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1.
QJM ; 111(2): 89-96, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29048544

RESUMO

BACKGROUND: Valproic acid (VPA) has shown potent anti-inflammatory effect and attenuates acute lung injury. AIM: To determine whether the use of VPA is associated with a decreased risk of acute respiratory failure (ARF) in patients with subarachnoid hemorrhage (SAH). DESIGN: The Taiwan National Health Insurance Research Database was used to analyse all patients newly diagnosed with SAH from 2000 to 2010. The VPA users were matched for age, gender and index date in 1:2 ratios with randomly selected non-VPA users as a comparison group. METHODS: Multivariate Cox regression was used to identify the predictors of ARF and to compare the incidence rates of ARF among SAH patients using and not using VPA. RESULTS: The study cohort included 16 228 newly diagnosed SAH patients, from which 521 VPA users and 1042 matched non-VPA-exposed individuals were selected. In the VPA-treated cohort and the non-VPA-treated cohort, 117 and 289 patients developed ARF, respectively. Any use of VPA was associated with a 16% decreased risk of ARF requiring mechanical ventilation in 30-day tracking of the SAH patients (adjusted hazard ratio [HR], 0.840, 95% confidence interval [CI], 0.676-0.945). Age, sepsis and pneumonia were identified as independent predictors of ARF in patients with SAH. After stratification, VPA users showed a lower risk of ARF among SAH patients complicated with pneumonia compared with non-users of VPA (adjusted HR, 0.816, 95% CI, 0.652-0.921). CONCLUSIONS: Any use of VPA was associated with a reduced risk of ARF in patients with SAH. VPA may be beneficial for decreasing the risk of pneumonia-induced ARF in patients with SAH.


Assuntos
Anti-Inflamatórios/uso terapêutico , Insuficiência Respiratória/prevenção & controle , Hemorragia Subaracnóidea/complicações , Ácido Valproico/uso terapêutico , Doença Aguda , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/epidemiologia , Distribuição Aleatória , Respiração Artificial , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Medição de Risco/métodos , Hemorragia Subaracnóidea/epidemiologia , Taiwan/epidemiologia , Ácido Valproico/efeitos adversos
2.
Plant Biol (Stuttg) ; 20(2): 365-373, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29139179

RESUMO

Shikonin and its derivatives are important medicinal secondary metabolites accumulating in roots of Lithospermum erythrorhizon. Although some membrane proteins have been identified as transporters of secondary metabolites, the mechanisms underlying shikonin transport and accumulation in L. erythrorhizon cells still remain largely unknown. In this study, we isolated a cDNA encoding LeMRP, an ATP-binding cassette transporter from L. erythrorhizon, and further investigated its functions in the transport and biosynthesis of shikonin using the yeast transformation and transgenic hairy root methods, respectively. Real-time PCR was applied for expression analyses of LeMRP and shikonin biosynthetic enzyme genes. Functional analysis of LeMRP using the heterologous yeast cell expression system showed that LeMRP could be involved in shikonin transport. Transgenic hairy roots of L. erythrorhizon demonstrated that LeMRP overexpressing hairy roots produced more shikonin than the empty vector (EV) control. Real-time PCR results revealed that the enhanced shikonin biosynthesis in the overexpression lines was mainly caused by highly up-regulated expression of genes coding key enzymes (LePAL, HMGR, Le4CL and LePGT) involved in shikonin biosynthesis. Conversely, LeMRP RNAi decreased the accumulation of shikonin and effectively down-regulated expression level of the above genes. Typical inhibitors of ABC proteins, such as azide and buthionine sulphoximine, dramatically inhibited accumulation of shikonin in hairy roots. Our findings provide evidence for the important direct or indirect role of LeMRP in transmembrane transport and biosynthesis of shikonin.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Lithospermum/metabolismo , Naftoquinonas/metabolismo , Proteínas de Plantas/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Lithospermum/genética , Proteínas de Membrana Transportadoras/metabolismo , Filogenia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA
3.
Int J Immunopathol Pharmacol ; 28(1): 14-20, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25816401

RESUMO

Stanniocalcin (STC), first isolated from the corpuscles of stannius of teleost fishes, was originally known for its regulation on calcium/phosphate transport. Increasing evidence demonstrates that STCs display the important function in some physiological and pathological behaviors such as calcium regulation, oxidative stress, anti-inflammation, angiogenesis, ischemia reperfusion, nerve diseases, etc. Moreover, STCs are implicated in the development and progression of multiple malignancies through promoting cell growth, proliferation, invasion, metastasis, and apoptotic escape. Some studies have shown that NF-κB upregulates STC expression, thereby activating the downstream HIF-1/ERK1/2 signaling pathway, enhancing the transcriptional activity of tumor-related factors (MMP-2/9, cyclinD1, Bcl-2, N-cadherin, etc) and contributing to tumorigenesis. Here, this brief review describes recent progress of STCs in mammalians, focused mainly on their critical functions in cancer.


