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










Base de dados
Intervalo de ano de publicação
1.
J Membr Biol ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32002589

RESUMO

Endosomal escape is a rate-limiting step in the cytosolic delivery of therapeutic drugs. Overcoming this barrier is crucial to achieve an effective biological based therapy. In this work, we evaluated the ability of a synthetic biomimetic peptide derived from the GALA to facilitate endosomal escape of protein drugs. Our results showed that the cytoplasmic distribution of GALA fusion proteins changed according to the hydrophobicity of GALA. One of the synthetic peptides, GALA3, significantly enhanced the endosomal escape efficiency of protein drugs. The cytosolic delivery capacity of GALA3 was significantly higher than that of several previously reported endosomal escape peptides, including hemagglutinin 2 (HA2). Moreover, when GALA3 was fused to BLF1-HBP, a ribosome-inactivating protein with cell-penetrating peptide HBP, the cytotoxicity of the fusion protein was significantly increased in various cell lines, including H460, HeLa, A549, and SMCC-7721. The growth inhibition effect of GALA3-BLF1-HBP was at least 20 times greater than that of BLF1-HBP alone in different tumor cell lines. GALA3 effectively promoted the endosomal escape of BLF1-HBP in a pH-dependent manner and greatly enhanced the apoptotic activity of BLF1-HBP. Taken together, our data show that by adjusting the hydrophobicity of GALA we obtained a more effective endosomal escape peptide. Therefore, GALA3-fusions can improve the efficiency of therapeutic protein drugs.

2.
Mol Pharm ; 17(2): 683-694, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31913047

RESUMO

Plant-based saponins are amphipathic glycosides composed of a hydrophobic aglycone backbone covalently bound to one or more hydrophilic sugar moieties. Recently, the endosomal escape activity of triterpenoid saponins has been investigated as a potentially powerful tool for improved cytosolic penetration of protein drugs internalized by endocytic uptake, thereby greatly enhancing their pharmacological effects. However, only a few saponins have been studied, and the paucity in understanding the structure-activity relationship of saponins imposes significant limitations on their applications. To address this knowledge gap, 12 triterpenoid saponins with diverse structural side chains were screened for their utility as endosomolytic agents. These compounds were used in combination with a toxin (MAP30-HBP) comprising a type I ribosome-inactivating protein fused to a cell-penetrating peptide. Suitability of saponins as endosomolytic agents was assessed on the basis of cytotoxicity, endosomal escape promotion, and synergistic effects on toxins. Five saponins showed strong endosomal escape activity, enhancing MAP30-HBP cytotoxicity by more than 106 to 109 folds. These saponins also enhanced the apoptotic effect of MAP30-HBP in a pH-dependent manner. Additionally, growth inhibition of MAP30-HBP-treated SMMC-7721 cells was greater than that of similarly treated HeLa cells, suggesting that saponin-mediated endosomolytic effect is likely to be cell-specific. Furthermore, the structural features and hydrophobicity of the sugar side chains were analyzed to draw correlations with endosomal escape activity and derive predictive rules, thus providing new insights into structure-activity relationships of saponins. This study revealed new saponins that can potentially be exploited as efficient cytosolic delivery reagents for improved therapeutic drug effects.

3.
World J Clin Cases ; 7(19): 3082-3089, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31624758

RESUMO

BACKGROUND: Hypoplasia of bilateral cruciate ligaments is a rare congenital malformation. The diagnosis of such diseases and indications for the various treatment options require further analysis and discussion. CASE SUMMARY: The patient is a 26-year-old Chinese woman who has been suffering from knee pain since the age of 8 years, 2-3 episodes a year. Three years ago, due to the practice of advanced yoga poses, the frequency of left knee pain increased, requiring prompt medical treatment. Magnetic resonance imaging demonstrated an absence of both anterior and posterior cruciate ligaments of both knees with abnormal posterior tilting of the tibial plateau. Bilateral subluxation of the knee joint was also found, therefore tibial osteotomy was performed. The patient reported at the 24 mo follow-up that the frequency of pain and instability had been reduced and function restored. CONCLUSION: Osteotomy may be an effective method to treat patients with congenital cruciate ligament deficiency with posterior tibial plateau tilting. The diagnosis of congenital cruciate ligament deficiency shall be based on the combination of patient's medical history, clinical manifestations, and findings from imaging to avoid possible misdiagnosis. Based on the symptoms, frequency of attacks, and intent of the individual, appropriate treatment options shall be identified.

