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This preliminary study investigated the feasibility of a combined model constructed using radiomic features based on computed tomography (CT) and clinical features to predict adverse clinical outcomes in acute pulmonary embolism (APE). Currently, there is no widely recognized predictive model. Patients with confirmed APE who underwent CT pulmonary angiography were retrospectively categorized into good and poor prognosis groups. Seventy-four patients were randomized into a training (n = 51) or validation (n = 23) cohort. Feature extraction was performed using 3D-Slicer software. The least absolute shrinkage and selection operator regression was used to identify the optimal radiomics features and calculate the radiomics scores; subsequently, the radiomics model was developed. A combined predictive model was constructed based on radiomics scores and selected clinical features. The predictive efficacy of the three models (radiomics, clinical and combined) was assessed by plotting receiver operating characteristic curves. Furthermore, the calibration curves were graphed and the decision curve analysis was performed. Four radiomic features were screened to calculate the radiomic score. Right ventricular to left ventricular ratio (RV/LV) ≥ 1.0 and radiomics score were independent risk factors for adverse clinical outcomes. In the training and validation cohorts, the areas under the curve (AUCs) for the RV/LV ≥ 1.0 (clinical) and radiomics score prediction models were 0.778 and 0.833 and 0.907 and 0.817, respectively. The AUCs for the combined model of RV/LV ≥ 1.0 and radiomics score were 0.925 and 0.917, respectively. The combined and radiomics models had high clinical assessment efficacy for predicting adverse clinical outcomes in APE, demonstrating the clinical utility of both models. Calibration curves exhibited a strong level of consistency between the predictive and observed probabilities of poor and good prognoses in the combined model. The combined model of RV/LV ≥ 1.0 and radiomics score based on CT could accurately and non-invasively predict adverse clinical outcomes in patients with APE.
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Hominidae , Embolia Pulmonar , Animales , Humanos , Enfermedad Aguda , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/terapia , Radiómica , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Coronary distensibility index (CDI), as an early predictor of cardiovascular diseases, has the potential to complement coronary computed tomography angiography (cCTA)-derived fractional flow reserve (CT-FFR) for predicting major adverse cardiac events (MACEs). Thus, the prognostic value of CT-FFR combined with CDI for MACEs is worth exploring. METHODS: Patients with a moderate or severe single left anterior descending coronary artery stenosis were included and underwent FFR and CDI analysis based on cCTA, followed up at least 1 year, and recorded MACEs. Multivariate logistic regression analysis was performed to determine independent predictors of MACEs. The area under of receiver operating characteristic (ROC) curve was used to evaluated evaluate the diagnostic performance of CT-FFR, CDI, and a combination of the two. RESULTS: All the vessel-specific data were from LAD. 150 patients were analysed. 55 (37%) patients experienced MACEs during follow-up. Patients with CT-FFR ≤ 0.8 had higher percentage of MACEs compared with CT-FFR > 0.8 (56.3% vs.7.3%, p < 0.05). Patients' CDI was significantly decreased in MACEs group compared with non-MACEs group (p < 0.05). Multivariate analysis revealed that diabetes (p = 0.025), triglyceride (p = 0.015), CT-FFR ≤ 0.80 (p = 0.038), and CDI (p < 0.001) are independent predictors of MACEs. According to ROC curve analysis, CT-FFR combined CDI showed incremental diagnostic performance over CT-FFR alone for prediction of MACEs (AUC = 0.831 vs. 0.656, p = 0.0002). CONCLUSION: Our study provides initial evidence that combining CDI with CT-FFR shows incremental discriminatory power for MACEs over CT-FFR alone, independent of clinical risk factors. Diabetes and triglyceride are also associated with MACEs.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico , Humanos , Valor Predictivo de las Pruebas , Pronóstico , Tomografía Computarizada por Rayos X/efectos adversos , TriglicéridosRESUMEN
Anterior cruciate ligament (ACL) rupture is a common musculoskeletal injury, most frequently affecting young and physically active patients. Platelet-rich plasma (PRP) has been widely used in ACL reconstruction to augment the graft healing. However, high-level studies addressing its clinical efficacy could not reach a consensus. In this study, we assess the efficacy of PRP on pain relief, functional improvement along with radiological changes in patients who underwent ACL reconstruction. We performed comprehensive literature search and included 17 RCTs containing 970 participants who underwent ACL reconstruction. The combined data showed significant difference between PRP and control with regard to VAS score (MD: -1.12, 95% CI -1.92, -0.31; P = .007), subjective IKDC score (MD: 6.08, 95% CI 4.39, 7.77; P < .00001) and Lysholm score (MD: 8.49, 95% CI 1.63, 15.36; P = .02) by postoperative 6 months, but only pain reduction was deemed clinically important. At the end of one year's follow-up, no clinically meaningful improvement in VAS (MD: -0.47, P = .04), subjective IKDC score (MD: 3.99, P = .03), Lysholm score (MD: 2.30, P = .32), objective IKDC score (RR: 1.03, P = .09) and knee joint laxity (MD: 0.17, P = .28) was seen. In terms of radiological findings, about one-third of the studies favored PRP to facilitate the graft healing, improve the harvest site morbidity and prevent tunnel widening. In summary, moderate quality of evidence suggested that PRP could provide short-term but not long-term clinically important pain reduction.
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Reconstrucción del Ligamento Cruzado Anterior/métodos , Plasma Rico en Plaquetas/metabolismo , Humanos , Medición de RiesgoRESUMEN
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. METHODS: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. RESULTS: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. CONCLUSIONS: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.
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Necrosis de la Cabeza Femoral/patología , Lipoproteínas LDL/metabolismo , Necrosis de la Cabeza Femoral/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Osteocitos/metabolismo , Osteocitos/patología , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
We aimed to explore the relationship between pulmonary artery distensibility obtained from computed tomography pulmonary angiography (CTPA) and short-term adverse clinical outcomes in patients with acute pulmonary embolism (APE). We included patients who underwent retrospective electrocardiogram-gated CTPA and were subsequently diagnosed with APE. Patients were categorized into good and poor outcome groups based on short-term clinical outcomes. Pulmonary artery distensibility (AD), right ventricle/left ventricle (RV/LV) ratio, and pulmonary artery obstruction index (PAOI) were measured, and the receiver operating characteristic curves were constructed. Sixty-four patients with APE (good outcome, 46; poor outcome, 18) were enrolled. AD, RV/LV ratio, and PAOI differed significantly between groups (P < 0.05). Pulmonary artery AD in the good outcome group was greater than that in the poor outcome group (P < 0.001). The poor outcome group exhibited a higher RV/LV ratio and PAOI than the good outcome group (P < 0.05). AD and PAOI were independent predictors of adverse clinical outcomes. Areas under the curve for AD and PAOI were 0.860 (95% confidence interval [CI]: 0.750-0.934) and 0.675 (95%CI: 0.546-0.786), and the combined curve of the AD and RV/LV ratio was 0.906 (95%CI: 0.806-0.965). The calibration curve showed a combined curve superior to the other curves. The decision curve showed high clinical application value of the combined curve. Retrospective electrocardiogram-gated CTPA-derived AD could serve as an indicator for predicting short-term adverse clinical outcomes in APE. Combining AD and PAOI has a high predictive value for short-term adverse clinical outcomes.
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Hominidae , Embolia Pulmonar , Humanos , Animales , Arteria Pulmonar , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Enfermedad AgudaRESUMEN
The global prevalence of osteoporosis is being exacerbated by the increasing number of aging societies and longer life expectancies. In response, numerous drugs have been developed in recent years to mitigate bone resorption and enhance bone density. Nonetheless, the efficacy and safety of these pharmaceutical interventions remain constrained. Corylin (CL), a naturally occurring compound derived from the anti-osteoporosis plant Psoralea corylifolia L., has exhibited promising potential in impeding osteoclast differentiation. This study aims to evaluate the effect and molecular mechanisms of CL regulating osteoclast differentiation in vitro and its potential as a therapeutic agent for osteoporosis treatment in vivo. Our investigation revealed that CL effectively inhibits osteoclast formation and their bone resorption capacity by downregulating the transcription factors NFATc1 and c-fos, consequently resulting in the downregulation of genes associated with bone resorption. Furthermore, it has been observed that CL can effectively mitigate the migration and fusion of pre-osteoclast, while also attenuating the activation of mitochondrial mass and function. The results obtained from an in vivo study have demonstrated that CL is capable of attenuating the bone loss induced by ovariectomy (OVX). Based on these significant findings, it is proposed that CL exhibits considerable potential as a novel drug strategy for inhibiting osteoclast differentiation, thereby offering a promising approach for the treatment of osteoporosis.
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Resorción Ósea , Diferenciación Celular , Osteoclastos , Osteoporosis , Animales , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoporosis/tratamiento farmacológico , Diferenciación Celular/efectos de los fármacos , Ratones , Resorción Ósea/tratamiento farmacológico , Femenino , Ovariectomía/efectos adversos , Factores de Transcripción NFATC/metabolismo , Factores de Transcripción NFATC/genética , Células RAW 264.7 , Osteogénesis/efectos de los fármacos , FlavonoidesRESUMEN
The aim of the present study was to determine whether coronary stenosis and computed tomography-derived fractional flow reserve (CT-FFR), detected by coronary computed tomography angiography (CCTA), can potentially contribute to distinguish acute myocardial infarction (AMI) from unstable angina (UA). The study retrospectively collected data from consecutive patients who were admitted with obstructive coronary artery disease (CAD) and who received CCTA and invasive coronary angiography (ICA) as part of their clinical workup. According to the inclusion criteria, the patients were divided into the AMI group and UA group, and the basic clinical data, CCTA stenosis degree and CT-FFR values were compared between the two groups. Univariate and multivariate logistic regression methods were used to analyze the association between ≥70% CCTA stenosis, ≤0.80 CT-FFR and AMI. A diagnostic model of AMI was established (model 1, ≤0.80 CT-FFR; model 2, ≥70% CCTA stenosis; and model 3, ≤0.80 CT-FFR combined with ≥70% CCTA stenosis), and the diagnostic efficacy of the three models for AMI was compared. The significance level was set at P<0.05. A total of 116 participants were finally enrolled in this study. There were 37 patients in the AMI group, with an average age of 62.06±7.74 years, and 79 patients in the UA group, with an average age of 58.11±10.0 years; there was no significant difference in age (P>0.05). The multivariate regression analysis revealed that ≤0.80 CT-FFR (HR=28.074; 95% CI: 5.712-137.973; P<0.001), and ≥70% CCTA stenosis (HR=10.796; 95% CI: 2.566-45.425; P=0.001) were independent risk factors for AMI. The diagnostic model of ≤0.80 CT-FFR combined with ≥70% CCTA stenosis (AUC=0.914; 95% CI: 0.847-0.958) exhibited increased diagnosis performance than the ≤0.80 CT-FFR model (AUC=0.865; 95% CI: 0.790-0.922; P=0.0060) and the ≥70% CCTA stenosis model (AUC=0.827; 95% CI: 0.745-0.891; P=0.0008). Collectively, it was demonstrated that ≤0.80 CT-FFR and ≥70% CCTA stenosis were independent risk factors for the diagnosis of AMI, and the combination of CT-FFR and CCTA stenosis further improved AMI diagnosis performance.
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CT-based flow reserve fraction (CT-FFR) and CT perfusion (CTP), as a complement to coronary computed tomographic angiography (CCTA) have been revealed to be associated with the prognosis of patients with obstructive coronary artery disease (CAD). However, the prognostic value of coronary stenosis combined with CT-FFR and resting-state CTP based on CCTA for major adverse cardiac events (MACE) is not known and requires further investigation. Fifty-two patients with obstructive CAD (50%-90% stenosis) examined by CCTA were retrospectively collected and followed-up for the occurrence of MACE. Logistic regression was performed to analyze the effects of the degree of coronary stenosis, resting-state CTP, and CT-FFR in predicting the risk of MACE. MACE prediction models were developed, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive validity of different models for MACE. Ethics approval was provided by the First Affiliated Hospital of Hebei North University (Zhangjiakou, China; No. K2020237). Logistic regression analysis showed that coronary artery stenosis ≥ 70%, CT-FFR ≤ 0.80, and perfusion index (PI) were independent predictors for MACE in patients with obstructive CAD (P < .05). The model based on coronary stenosis combined with PI and CT-FFR (AUC = 0.944) was better than those based on the degree of coronary stenosis combined with PI (AUC = 0.874), coronary stenosis degree combined with CT-FFR (AUC = 0.895), and any single index (P < .05). The combined model established by coronary stenosis, CT-FFR, and resting-state CTP based on a "1-stop" CCTA examination for predicting MACE among patients with obstructive CAD has good diagnostic efficacy and shows incremental discriminatory power.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Retrospectivos , Angiografía Coronaria/métodos , Estenosis Coronaria/complicaciones , Estenosis Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Angiografía por Tomografía Computarizada/métodos , Valor Predictivo de las PruebasRESUMEN
Fibroblast activation protein (Fap) is a serine protease that degrades denatured type I collagen, α2-antiplasmin and FGF21. Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin (Oln). Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis (RA). However, whether Fap plays a critical role in osteoarthritis (OA) remains poorly understood. Here, we found that Fap is significantly elevated in osteoarthritic synovium, while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice. Mechanistically, we found that Fap degrades denatured type II collagen (Col II) and Mmp13-cleaved native Col II. Intra-articular injection of rFap significantly accelerated Col II degradation and OA progression. In contrast, Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA. Genetic deletion of Oln significantly exacerbated OA progression, which was partially rescued by Fap deletion or inhibition. Intra-articular injection of rOln significantly ameliorated OA progression. Taken together, these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.
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Bone-resorbing osteoclasts are essential for skeletal remodelling, and the hyperactive formation and function of osteoclasts are common in bone metabolic diseases, especially postmenopausal osteoporosis. Therefore, regulating the osteoclast differentiation is a major therapeutic target in osteoporosis treatment. Icariin has shown potential osteoprotective effects. However, existing studies have reported limited bioavailability of icariin, and the material basis of icariin for anti-osteoporosis is attributed to its metabolites in the body. Here, we compared the effects of icariin and its metabolites (icariside I, baohuoside I, and icaritin) on osteoclastogenesis by high-content screening followed by TRAP staining and identified baohuoside I (BS) with an optimal effect. Then, we evaluated the effects of BS on osteoclast differentiation and bone resorptive activity in both in vivo and in vitro experiments. In an in vitro study, BS inhibited osteoclast formation and bone resorption function in a dose-dependent manner, and the elevated osteoclastic-related genes induced by RANKL, such as NFATc1, cathepsin K, RANK, and TRAP, were also attenuated following BS treatment. In an in vivo study, OVX-induced bone loss could be prevented by BS through interrupting the osteoclast formation and activity in mice. Furthermore, mechanistic investigation demonstrated that BS inhibited osteoclast differentiation by ameliorating the activation of the MAPK and NF-kB pathways and reducing the expression of uPAR. Our study demonstrated that baohuoside I could inhibit osteoclast differentiation and protect bone loss following ovariectomy.
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PURPOSE: Oxidative stress-induced chondrocyte apoptosis and extracellular matrix (ECM) degradation plays an important role in the progression of osteoarthritis (OA). Bardoxolone methyl (BM), a semisynthetic triterpenoid, exerts strong effect against oxidative stress. The purpose of the present study was to determine the effectiveness of bardoxolone-methyl (BM) in preventing oxidative stress-induced chondrocyte apoptosis and extracellular ECM degradation in vitro and the role of alleviating OA progression in vivo. METHODS: Oxidative damage was induced by 25 mM tert-butyl hydroperoxide (TBHP) for 24 h in rat chondrocytes. 0.025 and 0.05 µM bardoxolone-methyl (BM) were used in vitro treatment. Ex-vivo cartilage explant model was established to evaluate the effect of BM on oxidative stress-induced ECM degradation. The mouse OA model was induced by surgical destabilization of the medial meniscus. RESULTS: In vitro, 0.025 and 0.05 µM BM reduced TBHP-induced excessive ROS generation, improved cell viability, increased malondialdehyde level and decreased superoxide dismutase level. 0.025 and 0.05 µM BM prevented TBHP-induced mitochondrial damage and apoptosis in chondrocytes BM activated heme oxygenase-1 (HO-1)/NADPH quinone oxidoreductase 1 (NOQ1) signaling pathway through targeting nuclear factor erythroid derived-2-related factor 2 (Nrf2). Additionally, BM treatment enhanced the expression levels of aggrecan and collagen II and inhibited the expression levels of matrix metalloproteinase 9 (MMP 9), MMP 13, Bax and cleaved-caspase-3. BM increased proteoglycan staining area and IOD value in ex vivo cultured experiment cartilage explants and improved the OARSI score, stands, max contact mean intensity, print area and duty cycle in mouse OA model. CONCLUSION: BM prevented oxidative stress-induced chondrocyte apoptosis and ECM degradation in vitro and alleviated OA in vivo, suggesting that BM serves as an effective drug for treatment with OA.
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Artritis Experimental/tratamiento farmacológico , Ácido Oleanólico/análogos & derivados , Osteoartritis/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Artritis Experimental/patología , Cartílago/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Condrocitos/patología , Relación Dosis-Respuesta a Droga , Matriz Extracelular/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ácido Oleanólico/administración & dosificación , Ácido Oleanólico/farmacología , Osteoartritis/patología , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: As a dental material, polyetheretherketone (PEEK) is bioinert that does not induce cellular response and bone/gingival tissues regeneration. This study was to develop bioactive coating on PEEK and investigate the effects of coating on cellular response. MATERIALS AND METHODS: Tantalum pentoxide (TP) coating was fabricated on PEEK surface by vacuum evaporation and responses of rat bone marrow mesenchymal stem (RBMS) cells/human gingival epithelial (HGE) were studied. RESULTS: A dense coating (around 400 nm in thickness) of TP was closely combined with PEEK (PKTP). Moreover, the coating was non-crystalline TP, which contained many small humps (around 10 nm in size), exhibiting a nanostructured surface. In addition, the roughness, hydrophilicity, surface energy, and protein adsorption of PKTP were remarkably higher than that of PEEK. Furthermore, the responses (adhesion, proliferation, and osteogenic gene expression) of RBMS cells, and responses (adhesion and proliferation) of HGE cells to PKTP were remarkably improved in comparison with PEEK. It could be suggested that the nanostructured coating of TP on PEEK played crucial roles in inducing the responses of RBMS/HGE cells. CONCLUSION: PKTP with elevated surface performances and outstanding cytocompatibility might have enormous potential for dental implant application.
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Células Epiteliales/citología , Encía/citología , Cetonas/farmacología , Células Madre Mesenquimatosas/citología , Nanoestructuras/química , Óxidos/farmacología , Polietilenglicoles/farmacología , Tantalio/farmacología , Adsorción , Fosfatasa Alcalina/metabolismo , Animales , Benzofenonas , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/ultraestructura , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/enzimología , Nanoestructuras/ultraestructura , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Polímeros , Ratas Sprague-Dawley , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Difracción de Rayos XRESUMEN
PURPOSE: Osteoarthritis (OA) is a progressive disease characterized by pain and impaired joint functions. Engeletin is a natural compound with anti-inflammatory and antioxidant effects on other diseases, but the effect of engeletin on OA has not been evaluated. This study aimed to elucidate the protective effect of engeletin on cartilage and the underlying mechanisms. METHODS: Chondrocytes were isolated from rat knee cartilage, and TNF-α was used to simulate OA in vitro. After treatment with engeletin, the expression of extracellular matrix (ECM) components (collagen II and aggrecan) and matrix catabolic enzymes (MMP9 and MMP3) was determined by Western blotting and qPCR. Chondrocyte apoptosis was evaluated using Annexin V-FITC/PI and flow cytometry. Apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were evaluated by Western blotting. The mitochondrial membrane potential of chondrocytes was measured with JC-1, and intracellular reactive oxygen species (ROS) levels were determined with DCFH-DA. Changes in signaling pathways (Nrf2, NF-κB and MAPK) were evaluated by Western blotting. In vivo, anterior cruciate ligament transection (ACLT) was used to induce the rat OA model, and engeletin was administered intraarticularly. The therapeutic effect of engeletin was analyzed by histopathological analysis. RESULTS: Pretreatment with engeletin alleviated TNF-α-induced inhibition of ECM components (collagen II and aggrecan) and upregulation of matrix catabolic enzymes (MMP9 and MMP3). Engeletin ameliorated chondrocyte apoptosis by inhibiting Bax expression and upregulating Bcl-2 expression. Engeletin maintained the mitochondrial membrane potential of chondrocytes and scavenged intracellular ROS by activating the Nrf2 pathway. The NF-κB and MAPK pathways were inhibited by treatment with engeletin. In vivo, ACLT-induced knee OA in rats was alleviated by intraarticular injection of engeletin. CONCLUSION: Engeletin ameliorated OA in vitro and in vivo. It may be a potential therapeutic drug for OA.
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Articular cartilage repair remains a great clinical challenge. Tissue engineering approaches based on decellularized extracellular matrix (dECM) scaffolds show promise for facilitating articular cartilage repair. Traditional regenerative approaches currently used in clinical practice, such as microfracture, mosaicplasty, and autologous chondrocyte implantation, can improve cartilage repair and show therapeutic effect to some degree; however, the long-term curative effect is suboptimal. As dECM prepared by proper decellularization procedures is a biodegradable material, which provides space for regeneration tissue growth, possesses low immunogenicity, and retains most of its bioactive molecules that maintain tissue homeostasis and facilitate tissue repair, dECM scaffolds may provide a biomimetic microenvironment promoting cell attachment, proliferation, and chondrogenic differentiation. Currently, cell-derived dECM scaffolds have become a research hotspot in the field of cartilage tissue engineering, as ECM derived from cells cultured in vitro has many advantages compared with native cartilage ECM. This review describes cell types used to secrete ECM, methods of inducing cells to secrete cartilage-like ECM and decellularization methods to prepare cell-derived dECM. The potential mechanism of dECM scaffolds on cartilage repair, methods for improving the mechanical strength of cell-derived dECM scaffolds, and future perspectives on cell-derived dECM scaffolds are also discussed in this review.
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Cartílago Articular/cirugía , Matriz Extracelular/fisiología , Ingeniería de Tejidos/métodos , Andamios del Tejido , Cartílago Articular/lesiones , Condrogénesis , HumanosRESUMEN
PURPOSE: Intervertebral disc degeneration (IDD) is one of the most prevalent musculoskeletal disorders. The nucleus pulposus is the major component of the intervertebral disc, and nucleus pulposus cells (NPCs) play a significant role in the normal functioning of the intervertebral disc. Reactive oxygen species (ROS) generation, inflammation and extracellular matrix degradation in NPCs contribute to the degeneration of intervertebral discs. Acacetin is a drug that exerts antioxidant and anti-inflammatory effects on many types of cells. However, whether acacetin can relieve the degeneration of NPCs remains unknown. METHODS: NPCs were extracted from rat intervertebral discs. The NPCs were treated with tert-butyl peroxide (TBHP) to simulate a high-ROS environment, and acacetin was subsequently added. The contents of ROS, inflammatory mediators (COX-2, iNOS) and extracellular matrix components (aggrecan, collagen II, MMP13, MMP9, MMP3) were measured. Components of related signaling pathways (Nrf2, MAPK) were also evaluated. To determine the effect of acacetin in vivo, we simulated disc degeneration via needle puncture. Acacetin was then applied intraperitoneally, and the degenerative status was evaluated using MRI and histopathological analysis. RESULTS: In vitro, acacetin alleviated TBHP-induced ROS generation and upregulated the expression of antioxidant proteins, including HO-1, NQO1, and SOD. In addition, acacetin relieved the TBHP-induced generation of inflammatory mediators (COX-2, iNOS) and degradation of the extracellular matrix (aggrecan, collagen II, MMP13, MMP9, and MMP3). Acacetin exerted its effect by activating the Nrf2 pathway and inhibiting p38, JNK and ERK1/2 phosphorylation. In vivo, acacetin ameliorated puncture-induced disc degeneration in a rat tail model, which was evaluated using MRI and histopathological analysis. CONCLUSION: Acacetin alleviated IDD in vitro and in vivo and may have the potential to be developed as an effective treatment for IDD.
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Matriz Extracelular/efectos de los fármacos , Flavonas/farmacología , Mediadores de Inflamación/farmacología , Inflamación/tratamiento farmacológico , Degeneración del Disco Intervertebral/tratamiento farmacológico , Núcleo Pulposo/efectos de los fármacos , Animales , Células Cultivadas , Matriz Extracelular/metabolismo , Flavonas/administración & dosificación , Inflamación/metabolismo , Mediadores de Inflamación/administración & dosificación , Inyecciones Intraperitoneales , Degeneración del Disco Intervertebral/metabolismo , Masculino , Núcleo Pulposo/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Currently published papers regarding the relationship between integrin alpha V (ITGAV) gene polymorphisms and rheumatoid arthritis (RA) are contradictory. The aim of this meta-analysis was to evaluate the associations between the ITGAV gene polymorphisms and RA risk. METHODS: Comprehensive literature search based on four electronic databases was applied to retrieve all related data. Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess associations between ITGAV gene polymorphisms and RA. RESULTS: Six articles involving 5794 RA patients and 5297 healthy controls were included in this meta-analysis. The combined data indicated that rs3911238, rs3738919, rs3768777, and rs10174098 in ITGAV gene were not associated with RA risk in the overall population. However, stratification analysis by ethnicity suggested that rs3768777 was related with risk of RA among Caucasian population (OR 3.51, 95%CI 2.06, 5.97; P < 0.0001), but not among Asian population (OR 1.06, 95%CI 0.67, 1.69; P = 0.81). CONCLUSIONS: Our meta-analysis confirmed that the ITGAV gene rs3768777 polymorphisms might be a risk factor among Caucasians. However, larger-scale studies in Caucasian population are still warranted to confirm the findings of our study.
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Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad , Integrinas/genética , Polimorfismo de Nucleótido Simple , Artritis Reumatoide/epidemiología , Artritis Reumatoide/inmunología , Pueblo Asiatico/genética , Humanos , Integrinas/inmunología , Factores de Riesgo , Población Blanca/genéticaRESUMEN
Magnesium and Mg-based alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. However, the drawbacks of these materials include high hydrogen gas production, unexpected corrosion resistance, and insufficient mechanical strength duration. Surface modification can protect these biomaterials and induce osteogenesis. In this work, a SrHPO4 coating was developed for our patented biodegradable Mg-Nd-Zn-Zr alloy (abbr. JDBM) through a chemical deposition method. The coating was characterized by in vitro immersion, ion release, and cytotoxicity tests, which showed a slower corrosion behavior and excellent cell viability. RNA sequencing of MC3T3E1 cells treated with SrHPO4-coated JDBM ion release test extract showed increased Tlr4, followed by the activation of the downstream PI3K/Akt signaling pathway, causing proliferation and growth of pre-osteoblasts. An intramedullary nail (IMN) was implanted in a femoral fracture rat model. Mechanical test, radiological and histological analysis suggested that SrHPO4-coated JDBM has superior mechanical properties, induces more bone formation, and decreases the degradation rate compared with uncoated JDBM and the administration of TLR4 inhibitor attenuated the new bone formation for fracture healing. SrHPO4 is a promising coating for JDBM implants, particularly for long-bone fractures.
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Fracturas del Fémur , Osteogénesis , Aleaciones , Animales , Materiales Biocompatibles Revestidos , Corrosión , Ensayo de Materiales , Fosfatidilinositol 3-Quinasas , RatasRESUMEN
BACKGROUND: Osteoarthritis (OA) is characterized by inflammation and extracellular matrix (ECM) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults. Urolithin A (UA) has been widely reported for its anti-inflammatory properties in several chronic diseases. However, the effects of UA on OA remain unclear. The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1ß (IL-1ß)-induced chondrocytes. RESULTS: No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1ß stimulation in micromasses. Moreover, UA promoted the expression of anabolic factors including Sox-9, Collagen II, and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) in rat chondrocytes. Protective effects of UA were also observed in ex vivo organ culture of articular cartilage. Mechanistically, IL-1ß significantly activated and upregulated the expression of p-ERK 1/2, p-JNK, p-P38, and p-P65, while UA protected chondrocytes against IL-1ß-induced injury by activating the mitogen-activated kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways. CONCLUSION: Our results provide the evidence that UA could attenuate IL-1ß-induced cell injury in chondrocytes via its anti-inflammatory action. UA may be a promising therapeutic agent in the treatment of OA.
RESUMEN
Hypertrophic scar (HPS) is a manifestation of abnormal tissue repair, representing excessive extracellular matrix production and abnormal function of fibroblasts, for which no satisfactory treatment is available at present. Here we identified a natural product of flavonoid, dihydromyricetin, could effectively attenuate HPS formation. We showed that local intradermal injection of dihydromyricetin (50⯵M) reduced the gross scar area, cross-sectional size of the scar and the scar elevation index in a mechanical load-induced mouse model. In addition, dihydromyricetin treatment also markedly decreased collagen density of the scar tissue. Furthermore, both in vitro and in vivo study both demonstrated that dihydromyricetin inhibited the proliferation, activation, contractile and migration abilities of hypertrophic scar-derived fibroblasts (HSFs) but did not affect HSFs apoptosis. Western blot analysis revealed that dihydromyricetin could down-regulate the phosphorylation of Smad2 and Smad3 of TGF-ß signaling. Such bioactivity of dihydromyricetin may result from its selective binding to the catalytic region of activin receptor-like kinase 5 (ALK5), as suggested by the molecular docking study and kinase binding assay (12.26⯵M). Above all, dihydromyricetin may prove to be a promising agent for the treatment of HPS and other fibroproliferative disorders.