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1.
J Helminthol ; 98: e13, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38263743

RESUMO

To investigate the effects of co-infection with Clonorchis sinensis (C. sinensis) on T cell exhaustion levels in patients with chronic hepatitis B, we enrolled clinical cases in this study, including the patients with concomitant C. sinensis and HBV infection. In this study, we detected inhibitory receptors and cytokine expression in circulating CD4+ and CD8+ T cells by flow cytometry. PD-1 and TIM-3 expression levels were significantly higher on CD4+ T and CD8+ T cells from co-infected patients than on those from the HBV patients. In addition, CD4+ T cells and CD8+ T cells function were significantly inhibited by C. sinensis and HBV co-infection compared with HBV single infection, secreting lower levels of Interferon gamma (IFN-γ), Interleukin-2 (IL-2), and TNF-α. Our current results suggested that C. sinensis co-infection could exacerbate T cell exhaustion in patients with chronic hepatitis B. PD-1 and TIM-3 could be novel biomarkers for T cell exhaustion in patients with Clonorchis sinensis and chronic hepatitis B co-infection. Furthermore, it may be one possible reason for the weaker response to antiviral therapies and the chronicity of HBV infection in co-infected patients. We must realize the importance of C. sinensis treatment for HBV-infected patients. It might provide useful information for clinical doctors to choose the right treatment plans.


Assuntos
Clonorquíase , Clonorchis sinensis , Coinfecção , Hepatite B Crônica , Animais , Humanos , Receptor Celular 2 do Vírus da Hepatite A , Receptor de Morte Celular Programada 1 , Exaustão das Células T
2.
J Clin Lab Anal ; 36(9): e24663, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36082466

RESUMO

OBJECTIVE: We evaluated the levels of sex hormones in male hepatitis B patients co-infected with Clonorchis sinensis (C. sinensis). METHODS: A total of 136 male individuals were enrolled in this study, including 27 healthy controls, 28 patients with C. sinensis mono-infection, 19 patients with only chronic hepatitis B, 18 patients with post-hepatitis B liver cirrhosis, 26 chronic hepatitis B patients co-infected with C. sinensis, and 18 post-hepatitis B liver cirrhosis patients coinfected with C. sinensis. Serum levels of progesterone (P), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), and follicle stimulating hormone (FSH) in these groups were measured. RESULTS: The results showed that compared with the LC group, the LC+ C. sinensis co-infected group had an increase in E2 but decrease in T and FSH. The levels of E2 in CHB+ C. sinensis co-infected patients were significantly higher than those in CHB mono-infected patients, but the significantly lower levels of T were observed. Compared with HCs group, the LC group showed significant increase in all terms of sex hormones, except PRL. By contrast, the CHB mono-infected group presented an apparent decrease in E2, T, and PRL than the HCs group. However, there were no significant differences in sex hormone levels between the C. sinensis mono-infected patients and HCs. CONCLUSION: This study suggests that C. sinensis co-infection aggravates the sex hormone disturbance in HBV patients at both chronic hepatitis and cirrhosis stages, providing evidences for potential strategies in disease prevention and treatment.


Assuntos
Clonorchis sinensis , Coinfecção , Hepatite B Crônica , Hepatite B , Animais , Coinfecção/epidemiologia , Hormônio Foliculoestimulante , Hormônios Esteroides Gonadais , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática , Masculino , Prolactina
3.
J Med Virol ; 91(4): 642-649, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30537157

