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1.
J Colloid Interface Sci ; 586: 412-422, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189324

RESUMO

Reducing the material size could be an effective approach to enhance the electrochemical performance of porous carbons for supercapacitors. In this work, ultra-fine porous carbon nanofibers are prepared by electrospinning using lignin/ polyvinylpyrrolidone as carbon precursor and zinc nitrate hexahydrate (ZNH) as an additive, followed by pre-oxidation, carbonization, and pickling processes. Assisted by the ZnO template, the pyrolytic product of ZNH, abundant micropores are yielded, leading to the formation of microporous carbon nanofibers with specific surface area (SSA) up to 1363 m2 g-1. The average diameter of the lignin-based ultra-fine porous carbon nanofibers (LUPCFs) is effectively controlled from 209 to 83 nm through adjusting the ZNH content. With good flexibility and self-standing nature, the LUPCFs could be directly cut into electrodes for use in supercapacitors. High accessible surface, enriched surface N/O groups, and reduced fiber diameters endow the LUPCFs-based electrodes with an excellent specific capacitance of 289 F g-1. The reduction of fiber diameters remarkably improves the rate performance of the LUPCFs and leads to a low relaxation time constant of 0.37 s. The high specific capacitance of 162 F g-1 is maintained when the current density is increased from 0.1 to 20 A g-1. Besides, the fabricated LUPCFs show exceptional cycling stability in symmetrical supercapacitors, manifesting a promising application prospect in the next generation of supercapacitors.

2.
Bioorg Chem ; 99: 103790, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32279037

RESUMO

Lung cancer is the most common cancer and leading cause of cancer-related deaths worldwide. The first-generation reversible, ATP-competitive inhibitors gefetinib and elotinib showed good clinical responses in lung adenocarcinoma tumors (NSCLC). But almost all patients developed resistance to these inhibitors over time. Such resistance of EGFR inhibitors was frequently linked to the acquired L858R and T790M point mutations in the kinase domain of EGFR. To overcome these resistance problems, the second and the third generation inhibitors have been discovered. FDA approved afatinib, the second generation irreversible inhibitor and osimitinib, the third generation irreversible EGFR inhibitors for the treatments of NSCLC. We identified new covalent quinazoline inhibitors (E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide (6d) and (E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4-(dimethyl-amino)but-2-enamide (6h) that exhibited potent EGFR kinase inhibitory activities on L858R and T790M mutations. The compound 6 h showed selectivity similar to AZD9291 (osimertinib) in mutated and wild type tumor cell lines. In vitro cell assay 6d and 6h were better than afatinib and osimertinib. In vivo antitumor efficacy studies of these compounds were done in NCI-H1975 mice xenografts.


Assuntos
Antineoplásicos/farmacologia , Modelos Animais de Doenças , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Receptor ErbB-2/metabolismo , Relação Estrutura-Atividade
3.
Cell Cycle ; 18(22): 3072-3084, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31550968

RESUMO

HCMV is a common pathogen for human with relatively high prevalence, which could be life-threatened in immunodeficient patients and lead to significant birth defects in newborns. In this study, we firstly report that HCMV infection significantly enhances the expression of microRNA-221 (miR-221) in Neural Precursor Cells (NPCs). We found that miR-221 directly targets at the 3'-UTR of suppressor of cytokine signaling 1 (SOCS1) and suppresses SOCS1 expression at the both mRNA and protein levels. MiR-221 overexpression restrained HCMV replication by promoting type I interferon (IFN) and interferon stimulating genes (ISGs) production, whereas reintroduction of SOCS1 abrogated the miR-221-induced effects on HCMV replication. Importantly, miR-221 positively regulated the phosphorylation and activation of NF-κB by suppressing SOCS1. What's more, miR-221 agomir alleviated MCMV-induced tissue injury by promoting type I IFN antiviral activities in vivo. Thus, miR-221 modulates the infection and replication of HCMV as an intrinsic antiviral factor, and could be developed as a treatment target for anti-HCMV treatment.


