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1.
Ann Transplant ; 25: e920224, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32029699

RESUMO

BACKGROUND ABO-incompatible (ABOi) living-donor kidney transplantation (KTx) is well established in developed countries, but not yet in China. MATERIAL AND METHODS We developed individualized preconditioning protocols for ABOi KTx based on initial ABO antibody titers. After propensity score matching of ABOi with ABO-compatible (ABOc) KTx, post-transplant outcomes were compared. RESULTS Between September 2014 and June 2018, 48 ABOi living-donor KTx candidates received individualized preconditioning, and all underwent subsequent KTx (median initial ABO titers: 16 for IgM and 16 for IgG). Thirty-one recipients (64.6%) were preconditioned with rituximab (median dose: 200 mg, range: 100-500 mg). Among 37 patients (77.1%) who received pre-transplant antibody removal, the median number of sessions of antibody removal required to achieve ABOi KTx was 2 (range: 1-5), which was conducted between days -10 and -1. Eleven ABOi recipients (22.9%) were preconditioned with oral immunosuppressants alone. Hyperacute rejection led to the loss of 2 grafts in the ABOi group. After a median follow-up of 27.6 months (ABOi group) and 29.8 months (ABOc group), there were no significant differences in graft/recipient survival, rejection, and infection. There were marginally higher rates of severe thrombocytopenia (<50×109/L) (P=0.073) and delayed wound healing (P=0.096) in ABOi recipients. CONCLUSIONS Our individualized preconditioning protocol evolved as our experience grew, and the short-term clinical outcomes of ABOi KTx did not differ from those of matched ABOc patients. ABOi KTx may be a major step forward in expanding the kidney living-donor pool in China.

2.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4940-4946, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872604

RESUMO

Pelvic inflammatory disease( PID) rat model was induced by the mixture of Escherichia coli,Staphylococcus aureus,and Streptococcus hemolytic-ß. Gas chromatography-mass spectrometry( GC-MS) based metabolic profiling method was combined with multivariate statistical analysis,such as PCA,PLS-DA and OPLS-DA to analyze endogenous small molecule metabolites in serum of rats after treatment of Fuke Qianjin Capsules. The results showed that Fuke Qianjin Capsules could significantly improve the inflammatory pathological characteristics and tissue damages in model rats. Based on the principle of VIP>1 and P<0. 05,a total of 6 different metabolic biomarkers were identified,including L-valine,L-isoleucine,L-threonine,butanedioic acid,serine and D-glucose,respectively.The contents of these six different metabolites were significantly reversed after administration. Further analysis of the metabolite pathways through KEGG database showed that Fuke Qianjin Capsules achieved the effect possibly through glycine,serine and threonine metabolism,aminoacyl-tRNA biosynthesis and valine,leucine and isoleucine biosynthesis. Therefore,this study came to the conclusion that Fuke Qianjin Capsules can be used in the treatment of mixed bacteria induced pelvic inflammatory disease possibly by regulating amino acid and its derivative metabolism.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Doença Inflamatória Pélvica/tratamento farmacológico , Animais , Biomarcadores , Cápsulas , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Metabolômica , Ratos
3.
BMC Nephrol ; 20(1): 291, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375084

RESUMO

BACKGROUND: Neutrophil gelatinase-assoicated lipocalin (NGAL) appears to be a promising proximal tubular injury biomarker for early prediction of delayed graft function (DGF) in kidney transplant recipients. However, its predictive values in urine and blood were varied among different studies. Here, we performed the meta-analysis to compare the predictive values of urine NGAL (uNGAL) and blood NGAL (bNGAL) for DGF in adult kidney transplant recipients. METHODS: We systematically searched Medline, Cochrane library and Embase for relevant studies from inception to May 2018. The summary receiver operating characteristic (SROC) curves, the pooled sensitivity, specificity and diagnostic odds ratio (DOR) were used to evaluate the prognostic performance of uNGAL and bNGAL for the identification of DGF. RESULTS: A total of 1036 patients from 14 eligible studies were included in the analysis. 8 studies focused on NGAL in urine and 6 reported NGAL in serum or plasma. The composite area under the ROC (AUC) for 24 h uNGAL was 0.91 (95% CI, 0.89-0.94) and the overall DOR for 24 h uNGAL was 24.17(95% CI, 9.94-58.75) with a sensitivity of 0.88 (95% CI, 0.75-0.94) and a specificity of 0.81 (95% CI, 0.68-0.89). The composite AUC for 24 h bNGAL was 0.95 (95% CI, 0.93-0.97) and the overall DOR for 24 h bNGAL was 43.11 (95% CI, 16.43-113.12) with a sensitivity of 0.91 (95% CI, 0.81-0.96) and a specificity of 0.86 (95% CI, 0.78-0.92). CONCLUSIONS: Urine and serum/plasma NGAL were valuable biomarkers for early identification of DGF in kidney transplantation. In addition, the bNGAL was superior to uNGAL in early prediction of DGF.