4.
J Pept Sci ; 25(9): e3201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31309656

RESUMO

Targeted delivery of antitumor drugs is especially important for tumor therapy. Cell-penetrating peptides (CPPs) have been shown to be very effective drug carriers for tumor therapy. However, most CPPs lack tumor cell specificity. Here, we identified a highly efficient CPP, CAT, from the newly identified buffalo-derived cathelicidin family, which exhibits a preferential binding capacity for multiple tumor cell lines and delivers carried drug molecules into cells. CAT showed an approximately threefold to sixfold higher translocation efficiency than some reported cell-penetrating antimicrobial peptides, including the well-known classical CPP TAT. Moreover, the delivery efficiency of CAT was greater in a variety of tested tumor cells than in normal cells, especially for the human hepatoma cell line SMMC-7721, for which delivery was 7 times more efficient than the normal human embryonic lung cell line MRC-5, according to fluorescent labeling experiment results. CAT was conjugated to the Momordica charantia-derived type-I ribosome-inactivating protein MAP 30, and the cytotoxicity of the MAP 30-CAT fusion protein in the tumor cell line SMMC-7721 was significantly enhanced compared with that of the unconjugated MAP 30. The IC50 value of MAP 30-CAT was approximately 83 times lower than the IC50 value of the original MAP 30. Interestingly, the IC50 value of MAP 30 alone for MRC-5 was approximately twofold higher than the value for SMMC-7721, showing a small difference. However, when MAP 30 was conjugated to CAT, the difference in IC50 values between the two cell lines was significantly increased by 38-fold. The results of the flow cytometric detection of apoptosis revealed that the increase in cytotoxicity after CAT conjugation was mainly caused by the increased induction of apoptosis by the fusion protein. These results suggest that CAT, as a novel tumor-homing CPP, has great potential in drug delivery applications in vivo and will be beneficial to the development of tumor therapeutics.

5.
Chin Med J (Engl) ; 131(21): 2544-2550, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30381587

RESUMO

Background: In a small proportion of cases, spontaneous osteonecrosis of the knee (SONK) involves the medial tibial plateau (MT). Here, we introduced the clinical characteristics of spontaneous osteonecrosis of the MT and unicompartmental knee arthroplasty (UKA) as the favorable treatment for this situation based on a retrospective case study. Methods: Patients with spontaneous osteonecrosis of the MT, confirmed by magnetic resonance imaging (MRI) at Guangdong Provincial Hospital of Chinese Medicine (China) from March 2015 to June 2016, were included as a case serial and analyzed retrospectively. All patients underwent Oxford Medial UKA. The characteristics of their lesions, corresponding treatment, and results of follow-up were presented. The lesion scores and grade were determined according to the criteria of Ficat and Arlet. Results: In total, 22 patients (5 men, 17 women; mean age, 64.1 years) with spontaneous osteonecrosis of the MT were analyzed. The lesion stages assessment showed that 3 (14%) were Stage II, 10 (45%) were Stage III, 7 (32%) were Stage IV, and 2 (9%) were Stage V. In the sagittal plane, 7 (32%) were in the anterior region (MTa) and 15 (68%) were central (MTc). The lesion volume averaged 2.24 ± 0.79 cm3 (range: 1.57-3.08 cm3). Seventeen patients (77%) had Level III posterior medial meniscus root tears (MMRTs). All the patients underwent UKA. Average follow-up was 30.0 ± 6.4 months with a range of 23.0-38.0 months. The visual analog scale score was 7.78 ± 0.67 before surgery while decreased to 2.22 ± 1.09 at the final follow-up (P < 0.001). The Hospital for Special Surgery scores of pre-/post-surgery were 65.67 ± 5.45 and 84.10 ± 4.20, respectively (P < 0.001). Conclusions: SONK often occurs in the anterior and central tibial plateau due to abnormal stresses. Most of the patients had Level III posterior medial meniscus root tears. MRI is recommended for suspected cases to identify SONK at an early stage. The use of the Oxford Medial UKA for SONK of the MT is reliable both immediately and at follow-up.


