Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
1.
J Cell Physiol ; 236(3): 1939-1949, 2021 03.
Article in English | MEDLINE | ID: mdl-32730652

ABSTRACT

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1ß (IL-1ß) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1ß-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.


Subject(s)
Inflammation/prevention & control , NF-kappa B/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Triterpenes/therapeutic use , Aged , Animals , Cell Survival/drug effects , Chondrocytes/drug effects , Chondrocytes/metabolism , Chondrocytes/pathology , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Disease Models, Animal , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Female , Humans , Inflammation/complications , Interleukin-1beta/adverse effects , Interleukin-6/metabolism , Male , Mice, Inbred C57BL , Models, Biological , NF-KappaB Inhibitor alpha/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Protein Transport/drug effects , Proteolysis/drug effects , Transcription Factor RelA/metabolism , Triterpenes/chemistry , Triterpenes/pharmacology , Tumor Necrosis Factor-alpha/metabolism
2.
BMJ Open ; 9(10): e024595, 2019 10 16.
Article in English | MEDLINE | ID: mdl-31619412

ABSTRACT

OBJECTIVE: Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: Randomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017. OUTCOMES: Total fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted. RESULTS: A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures. CONCLUSIONS: The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully. PROSPERO REGISTRATION NUMBER: CRD42017079624.


Subject(s)
Calcium-Regulating Hormones and Agents/administration & dosage , Calcium/administration & dosage , Dietary Supplements , Fractures, Bone/prevention & control , Vitamin D/administration & dosage , Vitamins/administration & dosage , Drug Therapy, Combination , Fractures, Bone/epidemiology , Humans , Independent Living , Network Meta-Analysis , Randomized Controlled Trials as Topic , Risk Assessment
3.
Front Pharmacol ; 10: 393, 2019.
Article in English | MEDLINE | ID: mdl-31040782

ABSTRACT

Osteoarthritis (OA), defined as a long-term progressive joint disease, is characterized by cartilage impairment and erosion. In recent decades, magnolol, as a type of lignin extracted from Magnolia officinalis, has been proved to play a potent anti-inflammatory role in various diseases. The current research sought to examine the latent mechanism of magnolol and its protective role in alleviating the progress of OA in vivo as well as in vitro experimentations. In vitro, the over-production of Nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6), induced by interleukin-1 beta (IL-1ß), were all inhibited notably by magnolol in a concentration-dependent manner. Moreover, magnolol could also downregulate the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5). All these changes ultimately led to the deterioration of the extracellular matrix (ECM) induced by IL-1ß. Mechanistically, magnolol suppressed the activation of PI3K/Akt/NF-κB pathway. Furthermore, a powerful binding capacity between magnolol and PI3K was also revealed in our molecular docking research. In addition, magnolol-induced protective effects in OA development were also detected in a mouse model. In summary, this research suggested that magnolol possessed a new therapeutic potential for the development of OA.

4.
J Orthop Surg Res ; 14(1): 77, 2019 Mar 13.
Article in English | MEDLINE | ID: mdl-30866978

ABSTRACT

OBJECTIVES: There is an increased interest in enhanced recovery after surgery (ERAS) minimizing adverse events after orthopedic surgery. Little consensus supports the effectiveness of these interventions. The purpose of present systematic review and meta-analysis is to comprehensively analyze and evaluate the significance of ERAS interventions for postoperative outcomes after orthopedic surgery. METHODS: PubMed, EMBASE, and Cochrane databases were totally searched from the inception dates to May 31, 2018. Two reviewers independently extracted the data from the selected articles using a standardized form and assessed the risk of bias. The analysis was performed using STATA 12.0. RESULTS: A total of 15 published studies fulfilled the requirements of inclusion criteria. We found that the ERAS group showed a significant association with lower incidence of postoperative complications (OR, 0.70; 95% CI, 0.64 to 0.78). Meanwhile, ERAS was also associated with the decline in 30-day mortality rate and Oswestry Disability Index (ODI). However, no significant differences were identified between the two groups regarding the 30-day readmission rate (P = 0.397). CONCLUSIONS: Our meta-analysis suggested that the ERAS group had more advantages in reducing incidence of postoperative complications, 30-day mortality rate, and ODI after orthopedic surgery, but not of 30-day readmission rate. However, further research with standardized, unbiased methods and larger sample sizes is required for deeper analysis.


