RESUMO
BACKGROUND: Proteasome inhibition is a promising strategy for cancer therapy. Bortezomib, which primarily targets the chymotrypsin-like activity of PSMB5, has demonstrated efficacy in various tumors. However, there is variable sensitivity to bortezomib, which could be attributed, in part, to variations in the expression of proteasome subunits. METHODS AND RESULTS: In this study, we investigated whether miR-383 affects the expression of proteasome subunits in osteosarcoma (OS) cells, and if so, whether OS cells display differential sensitivity to bortezomib concerning miR-383 expression. We detected a decreased miR-383 expression in OS cells and tissues. Then we found a negative correlation between the cytotoxicity of bortezomib and the expression level of the proteasome 20S core particle subunit ß5 (PSMB5). Intriguingly, we identified PSMB5 as a direct target of miR-383. Increased expression of miR-383 resulted in decreased PSMB5 expression and increased sensitivity to bortezomib in OS cells. CONCLUSIONS: In summary, our findings present the initial comprehensive analysis of the function of miR-383 in OS. The outcomes indicate that miR-383 may augment the anticancer effect of bortezomib through PSMB5 repression, offering a novel therapeutic approach in OS and a fresh pathway for proteasome regulation.
Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Humanos , Bortezomib/farmacologia , Complexo de Endopeptidases do Proteassoma/genética , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , MicroRNAs/genéticaRESUMO
The severe anatomic deformities render acetabular reconstruction as one of the greatest challenges in total hip arthroplasty (THA) for patients with Crowe III/IV developmental dysplasia of the hip (DDH). Thorough understanding of acetabular morphology and bone defect is the basis of acetabular reconstruction techniques. Researchers have proposed either true acetabulum position reconstruction or high hip center (HHC) position reconstruction. The former can obtain the optimal hip biomechanics, including bulk femoral head autograft, acetabular medial wall displacement osteotomy, and acetabular component medialization, while the latter is relatively easy for hip reduction, as it can avoid neurovascular lesions and obtain more bone coverage; however, it cannot achieve good hip biomechanics. Both techniques have their own advantages and disadvantages. Although there is no consensus on which approach is better, most researchers suggest the true acetabulum position reconstruction. Based on the various acetabular deformities in DDH patients, evaluation of acetabular morphology, bone defect, and bone stock using the 3D image and acetabular component simulation techniques, as well as the soft tissue tension around the hip joint, individualized acetabular reconstruction plans can be formulated and appropriate techniques can be selected to acquire desired clinical outcomes.
Assuntos
Artroplastia de Quadril , Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Prótese de Quadril , Humanos , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Luxação Congênita de Quadril/cirurgia , Displasia do Desenvolvimento do Quadril/cirurgia , Cabeça do Fêmur/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Metabolism reprogramming plays an important role in tumorigenesis and osteosarcoma metastasis. Sine oculis homeobox 4 (SIX4) is reported to be a key transcription factor that is involved in glycolysis reprogramming of cancer cells. However, the role of SIX4 in osteosarcoma progression remains unknown. The expression profile of SIX4 in OS was evaluated in surgery samples of osteosarcoma patients. Functional studies were performed in vitro and in vivo. We found that SIX4 is significantly overexpressed in osteosarcoma and related to the undesirable prognosis of osteosarcoma patients. SIX4 promotes progression of osteosarcoma via upregulating isocitrate dehydrogenase 1 (IDH1), which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.