Assuntos
Infecções por Citomegalovirus/metabolismo , Citomegalovirus/fisiologia , Interferon Tipo I/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/virologia , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Regiões 3' não Traduzidas , Animais , Infecções por Citomegalovirus/genética , Interações Hospedeiro-Patógeno/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Proteína 1 Supressora da Sinalização de Citocina/genética , Replicação Viral
4.
Respir Med ; 155: 127-132, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31344662

RESUMO

AIM: To describe and expand the phenotype of isolated anti-Ro-52-associated rapid progressive interstitial lung disease (RP-ILD) in Dermatomyositis(DM) in Chinese patients. METHODS: 491 patients with PM/DM-ILD hospitalized in the China-Japan Friendship Hospital from 2000 to 2017 were screened retrospectively. All proven cases of isolated anti-Ro-52-associated RP-ILD were selected for inclusion. The clinical features in this group were recorded. RESULTS: Isolated Ro-52 antibodies existed in 20 PM/DM-ILD patients. Among them 5 patients developed RP-ILD. The 5 patients had typical rashes including Gottron's sign (80%), Helitrope rash (80%) and mechanic's hands (100%), but only few patients (20%) had arthralgia and muscle weakness. All patients had elevated levels of serum ferritin and decreased counts of CD3+ T cells. The estimated high-resolution computed tomography (HRCT) patterns of the five patients showed organizing pneumonia (OP) while RP-ILD patients without Ro-52 antibodies and non-RP-ILD patients with isolated Ro-52 antibodies mainly showed non-specific interstitial pneumonia (NSIP) patterns(P < 0.05). Although one patient died of infection after one month, 80%(4/5) of patients had good response to glucocorticoid treatment and these four patients survived were all alive at the end of follow-up. The survival rate in this group was the highest than those in RP-ILD patients with other myositis specific autoantibodies though the difference had no statistically significance. CONCLUSIONS: A small group of patients with isolated anti-Ro-52 antibody in DM could develop RP-ILD, which mainly presented OP on HRCT. Patients with isolated anti-Ro-52 antibody associated RP-ILD responded well to therapy and had good prognosis in DM.


Assuntos
Autoanticorpos , Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/etiologia , Ribonucleoproteínas/imunologia , China , Dermatomiosite/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
J Cell Biochem ; 120(10): 18378-18387, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31190356

RESUMO

Long noncoding RNA LINC00261 has been experimentally validated to function as a tumor suppressor in several cancers, but its pathological role and functional mechanism in non-small cell lung cancer (NSCLC) are largely unclear. In this study, LINC00261 was delineated in NSCLC to be significantly downregulated in cancer tissues compared with corresponding adjacent normal tissues. Low expression of LINC00261 predicted worse survival for patients with NSCLC. Overexpression of LINC00261 in NSCLC cell lines inhibited cell proliferation and invasion, meanwhile promoted apoptosis. Subcellular fractionation assay showed that LINC00261 existed mainly in the cytoplasm of NSCLC A549 cells and luciferase assay validated its direct interaction with miR-522-3p. Overexpression of miR-522-3p significantly ameliorated suppressive effects of LINC00261 on proliferation and invasion of NSCLC cells. Besides, miR-522-3p was found to be able to directly combine with the 3'-untranslated region of SFRP2, which was generally regarded as a suppressor of Wnt signaling. Further quantitative reverse transcription polymerase chain reaction and Western blot experiments showed that LINC00261 upregulation potentiated the expression of SFRP2 and inhibited Wnt signaling pathway, which could both be reversely modulated by miR-522-3p. Taken together, our study demonstrated that LINC00261 suppressed NSCLC cells progression via sponging miR-522-3p and inhibiting Wnt signaling. These results supported us to better understand the pathogenic mechanism of NSCLC and revealed a potential molecular target for this fatal disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células/fisiologia , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/metabolismo , Células A549 , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , RNA Longo não Codificante/genética , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia
6.
Bioorg Med Chem Lett ; 29(12): 1514-1517, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31005443

RESUMO

Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of non-small cell lung cancer (NSCLC). Within our ALK drug discovery program, we identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound 11 showed better in vitro activity and in vivo efficacy with good pharmacokinetic profile. In vivo efficacy of compound 11 was better than standard drug ceritinib in NCI-H2228 xenograft mice model.


