Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
BMC Surg ; 24(1): 182, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877438

RESUMO

PURPOSE: We describe a surgical technique for ACL reconstruction combined with anterolateral structure reinforcement and report early clinical follow-up results. METHODS: The semitendinosus and gracilis tendons are braided into 5 strands and the ACL femoral tunnel and tibial tunnel are created. The graft is passed through the tunnel with the use of a traction suture and the tibial end is fixed with absorbable interference screws at 30° of knee flexion. The ACL graft traction suture is used as an anterolateral reconstruction structure to pass through the proximal exit of the ACL femoral tunnel and then through the depth of the iliotibial bundle to the anterior to Gerdy's tubercle, a bony tunnel is created from the anterior to Gerdy's tubercle to the goose foot, and the traction suture is passed through this bony tunnel to form a Loop structure at 20° of knee flexion. Between March 2021 and May 2022 IKDC score, Lysholm score, and Tegner score were performed preoperatively and 6-12 months postoperatively in 24 consecutive patients who met the indications for this procedure and underwent surgery. The patient's maximum flexion angle, the circumference of the thigh, and the stress X-ray between the operated and healthy knee were measured. RESULTS: Patients showed significant improvement in IKDC score, Lysholm score and Tegner score at a mean follow-up of 7 months postoperatively compared to preoperatively. No significant increase in anterior tibial displacement was found between the patient's operated side and the healthy side. CONCLUSION: The Loop technique ACLR combined with ALSA can be used in patients with an ACL tear combined with a high degree of positive pivot shift. The patient's subjective perception was significantly improved from the preoperative period and knee stability was restored. LEVEL OF EVIDENCE: IV, therapeutic study.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Humanos , Reconstrução do Ligamento Cruzado Anterior/métodos , Adulto , Masculino , Feminino , Lesões do Ligamento Cruzado Anterior/cirurgia , Resultado do Tratamento , Adulto Jovem , Seguimentos , Técnicas de Sutura , Amplitude de Movimento Articular/fisiologia , Pessoa de Meia-Idade , Tendões/transplante , Tíbia/cirurgia , Adolescente
2.
Angew Chem Int Ed Engl ; 63(21): e202401118, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38433100

RESUMO

Inorganic zeolites have excellent molecular sieving properties, but they are difficult to process into macroscopic structures. In this work, we use metal-organic framework (MOF) glass as substrates to engineer the interface with inorganic zeolites, and then assemble the discrete crystalline zeolite powders into monolithic structures. The zeolites are well dispersed and stabilized within the MOF glass matrix, and the monolith has satisfactory mechanical stabilities for membrane applications. We demonstrate the effective separation performance of the membrane for 1,3-butadiene (C4H6) from other C4 hydrocarbons, which is a crucial and challenging separation in the chemical industry. The membrane achieves a high permeance of C4H6 (693.00±21.83 GPU) and a high selectivity over n-butene, n-butane, isobutene, and isobutane (9.72, 9.94, 10.31, and 11.94, respectively). This strategy opens up new possibilities for developing advanced membrane materials for difficult hydrocarbon separations.

3.
ChemMedChem ; 19(2): e202300467, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38031642

RESUMO

As a critical epigenetic modulator of gene expression, histone deacetylases (HDACs) have been involved in the pathogenesis and therapeutic investigation of cancer. Quinolizidine alkaloid sophoridine is known to have anticancer efficacy but with limited indication. By incorporating the pharmacophore of the HDAC inhibitor into the ring-opened sophoridine core, a new series of sophoridine hydroxamic acid derivatives were synthesized. After structure-activity studies, a selected compound was found to exert significant cytotoxicity in triple-negative breast cancer CAL-51 cells (IC50 1.17 µM), and demonstrated low nanomolar inhibitory potency toward HDAC1/3/6. Cellular functional assays indicated that this compound was able to induce apoptosis and cause accumulation of cells in the S phase of the cell cycle. Western blot analysis revealed it to decrease the expression of DNMT1, DNMT3a and DNMT3b by down-regulating phosphor-ERK1/2. Furthermore, treatment with this compound proved to block the PI3K/AKT/mTOR signaling in the PI3KCA and PTEN-mutant CAL-51 cells. Collectively, this work provides a novel lead compound for the development of potential therapeutics against triple-negative breast cancers, possibly mesenchymal-like subtype.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Inibidores de Histona Desacetilases/farmacologia , Matrinas , Alcaloides Quinolizidínicos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Ácidos Hidroxâmicos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Histona Desacetilase 1 , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais
4.
Heliyon ; 9(9): e20024, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809922