Assuntos
Osteonecrose/cirurgia , Idoso , Ligamento Cruzado Anterior/patologia , Ligamento Cruzado Anterior/cirurgia , Artroplastia do Joelho , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteonecrose/patologia , Patela/patologia , Patela/cirurgia , Estudos Retrospectivos , Tíbia/patologia , Tíbia/cirurgia
6.
J Drug Target ; 26(9): 777-792, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29303375

RESUMO

Cell-penetrating peptide (CPP) is used for the delivery of biomacromolecules across the cell membrane and is limited in cancer therapy due to the lack of cell selectivity. Epidermal growth factor receptor (EGFR) has been widely used in clinical targeted therapy for tumours. Here, we reported a novel tumour targeting cell-penetrating peptide (TCPP), EHB (ELBD-C6H) with 20-fold and 3000-fold greater transmembrane ability and tumour cell selectivity than our previously reported S3-HBD and classic CPP TAT, respectively. In this new TCPP, a specific alpha helix structure was inserted into a repeated amino acid (AA) sequence formed by tandem multiple selected key AA residues of vaccinia growth factor (VGF), and this sequence was then fused to a tailored heparin binding domain sequence (C6H) derived from heparin-binding epidermal growth factor-like growth factor to intensify its targeting delivery ability. EHB could carry anticancer proteins such as MAP30 (Momordica Antiviral Protein 30 kDa) into EGFR-overexpressing cancer cell and inhibit cell growth, but it had a greatly reduced interaction with normal cells. These results indicated that EHB, as a novel efficient TCPP for the selective delivery of drug molecules into cancer cells, would help to improve the efficacy and safety of anti-tumour drugs.


Assuntos
Peptídeos Penetradores de Células/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Linhagem Celular Tumoral , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/metabolismo , Humanos , Conformação Proteica
7.
Medicine (Baltimore) ; 96(44): e8475, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29095303

RESUMO

BACKGROUND: Recently, platelet-rich plasma (PRP) has been used as an alternative therapy for plantar fasciitis (PF) to reduce heel pain and improve functional restoration. We evaluated the current evidence concerning the efficacy and safety of PRP as a treatment for PF compared with the efficacy and safety of steroid treatments. METHODS: Databases (PubMed, EMBASE, and The Cochrane Library) were searched from their establishment to January 30, 2017, for randomized controlled trials (RCTs) comparing PRP with steroid injections as treatments for PF. The Cochrane risk of bias (ROB) tool was used to assess the methodological quality. Outcome measurements were the visual analogue scale (VAS), Foot and Ankle Disability Index (FADI), American Orthopedic Foot and Ankle Society (AOFAS) scale, and the Roles and Maudsley score (RMS). The statistical analysis was performed with RevMan 5.3.5 software. RESULTS: Nine RCTs (n = 430) were included in this meta-analysis. Significant differences in the VAS were not observed between the 2 groups after 4 [weighted mean difference (WMD) = 0.56, 95% confidence interval (95% CI): -1.10 to 2.23, P = .51, I = 89%] or 12 weeks of treatment (WMD = -0.49, 95% CI: -1.42 to 0.44, P = .30, I = 89%). However, PRP exhibited better efficacy than the steroid treatment after 24 weeks (WMD = -0.95, 95% CI: -1.80 to -0.11, P = .03, I = 85%). Moreover, no significant differences in the FADI, AOFAS, and RMS were observed between the 2 therapies (P > .05). CONCLUSION: Limited evidence supports the conclusion that PRP is superior to steroid treatments for long-term pain relief; however, significant differences were not observed between short and intermediate effects. Because of the small sample size and the limited number of high-quality RCTs, additional high-quality RCTs with larger sample sizes are required to validate this result.


