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2.
J Cell Mol Med ; 28(8): e18327, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38661437

RESUMO

Cartilage defects in the knee are often associated with the progression of degenerative osteoarthritis (OA), and cartilage repair is a useful strategy for managing this disease. However, cartilage repair is challenging because of the unique environment within the tissue. Recently, stem cell-based therapies have shed new light on this issue. In this study, we prepared exosomes (EXOs) from cartilage stem/progenitor cells (CSPCs) and found that treatment with EXOs increased the viability, migration, and proliferation of cultured primary chondrocytes. In a subacute OA rat model, the application of EXOs facilitated cartilage regeneration as evidenced by histological staining. Exosomal protein analysis together with bioinformatics suggested that cyclin-dependent kinase 9 (CDK9) is a key factor for chondrocyte growth and migration. Functional studies confirmed this prediction, that is, inhibiting CDK9 reduced the beneficial effects induced by EXOs in primary chondrocytes; while overexpression of CDK9 recapitulated the EXOs-induced phenotypes. RNA-Seq data showed that a set of genes involved in cell growth and migration were up-regulated by EXOs in chondrocytes. These changes could be partially reproduced by CDK9 overexpression. Overall, our data suggest that EXOs derived from primary CSPCs hold great therapeutic potential for treating cartilage defect-associated disorders such as degenerative OA, and that CDK9 is a key factor in this process.


Assuntos
Cartilagem Articular , Proliferação de Células , Condrócitos , Modelos Animais de Doenças , Exossomos , Animais , Exossomos/metabolismo , Ratos , Condrócitos/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Células-Tronco/metabolismo , Células-Tronco/citologia , Movimento Celular , Ratos Sprague-Dawley , Quinase 9 Dependente de Ciclina/metabolismo , Quinase 9 Dependente de Ciclina/genética , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/terapia , Masculino , Células Cultivadas , Regeneração , Osteoartrite/patologia , Osteoartrite/metabolismo , Osteoartrite/terapia
3.
Huan Jing Ke Xue ; 45(5): 2891-2904, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629551

RESUMO

The increasing use of nitrogen fertilizers exerts extreme pressure on the environment (e.g., greenhouse gas emissions, GHGs) for winter wheat-summer maize rotation systems in the North China Plain. The application of controlled-release fertilizers is considered as an effective measure to improve crop yield and nitrogen fertilizer utilization efficiency. To explore the impact of one-time fertilization of controlled-release blended fertilizer on crop yield and GHGs of a wheat-maize rotation system, field experiments were carried out in Dezhou Modern Agricultural Science and Technology Park from 2020 to 2022. Five treatments were established for both winter wheat and summer maize, including no nitrogen control (CK), farmers' conventional nitrogen application (FFP), optimized nitrogen application (OPT), CRU1 (the blending ratio of coated urea and traditional urea on winter wheat and summer maize was 5:5 and 3:7, respectively), and CRU2 (the blending ratio of coated urea and traditional urea on winter wheat and summer maize was 7:3 and 5:5, respectively). The differences in yield, nitrogen fertilizer utilization efficiency, fertilization economic benefits, and GHGs among different treatments were compared and analyzed. The results showed that nitrogen application significantly increased the single season and annual crop yields of the wheat-maize rotation system (P < 0.05). Compared with those of FFP, the CRU1 and CRU2 treatments increased the yields of summer maize by 0.4% to 5.6%, winter wheat by -5.4% to 4.1%, and annual yields by -1.1% to 3.9% (P > 0.05). N recovery efficiency (NRE), N agronomic efficiency (NAE), and N partial factor productivity (NPFP) were increased by -8.6%-43.4%, 2.05-6.24 kg·kg-1, and 4.24-10.13 kg·kg-1, respectively. Annual net income increased by 0.2% to 6.3%. Nitrogen application significantly increased the annual emissions of soil N2O and CO2 in the rotation system (P < 0.05) but had no effect on the annual emissions of CH4 (except for in the FFP treatment in the first year). The annual total N2O emissions under the CRU1 and CRU2 treatments were significantly reduced by 23.4% to 30.2% compared to those under the FFP treatment (P < 0.05). Additionally, nitrogen application significantly increased the annual global warming potential (GWP) of the rotation system (P < 0.05), but the intensity of greenhouse gas emissions was reduced due to the increase in crop yields. Compared with that under FFP, the annual GWP under the CRU1 and CRU2 treatments decreased by 9.6% to 11.5% (P < 0.05), and the annual GHGs decreased by 11.2% to 13.8% (P > 0.05). In summary, the one-time application of controlled-release blended fertilizer had a positive role in improving crop yield and economic benefits, reducing nitrogen fertilizer input and labor costs, and GHGs, which is an effective nitrogen fertilizer management measure to promote cleaner production of food crops in the North China Plain.