RESUMO

Spinal cord injury (SCI) is a highly complex neurological disease, but there is no effective repair method. Quercetin is a flavonol drug and has a variety of biological activities, such as scavenging oxygen free radicals in the body to resist oxidation, inhibiting inflammation, and so on. In this study, quercetin was firstly demonstrated to reduce tissue damage, promote neuron survival and repair motor function after SCI in rats through in vivo experiments. Then, 293 potential targets of quercetin repair for SCI were predicted by network pharmacology. GO analysis revealed that the biological processes of potential targets focused mainly on signal transduction, negative regulation of the apoptotic process, protein phosphorylation, drug response, and so on. Similarly, KEGG analysis suggested that these potential targets were involved in cell growth regulation, differentiation, apoptosis, and a few metabolic pathways. PPI network analysis predicted that the key genes were EP300, CREBBP, SRC, HSP90AA1, TP53, PIK3R1, EGFR, ESR1, and CBL. Further, the molecular docking showed that quercetin binds well with these proteins. Finally, RT-qPCR and Western blotting experiments verified that quercetin downregulated the expression levels of PIK3R1 and EGFR. It is suggested that quercetin can repair SCI in rats through PI3K-AKT signaling pathway and EGFR/MAPK pathway, which may provide a new theoretical basis for the repair of spinal cord injury.

5.
Nat Mater ; 22(7): 888-894, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37169976

RESUMO

Membranes with ultrahigh permeance and practical selectivity could greatly decrease the cost of difficult industrial gas separations, such as CH4/N2 separation. Advanced membranes made from porous materials, such as metal-organic frameworks, can achieve a good gas separation performance, although they are typically formed on support layers or mixed with polymeric matrices, placing limitations on gas permeance. Here an amorphous glass foam, agfZIF-62, wherein a, g and f denote amorphous, glass and foam, respectively, was synthesized by a polymer-thermal-decomposition-assisted melting strategy, starting from a crystalline zeolitic imidazolate framework, ZIF-62. The thermal decomposition of incorporated low-molecular-weight polyethyleneimine evolves CO2, NH3 and H2O gases, creating a large number and variety of pores. This greatly increases pore interconnectivity but maintains the crystalline ZIF-62 ultramicropores, allowing ultrahigh gas permeance and good selectivity. A self-supported circular agfZIF-62 with a thickness of 200-330 µm and area of 8.55 cm2 was used for membrane separation. The membranes perform well, showing a CH4 permeance of 30,000-50,000 gas permeance units, approximately two orders of magnitude higher than that of other reported membranes, with good CH4/N2 selectivity (4-6).


Assuntos
Gases , Estruturas Metalorgânicas , Peso Molecular , Polietilenoimina , Polímeros
6.
Angew Chem Int Ed Engl ; 62(28): e202304535, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37170008

RESUMO

Metal-organic framework (MOF) glass is an easy to process and self-supported amorphous material that is suitable for fabricating gas separation membranes. However, MOF glasses, such as ZIF-62 and ZIF-4 have low porosity, which makes it difficult to obtain membranes with high permeance. Here, a self-supported MOF crystal-glass composite (CGC) membrane was prepared by melt quenching a mixture of ZIF-62 as the membrane matrix and ZIF-8 as the filler. The conversion of ZIF-62 from crystal to glass and the simultaneous partial melting of ZIF-8 facilitated by the melt state of ZIF-62 make the CGC membrane monolithic, eliminating non-selective grain boundaries and improving selectivity. The thickness of CGC membrane can be adjusted to fabricate a membrane without the need of a support substrate. CGC membranes exhibit a C2 H6 permeance of 41 569 gas permeation units (GPU) and a C2 H6 /C2 H4 selectivity of 7.16. The CGC membrane has abundant pores from the glassy state of ZIF-62 and the crystalline ZIF-8, which enables high gas permeance. ZIF-8 has preferential adsorption for C2 H6 and promotes C2 H6 transport in the membrane, and thus the GCG membrane exhibits ultrahigh C2 H6 permeance and good C2 H6 /C2 H4 selectivity.