Assuntos
Fasciíte Plantar/terapia , Manejo da Dor/métodos , Troca Plasmática/métodos , Plasma Rico em Plaquetas , Esteroides/uso terapêutico , Adulto , Fasciíte Plantar/complicações , Feminino , Calcanhar , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
8.
Biotechnol Appl Biochem ; 64(6): 918-926, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28090686

RESUMO

Alpha-momorcharin (α-MMC), a type I ribosome-inactivating protein, has attracted a great deal of attention because of its antitumor activity. However, the cytotoxicity of α-MMC is limited due to insufficient cellular internalization in cancer cells. To enhance the cytotoxicity of α-MMC, a heparin-binding domain derived from heparin-binding epidermal growth factor (named heparin-binding peptide [HBP]) was used as a cell-penetrating peptide and fused to the C-terminus of α-MMC. This novel α-MMC-HBP fusion protein was expressed and purified with a Ni2+ -resin. The N-glycosidase activity and DNase activity assay indicated that the introduction of HBP did not interfere with the intrinsic bioactivities of α-MMC. HBP was able to efficiently carry α-MMC into the tested cancer cells and significantly enhance the cytotoxic effects of α-MMC in a dose-dependent manner. This enhanced cytotoxic ability occurred due to the higher level of cell apoptosis induced by α-MMC-HBP, which was demonstrated in western blot analysis in which α-MMC-HBP triggered caspase 8, caspase 9, casapase 3, and PARP more intensely than α-MMC alone. α-MMC-HBP led to an upregulation of cleaved PARP and an increase in the Bax/Bcl-2 ratio. Our study provided a new practical way to greatly improve the antitumor activity of α-MMC, which could significantly expand the pharmaceutical applications of α-MMC.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Sanguíneas/metabolismo , Proteínas de Transporte/metabolismo , Proteínas Inativadoras de Ribossomos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antineoplásicos Fitogênicos/metabolismo , Proteínas Sanguíneas/química , Proteínas de Transporte/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Células MCF-7 , Proteínas Inativadoras de Ribossomos/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
9.
Biotechnol Lett ; 39(1): 71-78, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27714558

RESUMO

OBJECTIVE: To evaluate the anti-tumor effects of trichosanthin after fusion with a cell penetrating peptide, heparin-binding peptide (HBP), derived from human heparin-binding EGF-like growth factor (HB-EGF). RESULTS: The fusion protein of trichosanthin-HBP was expressed in Escherichia coli BL21 and purified by Ni-NTA affinity chromatography. The HBP domain had no influence on the topological inactivation activity and N-glycosidase activity of trichosanthin. Trichosanthin-HBP significantly inhibited the growth of tested cancer cells which are impervious to trichosanthin. Tumor cell apoptosis and both the mitochondrial- and death receptor-mediated apoptotic signaling pathways induced by trichosanthin-HBP were more significant than those induced by trichosanthin in HeLa cells. CONCLUSION: HBP is an efficient intracellular delivery vehicle for trichosanthin and makes trichosanthin-HBP become a promising agent for cancer therapy.


Assuntos
Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/química , Peptídeos/metabolismo , Peptídeos/farmacologia , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Tricosantina/metabolismo , Tricosantina/farmacologia , Apoptose/efeitos dos fármacos , Células HeLa , Humanos , Peptídeos/genética , Proteínas Recombinantes de Fusão/genética , Tricosantina/genética
10.
J Pept Sci ; 22(11-12): 689-699, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27739168

RESUMO

Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30. The intrinsic bioactivities of recombinant MAP30-HBP were well preserved compared to those of free MAP30. Furthermore, HBP conjugated to the C-terminus of MAP30 promoted the cellular uptake of recombinant MAP30-HBP. Moreover, the fusion of HBP to MAP30 gave rise to significantly enhanced cytotoxic effects in all of the tumor cell lines tested. In HeLa cells, this cytotoxicity was mainly caused by the induction of cell apoptosis. Further investigation revealed that HBP enhanced MAP30-induced apoptosis through the activation of the mitochondrial- and death receptor-mediated signaling pathways. In addition, the MAP30-HBP fusion protein caused more HeLa cells to become arrested in S phase compared to MAP30 alone. These results highlight the MAP30-HBP fusion protein as a promising drug candidate for cancer therapy and demonstrate HBP, a novel CPP derived from human HB-EGF, as a new potential vector for antitumor drug delivery. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.


