ABSTRACT
RATIONALE: Widely applied in the treatment of severe ankle arthritis (AA), ankle distraction arthroplasty (ADA) can avoid not only the ankle range of motion loss but also ankle fusion. However, the clinical outcomes of ADA for severe AA are poorly understood. This study aims to present our clinical outcomes of severe AA treated by ADA. PATIENT CONCERNS: A 53-year-old man suffered right ankle sprain 10 years ago, endured right ankle pain and limited movement for 6 years. DIAGNOSIS: The patient was diagnosed as severe AA. INTERVENTIONS: He received ankle distraction arthroplasty. No adjuvant procedures were performed. The visual analog scale (VAS), the American Orthopaedic Foot and Ankle Society (AOFAS) score, the short-form (SF)-36 physical component summary (PCS) score and ankle activity score (AAS) were recorded to access the clinical outcomes pre- and postoperatively. Moreover, ankle joint space distance was evaluated on weight-bearing radiographs. OUTCOMES: The patient derived effective pain relief and restored a satisfactory range of movement. There was a 13-month follow-up period after frame removal. The AOFAS score improved from 56 preoperatively to 71 postoperatively. The VAS score decreased from 6 prior to surgery to 1 after surgery. The SF-36 PCS was 47.2 and 71.8 pre- and postoperative, respectively. The AAS scores were improved from 3.4 preoperatively to 7.3 postoperatively. LESSONS: ADA is reliable to achieve pain relief, functional recovery, and serve AA resolution. Besides, it is an alternative to ankle arthrodesis or total ankle arthroplasty in selected patients with severe AA.
Subject(s)
Ankle Injuries/complications , Ankle Joint/pathology , Arthritis/surgery , Osteogenesis, Distraction/adverse effects , Aftercare , Ankle Injuries/physiopathology , Ankle Joint/diagnostic imaging , Arthroplasty/methods , Humans , Male , Middle Aged , Osteogenesis, Distraction/instrumentation , Radiography/methods , Range of Motion, Articular , Recovery of Function , Severity of Illness Index , Treatment Outcome , Visual Analog Scale , Weight-BearingABSTRACT
Osteosarcoma is a type of malignant bone tumor with high metastasis and poor prognosis. Previous studies have demonstrated the involvement of LIM kinase 1 (LIMK1) in the proliferation of osteosarcoma cells. LIMK1 is overexpressed in human osteosarcoma tissues and cell lines. To further study LIMK1-associated mechanisms, we used shRNA targeted to the LIMK1 gene to block its expression in the osteosarcoma cell lines MG63 and U2OS. Insulin promoted the proliferation of MG63 cells in a time- and dose-dependent manner, however, this insulin induced proliferation was significantly inhibited by transfection of shRNA targeted to the LIMK1 gene, as well as by the PI3K inhibitor LY294002, but not by the mitogenactivated protein kinase (MAPK) inhibitor PD98059. The level of cofilin phosphorylation was increased significantly following stimulation of insulin for 24 h, indicating the activation of LIMK1. MG63 cell proliferation was also significantly inhibited by 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in a time-dependent manner. Furthermore, 1,25(OH)2D3 negated the inhibitory effect of LIMK1 shRNA, indicating that LIMK1 is important in the inhibitory pathway of 1,25(OH)2D3. The present study confirms that LIMK1 is important in regulating osteosarcoma cell proliferation via the insulin/PI3K/LIMK1 signaling pathway, thus the development of gene therapy for osteosarcoma targeting LIMK1 is warranted.
Subject(s)
Cell Proliferation/drug effects , Insulin/pharmacology , Lim Kinases/metabolism , Actin Depolymerizing Factors/metabolism , Cell Line, Tumor , Cholecalciferol/pharmacology , Chromones/pharmacology , Flavonoids/pharmacology , Humans , Lim Kinases/antagonists & inhibitors , Lim Kinases/genetics , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Morpholines/pharmacology , Osteosarcoma/metabolism , Osteosarcoma/pathology , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , RNA Interference , RNA, Small Interfering/metabolism , Signal Transduction/drug effectsABSTRACT
Cofilin promotes actin filament turnover by severing and depolymerizing actin filaments. Cofilin is inactivated by phosphorylation on Ser-3 by LIM-kinase1 (LIMK1) and is activated when protein phosphatase Slingshot-1L (SSH1L) dephosphorylates this residue. The authors have shown that Ca-induced cofilin dephosphorylation is mediated by calcineurin (Cn)-dependent activation of SSH1L. In this study, Ca/calmodulin-dependent protein kinase II (CaMKII) is shown to negatively regulate SSH1L activity and bind to SSH1L in a complex with 14-3-3. Phosphorylation of LIMK1 by CaMKII and its subsequent activation regulates the subcellular localization of SSH1L. Based on these findings, the authors suggest that CaMKII and Cn provide a switch-like mechanism that controls Ca-dependent LIMK1, SSH1L and cofilin activation, and subsequently actin cytoskeletal reorganization.
Subject(s)
Calcineurin/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Cofilin 1/metabolism , 14-3-3 Proteins/metabolism , Actin Cytoskeleton/chemistry , Actin Cytoskeleton/metabolism , Calcimycin/pharmacology , Calcium/metabolism , Calcium Ionophores/pharmacology , Enzyme Activation/drug effects , Gene Knockdown Techniques , HEK293 Cells , Humans , Lim Kinases/antagonists & inhibitors , Lim Kinases/genetics , Lim Kinases/metabolism , MCF-7 Cells , Models, Biological , Phosphoprotein Phosphatases/antagonists & inhibitors , Phosphoprotein Phosphatases/genetics , Phosphoprotein Phosphatases/metabolism , Phosphorylation , Protein Binding , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Serine/chemistry , Signal TransductionABSTRACT
OBJECTIVE: To investigate the alkaloids from the stem of Artabotrys hainanensis. METHOD: Compounds in plant extracts were separated by silica gel and sephadex LH-20 column chromatography. Chemical structures were elucidated by chemical and spectral analyses including UV, 1H-NMR, 13C-NMR, ESIMS and ESI-MS-MS. RESULT: Eight alkaloids were isolated and identified as spinosine (1), 3-hydroxynornuciferine (2), juzirine (3), artabotrine (4), liridine (5), assimilobine (6), isococlaurine (7), N-demethylarmepavine (8). CONCLUSION: All alkaloids were isolated from this plant for the first time and compounds 1, 3, 7 and 8 were isolated from genus Artabotrys for the first time.