Assuntos
Gases de Efeito Estufa , Fertilizantes , Triticum , Zea mays , Preparações de Ação Retardada , Óxido Nitroso/análise , Agricultura/métodos , Solo , China , Nitrogênio , Ureia
4.
Proc Natl Acad Sci U S A ; 120(28): e2305236120, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37399400

RESUMO

Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.


Assuntos
Ácidos Nucleicos Livres , Aprendizado Profundo , Humanos , Ácidos Nucleicos Livres/genética , Metilação de DNA , Biomarcadores , Regiões Promotoras Genéticas , Biomarcadores Tumorais/genética
5.
Front Surg ; 10: 1176254, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37292486

RESUMO

Objective: To explore the clinical outcomes of a 3D printing-assisted posterolateral approach for the treatment of ankle fractures involving the posterior malleolus. Methods: A total of 51 patients with ankle fractures involving the posterior malleolus admitted to our hospital from January 2018 to December 2019 were selected. The patients were divided into 3D printing group (28 cases) and control group (23 cases). 3D printing was performed for ankle fractures, followed by printing of a solid model and simulation of the operation on the 3D model. The operation was then performed according to the preoperative plan, including open reduction and internal fixation via the posterolateral approach with the patient in the prone position. Routine x-ray and CT examinations of the ankle joint were performed, and ankle function was evaluated using the American Foot and Ankle Surgery Association (AOFAS) ankle-hindfoot score. Results: All patients underwent x-ray and CT examinations. All fractures healed clinically, without loss of reduction or failure of internal fixation. Good clinical effects were achieved in both groups of patients. The operation time, intraoperative blood loss and intraoperative fluoroscopy frequency in the 3D printing group were significantly less than those in the control group (p < 0.05). There was no significant difference between the two groups in the anatomical reduction rate of fractures or the incidence of surgical complications (p > 0.05). Conclusion: The 3D printing-assisted posterolateral approach is effective in the treatment of ankle fractures involving the posterior malleolus. The approach can be well planned before the operation, is simple to perform, yields good fracture reduction and fixation, and has good prospects for clinical application.

6.
RSC Adv ; 13(22): 14863-14877, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37197179

RESUMO

Titanium is widely used in implants because of its good mechanical properties and biocompatibility. However, titanium has no biological activity and is prone to causing implant failure after implantation. In this study, we prepared a manganese- and fluorine-doped titanium dioxide coating on a titanium surface by microarc oxidation technology. The surface characteristics of the coating were evaluated by field emission scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and atomic force microscopy and profiler, and the corrosion resistance and wear resistance of the coating were also evaluated. The bioactivity of the coating on bone marrow mesenchymal stem cells was evaluated by in vitro cell experiments, and the antibacterial properties of the coating were evaluated by in vitro bacterial experiments. The results confirmed that the manganese- and fluorine-doped titanium dioxide coating was successfully prepared on the titanium surface, and manganese and fluorine were successfully introduced into the coating. The doping of manganese and fluorine did not change the surface morphology of the coating, and the coating had good corrosion resistance and wear resistance. The results of the in vitro cell experiment showed that the titanium dioxide coating with manganese and fluoride could promote the proliferation, differentiation and mineralization of bone marrow mesenchymal stem cells. The results of the bacterial experiment in vitro showed that the coating material could inhibit the propagation of Staphylococcus aureus and had a good antibacterial effect. Conclusion: it is feasible to prepare a manganese- and fluorine-doped titanium dioxide coating on titanium surfaces by microarc oxidation. The coating not only has good surface characteristics but also has good bone-promoting and antibacterial properties and has potential for clinical application.