7.
Phytomedicine ; 116: 154840, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37172477

RESUMO

BACKGROUND: Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which is a highly malignant tumor and lack of effective treatment. Although Xiao Chai Hu Tang (XCHT) has a good therapeutic effect on pancreatic cancer patients with advanced stage, the effect and mechanism of XCHT remains unclear in pancreatic tumorigenesis. PURPOSE: To assess the therapeutic effects of XCHT on the malignant transformation from PanIN to PDAC and to reveal its mechanisms of pancreatic tumorigenesis. METHODS: Syrian golden hamster were induced by N-Nitrosobis (2-oxopropyl) amine (BOP) to establish the pancreatic tumorigenesis model. The morphological changes of pancreatic tissue were observed by H&E and Masson staining; the Gene ontology (GO) analysis the transcriptional profiling changes; the mitochondrial ATP generation, mitochondrial redox status, mitochondrial DNA (mtDNA) N6-methyladenine (6mA) level and relative mtDNA genes expressions were examined. In addition, immunofluorescence detect the cell localization of 6mA in human pancreatic cancer PANC1 cell. Using the TCGA database, the prognostic effect of mtDNA 6mA demethylation ALKBH1 expression on pancreatic cancer patients was analyzed. RESULTS: We confirmed the mtDNA 6mA levels were gradually increased with the mitochondrial dysfunction in PanINs progression. XCHT showed the effect to inhibit the occurrence and development of pancreatic cancer in Syrian hamster pancreatic tumorigenesis model. In addition, the lack of ALKBH1 mediated mtDNA 6mA increase, mtDNA coded genes down-expression and abnormal redox status were rescued by XCHT. CONCLUSIONS: ALKBH1/mtDNA 6mA mediated mitochondrial dysfunction to induce the occurrence and progression of pancreatic cancer. XCHT can improve ALKBH1 expression and mtDNA 6mA level, regulate the oxidative stress and expression of mtDNA coded genes. This study investigated a new molecular mechanism of pancreatic tumorigenesis, and revealed the therapeutic efficacy of XCHT in pancreatic tumorigenesis for the first time.


Assuntos
Bupleurum , Neoplasias Pancreáticas , Animais , Cricetinae , Humanos , DNA Mitocondrial/genética , Mesocricetus , Carcinogênese , Transformação Celular Neoplásica , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Mitocôndrias , Homólogo AlkB 1 da Histona H2a Dioxigenase , Neoplasias Pancreáticas
8.
Theor Appl Genet ; 136(5): 110, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37039971

RESUMO

KEY MESSAGE: KLW1 was localized to a 0.6 cM interval near the centromere of chromosome 4B and found to be dominant in conditioning longer kernels and higher kernel weight. Kernel weight is a major wheat yield component and affected by kernel dimensions, filling process and kernel density. Because of this complexity, the mechanism underlying kernel weight is still far from clear. Qtgw.nau-4B or KLW1 was a major kernel weight QTL identified in the Nanda2419 × Wangshuibai population. We showed that introduction of the Nanda2419 allele into elite cultivar Wenmai6 resulted in longer kernels as well as higher kernel weight, without affecting other traits such as spike number per plant, plant height, spike length, spikelet number per spike, and kernel number per spike. KLW1 was dominant in conditioning higher kernel weight and functioned mainly through affecting kernel length. Using F2 plants derived from KLW1 NIL, a high-density genetic map covering the QTL was constructed. KLW1 was consequently confined to the 0.6 cM Xwgrc4219-Xwgrc4067 interval by evaluating the recombinant lines in three field trials. KLW1 is complementary to KT1, the QTL on chromosome 5A of Nanda2419 for thicker and heavier kernels, in producing larger kernels with higher commercial value, augmenting its usefulness in wheat breeding.