Assuntos
Quinase do Linfoma Anaplásico/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Antineoplásicos/farmacologia , Modelos Animais de Doenças , Xenoenxertos , Camundongos , Inibidores de Proteínas Quinases/farmacologia
7.
Bioorg Med Chem Lett ; 29(4): 591-596, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30600209

RESUMO

Overexpression of EGFR and HER2 are observed in many breast, ovarian, colon and prostate cancers. The second and third generation irreversible EGFR/HER2 dual kinase inhibitors became popular after the approval of Afatinib by FDA to overcome the mutation related problem. To find efficacious drug candidates, a series of novel quinazoline derivatives were designed, synthesized and evaluated as dual EGFR/HER2 tyrosine kinase (TK) inhibitors. Selected twenty four compounds were reported here with significant inhibitory activities against EGFR/HER2 tyrosine kinases. Several compounds showed nanomolar IC50 values. In vitro studies of quinazoline derivatives were done on NCI-H1975, HCC827, A431, MDA MB-453 cell lines. The compounds 1a, 1d and 1v were found more potent compared to standard drug afatinib. In vivo efficacy study of 1d on nude mice NCI-H1975 tumour xenograft model was discussed.


Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas , Receptores ErbB/antagonistas & inibidores , Quinazolinas/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
8.
J Nanosci Nanotechnol ; 18(1): 699-704, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29768897

RESUMO

Microporous carbon nanofibers (Mi-CNFs) and mesoporous carbon nanofibers (Me-CNFs) with high surface area were prepared by electrospinning resol resin/PVP/TEOS/F127 ethanol solution, followed by curing, carbonization and pickling process. TEOS was responsible for structural stability and producing micropores, while F127 for forming mesopores. Mi-CNFs showed high specific surface area of 1841 m2 g-1, while Me-CNFs possessed both high specific surface area of 1674 m2 g-1 and mesoporosity of 64%. The electrochemical test revealed that Mi-CNFs had higher capacitance (276 F g-1 at 0.5 A g-1) and Me-CNFs possessed higher capacitance retention (71%, 150 F g-1 at 30 A g-1).

9.
Arthritis Res Ther ; 20(1): 71, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29642946

RESUMO

After publication of the article [1], it has been brought to our attention that the labels in Fig. 2b have been switched and are as a result incorrect. The label for the red line should have the label "non-CAM" and the yellow line "CAM".

10.
Clin Rheumatol ; 37(6): 1573-1580, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29541951

RESUMO

Autoantibodies against poly-U-binding factor 60 kDa protein (PUF60) have been reported in Caucasian dermatomyositis (DM) patients. However, their clinical significance in idiopathic inflammatory myopathy (IIM) remains to be fully clarified. Our objective was to analyze the prevalence and clinical significance of anti-PUF60 antibodies in a large cohort of Chinese IIM patients. In our study, 388 IIM patients, 301 disease controls, and 167 healthy controls (HCs) were involved. An enzyme-linked immunosorbent assay (ELISA) was developed to detect serum anti-PUF60 levels and was validated using immunoblotting methods. Unpaired Mann-Whitney U test and Spearman correlation analysis were used when appropriate. Anti-PUF60 antibodies were observed in IIM patients at a frequency of 10.6% (41/388). Subgrouping analysis revealed that the prevalence of anti-PUF60 antibodies was 10% in DM, 5.5% in polymyositis (PM), 10% in immune-mediated necrotizing myositis (IMNM), and 26.5% in myositis-overlap syndrome. Anti-PUF60 antibodies were also observed in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) patients at a positive rate of 17.3, 14.5, and 10.1% respectively. Intriguingly, anti-PUF60 antibodies were frequently observed in clinically amyopathic dermatomyositis (CADM) patients and DM patients without currently known myositis autoantibodies. Furthermore, DM patients with anti-PUF60 antibodies had higher prevalence of skin ulcerations. Moreover, longitudinal investigation in eight DM patients with anti-PUF60 antibodies revealed that the antibodies levels decreased with disease remission. Anti-PUF60 antibodies were nonspecific for myositis, since they could be detected in other rheumatic diseases. Further investigation of anti-PUF60 antibodies may reveal shared pathogenic pathways in systemic autoimmune disorders.