Assuntos
Osteossarcoma , Transativadores , Humanos , Transativadores/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Regulação da Expressão Gênica , Osteossarcoma/genética , Isocitrato Desidrogenase/genéticaRESUMO
Surgery is the primary treatment for recurrent patellar dislocation. However, there is still a lack of consensus regarding the choice of combined surgical methods due to the complexity of the anatomical factors. This study aimed to investigate the efficacy and radiological changes in medial patellofemoral ligament reconstruction (MPFLR) and lateral retinacular release (LRR) with and without tibial tubercle osteotomy (TTO) for recurrent patellar dislocation in patients with a tibial tubercle-trochlear groove (TT-TG) distance of 15 to 20 mm. Fifty-four patients were enrolled in this retrospective study between 2010 and 2014. The average patient age was 21.6 ± 5.0 years. All patients underwent MPFLR and LRR, and in 18 patients, these procedures were combined with TTO. Patients were evaluated preoperatively and postoperatively for patellar lateral shift, patellar tilt angle, TT-TG distance, Q-angle, Caton-Deschamps index (CDI), Kujala, and Lysholm scores. The minimally clinical important difference was used to compare clinical outcomes between two groups. In the mean follow-up of 82.6 ± 15.9 months, functional scores improved significantly in both groups (p < 0.01). There were no significant differences in postoperative function scores between the two groups (Kujala, p = 0.25, mean difference = 1.5, 95% confidence interval [CI]: -1.4-4.4; Lysholm, p = 0.76, mean difference = -0.6, 95% CI: -5.9-4.7). Additionally, TTO significantly decreased Q-angle (23.6 ± 2.4 vs. 17.4 ± 2.9, p < 0.01), TT-TG (17.1 ± 1.5 vs. 10.4 ± 1.8, p < 0.01), and CDI (1.18 ± 0.12 vs. 1.08 ± 0.07, p < 0.01). Combined MPFLR and LRR with and without TTO are both effective techniques for recurrent patellar dislocation. Additional osteotomy can correct patellar alta and tibial tubercle lateralization. However, given that there were no significant differences in postoperative functional scores or recurrence rate between groups, we may not recommend TTO in addition to MPFLR and LRR in patients with TT-TG of 15 to 20 mm. Long-term and prospective cohort studies are required to assess further outcomes.
Assuntos
Luxações Articulares , Instabilidade Articular , Luxação Patelar , Articulação Patelofemoral , Humanos , Adolescente , Adulto Jovem , Adulto , Luxação Patelar/cirurgia , Articulação Patelofemoral/cirurgia , Estudos Retrospectivos , Estudos Prospectivos , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Recidiva , Tíbia/cirurgia , Osteotomia/métodos , Ligamentos Articulares/cirurgiaRESUMO
Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system mistakenly attacks joints. The molecular mechanisms underlying RA pathology are still under investigation. In this study, we discovered overexpression of nuclear receptor coactivator 3 (NCOA3) in the joint tissues of type II collagen-induced arthritis (CIA) mice, an important autoimmune model of human RA. Administration of two NCOA3 inhibitors, gossypol (GSP) and SI-2 hydrochloride (SHC), significantly alleviated inflammation and improved the outcomes of CIA mice. In vivo and in vitro experiments revealed that NCOA3 assembled a transcriptional complex with a histone acetyltransferase p300 and two subunits of nuclear factor kappa B (NF-κB). This complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Knockdown of NCOA3 or in vitro treatments with GSP and SHC impaired the assembly of NCOA3-p300-NF-κB complex and decreased the expression of proinflammatory cytokine genes. Taken together, our results demonstrated that NCOA3 acts as a mediator of proinflammatory cytokine genes in CIA mice and that inhibition of the NCOA3-p300-NF-κB complex may represent a new avenue for improving RA outcomes.
Assuntos
Artrite Experimental , Artrite Reumatoide , Coativador 3 de Receptor Nuclear , Animais , Humanos , Camundongos , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , NF-kappa B/metabolismo , Coativador 3 de Receptor Nuclear/genética , Coativador 3 de Receptor Nuclear/metabolismoRESUMO
