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1.
Dose Response ; 18(2): 1559325820917824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32284703

RESUMO

Objective: The prognostic value of C-reactive protein to albumin ratio (CAR) has been identified in several cancers but not in extranodal natural killer T-cell lymphoma (ENKTL) as yet. We aimed to evaluate the prognostic value of CAR in ENKTL. Methods: A retrospective study with 246 patients with ENKTL was performed to determine the prognostic value of pretreatment CAR and examine the prognostic performance of CAR incorporating with International Prognostic Index (IPI) or natural killer/T-cell lymphoma prognostic index (NKPI) by nomogram. Results: The Cox regression analyses showed that high CAR (>0.3) independently predicted unfavorable progression-free survival (PFS, P = .011) and overall survival (OS, P = .012). In the stratification analysis, the CAR was able to separate patients into different prognoses regarding both OS and PFS in Ann Arbor stage I+II as well as III+IV, IPI score 0 to 1, and NKPI score 1 to 2 subgroups (all P < .05). Additionally, the predictive accuracy of the IPI-based nomogram incorporating CAR, albumin to globulin ratio (AGR), and IPI for OS and PFS appeared to be lower than the NKPI-based nomogram incorporating CAR, age, AGR, extranodal site, and NKPI. Conclusion: Pretreatment CAR is a simple and easily accessible parameter for independently predicting OS and PFS in patients with ENKTL.

2.
Eur J Drug Metab Pharmacokinet ; 45(4): 453-466, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32170643

RESUMO

BACKGROUND AND OBJECTIVES: Tacrolimus is a widely used immunosuppressive agent with narrow therapeutic window. Nowadays, tacrolimus has gained acceptance as a therapeutic option in myasthenia gravis (MG) treament, however, little is known about its pharmacokinetic characteristics in MG population. In this study, we aimed to investigate the population pharmacokinetic (PopPK) of tacrolimus in patients with MG and to develop model-informed dosing regimens. METHODS: Trough concentrations of tacrolimus (267 measurements) and cytochrome P450 (CYP) genotypes were determined in 97 Chinese adults. The non-linear mixed-effects model was used for PopPK modeling. Monte Carlo simulations based on the established model were employed to design dosing regimens. RESULTS: The PopPK model was described using a one-compartment model with first-order absorption and elimination. The mean apparent clearance (CL/F) of tacrolimus was 17.1 L/h, with a between-subject variability of 20.1%. Covariate screening of demographic characteristics, blood test results, co-medications, and CYP3A5*3 or CYP3A4*1G polymorphisms showed that the CYP3A5*3 genotype and co-administration of a Wuzhi capsule significantly affected tacrolimus CL/F. CONCLUSIONS: For patients with the CYP3A5*3*3 allele, the required tacrolimus dose for 75% of subjects to achieve target trough concentrations of 4.8-15 ng/mL was 2 mg every 12 h (q12h). For patients with the CYP3A5*1*1 allele, the required dose was 2 mg tacrolimus q12h with a Wuzhi capsule, and for patients with the CYP3A5*1*3 allele, the required dose was 3 mg of tacrolimus q12h or 4 mg q24h co-administered with a Wuzhi capsule. This model could be employed to optimize individualized therapies for patients with MG.


Assuntos
Imunossupressores/farmacocinética , Modelos Biológicos , Miastenia Gravis/tratamento farmacológico , Tacrolimo/farmacocinética , Adolescente , Adulto , Idoso , China , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/etnologia , Variantes Farmacogenômicos , Medicina de Precisão , Estudos Prospectivos , Tacrolimo/administração & dosagem , Tacrolimo/sangue , Resultado do Tratamento , Adulto Jovem
3.
Ann N Y Acad Sci ; 1452(1): 18-33, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31393614

RESUMO

Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell dependence and complement involvement. Cholinesterase inhibitors (e.g., pyridostigmine bromide), glucocorticoids, and azathioprine are currently recommended as first-line treatments for MG, though they have limitations, including potential toxicity and ineffectiveness in patients with refractory MG. In recent years, owing to an increasing understanding of MG pathogenesis the development and execution of clinical trials with novel biologics, including monoclonal antibodies (mAbs) that have demonstrated higher safety and more specificity, provide new opportunities for the treatment of MG. In this article, we review recent advances in MG pathogenesis and the mAbs that have been used for target-specific MG therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoterapia/métodos , Miastenia Gravis/tratamento farmacológico , Azatioprina/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Miastenia Gravis/imunologia , Brometo de Piridostigmina/uso terapêutico , Resultado do Tratamento
4.
PLoS One ; 14(1): e0210205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30620750