7.
Front Bioeng Biotechnol ; 10: 1001514, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338114

RESUMO

Implant materials are mainly used to repair and replace defects in human hard tissue (bones and teeth). Titanium (Ti) and Ti alloys are widely used as implant materials because of their good mechanical properties and biocompatibilities, but they do not have the ability to induce new bone formation and have no antibacterial properties. Through surface modification, Ti and its alloys have certain osteogenic and antibacterial properties such that Ti implants can meet clinical needs and ensure integration between Ti implants and bone tissue, and this is currently an active research area. In this study, bioactive Si and Ag were introduced onto a Ti surface by plasma oxidation. The surface morphology, structure, elemental composition and valence, surface roughness, hydrophilicity and other physical and chemical properties of the coating were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), a profiler and a contact angle meter (CA). Adhesion and extensions of osteoblasts on the surface of the material were observed by scanning electron microscopy, and mineralization of osteoblasts on the surface of the material were observed by alizarin red staining. The antibacterial properties of the material were tested by culturing Staphylococcus aureus on the surface of the material. The osteogenic properties of Ti implants with porous Si/Ag TiO2 (TCP-SA) coatings were evaluated with in vivo experiments in rats. The results showed that Si and Ag were successfully introduced onto the Ti surface by plasma oxidation, and doping with Si and Ag did not change the surface morphology of the coating. The osteoblasts showed good adhesion and extension on the surfaces of Si/Ag coated samples, and the porous Si/Ag TiO2 coating promoted cell proliferation and mineralization. The bacterial experiments showed that the porous TiO2 coatings containing Si/Ag had certain antibacterial properties. The animal experiments showed that Si/Ag-coated Ti implants promoted integration between the implants and the surrounding bone. It was concluded that the porous Si/Ag TiO2 coating on the Ti surface had good osteogenic and antibacterial properties and provides an optimal strategy for improving the osteogenic and antibacterial properties of Ti implants.

8.
Nat Commun ; 13(1): 5566, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175411

RESUMO

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Gástricas , Ácidos Nucleicos Livres/genética , Análise Custo-Benefício , Detecção Precoce de Câncer , Epigenoma , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética
9.
Sci Rep ; 12(1): 14007, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35977982

RESUMO

Wood fiber/polypropylene (WF/PP) composites are environmentally friendly materials with high dimensional stability and mechanical properties. However, the applications of WF/PP composites are limited by an unattractive surface texture. In this study, the WF/PP composites were decorated with poplar wood veneer using chlorinated polypropylene (CPP) as a hot melt adhesive, the bonding strength is over 1.18 MPa. Surface bonding strength tests and scanning electron microscopy (SEM) were performed to analyze the quality of the CPP bonding layer. The physical and mechanical properties of the veneered WF/PP boards and unveneered controls were examined to determine the effects of reinforcement. The result shows that after veneered the tension strength and modulus of the whole composite board were increased over 30% and 10%; the flexural strength and modulus were increased over 10% and 20%. Low-velocity impact testing was performed to determine the impact resistance properties of the composites. Higher ratios of wood fiber in the WF/PP composite led to a higher surface bonding strength, which was evident in the SEM images. Wood veneer decoration increased the mechanical strength of the whole composite board. A tighter bond along the CPP layer would provide additional reinforcement of the veneered composite's mechanical properties.


Assuntos
Polipropilenos , Populus , Teste de Materiais , Microscopia Eletrônica de Varredura , Polipropilenos/química , Madeira/química
10.
Clin Cancer Res ; 28(9): 1841-1853, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35149536

