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Retraction of 'Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils' by Tao Li et al., Biomater. Sci., 2021, 9, 2931-2946, https://doi.org/10.1039/D0BM02126A.
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Crosstalk between nerves and bone is essential for bone repair, for which Schwann cells (SCs) are crucial in the regulation of the microenvironment. Considering that exosomes are critical paracrine mediators for intercellular communication that exert important effects in tissue repair, the aim of this study is to confirm the function and molecular mechanisms of Schwann cell-derived exosomes (SC-exos) on bone regeneration and to propose engineered constructs that simulate SC-mediated nerve-bone crosstalk. SCs promoted the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) through exosomes. Subsequent molecular mechanism studies demonstrated that SC-exos promoted BMSC osteogenesis by regulating the TGF-ß signaling pathway via let-7c-5p. Interestingly, SC-exos promoted the migration and tube formation performance of endothelial progenitor cells. Furthermore, the SC-exos@G/S constructs were developed by bioprinting technology that simulated SC-mediated nerve-bone crosstalk and improved the bone regeneration microenvironment by releasing SC-exos, exerting the regulatory effect of SCs in the microenvironment to promote innervation, vascularization, and osteogenesis and thus effectively improving bone repair in a cranial defect model. This study demonstrates the important role and underlying mechanism of SCs in regulating bone regeneration through SC-exos and provides a new engineered strategy for bone repair.
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INTRODUCTION: Recent studies have suggested that cartilage progenitor cells (CPCs) could be activated and differentiated into chondrocytes to produce matrix and to restore the integrity of damaged cartilage after injury. However, the mechanism involved in CPC activation upon damage is still unclear. This study aims to investigate the role of high mobility group box chromosomal protein 1 (HMGB1) in both activation and migration of CPCs during cartilage injury. MATERIAL AND METHODS: Explants harvested from mature bovine stifle joints were used for impact injury. The proliferation and migration of CPCs were examined via confocal imaging. Gene and protein expression of Hmbg1, Cxcl12, and Cxcr4 was also examined by quantitative polymerase chain reaction (qPCR), ELISA, and western blot. Each experiment was repeated 3 times. ANOVA and Student's t-test were performed for statistical analysis. RESULTS: HMGB1 released from dead and damaged chondrocytes after an impact injury could activate CPCs in the superficial zone of cartilage and promote their migration and proliferation to injury sites. However, the block of HMGB1 activation with its specific binding inhibitor glycyrrhizin inhibits the proliferation and migration of CPCs. Further investigations demonstrate that HMGB1 promotes CPCs migration through the pathway of C-X-C motif chemokine 12 (CXCL12) and its receptor CXCR4. Quantitative analysis of HMGB1 in cell culture medium also indicates that CPCs may have a self-activation property after the HMGB1 released from dead cells has been exhausted. CONCLUSION: HMGB1 is a pivotal factor that could enhance the migration and proliferation of CPCs through the CXCL12/CXCR4 pathway after cartilage injury, which could provide useful information for cartilage repair and osteoarthritis treatment.