Assuntos
Miosite/imunologia , Fatores de Processamento de RNA/imunologia , Proteínas Repressoras/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
11.
Arthritis Rheumatol ; 70(8): 1288-1297, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29534337

RESUMO

OBJECTIVE: To investigate the associations between anti-nuclear matrix protein 2 (anti-NXP-2) autoantibody levels and disease activity as well as calcinosis severity in patients with idiopathic inflammatory myopathies (IIMs). METHODS: Serum levels of anti-NXP-2 autoantibodies were determined in 709 patients with IIMs and also serially measured in the patients' sera with an in-house enzyme-linked immunosorbent assay using MORC3 recombinant protein. Patients with anti-NXP-2 autoantibodies were divided into 2 subgroups: those with and those without calcinosis. Associations of anti-NXP-2 autoantibody levels with organ-specific disease activity (using 10-cm visual analog scale [VAS] scores), serum creatine kinase (CK) levels, and calcinosis severity were investigated in cross-sectional and longitudinal analyses. RESULTS: A cross-sectional analysis of 56 IIM patients with anti-NXP-2 autoantibodies (38 without calcinosis and 18 with calcinosis) showed that in patients without calcinosis, the levels of anti-NXP-2 autoantibodies were positively correlated with the physician's global assessment of disease activity and muscle VAS scores and serum CK levels, whereas no such association was found in patients with calcinosis. Results of the longitudinal study revealed strong correlations of anti-NXP-2 antibody levels with the physician's global assessment and constitutional, cutaneous, gastrointestinal, and muscle VAS scores and serum CK levels in patients without calcinosis, but in patients with calcinosis, only a moderate correlation was observed between anti-NXP-2 antibody levels and the physician's global VAS and constitutional VAS scores. Of note, in patients without calcinosis, anti-NXP-2 autoantibodies were found to disappear during periods of clinical remission, but reappeared with disease relapse. No association between anti-NXP-2 antibody levels and the severity of calcinosis was observed. CONCLUSION: These findings indicate that anti-NXP-2 autoantibodies serve as a useful marker for disease activity in patients with IIMs, especially in the absence of calcinosis. The differential associations observed between anti-NXP-2 autoantibody levels and disease activity suggest that there may be a phenotypic difference between patients with and those without calcinosis.


Assuntos
Autoanticorpos/sangue , Calcinose/sangue , Proteínas de Ligação a DNA/imunologia , Miosite/sangue , Índice de Gravidade de Doença , Fatores de Transcrição/imunologia , Adulto , Autoanticorpos/imunologia , Biomarcadores/sangue , Calcinose/imunologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Miosite/complicações , Miosite/imunologia
12.
J Rheumatol ; 45(6): 835-840, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29419471

RESUMO

OBJECTIVE: To investigate the levels of soluble programmed death ligand 1 (sPD-L1) and evaluate its association with malignancy in patients with dermatomyositis (DM). METHODS: Levels of sPD-L1 were measured in serum from 88 DM patients without malignancies (sDM), 40 with cancer-related DM (CRDM), and 30 healthy controls (HC) using ELISA. The CRDM subjects were divided into new-onset cancers (nCRDM) and stable cancers (sCRDM). Receiver-operating characteristic (ROC) curve analysis was performed to determine the cutoff sPD-L1 value that distinguished patients with nCRDM from those who were sDM. Serum antitranscriptional intermediary factor 1-γ (TIF1-γ) antibodies were detected using immunoblot, and the diagnostic values for malignancy were compared with sPD-L1 levels in patients with DM. RESULTS: Serum sPD-L1 levels were significantly higher in sDM [median 12.3 ng/ml, interquartile range (IQR) 8.4-16.2] than in HC (median 1.3 ng/ml, IQR 0.4-2.2, p = 0.0001). Extremely high sPD-L1 levels were seen in nCRDM (median 18.5 ng/ml, IQR 13.8-22.4), much higher than those in sCRDM (median 8.5 ng/ml, IQR 6.8-11.8, p = 0.0001). The sPD-L1 levels in 4 patients with nCRDM decreased after curative cancer treatment (p = 0.013). ROC curve analysis revealed that the sPD-L1 value distinguishing nCRDM from sDM was 16.1 ng/ml, with an area under the curve value of 0.72 ± 0.04 (p = 0.0001). The combination of sPD-L1 and anti-TIF1-γ antibodies yielded greater specificity and positive predictive value in diagnosing cancer, reaching values of 95% and 70%, respectively. CONCLUSION: Serum sPD-L1 levels increased significantly in sDM, and markedly high sPD-L1 levels could be a diagnostic indicator for malignancies in patients with DM, especially in those with anti-TIF1-γ antibodies.