RESUMO

PURPOSE: Cell-free DNA (cfDNA) offers a noninvasive approach to monitor cancer. Here we develop a method using whole-exome sequencing (WES) of cfDNA for simultaneously monitoring the full spectrum of cancer treatment outcomes, including minimal residual disease (MRD), recurrence, evolution, and second primary cancers. EXPERIMENTAL DESIGN: Three simulation datasets were generated from 26 patients with cancer to benchmark the detection performance of MRD/recurrence and second primary cancers. For further validation, cfDNA samples (n = 76) from patients with cancer (n = 35) with six different cancer types were used for performance validation during various treatments. RESULTS: We present a cfDNA-based cancer monitoring method, named cfTrack. Taking advantage of the broad genome coverage of WES data, cfTrack can sensitively detect MRD and cancer recurrence by integrating signals across known clonal tumor mutations of a patient. In addition, cfTrack detects tumor evolution and second primary cancers by de novo identifying emerging tumor mutations. A series of machine learning and statistical denoising techniques are applied to enhance the detection power. On the simulation data, cfTrack achieved an average AUC of 99% on the validation dataset and 100% on the independent dataset in detecting recurrence in samples with tumor fractions ≥0.05%. In addition, cfTrack yielded an average AUC of 88% in detecting second primary cancers in samples with tumor fractions ≥0.2%. On real data, cfTrack accurately monitors tumor evolution during treatment, which cannot be accomplished by previous methods. CONCLUSIONS: Our results demonstrated that cfTrack can sensitively and specifically monitor the full spectrum of cancer treatment outcomes using exome-wide mutation analysis of cfDNA.


Assuntos
Ácidos Nucleicos Livres , Segunda Neoplasia Primária , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Exoma/genética , Humanos , Mutação , Recidiva Local de Neoplasia/genética , Neoplasia Residual/genética , Segunda Neoplasia Primária/genética , Resultado do Tratamento , Sequenciamento do Exoma
11.
Nanoscale Res Lett ; 16(1): 146, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542720

RESUMO

Due to their excellent mechanical properties and good biocompatibility, titanium alloys have become a popular research topic in the field of medical metal implants. However, the surface of the titanium alloy does not exhibit biological activity, which may cause poor integration between the interface of the titanium implant and the interface of the bone tissue and subsequently may cause the implant to fall off. Therefore, surface biological inertness is one of the problems that titanium alloys must overcome to become an ideal orthopedic implant material. Surface modification can improve the biological properties of titanium, thereby enhancing its osseointegration effect. Copper is an essential trace element for the human body, can promote bone formation and plays an important role in maintaining the physiological structure and function of bone and bone growth and development. In this study, a microporous copper-titanium dioxide coating was prepared on the surface of titanium by microarc oxidation. Based on the evaluation of its surface characteristics, the adhesion, proliferation and differentiation of MC3T3-E1 cells were observed. A titanium rod was implanted into the rabbit femoral condyle, and the integration of the coating and bone tissue was evaluated. Our research results show that the microporous copper-titanium dioxide coating has a nearly three-dimensional porous structure, and copper is incorporated into the coating without changing the structure of the coating. In vitro experiments found that the coating can promote the adhesion, proliferation and differentiation of MC3T3-E1 cells. In vivo experiments further confirmed that the titanium copper-titanium dioxide microporous coating can promote the osseointegration of titanium implants. In conclusion, copper-titanium dioxide microporous coatings can be prepared by microarc oxidation, which can improve the biological activity and biocompatibility of titanium, promote new bone formation and demonstrate good osteoinductive properties. Therefore, the use of this coating in orthopedics has potential clinical application.

12.
Neurosciences (Riyadh) ; 26(3): 236-241, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230077

RESUMO

OBJECTIVES: To compare the clinical efficacy of unilateral and bilateral puncture PKP in the treatment of OVCFs and explored whether there is a difference in the efficacy of unilateral and bilateral puncture PKP after surgery. METHODS: A total of 98 patients with OVCFs treated by PKP from August 2016 to June 2018 were selected. There were 62 cases in the unilateral puncture group and 36 cases in the bilateral puncture group. The operation time, the amount of bone cement injection, the height of the anterior edge of the vertebral body and the visual analog scale (Visual Analog Scale, VAS) scores before and after the operation were analyzed, and whether the differences between the 2 groups were statistically significant was analyzed. RESULTS: All patients were followed up completely. The operation time and the number of X-ray fluoroscopies of the unilateral puncture group were significantly reduced compared to those of the bilateral group, and the difference was statistically significant (p<0.05). In terms of the bone cement injection volume, the average injection volume of the bilateral group was greater than that of the unilateral group, and the difference was statistically significant (p<0.05); the postoperative VAS scores of the 2 groups of patients were significantly improved, and the difference was statistically significant compared with that before surgery (p<0.05) but that of the unilateral group was not statistically significant compared with that of the bilateral group (p>0.05). The height of the anterior edge of the vertebral body in both groups was significantly improved compared with that before the operation, and the difference was statistically significant (p<0.05). CONCLUSION: Unilateral and bilateral puncture PKP can achieve good clinical efficacy in the treatment of osteoporotic vertebral compression fractures, but unilateral PKP has the advantages of short operation time and low X-ray exposure.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Punções , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento
13.
Nat Commun ; 12(1): 4172, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234141