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Cartílago , Condrocitos , Proteína HMGB1 , Animales , Bovinos , Cartílago/lesiones , Cartílago/metabolismo , Movimiento Celular , Quimiocina CXCL12/metabolismo , Condrocitos/metabolismo , Proteína HMGB1/metabolismo , Receptores CXCR4/metabolismo , Transducción de Señal , Células Madre/metabolismoRESUMEN
OBJECTIVE: Understanding the anatomy behind a pelvic fracture can be a significant challenge to medical students. Recent advances in three-dimensional printing technology offers a novel approach to facilitate the learning of complex fracture. We have described here how the 3-dimension printing (3Dp) models can help medical students improve their understanding in and identification of pelvic fractures. DESIGN: One hundred students were randomized into 2 teaching module groups (with or without 3Dp models). Prior to randomization assignment, a 50-minute didactic lecture covering elementary knowledge of anatomy, Young-Burgess classification, and traumatic mechanism of pelvic fracture was delivered to all students. The 3Dp group received X-rays, CT images, and 3Dp models of the eight pelvic fractures during presentation, while the students in the control group only obtained X-rays and CT scans of the same 8 pelvic fractures. Young-Burgess classification system and injury mechanism of pelvic fracture, time for evaluation, and subjective questions were conducted to assess the learning outcomes. SETTING: A medical student program based in a Levelâ trauma center PARTICIPANTS: One hundred students in their 4th year of a 5-year clinical medicine program (for a medical bachelor degree) RESULTS: Students receiving 3Dp model had a higher rate of identifying the correct pelvic fracture via Young-Burgess identification compared to these without 3Dp model. Moreover, the accuracy of identifying the injury mechanism was significantly higher in the 3Dp group than that in group without 3Dp model. Participant in 3Dp group had faster assessment time compared to the control group. Subjective survey results suggested that 3Dp model would increase the learning interest and enhance the understanding of pelvic fracture. In addition, majority of students (83%) reported that they would like to use 3Dp model in other surgical course education. CONCLUSIONS: 3Dp model increased the perceived accuracy of pelvic fracture identification and understanding of injury mechanism. Moreover, 3Dp model promoted the subjective interest and motivation of students in pelvic fracture learning. Therefore, 3Dp model can be considered as a valuable educational tool for learning pelvic fracture in medical students.
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Fracturas Óseas , Estudiantes de Medicina , Humanos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Aprendizaje , Impresión Tridimensional , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Congenital pseudarthrosis of the clavicle (CPC) is a rare congenital entity with unresolved aetiology and pathogenesis. Nearly 250 cases have been reported to date. CPC is characterized by a definite defect in the mid-clavicle at birth and is usually diagnosed when the deformity becomes evident in late childhood or adolescence. Surgical management is controversial, especially in asymptomatic children, with various techniques reported in the literature. CASE REPORT: We report a case of a 6-year-old boy who was diagnosed with CPC during a medical examination for primary school enrollment. Operative treatment included debridement of pseudoarthrosis, internal fixation with third tube plate, and barrel-shaped mono-cortical iliac crest autograft. RESULTS: A complete bone union was obtained 9 months after the operation, and satisfactory function and cosmetic appearance were observed 4 years and 3 months postoperatively. CONCLUSION: In our opinion, reconstruction with barrel-shaped mono-cortical iliac crest autograft was an effective and reproducible surgical technique to treat CPC.
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Clavícula , Seudoartrosis , Adolescente , Autoinjertos/patología , Niño , Clavícula/anomalías , Clavícula/patología , Clavícula/cirugía , Humanos , Ilion , Recién Nacido , Masculino , Seudoartrosis/congénito , Seudoartrosis/cirugíaRESUMEN
BACKGROUND: Relapsed childhood polymicrobial osteomyelitis associated with dermatophytosis has not been reported in the literature. CASE PRESENTATION: Here we report on a case of a 45-year-old man who had left tibial osteomyelitis for 29 years, accompanied by skin fungal infection of the ipsilateral heel for 20 years, and underwent a second operation due to recurrence of polymicrobial infection 6 years ago. The patient had a history of injury from a rusty object, which penetrated the anterior skin of the left tibia middle segment causing subsequent bone infection, but was asymptomatic after receiving treatments in 1983. The patient was physically normal until dermatophytosis occurred on the ipsilateral heel skin in 1998. The patient complained that the dermatophytosis was gradually getting worse, and the tibial wound site became itchy, red, and swollen. The left tibial infection resurged in May 2012, leading to the patient receiving debridement and antibiotic treatment. H&E and Gram-stained histology was performed on biopsy specimens of sequestrum and surrounding inflammatory tissue. Tissue culture and microbiology examination confirmed polymicrobial infection with Staphylococcus aureus (S. aureus) and Corynebacterium and a fungus. Additionally, the patient also received potassium permanganate for dermatophytosis when he was admitted into the hospital. CONCLUSIONS: Together with longitudinal follow-up of medical history, surgical findings, histopathological and microbiology culture evidence, we conclude that boyhood tibia polymicrobial osteomyelitis with S. aureus and Corynebacterium occurred in this patient, and the fungal activation of dermatophytosis may have led to osteomyelitis relapse.