BACKGROUND: How the hip dysplasia affects the spinopelvic alignment in developmental dysplasia of the hip (DDH) patients is unclear, but it is an essential part for the management of this disease. This study aimed to investigate the coronal and sagittal spinopelvic alignment and the correlations between the spinopelvic parameters and the extent of hip dysplasia or the low back pain in unilateral DDH patients. METHODS: From September 2016 to March 2021, 22 unilateral patients were enrolled in the DDH group with an average age of 43.6 years and 20 recruited healthy volunteers were assigned to the control group with an average age of 41.4 years. The Cobb angle, seventh cervical vertebra plumbline-central sacral vertical line (C7PL-CSVL), third lumbar vertebra inclination angle (L3IA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK) and lumbar lordosis (LL) were measured on the standing anteroposterior and lateral full-length standing spine radiographs. Additionally, the Oswestry Disability Index (ODI) and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were used to assess the degree of low back pain. RESULTS: Cobb angle (8.68 ± 6.21° vs. 2.31 ± 0.12°), L3IA (4.80 ± 5.47° vs. 0.83 ± 0.51°), C7PL-CSVL (1.65 ± 1.57 cm vs. 0.48 ± 0.33 cm), PT (15.02 ± 9.55° vs. 9.99 ± 2.97°) and TLK (7.69 ± 6.66° vs. 3.54 ± 1.63°) were significantly larger in DDH patients, whereas LL (37.41 ± 17.17° vs. 48.79 ± 7.75°) was significantly smaller (P < 0.05). No correlation was found between significantly different spinopelvic parameters and the extent of dysplasia. Statistical analysis revealed correlations between ODI and Cobb angle (r = 0.59, P < 0.01), PT (r = 0.49, P = 0.02), TK (r = -0.46, P = 0.03) and TLK (r = 0.44, P = 0.04). Correlations between JOABPQE score and the Cobb angle (r = -0.44, P = 0.04), L3IA (r = -0.53, P = 0.01), PT (r = -0.44, P = 0.04), and TK (r = 0.46, P = 0.03) were also observed. CONCLUSIONS: Cobb angle, L3IA, C7PL-CSVL in coronal plane and PT, TLK in sagittal plane increased, while LL decreased in unilateral DDH patients. These significantly different spinopelvic parameters have no correlation with the extent of dysplasia. Changes in coronal and sagittal plane including Cobb angle, L3IA, PT, TK and TLK were associated with the low back pain in the patients with unilateral DDH.
Assuntos
Displasia do Desenvolvimento do Quadril , Luxação do Quadril , Cifose , Dor Lombar , Adulto , Humanos , Vértebras Lombares , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Ferroptosis is a non-necrotic form of regulated cell death (RCD) that is primarily characterized by iron-dependent membrane lipid peroxidation and is regulated by cysteine transport, glutathione synthesis, and glutathione peroxidase 4 function as well as other proteins including ferroptosis suppressor protein 1. It has been found that ferroptosis played an important role in many diseases, such as neurodegenerative diseases and ischemia-reperfusion injury. Spinal cord injury (SCI), especially traumatic SCI, is an urgent problem worldwide due to its high morbidity and mortality, as well as the destruction of functions of the human body. Various RCDs, including ferroptosis, are found in SCI. Different from necrosis, since RCD is a form of cell death regulated by various molecular mechanisms in cells, the study of the role played by RCD in SCI will contribute to a deeper understanding of the pathophysiological process, as well as the treatment and functional recovery. The present review mainly introduces the main mechanism of ferroptosis and its role in SCI, so as to provide a new idea for further exploration.
RESUMO
Most tumors, including osteosarcomas, have deficiencies in DNA damage repair. However, the regulatory mechanisms underlying dysregulation of DNA damage repair genes are still being investigated. In this study, we reveal that C-terminal binding protein (CtBP) interacting protein (CtIP) couples with three transcriptional regulators, CtBP1/2 heterodimer, histone deacetylase 1 (HDAC1), and two subunits of the activating protein 1 (AP1) transcription factor to assemble a transcriptional complex. This complex specifically controls the expression of four genes involved in DNA damage and repair processes: MutL homolog 1 (MLH1), MutS Homolog 3 (MSH3), breast cancer type 1 (BRCA1), and cyclin dependent kinase inhibitor 1A (CDKN1A). Chromatin immunoprecipitation (ChIP) assay results revealed that the CtIP-CtBP1/2-HDAC1-AP1 complex regulated these four genes by binding to their promoters through the TGAT/CTCA consensus sequence. The depletion of CtIP, CtBP1/2, and HDAC1 increased the expression levels of MLH1, MSH3, BRCA1, and CDKN1A and inhibited in vitro and in vivo osteosarcoma cell growth. Overexpression of MLH1, MSH3, BRCA1, or CDKN1A in osteosarcoma cells can reduce cell viability, colony formation, cell migration, and tumor growth. Our findings suggest that the CtIP-CtBP1/2-HDAC1-AP1 complex is required for mediation of DNA damage processes for the pathogenesis of osteosarcoma.