Assuntos
Locos de Características Quantitativas , Triticum , Mapeamento Cromossômico/métodos , Triticum/genética , Melhoramento Vegetal , Cromossomos de Plantas
9.
Bioorg Med Chem Lett ; 76: 129007, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36174835

RESUMO

Erythropoietin (EPO) is the predominant regulating factor in erythropoiesis. Herein we describe the identification of (4-hydroxy-2-(substitued sulfonamido)pyrimidine-5-carbonyl) glycine-based oral EPO secretagogues. Most of these compounds obviously increased the EPO level in Hep3B cells by stabilizing the hypoxia-inducible factor-α (HIF-α). Furthermore, their potential inhibitory activities against HIF prolyl hydroxylase domain (PHD) revealed their function as PHD inhibitors in PHD-HIF pathway. Compound 6i, with a biphenyl substituent on the sulfonamido group, particularly increased plasma EPO level in mice and could serve as a candidate of EPO stimulating agent for anemia treatment.


Assuntos
Eritropoetina , Glicina , Camundongos , Animais , Glicina/farmacologia , Secretagogos , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Eritropoetina/farmacologia , Eritropoetina/metabolismo , Prolil Hidroxilases , Pirimidinas/farmacologia
10.
J Biomed Mater Res A ; 110(4): 838-850, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34859573

RESUMO

Hyaluronan (HA) provides a favorable environment for chondrogenesis of bone marrow mesenchymal stem cells (BMSCs). A previous report from our group indicated that addition of HA increases the chondro-inductive capacity of scaffolds. Therefore, this study aimed to investigate whether the Mw of the HA could affect chondrogenesis of BMSCs seeded on TCP-COL-HA scaffolds. Human BMSCs (hBMSCs) and rabbit BMSCs (rBMSCs) were isolated and expanded. TCP-COL scaffolds and TCP-COL-HA scaffolds with two different HA Mws were assessed for their capacity to induce cartilage regeneration from hBMSCs in vitro and in vivo. The results showed that about 96.96% of hBMSCs expressed CD44. Moreover, Hyal-1 and chondrogenic marker genes expressions were increased in hMSCs seeded on TCP-COL-HA scaffolds, and blocking the HA-CD44 interaction with an anti-CD44 antibody reduced the expression levels of Hyal-1 and chondrogenic marker genes. Additionally, TCP-COL-HA scaffolds with 2000 kDa Mw showed greater induction of BMSC chondrogenesis induction compared with those with 80 kDa Mw. Similar results were observed in an ectopic implantation nude mouse model. In a rabbit osteochondral defect repair model, rBMSCs seeded on TCP-COL-HA scaffolds with 2000 kDa Mw showed greater cartilage regeneration than those seeded with 80 kDa Mw. In addition, hBMSC-seeded TCP-COL-HA scaffolds with 2000 kDa Mw showed a significantly higher mechanical strength than those with 80 kDa Mw. Collectively, these results indicate that the Mw of HA could affect chondrogenesis of BMSCs seeded on TCP-COL-HA scaffolds. The TCP-COL-HA scaffolds might be used as allogenic off the shelf products in cartilage tissue engineering in future.


Assuntos
Condrogênese , Células-Tronco Mesenquimais , Animais , Fosfatos de Cálcio , Diferenciação Celular , Células Cultivadas , Colágeno/farmacologia , Humanos , Ácido Hialurônico/metabolismo , Ácido Hialurônico/farmacologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Coelhos , Engenharia Tecidual/métodos , Alicerces Teciduais
11.
ChemMedChem ; 17(1): e202100434, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34569159

RESUMO

In order to improve the antitumor potency and therapeutic margins of natural product sophoridine, its novel nitrogen mustard carbamate derivatives were designed and synthesized. In screening their in vitro activity, we found all the tested compounds were more potent against the highly aggressive triple-negative breast cancer cell line MDA-MB-231. Cellular functional assays showed that representative compounds could induce G1-phase arrest and trigger apoptosis, evidenced by the alteration of Bax, Bcl-2, caspase-3 and PARP levels. Furthermore, these compounds significantly enhanced the autophagic flux with increased expression of LC3-II and Beclin-1, as well as decreased level of p62, which may attribute to simultaneously inhibition of the phosphorylation of p70S6K, 4E-BP1 and AKT, the key substrates of the mTOR signaling pathway. In vivo, two compounds revealed potent antitumor activity in mice bearing MDA-MB-231. Altogether, our work describes novel leads to yield more potent chemotherapeutics against triple-negative breast cancers, possibly mesenchymal stem-like subtype.