Assuntos
Peptídeos Penetradores de Células/farmacologia , Portadores de Fármacos/farmacologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Inativadoras de Ribossomos Tipo 2/farmacologia , Sequência de Aminoácidos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Peptídeos Penetradores de Células/biossíntese , Peptídeos Penetradores de Células/genética , Clonagem Molecular , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Células HeLa , Heparina/química , Heparina/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/biossíntese , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética , Humanos , Momordica charantia/química , Ligação Proteica , Domínios Proteicos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Inativadoras de Ribossomos Tipo 2/biossíntese , Proteínas Inativadoras de Ribossomos Tipo 2/genética , Fase S/efeitos dos fármacos , Transdução de Sinais
11.
Fitoterapia ; 112: 183-90, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27050721

RESUMO

Trichosanthin (TCS), a type I ribosome-inactivating protein (RIP-I) and renowned Chinese traditional medicine, displays a broad spectrum of biological and pharmacological properties. Particularly, its anti-tumor activity has received a great deal of attention. However, the cellular mechanism for TCS uptake varies with different tumor cell lines, leading to discrepancies in its reported ability to penetrate cells. In this study, HBD, a human derived cell-penetrating peptide (CPP), was used to improve the delivery of TCS into several types of tumor cells, including HeLa cells. Recombinant TCS (rTCS) with or without the fused HBD peptide was expressed in Escherichia coli cells and successfully purified by Ni-NTA affinity chromatography. The cellular uptake efficiency of FITC-labelled-rTCS-HBD was observed in HeLa cells and compared with the uptake efficiency of non-HBD conjugated rTCS under the same conditions using laser confocal microscopy. Moreover, the IC50 value of rTCS-HBD in the tested tumor cells was much lower than that of rTCS, indicating that HBD could efficiently deliver the rTCS into tumor cells. When compared with rTCS, rTCS-HBD induced higher rates of apoptosis in HeLa cells as analyzed by flow cytometry. Furthermore, the apoptotic events observed in HeLa cells incubated with HBD-fused rTCS included activation of Caspase-9, decrease in the Bcl-2/Bax ratio, and cleavage of PARP. These results strongly suggest the participation of mitochondria in apoptosis. This report illustrates one possible method for achieving the efficient transport of TCS into cells using a CPP as a vector, and increases the likelihood that TCS can be used in the clinic.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Peptídeos Penetradores de Células/química , Portadores de Fármacos/química , Tricosantina/farmacologia , Apoptose , Linhagem Celular Tumoral , Células HeLa , Humanos , Proteínas Recombinantes de Fusão/farmacologia
12.
Trials ; 17: 3, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26728982

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is a major public health issue causing chronic disability as well as a burden on healthcare resources. In China, a herbal drug tablet has been used as an effective and conventional therapy to alleviate clinical symptoms caused by KOA. However, evidence gathered from systematic reviews or randomized controlled trials that validated herbal drugs for the management of osteoarthritic pain is weak. The purpose of this study is to explore the efficacy and safety of the Shaoyao Shujin tablet for the management of KOA in a short-term study. METHODS/DESIGN: This trial is a multicenter randomized, double-blind, placebo-controlled study. A total of 276 patients will be randomized into 3 groups: (1) the high-dose Shaoyao Shujin tablet group (HD group), (2) the low-dose Shaoyao Shujin tablet group (LD group), and (3) the placebo tablet group (control group). In the three groups, four tablets will be administered three times per day for 6 weeks. Follow-up will be at regular intervals during a 10-week period with the Western Ontario and McMaster Universities Index (WOMAC) score, visual analog scale (VAS) score, and rescue medication use assessed as outcome measures. DISCUSSION: This study will provide clinical evidence on the efficacy and safety of the Shaoyao Shujin tablet in treating KOA. TRIAL REGISTRATION: Chinese Cochrane Center ChiCTR-IPR- 15006194 , registered 4 April 2015.


Assuntos
Protocolos Clínicos , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Interpretação Estatística de Dados , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Tamanho da Amostra , Comprimidos
13.
Immunol Lett ; 168(2): 246-53, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26404854