4.
Int Immunopharmacol ; 75: 105803, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401383

RESUMO

Infection remains a major cause of morbidity and mortality after kidney transplantation (KT). Reliable biomarkers to predict post-transplant infection are lacking. We investigated the predictive performance of pre- and post-transplant levels of T-cell immunoglobulin and mucin domain-3 (Tim-3) and Galectin-9 (Gal-9), two pleiotropic immunomodulatory molecules, in early identification of infection. Serum Tim-3 and Gal-9 were paired measured before and 30 days after transplantation (PTD 30) in 95 KT recipients (KTRs). The decline rates of Tim-3 and Gal-9 were calculated relative to pre-transplant levels. KTRs with infection history had significantly higher levels of PTD 30 Tim-3 and Gal-9, and slower decrease rates of Gal-9 compared to non-infected recipients, while no difference was observed between two groups regarding pre-transplant levels. The AUCs for predicting 1-year post-transplant infection were 0.653 and 0.711 for post-transplant Tim-3 and Gal-9, 0.664 and 0.670 for relative Tim-3 and Gal-9, respectively. After adjusting for potential confounders, PTD 30 Tim-3, Gal-9 and relative Gal-9 remained as independent risk factors for post-transplant infection. Our results suggested that PTD 30 Tim-3 and Gal-9 and relative decrease of Gal-9 were promising predictors for identifying KTRs with high risk of infection, while pre-transplant Tim-3 and Gal-9 showed no predictive power to infection.


Assuntos
Galectinas/sangue , Receptor Celular 2 do Vírus da Hepatite A/sangue , Transplante de Rim , Complicações Pós-Operatórias/sangue , Adulto , Feminino , Humanos , Masculino , Risco
5.
Gene ; 703: 65-70, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30890475

RESUMO

As a progressive and chronic disease, type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia with rising prevalence worldwide. The ε4 allele of the apolipoprotein E (ApoE) gene may be risk factor of severe peripheral neuropathy in T2DM patients. The association of ApoE polymorphism and Alzheimer's disease (AD) in T2DM patients remains largely unknown. Totally 156 T2DM patients with AD and 145 T2DM patients were included. The genotypes and allele frequency of ApoE were analyzed to explore the role of ApoE in AD in T2DM patients. The levels of total cholesterol (TC), triglyeride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) were detected to further investigate mechanism of ApoE. Genotype frequency ratio of genotype ε3/4, ε4/4 and allele ε4 among the T2DM patients with AD was obviously increased. The TC, TG and LDL-C levels of T2DM patients with ε3/4 genotype were higher than those with ε3/3 or ε2/3 genotype and the ε3/4 genotype, while the HDL-C level was on the contrary, suggesting that ε3/4 genotype elevated blood lipid levels in T2DM patients with AD, thus increasing the risk of AD in T2DM patients. ApoE polymorphism was associated with AD in T2DM patients. ApoE ε3/4 genotype was possibly to serve as a risk factor for AD in T2DM patients by enhancing the blood lipid levels.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Diabetes Mellitus Tipo 2/complicações , Frequência do Gene , Estudos de Associação Genética/métodos , Idoso , Doença de Alzheimer/metabolismo , Estudos de Casos e Controles , Colesterol/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Triglicerídeos/metabolismo
7.
Medicine (Baltimore) ; 98(3): e14137, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30653146