RESUMO

Chronic liver inflammation caused by chronic hepatitis B virus (CHB) infection leads to liver cirrhosis and hepatocellular carcinoma. Recently, the role of alanine aminotransferase (ALT) as a predictor of liver inflammation has been questioned. The aim of this study was to investigate the utility of noninvasive fibrosis markers including hyaluronic acid (HA), collagen type IV (CIV), N-terminal propeptide of type III procollagen (PIIINP), and laminin (LN) in identifying significant liver inflammation in patients with CHB, especially in patients with normal or near-normal ALT. A total of 242 CHB patients who underwent liver biopsy were enrolled. The serum levels of ALT, aspartate aminotransferase, HA, CIV, PIIINP, and LN were quantified and the relationship between histological staging and serum markers was systematically analyzed. Serum CIV, PIIINP, HA, and LN levels increased significantly along with the increasing severity of liver inflammation. Multivariate analysis showed that CIV and LN were independently associated with significant inflammation. CIV, PIIINP, HA, and LN levels were found to have high diagnostic values for predicting significant inflammation in patients with CHB (area under the curve, AUC = 0.807, 0.795, 0.767, and 0.703, respectively). The combined index for the identification of significant inflammation, including CIV, PIIINP, HA, and LN levels, significantly improved diagnostic performance (AUC = 0.851). Moreover, the combined index also achieved excellent diagnostic accuracy (AUC = 0.861) in patients with CHB with normal or near-normal ALT. In conclusion, the combined index may be a strong indicator for discriminating significant liver inflammation, especially in patients with CHB with normal or near-normal ALT.


Assuntos
Alanina Transaminase/sangue , Biomarcadores/sangue , Testes Diagnósticos de Rotina/métodos , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Adolescente , Adulto , Idoso , Biópsia , Feminino , Histocitoquímica , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
4.
Rheumatology (Oxford) ; 54(6): 1093-102, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25406358

RESUMO

OBJECTIVE: The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells. METHODS: The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined. RESULTS: We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2-8 µmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD (P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group (P < 0.05). CONCLUSION: The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner.


Assuntos
Apoptose/fisiologia , Artrite Reumatoide/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Western Blotting , Estudos de Casos e Controles , Sobrevivência Celular/fisiologia , Dactinomicina/farmacologia , Feminino , Citometria de Fluxo , Proteínas Hedgehog/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/fisiologia , Receptor Smoothened , Membrana Sinovial/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Alcaloides de Veratrum/farmacologia
5.
Mar Drugs ; 12(5): 2790-801, 2014 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-24824025

RESUMO

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.


Assuntos
Inibidores da Angiogênese/farmacologia , Catecóis/farmacologia , Lignanas/farmacologia , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Proteína Oncogênica v-akt/efeitos dos fármacos , Nadadeiras de Animais/efeitos dos fármacos , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Catecóis/química , Movimento Celular/efeitos dos fármacos , Embrião não Mamífero , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lignanas/química , Fosforilação/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/farmacologia , Peixe-Zebra
6.
J Colloid Interface Sci ; 661: 259-270, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38301464

RESUMO

Microplastics (MPs), a newly emerging class of environmental contaminants, pose a severe threat to the entire ecosystem. The development of efficient and environmentally responsible adsorbents for removing the MPs is a particularly urgent research. Herein, a kind of monolithic ZIF-8 based adsorbents featuring stable hydrophobicity and micropore-mesopore-macropore hierarchical porous structure were fabricated by in situ growth of ZIF-8 nanoparticles on sodium alginate (SA) framework, and using polydimethylsiloxane (PDMS) as a hydrophobic agent. The monolithic nature of ZIF-8/SA allowed an easy solid-liquid separation process for adsorbents from water environment compared to powdered materials. The hierarchical porous structure ensures a remarkable MPs removal performance. The ZIF-8/SA showed high adsorption capacities of 594, 585, and 282 mg/g for polymethyl methacrylate (PMMA), poly (vinylidene difluoride) (PVDF), and polyvinyl chloride (PVC) respectively, and rapid adsorption kinetic progress within 120 min. The ZIF-8/SA adsorbents also exhibited excellent stability in the presence of interfering ions, acid/alkali, and humic acid, and displayed adsorption performance of > 70 % even in actual aquatic environment such as tap water, river water, and seawater. The results of characterizations showed that the synergistic effect of electrostatic interaction, hydrogen bonding, hydrophobic force, and van der Waals force was the main adsorption mechanism. The well-designed hydrophobic ZIF-8/SA monolithic materials would be promising to rapidly remove the MPs from the water environment.