RESUMO
Aberrant chondrocyte apoptosis and inflammation are the most critical causes of osteoarthritis (OA) development. This study was designed to demonstrate the relationship between S100A10 and OA. In this study, S100A10 was overexpressed or silenced in rat chondrocytes. Cell viability, apoptosis, reactive oxidative species (ROS), and calcium ion detection were assessed using Cell Counting Kit-8 assay and flow cytometry. The levels of key oxidation-related enzymes and tumor necrosis factor-alpha (TNF-α) were quantified using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and Western blotting. S100A10 was highly expressed in patients with OA and positively correlated with TNF-α level. Knockdown of S100A10 effectively counteracted TNF-α-induced ROS level, apoptosis, and calcium level and associated with decreased inflammation-related metalloproteinase 1 (MMP1), MMP13, and nuclear necrosis factor-kappa B (NF-κB)-p65 and increased survivin and cytoplasmic NF-κB-p65. Overexpression of S100A10 had an effect similar to TNF-α, which was significantly counteracted by pyrrolidine dithiocarbamate, an NF-κB inhibitor, or verapamil, a calcium-channel blocker. S100A10 contributed to chondrocyte apoptosis through the ROS/NF-κB pathway. This study has established the relationship between S100A10 and the NF-κB pathway, thus providing novel perspectives for exploring S100A10 functions.
Assuntos
NF-kappa B , Osteoartrite , Proteínas S100 , Animais , Ratos , Apoptose , Cálcio/metabolismo , Condrócitos , Inflamação/metabolismo , NF-kappa B/metabolismo , Osteoartrite/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/farmacologia , Proteínas S100/metabolismoRESUMO
OBJECTIVE: To investigate whether exosomes derived from miR-27a-overexpressing human umbilical vein endothelial cells (HUVECs)-exo (miR-27a) can promote bone regeneration and improve glucocorticoids (GC) induced osteonecrosis of femoral head (ONFH) (GC-ONFH). METHODS: The exo (miR-27a) were intended to be constructed and identified by transmission electron microscopy, nanoparticle tracking analysis, Western blot, and real-time fluorescent quantitative PCR (qRT-PCR). qRT-PCR was used to evaluate the effect of exo (miR-27a) in delivering miR-27a to osteoblasts (MC3T3-E1 cells). Alkaline phosphatase staining, alizarin red staining, and qRT-PCR were used to evaluate its effect on MC3T3-E1 cells osteogenesis. Dual-luciferase reporter (DLRTM) assay was used to verify whether miR-27a targeting Dickkopf WNT signaling pathway inhibitor 2 (DKK2) was a potential mechanism, and the mechanism was further verified by qRT-PCR, Western blot, and alizarin red staining in MC3T3-E1 cells. Finally, the protective effect of exo (miR-27a) on ONFH was verified by the GC-ONFH model in Sprague Dawley (SD) rats. RESULTS: Transmission electron microscopy, nanoparticle tracking analysis, Western blot, and qRT-PCR detection showed that exo (miR-27a) was successfully constructed. exo (miR-27a) could effectively deliver miR-27a to MC3T3-E1 cells and enhance their osteogenic capacity. The detection of DLRTM showed that miR-27a promoted bone formation by directly targeting DDK2. Micro-CT and HE staining results of animal experiments showed that tail vein injection of exo (miR-27a) improved the osteonecrosis of SD rat GC-ONFH model. CONCLUSION: exo (miR-27a) can promote bone regeneration and protect against GC-ONFH to some extent.
Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Animais , Cabeça do Fêmur , MicroRNAs/genética , Osteogênese , Ratos , Ratos Sprague-DawleyRESUMO
Chemoresistance is a major barrier for the chemotherapy of osteosarcoma. The induction of multidrug resistance protein 1 (MDR1), an ATP-dependent transporter, can efflux anti-cancer drugs, thereby decreasing chemosensitivity. However, an actual involvement of MDR1 in the chemoresistance of osteosarcoma cells has not been established. We obtained two cisplatin (CDDP)-resistant osteosarcoma cancer stem cell (CSC) lines using sphere formation medium supplemented with CDDP. These two CDDP-resistant CSC cell lines showed substantial cell proliferation, colony formation, cell invasion, and in vivo tumor growth in the presence of CDDP. Microarray analysis revealed that three genes, MDR1, FOXM1 (forkhead box M1), and CtBP1 (C-Terminal binding protein 1), showed significant overexpression in both cell lines. Mechanistically, CtBP1 assembled with FOXM1 to form a transcriptional complex, which docked onto the MDR1 promoter to activate MDR1 expression. Knockdown or inhibition of the CtBP1-FOXM1 components with specific small molecules, including NSM00158 and NSC95397 for CtBP1 and RCM1 for FOXM1, significantly repressed MDR1 expression. Administration of these three small molecules also significantly inhibited tumor growth in mouse tumor xenograft model. The MDR1-mediated chemoresistance could be reversed by NSM00158 and RCM1. Collectively, our data revealed that the CtBP1-FOXM1 complex activated MDR1 expression and that targeting this complex with their specific inhibitors could reverse MDR1-mediated chemoresistance both in vitro and in vivo. Our results indicate a new therapeutic strategy for overcoming chemoresistance during osteosarcoma treatment.