RESUMO

Cell-free DNA (cfDNA) is attractive for many applications, including detecting cancer, identifying the tissue of origin, and monitoring. A fundamental task underlying these applications is SNV calling from cfDNA, which is hindered by the very low tumor content. Thus sensitive and accurate detection of low-frequency mutations (<5%) remains challenging for existing SNV callers. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this challenge. Furthermore, by leveraging cfDNA's comprehensive coverage of tumor clonal landscape, cfSNV can profile mutations in subclones. In both simulated and real patient data, cfSNV outperforms existing tools in sensitivity while maintaining high precision. cfSNV enhances the clinical utilities of cfDNA by improving mutation detection performance in medium-depth sequencing data, therefore making Whole-Exome Sequencing a viable option. As an example, we demonstrate that the tumor mutation profile from cfDNA WES data can provide an effective biomarker to predict immunotherapy outcomes.


Assuntos
DNA Tumoral Circulante/genética , Análise Mutacional de DNA/métodos , Sequenciamento do Exoma/métodos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias/genética , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biópsia , DNA Tumoral Circulante/sangue , Simulação por Computador , Conjuntos de Dados como Assunto , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Intervalo Livre de Progressão , Sensibilidade e Especificidade
14.
Biochem Biophys Res Commun ; 529(4): 970-976, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32819607

RESUMO

In this study, the role of ubiquitin conjugating enzyme E2 M (UBE2M) and molecular mechanisms associated with osteoarthritis (OA) were explored. Cartilage tissues and corresponding healthy tissues from OA patients were isolated. Our data suggested that the expression level of UBE2M in OA patients was significantly higher compared to that in healthy individuals (P < 0.01). The apoptosis of human OA chondrocytes was inhibited when silencing UBE2M and increased when overexpressing UBE2M. XAV939, as a tankyrase 1 inhibitor, could block the signaling pathway of Wnt/ß-catenin, which significantly reversed the change introduced by UBE2M. The expression level of cytoplasmic ß-catenin in siUBE2M cells dramatically increased, and the expression levels of nuclear ß-catenin, cleaved caspase-3 (C-caspase-3), and MMP13 remarkably downregulated. Moreover, the ubiquitination of Axin was enhanced by the overexpression of UBE2M. The expression level of Axin significantly decreased in OA chondrocytes with UBE2M overexpression and increased after MG132 treatment. Moreover, UBE2M enhanced the apoptosis of OA chondrocytes by activating the Axin-dependent Wnt/ß-catenin pathway. In this process, UBE2M downregulated Axin in an ubiquitination-dependent degradation pathway and subsequently activated Wnt/ß-catenin signaling.


Assuntos
Condrócitos/metabolismo , Osteoartrite/genética , Tanquirases/genética , Enzimas de Conjugação de Ubiquitina/genética , Proteínas Wnt/genética , beta Catenina/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteína Axina/genética , Proteína Axina/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Estudos de Casos e Controles , Caspase 3/genética , Caspase 3/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Fêmur/metabolismo , Fêmur/patologia , Regulação da Expressão Gênica , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Leupeptinas/farmacologia , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Tanquirases/antagonistas & inibidores , Tanquirases/metabolismo , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Enzimas de Conjugação de Ubiquitina/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo
15.
Int J Clin Exp Pathol ; 13(3): 616-623, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32269703