Assuntos
Alcaloides/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Quinolizinas/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Alcaloides/síntese química , Alcaloides/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Quinolizinas/síntese química , Quinolizinas/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Matrinas
12.
Front Plant Sci ; 12: 694023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335661

RESUMO

Wheat production is increasingly threatened by the fungal disease, Fusarium head blight (FHB), caused by Fusarium spp. The introduction of resistant varieties is considered to be an effective measure for containment of this disease. Mapping of FHB-resistance quantitative trait locus (QTL) has promoted marker-assisted breeding for FHB resistance, which has been difficult through traditional breeding due to paucity of resistance genes and quantitative nature of the resistance. The lab of Ma previously cloned Fhb1, which inhibits FHB spread within spikes, and fine mapped Fhb4 and Fhb5, which condition resistance to initial infection of Fusarium spp., from FHB-resistant indigenous line Wangshuibai (WSB). In this study, these three QTLs were simultaneously introduced into five modern Chinese wheat cultivars or lines with different ecological adaptations through marker-assisted backcross in early generations. A total of 14 introgression lines were obtained. All these lines showed significantly improved resistance to the fungal infection and disease spread in 2-year field trials after artificial inoculation. In comparison with the respective recipient lines, the Fhb1, Fhb4, and Fhb5 pyramiding could reduce the disease severity by 95% and did not systematically affect plant height, productive tiller number, kernel number per spike, thousand grain weight, flowering time, and unit yield (without Fusarium inoculation). These results indicated the great value of FHB-resistance QTLs Fhb1, Fhb4, and Fhb5 derived from WSB, and the feasibility and effectiveness of early generation selection for FHB resistance solely based on linked molecular markers.

13.
Mol Ther Nucleic Acids ; 22: 832-845, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230479

RESUMO

Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease in aged people. Progressive cartilage degradation is the hallmark of KOA, but its deeper mechanism remains unclear. Substantial evidence indicates the importance of the synovium for joint homeostasis. The present study aimed to determine whether the synovium regulates cartilage metabolism through chondrogenesis-related microRNAs (miRNAs) in the KOA microenvironment. Clinical sample testing and in vitro cell experiments screened out miR-455 and miR-210 as effective miRNAs. The levels of both were significantly reduced in KOA cartilage but increased in KOA synovial fluid compared with controls. We further revealed that transforming growth factor ß1 (TGF-ß1) can significantly upregulate miR-455 and miR-210 expression in synoviocytes. The upregulated miRNAs can be secreted into the extracellular environment and prevent cartilage degeneration. Through bioinformatics and in vitro experiments, we found that Runx1 can bind to the promoter regions of miR-455 and miR-210 and enhance their transcription in TGF-ß1-treated synoviocytes. Collectively, our findings demonstrate a protective effect of the synovium against cartilage degeneration mediated by chondrogenesis-related miRNAs, which suggests that Runx1 is a potential target for KOA therapy.

14.
ACS Med Chem Lett ; 10(9): 1328-1335, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531205

RESUMO

Five innovative ternary copper(II) complexes [Cu(OH-PIP)(Phe)Cl](1), [Cu(OH-PIP)(Gly)(H2O)]NO3·2H2O (2), [Cu(OH-PIP)(Ala)(Cl)]·H2O (3), [Cu(OH-PIP)(Met)]PF6·2H2O (4), and [Cu(OH-PIP)(Gln)(H2O)](Cl)·3H2O (5) have been synthesized and characterized by infrared spectroscopy, elemental analysis, and single crystal X-ray diffraction analysis. X-ray crystallography indicates that all Cu atoms are five-coordinated in a square-pyramidal configuration. The complexes have been screened for cytotoxicity against human breast cancer cell lines MCF-7, MDA-MB-231, and CAL-51. The best anticancer activity is obtained with triple-negative breast cancer CAL-51 and MDA-MB-231 cell lines, with IC50 values in the range of 0.082-0.69 µM. Importantly, the copper compounds were more effective than carboplatin at triggering cell death. Mechanistically, the complexes inhibit proteasomal chymotrypsin-like activity, and docking studies reveal their 20S proteasome binding sites. As a consequence, they cause the accumulation of ubiquitinated proteins, inhibit cell proliferation, and induce apoptosis. In addition, these copper complexes decrease the stemness of triple-negative breast cancer cells and have synergistic effects with CBP on TNBC cells, indicating their great potential as a novel therapy for triple-negative breast cancer.