RESUMO

BACKGROUND: We aimed to elucidate the molecular mechanisms underlying rheumatoid arthritis (RA) and osteoarthritis (OA) and analyze the mechanism differences between them. METHODS: The gene expression profile of GSE1919, GSE12021, GSE21959 and GSE48780 were downloaded from Gene Expression Omnibus. Total 165 samples of synovial fibroblasts (118 RA samples, 15 OA samples and 32 normal controls) were used. The differentially expressed genes (DEGs) in RA samples but no differences in OA samples (RA.DEGs) and genes in OA samples but no differences in RA samples (OA.DEGs) were screened using limma package. Functional enrichment analysis was performed using DAVID. Moreover, transcriptional regulatory network (TRN) and microRNA regulatory network were constructed. RESULTS: Total 211 RA.DEGs (96 up- and 115 down-regulate) and 497 OA.DEGs (224 up- and 273 down-regulated) were identified. TRN analysis showed that C-ETS-1 and P53 were important transcription factors. C-ETS-1 could interact with matrix metallopeptidase 1 (MMP1) and CD53 while P53 could interact with epidermal growth factor receptor (EGFR) and dual specificity phosphatase 1 (DUSP1). Besides, v-myc avian myelocytomatosis viral oncogene homolog (MYC) and interleukin 1, beta (IL1B) could be regulated by the most microRNAs in microRNA regulatory network. Our study indicates that ETS-1 may contribute to RA progression by up-regulation of MMP1 and result in OA progression via up-regulating CD53. CONCLUSIONS: P53 may be involved in the progression of RA and OA via targeting downstream EGFR and DUSP1 respectively. Besides, MYC and IL1B may play an important role in OA progression via the regulation of microRNAs.


Assuntos
Artrite Reumatoide/genética , Perfilação da Expressão Gênica/métodos , Osteoartrite/genética , Transcriptoma/genética , Artrite Reumatoide/patologia , Progressão da Doença , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes/genética , Humanos , MicroRNAs/genética , Modelos Genéticos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Osteoartrite/patologia , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
14.
Trials ; 16: 124, 2015 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-25872665

RESUMO

BACKGROUND: Knee osteoarthritis is a major cause of disability in the aging population. Based on pathological, magnetic resonance imaging (MRI) and arthroscopy studies, progressive osteoarthritis involves all tissues of the joint and includes bone marrow lesions, synovial proliferation, fat pad inflammation, and high subchondral bone turnover. Recent research suggests that abnormal perfusion in bone marrow lesions, fat pads, and subchondral bone is associated with pain in knee osteoarthritis, and that dynamic contrast-enhanced MRI is a promising method for studying micro-perfusion alteration in knee osteoarthritis. Traditional Chinese Medicine approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the Jingui external lotion is the preferred and most commonly used method in China to reduce pain in patients with knee osteoarthritis; however, there is a lack of validated evidence for its effectiveness. The purpose of this study is to explore the effectiveness of Jingui external lotion for the management of painful knee osteoarthritis in a short-term study. In addition, we will assess micro-perfusion alteration in the patellar fat pad as well as the femur and tibia subchondral bone via dynamic contrast-enhanced MRI. METHODS/DESIGN: This trial is a randomized, controlled study. A total of 168 patients will be randomized into the following two groups: 1) the Jingui external lotion group (treatment group); and 2) the placebo lotion group (control group). In both groups, lotion fumigation and external washing of the patients' knees will be administered twice a day for 14 consecutive days. Follow-up will be at regular intervals during a 4-week period with a visual analog scale to assess pain, and additional characterization with the Western Ontario and McMaster Universities Index score; rescue medication will be recorded as the extent and time pattern. In addition, micro-perfusion alteration in the patellar fat pad, femur and tibia subchondral bone will be assessed via dynamic contrast-enhanced MRI. DISCUSSION: This study will provide clinical evidence of the efficacy of Jingui external lotion in treating knee osteoarthritis, and it will be the first randomized controlled trial to investigate micro-perfusion alteration of knee osteoarthritis with Traditional Chinese Medicine external lotion via dynamic contrast-enhanced MRI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR-TRC-14004727 ; 31 May 2014.