Assuntos
Carcinogênese/metabolismo , Glicoproteínas/metabolismo , Neoplasias/metabolismo , Animais , Carcinogênese/patologia , Peixes/metabolismo , Humanos , Neoplasias/patologia
4.
Int J Clin Pract ; 63(8): 1161-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19624786

RESUMO

OBJECTIVE: The purpose of this study was to determine whether initial serum glucose levels, therapeutic responses to intravenous glucose replacement and changes in serum glucose levels over time could predict serum glucose patterns. METHODS: The patients enrolled in this retrospective chart review had been previously diagnosed with diabetes mellitus and were later hospitalised for severe hypoglycaemia (SH). They were all admitted to the emergency department (ED) during a 4-year period between January 2003 and December 2006. Comparison of the therapeutic responses to glucose replacement according to the serum glucose patterns [categorised into recurrent hypoglycaemia (RH), overshoot hyperglycaemia (OH) and favourable groups] during the first 48 h was performed. RESULTS: Compared with the favourable group, therapeutic responses to glucose replacement were significantly lower in the RH group and higher in the OH group; the changes in serum glucose levels over time were also significantly lower in the RH group and higher in the OH group. CONCLUSION: Therapeutic responses to glucose replacement and changes in serum glucose levels over time can differentiate diabetic patients with RH and OH from those with favourable glucose patterns during the first 48 h after presentation in the ED with SH. We believe that a 'response-to-treatment' based strategy is useful in determining the ED disposition of diabetic patients presenting with SH.


Assuntos
Glicemia/metabolismo , Complicações do Diabetes/prevenção & controle , Glucose/administração & dosagem , Hipoglicemia/prevenção & controle , Idoso , Complicações do Diabetes/sangue , Feminino , Humanos , Hipoglicemia/sangue , Infusões Intravenosas , Tempo de Internação , Masculino , Recidiva , Estudos Retrospectivos
5.
BMJ Case Rep ; 2009: bcr2006037556, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21687054
6.
BMJ Case Rep ; 2009: bcr2006039149, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21687060
7.
BMJ Case Rep ; 2009: bcr2006039172, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21687061
8.
BMJ Case Rep ; 2009: bcr2006039412, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21687062
9.
BMJ Case Rep ; 2009: bcr2006045922, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21687088
10.
BMJ Case Rep ; 2009: bcr2007050450, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21687251
15.
Rheumatology (Oxford) ; 46(8): 1266-73, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17569750

RESUMO

OBJECTIVES: To explore the source of the p19 subunit of interleukin-23 (IL-23) in joints with rheumatoid arthritis (RA), the effects of IL-1beta and tumour necrosis factor (TNF)-alpha on IL-23 gene expression in RA fibroblast-like synoviocytes and the effect of IL-23 on proinflammatory cytokines. METHODS: Expression of IL-23 p19 in joints was examined by immunohistochemical analysis of patients with RA and osteoarthritis (OA). The effects of IL-1beta and TNF-alpha on the expression, of IL-23 p19 and IL-12 p35 subunits in human fibroblast-like synoviocytes from RA patients (HFLS-RA) were determined by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and western blotting assay. Blockade of nuclear factor kappaB (NF-kappaB) or AP-1 activation was used to verify the involvement of intracellular signal pathways of the induction of p19. IL-23-induced IL-8 and IL-6 productions were determined in HFLS-RA by RT-PCR and enzyme-linked immunosorbent assay. RESULTS: IL-23 p19 was expressed in the synovium from RA, but not from OA patients. Similar to the protein expression, IL-23 p19 mRNA could be detected by RT-PCR in four of five RA synovial fluid mononuclear cells (SFMC). IL-1beta and TNF-alpha could induce RA fibroblast-like synoviocytes to produce the IL-23 p19 subunit. The effects of IL-1beta were much stronger than TNF-alpha. These responses were observed in both a dose-responsive and time-dependent manner. IL-1beta produced weakly enhanced gene expression of the p35 subunits of IL-12. IL-1beta also promotes the p35 expression, a subunit of IL-12, but weakly. In addition, the NF-kappaB and the AP-1 inhibitors down-regulated the expression of IL-23 p19 mRNA induced by IL-1beta. IL-23 receptor (IL-23R) was of constitutive expression in HFLS-RA. Moreover, IL-23 up-regulated the IL-8 and IL-6 mRNA and protein levels in a dose-dependent manner in HFLS-RA. CONCLUSIONS: Our results demonstrate that IL-23, produced by mononuclear cells in synovial fluid with RA and HFLS-RA, promotes inflammatory responses in RA by inducing IL-8 and IL-6 production from HFLS. IL-1beta regulates IL-23 p19 expression via NF-kappaB and AP-1 pathways. This report also demonstrates that IL-23 could promote inflammatory responses in HFLS-RA by stimulating IL-8 and IL-6 production.


Assuntos
Artrite Reumatoide/imunologia , Interleucina-1beta/imunologia , Subunidade p19 da Interleucina-23/metabolismo , Membrana Sinovial/patologia , Artrite Reumatoide/patologia , Células Cultivadas , Relação Dose-Resposta Imunológica , Regulação da Expressão Gênica/imunologia , Humanos , Interleucina-17/biossíntese , Subunidade p19 da Interleucina-23/genética , Subunidade p19 da Interleucina-23/imunologia , Interleucina-6/biossíntese , Interleucina-8/biossíntese , NF-kappa B/fisiologia , RNA Mensageiro/genética , Receptores de Interleucina/metabolismo , Líquido Sinovial/imunologia , Membrana Sinovial/imunologia , Fator de Transcrição AP-1/fisiologia , Fator de Necrose Tumoral alfa/imunologia
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