15.
Molecules ; 23(8)2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30082625

RESUMO

Novel mustard functionalized sophoridine derivatives were synthesized and evaluated for their cytotoxicity against of a panel of various cancer cell lines. They were shown to be more sensitive to S180 and H22 tumor cells with IC50 values ranging from 1.01⁻3.65 µM, and distinctly were more cytotoxic to cancer cells than normal cell L929. In addition, compounds 7a, 7c, and 7e displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Furthermore, they arrested tumor cells in the G1 phase and induced cellular apoptosis. Their potential binding modes with DNA-Top I complex have also been investigated.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Mostardas de Fosforamida/química , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Relação Estrutura-Atividade
16.
Theranostics ; 8(10): 2862-2883, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29774080

RESUMO

Histone deacetylase 3 (HDAC3) plays a pivotal role in the repression of cartilage-specific gene expression in human chondrocytes. The aim of this study was to determine whether microRNA-193b-3p (miR-193b-3p) regulates the expression of HDAC3 during chondrogenesis and chondrocyte metabolism. Methods: miR-193b-3p expression was assessed in a human mesenchymal stem cell (hMSC) model of chondrogenesis, in interleukin-1ß (IL-1ß)-treated primary human chondrocytes (PHCs), and in non-degraded and degraded cartilage. hMSCs and PHCs were transfected with miR-193b-3p or its antisense inhibitor. A direct interaction between miR-193b-3p and its putative binding site in the 3'-untranslated region (3'-UTR) of HDAC3 mRNA was confirmed by performing luciferase reporter assays. Chondrocytes were transfected with miR-193b-3p before performing a chromatin immunoprecipitation assay with an anti-acetylated histone H3 antibody. To investigate miR-193b-3p-transfected PHCs in vivo, they were seeded in tricalcium phosphate-collagen-hyaluronate (TCP-COL-HA) scaffolds, which were then implanted in nude mice. In addition, plasma exosomal miR-193b-3p in samples from normal controls and patients with osteoarthritis (OA) were measured. Results: miR-193b-3p expression was elevated in chondrogenic and hypertrophic hMSCs, while expression was significantly reduced in degraded cartilage compared to non-degraded cartilage. In addition, miR-193b-3p suppressed the activity of reporter constructs containing the 3'-UTR of HDAC3, inhibited HDAC3 expression, and promoted histone H3 acetylation in the COL2A1, AGGRECAN, COMP, and SOX9 promoters. Treatment with the HDAC inhibitor trichostatin A (TSA) increased cartilage-specific gene expression and enhanced hMSCs chondrogenesis. TSA also increased AGGRECAN expression and decreased MMP13 expression in IL-1ß-treated PHCs. Further, 8 weeks after implanting PHC-seeded TCP-COL-HA scaffolds subcutaneously in nude mice, we found that miR-193b overexpression strongly enhanced in vivo cartilage formation compared to that found under control conditions. We also found that patients with OA had lower plasma exosomal miR-193b levels than control subjects. Conclusions: These findings indicate that miR-193b-3p directly targets HDAC3, promotes H3 acetylation, and regulates hMSC chondrogenesis and metabolism in PHCs.