RESUMO
INTRODUCTION: The purpose of this study was to investigate whether TXA can effectively reduce blood loss after HTO and related complications and to evaluate its safety. MATERIALS AND METHODS: From March 2016 to March 2018, 100 patients who underwent medial opening wedge HTO in the Department of Orthopedics, the second affiliated hospital of xi'an jiaotong university, with an average age of 52.8 ± 3.2 years, were randomly divided into the TXA group (using intravenous TXA) and the control group (using the same amount of normal saline), with 50 patients in each group. The postoperative wound drainage volume, decrease in hemoglobin and hematocrit value, total blood loss, wound healing, blood transfusion, deep venous thrombosis (DVT) and pulmonary embolism (PE) were compared between the two groups. RESULTS: The drainage volume on the first postoperative day and the total drainage volume of the TXA group were significantly lower compared with those of the control group (145.7 vs 264.5 ml, 282.3 vs 413.2 ml, P < 0.05). The decreases in the hemoglobin and hematocrit values on the postoperative first, second and fifth days were lower in the TXA group than those in the control group (1.4 VS 3.5, 2.6 vs 3.3, 1.9 vs 2.9 g, P < 0.05; 3.3 vs 5.5, 5.0 vs 9.1, 3.8 vs 7.2%, P < 0.05), and the mean total blood loss was also lower in the TXA group than that in the control group (477.9 vs 834.6 ml, P < 0.05). In the control group, 1 patient had wound hematoma requiring additional paracentesis and pressure dressing, 1 patient had superficial wound infection requiring additional debridement, and 1 patient had postoperative blood transfusion compared to none in the TXA group (P > 0.05). There was no symptomatic DVT or PE in either of the groups. CONCLUSION: Intravenous TXA can effectively and safely reduce blood loss and bleeding-related complications after HTO and was beneficial for the blood management of HTO.
Assuntos
Osteotomia , Tíbia/cirurgia , Antifibrinolíticos , Perda Sanguínea Cirúrgica/prevenção & controle , Humanos , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/prevenção & controle , Ácido TranexâmicoRESUMO
Nischarin (NISCH) is a key protein functioning as a molecular scaffold and thereby hosting interactions with several protein partners. Here, we aimed to investigate whether NISCH downregulation could protect rat pheochromocytoma (PC12) cells against oxidative stress-induced injury using a model of cell injury induced by hydrogen peroxide (H2O2). Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis rate was evaluated using flow cytometry. The expressions of apoptosis-related proteins Bax, Bcl-2, caspase-3 and NISCH were examined via Western blot analysis and immunofluorescence staining analyses. The expressions of NISCH, glycogen synthase kinase-3ß (GSK-3ß) and T-cell factor-1 (TCF-1) were examined using Western blot analysis. The results showed that incubation of H2O2 for 48 h significantly decreased the cell viability, increased the cell apoptosis rate and the NISCH expression in PC12 cells, whereas NISCH downregulation blocked the effects of H2O2 on cells. In addition, the expression of Bcl-2 was significantly reduced, and the expression of Bax and caspase-3 were significantly increased by H2O2 treatment. However, these effects were partially inhibited by the downregulation of NISCH. Furthermore, H2O2 significantly weakened the transduction of Wnt signaling, including the increases of GSK-3ß and TCF-1 expressions and the decrease of ß-catenin expression, while NISCH downregulation attenuated the effect of H2O2 on Wnt signaling. Moreover, inhibition of the Wnt pathway further decreased the cell viability and promoted the cell apoptosis induced by H2O2 in PC12 cells. Our results suggest that NISCH downregulation may protect cells against oxidative stress-induced injury through regulating the transduction of Wnt signaling.