7.
J Neuroimmunol ; 384: 578221, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37864934

RESUMO

INTRODUCTION: Uric acid (UA) is an important natural antioxidant and strong peroxynitrite scavenger, but little is known about central nervous system (CNS) levels of UA in patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDARE). METHODS: Cerebrospinal fluid (CSF) and serum levels of UA were determined in 72 patients with anti-NMDARE and 111 controls with non-inflammatory neurological diseases (NINDs). Serum UA levels were also evaluated in 132 healthy controls (HCs). CSF neuron-specific enolase (NSE) and blood-brain barrier (BBB) index were evaluated in patients with anti-NMDARE. The association of CSF UA levels with anti-NMDARE and its clinical parameters were evaluated in the patients. RESULTS: CSF UA levels were lower in patients with anti-NMDARE than in patients with NINDs, especially in patients with severe impairments (modified Rankin Scale [mRS] scores >3 vs. ≤ 3, p = 0.006). Furthermore, serum UA levels in patients with anti-NMDARE were significantly lower than in patients with NINDs and HCs. CSF UA levels were significantly associated with mRS scores, and serum UA levels in patients with anti-NMDARE. Furthermore, CSF/serum UA ratio was significantly associated with BBB index. CONCLUSIONS: CSF UA levels associated with disease severity and serum UA levels in patients with anti-NMDARE. And CSF/serum UA ratio correlated with BBB index, indicating that CSF and serum UA levels change similarly with BBB permeability in anti-NMDARE patients.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Doenças do Sistema Nervoso , Humanos , Ácido Úrico/líquido cefalorraquidiano , Barreira Hematoencefálica , Gravidade do Paciente
8.
J Neuroimmunol ; 369: 577900, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35661900

RESUMO

BACKGROUND: Cystatin C has neuroprotective and immunomodulatory effects on the central nervous system. However, the role of cerebrospinal fluid (CSF) cystatin C in anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) remains unknown. METHODS: In this study, CSF levels of cystatin C were determined in 73 patients with anti-NMDARE; 496 patients with other neurological diseases, comprising 108 with neuromyelitis optica, 77 with multiple sclerosis, 71 with schizophrenia, 68 with cryptococcus meningitis or meningoencephalitis, 43 with tuberculous meningitis or meningoencephalitis, 43 with bacterial meningitis or meningoencephalitis (BM), 35 with Guillain-Barré syndrome, 23 with spinal cord injury (SCI), 14 with amyotrophic lateral sclerosis (ALS), and 14 with idiopathic epilepsy; and 136 control patients with non-inflammatory diseases. The associations of CSF cystatin C with anti-NMDARE and its clinical parameters were evaluated. RESULTS: CSF cystatin C levels were significantly lower in patients with anti-NMDARE than in patients with BM, SCI, and ALS, especially among those with poor functional status (modified Rankin Scale [mRS] ≥4). CSF cystatin C levels were also significantly lower in anti-NMDARE patients with poor functional status (mRS ≥4) than in those with good functional status (mRS <4). CSF cystatin C levels were significantly associated with mRS scores and CSF white blood cell counts in anti-NMDARE patients. CONCLUSIONS: CSF levels of cystatin C are decreased in anti-NMDARE patients and negatively associated with disease severity.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Cistatina C , Doenças do Sistema Nervoso , Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Cistatina C/líquido cefalorraquidiano , Humanos , Meningoencefalite/líquido cefalorraquidiano , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano
9.
Cell Death Dis ; 11(11): 973, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184267

RESUMO

Long-lived plasma cells (LLPCs) are robust specialized antibody-secreting cells that mainly stay in the bone marrow and can persist a lifetime. As they can be generated by inducing the differentiation of B-lymphocytes, we investigated the possibility that human LLPCs might be engineered to express α-PD-1 monoclonal antibody to substitute recombinant α-PD-1 antitumor immunotherapy. To this end, we inserted an α-PD-1 cassette into the GAPDH locus through Cas9/sgRNA-guided specific integration in B-lymphocytes, which was mediated by an integrase-defective lentiviral vector. The edited B cells were capable of differentiating into LLPCs both in vitro and in vivo. Transcriptional profiling analysis confirmed that these cells were typical LLPCs. Importantly, these cells secreted de novo antibodies persistently, which were able to inhibit human melanoma growth via an antibody-mediated checkpoint blockade in xenograft-tumor mice. Our work suggests that the engineered LLPCs may be utilized as a vehicle to constantly produce special antibodies for long-term cellular immunotherapy to eradicate tumors and cellular reservoirs for various pathogens including human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV).