RESUMO

The aim of this study was to investigate the correlation between CYP2C19 genotype and dose-adjusted voriconazole (VCZ) trough concentrations (C0/dose).We analyzed the correlation between CYP2C192(681G>A), CYP2C193(636G>A), and CYP2C1917(-806C>T) genetic polymorphisms and the dose-corrected pre-dose concentration (C0/dose) in 106 South-western Chinese Han patients.The frequencies of variant alleles of CYP2C192, 3, and 17 were 29.7%, 4.25%, and 0.92%. For 49.3% of the VCZ samples, the therapeutic window between 1.5 and 5.5 µg/ml was reached. Following the first dose VCZ measurement, in subsequent samples the proportion of VCZ C0 within the therapeutic window increased, suggesting effective therapeutic drug monitoring (TDM) (P = .001). The VCZ C0 was significantly different (P = .010) between patients with normal metabolism (NMs), intermediate metabolism (IMs), and poor metabolism (PMs). The VZC C0/dose was 12.2 (interquartile range (IQR), 8.33-18.2 µg·ml/kg·day), and 7.68 (IQR, 4.07-16.3 µg·ml/kg·day) in PMs and IMs patients, respectively, which was significantly higher than in NMs phenotype patients (4.68; IQR, 2.51-8.87 µg·ml/kg·day, P = .008 and P = .014).This study demonstrated that the VCZ C0/dose was significantly influenced by the CYP2C19 genotype in South-western Chinese Han patients. In this patient population, more over-exposure was observed in patients with a CYP2C19 genotype associated with poor or intermediate metabolism. CYP2C19 genotype-based dosing combined with TDM will support individualization of VCZ dosing, and potentially will minimize toxicity and maximize therapeutic efficacy.


Assuntos
Antifúngicos/administração & dosagem , Citocromo P-450 CYP2C19/genética , Monitoramento de Medicamentos/métodos , Infecções Fúngicas Invasivas/tratamento farmacológico , Voriconazol/administração & dosagem , Adulto , Alelos , Antifúngicos/sangue , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Coortes , Feminino , Genótipo , Humanos , Infecções Fúngicas Invasivas/genética , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos , Fenótipo , Polimorfismo Genético , Estudos Retrospectivos , Voriconazol/sangue
9.
Artigo em Inglês | MEDLINE | ID: mdl-30538766

RESUMO

In this study, optimization of enzyme-assisted extraction, purification, characterization, and its bioactivities of polysaccharides from Hedyotis corymbosa (HCP) was investigated. It was found that the optimum extraction conditions were 3% of enzyme concentration (X 1 ), 30 of liquid-to-solid ratio (X 2 ), 56°C of extraction temperature (X 3 ), 200W of ultrasonic power (X 4 ), 10 min of extraction time (X 5 ), and 5 of pH value (X 6 ). Under optimum conditions, the experimental yield (4.10 ± 0.16%) was closed to the predicted value (4.02%). The crude HCP was further purified using DEAE-52 and Sephadex G-150 gel column, and a major polysaccharide fraction from HCP, designed as HCP-1a with molecular weight of 33.9 kDa, was obtained. The HCP and HCP-1a were characterized by chemical analysis, FT-IR, and HPLC. For antioxidant activities in vitro, HCP possessed strong hydroxyl radical scavenging, DPPH radical scavenging, and Fe2+ chelating activities. In subsequent immunostimulatory studies, significantly decreased NO, IL-1ß, and TNF-α concentrations were observed in both of HCP and HCP-1a treated RAW264.7 cells. Therefore, this study may indicate some insights into the application of polysaccharides from Hedyotis corymbosa as potential natural antioxidants and immunostimulants.