Subject(s)
Length of Stay/trends , Orthopedic Procedures/trends , Patient Readmission/trends , Postoperative Care/trends , Recovery of Function/physiology , Aged , Aged, 80 and over , Humans , Middle Aged , Orthopedic Procedures/adverse effects , Orthopedic Procedures/methods , Postoperative Care/methods
5.
BMJ Open ; 9(1): e024110, 2019 01 28.
Article in English | MEDLINE | ID: mdl-30696677

ABSTRACT

INTRODUCTION: The optimal treatment for burst fractures of the thoracolumbar spine is controversial. The addition of screws in the fractured segment has been shown to improve construct stiffness, but can aggravate the trauma to the fractured vertebra. Therefore, optimised placement of two pedicle screws at the fracture level is required for the treatment of thoracolumbar burst fractures. This randomised controlled study is the first to examine the efficacy of diverse orders of pedicle screw placement and will provide recommendations for the treatment of patients with thoracolumbar burst fractures. METHODS AND ANALYSIS: A randomised controlled trial with blinding of patients and the statistician, but not the clinicians and researchers, will be conducted. A total of 70 patients with single AO type A3 or A4 thoracolumbar fractures who are candidates for application of short-segment pedicle screws at the fractured vertebral level will be allocated randomly to the distraction-screw and screw-distraction groups at a ratio of 1:1. The primary clinical outcome measures will be the percentage loss of vertebral body height, screw depth in the injured vertebrae and kyphosis (Cobb angle). Secondary clinical outcome measures will be complications, Visual Analogue Scale scores for back and leg pain, neurological function, operation time, intraoperative blood loss, Japanese Orthopaedic Association score and Oswestry Disability Index. These parameters will be evaluated preoperatively, intraoperatively, on postoperative day 3, and at 1, 3, 6, 12 and 24 months postoperatively. ETHICS AND DISSEMINATION: The Institutional Review Board of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University have reviewed and approved this study (batch: LCKY2018-05). The results will be presented in peer-reviewed journals and at an international spine-related meeting after completion of the study. TRIAL REGISTRATION NUMBER: NCT03384368; Pre-results.


Subject(s)
Fracture Fixation, Internal/methods , Fractures, Compression/surgery , Lumbar Vertebrae/surgery , Pedicle Screws , Spinal Fractures/surgery , Thoracic Vertebrae/surgery , Humans , Lumbar Vertebrae/injuries , Single-Blind Method , Thoracic Vertebrae/injuries , Treatment Outcome
6.
J Cell Physiol ; 234(5): 6940-6950, 2019 05.
Article in English | MEDLINE | ID: mdl-30417459

ABSTRACT

Osteoarthritis (OA) is characterized as the degeneration and destruction of articular cartilage. In recent decades, leonurine (LN), the main active component in medical and edible dual purpose plant Herba Leonuri, has been shown associated with potent anti-inflammatory effects in several diseases. In the current study, we examined the protective effects of LN in the inhibition of OA development as well as its underlying mechanism both in vitro and in vivo experiments. In vitro, interleukin-1 beta (IL-1ß) induced over-production of prostaglandin E2, nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6 and tumor necrosis factor alpha were all inhibited significantly by the pretreatment of LN at a dose-dependent manner (5, 10, and 20 µM). Moreover, the expression of thrombospondin motifs 5 (ADAMTS5) and metalloproteinase 13 (MMP13) was downregulated by LN. All these changes led to the IL-1ß induced degradation of extracellular matrix. Mechanistically, the LN suppressed IL-1ß induced activation of the PI3K/Akt/NF-κB signaling pathway cascades. Meanwhile, it was also demonstrated in our molecular docking studies that LN had strong binding abilities to PI3K. In addition, LN was observed exerting protective effects in a surgical induced model of OA. To sum up, this study indicated LN could be applied as a promising therapeutic agent in the treatment of OA.


Subject(s)
Gallic Acid/analogs & derivatives , NF-kappa B/metabolism , Osteoarthritis/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Animals , Cells, Cultured , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Down-Regulation/drug effects , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Gallic Acid/pharmacology , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Male , Mice , Mice, Inbred C57BL , Molecular Docking Simulation/methods , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Osteoarthritis/metabolism
7.
Food Funct ; 9(8): 4443-4456, 2018 Aug 15.
Article in English | MEDLINE | ID: mdl-30070297

ABSTRACT

The inflammatory environment has been demonstrated to be strongly associated with the progression of osteoarthritis (OA). HSYA, the main active component in the medical and edible dual purpose plant safflower, has previously showed significant anti-inflammatory effects in several diseases. In the current study, the protective effects of HSYA in the inhibition of OA development and its underlying mechanism were examined by both in vitro and in vivo experiments. Our data indicated that interleukin-1 beta (IL-1ß) induced over-production of pro-inflammatory cytokines, such as nitric oxide (NO) and prostaglandin E2 (PGE2); also, the expression of cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) were all inhibited by pretreatment with HSYA in a dose-dependent manner (2.5 to 40 µM). Furthermore, HSYA attenuated IL-1ß-induced degradation of the extracellular matrix (ECM) by decreasing the expression of metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS5). Mechanistically, HSYA suppressed IL-1ß-induced activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) cascades. Meanwhile, molecular docking studies revealed that HSYA has excellent binding abilities to p65, extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK). In addition, the protective effects of HSYA were observed in a surgically induced mouse OA model. In summary, this study provides evidence that HSYA can be applied as a potential therapeutic agent in the treatment of OA.


Subject(s)
Chalcone/analogs & derivatives , MAP Kinase Signaling System/drug effects , NF-kappa B/metabolism , Osteoarthritis/prevention & control , Quinones/administration & dosage , ADAMTS5 Protein/genetics , ADAMTS5 Protein/metabolism , Animals , Chalcone/administration & dosage , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , Mice , Mice, Inbred C57BL , NF-kappa B/genetics , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Osteoarthritis/genetics , Osteoarthritis/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
8.
Food Funct ; 9(9): 4865-4875, 2018 Sep 19.
Article in English | MEDLINE | ID: mdl-30160278

ABSTRACT

Osteoarthritis (OA) is characterized by the degeneration and destruction of articular cartilage. Allicin, a dietary garlic active constituent, exerts anti-inflammatory effects on several diseases. However, its effects on OA have not been clearly elucidated. In this study, we explored the effects of allicin on OA in both in vitro and in vivo models. Allicin inhibited interleukin-1ß (IL-1ß) induced overproduction of nitric oxide, inducible nitric oxide synthase, prostaglandin E2, and cyclooxygenase-2, as well as pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in chondrocytes in a dose-dependent manner. Meanwhile, allicin reversed the overproduction of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 and the decrease of aggrecan and type II collagen. Furthermore, allicin dramatically suppressed IL-1ß-stimulated PI3K/Akt/NF-κB activation in chondrocytes. In vivo, treatment with allicin prevented the destruction of cartilage and inhibited PI3K/Akt/NF-κB activation in the cartilage of mice OA models. Taken together, these results indicate that allicin may be a potential therapeutic agent for OA.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Chondrocytes/metabolism , Dietary Supplements , Disease Models, Animal , Osteoarthritis, Knee/therapy , Phosphoinositide-3 Kinase Inhibitors , Sulfinic Acids/therapeutic use , Animals , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/metabolism , Cell Survival , Cells, Cultured , Chondrocytes/cytology , Chondrocytes/pathology , Dietary Supplements/adverse effects , Disease Progression , Disulfides , Female , Gene Expression Regulation , Humans , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , Mice, Inbred C57BL , NF-kappa B/agonists , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Osteoarthritis, Knee/metabolism , Osteoarthritis, Knee/pathology , Osteoarthritis, Knee/physiopathology , Phosphatidylinositol 3-Kinase/chemistry , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/agonists , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Random Allocation , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Signal Transduction , Sulfinic Acids/adverse effects , Sulfinic Acids/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...