RESUMO

PURPOSE: To investigate the relationship between anterior capsule polish and visual function. METHODS: Data were obtained from Pubmed, Embase, Web of Science, WanFang, VIP and CNKI up to the end of May 2018, without any date or language restrictions for trials. The modified Jadad scale and the newcastle-ottawa scale were used to assess the quality of included studies. Uncorrected visual acuity (UCVA) and posterior capsule opacification (PCO) were used as outcome variables. Data on anterior capsule polish were pooled using weighted, random-effect meta-analysis. RESULTS: One randomized controlled trial and 4 observational cohort studies involving 2533 patients were included in the analyses. There was a statistically significant difference of UCVA (OR 1.92, 95% CI 1.41-2.61) between the polish group and the control group, indicating that anterior capsule polish improved UCVA. Further studies with continuous data also suggested that anterior capsule polish was associated with good UCVA (MD 0.11, 95% CI 0.06-0.16). Posterior capsule opacification rate for 1-year or longer follow-up were extracted for 2561 eyes in 3 studies. Posterior capsule opacification rate was lower in the anterior capsule polish group according to summary odds ratio on PCO rate (OR 0.42 95% CI 0.24-0.73). CONCLUSIONS: Anterior capsule polish prevents complication of modern cataract surgery and benefits on visual function in short term follow-up period.


Assuntos
Cápsula Anterior do Cristalino/cirurgia , Opacificação da Cápsula/epidemiologia , Facoemulsificação/métodos , Complicações Pós-Operatórias/epidemiologia , Acuidade Visual/fisiologia , Cápsula Anterior do Cristalino/fisiologia , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/prevenção & controle , Humanos , Estudos Observacionais como Assunto , Facoemulsificação/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Brain Res Bull ; 143: 171-180, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30086352

RESUMO

OBJECTIVE: To characterize the microenvironment following blood-spinal cord barrier (BSCB) damage and to evaluate the role of BSCB disruption in secondary damage of spinal cord injury (SCI). METHODS: A model of BSCB damage was established by co-culture of primary microvascular endothelial cells and glial cells obtained from rat spinal cord tissue followed by oxygen glucose deprivation/re-oxygenation (OGD/R). Permeability was evaluated by measuring the transendothelial electrical resistance (TEER) and the leakage test of Fluorescein isothiocyanate-dextran (FITC-dextran). The expression of tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1) were evaluated by Western blot and immunofluorescence microscopy. Proinflammatory factors (TNF-α, iNOS, COX-2 and IL-1ß), leukocyte chemotactic factors (MIP-1α, MIP-1ß) and leukocyte adhesion factors (ICAM-1, VCAM-1) were detected in the culture medium under different conditions by enzyme-linked immuno sorbent assay (ELISA). RESULTS: The model of BSCB damage induced by OGD/R was successfully constructed. The maximum BSCB permeability occurred 6-12 hours but not within the first 3 h after OGD/R-induced damage. Likewise, the most significant period of TJ protein loss was also detected 6-12 hours after induction. During the hyper-acute period (3 h) following OGD/R-induced damage of BSCB, leukocyte chemotactic factors and leukocyte adhesion factors were significantly increased in the BSCB model. Pro-inflammation factors (TNF-α, IL-1ß, iNOS, COX-2), leukocyte chemotactic factors (MIP-1α, MIP-1ß) and leukocyte adhesion factors (ICAM-1, VCAM-1) were also sharply produced during the acute period (3-6 hours) and maintained plateau levels 6-12 hours following OGD/R-induced damage, which overlapped with the period of BSCB permeability maximum. A negative linear correlation was observed between the abundance of proinflammatory factors and the expression of TJ proteins (ZO-1 and occludin) and transepithelial electrical resistance (TEER), and a positive linear correlation was found with transendothelial FITC-dextran. CONCLUSIONS: Secondary damage continues after primary BSCB damage induced by OGD/R, exhibiting close ties with inflammation injury.