Assuntos
Anticorpos Monoclonais/imunologia , Sistemas CRISPR-Cas , Imunoterapia/métodos , Plasmócitos/imunologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/genética , Linfócitos B/citologia , Linfócitos B/imunologia , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Células HEK293 , Humanos , Camundongos , Plasmócitos/citologia , Linfócitos T/imunologia , Transgenes
10.
Clin Chem Lab Med ; 47(10): 1239-45, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19743957

RESUMO

BACKGROUND: High-density lipoprotein (HDL) is a major plasma lipoprotein directly associated with cholesterol metabolism. The ATP binding cassette transporter 1 gene (ABCA1) is one of the major genes modulating plasma levels of HDL-cholesterol (HDL-C). Rare alleles of ABCA1 associated with extreme HDL-C concentrations have not been previously investigated in the Chinese. METHODS: Blood samples were collected from 470 subjects whose HDL-C concentrations were within the top 5% of the distribution, 335 subjects in the lowest 5%, and 220 within the range 5%-95%. First, we sequenced all exons of the ABCA1 gene from 50 subjects from the group with extremely high HDL-C, and 50 from the group with extremely low HDL-C concentrations. Next, in the remaining subjects, we genotyped the non-synonymous variants identified exclusively with either extreme group. RESULTS: Four novel non-synonymous alleles were identified; all were rare. Alleles c.3029C>T (p.Ala1010Val) and c.5399A>G (p.Asn1800Ser) were found exclusively in the low group, c.2031C>A (p.Asp677Glu) and c.2660G>T (p.Cys887Phe) exclusively in the high group. CONCLUSIONS: Our results show that some rare alleles of ABCA1 are associated with marked phenotypes, supporting the "rare-variant common-disease" hypothesis. Certain alleles also provide tools for identifying individuals at high risk of dyslipidaemia, allowing for early therapeutic intervention.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Alelos , Povo Asiático/genética , HDL-Colesterol/metabolismo , Transportador 1 de Cassete de Ligação de ATP , Animais , Sequência de Bases , Membrana Celular/metabolismo , China/etnologia , Sequência Conservada , Feminino , Genótipo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Fenótipo , Ratos , Especificidade da Espécie , Taq Polimerase/metabolismo
11.
J Ethnopharmacol ; 114(2): 180-5, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17869461

RESUMO

Sinomenine (SN), an alkaloid prepared from the root of Sinomenium acutum Rehd. Et wils, is used to alleviate the symptoms of rheumatism in Chinese medicine. In the present study, the potential inhibition of TNF-alpha-induced VCAM-1 expression on human umbilical vein endothelial cells (HUVECs) was evaluated in vitro. HUVECs were isolated from freshly collected umbilical cords. Positive controls were stimulated with TNF-alpha, omitting SN. Negative controls were cultured omitting TNF-alpha and SN. Experimental groups were co-cultured with TNF-alpha and SN at different concentrations (0.25, 0.5, and 1.0 mol/L), or TNF-alpha and Dexamethasone (Dex) at a concentration of 1.0 x 10(-6) mol/L. Cells were harvested after culturing with the above drugs for 12 h. VCAM-1 mRNA expression was detected by real-time quantitative PCR, and VCAM-1 expression was detected by flow cytometry. The experimental data indicated that VCAM-1 mRNA and VCAM-1 were induced by TNF-alpha. The relative VCAM-1 mRNA expression decreased in the experimental groups (p<0.05). Concentrations of SN at 0.5 and 1.0 mol/L inhibited expression of VCAM-1 (p<0.05). SN at concentration of 0.25 mol/L and Dex at concentration of 1.0 x 10(-6) mol/L did not show an inhibitory effect on VCAM-1 expression in TNF-alpha-induced HUVECs. Our preliminary data indicates that SN has an inhibitory effect in vitro on TNF-alpha-induced VCAM-1 expression at both mRNA level and protein level in HUVECs, and suggests that SN may be a novel method of immunotherapy for rheumatic carditis or rheumatic heart disease.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Morfinanos/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Veias Umbilicais/metabolismo , Molécula 1 de Adesão de Célula Vascular/biossíntese , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Fator VIII/metabolismo , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Indicadores e Reagentes , NF-kappa B/biossíntese , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estimulação Química , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacos
12.
Cell Mol Immunol ; 14(2): 214-222, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26189371