Assuntos
Medicina Tradicional Chinesa , Osteoartrite do Joelho/terapia , Fitoterapia , Preparações de Plantas/uso terapêutico , Creme para a Pele/uso terapêutico , Protocolos Clínicos , Humanos , Projetos de Pesquisa
15.
Trials ; 15: 245, 2014 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-24958315

RESUMO

BACKGROUND: Postoperative pain control after total knee arthroplasty (TKA) remains a great challenge. The management of pain in the immediate postoperative period is one of the most critical aspects to allow speedier rehabilitation and reduce the risk of postoperative complications. Recently, periarticular infiltration anesthesia has become popular, but the outcome is controversial. Some studies have shown transient effects, "rebound pain", or no effectiveness in pain control. Continuous intra-articular infusion technique has been introduced to improve these transient effects, but more clinical studies are needed. Furthermore, the potential risk of early periprosthetic joint infection is causing concerning. We plan to compare continuous intra-articular infusion anesthesia with epidural infusion anesthesia after TKA to assess the effectiveness of this technique in reducing pain, in improving postoperative function, and to look at the evidence for risk of early infection. METHODS/DESIGN: This trial is a randomized, controlled study. Patients (n = 214) will be randomized into two groups: to receive continuous intra-articular infusion anesthesia (group C); and epidural infusion anesthesia (group E). For the first 3 postoperative days, pain at rest, active range of motion (A-ROM), rescue analgesia and side effects will be recorded. At 3-month and 6-month follow-up, A-ROM, C-reactive protein, erythrocyte sedimentation rate, and synovial fluid cell count and culture will be analyzed. DISCUSSION: The results from this study will provide clinical evidence on the efficacy of a continuous intra-articular infusion technique in reducing pain, postoperative functional improvement and safety. It will be the first randomized controlled trial to investigate infection risk with local anesthesia after TKA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR-TRC-13003999.


Assuntos
Anestesia/métodos , Anestésicos Locais/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Osteoartrite do Joelho/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Analgesia Epidural/métodos , Artroplastia do Joelho/reabilitação , Humanos , Infusões Intra-Arteriais , Medição da Dor , Estudos Prospectivos , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Projetos de Pesquisa
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(2): 209-13, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24672947

RESUMO

OBJECTIVE: To observe the effect of single herb pilose antler (PA) on the expression of Smad2 and Smad3 in the cartilage of osteoarthritis (OA) rats. METHODS: One hundred 3-month old female healthy SD rats, (200 +/- 20) g, were recruited and routinely fed for 1 week. They were randomly divided into 5 groups, i.e., the low dose PA group, the high dose PA group, the normal saline control group, the model group, and the normal control group, 20 in each group. The model was prepared using classic Hulth method except the normal control group. After 6-week modeling, the model was confirmed successful by pathologic observation. PA at 0.021 g/100 g and 0.084 g/1 00 g was given by gastrogavage to rats in the low dose PA group and the high dose PA group respectively. Normal saline was administered to those in the normal saline control group. No treatment was given to rats in the normal control group and the model group. Bilateral knee cartilages were harvested at week 2,4, and 6. mRNA and protein expressions of Smad2 and Smad3 were detected by immunohistochemical assay, fluorescent quantitative PCR, and Western blot. RESULTS: OA model was successfully prepared by pathological observation. Results of immunohistochemical assay showed that Smad2 and Smad3 expressed extensively in the cartilage, and located inside the chondrocyte membrane. Compared with the model group, mRNA expression of Smad2 and Smad3 obviously increased in the low dose PA group and the high dose PA group at week 2, 4, and 6, showing statistical difference (P < 0.05). Compared with the same group at week 4 after gastrogavage, mRNA expression of Smad2 and Smad3 obviously decreased in the low dose PA group and the high dose PA group at week 6, showing statistical difference (P < 0.05). Compared with the model group, protein expression of Smad2 and Smad3 obviously increased in the chondrocytes of the low dose PA group and the high dose PA group at week 2 and 4, showing statistical difference (P < 0.01). Compared with the same group at week 2 after gastrogavage, protein expression of Smad2 and Smad3 obviously increased in the low dose PA group and the high dose PA group at week 4, showing statistical difference (P < 0.01). Compared with the same group at week 4 after gastrogavage, protein expression of Smad2 and Smad3 obviously decreased in the low dose PA group and the high dose PA group at week 6, showing statistical difference (P < 0.01). CONCLUSIONS: (1) The pilose antler could repair cartilages by regulating mRNA and protein expressions of Smad2 and Smad3. (2) Up-regulating mRNA and protein expressions of Smad2 and Smad3 might be one of important mechanisms for the pathogenesis of OA.