Assuntos
Barreira Hematoencefálica/metabolismo , Animais , Microambiente Celular , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Glucose/metabolismo , Interleucina-1beta/metabolismo , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Ocludina/metabolismo , Oxigênio/metabolismo , Cultura Primária de Células , Ratos , Medula Espinal/metabolismo , Medula Espinal/fisiologia , Traumatismos da Medula Espinal/metabolismo , Junções Íntimas , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
6.
J Cell Biochem ; 119(10): 8336-8345, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29932239

RESUMO

Minimal hepatic encephalopathy (MHE), a complex neuropsychological complication of cirrhosis, is characterized by delayed reaction time and the inhibition of abnormal response. This network meta-analysis (NMA) was adopted to compare the efficacy of five drugs including lactulose, probiotics, rifaximin, acetyl-L-carnitine (ALC), and L-Ornithine L-aspartate (LOLA) in the treatment of MHE. The Cochrane Library, PubMed, and Embase databases were searched for any existing entail on these five drugs from the inception to February 2018, including Randomized controlled trials (RCTs). The NMA of the five drugs, accounting for both direct and indirect comparisons to assess WMD (weighted mean difference) and SUCRA (surface under the cumulative ranking curves) was conducted. In total, 10 RTCS with 826 MHE patients met the inclusion criteria and were included in the NMA. The meta-analysis revealed that compared with placebo, lactulose, and probiotics had better efficacy in reducing ammonia serum levels and total SIP (Sickness Impact Profil) score; ALC had better efficacy in lowering serum level of ammonia and increasing the serum level of albumin; rifaximin and LOLA had better efficacy in reducing total SIP score. The results from SUCRA revealed that in terms of ammonia and albumin serums, ALC presented with the highest rankings when it comes to efficacy (serum ammonia: 87.2%; serum albumin: 92.25%). Hence, the key findings from the present study highly suggested that ALC had the best efficacy in the treatment of MHE patients.


Assuntos
Acetilcarnitina/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Lactulose/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Probióticos/uso terapêutico , Adulto , Amônia/sangue , Dipeptídeos/uso terapêutico , Feminino , Encefalopatia Hepática/metabolismo , Encefalopatia Hepática/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Rifaximina/uso terapêutico , Albumina Sérica/metabolismo , Resultado do Tratamento
7.
Biosci Rep ; 38(1)2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29176000

RESUMO

The present study was conducted with the aim being to investigate the effect γ-aminobutyric acid type B (GABAB) receptor activation have on spatial cognitive function and hippocampal neurones found in the rat models of type 2 diabetes mellitus (T2DM). T2DM rat models were then established, randomized, and subsequently assigned into normal control (NC), T2DM, T2DM + chemical grade propylene (CGP), T2DM + baclofen, and T2DM + CGP + baclofen groups. T2DM rats' weight and blood sugar concentrations were monitored. The DMS-2 Morris water maze testing system was performed in order to figure out the spatial cognitive function of these rats. Reverse-transcription quantitative PCR (RT-qPCR) and Western blotting were also performed in order to detect GABAB mRNA and protein expressions. We used the Nissl staining method in order to detect the number of hippocampal neurones, TUNEL (terminal deoxyribonucleotidy transferase-mediated dUTP nick labeling) staining to detect cell apoptosis, and Western blotting method in order to measure the expressions of the apoptosis-related proteins (Bax, cytochrome c (Cyt-c), Caspase-3, and Bcl-2). In comparison with the T2DM group, the weight decreased, blood sugar concentration increased, and spatial cognitive function as well as hippocampal neurones were both impaired in the T2DM + CGP group, contrary to the rats in the T2DM + baclofen group who showed an opposite trend. The situation in the T2DM + CGP + baclofen group was better than that found in the T2DM + CGP group while proving to be more serious than that of the NC and T2DM + baclofen groups. Conclusively, activating the GABAB receptor improved spatial cognitive function and hippocampal neurones in the T2DM rats.


Assuntos
Cognição/efeitos dos fármacos , Diabetes Mellitus Tipo 2/genética , Neurônios/efeitos dos fármacos , Receptores de GABA-B/genética , Animais , Apoptose/efeitos dos fármacos , Baclofeno/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Neurônios/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Ativação Transcricional/genética
8.
BMC Ophthalmol ; 17(1): 219, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29179705

