate (EV), CAL group treated with 15 mg/kg/d of CA and CAH group treated with 30 mg/kg/d of CA for 12 weeks. Bone mineral density (BMD), histopathology, body weight, parameters in serum and urine were observed. Gene expression and protein level of OPG/RANKL were also studied by real-time PCR and western blot, respectively. We further identified the effect of CA on mitogen-activated protein kinase (MAPK) signaling. In comparison with OVX rats, CAL and CAH significantly increased the BMD by 8.3% and 19.0%. Treatment with CA notably inhibited the excretion of Ca, P and Cr. CAH also significantly increased the level of alkaline phosphatase (ALP) and decreased the level of tartrate-resistant acid phosphatase (TRAP) in serum of OVX rats. CA could improve the trabecular bone area, and increased the trabecular number and the trabecular connection after 12-week. CA also increased the expression of osteoprotegerin (OPG) and decreased the Receptor Activator for Nuclear Factor-κB Ligand (RANKL) mRNA expression compared with the OVX rats. In addition, CA could effectively decrease the phosphorylation of MAPKs induced by ovariectomy. In conclusion, CA had remarkable antiosteoporotic activity and therefore can be a promising candidate for the treatment of postmenopausal osteoporosis.
[Mh] Termos MeSH primário: Conservadores da Densidade Óssea/uso terapêutico
Isoflavonas/uso terapêutico
Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos
Osteoporose/tratamento farmacológico
Osteoprotegerina/genética
Ligante RANK/genética
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Densidade Óssea/efeitos dos fármacos
Conservadores da Densidade Óssea/farmacologia
Reabsorção Óssea/prevenção & controle
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Proteínas de Choque Térmico HSP90/biossíntese
Proteínas de Choque Térmico HSP90/genética
Isoflavonas/farmacologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Osteoporose/genética
Osteoprotegerina/biossíntese
Ovariectomia
Fosforilação
Ligante RANK/biossíntese
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Density Conservation Agents); 0 (HSP90 Heat-Shock Proteins); 0 (Isoflavones); 0 (Osteoprotegerin); 0 (RANK Ligand); 0 (TRAP1 protein, rat); 0 (Tnfrsf11b protein, rat); 09N3E8P7TA (7,3'-dihydroxy-4'-methoxyisoflavone); EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6627


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[PMID]:29025654
[Au] Autor:Cheng Z; Landish B; Chi Z; Nannan C; Jingyu D; Sen L; Xiangjin L
[Ad] Endereço:Department of Orthopaedic Orthopaedics, First Affiliated Hospital, College of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, People's Republic of China; The Sport Medicine Center of the First Affiliated Hospital, College of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou
[Ti] Título:3D printing hydrogel with graphene oxide is functional in cartilage protection by influencing the signal pathway of Rank/Rankl/OPG.
[So] Source:Mater Sci Eng C Mater Biol Appl;82:244-252, 2018 Jan 01.
[Is] ISSN:1873-0191
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:3Dprinting is defined as the use of printing technology to deposit living cells, and biomaterials on a given /a substrate. Graphene oxide nanoparticles (GO-np) have been used as a delivery vehicle for small molecule drugs in order to investigate the state of GO-np within 3D tissue constructs in terms of a composite 3D printing scaffold, which in turn is relevant to the protection of cartilage. We transplanted rats with hydrogel/GO-np and hydrogel, which in turn showed that hydrogel/GO-np protected the tissue of cartilage by the signal pathway of Rank/Rankl/OPG. Those findings indicated that GO-np may be potentially used to control the release of carrier materials and influence the signal pathway of Rank/Rankl/OPG.
[Mh] Termos MeSH primário: Materiais Biocompatíveis/química
Cartilagem/metabolismo
Grafite/química
Hidrogéis/química
Osteoprotegerina/metabolismo
Ligante RANK/metabolismo
Receptor Ativador de Fator Nuclear kappa-B/metabolismo
[Mh] Termos MeSH secundário: Animais
Materiais Biocompatíveis/farmacologia
Proteína Morfogenética Óssea 7/química
Proteína Morfogenética Óssea 7/metabolismo
Proteína Morfogenética Óssea 7/farmacologia
Cartilagem/efeitos dos fármacos
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Condrócitos/citologia
Condrócitos/efeitos dos fármacos
Condrócitos/metabolismo
Portadores de Fármacos/química
Seres Humanos
Masculino
Nanopartículas/química
Óxidos/química
Ratos
Ratos Sprague-Dawley
Transdução de Sinais/efeitos dos fármacos
Tecidos Suporte/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biocompatible Materials); 0 (Bone Morphogenetic Protein 7); 0 (Drug Carriers); 0 (Hydrogels); 0 (Osteoprotegerin); 0 (Oxides); 0 (RANK Ligand); 0 (Receptor Activator of Nuclear Factor-kappa B); 7782-42-5 (Graphite)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE


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[PMID]:29253005
[Au] Autor:Li S; Jiang H; Du N
[Ad] Endereço:Department of rehabilitation, People's Hospital of Jilin Province, Changchun, China.
[Ti] Título:Association between osteoprotegerin gene T950C polymorphism and osteoporosis risk in the Chinese population: Evidence via meta-analysis.
[So] Source:PLoS One;12(12):e0189825, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Osteoporosis has been reported to be at least partially developed in response to functional polymorphisms of the osteoprotegerin (OPG). However, conflicting results have been found. This meta-analysis aimed to provide an assessment of the relationship between the risk for developing osteoporosis and OPG T950C polymorphism in the Chinese population. Studies to be analyzed were identified with the literature search in PubMed, Embase, Web of Science, the Cochrane Library, and the Chinese National Knowledge Infrastructure during May 2017. Seven case-control studies that included a total of 1850 osteoporosis cases and 3074 controls were assessed in this meta-analysis. Overall, no significant associations could be detected between OPG T950C polymorphism and osteoporosis when all included studies were pooled into this meta-analysis. In a subgroup analyses, OPG T950C polymorphism was significantly associated with the osteoporosis risk in South China (CC+TC vs. TT: OR = 1.34, 95% CI = 1.17-1.54; CC vs. TC+TT: OR = 0.79, 95% CI = 0.69-0.95) and for studies that included postmenopausal osteoporosis (CC vs. TC+TT: OR = 0.78, 95% CI = 0.64-0.94) or hospital-based controls (CC vs. TC+TT: OR = 0.81, 95% CI = 0.68-0.96). In conclusion, the results of this meta-analysis suggest that OPG T950C polymorphism might be associated with an increased osteoporosis risk in the Chinese population.
[Mh] Termos MeSH primário: Osteoporose Pós-Menopausa/genética
Osteoprotegerina/genética
Polimorfismo Genético
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Grupo com Ancestrais do Continente Asiático
Estudos de Casos e Controles
China
Feminino
Predisposição Genética para Doença
Variação Genética
Hospitais
Seres Humanos
Meia-Idade
Osteoporose Pós-Menopausa/epidemiologia
Fatores de Risco
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Osteoprotegerin); 0 (TNFRSF11B protein, human)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189825


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[PMID]:29262817
[Au] Autor:Park B; Song HS; Kwon JE; Cho SM; Jang SA; Kim MY; Kang SC
[Ad] Endereço:Department of Oriental Medicine and Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, 17104, Republic of Korea.
[Ti] Título:Effects of Salvia miltiorrhiza extract with supplemental liquefied calcium on osteoporosis in calcium-deficient ovariectomized mice.
[So] Source:BMC Complement Altern Med;17(1):545, 2017 Dec 20.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Extracts from Salvia miltiorrhiza Bunge have been used in traditional Asian medicine to treat coronary heart disease, chronic renal failure, atherosclerosis, myocardial infraction, angina pectoris, myocardial ischemia, dysmenorrheal, neurasthenic insomnia, liver fibrosis and cirrhosis. The aim of the study was to investigate the anti-RANK signal effect of the combination of S.miltiorrhiza Bunge (SME) and liquefied calcium (LCa) supplement with ovariectomized (OVX-SML) mice, a osteoporosis animal model. Results were compared to 17ß-estradiol (E ) treatment. METHODS: A total of 70 female ICR strain mice (7 weeks) were randomly divided into 10 groups with 7 mice in each group as follows: (1) sham-operated control mice (sham) received daily oral phosphate-buffered-saline (PBS) of equal volumes through oral administration. (2) OVX mice received a daily oral administration of PBS (OVX). (3) OVX mice treated daily with 50 mg/kg b.w./ day of SME (4) with 100 mg/kg b.w./day of SME or (5) with 200 mg/kg b.w./day of SME via oral administration. (6) OVX mice treated daily with 50 mg/kg b.w./day of SML (7) with 100 mg/kg b.w./day of SML or (8) with 200 mg/kg b.w./day of SML via oral administration. (9) OVX mice treated daily with 10 ml/kg b.w./day of LCa (10) OVX mice received i.p. injections of 17ß-estradiol (E ) (0.1 mg/kg b.w./day) three times per week for 12 weeks. RESULTS: micro-CT analysis revealed that oral administration of SML inhibited tibial bone loss, sustained trabecular bone state, and ameliorated bone biochemical markers. In addition, SML administration compared to SEM and LCa reduced serum levels of RANKL, osteocalcin and BALP through increased serum levels of OPG and E in OVX mice. SML also had more beneficial effects on protection of estrogen-dependent bone loss through blocking expression of TRAF6 and NFTAc1 and produces cathepsin K and calcitonin receptor to develop osteoclast differentiation. CONCLUSION: These data suggest that S. miltiorrhiza Bunge combined with liquefied calcium supplement has an inhibitory activity in OVX mice. This result implies the possibility of a pharmacological intervention specifically directed toward a disease such as osteoporosis where decreased bone strength increases the risk of a broken bone .
[Mh] Termos MeSH primário: Cálcio/uso terapêutico
Osteoporose/tratamento farmacológico
Extratos Vegetais/uso terapêutico
Salvia miltiorrhiza
[Mh] Termos MeSH secundário: Animais
Biomarcadores/sangue
Densidade Óssea/efeitos dos fármacos
Cálcio/administração & dosagem
Cálcio/deficiência
Cálcio/farmacologia
Modelos Animais de Doenças
Feminino
Camundongos
Camundongos Endogâmicos ICR
Tamanho do Órgão/efeitos dos fármacos
Osteoporose/metabolismo
Osteoprotegerina/sangue
Ovariectomia
Extratos Vegetais/administração & dosagem
Extratos Vegetais/farmacologia
Ligante RANK/sangue
Útero/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Osteoprotegerin); 0 (Plant Extracts); 0 (RANK Ligand); 0 (Tnfrsf11b protein, mouse); 0 (Tnfsf11 protein, mouse); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180103
[Lr] Data última revisão:
180103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2047-y


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[PMID]:28957555
[Au] Autor:Tao Y; Wang Z; Wang L; Shi J; Guo X; Zhou W; Wu X; Liu Y; Zhang W; Yang H; Shi Q; Xu Y; Geng D
[Ad] Endereço:Department of Orthopedics, First Affiliated Hospital of Soochow University, Suzhou.
[Ti] Título:Downregulation of miR-106b attenuates inflammatory responses and joint damage in collagen-induced arthritis.