Assuntos
Regulação para Baixo/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Estresse Oxidativo/fisiologia , Via de Sinalização Wnt/fisiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Regulação para Baixo/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
BACKGROUND: Fixing a tibial eminence fracture with a tri-pulley is a new technique. The purpose of this study was to present the early clinical outcome of arthroscopic tri-pulley suture fixation for tibial eminence fractures in children. METHODS: Twenty-one pediatric patients with type II or type III anterior tibial eminence fractures were included in this retrospective study. All Patients underwent surgical fixation by tri-pulley technology and were followed up for at least 24 months. They were evaluated preoperatively and postoperatively by physical, X-ray, and computed tomography (CT) examination and subjectively with the International Knee Documentation Committee (IKDC), and Lysholm questionnaires. RESULTS: The patients included 12 males and 9 females; mean age, 12.5 years (range, 8 ~ 16 years). They were followed-up for a median of 27 months (range, 24 ~ 39 months). We did not find post-operative instability in any of the patients by physical examination. The KT-2000 difference of both knees decreased from 9.3 ± 1.2 mm preoperatively to 2.6 ± 0.8 mm 24 months postoperatively (P < 0.001); the IKDC subjective knee evaluation score improved from 43.1 ± 13.2 preoperatively to 83.8 ± 6.3 postoperatively (P < 0.001); and Lysholm improved from 48.3 ± 6.21 to 87.1 ± 9.8 (P < 0.001). No unhealed fractures or epiphyseal damage were reported in the postoperative X-ray and CT. CONCLUSIONS: Arthroscopic tri-pulley fixation technology may provide a suitable technique for repair of tibial eminence fractures in skeletally immature patients. LEVEL OF EVIDENCE: Case series; Level of evidence IV.
Assuntos
Artroscopia/métodos , Epífises/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/cirurgia , Adolescente , Ligamento Cruzado Anterior/cirurgia , Desenvolvimento Ósseo , Criança , Feminino , Fixação Interna de Fraturas/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Imageamento por Ressonância Magnética , Masculino , Radiografia , Estudos Retrospectivos , Técnicas de Sutura/efeitos adversos , Tíbia/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Meniscal repair has received increasing attention, but for inexperienced doctors, unilateral suture anchor pulling out may occur during all-inside meniscal repair, and the treatment outcome may be affected. When the errors happened intraoperatively, how to minimize the loss under guaranteeing of treatment effectiveness is a topic worth studying. PURPOSE: To explore the practicability and effectiveness of the modified cross-suture method for arthroscopic remediation of unilateral suture anchor pulling out of an all-inside meniscal repair system. METHODS: From May 2014 to May 2017, 28 patients diagnosed with injuries of the meniscus and anterior cruciate ligaments (ACL) from the First Department of Orthopaedics of the Second Affiliated Hospital of Xi'an Jiaotong University were enrolled in the study as the observation group, including 18 males and 10 females with an average age of 25.5 ± 2.3 years (range 18-42 years). All patients underwent ACL reconstruction concurrently. All meniscus injuries were repaired with an all-inside meniscal repair technique, and 1-3 needles of unilateral suture anchor pulling out occurred intraoperatively. The modified cross-suture method was used to remedy the error of anchor pulling out and to eventually complete an effective repair. Another 30 patients who underwent ACL reconstruction and all-inside meniscal concurrently without unilateral suture anchor pulling out, including 20 males and 10 females with an average age of 26.3 ± 1.9 years (range 19-45 years), were enrolled as the control group. During postoperative follow-up, range of motion, Lachman test and pivot shift test were performed during the physical examination. The clinical healing of the meniscus was evaluated according to the Barrett standard. The meniscus healing status was also confirmed with magnetic resonance imaging (MRI). The function of the knee joint was evaluated according to the IKDC, Lysholm and Tegner scores. RESULTS: Twenty-five patients in the observation group and 28 patients in the control group completed the follow-up, with an average follow-up of 18.4 ± 5.2 months. All operations were performed by the same surgeon. At the follow-up 1 year after the operation, the average knee ROM of the two groups was 125.2 ± 4.3 degrees and 124.7 ± 3.8 degrees, the clinical healing rate of the meniscus of the two groups was 92.0% (23/25) and 92.9% (26/28), the MRI healing rate of the menniscus of the two groups was 72.0% (18/25) and 71.4% (20/28), and the IKDC, Lysholm and Tegner scores of the two groups were 90.52 ± 2.8, 89.17 ± 3.1, and 6.81 ± 1.7 and 91.42 ± 1.9, 90.32 ± 3.4, and 7.02 ± 1.4, respectively. The differences were not statistically significant (P > 0.05). CONCLUSIONS: The modified cross-suture method is practicable and effective for arthroscopic remediation of unilateral suture anchor pulling out in an all-inside meniscal repair system.