RESUMO

BACKGROUND: To evaluate the effects on vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with inverted internal limiting membrane flap technique for macular hole-induced retinal detachment (MHRD). METHODS: Pubmed, Cochrane Library, and Embase were systematically searched for studies that compared ILM peeling with inverted ILM flap technique for macular hole-induced retinal detachment. The primary outcomes are the rate of retinal reattachment and the rate of macular hole closure 6 months later after initial surgery, the secondary outcome is the postoperative best-corrected visual acuity (BCVA) 6 months later after initial surgery. RESULTS: Four studies that included 98 eyes were selected. All the included studies were retrospective comparative studies. The preoperative best-corrected visual acuity was equal between ILM peeling and inverted ILM flap technique groups. It was indicated that the rate of retinal reattachment (odds ratio (OR) = 0.14, 95% confidence interval (CI):0.03 to 0.69; P = 0.02) and macular hole closure (OR = 0.06, 95% CI:0.02 to 0.19; P < 0.00001) after initial surgery was higher in the group of vitrectomy with inverted ILM flap technique than that in the group of vitrectomy with ILM peeling. However, there was no statistically significant difference in postoperative best-corrected visual acuity (mean difference (MD) 0.18 logarithm of the minimum angle of resolution; 95% CI -0.06 to 0.43 ; P = 0.14) between the two surgery groups. CONCLUSION: Compared with ILM peeling, vitrectomy with inverted ILM flap technique resulted significantly higher of the rate of retinal reattachment and macular hole closure, but seemed does not improve postoperative best-corrected visual acuity.


Assuntos
Membrana Epirretiniana/cirurgia , Descolamento Retiniano/cirurgia , Perfurações Retinianas/cirurgia , Retalhos Cirúrgicos , Vitrectomia/métodos , Humanos , Descolamento Retiniano/etiologia , Perfurações Retinianas/complicações , Estudos Retrospectivos
9.
Mol Med Rep ; 16(6): 9029-9034, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28990094

RESUMO

The present study aimed to identify potential dysregulated pathways to further reveal the molecular mechanisms of postmenopausal osteoporosis (PMOP) based on pathway­interaction network (PIN) analysis, which considers crosstalk between pathways. Protein­protein interaction (PPI) data and pathway information were derived from STRING and Reactome Pathway databases, respectively. According to the gene expression profiles, pathway data and PPI information, a PIN was constructed with each node representing a biological pathway. Principal component analysis was used to compute the pathway activity for each pathway, and the seed pathway was selected. Subsequently, dysregulated pathways were extracted from the PIN based on the seed pathway and the increased classification accuracy, which was measured using the area under the curve (AUC) index according to 5­fold cross validation. A PIN comprising 2,725 interactions was constructed, which was used to detect dysregulated pathways. Notably, the 'mitotic prometaphase' pathway was selected and defined as a seed pathway. Starting with the seed pathway, network­based analysis successfully identified one pathway set for PMOP comprising eight dysregulated pathways (such as mitotic prometaphase, resolution of sister chromatid cohesion, mRNA splicing and mRNA splicing­major) with an AUC score of 0.85, which may provide potential biomarkers for targeted therapy for PMOP.


Assuntos
Regulação da Expressão Gênica , Redes Reguladoras de Genes , Osteoporose Pós-Menopausa/genética , Humanos , Mapas de Interação de Proteínas , Transcriptoma
10.
J Obstet Gynaecol Res ; 43(9): 1428-1440, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28613016

RESUMO

AIM: The association between parity and rheumatoid arthritis (RA) risk has been investigated, but results are controversial. Thus, our aim was to systematically analyze the effect of number of parity on the risk of RA in women. METHODS: Relevant published studies were identified using PubMed and embase databases through 1 April 2016. We pooled the relative risks (RR) and 95% confidence intervals (CI) using random-effects models. RESULTS: In all, 12 studies with a total of 2 497 580 participants and 11 521 RA cases were included. A borderline significant inverse association was observed when we compared parity with nulliparity for RA, with summarized RR = 0.90 (95%CI: 0.79-1.02; I2  = 58.5%, Pheterogeneity  = 0.010). In dose-response analysis, we observed a significant nonlinear (Pnonlinearity  = 0.000) relation between parity number and the risk of RA. Compared with null parity, the pooled RR of RA were 0.89 (95%CI: 0.86-0.93), 0.84 (95%CI: 0.79-0.89), 0.85 (95%CI: 0.79-0.90), 0.88 (95%CI: 0.81-0.95), 0.90 (95%CI: 0.83-0.97), 0.92 (95%CI: 0.84-1.02), and 0.94 (95%CI: 0.83-1.07) for 1, 2, 3, 4, 5, 6, and 7 live births, respectively. Subgroup and sensitivity analyses showed similar associations. No publication bias was found. CONCLUSION: The findings from the current meta-analysis indicate that parity was related to decreased risk of RA. The greatest risk reduction appeared when the parity number reached two. Further studies are warranted to confirm our findings.