RESUMO

Cartilage degeneration is considered the main pathologic feature of osteoarthritis (OA). Cumulative evidence indicates that chondrocyte apoptosis is associated with cartilage degradation. However, the underlying molecular mechanism of chondrocyte apoptosis remains unclear. Growth factor receptor-bound protein 2 (GAB2), an adaptor protein, belongs to the Gab family and is involved in various biologic processes. Here, we explored the role of GAB2 in the pathogenesis of osteoarthritis (OA). GAB2 expression was markedly increased in OA articular cartilage. GAB2 expression was also increased in an in vitro model of TNFα-induced apoptosis. GAB2 depletion by siRNA promoted expression of the apoptosis markers, PARP and caspase-3, and increased the number of apoptotic cells, indicating that GAB2 might have an anti-apoptotic effect in chondrocytes. Moreover, GAB2 knockdown inhibited AKT phosphorylation, increased BAX expression, and decreased BCL2 expression, which indicated that GAB2 regulates chondrocyte apoptosis through PI3K-AKT signaling. Taken together, our study indicates that GAB2 plays a vital role in chondrocyte apoptosis and provides a new therapeutic target for OA.

16.
Clin Cancer Res ; 25(16): 5049-5060, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31113842

RESUMO

PURPOSE: Genomic analyses of small-cell lung cancer (SCLC) are limited by the availability of tumor specimens. This study aimed to investigate the suitability of single-cell sequencing of circulating tumor cells (CTC) as a method of inferring the evolution and progression of SCLCs. EXPERIMENTAL DESIGN: Between July 1, 2011, and July 28, 2014, 48 consecutively diagnosed patients with SCLC were recruited for this study. CTCs were captured from each patient with CellSearch system. Somatic mutations and copy number alterations (CNA) were monitored by single-cell sequencing of CTCs during chemotherapy. RESULTS: Single-cell sequencing of CTCs can provide a mutational atlas for SCLC. A 10-CNA score based on single CTCs was established as a classifier for outcomes of initial chemotherapy in patients with SCLC. The survival analyses demonstrated that patients with low CNA scores (<0) had significantly prolonged progression-free survival (PFS) and overall survival (OS) after first-line chemotherapy in comparison with those with high scores (≥0; PFS: 212 days vs. 110.5 days, P = 0.0042; and OS: 223.5 days vs. 424 days, P = 0.0006). The positive predictive value and negative predictive value of the CNA score for clinical subtype (refractory vs. sensitive) were 80.0% and 93.7%, respectively. By tracing allele-specific CNAs in CTCs isolated at different time points during chemotherapy, we showed that CNA heterogeneity might result from allelic losses of initially consistent CNAs. CONCLUSIONS: Single CTC-based sequencing can be utilized to depict the genomic profiles and evolutionary history of SCLC, thus offering the potential for clinical stratification of patients with SCLC.


Assuntos
Biomarcadores Tumorais , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Células Neoplásicas Circulantes/patologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/genética , Adulto , Idoso , Biologia Computacional/métodos , Variações do Número de Cópias de DNA , Progressão da Doença , Feminino , Heterogeneidade Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Célula Única , Carcinoma de Pequenas Células do Pulmão/mortalidade
17.
Medicine (Baltimore) ; 98(20): e15668, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096497

RESUMO

INTRODUCTION: Intravascular migration of a double J stent into the inferior vena cava is an uncommon complication. The management of such complication is less reported in the literature. This study aimed to reveal the diagnosis and treatment process of migration of a double J stent into the inferior vena cava. PATIENT CONCERNS: A 53-year-old male patients was transferred to our hospital because of migration of a double J stent into the inferior vena cava after left-side pyelolithotomy. DIAGNOSIS: In accordance with manifestations on computed tomography urography, the patient was diagnosed with migration of a double J stent into the inferior vena cava. INTERVENTIONS: Percutaneous nephroscope under C-arm guidance was performed to remove the migrated stent. After the operation, the patient was treated with continued anticoagulants and antibiotics. OUTCOMES: The migrated stent was removed successfully without any complications, and a new double J stent was placed and its location was confirmed under C-arm. The patient was discharged in good condition and the follow-up was uneventful. CONCLUSION: Intravascular migration of a double J stent into the inferior vena cava is an uncommon complication. Radiologic imaging after placement of ureteral stent is critical for prevention of this complication. Percutaneous nephroscope under C-arm guidance is a safe and effective approach to remove the migrated DJS in the IVC.