RESUMO

Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P < 0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls (P < 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P < 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P < 0.05). The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.


Assuntos
Artrite Reumatoide/patologia , Receptor Smoothened/antagonistas & inibidores , Sinoviócitos/patologia , Apoptose/genética , Proliferação de Células/genética , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Receptor Smoothened/agonistas , Receptor Smoothened/metabolismo
13.
J Immunol Res ; 2014: 401903, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24741597

RESUMO

Sonic hedgehog (Shh) signaling controls many aspects of human development, regulates cell growth and differentiation in adult tissues, and is activated in a number of malignancies. Rheumatoid arthritis (RA) is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS). We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1) in RA synovial tissues was examined by immunohistochemistry (IHC) and in FLS by IHC, immunofluorescence (IF), quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (P < 0.05). Cyclopamine (a specific inhibitor of Shh signaling) decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G1 phase. Our data show that Shh signaling is activated in synovium of RA patients in vivo and in cultured FLS form RA patients in vitro, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA.


Assuntos
Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Proteínas Hedgehog/metabolismo , Transdução de Sinais , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Adulto , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Estudos de Casos e Controles , Proliferação de Células , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Hedgehog/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Receptores Patched , Receptor Patched-1 , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor Smoothened , Transativadores/genética , Transativadores/metabolismo , Alcaloides de Veratrum/farmacologia , Proteína GLI1 em Dedos de Zinco
15.
J Acquir Immune Defic Syndr ; 50(1): 1-8, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19295329

RESUMO

OBJECTIVE: To determine the prevalence of drug-resistant HIV-1 and the efficacy of first-line highly active antiretroviral therapy (HAART) regimens consisted of generic nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor among 339 study subjects in rural areas of Hubei province, China. METHODS: Two cross-sectional studies were conducted to investigate 150 HAART-naive (99 received subsequent therapy) between 2003 and 2005 and 288 HAART-experienced patients mainly between 2005 and 2006. Patients' CD4+ T-cell count and viral load were determined. HIV-1 pol gene fragments were amplified from patients' plasma by reverse transcriptase-polymerase chain reaction, subsequently sequenced and analyzed. RESULTS: About 83.5% of the patients were from rural villages. They were dominantly infected with subtype B' HIV-1 (96.7%) through paid blood donation (64.6%) and related blood transfusion (28.3%). We found that there was a steady increase of CD4 count over time among treated patients without detectable viral load (186/288, 64.6%). There was, however, an increasing prevalence of nucleoside reverse transcriptase inhibitor- and nonnucleoside reverse transcriptase inhibitor-resistant mutations among patients with detected viremia (102/288, 35.4%) after treatment for 3-6 (24.3%), 9-12 (57.1%), and 20-24 (63.3%) months, respectively. The increasing rates were associated with significant CD4 count drop and viral load increase. Some patients also developed multidrug-resistant mutants. CONCLUSIONS: : We report the first HIV-1 drug resistance study after 2 years on HAART among Chinese patients living in rural villages. Our data suggest that a significant portion of patients are failing first-line regimens with a trend of AIDS progression. It is therefore necessary to maximize the drug adherence and to make affordable second-line HAART regimens available immediately. Our results have implications for implementing HAART in underresourced developing country settings.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral Múltipla , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adulto , Terapia Antirretroviral de Alta Atividade , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Prevalência , Inibidores da Transcriptase Reversa/farmacologia , População Rural , Carga Viral , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
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