10.
Zhongguo Zhong Yao Za Zhi ; 43(17): 3484-3492, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30347916

RESUMO

Flavonoids have attracted much attention due to their good anti-inflammatory, anti-oxidation and anti-tumor effects. At present, the extraction of flavonoids is mainly based on organic solvent, while the researches on the use of green and safe solvents are quite limited. Therefore, in the present study, different types of deep eutectic solvents (DESs) were applied to investigate their effect on extraction of flavonoids and optimize the process, also investigate the recovery efficiency of DESs and evaluate the recovery method for total flavonoids. The extraction yield of the total flavonoids acted as the comprehensive evaluation indexes, and a central composite design (CCD) of response surface methodology (RSM) was employed to further optimize the alcohol-based DES extraction conditions. The results showed that the optimized extraction conditions were as follows: water-DES ratio of 27%, solid-liquid ratio of 15 mL·g⁻¹, extraction temperature of 83 °C and extraction time of 42 min in ChCl-glycerol at 1:4 ratio. Under these conditions, the mean experimental value of the extraction yield (75.05 mg·g⁻¹) corresponded well with the predicted value (77.86 mg·g⁻¹). Moreover, these experimental results showed more advantages such as in higher efficiency, economy and environmental protection as compared with previously reported conventional extraction methods. In addition,the recovery yield of the total flavonoids from the DESs extraction solution achieved 97.88% by using AB-8 macroporous resin, and 88.12% desorption ratio can be achieved by 100% ethanol with 5 times resin content. After the above treated DESs were collected, the extraction yield with the same method reached 95.23%, indicating that the method of macroporous resin can be used for efficient and simple recovery and reuse. This study suggests that DESs can be used as a kind of sustainable and efficient natural extraction solvents for extraction of flavonoids from Prunella vulgaris.


Assuntos
Flavonoides/isolamento & purificação , Prunella/química , Solventes , Compostos Fitoquímicos/isolamento & purificação , Água
11.
Chin Med J (Engl) ; 131(18): 2172-2178, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30203791

RESUMO

Background: The effectiveness of the combination of electroacupuncture (EA) and behavioral training (BT) for mid/advanced cerebral infarction (M/ACI) and related mechanisms remains unclear. This study aimed to investigate the combined effects on the learning-memory ability and event-related potential P300 in rats with M/ACI. Methods: Eighty rats with M/ACI were divided into Group Model (M), Group EA, Group BT, and Group EA-BT (n = 20) according to the random number with five healthy rats in Group Control (CON). On the 6th week after modeling, EA, BT, and EA-BT were given to Group EA, Group BT, and Group EA-BT, respectively, whereas Group M and Group CON were not given any intervention. Y-maze test and P300 were recorded before and after the intervention. Results: After intervention, the P300 latency was lower and the amplitude was higher in the Group EA-BT, Group EA, and Group BT than before (for latency, t = -7.638, -4.334, and -5.916; for amplitude, t = 8.125, 3.846, and 5.238; P < 0.01), with Group EA-BT superior to Group EA (for latency, t = -3.708; for amplitude, t = 3.653; P < 0.01) and Group BT (for latency, t = -2.067; for amplitude, t = 2.816; P < 0.05), with no significant difference between Group BT and EA (for latency, t = -1.439; for amplitude, t = 1.075; P > 0.05). While the performances of Y-maze tests in the Group EA-BT, Group EA, and Group BT were all better than before (t = 10.359, 4.520, and 7.791, P < 0.01), with Group EA-BT better than Group EA (t = 5.627, P < 0.01) and Group BT (t = 2.913, P < 0.01) respectively, and Group BT better than Group EA (t = 2.912, P < 0.01). Conclusion: EA or BT can affect P300 in rats with M/ACI, and the combination of these two methods can significantly improve the learning-memory ability.


Assuntos
Infarto Cerebral , Eletroacupuntura , Potenciais Evocados , Pontos de Acupuntura , Animais , Modelos Animais de Doenças , Humanos , Ratos , Ratos Endogâmicos ACI , Ratos Sprague-Dawley
12.
Arthritis Res Ther ; 20(1): 200, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157931

RESUMO

BACKGROUND: Follicular helper T (Tfh) cells are specialized in helping B lymphocytes, which play a central role in autoimmune diseases that have a major B cell component, such as in rheumatoid arthritis (RA). Follicular regulatory T (Tfr) cells control the over-activation of Tfh and B cells in germinal centers. Dysregulation of Tfh cells and Tfr cells has been reported to be involved in the pathogenesis of some autoimmune diseases. However, the balance of Tfh and Tfr cells, and their roles in the development and progression of RA are still not clear. METHODS: In this study, we enrolled 44 patients with RA (20 patients with active RA and 24 patients with inactive RA) and 20 healthy controls, and analyzed the frequencies of circulating Tfh and Tfr cells, expression of programmed death-1 (PD-1), inducible co-stimulator (ICOS), intracellular IL-21, and pSTAT3 in Tfh cells, and serum levels of IL-6. The correlation among these parameters and that of Tfh or Tfr cells with disease activity were also analyzed. RESULTS: Patients with RA (especially active RA) had higher frequencies of Tfh cells, but lower percentages of Tfr cells, thereby resulting in elevated ratios of Tfh/Tfr. Expression levels of PD-1 and IL-21 in Tfh cells were higher in patients with RA than in healthy subjects, while no difference in ICOS expression was observed between patients and controls. Both pSTAT3 expression and serum IL-6 levels increased in patients with RA, and positive correlation between them was observed. Additionally, pSTAT3 expression was positively correlated with Tfh cell frequency. The Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) was negatively correlated with Tfr cell frequency, but was positively correlated with both Tfh/Tfr ratio and PD-1 expression. CONCLUSIONS: Results demonstrated that enhanced IL-6/pSTAT3 signaling may contribute to promotion of Tfh cells, consequently skewing the ratio of Tfh to Tfr cells, which may be crucial for disease progression in RA.