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Coinfección , Osteomielitis , Infecciones Estafilocócicas , Tiña , Antibacterianos , Niño , Coinfección/complicaciones , Coinfección/diagnóstico , Desbridamiento , Humanos , Masculino , Persona de Mediana Edad , Osteomielitis/complicaciones , Osteomielitis/diagnóstico , Infecciones Estafilocócicas/complicaciones , Staphylococcus aureus , Tibia/cirugía , Tiña/complicacionesRESUMEN
Osteosarcoma is a bone tumor that often affects children, adolescents and young people. Non-coding RNA activated by DNA damage (NORAD) can promote the proliferation of cancer cells in multiple tumors. Thus, the current study set out to explore the role of NORAD derived from extracellular vesicles (EVs) of bone mesenchymal stem cells (BMSCs) in osteosarcoma. First, NORAD was highly expressed in osteosarcoma cells and tissues, which might be associated with the progression and metastasis of osteosarcoma. We isolated EVs from the characterized BMSCs, and found that NORAD was transferred from BMSCs to osteosarcoma cells via EVs in the co-culture system. Consequently, NORAD delivered by BMSC-derived EVs promoted the proliferation and invasion of osteosarcoma cells. Subsequently, bioinformatics analyses suggested potential binding relationship between NORAD and microRNA-30c-5p (miR-30c-5p) as well as between miR-30c-5p and Krueppel-like factor 10 (KLF10), and the results of which were further verified by dual luciferase reporter gene assay, RNA immunoprecipitation, and RNA pull-down assay. Mechanistically, NORAD acted as a sponge of miR-30c-5p and up-regulated the expression of KLF10 where miR-30-c-5p mimic declined the effect induced by NORAD on cancer cells. The osteosarcoma cells were injected into mice to develop tumor growth and metastasis models. In these two models, injection of BMSC-EVs elevated NORAD expression and KLF10 but reduced miR-30c-5p expression, whereby suppressing tumor growth and lung metastasis. To conclude, BMSC-EVs deliver NORAD to osteosarcoma cells to regulate the miR-30c-5p/KLF10 axis, thereby accelerating the progression and metastasis of osteosarcoma.
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Neoplasias Óseas , Vesículas Extracelulares , Células Madre Mesenquimatosas , MicroARNs , Osteosarcoma , ARN Largo no Codificante , Animales , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Vesículas Extracelulares/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Células Madre Mesenquimatosas/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Osteosarcoma/genética , Osteosarcoma/patología , ARN Largo no Codificante/metabolismoRESUMEN
Background: Osteoporosis is a common complication of acute fracture, which can lead to fracture delayed union or other complications and resulting in poor fracture healing. Bisphosphate is a common anti-osteoporosis drug, but its application in fracture patients is still controversial because of its inhibitory effect on bone resorption. Method: Studies were acquired from literature databases in accordance with established inclusion criteria. Standard mean difference (SMD) and 95% confidence intervals (Cls) were calculated to evaluate the effectiveness of the bisphosphonates treatment in fracture patients. Data analysis was conducted with the Review Manager 5.4.1 software. Results: A total of 16 studies involving 5022 patients obtained from selected databases were examined. As expected, bisphosphate had no significant effect on fracture healing time, but it could significantly increase BMD and prevent osteoporosis. Meanwhile, bisphosphate can inhibit both bone resorption and bone formation markers, resulting in low bone turnover state. Conclusion: This meta-analysis showed that bisphosphonate have no significant effect on fracture healing time but they do increase the changes in BMD and reduce bone synthesis and resorption markers. Early application of bisphosphonates after injury in the appropriate patient population should be considered.