Assuntos
Artrite Reumatoide/epidemiologia , Estudos Observacionais como Assunto , Paridade , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
11.
Oncotarget ; 8(18): 30455-30463, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-27458166

RESUMO

Proprotein convertase-subtilisin/kexin type 9 (PCSK9) monoclonal antibody is a new therapy to reduce low-density lipoprotein cholesterol (LDL-C) level in patients with familial hypercholesterolemia (FH). This pooled analysis aimed to estimate the efficacy and safety of PCSK9 antibody therapy in FH. Reports of randomized controlled trials (RCTs) comparing PCSK9 antibody to placebo were retrieved by a search of MEDLINE via PubMed, EMBASE, the Cochrane Library databases, ClinicalTrials.gov and Clinical Trial Results (up to November 30, 2015) with no language restriction. Data were abstracted by a standardized protocol. We found eight RCTs (1,879 patients with FH) for the pooled analysis. As compared with placebo, PCSK9 antibody therapy remarkably reduced LDL-C level (mean reduction: -48.54 %, 95 % CI: -53.19 to -43.88), total cholesterol (mean reduction: -31.08%, 95 % CI: -35.20 to -26.95), lipoprotein (a) (mean reduction: -20.44%, 95 % CI: -25.21 to -15.66), and apolipoprotein B (mean reduction: -36.32%, 95 % CI: -40.75 to -31.90) and elevated the level of high-density lipoprotein cholesterol (mean change: 6.29 %, 95 % CI: 5.12 to 7.46) and apolipoprotein A1(mean change: 4.86%, 95 % CI: 3.77 to 5.95). Therapy with and without PCSK9 antibodies did not differ in rate of adverse events (pooled rate: 50.86 % vs. 48.63%; RR: 1.03; 95 % CI: 0.92 to 1.15; P = 0.64; heterogeneity P = 0.13; I2= 40%) or serious adverse events (pooled rate: 7.14% vs. 6.74%; RR: 1.05; 95 % CI: 0.70 to 1.58; P = 0.80; heterogeneity P = 0.69; I2= 0%). PCSK9 antibody may be an effective and safe treatment for FH.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Biomarcadores , Ensaios Clínicos como Assunto , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/metabolismo , Lipídeos/sangue , Viés de Publicação , Resultado do Tratamento
12.
Med Sci Monit ; 22: 3352-3361, 2016 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-27654003

RESUMO

BACKGROUND 5-Fluorouracil (5-FU) based treatment is the standard therapy for metastatic colorectal cancer (CRC), but the development of chemoresistance is inevitable. Increasing evidence shows that dysregulation of microRNAs (miRNAs) is involved in malignant transformation. Thus, it is imperative that we find new diagnostic and prognostic marker for chemotherapy in CRC. MATERIAL AND METHODS For clinical parameter analysis, 78 CRC tissues and adjacent normal tissues and 45 serum specimens from CRC patients were included in this study. For chemo-response analysis, 116 primary tissues were collected from the patients receiving first-line 5-FU treatment. Quantitative Real-Time PCR (qRT-PCR) was used to detect microRNAs expression. RESULTS The expression of miR-429 was significantly increased in both serum and primary tissues from CRC patients, and enhanced miR-429 level was associated with tumor size, lymph node metastasis, and TNM stage. The diagnostic and prognostic values were also confirmed in CRC by using primary tissues. For patients receiving 5-FU-based treatment, miR-429 levels were significantly lower in responding group. The proportions of patients that did not experience response to therapy were higher in primary tumors with high miR-429 expression levels as compared with primary tumors with low miR-429 expression levels. Finally, Kaplan-Meier survival analysis showed that miR-429 is an independent prognostic indicator for chemo-response to 5-FU therapy among CRC patients. CONCLUSIONS High level of miR-429 expression was correlated with enhanced malignant potential and poor prognosis of CRC patients. Furthermore, miR-429 could affect the chemo-sensitivity of CRC patients to 5-FU therapy and was associated with poor response to 5-FU-based chemotherapy in patients with CRC.