Assuntos
Lesões do Ligamento Cruzado Anterior , Lesões do Menisco Tibial , Adolescente , Adulto , Ligamento Cruzado Anterior/cirurgia , Artroscopia , Feminino , Humanos , Masculino , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/cirurgia , Pessoa de Meia-Idade , Técnicas de Sutura , Lesões do Menisco Tibial/diagnóstico por imagem , Lesões do Menisco Tibial/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: For various reasons, some elderly patients with femoral neck fracture undergo delayed surgical treatment. There is little information about the effect of delayed treatment on postoperative hip function and quality of life. The aim of this study was to investigate the effect of delayed hip arthroplasty on hip function, quality of life, and satisfaction in patients with femoral neck fractures. METHODS: Forty-seven patients with femoral neck fracture and hip replacement delayed over 21 days served as the delayed group (D group). Patients with femoral neck fracture, matched 1:1 for age and sex, and hip replacement within 7 days served as the control group (C group). The Harris hip score (HHS) and health-related quality of life (HRQoL) were assessed before surgery and 3 months, 6 months and 1 year postoperatively. The satisfaction questionnaires were completed by the patients themselves at the last follow-up. RESULTS: The HHS in the C group was lower than that in the D group (32.64 ± 9.11 vs. 46.32 ± 9.88, P < 0.05) before surgery but recovered faster after surgery. The HHS in the D group was lower than that in the C group 1 year postoperatively (85.2 ± 3.80 vs. 89.8 ± 3.33, P < 0.05). The patients' quality of life changed similarly to their HHS. The HHS 1 year after surgery was related to the preoperative HHS in group D (rs = 0.521, P < 0.01). Patients in the D group showed significantly higher satisfaction scores than those in the C group (P < 0.05). CONCLUSIONS: Hip function in patients with femoral neck fracture surgery delayed over 21 days recovered more slowly than that in those who underwent surgery within 7 days. However, they were more satisfied with the surgery. Moderate hip movement to ameliorate the lower limb muscle atrophy was recommended for patients facing a temporary inability to undergo surgery.
Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Idoso , Artroplastia de Quadril/efeitos adversos , Fraturas do Colo Femoral/cirurgia , Humanos , Período Pós-Operatório , Qualidade de Vida , Resultado do TratamentoRESUMO
Carboxyl-terminal binding proteins (CtBPs) are transcription regulators that control gene expression in multiple cellular processes. Our recent findings indicated that overexpression of CtBP2 caused the repression of multiple bone development and differentiation genes, resulting in atrophic nonunion. Therefore, disrupting the CtBP2-associated transcriptional complex with small molecules may be an effective strategy to prevent nonunion. In the present study, we developed an in vitro screening system in yeast cells to identify small molecules capable of disrupting the CtBP2-p300 interaction. Herein, we focus our studies on revealing the in vitro and in vivo effects of a small molecule NSM00158, which showed the strongest inhibition of the CtBP2-p300 interaction in vitro. Our results indicated that NSM00158 could specifically disrupt CtBP2 function and cause the disassociation of the CtBP2-p300-Runx2 complex. The impairment of this complex led to failed binding of Runx2 to its downstream targets, causing their upregulation. Using a mouse fracture model, we evaluated the in vivo effect of NSM00158 on preventing nonunion. Consistent with the in vitro results, the NSM00158 treatment resulted in the upregulation of Runx2 downstream targets. Importantly, we found that the administration of NSM00158 could prevent the occurrence of nonunion. Our results suggest that NSM00158 represents a new potential compound to prevent the occurrence of nonunion by disrupting CtBP2 function and impairing the assembly of the CtBP2-p300-Runx2 transcriptional complex.