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Conservadores de la Densidad Ósea/administración & dosificación , Densidad Ósea/efectos de los fármacos , Difosfonatos/administración & dosificación , Curación de Fractura/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Conservadores de la Densidad Ósea/uso terapéutico , Remodelación Ósea/efectos de los fármacos , Difosfonatos/uso terapéutico , HumanosRESUMEN
Osteoporosis is a common skeletal disease characterized by reduced bone mass partially caused by an imbalance between bone resorption and formation. Considering the potential role of microRNAs (miRNAs) in osteoporosis, we attempted to identify deregulated miRNA that participates in the pathogenesis of osteoporosis. We analyzed online datasets for differentially expressed miRNAs and predicted deregulated miRNA target genes, applied these genes for signaling pathway enrichment annotation, and selected the possible miR-99b-5p/FGFR3 axis. Within osteoporosis bone tissues, miR-99b-5p was upregulated and FGFR3 was downregulated. miR-99b-5p overexpression inhibited osteoblast proliferation and osteogenesis-related genes expression, whereas FGFR3 overexpression exerted opposite effects upon the proliferation of osteoblasts and osteogenesis-related genes expression. By direct targeting, miR-99b-5p inhibited FGFR3 expression. Moreover, FGFR3 silencing significantly reversed the roles of miR-99b-5p inhibition in the proliferation of osteoblasts and osteogenesis-related genes expression. In conclusion, we identify a deregulated miRNA/mRNA axis in osteoporosis and osteogenic differentiation, namely the miR-99b-5p/FGFR3 axis; through targeting FGFR3, miR-99b-5p inhibits osteoblast proliferation and activity, which might subsequently affect the bone formation in osteoporosis progression.
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Proliferación Celular/genética , Regulación del Desarrollo de la Expresión Génica/genética , MicroARNs/fisiología , Osteoblastos/fisiología , Osteoporosis/genética , Osteoporosis/patología , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Anciano , Células Cultivadas , Femenino , Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Osteogénesis/genética , Osteogénesis/fisiología , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Obturator dislocation is a rare type of hip dislocation, accounting for about 2%-5% of all hip dislocations. The occurrence of old unreduced obturator dislocation is even more infrequent, with only 17 cases reported in nine studies, most of which were from the 1950s to 1980s in developing countries. CASE SUMMARY: A 38-year-old woman from Hunan Province, China presented with stiffness of the left hip in abduction, flexion, and external rotation after falling from a 2-meter-tall tree onto her left knee 1.5 mo prior. Pelvic radiograph and computed tomography revealed obturator dislocation of the left hip accompanied by impaction fracture at the superolateral aspect of the left femoral head without associated acetabulum fracture. Open reduction was performed, resulting in restoration of the concentric alignment of the left hip. After surgery, 6-wk skin traction was applied and the patient was kept in bed for an additional 2 wk. At 3 mo after surgery, the patient reported experiencing some pain, which did not affect the function of the affected limb, and some movement restriction but no abduction deformity or claudication was present. An X-ray showed that the left hip was homocentric, and there was no sign of posttraumatic arthritis or avascular necrosis. CONCLUSION: Open reduction may be an effective treatment strategy for the rare condition of old unreduced obturator dislocation with short neglect time.