13.
Biomed Pharmacother ; 83: 930-935, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27522255

RESUMO

Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted from a traditional Chinese herb pogostemonis herba. Literatures have proven that PA could inhibit inflammatory responses in various inflammatory disease models. However, whether PA could protect against atherosclerosis, a chronic vascular inflammation, is unknown. In this study, we sought to explore this issue in atherosclerosis-prone apolipoprotein E knockout mice fed an atherogenic diet, with or without daily PA intragastrical administration (40mg/kg). Our results showed that PA administration did not change plasma lipids metabolism, however, it significantly attenuated atherosclerotic plaque burdens in both the aorta and the aortic root. The lesional macrophage content, shown as Mac2 positive areas, was reduced, while the lesional smooth muscle cell and collagen content, shown as α-SMA positive areas and by Sirius red staining, respectively, was not affected in PA-treated mice, compared with non-treated controls. Aortic mRNA expression of macrophage inflammatory cytokines, including MCP-1, iNOS, IL-1ß, IL-6, CXCL9 and CXCL11, was also reduced in PA-treated mice. Therefore, we demonstrated that PA could attenuate atherosclerosis, possibly by inhibiting macrophage infiltration and its inflammatory responses.


Assuntos
Aterosclerose/tratamento farmacológico , Inflamação/patologia , Macrófagos/patologia , Sesquiterpenos/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Placa Aterosclerótica/patologia , Sesquiterpenos/farmacologia
14.
Eur Spine J ; 25 Suppl 1: 224-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27002614

RESUMO

Symptomatic postoperative spinal epidural hematoma (SEH) and spontaneous spinal epidural hematoma (SSEH) are both rare conditions, and recurrent SEH occurs even less frequently. Therefore, we describe a case of symptomatic postoperative SEH after surgical evacuation of SSEH, which was diagnosed using magnetic resonance imaging (MRI) and managed with negative pressure wound therapy (NPWT). The authors classified the reported recurrent SEHs into two types based on the cause of their previous hematoma, which can be classified as spontaneous or postoperative. The characteristics, diagnosis, managements, and results of recurrent SEHs were analyzed. The authors suggest that the postoperative SEH in the Type II will be treated with NPWT, and the new classification will be helpful for prognosis, diagnosis, and management of the recurrent SEHs.


Assuntos
Hematoma Epidural Espinal/cirurgia , Adulto , Hematoma Epidural Espinal/complicações , Hematoma Epidural Espinal/diagnóstico por imagem , Hematoma Epidural Espinal/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tratamento de Ferimentos com Pressão Negativa/métodos , Hemorragia Pós-Operatória/diagnóstico por imagem , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/terapia , Doenças Raras , Recidiva , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/terapia
16.
Photodiagnosis Photodyn Ther ; 13: 201-204, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26162501

RESUMO

OBJECTIVE: To investigate the anti-tumor and immune efficacy of photodynamic immune-therapy (PIT), the combination of photodynamic therapy and dendritic cells (DC), on murine Heps hepatoma. METHODS: DCs were derived from syngeneic mouse bone marrow and then labeled with DAPI in vitro. The hepatoma model was established by subcutaneous inoculation with Heps cells in one hundred and twenty-eight mice. They were then divided into four groups at random: control group, PDT group, DC group and PIT group. Tumors in the control group were injected with normal saline. Mice in the PDT group were injected with the photosensitizer Deuteporfin 24 h before irradiation. Mice in the DC group were injected with DAPI labeled dendritic cells intratumorally. Mice in the PIT group were further given an injection of DCs after photoirradiation. Tumor growth and survival time were recorded after treatment. Fluorescence of tumor draining lymph nodes was evaluated under fluorescence microscope. Cytotoxic activity of splenocytes was tested by standard lactate dehydrogenase (lactate dehydrogenase, LDH) release assay. RESULTS: (1) Tumor growth was significantly slowed down in the PDT and PIT group compared to the control group (P<0.01). (2) The mean survival time was significantly prolonged in the PDT and PIT group. (3) The number of fluorescent cells in the draining lymph nodes from DC group was higher than that of the PIT group. (4) The anti-tumor activity of splenocytes in the PDT and PIT group was significantly higher than that of the DC and control groups (P<0.01, P<0.01). CONCLUSIONS: The present study suggests that PDT can inhibit tumor growth and induce anti-tumour immune response. The combination of PDT induced by Deuteporfiin and dendritic cell is capable of amplifying the antitumor immune response.


Assuntos
Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Células Dendríticas/transplante , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/imunologia , Fotoquimioterapia/métodos , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Terapia Combinada/métodos , Células Dendríticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Camundongos , Fármacos Fotossensibilizantes/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento
17.
Clin Chim Acta ; 452: 199-203, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26633854

RESUMO

BACKGROUND: The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. METHODS: A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. RESULTS: Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. CONCLUSION: The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma.


Assuntos
Índices de Eritrócitos , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/diagnóstico , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos
19.
PLoS One ; 9(3): e89123, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24598793

RESUMO

Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Biologia Computacional , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas
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