Assuntos
Antígeno B7-H1/sangue , Dermatomiosite/sangue , Neoplasias/sangue , Adulto , Idoso , Dermatomiosite/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Adulto Jovem
13.
Am J Med Sci ; 355(1): 48-53, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29289262

RESUMO

BACKGROUND: The aim of this study was to compare the heterogeneity of interstitial lung disease (ILD) in patients with polymyositis and dermatomyositis (PM/DM) according to serological type. METHODS: A total of 182 patients with PM/DM-ILD were observed retrospectively. Antiaminoacyl-tRNA synthetase (ARS) and antimelanoma differentiation-associated gene5 (MDA5) antibodies were screened using immunoblotting approach. The patients with ILD were divided into 3 groups: MDA5 (with anti-MDA5 antibody), ARS (with anti-ARS antibody) and MSN (without anti-MDA5 or anti-ARS antibody) group. Pulmonary features, treatment responses and prognoses were compared among the groups. RESULTS: A higher percentage of rapidly progressive ILD (RP-ILD) occurrences (55.8% versus 25% versus 16.9%, P < 0.001) was observed in the MDA5 group compared to ARS and MSN groups. The MSN group experienced lower dyspnea (48.2% versus 79% versus 71.4%, P = 0.001) and fever (18.1% versus 39.5% versus 37.5%, P = 0.01) frequencies compared to MDA5 and ARS groups. Response to 6-month treatment among 95 patients showed highest deterioration ratio (70%, P = 0.001) of ILD in the MDA5 group. Additionally, the highest frequency of ILD improvement (60%, P = 0.04) was observed in the ARS group. During the observation period, 24 patients died of respiratory failure. The 5-year survival rates were significantly lower in MDA5 group (50.2%) compared to ARS group (97.7%) or the MSN group (91.4%) (P < 0.001). CONCLUSIONS: MDA5-ILD was associated with severe pulmonary manifestations, poor response to treatment and aggravated prognosis. The ARS-ILD group had favorable treatment response and prognosis. MSN-ILD patients had relatively worse treatment response and prognosis compared to the ARS group, even though they expressed milder pulmonary manifestation.


Assuntos
Autoanticorpos/sangue , Dermatomiosite/sangue , Doenças Pulmonares Intersticiais/sangue , Polimiosite/sangue , Adulto , Idoso , China/epidemiologia , Dermatomiosite/diagnóstico , Dermatomiosite/mortalidade , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimiosite/diagnóstico , Polimiosite/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendências
14.
Arthritis Res Ther ; 19(1): 259, 2017 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-29178913