Assuntos
Oxirredutases do Álcool/metabolismo , Proteínas Correpressoras/metabolismo , Proteína p300 Associada a E1A/metabolismo , Fraturas não Consolidadas/prevenção & controle , Proteínas Repressoras/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Consolidação da Fratura/efeitos dos fármacos , Consolidação da Fratura/genética , Fraturas não Consolidadas/genética , Fraturas não Consolidadas/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Modelos Biológicos , NAD/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
The neuroprotective effects of netrin-1 after spinal cord injury and its specific molecular mechanisms have not been elucidated. In our study, Western blot, transferase UTP nick end labeling staining and immunofluorescence staining first showed that netrin-1 significantly decreased the expression levels of caspase-3, caspase-9, transferase UTP nick end labeling-positive neurons, nuclear factor kappa-B, and tumor necrosis factor-α after spinal cord injury, which inhibited neuronal apoptosis and inflammatory response. Using Nissl and HE staining, we also found that netrin-1 significantly increased the number of Nissl bodies in the anterior horn of spinal cord and promoted the recovery of injured tissue after spinal cord injury, consequently providing a good microenvironment for recovery of motor function. Finally, the results of Basso, Beattie, and Bresnahan score further confirmed that netrin-1 promoted the recovery of neurological function after spinal cord injury. Furthermore, netrin-1 significantly promoted the expression of ß-catenin and inhibited the expression of glycogen synthase kinase-3ß, which activated Wnt/ß-catenin signaling pathway after spinal cord injury. However, XAV939 inhibited Wnt/ß-catenin signaling pathway, which significantly inhibited the regulatory effect of netrin-1 on apoptosis, inflammation, Nissl bodies, damaged tissues, and neuroprotection. These results demonstrate for the first time the correlation between netrin-1 and Wnt/ß-catenin signaling pathway after spinal cord injury and show that netrin-1 exerts its neuroprotective effect by activating this signaling pathway after spinal cord injury.
Assuntos
Netrina-1/administração & dosagem , Netrina-1/metabolismo , Neuroproteção , Fármacos Neuroprotetores/administração & dosagem , Traumatismos da Medula Espinal/metabolismo , Via de Sinalização Wnt , Animais , Apoptose/efeitos dos fármacos , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/complicaçõesRESUMO
Mechanically induced biological responses in bone cells involve a complex biophysical process. Although various mechanosensors have been identified, the precise mechanotransduction pathway remains poorly understood. PIEZO1 is a newly discovered mechanically activated ion channel in bone cells. This study aimed to explore the involvement of PIEZO1 in mechanical loading (fluid shear stress)-induced signaling cascades that control osteogenesis. The results showed that fluid shear stress increased PIEZO1 expression in MC3T3-E1 cells. The fluid shear stress elicited the key osteoblastic gene Runx-2 expression; however, PIEZO1 silencing using small interference RNA blocked these effects. The AKT/GSK-3ß/ß-catenin pathway was activated in this process. PIEZO1 silencing impaired mechanically induced activation of the AKT/GSK-3ß/ß-catenin pathway. Therefore, the results demonstrated that MC3T3-E1 osteoblasts required PIEZO1 to adapt to the external mechanical fluid shear stress, thereby inducing osteoblastic Runx-2 gene expression, partly through the AKT/GSK-3ß/ß-catenin pathway.
Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Canais Iônicos/metabolismo , Estresse Mecânico , Animais , Camundongos , Osteoblastos/metabolismo , Osteócitos/metabolismo , Osteogênese/fisiologia , Transdução de Sinais/fisiologia , Ativação TranscricionalRESUMO
The hub genes and signaling pathways associated with Duchenne muscular dystrophy (DMD) were predicted by bioinformatic methods to improve the therapeutic effect and quality of life of patients. Microarray data sets GSE465, GSE1004, and GSE1007 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by GEO2R, and function enrichment analyses were performed by DAVID. The protein-protein interaction (PPI) network was constructed and the module analysis was performed using STRING and Cytoscape. A total of 195 DEGs were identified. The enriched functions and pathways of the DEGs include extracellular exosome, focal adhesion, extracellular matrix (ECM), focal adhesion, PI3K-Akt signaling pathway, calcium signaling pathway, and ECM-receptor interaction. Fifteen hub genes were identified. DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the pathogenesis and progression of DMD, and provide candidate targets for treatment of DMD.