[So] Source:Rheumatology (Oxford);56(10):1804-1813, 2017 Oct 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objective: miRNAs are small, signal-strand, non-coding RNAs that function in post-transcriptional regulation. We analysed the in vivo effect of miR-106b (miR-106b-5p) on inflammatory bone loss in CIA mice. Methods: CIA mice are developed by injecting DAB/1 mice with bovine type II collagen containing Freund's adjuvant and then the in vivo effect of miR-106b is examined. On day 22, mice were given lentiviral negative control, lentiviral-mediated miR-106b mimics or lentiviral-mediated miR-106b inhibitor via orbital injection on a weekly basis. Morphological changes in the ankle joints were assessed via micro-CT and histopathology and cytokine expression levels were examined via immunohistochemical staining, ELISA or flow cytometric analysis. miR-106b and osteoclastic-related gene expression was evaluated via quantitative real-time PCR. Results: CIA mice were found to have increased miR-106b expression and CIA-associated bone loss and inflammatory infiltration. miR-106b inhibitor treatment markedly decreased arthritis incidence and attenuated bone destruction and histological severity compared with the control group. Moreover, miR-106b inhibitor treatment suppressed RANK ligand (RANKL) expression, increased osteoprotegerin (OPG) expression and reduced the RANKL:OPG ratio in CIA mice. miR-106b inhibition also significantly decreased inflammatory mediator production in joint sections and reduced serum pro-inflammatory cytokine levels when compared with the control group. Additionally, miR-106b inhibition decreased tartrate-resistant acid phosphatase-positive cell numbers and suppressed murine bone marrow macrophage differentiation. Conclusion: These findings indicate that miR-106b inhibition can ameliorate CIA-associated inflammation and bone destruction and thus may serve as a potential therapeutic for human RA treatment.
[Mh] Termos MeSH primário: Artrite Experimental/genética
Osso e Ossos/patologia
Regulação para Baixo
Articulações/patologia
MicroRNAs/metabolismo
[Mh] Termos MeSH secundário: Animais
Artrite Experimental/induzido quimicamente
Artrite Experimental/tratamento farmacológico
Osso e Ossos/metabolismo
Colágeno Tipo II
Citocinas/sangue
Regulação da Expressão Gênica/efeitos dos fármacos
Mediadores da Inflamação/fisiologia
Articulações/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos DBA
MicroRNAs/antagonistas & inibidores
Osteoclastos/metabolismo
Osteoprotegerina/metabolismo
Ligante RANK/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type II); 0 (Cytokines); 0 (Inflammation Mediators); 0 (MicroRNAs); 0 (Mirn106 microRNA, mouse); 0 (Osteoprotegerin); 0 (RANK Ligand); 0 (Tnfrsf11b protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170929
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex233


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[PMID]:28937990
[Au] Autor:Ozaki Y; Koide M; Furuya Y; Ninomiya T; Yasuda H; Nakamura M; Kobayashi Y; Takahashi N; Yoshinari N; Udagawa N
[Ad] Endereço:Graduate School of Oral Medicine, Matsumoto Dental University, Shiojiri, Nagano, Japan.
[Ti] Título:Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis.
[So] Source:PLoS One;12(9):e0184904, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RANKL. OPG-deficient (OPG-/-) mice exhibit severe alveolar bone loss with enhanced bone resorption. WP9QY (W9) peptide binds to RANKL and blocks RANKL-induced osteoclastogenesis. W9 is also reported to stimulate bone formation in vivo. Here, we show that treatment with W9 restores alveolar bone loss in OPG-/-mice by suppressing osteoclastogenesis and enhancing osteoblastogenesis. Administration of W9 or risedronate, a bisphosphonate, to OPG-/-mice significantly decreased the osteoclast number in the alveolar bone. Interestingly, treatment with W9, but not risedronate, enhanced Wnt/ß-catenin signaling and induced alveolar bone formation in OPG-/-mice. Expression of sclerostin, an inhibitor of Wnt/ß-catenin signaling, was significantly lower in tibiae of OPG-/-mice than in wild-type mice. Treatment with risedronate recovered sclerostin expression in OPG-/-mice, while W9 treatment further suppressed sclerostin expression. Histomorphometric analysis confirmed that bone formation-related parameters in OPG-/-mice, such as osteoblast number, osteoblast surface and osteoid surface, were increased by W9 administration but not by risedronate administration. These results suggest that treatment of OPG-/-mice with W9 suppressed osteoclastogenesis by inhibiting RANKL signaling and enhanced osteoblastogenesis by attenuating sclerostin expression in the alveolar bone. Taken together, W9 may be a useful drug to prevent alveolar bone loss in periodontitis.
