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Metal-organic frameworks (MOFs), with biocompatible and bio-friendly properties, exhibit intriguing potential for the drug delivery system and imaging-guided synergistic cancer theranostics. Even though tremendous attention has been attracted on MOFs-based therapeutics, which play a crucial role in therapeutic drugs, gene, and biomedical agents delivery of cancer therapy, they are often explored as simple nanocarriers without further "intelligent" functions. Herein, Fe-doped MOFs with CoP nanoparticles loading were rationally designed and synthesized for photothermal enhanced reactive oxygen species (ROS)-mediated treatment. Fe-ZIFs@CoP could generate efficient ROS through the Fenton reaction while depleting glutathione for amplifying oxidative stress. Particularly, due to the photothermal effect of Fe-ZIFs@CoP, the hyperthermia generated by as-synthesized Fe-ZIFs@CoP facilitated the advanced performance of the Fenton effect for a high amount of ROS generation. The promising "all-in-one" synergistic MOFs platform herein reported provides some prospects for future directions in this area.
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Introduction: Menstrual blood-derived stem cells (MenSCs) are vital in treating many degenerative and traumatic disorders. However, the underlying molecular mechanisms remain obscure in MenSCs-treating spinal cord injury (SCI) rats. Methods: MenSCs were adopted into the injured sites of rat spinal cords at day 7 post surgery and the tissues were harvested for total RNA sequencing analysis at day 21 after surgery to investigate the expression patterns of RNAs. The differentially expressed genes (DEGs) were analyzed with volcano and heatmap plot. DEGs were sequentially analyzed by weighted gene co-expression network, functional enrichment, and competitive endogenous RNAs (ceRNA) network analysis. Next, expression of selected miRNAs, lncRNAs, circRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics packages and extra databases were enrolled to scoop the genes functions and their interaction relationships. Results: A total of 89 lncRNAs, 65 circRNAs, 120 miRNAs and 422 mRNAs were significantly upregulated and 65 lncRNAs, 72 circRNAs, 74 miRNAs, and 190 mRNAs were significantly downregulated in the MenSCs treated rats compared to SCI ones. Current investigation revealed that MenSCs treatment improve the recovery of the injured rats and the most significantly involved pathways in SCI regeneration were cell adhesion molecules, nature killer cell mediated cytotoxicity, primary immunodeficiency, chemokine signaling pathway, T cell receptor signaling pathway and B cell receptor signaling pathway. Moreover, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA network of SCI was constructed. Finally, the protein-protein interaction (PPI) network was constructed using the top 100 DE mRNAs. The constructed PPI network included 47 nodes and 70 edges. Discussion: In summary, the above results revealed the expression profile and potential functions of differentially expressed (DE) RNAs in the injured spinal cords of rats in the MenSCs-treated and SCI groups, and this study may provide new clues to understand the mechanisms of MenSCs in treating SCI.
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Functional limitation caused by spinal cord injury (SCI) has the problem of significant clinical and economic burden. Damaged spinal axonal connections and an inhibitory environment severely hamper neuronal function. Regenerative biomaterials can fill the cavity and produce an optimal microenvironment at the site of SCI, inhibiting apoptosis, inflammation, and glial scar formation while promoting neurogenesis, axonal development, and angiogenesis. Decellularization aims to eliminate cells from the ultrastructure of tissues while keeping tissue-specific components that are similar to the structure of real tissues, making decellularized extracellular matrix (dECM) a suitable scaffold for tissue engineering. dECM has good biocompatibility, it can be widely obtained from natural organs of different species, and can be co-cultured with cells for 3D printing to obtain the target scaffold. In this paper, we reviewed the pathophysiology of SCI, the characteristics of dECM and its preparation method, and the application of dECM in the treatment of SCI. Although dECM has shown its therapeutic effect at present, there are still many indicators that need to be taken into account, such as the difficulty in obtaining materials and standardized production mode for large-scale use, the effect of decellularization on the physical and chemical properties of dECM, and the study on the synergistic effect of dECM and cells.