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OBJECTIVE: The aim of the present study was to compare the clinical results for unstable femoral intertrochanteric fractures treated with a double reverse traction repositor (DRTR) and those treated using a traction table with the Asia proximal femoral nail antirotation (PFNA-II). METHODS: A retrospective study was performed including 95 patients with AO/OTA type 31-A2 and 31-A3 unstable femoral intertrochanteric fractures who underwent DRTR or traction table-facilitated PFNA-II nailing from April 2015 to December 2018 in our traumatic center. Demographics, duration of operation, blood loss, part loading time after surgery, fracture healing time, and early and late complications were assessed. Clinical and radiological outcomes were collected to compare the differences between the two groups. RESULTS: A total of 95 unstable intertrochanteric fracture patients treated with the PFNA-II were analyzed. Of these cases, 56 patients were treated with a DRTR and the other 39 patients were treated using a traction table to achieve fracture reduction. No patients died during surgery and hospitalization. There were no significant differences in respect to demographics and fracture characteristics of cases enrolled. The total operative time was significantly longer in the traction table group than in the DRTR group (72.5 ± 6.1 min for the traction table and 63.0 ± 4.1 min for the DRTR group, P < 0.001). No significant differences were observed in intraoperative blood loss and duration of hospitalization. The periods of follow up ranged from 12 to 31 months among all patients. At the last follow up, the Harris hip score (HHS) in the DRTR group was excellent in 10 patients (17.9%), good in 36 (64.3%), fair in 8 (14.3%), and poor in 2 (3.6%). These scores were comparable to those in the traction table group, which were: excellent in 8 patients (20.5%), good in 24 (61.5%), fair in 6 (15.4%), and poor in 1 (2.6%). Regarding the radiological evaluation, excellent rates of reduction rate were achieved in 39 cases (69.6%) in the DRTR group, which was comparable to 19 cases (48.7%) in the traction table group. In addition, the mean fracture healing time after surgery was 20.6 ± 2.3 weeks in the DRTR group and 21.4 ± 3.4 weeks in the traction table group, which did not reach a significant difference (P = 0.18). During the follow up, 6 cases of thigh pain, 4 cases of deep vein thrombosis, and 1 case of fracture of the anterior superior iliac spine were reported in the DRTR group. In the traction table group, there were 2 cases of deep vein thrombosis and 3 cases of thigh pain. CONCLUSION: When using the PFNA-II for unstable intertrochanteric fractures, the DRTR was superior to the traction table in respect to operative time and duration of patient position, despite an additional ipsilateral anterior superior iliac spine (ASIS) incision and drilling of the ASIS and the femur condyle.
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Fijación Intramedular de Fracturas/métodos , Fracturas de Cadera/cirugía , Tracción/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
The immune system mediates inflammation, vascularization and the first response to injuries or implanted biomaterials. Although the function of neutrophils in tissue repair has been extensively studied, its complete role in the tissue regeneration of biomaterials, specifically the resolution of inflammation and promotion of angiogenesis, is unclear. Here, we fabricate nanofibrous gelatin scaffolds containing 10% (w/w) strontium-hydroxyapatite (SrHA) via phase-separation methods to investigate Sr-mediated regulation of neutrophil polarization and, subsequently, the effects on angiogenesis and macrophage polarization. Compared with neutrophils cultured on pure gelatin or HA-incorporated gelatin scaffolds, neutrophils on SrHA-incorporated gelatin scaffolds show more N2 polarization in vitro and in vivo and significantly greater production of immunomodulatory and angiogenic factors. The Sr-induced immunomodulatory and proangiogenic functions of neutrophils are mediated through NF-κB pathway downregulation and increased STAT3 phosphorylation. Thus, neutrophils play a vital role in tissue engineering, and Sr-incorporated scaffolds efficiently promote neutrophil polarization to the N2 phenotype, enhancing resolution of inflammation and ultimately promoting angiogenesis and tissue regeneration. Thus, incorporation of neutrophils in analyses of the immune characteristics of scaffolds and the development of immunomodulatory biomaterials that can regulate neutrophils are novel and promising strategies in tissue engineering.
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Gelatina , Neutrófilos , Macrófagos , Estroncio , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
BACKGROUND: Acetabular anterior wall fracture with preservation of the pelvic brim is extremely rare. It is different from anterior wall fracture classified by Judet and Letournel. Few studies have reported cases treated by open reduction and internal fixation via the Smith-Petersen or iliofemoral approach. CASE SUMMARY: We report a 48-year-old Chinese woman who had difficulty moving her right hip from abduction and external rotation after falling from 3 m. Pelvic radiograph and three-dimensional reconstruction of computed tomography revealed acetabular anterior wall fractures combined with fractures of the anterior inferior iliac spine and the iliac wing but not involving the pelvic brim. First, the patient underwent interim management by closed reduction of the hip dislocation and skin traction for 6 d. Then, we used a modified pararectus approach for treatment to fix the acetabular fractures with a reconstruction plate and nonlocking T-shape plate. At the 9-mo follow-up, the patient could walk painlessly without necrosis of the femoral head or heterotopic ossification, and the X-rays and computed tomography scan reconstructions showed good bone union. CONCLUSION: The modified pararectus approach described here can facilitate exposure, reduction, and osteosynthesis for atypical acetabular fracture with less invasiveness.