RESUMO

BACKGROUND: Cancer is a significant complication contributing to increased mortality in idiopathic inflammatory myopathies (IIMs), and the association between IIMs and cancer has been extensively reported. Myositis-specific autoantibodies (MSAs) can help to stratify patients into more homogeneous groups and may be used as a biomarker for cancer-associated myositis. In this study, we aimed to systematically define the cancer-associated MSAs in IIMs. METHODS: Serum from 627 patients with IIMs was tested for MSAs. The cancer risk with different MSAs was estimated by standardized incidence ratio (SIR). Paraneoplastic manifestation, such as the close temporal relationship between myositis onset and cancer diagnoses in patients with different MSAs, was also evaluated. RESULTS: Compared with the general Chinese population, patients with IIMs and anti-transcriptional intermediary factor (TIF1)-γ antibodies (SIR = 17.28, 95% CI 11.94 to 24.14), anti-nuclear matrix protein (NXP2) antibodies (SIR = 8.14, 95% CI 1.63 to 23.86), or anti-SAE1 antibodies (SIR = 12.92, 95% CI 3.23 to 32.94), or who were MSAs-negative (SIR = 3.99, 95% CI 1.96 to 7.14) faced increased risk of cancer. There was no association between specific MSAs subtypes and certain types of cancer. Paraneoplastic manifestations were observed in the patients carrying anti-TIF1-γ, as well as other MSAs. There were no prognostic differences among the patients with cancer-associated myositis (CAM) from different MSAs subgroups. However, in comparison to those with cancer unrelated to myositis, CAM had a worse prognosis, with an age-adjusted and sex-adjusted Cox hazard ratio (HR) of 10.8 (95% CI 1.38-84.5, p = 0.02) for all-cause mortality. CONCLUSIONS: Our study demonstrates in what is, to our knowledge, the largest population examined to date, that anti-SAE1, and previously reported anti-TIF1-γ and anti-NXP2 antibodies, are all associated with an increased risk of cancer in patients with IIMs. Moreover, our data suggest that in some cases, anti-HMGCR, anti-Jo-1 and anti-PL-12 antibody production might also be driven by malignancy. This can aid in the etiologic research of paraneoplastic myositis and clinical management.


Assuntos
Autoanticorpos/imunologia , Miosite/complicações , Miosite/imunologia , Neoplasias/epidemiologia , Síndromes Paraneoplásicas/imunologia , Adulto , Autoantígenos/imunologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
15.
Oncotarget ; 8(46): 80651-80665, 2017 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-29113333

RESUMO

Excessive skin scars due to elective operations or trauma represent a challenging clinical problem. Pathophysiology of hypertrophic scars entails a prolonged inflammatory and proliferative phase of wound healing. Over expression of TGF-ß1 and COX-2 play key regulatory roles of the aberrant fibrogenic responses and proinflammatory mediators. When we silenced TGF-ß1 and COX-2 expression simultaneously in primary human fibroblasts, a marked increase in the apoptotic cell population occurred in contrast to those only treated with either TGF-ß1 or COX-2 siRNA alone. Furthermore, using human hypertrophic scar and skin graft implant models in mice, we observed significant size reductions of the implanted tissues following intra-scar administration of TGF-ß1/COX-2 specific siRNA combination packaged with Histidine Lysine Polymer (HKP). Gene expression analyses of those treated tissues revealed silencing of the target gene along with down regulations of pro-fibrotic factors such as α-SMA, hydroxyproline acid, Collagen 1 and Collagen 3. Using TUNEL assay detection, we found that the human fibroblasts in the implanted tissues treated with the TGF-ß1/COX-2siRNAs combination exhibited significant apoptotic activity. Therefore we conclude that a synergistic effect of the TGF-ß1/COX-2siRNAs combination contributed to the size reductions of the hypertrophic scar implants, through activation of fibroblast apoptosis and re-balancing between scar tissue deposition and degradation.

16.
J Rheumatol ; 44(7): 1051-1057, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28461650

RESUMO

OBJECTIVE: To compare the clinical characteristics and identify the longterm outcomes of Chinese patients with different antisynthetase antibodies. METHODS: We investigated retrospectively 124 consecutive patients with antisynthetase syndrome. Medical records, laboratory results, and computed tomography images were obtained. RESULTS: The antisynthetase antibodies we investigated were anti-Jo1 (n = 62), anti-PL7 (n = 31), anti-PL12 (n = 12), and anti-EJ (n = 19). The overall prevalence of interstitial lung disease (ILD) reached 94.4% among study patients. Eleven patients (8.9%) developed rapidly progressive ILD (RP-ILD). Eight patients (6.5%) experienced malignancy. RP-ILD was statistically more prevalent in patients with antisynthetase syndrome with anti-PL7 than those without anti-PL7 (p = 0.028). Anti-Ro52-positive patients with antisynthetase syndrome experienced higher frequency of RP-ILD than those without anti-Ro52 (p = 0.001). Further, anti-PL7-positive patients coexisting with anti-Ro52 exhibited more RP-ILD than those without anti-Ro52 (p = 0.001). Patients with antisynthetase syndrome with RP-ILD had a higher proportion of neutrophils in bronchoalveolar lavage fluid and serum ferritin than those without RP-ILD (p = 0.006 and p = 0.013, respectively). Although no differences were observed between the Kaplan-Meier curves of the 4 antisynthetase antibodies subgroups (p = 0.349), the survival rate of patients with anti-PL7 decreased more rapidly in the early stage of longterm followup compared with those with other antisynthetase antibodies. The presence of RP-ILD, malignancy, and elevated serum ferritin was identified to be associated with poor prognosis in patients with antisynthetase syndrome. CONCLUSION: Our study investigates the clinical phenotypes and outcomes of patients with antisynthetase syndrome with distinct antisynthetase antibodies and highlights the link between the anti-PL7 antibody and RP-ILD.