Assuntos
Condrócitos/metabolismo , Condrogênese , Histona Desacetilases/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Animais , Células Cultivadas , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/transplante , Exossomos/metabolismo , Feminino , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Regeneração
17.
J Invest Surg ; 31(5): 431-437, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28722498

RESUMO

PURPOSE: To compare the postoperative survival and mortality rates in intertrochanteric femoral fracture (IFF) patients who underwent either open reduction internal fixation (ORIF) or hip arthroplasty. METHODS: Clinical data from senior patients who had IFF and underwent ORIF or hip arthroplasty were analyzed retrospectively. Survival curves were compared between groups with Kaplan-Meier method and log-rank test. Significant independent prognostic factors were identified by Cox multivariate regression analysis. RESULTS: All patients recovered fully post-surgery. Although 31 patients died during the follow-up period (ORIF, mean 45.4 months; arthroplasty, mean 51.6 months), mortality rate did not differ significantly between the groups. The 1-yr and 2-yr survival rate estimates for the ORIF group were 92.2%, and 86%, respectively; they were 85% and 74% for the arthroplasty group. Average survival lengths for ORIF and arthroplasty groups were 88 and 67 months, respectively. The effect of surgical approaches on survival differed significantly (log-rank test c2 = 6.402, p = 0.011). Multivariate Cox regression model indicated that surgical choice (p = 0.036) was a significant independent risk factor for the prognosis of senile IFF, even with adjustment for age (p = 0.002). CONCLUSION: The overall postoperative prognosis was superior in senile IFF patients treated with ORIF.


Assuntos
Artroplastia de Quadril/métodos , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/cirurgia , Fraturas por Osteoporose/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Parafusos Ósseos , China/epidemiologia , Feminino , Seguimentos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Fraturas do Quadril/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Fraturas por Osteoporose/mortalidade , Seleção de Pacientes , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
Chin Med J (Engl) ; 129(21): 2524-2529, 2016 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-27779156

RESUMO

BACKGROUND: Accuracy of implant placement in total knee arthroplasty (TKA) is crucial. Traditional extramedullary alignment instruments are fairly effective for achieving the desired mean tibial component coronal alignment. We modified the traditional tibial plateau resection technique and evaluated its effect on alignment restoration. METHODS: Two hundred and eighty-two primary TKAs in our hospital between January 2013 and December 2014 were enrolled in this retrospective study. Group A consisted of 128 primary TKAs performed by one senior surgeon. Preoperative measurement of the tibial resection was conducted on radiographs, and the measured thicknesses of the lateral and medial plateau resection were used to place the tibial alignment guide. Group B consisted of 154 primary TKAs performed by the other senior surgeon, using a traditional tibial plateau resection technique. In all patients, an extramedullary guide was used for tibial resection, and preoperative and postoperative full-leg standing radiographs were used to assess the hip-knee-ankle angle (HKA), femoral component alignment angle (FA), and tibial component alignment angle (TA). A deviation ≥3° was considered unsatisfactory. Data were analyzed by unpaired Student's t-test. RESULTS: The mean postoperative HKA and TA angles were significantly different between Groups A and B (178.2 ± 3.2° vs. 177.0 ± 3.0°, t = 2.54, P = 0.01; 89.3 ± 1.8° vs. 88.3 ± 2.0°, t = 3.75, P = 0.00, respectively). The mean postoperative FA was 88.9 ± 2.5° in Group A and 88.9 ± 2.6° in Group B, and no significant difference was detected (t = 0.10, P = 0.92). There were 90 (70.3%) limbs with restoration of the mechanical axis to within 3° of neutral alignment and 38 (29.7%) outliers (>3° deviation) in Group A, whereas there were 89 (57.8%) limbs with restoration of the mechanical axis to within 3° of neutral alignment and 65 (42.2%) outliers (>3° deviation) in Group B. The severity of the preoperative alignment deformity was a strong predictor for postoperative alignment. CONCLUSIONS: Using conventional surgical instruments, preoperative measurement of resection thickness of the tibial plateau on radiographs could improve the accuracy of conventional surgical techniques.


Assuntos
Artroplastia do Joelho/métodos , Mau Alinhamento Ósseo/prevenção & controle , Articulação do Joelho/cirurgia , Tíbia/cirurgia , Idoso , Feminino , Humanos , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Tíbia/anatomia & histologia
19.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 30(11): 1349-1353, 2016 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-29786384