[Mh] Termos MeSH primário: Perda do Osso Alveolar/tratamento farmacológico
Conservadores da Densidade Óssea/farmacologia
Osteoblastos/efeitos dos fármacos
Osteoclastos/efeitos dos fármacos
Osteogênese/efeitos dos fármacos
Peptídeos Cíclicos/farmacologia
[Mh] Termos MeSH secundário: Perda do Osso Alveolar/metabolismo
Perda do Osso Alveolar/patologia
Animais
Modelos Animais de Doenças
Avaliação Pré-Clínica de Medicamentos
Glicoproteínas/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Camundongos Knockout
Osteoblastos/metabolismo
Osteoblastos/patologia
Osteoclastos/metabolismo
Osteoclastos/patologia
Osteogênese/fisiologia
Osteoprotegerina/deficiência
Osteoprotegerina/genética
Ligante RANK/metabolismo
Risedronato Sódico/farmacologia
Tíbia/efeitos dos fármacos
Tíbia/metabolismo
Tíbia/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Density Conservation Agents); 0 (Glycoproteins); 0 (Osteoprotegerin); 0 (Peptides, Cyclic); 0 (RANK Ligand); 0 (Sost protein, mouse); 0 (Tnfrsf11b protein, mouse); 0 (Tnfsf11 protein, mouse); 0 (WP9QY peptide); OFG5EXG60L (Risedronate Sodium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184904


  9 / 4035 MEDLINE  
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[PMID]:28845932
[Au] Autor:Apolikhin OI; Sivkov AV; Konstantinova OV; Slominskii PA; Tupitsyna TV; Kalinichenko DN
[Ad] Endereço:N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology branch of National Medical Radiological Research Center of Minzdrav of Russia, Moscow, Russia.
[Ti] Título:[Early diagnosis of risk for developing calcium oxalate urolithiasis].
[So] Source:Urologiia;(3):5-8, 2017 Jul.
[Is] ISSN:1728-2985
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:AIM: To identify risk groups for calcium oxalate urolithiasis among healthy individuals and patients with urolithiasis in the Russian population using molecular genetics. MATERIALS AND METHODS: The study comprised 72 patients with calcium oxalate urolithiasis (study group) and 189 healthy adults from the general Russian population (control group). The study group consisted of 39 (54.2%) men and 33 (45.8%) women. The mean age of urolithiasis patients was 41.5+/-12.4 years. Analysis of polymorphic variants of 8 candidate urolithiasis genes: tumor necrosis factor 11B (TNFRSF11B, rs3134057), -subunit of the nuclear estrogen receptor (ESR1, rs851982), Cloto gene (KL, rs526906), vitamin D receptor (VDR, rs1540339 ), an extracellular calcium-sensing receptor (CASR, rs2202127), membrane anion transporter family 26 (SLC26A6, rs2310996), tumor necrosis factor 11 (TNFSF11, rs9525641), the calcium release-activated calcium modulator 1 (ORAI1, rs7135617) in two groups was performed by real-time PCR using Applied Biosystems test. Statistical analysis was performed using Fishers angular transformation and 2. RESULTS: In the polymorphism of the ORAI1 gene (rs7135617), the differences in the frequencies of the GG genotype and the G allele in the control sample and in the sample of patients with calcium oxalate urolithiasis were significant: p=0.0004 and p=0.001, respectively. No statistically significant differences in the genotype and allele frequencies were found in the remaining seven gene polymorphisms. CONCLUSIONS: Healthy individuals and patients with urolithiasis in the Russian population who have the GG genotype and/or the G allele of the polymorphism of the ORAI1 gene (rs7135617) represent risk groups for the formation of calcium oxalate stones.