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Osteosarcoma is a malignant bone tumour with the lowest survival rates out of all paediatric cancers and is primarily diagnosed in children and adolescents. MNAT1 is a subunit in the cyclin-dependent kinase-activating kinase complex. Abnormal up-regulation of MNAT1 has been associated with the poor prognosis of multiple cancers. Bioinformatics analysis showed that has-circ-0001146 and miR-26a-5p were involved in the regulation of MNAT1 in osteosarcoma. The present study investigated the regulatory effects of has-circ-0001146 and miR-26a-5p on MNAT1 expression using luciferase reporter and RNA-pull down assays. The effects of the has-circ-0001146/miR26a-5p/Mnat1 network on the proliferation and invasion of osteosarcoma were evaluated by cell viability, apoptosis, migration, and invasion assays. Osteosarcoma tissues showed higher MNAT1 and has-circ-0001146 expression than adjacent normal tissues, although the expression of MNAT1 was not significantly up-regulated in sarcomas according to TCGA databases. As indicated by luciferase reporter and RNA-pull down assays, miR-26a-5p was able to bind to both has-circ-0001146 and MNAT1 mRNA. The depletion of has-circ-0001146 as well as the increase of miR-26a-5p decreased MNAT1 expression in osteosarcoma cells, while the reduction of miR-26a-5p was associated with increased MNAT1 expression. These data suggested that has-circ-0001146 promoted MNAT1 expression by competitively binding to miR-26a-5p with MNAT1 mRNA. The depletion of has-circ-0001146 or MNAT1 or the increase of miR-26a-5p inhibited osteosarcoma cell viability and invasion, and increased apoptosis. Reduction of miR-26a-5p conversely promoted osteosarcoma cell viability and invasion. The present study confirmed that has-circ-0001146 blocked miR-26a-5p targeting MNAT1 in osteosarcoma cells, thereby promoting the malignant behaviours of osteosarcoma cells.
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Neoplasias Óseas/metabolismo , Proteínas de Ciclo Celular/metabolismo , MicroARNs/metabolismo , Osteosarcoma/metabolismo , ARN Circular/metabolismo , Factores de Transcripción/metabolismo , Animales , Apoptosis , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Osteosarcoma/genética , Osteosarcoma/patología , ARN Circular/genética , Transducción de Señal , Factores de Transcripción/genética , Carga Tumoral , Adulto JovenRESUMEN
Osteoarthritis (OA) is the most common skeletal disease and the leading cause of pain and disability in the aged population (>65 years). However, the underlying factors involved in OA pathogenesis remain elusive which has resulted in failure to identify disease-modifying OA drugs. Altered metabolism has been shown to be a prominent pathological change in OA. As a critical bioenergy sensor, AMP-activated protein kinase (AMPK) mediates not only energy homeostasis but also redox balance in chondrocytes to counter various cell stress. Dysfunction of AMPK activity has been associated with reduced autophagy, impaired mitochondrial function, excessive reactive oxygen species generation, and inflammation in joint tissue. These abnormalities ultimately trigger articular cartilage degeneration, synovial inflammation, and abnormal subchondral bone remodeling. This review focuses on recent findings describing the central role of AMPK in joint homeostasis and OA development. We also highlight current advances that target AMPK as a novel therapeutic strategy for OA prevention.