Assuntos
Autoanticorpos/sangue , Doenças Pulmonares Intersticiais/imunologia , Miosite/imunologia , Adulto , Idoso , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/diagnóstico por imagem , Prevalência , Prognóstico , Estudos Retrospectivos , Avaliação de Sintomas , Tomografia Computadorizada por Raios X
17.
BMC Infect Dis ; 17(1): 154, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28212610

RESUMO

BACKGROUND: HIV-related stigma always is major obstacles to an effective HIV response worldwide. The effect of HIV-related stigma on HIV prevention and treatment is particularly serious in China. This study was to examine stigma attitude towards people living with HIV/AIDS (PLWHA) among general individuals in Heilongjiang Province, Northeast China and the factors associated with stigma attitude, including socio-demographic factors and HIV/AIDS Knowledge. METHODS: A cross-sectional survey was carried out in Heilongjiang Province, China. A total of 4050 general individuals with age 15-69 years in four villages in rural areas and two communities in urban areas were drawn using stratified cluster sampling. Standardized questionnaire interviews were administered. Univariate and multivariate log-binomial regression were performed to assess factors affecting stigma attitude towards PLWHA. RESULTS: The proportions of participants holding stigma attitude towards PLWHA were 49.6% among rural respondents and 37.0% among urban respondents (P < 0.001). Multivariate log binomial regression analysis among both rural participants (RR = 0.89, 95% CI: 0.87-0.91, P < 0.001) and urban participants (RR = 0.89, 95% CI: 0.87-0.91, P < 0.001) showed that greater knowledge of HIV transmission misconceptions was significantly associated with lower stigma attitude towards people living with HIV. And among urban participants, higher education level (high school vs. primary school or less: RR = 0.73, 95%CI: 0.62-0.87, P < 0.001; middle school vs. primary school or less: RR = 0.83, 95%CI: 0.71-0.97, P = 0.018) were also significantly associated with lower stigma attitude towards PLWHA. CONCLUSIONS: The level of stigma attitude towards PLWHA is higher in rural areas than in urban areas in Heilongjiang. Meanwhile, individuals who better were aware of HIV/AIDS transmission misconceptions may hold lower stigma attitude toward PLWHA whether among rural or urban residents.


Assuntos
Infecções por HIV , Conhecimentos, Atitudes e Prática em Saúde , População Rural , Estigma Social , População Urbana , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/transmissão , Adolescente , Adulto , Idoso , Conscientização , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
18.
Chin J Integr Med ; 22(9): 696-703, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27614452