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Matriz Extracelular Descelularizada , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/terapia , Apoptosis , Axones , Materiales BiocompatiblesRESUMEN
Spinal cord injury (SCI) is a serious and disabling disease with a high mortality rate. It often leads to complete or partial sensory and motor dysfunction and is accompanied by a series of secondary outcomes, such as pressure sores, pulmonary infections, deep vein thrombosis in the lower extremities, urinary tract infections, and autonomic dysfunction. Currently, the main treatments for SCI include surgical decompression, drug therapy, and postoperative rehabilitation. Studies have shown that cell therapy plays a beneficial role in the treatment of SCI. Nonetheless, there is controversy regarding the therapeutic effect of cell transplantation in SCI models. Meanwhile exosomes, as a new therapeutic medium for regenerative medicine, possess the advantages of small size, low immunogenicity, and the ability to cross the blood-spinal cord barrier. Certain studies have shown that stem cell-derived exosomes have anti-inflammatory effects and can play an irreplaceable role in the treatment of SCI. In this case, it is difficult for a single treatment method to play an effective role in the repair of neural tissue after SCI. The combination of biomaterial scaffolds and exosomes can better transfer and fix exosomes to the injury site and improve their survival rate. This paper first reviews the current research status of stem cell-derived exosomes and biomaterial scaffolds in the treatment of SCI respectively, and then describes the application of exosomes combined with biomaterial scaffolds in the treatment of SCI, as well as the challenges and prospects.
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Tamoxifen is the most commonly used treatment for estrogen-receptor (ER) positive breast cancer patients, but its efficacy is severely hampered by resistance. PI3K/AKT/mTOR pathway inhibition was proven to augment the benefit of endocrine therapy and exhibited potential for reversing tamoxifen-induced resistance. However, the vast majority of PI3K inhibitors currently approved for clinical use are unsatisfactory in terms of safety and efficacy. We developed two-dimensional CuPd (2D-CuPd) nanosheets with oxidase and peroxidase nanozyme activities to offer a novel solution to inhibit the activity of the PI3K/AKT/mTOR pathway. 2D-CuPd exhibit superior dual nanozyme activities converting hydrogen peroxide accumulated in drug-resistant cells into more lethal hydroxyl radicals while compensating for the insufficient superoxide anion produced by tamoxifen. The potential clinical utility was further demonstrated in an orthotopically implanted tamoxifen-resistant PDX breast cancer model. Our results reveal a novel nanozyme ROS-mediated protein mechanism for the regulation of the PI3K subunit, illustrate the cellular pathways through which increased p85ß protein expression contributes to tamoxifen resistance, and reveal p85ß protein as a potential therapeutic target for overcoming tamoxifen resistance. 2D-CuPd is the first reported nanomaterial capable of degrading PI3K subunits, and its high performance combined with further materials engineering may lead to the development of nanozyme-based tumor catalytic therapy.
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Neoplasias de la Mama , Tamoxifeno , Femenino , Humanos , Antineoplásicos Hormonales/farmacología , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Resistencia a Antineoplásicos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismo , Cobre , Plomo , NanoestructurasRESUMEN
BACKGROUND: We hypothesized that subluxating patellar during minimally invasive total knee arthroplasty (MIS-TKA) would affect intraoperative soft tissue balance and postoperative clinical outcome. METHODS: From December 2018 to May 2020, 189 patients receiving primary MIS-TKA were enrolled. The gap-balance technique was used, with patients randomly assigned to undergo osteotomy and balance of soft tissue with patella reduced (group A; n = 93) or subluxated (group B; n = 96). The gap and varus?valgus angle were compared between groups in both extension and flexion position. The gap and varus?valgus angle were also compared before and after reducing patellar in group B. Femoral prosthesis rotation, mechanical femoral axis-to-tibial axis angle, Knee Society Score (KSS), visual analog scale (VAS), and range of motion (ROM) were compared postoperatively between two groups. Follow-up was 12 months. RESULTS: The flexion gap and the varus angle were significantly greater (0.4 mm and 0.7 degree) after patella reduction than before reduction, but the extension joint gap and varus angle were comparable before and after patella reduction. The femoral prosthesis tended to be internally rotated (0.65 degree) in group B. ROM and VAS was better in the group A than in group B at 1 month after surgery, but the differences were not significant at 3, 6 and 12 months. KSS was comparable between the groups after surgery. CONCLUSIONS: During MIS-TKA, as far as possible, soft tissue balance should be achieved with the patella reduced; otherwise, the femoral prosthesis may be installed more internally and, after patella reduction, the flexion gap and varus angle would increase. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ChiCTR2000034106, https://www.chictr.org.cn/hvshowproject.aspx?id=39987.