[Mh] Termos MeSH primário: Nefrolitíase/diagnóstico
Nefrolitíase/genética
Proteína ORAI1/genética
[Mh] Termos MeSH secundário: Adulto
Alelos
Diagnóstico Precoce
Feminino
Glucuronidase/genética
Seres Humanos
Masculino
Meia-Idade
Nefrolitíase/epidemiologia
Osteoprotegerina/genética
Polimorfismo Genético
Reação em Cadeia da Polimerase em Tempo Real
Receptores de Calcitriol/genética
Receptores de Detecção de Cálcio/genética
Fatores de Risco
Federação Russa/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ORAI1 Protein); 0 (ORAI1 protein, human); 0 (Osteoprotegerin); 0 (Receptors, Calcitriol); 0 (Receptors, Calcium-Sensing); 0 (TNFRSF11B protein, human); 0 (VDR protein, human); EC 3.2.1.31 (Glucuronidase); EC 3.2.1.31 (klotho protein)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


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Texto completo
[PMID]:28837646
[Au] Autor:Tschiderer L; Willeit J; Schett G; Kiechl S; Willeit P
[Ad] Endereço:Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
[Ti] Título:Osteoprotegerin concentration and risk of cardiovascular outcomes in nine general population studies: Literature-based meta-analysis involving 26,442 participants.
[So] Source:PLoS One;12(8):e0183910, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Recent experimental and epidemiological studies have suggested that osteoprotegerin, a key regulator in bone metabolism, may be involved in vascular calcification and atherosclerosis. Our aim was to reliably quantify the associations of osteoprotegerin concentration and incidence of first-ever cardiovascular disease outcomes in the general population. METHODS: Using the electronic databases MEDLINE, EMBASE and Web of Science (January 1975 and April 2017, no language restrictions), nine relevant studies were identified involving a total of 26,442 participants recruited from the general population. Over a mean follow-up of 8.5 years, 2,160 cardiovascular disease, 2,123 coronary heart disease, and 1,102 stroke outcomes were recorded. Study-specific risk ratios were combined with random-effects meta-analysis. RESULTS: When comparing individuals in the top with those in the bottom third of osteoprotegerin concentration, the combined risk ratio was 1.83 (95% confidence interval: 1.46, 2.30; P<0.001; I2 = 76.8%) for cardiovascular disease, 1.72 for coronary heart disease (1.26, 2.37; P = 0.001; I2 = 83.5%), and 1.58 for stroke (1.18, 2.12; P = 0.002; I2 = 65.2%). Associations appeared stronger at younger age (P = 0.018 for cardiovascular disease), in studies that did not employ statistical adjustment (P = 0.023 for cardiovascular disease and 0.018 for coronary heart disease), and potentially in studies that measured osteoprotegerin in plasma rather than in serum (P = 0.005 for cardiovascular disease and 0.018 for coronary heart disease). Magnitudes of associations did not differ according to the proportion of males, geographical region, or osteoprotegerin assay manufacturer. There was no evidence for publication bias for any of the outcomes assessed (all P>0.05). CONCLUSIONS: Elevated osteoprotegerin concentration is associated with an increased risk of incident cardiovascular disease in the general population. The mechanisms underlying this observation deserve further investigation.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/epidemiologia
Osteoprotegerina/sangue
[Mh] Termos MeSH secundário: Doenças Cardiovasculares/sangue
Seres Humanos
Incidência
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Osteoprotegerin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183910



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