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AIMS: We aimed to elucidate the effects and mechanisms of MAT1 in the progression of osteosarcoma, especially for its lung metastasis. MAIN METHODS: CCK-8 and flow cytometry assays were carried out to detect the proliferation and apoptosis of osteosarcoma cells. Wound healing and transwell assays were used to determine cell migration and invasion abilities. Real time quantitative PCR (RT-PCR) and western blot technologies were applied to detect the expression levels of RNA and protein, respectively. KEY FINDS: The results showed that both the mRNA and protein expression levels of MAT1 were elevated in osteosarcoma tissues with lung metastasis and metastatic lung tissues, particularly in the metastatic lung tissues, as compared to the osteosarcoma tissues without lung metastasis. High expression level of MAT1 in osteosarcoma patients showed a negative association with the overall survival. In addition, upregulation of MAT1 induced significant increases in cell growth, migration and invasion and an obvious inhibition in cell apoptosis in osteosarcoma MG63 and 143B cells, as well as elevated AKT1 expression level. Moreover, knockdown of AKT1 obviously impaired MAT1-mediated promotions in cell migration and invasion in vitro, as well as repressed tumor growth and reduced the number of metastatic lung tumors in xenografted nude mice. SIGNIFICANCE: This study reveals that high expression of MAT1 closely related to the poor prognosis and malignant clinical process of osteosarcoma patients. MAT1 serves as a promoter in the lung metastasis of osteosarcoma through increasing AKT1 expression. Our study may provide a potent therapeutic target for the lung metastasis of osteosarcoma.
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Sistemas de Transporte de Aminoácidos Neutros/genética , Neoplasias Óseas/patología , Proteínas Portadoras/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/secundario , Osteosarcoma/patología , Proteínas Proto-Oncogénicas c-akt/genética , Adulto , Animales , Neoplasias Óseas/genética , Proteínas de Ciclo Celular , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Osteosarcoma/genética , Factores de Transcripción , Regulación hacia Arriba , Adulto JovenRESUMEN
PURPOSE: Chronic kidney disease (CKD) is known to increase morbidity and mortality after orthopedic surgery. The purpose of this study is to investigate how CKD affects perioperative complications in hip surgery patients. MATERIAL AND METHODS: From 2013 to 2016, a total of 230 patients (30 patients with CKD and 200 without CKD) undergoing hip surgery were enrolled in this study. Preoperative, intraoperative, and postoperative data was collected and analyzed between CKD and non-CKD patients. Logistic regression was used to evaluate the independent risk factor for postoperative complications. RESULTS: There were significant differences in the number of people with hypertension (90.0% vs 27.3%, P < 0.001), diabetes (33.3% vs 8.7%, P = 0.01), coronary heart disease (20.0% vs 2.0%, P = 0.001), smoking habits (56.7% vs 22.7%, P = 0.016), anemia (90.0% vs 19.3%, P < 0.001), and low hemoglobin levels (94.1 ± 19.7 vs 121.3 ± 18.8, P < 0.001) between CKD and non-CKD patients before surgery. Receiving a blood transfusion was significantly more common in CKD patients (50% vs 28.5%, P = 0.018). Postoperatively, significant differences were detected in the average number of patients who transferred to the ICU (73.3% vs 19.3%, P < 0.001). Furthermore, differences were found in the quantity of hemoglobin (92.5 ± 16.8 vs 107.5 ± 18.3, P < 0.001) and albumin (32.4 ± 4.1 vs 34.9 ± 5.5, P = 0.02) measured between CKD and non-CKD patients. Logistic regression analysis indicated that diabetes, alcohol, and anemia were all independent risk factors for obtaining a blood transfusion, while age, CKD, and osteoporosis were all independent risk factors for ICU transfers. CONCLUSION: Compared with non-CKD patients, CKD patients were accompanied with more cardiac diseases preoperatively. In addition, CKD patients were more likely to receive a blood transfusion and transfer to the ICU after hip surgery. Preoperative anemia should be restored sufficiently to decrease the incidence of blood transfusions.