RESUMO

OBJECTIVE: To investigate the influence of the degree of acetabular deformity and the learning-curve on the acetabular cup positions in total hip arthroplasty (THA) for adults with developmental dysplasia of hip (DDH). METHODS: Between January 2008 and December 2015, 130 patients (144 hips) with DDH underwent primary THA, and the clinical data were analyzed retrospectively. Fifty-three patients (59 hips) were admitted before 2012, and 77 patients (85 hips) were treated after 2012. There were 32 males and 98 females, aged from 31 to 83 years (mean, 61). Unilateral replacement was performed in 116 cases and bilateral replacement in 14 cases. Of 144 hips, 48 hips were rated as Crowe type I, 57 hips as type II, and 39 hips as type of III/IV. The standard pelvic radiograph was taken within 1 week after operation. The mediCAD software was adopted to measure the angle of anteversion and abduction, bony coverage, and the distance between true rotating center and optimal rotating center to the connection of teardrops and the horizontal distance between two centers to evaluate the qualified rate of acetabular cup positions. RESULTS: Compared with the patients with the same type in 2013-2015 group, the anteversion angle and qualified rate of acetabular cup position significantly decreased in patients with Crowe I (P<0.05); the horizontal distance significantly increased and qualified rate of acetabular cup position significantly decreased in patients with Crowe II (P<0.05); and the anteversion angle significantly decreased and the horizontal distance significantly increased in patients with Crowe III/IV (P<0.05) in 2008-2012 group. But no significant difference was shown in the other indexes (P>0.05). In all Crowe types, the vertical distance between the true rotating center and the optimal rotating center increased with the degree of acetabular deformity in both 2008-2012 group and 2013-2015 group, showing significant difference (P<0.05), but no significant difference was found in the other indexes (P>0.05). CONCLUSIONS: For adults with acetabular dysplasia, there are high potential risks for unsatisfactory acetabular cup positions during primary THA. So it is necessary to evaluate acetabular deformities and to sum up operative experience so as to improve the accuracy of cups installation.

20.
Zhongguo Gu Shang ; 28(8): 699-703, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26502518

RESUMO

OBJECTIVE: To determine the difference of post-operative mortality between ORIF (open reduction internal fixation) and hip replacement for the treatment of intertrochanteric fracture in elderly by using survival analysis. METHODS: The clinical data of 110 patients above 60 years old who underwent surgical treatment (ORIF or hip replacement) for the intertrochanteric fracture between April 2003 and May 2013 were retrospectively analyzed. Among the patients, 83 cases were treated with ORIF (ORIF group), there were 32 males and 51 females, aged from 61.44 to 98.75 years old with an average of (78.52 ± 7.98) years old; and 27 cases were treated with hip replacement (arthroplasty group), there were 8 males and 19 females, aged from 71.82 to 96.54 years old with an average of (79.99 ± 6.11) years old. A survival analysis was performed on the clinical data by using SPSS 110 software. The survival rate of 1-year,2-year, 5-year and the mean survival time for the total patients, the mortality rate of 1-year, 2-year in each group, the survival rate of 1-year, 2-year and mean survival time and survival curve in each group were included. RESULTS: All wounds achieved primary healing and no deaths were found in stay hospital. All patients were followed up from 1 to 125 months with an average of (46.93 ± 29.53) months. Among all 110 cases, 31 were dead and 79 survived. The survival rate of 1-year, 2-year and 5-year was (90.7 ± 2.8)%, (82.5 ± 3.9)% and (57.6 ± 6.5)%, respectively,while the ensemble mean survival time was (84.137 ± 5.902) months. The mortality rate of 1-year, 2-year in ORIF group was 7.2% and 12.0%, respectively; and in arthroplasty group, there was 14.8% and 25.9%, respectively. There was no significant difference in mortality rate of 1-year and 2-year between two groups. According to the survival analysis of the ORIF group, the survival rate of 1-year, 2-year was (92.6 ± 2.9)%, and (85.8 ± 4.3)%, respectively, and the mean survival time was (87.508 ± 6.063) months. In arthroplasty group, the survival rate of 1-year, 2-year was (85.2 ± 6.8)% and (73.9 ± 8.5)%,and the mean survival time was (67.294 ± 11.180) months. There was significant difference in mean survival time between two groups (P < 0.05). CONCLUSION: ORIF can achieve a better postoperative survival compare with hip replacement in treating intertrochanteric fracture in elderly.


Assuntos
Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril , Feminino , Fixação Interna de Fraturas , Fraturas do Quadril/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...