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PURPOSE: To develop a predictive model for the risk of metabolic syndrome (MetS). PATIENTS AND METHODS: Totally, 1556 residents without MetS were finally included in 2006 and they were observed for 8 years to check who developed MetS. Univariate and multivariate logistic regression analyses was adopted to explore the risk factors of MetS and develop the predictive model that used the medical examination information of MetS risk after 8 years. The receiver operating characteristic (ROC) curve was drawn to assess the predictive capacity of the model. RESULTS: The risk of MetS in overweight, prehypertension, hypertension subjects were 4.610 [95% confidence interval (CI): 2.415 to 8.800], 2.759 (95% CI: 1.519 to 5.011) and 3.589 (95% CI: 1.672 to 7.706) times higher than that in controls, respectively. The risk of MetS in people with high-density lipoprotein (HDL) <1.10 mmol/L was 3.716-fold in comparison with HDL ≥1.55 mmol/L [odds risk (OR) = 3.716, 95% CI: 1.483 to 9.313]. Individuals with fatty liver had a higher risk of MetS (OR = 2.577, 95% CI: 1.472 to 4.512). The AUC of the predictive model was 0.831 (95% CI: 0.798 to 0.865), with the sensitivity of 0.898 (95% CI: 0.831 to 0.941) and the specificity of 0.676 (95% CI: 0.651 to 0.700). CONCLUSION: The model performed well predictive power for the risk of MetS, which may provide a reference for clinicians to identify high-risk groups early.
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Point mutations within the DNA-binding domain of the TP53 gene occur in a significant percentage of human cancer, leading to cellular accumulation of highly stabilized mutant p53 proteins (mutp53) with tumor-promoting properties. Depletion of mutp53, through inducing either autophagic or proteasomal degradation, is an attractive strategy for the therapy of p53-mutated cancer, but the currently-known degradation inducers, almost exclusively small molecules, are inadequate. Here we show that pH-responsive zeolitic imidazolate framework-8 (ZIF-8) offers a novel solution to mutp53 degradation. ZIF-8 facilitated ubiquitination-mediated and glutathionylation-dependent proteasomal degradation of all of the nine mutp53 we tested, including six hot-spot mutp53, but not the wild-type p53 protein. Sustained elevation of intracellular Zn++ level, resulted from decomposition of the internalized ZIF-8 in the acidic endosomes, decreased the intracellular reduced glutathione (GSH): oxidized glutathione (GSSG) ratio and was essential for mutp53 glutathionylation and degradation. ZIF-8 modified with an Z1-RGD peptide, exhibiting enhanced cellular internalization and improved decomposition behavior, preferentially killed mutp53-expressing cancer cells and demonstrated remarkable therapeutic efficacy in a p53 S241F ES-2 ovarian cancer model as well as in a p53 Y220C patient-derived xenograft (PDX) breast cancer model. The ability to induce wide-spectrum mutp53 degradation gives ZIF-8 a clear advantage over other degradation-inducers, and engineered nanomaterials may be promising alternatives to small molecules for the development of mutp53-targeting drugs.
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Proteína p53 Supresora de Tumor , Zeolitas , Línea Celular Tumoral , Genes p53 , Humanos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutación , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Atherosclerosis (AS) is a chronic inflammatory disease, the main causes of which include abnormal lipid metabolism, endothelial injury, physical and chemical injury, hemodynamic injury, genetic factors and so on. These causes can lead to inflammatory injury of blood vessels and local dysfunction. Bunao-Fuyuan decoction (BNFY) is a traditional Chinese medicine compound that can treat cardiovascular and cerebrovascular diseases, but its effect on AS is still unknown. The aim of this study was to investigate the effect and mechanism of BNFY in proliferation and migration of vascular smooth muscle cells (VSMCs) on AS. At first, the expression of α-SMA protein in ox-LDL-induced VSMCs, which was detected by immunofluorescence staining and western blot. CCK-8 technique and cloning technique were used to detect the cell proliferation of ox-LDL-induced VSMCs after adding BNFY. Meanwhile, the expression of proliferating protein Ki67 was detected by immunofluorescence staining. Western blot was also used to detect the expression of proliferation-related proteins CDK2, CyclinE1 and P27. Flow cytometry was used to detect the effect of BNFY on cell cycle. The effects of BNFY on proliferation and migration of cells were detected by cell scratch test and Transwell. Western blot was used to detect the expression of adhesion factors ICAM1, VCAM1, muc1, VE-cadherin and RHOA/ROCK-related proteins in cells. We found that the expression of AS marker α-SMA protein increased significantly and cells shriveled and a few floated on the medium after induction of ox-LDL on VSCMs. The proliferation rate of ox-LDL VSMCs decreased significantly after adding different doses of BNFY, and BNFY can inhibit cell cycle. Meanwhile, we also found that cell invasion and migration rate were significantly inhibited and related cell adhesion factors ICAM1, VCAM1, muc1 and VE-cadherin were inhibited too by BNFY. Finally, we found that BNFY inhibited the expression of RHOA, ROCK1, ROCK2, p-MLC proteins in the RHOA/ROCK signaling pathway. Therefore, we can summarize that BNFY may inhibit the proliferation and migration of atherosclerotic vascular smooth muscle cells by inhibiting the activity of RHOA/ROCK signaling pathway.
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Aterosclerosis , Medicamentos Herbarios Chinos/farmacología , Músculo Liso Vascular , Miocitos del Músculo Liso/citología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética , Movimiento Celular , Proliferación Celular , Células Cultivadas , Humanos , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/efectos de los fármacosRESUMEN
A great variety of nanoparticles are known to induce autophagy, leading to either pro-death or pro-survival. Zeolitic imidazolate framework-8 (ZIF-8), a type of porous metal-organic framework (MOF) material and a promising drug delivery vector, has reportedly shown excellent efficacy for cancer therapy. However, less attention has been paid to the potential biological effect of ZIF-8 per se, and if so, how the effect impacts cell fate and therapy outcomes. Herein, we showed that ZIF-8 induced autophagy in HeLa cells, characterized by increased autophagosome formation without disruption of autophagic flux, in a dose- and time-dependent fashion. ZIF-8 also caused dephosphorylation of the transcription factor EB (TFEB) at serine-142 and serine-211, leading to the nucleus translocation of TFEB, an event that promoted lysosome biogenesis and is necessary for autophagy induction. We further pinpointed the inhibition of mTORC1 as the critical event upstream of ZIF-8-elicited TFEB dephosphorylation and the subsequent nucleus translocation. Furthermore, autophagy induced by ZIF-8 promoted cell survival, as inhibiting autophagy by either 3-methyladenine (3-MA) or ATG5 knockdown significantly enhanced ZIF-8-elicited HeLa cell death. Most importantly, doxorubicin-encapsulated ZIF-8 (DOX@ZIF-8) also elicited strong pro-survival autophagy, and the co-delivery of an autophagic inhibitor (3-MA) dramatically enhanced the cytotoxicity of DOX@ZIF-8 in HeLa cells. Our results revealed the unique ability of ZIF-8, both in a free and drug-loaded form, to induce pro-survival autophagy in certain cancer cells, a finding with important implications for potential clinical studies that utilize ZIF-8 as a drug carrier.
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Zeolitas , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Doxorrubicina , Células HeLa , Humanos , Diana Mecanicista del Complejo 1 de la RapamicinaRESUMEN
BACKGROUND: Despite the continued improvement in the surgical techniques during primary total knee arthroplasty (TKA), literatures indicate that up to 10 to 20% patients are not satisfied with their outcomes. Psychological factors in this dissatisfaction are yet to be clearly identified. The aim of this study is to develop a method to assess whether the patient's current mental state is suitable enough to accept a TKA surgery. METHODS: Preoperative demographic and clinical data of 532 patients who underwent TKA were prospectively obtained from January 2012 until December 2016. We recorded the scores evaluated by SF-36 questionnaire and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) preoperatively and 1 year postoperatively. Preoperative Life Satisfaction Rating (LSR) is emphatically evaluated. RESULTS: Poor preoperative score of LSR was a significant predictor of dissatisfaction after TKA. Patients with low LSR reported significant pain and stiffness, although there was no remarkable effect on functionality of the replaced joint. The results also showed that age and BMI were not strong predictors of satisfaction in TKA. CONCLUSION: Our outcomes can help clinicians evaluate whether a patient's current mental status is favorable for TKA. If patients have extreme low scores of LSR (less than 10), a psychological intervention should be recommended for better satisfaction following a TKA surgery. This would also allow surgeons to individually assess the risks and benefits of surgery.
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Artroplastia de Reemplazo de Rodilla/psicología , Artroplastia de Reemplazo de Rodilla/tendencias , Satisfacción Personal , Cuidados Preoperatorios/psicología , Cuidados Preoperatorios/tendencias , Encuestas y Cuestionarios , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/psicología , Osteoartritis de la Rodilla/cirugía , Valor Predictivo de las Pruebas , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Osteosarcoma (OS), the most common bone cancer, causes high morbidity in children and young adults. TRIM46 is a member of the family of tripartite motif (TRIM)-containing proteins that serve as important regulators of tumorigenesis. Here we investigate the possible role of TRIM46 in OS and the underlying molecular mechanism. We report an increase in the expression of TRIM46 in OS and its association with tumor size, Ennekings stage, and patient prognosis. TRIM46 knockdown inhibits OS cell viability and cell cycle progression and induces apoptosis, while TRIM46 overexpression exerts inverse effects, which are inhibited by peroxisome proliferator-activated receptor alpha (PPAR) overexpression and the nuclear factor kappa B (NF-B) inhibitor, pyrrolidine dithiocarbamate (PDTC). Furthermore, TRIM46 negatively regulates PPAR expression via ubiquitination-mediated protein degradation and modification. PPAR overexpression also inactivates NF-B signaling and NF-B promoter activity in OS cells overexpressing TRIM46. Moreover, TRIM46 knockdown inhibits tumor growth and induces apoptosis of OS cells in vivo. TRIM46 acts as an oncogene in OS by interacting with and ubiquitinating PPAR, resulting in the activation of NF-B signaling pathway. Thus, TRIM46 may be a potential biomarker of carcinogenesis.
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Neoplasias Óseas/metabolismo , FN-kappa B/metabolismo , Osteosarcoma/metabolismo , PPAR alfa/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Adolescente , Animales , Apoptosis , Biomarcadores de Tumor , Neoplasias Óseas/patología , Carcinogénesis , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Niño , Femenino , Humanos , Masculino , Ratones , Estadificación de Neoplasias , Proteínas del Tejido Nervioso/metabolismo , Osteosarcoma/patología , Pronóstico , UbiquitinaciónRESUMEN
Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.
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Neoplasias Óseas/genética , Carcinogénesis/genética , Macrófagos/inmunología , MicroARNs/metabolismo , Osteosarcoma/genética , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/genética , Adolescente , Animales , Neoplasias Óseas/inmunología , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Carcinogénesis/efectos de los fármacos , Carcinogénesis/inmunología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/inmunología , Técnicas de Silenciamiento del Gen , Humanos , Estimación de Kaplan-Meier , Macrófagos/metabolismo , Masculino , Ratones , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , Invasividad Neoplásica/genética , Invasividad Neoplásica/inmunología , Invasividad Neoplásica/prevención & control , Osteosarcoma/inmunología , Osteosarcoma/mortalidad , Osteosarcoma/patología , Células RAW 264.7 , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , Regulación hacia Arriba , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto JovenRESUMEN
N-phenylmaleimide (N-PMI) and its precursor, (Z)-4-oxo-4-(phenylamino)but-2-enoic acid, were synthesized from aniline and maleic anhydride. Copolymerization between N-phenylmaleimide and styrene was initiated in micropores and outside surface of porous polyvinyl chloride (PVC) resin suspended in aqueous phase. The modified PVC was characterized with Gel Permeation Chromatography, thermal gravimetric analysis and scanning electron microscopy. The result of high performance liquid chromatography shows that the purity of N-PMI reached 97.3%. Thermal gravimetric analysis indicated that the introduction of N-PMI could clearly affect the thermal degradation behavior of PVC, and when PMI was at 6.25% of the PVC mass, the decomposition temperature T0.5 of modified polymer was increased to 314.2°C. The glass transition temperature of modified polymer was increased from 70°C to 80°C.
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Recent studies show that lncRNAs involve in the initiation and progression of various cancers including osteosarcoma (OS). IncRNA Xist has been verified as an oncogene in several human cancers, and its abnormal expression was closely associated with tumor initiation and progression. Nevertheless, the role of Xist in OS remains unclear. Here, we revealed the Xist expression level was up-regulated in OS tissues and discovered that Xist knockdown significantly repressed OS cell proliferation. Additionally, mechanistic analysis revealed that Xist can repress P21 expression to regulate OS cell cycle and proliferation by binding to EZH2. Taking all into account, Xist may function in promoting OS cell proliferation and may potentially serve as a novel biomarker and therapeutic target for OS.
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MiR-329 has been proved to be a tumor suppressor gene in various malignancies, however, its role in osteosarcoma remains elusive. We found that miR-329 is remarkably downregulated in osteosarcoma tissues and relates to advanced stages. MiR-329 is able to inhibit osteosarcoma cell proliferation, promote apoptosis, and induce G0/G1 cell cycle arrest. In addition, miR-329 also suppresses wound-healing and migration ability of osteosarcoma cells and inhibits tumorigenicity in vivo. Rab10 was identified as a target of miR-329 in osteosarcoma and mediates its biofunction. These findings may shed light to the understanding of tumor development in osteosarcoma.
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MicroARNs/genética , Osteosarcoma/genética , Proteínas de Unión al GTP rab/biosíntesis , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/biosíntesis , Osteosarcoma/patología , Proteínas de Unión al GTP rab/genéticaRESUMEN
Tendon calcification has been widely regarded by researchers to result from the osteogenic differentiation of Tendon-Derived Stem Cells (TDSCs) and ectopic mineralization caused by the calcification of cellular matrix. Recent studies have revealed a correlation between the Mg(2+)/Ca(2+) balance and the degeneration or calcification of tendon tissues. Furthermore, the ATP-P2X/P2Y receptor pathway has been shown to play a decisive role in the process of calcification, with calcium exportation from mitochondria and calcium oscillations potentially representing the cohesive signal produced by this pathway. Our previous study demonstrated that matrix calcification is inhibited by magnesium. In this study, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and cellular pathways in TDSCs. The suppression of the export of calcium from mitochondria has also been detected. We found that a high concentration of extracellular Mg(2+) ([Mg(2+)]e) inhibited the mineralization of the extracellular matrix in TDSCs and that 100 µM ATP reversed this inhibitory effect in vitro. In addition, the spontaneous release of ATP was inhibited by high [Mg(2+)]e levels. A high [Mg(2+)]e suppressed the expression of P2X4, P2X5 and P2X7 and activated the expression of P2Y1, P2Y2, P2Y4 and P2Y14. The interaction between Mg(2+) and Ca(2+) is therefore contradictory, Mg(2+) inhibits mitochondrial calcium concentrations, meanwhile it reverses the opening of mPTP that is induced by Ca(2+). JC-1 staining verified the protective effect of Mg(2+) on mitochondrial membrane potential and the decrease induced by Ca(2+). Taken together, these results indicate that high [Mg(2+)]e interferes with the expression of P2 receptors, resulting in decreased extracellular mineralization. The balance between Mg(2+) and Ca(2+) influences mitochondrial calcium exportation and provides another explanation for the mechanism underlying matrix calcification in TDSCs.
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Calcificación Fisiológica/fisiología , Matriz Extracelular/metabolismo , Magnesio/administración & dosificación , Mitocondrias/metabolismo , Células Madre/metabolismo , Tendones/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Calcificación Fisiológica/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Matriz Extracelular/efectos de los fármacos , Masculino , Mitocondrias/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Células Madre/citología , Células Madre/efectos de los fármacos , Tendones/citologíaRESUMEN
PURPOSE: The aim of this study was to prove that it is feasible to diagnose discoid lateral meniscus in radiographs. Plain radiographic findings of discoid lateral menisci with matched controls were analysed and compared in a quantitative method. METHODS: Sixty consecutive patients (60 knees) who were diagnosed with discoid lateral meniscus (discoid group) by magnetic resonance imaging (MRI) were included. Another 60 age- and sex-matched controls with normal medial and lateral menisci on the basis of MRI findings were included as the control group. Each plain radiograph was evaluated from the anteroposterior view for the following variables: height of the fibular head (HFH), lateral joint space distance (LJSD), height of the lateral tibial spine (HLTS), obliquity of the lateral tibial plateau, obliquity of the lateral femoral condyle, distance from the lateral tibial spine to the lateral femoral condyle, height of the medial tibial spine, chordal distance of the femoral condyle (CDLF, CDMF), the HFH/LJSD, LJSD/HLTS and the CDLF/CDMF. RESULTS: A significant difference was found in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS between the two groups. The cut-off values of the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS were 12.9 mm, 6.6 mm, 7.8 mm, 3.0 mm, 2.7 mm, 2.0 and 0.9, respectively. Among the cut-off values in diagnosing discoid lateral meniscus, the sensitivity, specificity and ROC curve area of LJSD/HLTS were as high as 73.6 %, 83.0 % and 0.8, respectively. The corresponding values of the HFH/LJSD were as high as 66.0 %, 86.8 % and 0.8. For the first two indicators, the results of the HFH/LJSD and LJSD/HLTS were higher than that of most other parameters. At the same time, the ROC curve area of the HFH/LJSD and LJSD/HLTS ranked highest among all the results. CONCLUSION: There were significant differences in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS, especially the HFH/LJSD and the LJSD/HLTS, between plain radiographic findings of discoid lateral meniscus patients and normal controls. The results of the HFH/LJSD and the LJSD/HLTS showed a positive impact on the diagnosis of discoid lateral meniscus in this research. These findings enable radiographs to screen for discoid lateral meniscus. LEVEL OF EVIDENCE: II.
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Errores Diagnósticos/prevención & control , Meniscos Tibiales/patología , Radiografía , Adulto , Anciano , Artroscopía , Enfermedades de los Cartílagos/patología , Epífisis , Femenino , Humanos , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Curva ROC , Estudios RetrospectivosRESUMEN
By adopting gradient analysis combining with the analysis of urban land use degree, this paper studied the spatial layout characteristics of residential and industrial lands in new Yinzhou Town, and explored the location characters of various urban land use by selecting public green land, public facilities, and road as the location advantage factors. Gradient analysis could effectively connect with the spatial layout of urban land use, and quantitatively depict the spatial character of urban land use. In the new town, there was a new urban spatial center mostly within the radius of 2 km, namely, the urban core area had obvious location advantage in the cross-shaft direction urban development. On the south of Yinzhou Avenue, the urban hinterland would be constructed soon. In the future land use of the new town, the focus would be the reasonable vicissitude of industrial land after the adjustment of industrial structure, the high-efficient intensive use of the commercial land restricted by the compulsive condition of urban core area, and the agricultural land protection in the southeastern urban-rural fringe.
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Planificación de Ciudades , Productos Agrícolas/crecimiento & desarrollo , Planificación Ambiental , China , Ciudades , IndustriasRESUMEN
In recent years, chlorophyll fluorescence analysis has been developed into a kind of new, fast, simple, and accurate technique in photosynthesis research, and widely applied in agriculture and horticulture but few in forest tree cultivation. This paper introduced the relevant parameters of chlorophyll fluorescence analysis and their biological meanings, and summarized its application in forest tree cultivation and in the research of forest tree stress physiology. Some perspectives and suggestions were put forward.