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Procedimientos Quirúrgicos Electivos/efectos adversos , Complicaciones Intraoperatorias/epidemiología , Procedimientos Ortopédicos/efectos adversos , Huesos Pélvicos/cirugía , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Procedimientos Quirúrgicos Electivos/tendencias , Femenino , Humanos , Complicaciones Intraoperatorias/diagnóstico , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos/tendencias , Huesos Pélvicos/patología , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Osteosarcoma, which commonly occurs in young individuals, is a type of malignant tumor of growing bones. MicroRNAs (miRNAs) have been found to be involved in various cancer-related processes. In the present study, it was reported that miRNA-128 (miR-128) was overexpressed in pathological tissues from patients with osteosarcoma. The present study investigated the possible regulatory mechanism of miR-128 on the progression of osteosarcoma and offered a foundation for clinical therapeutics in osteosarcoma. First, the expressions levels of miR-128 and its target gene, SAM and SH3 domain-containing 1 (SASH1), were measured in tissues from patients with osteosarcoma, and their correlation with osteosarcoma in terms of the pathological level were examined. The effects of miR-128 on osteosarcoma cell proliferation and apoptosis were examined, and its regulation of the expression levels of SASH1 and associated proteins was analyzed. Subsequently, the association between SASH1 and miR-128 was evaluated using a dual luciferase gene reporter assay. Finally, an in vivo xenograft tumor mouse model of osteosarcoma was established to confirm the in vitro results. The results demonstrated a higher expression of miR-128 in pathological tissues, compared with that in normal tissues. From examining the patient osteosarcoma tissues, marked correlations were found between the expression of miR-128 and that of SASH1, particularly with tumor size, invasion depth, lymph node metastasis, and tumor-node-metastasis stage. Compared with the negative control group and blank control group, the results showed that the inhibition of miR-128 led to a lower cell proliferation rate and higher apoptotic rate in MG-63 cells (P<0.05). Additionally, the expression of B-cell lymphoma 2 (Bcl-2) was downregulated in the miR-128-inhibited group, compared with that in the control group, whereas the expression levels of SASH1, Bcl-2-associated X protein and caspase-3 were upregulated in the group with miR-128 inhibition (P<0.05). SASH1 was confirmed as a direct target of miR-128 using a dual luciferase gene reporter assay. Finally, the downregulation of miR-128 was found to induce tumor suppressive effects on xenograft tumor models of osteosarcoma in mice in vivo. The results of the present study suggested that miR-128 may regulate the tumorigenesis and evolution of osteosarcoma through targeting SASH1.
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RATIONALE: The knee joint is an important weight-bearing joint, tibial plateau fractures affect knee function and stability. High-energy intra-articular fractures involving the tibial plateau can cause management-related problems such as wound dehiscence; severe comminution leading to malalignment; and delayed complications such as varus collapse, implant failure, and arthritis of the knee joint. The treatment of severe or complex tibial plateau fractures can be quite difficult. Traditional methods of open reduction and plating require extensive exposures, which may further compromise soft tissue and devascularize bone fragments, leading to infection. In this case, a novel device, double reverse traction combined with MIPPO technique, was used and provided the possibility of minimally invasive and personalized orthopedic surgery to treat severe comminuted Schatzker type VI tibial plateau fracture and tibial shaft fracture and got satisfactory results. PATIENT CONCERNS: A previously healthy 56-year-old man presented to the emergency room after a fall from a height, who lost the movement of the left knee with pain and swelling. DIAGNOSES: X-rays showed a tibial plateau comminuted fracture, Schatzker type VI, and tibial shaft fracture. INTERVENTIONS: Applying less extensile exposure and the indirect reduction technique of double reverse traction and closed reduction combined with minimally invasive percutaneous plate osteosynthesis (MIPPO) technique, we got satisfactory recovery of the severe comminuted Schatzker type VI tibial plateau fracture and tibial shaft fracture. OUTCOMES: This severe comminuted fracture and tibial shaft fracture were successfully reduced and got satisfactory recovery of knee joint function. LESSONS: Double reverse traction combined with MIPPO technique can reduce the risk of surgical complications, such as bleeding, oozing, and wound infection. It can be applied in patients with comorbidities such as cardiac disease, hypertension, and heart failure who may otherwise not be candidates for surgery. The cost burden is lower than that of the traditional traction table.