RESUMO

OBJECTIVE: To study a non-drug therapy for hypertension disease by combining percutaneous laser and electric pulse stimulation to acupoint with music, and to test the efficiency of the combining treatment to grade 1 essential hypertension. METHODS: A total of 174 patients with grade 1 essential hypertension were randomly assigned to 3 groups with a random number table after Chinese medicine (CM) syndrome differentiation: the photoelectric and musical treatment group (Group 1, with a self-developed multi-mode audio frequency pulse photoelectric therapeutic apparatus), acupuncture group (Group 2), and oral placebo group (Group 3), 58 cases per group. The curative effect of each group was evaluated by the changes of blood pressure and CM syndrome integral before and after treatment. RESULTS: Compared with Group 3, there were significant decrease of blood pressure and CM syndrome integral in Group 1 and Group 2 (P<0.01). Compared with Group 2, Group 1 showed the highest decrease in systolic pressure (P<0.017). The total effective rate of anti-hypertension in Group 1 (91.38%, 53/58) was significantly higher than that in Group 2 (74.13%, 43/58) and Group 3 (18.97%, 11/58, P<0.05 or P<0.01); and that in Group 2 was also significantly higher than that in Group 3 (P<0.01). There were significant difference in the total effective rate of CM syndrome integral in both Group 1 (93.10%, 54/58) and Group 2 (84.48%, 49/58) as compared with Group 3 (17.24%, 10/58, P<0.01), while there was no significant difference between Group 1 and Group 2 (P>0.05). CONCLUSIONS: The multi-mode audio frequency pulse photoelectric therapeutic apparatus, combining music, laser and electric pulse stimulation, is clinically useful for grade 1 essential hypertension. This "three in one" therapy method is non-invasive, easy and simple to handle. It is expected to be popularized as a new alternative treatment.


Assuntos
Pontos de Acupuntura , Terapia por Estimulação Elétrica , Hipertensão/terapia , Lasers , Música , Pressão Sanguínea , Hipertensão Essencial , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Síndrome , Resultado do Tratamento
19.
J Colloid Interface Sci ; 461: 96-103, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26397915

RESUMO

A nitrogen-doped hierarchical porous carbon has been prepared through one-step KOH activation of pitch oxide/graphene oxide composite. At a low weight ratio of KOH/composite (1:1), the as-prepared carbon possesses high specific surface area, rich nitrogen and oxygen, appropriate mesopore/micropore ratio and considerable small-sized mesopores. The addition of graphene oxide plays a key role in forming 4 nm mesopores. The sample PO-GO-16 presents the characteristics of large surface area (2196 m(2) g(-1)), high mesoporosity (47.6%), as well as rich nitrogen (1.52 at.%) and oxygen (6.9 at.%). As a result, PO-GO-16 electrode shows an outstanding capacitive behavior: high capacitance (296 F g(-1)) and ultrahigh-rate performance (192 F g(-1) at 10 A g(-1)) in 6 M KOH aqueous electrolyte. The balanced structure characteristic, low-cost and high performance, make the porous carbon a promising electrode material for supercapacitors.

20.
Clin Rheumatol ; 34(12): 2097-103, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26328518

RESUMO

The purpose of this study is to examine the efficacy and safety of tacrolimus (FK506) in the management of polymyositis (PM)/dermatomyositis (DM). The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched to find articles published between May 1980 and April 2015 concerning tacrolimus therapy in PM/DM. The initial search yielded 107 articles. In the end, eight studies met our inclusion criteria and involved a total of 134 patients who received tacrolimus therapy for DM/PM. All studies were non-randomized. Oral tacrolimus of 0.075 mg/kg/day or 1.0-3.5 mg/d was administered twice daily or once daily together with glucocorticoids (GCs). According to comprehensive analysis of the studies, 93.3 % (42/45) and 64.7 % (11/17) of patients showed improvement in muscle strength and physical function status. The creatine kinase (CK) levels of 100 % (68/68) of patients decreased. The average dosage of GCs was reduced from 33.8 to 11.5 mg/day in PM/DM patients after the addition of tacrolimus. In the subject population, 65 patients had interstitial lung disease (ILD). After treatment, the forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) improved or stabilized in 89.3 % (25/28) and 81.3 % (13/16) of patients, respectively. The commonly adverse events were nephrotoxicity, hypomagnesemia, tremors, and hypertension, but they were slight among these patients. Current evidence appears to support the use of tacrolimus in refractory PM/DM and PM/DM-ILD patients. Tacrolimus seems to be a safe drug that improves both muscle strength and lung function, and it is well tolerated by patients. However, this conclusion should be confirmed by large-sample, randomized controlled studies.


Assuntos
Dermatomiosite/tratamento farmacológico , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Tacrolimo/uso terapêutico , Dermatomiosite/complicações , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Humanos , Doenças Pulmonares Intersticiais/complicações , Polimiosite/complicações , Polimiosite/tratamento farmacológico , Resultado do Tratamento
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