Assuntos
Migração de Corpo Estranho/cirurgia , Stents , Veia Cava Inferior/cirurgia , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Migração de Corpo Estranho/diagnóstico por imagem , Humanos , Cálculos Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Veia Cava Inferior/diagnóstico por imagem
18.
Carbohydr Polym ; 206: 29-37, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553325

RESUMO

An electrospinning process was utilized to fabricate composite nanofibers of poly(methyl methacrylate) (PMMA) reinforced with cellulose nanocrystals (CNCs). The effect of environmental relative humidity on the microstructure of CNC/PMMA nanofibers was investigated. Results showed that fiber surfaces of CNC/PMMA appeared smooth. Fibers had gradually decreasing diameters and lower diameter variations as CNC loading increased. The thermal property of CNC/PMMA nanofibers was also enhanced due to hydrogen bonding between PMMA molecular chains and CNC nanoparticles. Compared to pure PMMA fibers, the storage modulus and tensile strength of composite nanofibers were pronouncedly improved. By increasing relative humidity of the electrospinning environment, these nanofibers showed prominent nanoporous surfaces while the surface roughness and porosity of CNC/PMMA nanofibers increased. Furthermore, CNCs were critical to accelerating the evolution of pores and increasing surface roughness. Our findings can provide useful guidelines for the fabrication of nanofibers with desired properties and pore structure by electrospinning.

19.
Materials (Basel) ; 11(8)2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30072639

RESUMO

The agglomeration of silver nanoparticles (AgNPs) results in poor antibacterial performance, and the accumulation of silver in the human body threatens human health. Preparing a matrix is a technique worth considering as it not only prevents the aggregation of AgNPs but also reduces deposition of AgNPs in the human body. In this paper, carboxy-cellulose nanocrystals (CCNC) were prepared by a simple one-step acid hydrolysis method. Chito-oligosaccharides (CSos) were grafted onto the surface of CCNC to form CSos-CCNC composite nanoparticles. CCNC and CSos-CCNC were used as stabilizers for deposing AgNPs and two types of complexes-AgNPs-CCNC and AgNPs-CSos-CCNC-were obtained, respectively. The influence of the two stabilizer matrices-CCNC and CSos-CCNC-on the morphology, thermal behavior, crystal structure, antibacterial activity, and cell compatibility of AgNPs-CCNC and AgNPs-CSos-CCNC were examined. The results showed that the AgNPs deposited on the CSos-CCNC surface had a smaller average diameter and a narrower particle size distribution compared with the ones deposited on CCNC. The thermal stability of AgNPs-CSos-CCNC was better than that of AgNPs-CCNC. AgNPs did not affect the crystalline structure of CCNC and CSos-CCNC. The antibacterial activity of AgNPs-CSos-CCNC was better than that of AgNPs-CCNC based on antibacterial studies using Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae. The cytotoxicity of AgNPs-CSos-CCNC was remarkably lower than that of AgNPs-CCNC.

20.
Polymers (Basel) ; 10(10)2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30960971

RESUMO

Cellulose nanocrystals/chitosan/polyvinyl alcohol (CNC/CS/PVA) composite nanofibrous films were prepared while using an electrospinning technique and successfully thiol-functionalized. Then, the modified films were used for the sorption-desorption of Cu(II) and Pb(II) ions. Subsequently, the adsorption capacity of the films was investigated by changing the CNC loading level, solution pH, and adsorption time. Results showed that the adsorption of metal ions by the films was the best with CNC loading level of 5 wt %, pH of 6, and adsorption time of 4 h. The adsorption behavior of the films was agreed with the Freundlich model. The adsorption equation of metal ions could be described while using a pseudo-second order model. Based on the Langmuir model, the maximum adsorption capacities of Cu(II) and Pb(II) ions were estimated to be 484.06 and 323.49 mg/g, respectively. The Cu(II) and Pb(II) ions adsorption efficiencies of the films after 4 adsorption-desorption cycles were 90.58% and 90.21%, respectively. This study may provide a feasible approach for the application of functional CNC/CS/PVA nanofibrous films in the treatment of water.

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