Assuntos
Chifres de Veado/química , Cartilagem/metabolismo , Condrócitos/metabolismo , Medicina Tradicional Chinesa , Osteoartrite/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Animais , Cartilagem/citologia , Condrócitos/efeitos dos fármacos , Feminino , Osteoartrite/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
17.
Opt Express ; 22(1): 537-46, 2014 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-24515014

RESUMO

We study the diffraction of optical waves by a single layer of gyromagnetic cylinders. We show that a nonvanishing rotating dipole momentum is excited in a single gyromagnetic cylinder because of the classic analog of the Zeeman effect on photonic angular momentum states (PAMSs). Consequently, different collective dipole modes are excited in a gyromagnetic cylinder array at opposite incident angles. Nonreciprocal optical diffraction effects can be observed, where the transmission and reflection coefficients depend on the sign of the incident angle. A novel phenomenon of nonreciprocal negative directional transmission is demonstrated and numerically analyzed. This work highlights the potential of PAMSs in manipulating the propagation of optical waves for various applications.

18.
Opt Express ; 21(11): 13368-79, 2013 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-23736588

RESUMO

Complex metamaterials with multiple optical resonances in constituent elements possess many similarities with open quantum systems that can be described by non-Hermitian Hamiltonian. By analogy with a two-state open quantum system, we show that a classic analogue of exceptional points can be observed in the transmission spectra of dual subwavelength metallic gratings. Anti-crossing (crossing) between the two branches λ(R) of extraordinary optical transmission, with crossing (anti-crossing) of the corresponding widths Γ(R), is observed in the parameter space spanned by the lateral displacement L and the angle of incidence φ0. Exchanges of field patterns and phases, and the variation of field profile when circling the exceptional point are discussed. This work highlights the potential to transfer the concepts and applications from open quantum systems to optical metamaterials.

19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(4): 955-9, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21714237

RESUMO

Near-infrared (NIR) and mid-infrared (MIR) diffuse reflection spectra were compared and evaluated for hydrocarbon potential generation of source rocks. Near-infrared diffuse reflectance often exhibits significant differences in the spectra due to the non-homogeneous distribution of the particles, so the signal-to-noise ratio of NIR is much lower than MIR It is too difficult to get accurate results by NIR without using a strong spectral preprocessing method to remove systematic noise such as base-line variation and multiplicative scatter effects. In the present paper, orthogonal signal correction (OSC) and an improved algorithm of it, i.e. direct orthogonal signal correction (DOSC), are used as different methods to preprocess both the NIR and MIR spectra of the hydrocarbon source rocks. Another algorithm, wavelet multi-scale direct orthogonal signal correction (WMDOSC), which is a combination of discrete wavelet transform (DWT) and DOSC, is also used as a preprocessing method. Then, the calibration model of hydrocarbon source rocks before and after pretreatment was established by interval partial least square (iPLS). The experimental results show that WMDOSC is more successfully applied to preprocess the NIR spectra data of the hydrocarbon source rocks than other two algorithms, and NIR performed as good as MIR in the analysis of hydrocarbon potential generation of source rocks with WMDOSC-iPLS pretreatment calibration model.

20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 22(4): 580-3, 2002 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12938370

RESUMO

Single wall carbon nanotubes (SWNTs) were synthesized by electric are discharge method with a mixture of nickel and yttrium as catalysts. The examination results of scanning electronic microscope and transmission electronic microscope indicate that the yield of SWNTs in the sample were high. SWNTs have been investigated by Raman scattering techniques with excitation wavelengths in the range of 514.5 to 782.0 nm. We have observed some differences in the frequencies and intensities of the radial breathing modes. The electronic density of states of SWNTs was calculated using the Brillouin zone folding. A graphical method was proposed for assigning Raman peaks of the radial breathing modes (RMB) based on the data of diameters, RBM frequencies and electronic density of states of SWNTs. The radial breathing modes on SWNTs are assigned. The results indicate that the diameter distribution of SWNTs is in the range of 0.79-1.76 nm, and the SWNTs with diameter 1.45 nm are in the majority. The metallic and semiconductor tubes are all present in the sample.


Assuntos
Nanotubos de Carbono/química , Níquel/química , Ítrio/química , Catálise , Eletricidade , Microscopia Eletrônica de Varredura , Espalhamento de Radiação , Análise Espectral Raman
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA