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BACKGROUND: Tendon calcification is a common disease, and it could happen in the tendons of the shoulder, wrist, etc. However, tendon calcification in the superior and inferior gemellus is rare, and in this region is likely to be misdiagnosed. CASE PRESENTATION: Here, our case report first reported a 53-year-old female patient with an unusual case of calcific tendinitis of the gemellus superior and gemellus inferior muscles. The patient presented with severe pain in the right hip and lower extremities, not relieved using nonsteroidal anti-inflammatory drugs (NSAIDs). The preoperative physical examination indicated an abnormality in the hip joint. Preoperative imaging confirmed the results of the physical examination and showed a right hip lesion. We did not make a definite diagnosis preoperatively but considered that the patient might have an osteochondroma. However, surgical findings indicated that the lesion was not in the hip capsule on subsequent arthroscopic surgery, which suggested that the preoperative diagnosis might be wrong. We opened the posterior capsule and found a "toothpaste-like" lesion in the superior and inferior gemellus muscles' tendon. We thought this might be the calcified tendon. Then the arthroscopic surgery was finished to remove the lesion, and the removed tissue was sent to the pathology department for pathological examination. The pathological report confirmed the diagnosis of the calcified tendon. Postoperative follow-up was conducted. The effect of the operation was noticeable. Postoperative symptoms were relieved. CONCLUSIONS: Calcification of the tendons of the superior and inferior gemellus muscles can be easily misdiagnosed, and the disease can be treated minimally with arthroscopy.
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Tendinopatía , Artroscopía/métodos , Femenino , Cadera , Humanos , Persona de Mediana Edad , Tendinopatía/cirugía , Tendones/cirugía , Articulación de la MuñecaRESUMEN
Small nucleolar RNA host gene 6 (SNHG6) is a newly discovered long non-coding RNA (lncRNA), while the regulatory mechanism of SNHG6 in chondrosarcoma is largely unknown. Here we found that SNHG6 expression was upregulated and showed positive correlation with the progression of chondrosarcoma. Functional assays demonstrated that SNHG6 was required for the proliferation, migration, and invasion of chondrosarcoma cells. Mechanistic study revealed that SNHG6 could recruit EZH2 and maintain high level of H3K27me3 to repress the transcription of tumor-suppressor genes, including KLF6. KLF6 was found to bind to the promoter region of SP1 and restrained its transcription, while SP1 could be recruited to the promoter region of SNHG6 and promoted its transcription to form a positive loop. In summary, this study reveals that SP1-induced SNHG6 forms a positive loop to facilitate the carcinogenesis of chondrosarcoma through the suppression of KLF6 by recruiting EZH2, which manifests the oncogenic function of SNHG6 in chondrosarcoma.
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Neoplasias Óseas/metabolismo , Condrosarcoma/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Factor 6 Similar a Kruppel/metabolismo , ARN Largo no Codificante/metabolismo , Factor de Transcripción Sp1/metabolismo , Animales , Neoplasias Óseas/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Condrosarcoma/genética , Proteína Potenciadora del Homólogo Zeste 2/genética , Humanos , Factor 6 Similar a Kruppel/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , ARN Largo no Codificante/genética , Factor de Transcripción Sp1/genética , TransfecciónRESUMEN
Since December 2019, COVID-19, an acute infectious disease, has gradually become a global threat. We report a case of thoracolumbar fractures (T12 and L1) and incomplete lower limb paralysis in a patient with COVID-19. After a series of conservative treatment which did not work at all, posterior open reduction and pedicle screw internal fixation of the thoracolumbar fracture were performed in Wuhan Union Hospital. Three weeks later, the patient could stand up and the pneumonia is almost cured. We successfully performed a surgery in a COVID-19 patient, and to our knowledge it is the first operation for a COVID-19 patient ever reported.
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Betacoronavirus , Infecciones por Coronavirus/complicaciones , Vértebras Lumbares/lesiones , Parálisis/cirugía , Neumonía Viral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/lesiones , COVID-19 , Fijación Interna de Fracturas , Humanos , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Pandemias , Tornillos Pediculares , SARS-CoV-2 , Vértebras Torácicas/cirugíaAsunto(s)
Betacoronavirus , Infecciones por Coronavirus , Enfermedades Musculoesqueléticas , Pandemias , Neumonía Viral , COVID-19 , Consenso , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Epidemias , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Enfermedades Musculoesqueléticas/complicaciones , Enfermedades Musculoesqueléticas/terapia , Pandemias/prevención & control , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , SARS-CoV-2RESUMEN
Osteosarcoma is the most common primary malignant bone tumor mainly occurred in children and adolescence, and chemotherapy is limited for the side effects and development of drug resistance. Advances in nanotechnology and knowledge of cancer biology have led to significant improvements in developing tumor-targeted drug delivery nanocarriers, and some have even entered clinically application. Delivery of chemotherapeutic agents by functionalized smart nanocarriers could protect the drugs from rapid clearance, prolong the circulating time, and increase the drug concentration at tumor sites, thus enhancing the therapeutic efficacy and reducing side effects. Various drug delivery nanocarriers have been designed and tested for osteosarcoma treatment, but most of them are still at experimental stage, and more further studies are needed before clinical application. In this present review, we briefly describe the types of commonly used nanocarriers in osteosarcoma treatment, and discuss the strategies for osteosarcoma-targeted delivery and controlled release of drugs. The application of nanoparticles in the management of metastatic osteosarcoma is also briefly discussed. The purpose of this article is to present an overview of recent progress of nanoscale drug delivery platforms in osteosarcoma, and inspire new ideas to develop more effective therapeutic options.
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BACKGROUND: The optimal reconstructive method after diaphyseal malignant bone tumor resection remains controversial. This multicenter clinical study was designed to investigate the clinical value and complications of segmental prosthesis in the repair of diaphyseal defects. METHODS: We present 49 patients from three clinical centers treated with wide resection for primary or metastatic bone tumors involving the diaphysis of the femur, tibia, humerus, or ulna, followed by reconstruction using a modular intramedullary segmental prosthesis. RESULTS: Enrolled patients included 23 men and 26 women with a mean age of 63.3 years. Of these, seven patients had primary bone tumors and 42 patients had metastatic lesions. At the mean follow-up of 13.7 months, 17 patients were alive, 31 patients were deceased due to tumor progression, and one patient was dead of another reason. There were eight nononcologic complications (two with radial nerve injury, three with delayed incision healing, two with aseptic loosening in the proximal humerus prosthetic stem and one with structural failure) and three oncologic complications (three with primary tumor recurrence) among all patients. The incidence of complications in primary tumor patients (4/7, 57.1%) was higher than that in patients with metastatic tumors (7/42, 16.7%) (p = 0.036). Aseptic loosening and mechanical complications were not common for patients with primary tumors, although the reconstruction length difference was statistically significant (p = 0.023). No statistically significant differences were observed in limb function, while the mean musculoskeletal tumor society score was 21.2 in femora, 19.6 in humeri, and 17.8 in tibiae (p = 0.134). CONCLUSIONS: Segmental prostheses represent an optional method for the reconstruction of diaphyseal defects in patients with limited life expectancy. Segmental prostheses in the humerus experienced more complications than those used to treat lesions in the femur.
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Neoplasias Óseas/cirugía , Diáfisis/cirugía , Procedimientos de Cirugía Plástica/métodos , Prótesis e Implantes , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Diáfisis/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prótesis e Implantes/efectos adversos , Falla de Prótesis , Implantación de Prótesis , Procedimientos de Cirugía Plástica/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Mixed reality (MR) technology is a new digital holographic image technology, which appears in the field of graphics after virtual reality (VR) and augmented reality (AR) technology, a new interdisciplinary frontier. As a new generation of technology, MR has attracted great attention of clinicians in recent years. The emergence of MR will bring about revolutionary changes in medical education training, medical research, medical communication, and clinical treatment. At present, MR technology has become the popular frontline information technology for medical applications. With the popularization of digital technology in the medical field, the development prospects of MR are inestimable. The purpose of this review article is to introduce the application of MR technology in the medical field and prospect its trend in the future.
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Tecnología Biomédica/métodos , Atención a la Salud/métodos , Educación Médica/métodos , Simulación por Computador , Holografía , Humanos , Imagenología Tridimensional , Realidad VirtualRESUMEN
Due to the ethical concern and inability to detect inner stress distributions of intervertebral disc (IVD), traditional methods for investigation of intervertebral disc degeneration (IVDD) have significant limitations. Many researchers have demonstrated that finite element analysis (FEA) is an effective tool for the research of IVDD. However, the specific application of FEA for investigation of IVDD has not been systematically elucidated before. In the present review, we summarize the current finite element models (FEM) used for the investigation of IVDD, including the poroelastic nonlinear FEM, diffusive-reactive theory model and cell-activity coupled mechano-electrochemical theory model. We further elaborate the use of FEA for the research of IVDD pathogenesis especially for nutrition and biomechanics associated etiology, and the biological, biomechanical and clinical influences of IVDD. In addition, the application of FEA for evaluation and exploration of various treatments for IVDD is also elucidated. We conclude that FEA is an excellent technique for research of IVDD, which could be used to explore the etiology, biology and biomechanics of IVDD. In the future, FEA may help us to achieve the goal of individualized precision therapy.
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Degeneración del Disco Intervertebral/diagnóstico , Degeneración del Disco Intervertebral/fisiopatología , Animales , Fenómenos Biomecánicos , Simulación por Computador , Modelos Animales de Enfermedad , Análisis de Elementos Finitos , HumanosRESUMEN
This study is aimed to explore the clinical application of the guiding template designed by three-dimensional printing data for the insertion of sacroiliac screws. A retrospective study of 7 cases (from July 2016 to December 2016), in which the guiding template printed by the threedimensional printing technique was used for the insertion of sacroiliac screws of patients with posterior ring injuries of pelvis, was performed. Totally, 4 males and 3 females were included in template group, aged from 38 to 65 years old (mean 50.86±8.90). Of them, 5 had sacral fractures (3 with Denis type I and 2 with type II) and 2 the separation of sacroiliac joint. Guiding templates were firstly made by the three-dimensional printing technique based on the pre-operative CT data. Surgical operations for the stabilization of pelvic ring by applying the guiding templates were carried out. A group of 8 patients with sacroiliac injuries treated by percutaneous sacroiliac screws were analyzed as a control group retrospectively. The time of each screw insertion, volume of intra-operative blood loss, and the exposure to X ray were analyzed and the Matta's radiological criteria were used to evaluate the reduction quality. The Majeed score was used to evaluate postoperative living quality. The visual analogue scale (VAS) was applied at different time points to judge pain relief of coccydynia. All the 7 patients in the template group were closely followed up radiographically and clinically for 14 to 20 months, mean (16.57±2.44) months. Totally 9 sacroiliac screws for the S1 and S2 vertebra were inserted in the 7 patients. The time length for each screw insertion ranged from 450 to 870 s, mean (690.56±135.68) s, and the number of times of exposure to X ray were 4 to 8, mean (5.78±1.20). The intra-operative blood loss ranged from 45 to 120 mL, mean (75±23.32) mL. According to Matta's radiology criteria, the fracture and dislocation reduction were excellent in 6 cases and good in 1. The pre-operative VAS score ranged from 5.2 to 8.1, mean (7.13±1.00). The average one-week/six-month post-operative VAS was (5.33±0.78) and (1.33±0.66), respectively (P<0.05 when compared with pre-operative VAS). The 12-month postoperative Majeed score ranged from 86 to 92, mean (90.29±2.21). The three-dimensional printed guiding template for sacroiliac screw insertion, which could significantly shorten the operation time, provide a satisfied outcome of the stabilization of the pelvic ring, and protect doctors and patients from X-ray exposure, might be a practical and valuable new clinical technique.
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Fijación Interna de Fracturas/métodos , Articulación Sacroiliaca/cirugía , Adulto , Anciano , Tornillos Óseos , Femenino , Fracturas Óseas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Impresión Tridimensional , Radiografía/métodos , Estudios Retrospectivos , Articulación Sacroiliaca/lesiones , Sacro/lesiones , Sacro/cirugíaRESUMEN
BACKGROUD/AIMS: Abnormal activation of the Wnt/ß-catenin signaling, which may be antagonized by the members of secreted frizzled-related proteins family (SFRPs), is implicated in tumor occurrence and development. However, the function of SFRP5 relating to Wnt/ß-catenin pathway in chondrosarcoma is not clear yet. This study was undertaken to investigate the potential role of SFRP5 promoter methylation in chondrosarcoma metastasis and invasion through activating canonical Wnt signaling pathway. METHODS AND RESULTS: The results demonstrated that SFRP5 promoter was hypermethylated and SFRP5 expression was significantly reduced in chondrosarcoma cell lines at the mRNA and protein levels. The canonical Wnt/ß-catenin signaling was observably activated with ß-catenin stabilization by dephosphorylation and translocation into the nuclear. 5-Aza-2'-deoxycytidine (5-Aza-dC), the DNA methyltransferase inhibitor, significantly inhibited the proliferation of chondrosarcoma cells by cell cycle arrest through repressing the methylation of SFRP5 and promoting its expression. Both 5-Aza-dC treatment and SFRP5 overexpression could significantly inhibited the metastasis and invasion of chondrosarcoma cells by inactivating Wnt/ß-catenin signaling pathway and promoting chondrosarcoma cells mesenchymal-epithelial transition (MET). 5-Aza-dC also inhibited the xenograft growth and lung metastasis of chondrosarcoma cells in vivo via suppressing SFRP5 promotor methylation, inactivating Wnt/ß-catenin pathway and inducing epithelial markers expression. CONCLUSION: All of our results revealed the epigenetic silencing of SFRP5 by promoter methylation plays pivotal roles in chondrosarcoma development and metastasis through SFRP5/Wnt/ß-catenin signaling axis. Modulation of their levels may serve as potential targets and diagnostic tools for novel therapeutic strategies of chondrosarcoma.
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Condrosarcoma/genética , Condrosarcoma/patología , Epigénesis Genética/genética , Proteínas del Ojo/genética , Proteínas de la Membrana/genética , Invasividad Neoplásica/genética , Metástasis de la Neoplasia/genética , Vía de Señalización Wnt/genética , Proteínas Adaptadoras Transductoras de Señales , Animales , Antimetabolitos Antineoplásicos/química , Antimetabolitos Antineoplásicos/farmacología , Azacitidina/análogos & derivados , Azacitidina/química , Azacitidina/farmacología , Células Cultivadas , Condrosarcoma/tratamiento farmacológico , Condrosarcoma/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Epigénesis Genética/efectos de los fármacos , Proteínas del Ojo/antagonistas & inhibidores , Proteínas del Ojo/metabolismo , Humanos , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Relación Estructura-Actividad , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
Silk fibroin (SF) from Bombyx mori has received increasing interest in biomedical fields, because of its slow biodegradability, good biocompatibility, and low immunogenicity. Although SF-based hydrogels have been studied intensively as a potential matrix for tissue engineering, weak gelation performance and low mechanical strength are major limitations that hamper their widespread applicability. Therefore, searching for new strategies to improve the SF gelation property is highly desirable in tissue engineering research. Herein, we report a facile approach to induce rapid gelation of SF by a small peptide gelator (e.g., NapFF). Following the simple mixing of SF and NapFF in water, a stable hydrogel of SF was obtained in a short time period at physiological pH, and the minimum gelation concentration of SF can reach as low as 0.1%. In this process of gelation, NapFF not only can behave itself as a gelator for supramolecular self-assembly, but also can trigger the conformational transition of the SF molecule from random coil to ß-sheet structure via hydrophobic and hydrogen-bonding interactions. More importantly, for the generation of a scaffold with favorable cell-surface interactions, a new peptide gelator (NapFFRGD) with Arg-Gly-Asp (RGD) domain was applied to functionalize SF hydrogel with improved bioactivity for cell adhesion and growth. Following encapsulating the vascular endothelial growth factor (VEGF), the SF gel was subcutaneously injected in mice, and served as an effective matrix to trigger the generation of new blood capillaries in vivo.
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Péptidos/química , Animales , Bombyx , Fibroínas , Hidrogeles , Ratones , Seda , Ingeniería de Tejidos , Factor A de Crecimiento Endotelial VascularRESUMEN
AIMS: Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells. MATERIALS AND METHODS: Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca2+]i) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot. KEY FINDINGS: Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca2+]i. In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells. SIGNIFICANCE: These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD.
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Antipirina/análogos & derivados , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Núcleo Pulposo/efectos de los fármacos , Agrecanos/genética , Animales , Antipirina/administración & dosificación , Antipirina/farmacología , Células Cultivadas , Colágeno Tipo II/genética , Relación Dosis-Respuesta a Droga , Edaravona , Depuradores de Radicales Libres/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/fisiopatología , Potencial de la Membrana Mitocondrial , Núcleo Pulposo/patología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Giant cell tumor of bone (GCT), which frequently occurs in the patients' spine, is relatively prevalent in Chinese population. A group of GCT invades into vessels and appears to be circulating tumor cells (CTCs) responsible for the distal metastasis of the primary tumor. So far the cell surface markers of GCT have not been determined. In the current study, we aimed to identify a novel CTC marker with higher specificity in GCT. TRAIL-R1+ cells were purified from GCT cell lines. The TRAIL-R1+ cells were compared with total GCT cells for tumor sphere formation, chemo-resistance, tumor formation in nude mice, and frequency of developing distal metastases. We found that TRAIL-R1+ GCT cells appeared to be highly enriched for CTCs in GCT. Compared to total GCT cells, TRAIL-R1+ GCT cells generated significantly more tumor spheres in culture, were higher chemo-resistant, and had a higher frequency of being detected in the circulation after subcutaneous transplantation as well as development of distal metastases. Thus, we conclude that TRAIL-R1+ may be a novel CTC marker in GCT. Selective elimination of TRAIL-R1+ GCT cells may improve the current GCT therapy.
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BACKGROUND: The aim of the study was to explore the effects of microRNA-107 (miR-107) by targeting Dkk-1 on osteosarcoma (OS) via the Wnt/ß-catenin signaling pathway. METHODS: OS and adjacent tissues were collected from 67 patients diagnosed with OS. Expressions of miR-107, Dkk-1, LRP5, ß-catenin, and c-Myc were detected by the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The dual-luciferase reporter gene assay was performed to observe the relationship between miR-107 and Dkk-1.Transfected cells were divided into different investigating groups designated as Inhibitor, Mimic, siRNA, Inhibitor + siRNA, negative control (NC), and blank groups. qRT-PCR and Western blotting were used to detect expressions of miR-107, Dkk-1, ß-catenin, Bcl-2, c-Myc, Caspase-3, and PARP. Cell counting kit-8 (CCK-8), flow cytometry (FCM), colony-formation efficiency (CFE), and subcutaneous tumorigenicity assays were all utilized for to determine cell proliferation, apoptosis, colony-forming, and tumorigenic abilities. RESULTS: Dkk-1 is the target gene of miR-107. Decreased expressions of miR-107, LRP5, ß-catenin, and c-Myc, and increased expressions of Dkk-1 were found in OS tissues. The Mimic and siRNA groups exhibited decreased proliferation rates, colony-forming abilities, and tumorigenicity and increased apoptosis rates, whereas the inhibitor group showed opposite trends when compared to the blank group. On the other hand, expressions of miR-107, LRP5, ß-catenin, c-Myc, Caspase-3, and PARP were all elevated in the mimic group, whereas expressions of Dkk-1 and Bcl-2 were reduced; opposite trends were observed in the inhibitor group. CONCLUSION: We conclude that miR-107 is likely to inhibit the occurrence and development of OS by down-regulating Dkk-1 via the Wnt/ß-catenin signaling pathway, providing us with a new therapeutic target for the treatment of OS.
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Péptidos y Proteínas de Señalización Intercelular/metabolismo , MicroARNs/metabolismo , Osteosarcoma/metabolismo , Vía de Señalización Wnt/fisiología , Animales , Apoptosis/fisiología , Caspasa 3/metabolismo , Proliferación Celular/fisiología , Células Cultivadas , Humanos , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Ratones Desnudos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Trasplante de Neoplasias , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Interferente Pequeño , Distribución Aleatoria , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMEN
BACKGROUND: Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. OBJECTIVE: We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. METHODS: miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. RESULTS: We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. CONCLUSION: Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD.
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Colágeno Tipo II/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , MicroARNs/genética , Adolescente , Adulto , Anciano , Western Blotting , Estudios de Casos y Controles , Células Cultivadas , Niño , Colágeno Tipo II/genética , Femenino , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Humanos , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/patología , Masculino , Metaloproteinasa 13 de la Matriz/genética , Persona de Mediana Edad , Proteolisis , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Compression-induced programmed cell death of nucleus pulposus (NP) cells is an important contributor to intervertebral disc degeneration (IDD). Dynamin-related protein 1 (Drp1), a crucial mitochondrial fission protein, triggers programmed necrosis upon cellular injury. However, limited information is available about the role of Drp1 in compression-induced programmed necrosis of NP cells. In the present study, we found that compression resulted in upregulation and mitochondrial translocation of Drp1. Inhibition of Drp1 by siRNA or mitochondrial division inhibitor 1 (mdivi-1) effectively prevented the programmed necrosis of NP cells treated with compression. Furthermore, Drp1 promoted mitochondrial translocation of p53 and nuclear translocation of apoptosis-inducing factor (AIF) in compression-treated NP cells. Inhibition of p53 mitochondrial translocation by pifithrin-µ (PFT-µ) and silencing of AIF expression by siRNA significantly alleviated compression-induced NP cell programmed necrosis. These data indicates that Drp1 mediates compression-induced programmed necrosis of NP cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF.
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Factor Inductor de la Apoptosis/metabolismo , Dinaminas/metabolismo , Mitocondrias/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Núcleo Celular/metabolismo , Células Cultivadas , Fuerza Compresiva , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Necrosis/metabolismo , Necrosis/patología , Transporte de Proteínas , Ratas , Ratas Sprague-Dawley , Estrés MecánicoRESUMEN
In this study, a three-dimensional chitosan-gelatin/nanohydroxyapatite (ChG/nHaP) scaffold was successfully fabricated and characterized in terms of swelling, degradation, cell proliferation, cell attachment, and mineralization characterizations. The ChG/nHaP scaffold was fabricated with a mean pore size of 100-180 µm. Our results showed that the physicochemical and biological properties of the scaffolds were affected by the presence of HaP. The swelling and degradation characteristics of the ChG scaffold were remarkably decreased by the addition of HaP. On the other hand, the presence of HaP remarkably improved the MC3T3-E1 cell attachment and cell growth in the scaffold membrane. The biocompatible nature of the ChG/nHaP scaffold leads to the development of finely scaled mineral deposits on the scaffold membrane. Thus, HaP played an important role in improving the biological performance of the scaffold. Therefore, the ChG/nHaP scaffold could be applied as a suitable material for bone tissue engineering applications.
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This study is aimed at comparing the efficacy and safety of loxoprofen sodium hydrogel patch (LX-P) with loxoprofen sodium tablet (LX-T) in patients with knee osteoarthritis (OA). One hundred sixty-nine patients were enrolled in a randomized, controlled, double-blind, double-dummy, multicenter, non-inferiority trial of LX-P. Patients were randomly assigned to either LX-P or LX-T groups for a 4-week treatment. The primary efficacy endpoint was the proportion of patients with an overall improvement of ≥50%, and the secondary efficacy endpoint was the proportion of patients with an improvement of ≥25% from baseline in each of the seven main symptoms. The non-inferiority trial was based on a power of 80% and significance level of 2.5% with a non-inferiority margin of -10%. In both intention-to-treat (ITT) and per-protocol (PP) analyses, LX-P was as effective as LX-T in regard to the primary endpoint. In the ITT analysis, the difference between the two groups was 12.6% [95% confidence interval, -1.7 to 26.9%]. No significant differences were found between the two groups in any of the secondary efficacy outcomes. A lower incidence of adverse events was observed in LX-P group; however, the difference was not statistically significant. No serious adverse events were reported in the LX-P group, whereas one case was reported in LX-T group. Based on the present study, topical loxoprofen patch was non-inferior to oral loxoprofen in patients with knee osteoarthritis.
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Antiinflamatorios no Esteroideos/administración & dosificación , Osteoartritis de la Rodilla/tratamiento farmacológico , Fenilpropionatos/administración & dosificación , Comprimidos , Parche Transdérmico , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , China , Comorbilidad , Método Doble Ciego , Femenino , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/efectos adversos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Fenilpropionatos/efectos adversos , Comprimidos/efectos adversos , Parche Transdérmico/efectos adversos , Resultado del TratamientoRESUMEN
Traumatic gas gangrene is a fatal infection mainly caused by Clostridium perfringens. It is a challenge to manage gas gangrene in open wounds and control infection after debridement or amputation. The aim of the present study was to use vacuum sealing drainage (VSD) with continuous irrigation of potassium permanganate to manage infective wounds of gas gangrene and observe its clinical efficacy. A total of 48 patients with open traumatic gas gangrene infection were included in this study. Amputations were done for 27 patients, and limb salvage procedures were performed for the others. After amputation or aggressive debridement, the VSD system, including polyvinyl alcohol (PVA) foam dressing and polyurethane (PU) film, with continuous irrigation of 1:5000 potassium permanganate solutions, was applied to the wounds. During the follow-up, all the patients healed without recurrence within 8-18 months. There were four complications. Cardiac arrest during amputation surgery occurred in one patient who suffered from severe septic shock. Emergent resuscitation was performed and the patient returned to stable condition. One patient suffered from mixed infection of Staphylococcal aureus, and a second-stage debridement was performed. One patient suffered from severe pain of the limb after the debridement. Exploratory operation was done and the possible reason was trauma of a local peripheral nerve. Three cases of crush syndrome had dialysis treatment for concomitant renal failure. In conclusion, VSD can convert open wound to closed wound, and evacuate necrotic tissues. Furthermore, potassium permanganate solutions help eliminate anaerobic microenvironment and achieve good therapeutic effect on gas gangrene and mixed infection. VSD with continuous irrigation of potassium permanganate is a novel, simple and feasible alternative for severe traumatic open wounds with gas gangrene infection.