Assuntos
Artrite Reumatoide/metabolismo , Interleucina-6/sangue , Fator de Transcrição STAT3/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Artrite Reumatoide/sangue , Feminino , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Interleucinas/metabolismo , Masculino , Pessoa de Meia-Idade , Fosforilação , Receptor de Morte Celular Programada 1/metabolismo
13.
Ann Transplant ; 23: 300-309, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29735966

RESUMO

BACKGROUND We investigated whether a low fixed Tac starting dose regimen could lead to a better achievement of Tac target concentrations, as well as an effective immunosuppressive treatment, in Chinese kidney transplant recipients (KTRs). MATERIAL AND METHODS We collected whole-blood and serum samples from 189 KTRs and the Tac starting dose was 2, 2.5, or 3 mg/day. Information on Tac C0, dose, body weight, body mass index (BMI), Scr, eGFR, and CYP3A5 genotypes were collected from a routine therapeutic drug monitoring database. The correlation between Tac C0 and body weight (or BMI) was investigated by calculating the goodness of fit. Multivariable logistic regression was performed to estimate the independent associated factors. RESULTS The patients with 3 mg per day of Tac had higher C0 at day 7 compared to those with 2 or 2.5 mg. For patients receiving the same Tac starting dose, no significant difference was found in Tac C0 at day 7 among different body weight or BMI groups. There was no significant difference in Scr or eGFR at 1 year after transplant, nor was there a significant difference in the rates of DGF or AR at post-transplant day 30 among different Tac starting dose groups or among the 3 Tac C0 range groups. CYP3A5 genotype and Tac initial dose were independently associated with Tac C0. CONCLUSIONS CYP3A5 genotype and Tac initial dose were independently associated with Tac C0 in renal transplant recipients. Our results suggest that a low Tac target C0 range (5-8 ng/ml) with a low fixed starting dose (3 mg/day) would be safe and effective among Chinese KTRs.


Assuntos
Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Tacrolimo/administração & dosagem , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Peso Corporal , China , Citocromo P-450 CYP3A/genética , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Rejeição de Enxerto , Humanos , Imunossupressores/sangue , Transplante de Rim/efeitos adversos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Tacrolimo/sangue , Transplantados , Adulto Jovem
14.
Int Immunopharmacol ; 55: 330-335, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29310109

RESUMO

BACKGROUND: T cell immunoglobulin mucin-3 (Tim-3) has been reported to participate in the regulation of immune response and the induction of allograft tolerance. However, the association between Tim-3 and renal allograft dysfunction is unclear. We studied the expression of cellular and soluble Tim-3 (sTim-3), soluble galectin-9 (sGal-9) and carcinoembryonic antigen-related cell adhesion molecule-1 (sCEACAM-1) in kidney transplantation recipients (KTRs) to explore their roles in allograft dysfunction. METHODS: 96 KTRs (53 with stable graft and 43 with graft dysfunction) and 30 healthy controls (HC) were enrolled. Among the KTRs, 55 used Tacrolimus (TAC) and 41 used Sirolimus (SRL). In the dysfunction group, 29 recipients have undergone graft biopsy and 14 were classified as biopsy-proven rejection (BPR). Cellular Tim-3 was determined by flow cytometry. sTim-3 was determined by ELISA. sGal-9 and sCEACAM-1 were determined by Bio-Plex® suspension array system. RESULTS: KTRs with renal dysfunction showed significantly higher levels of sTim-3 and sGal-9 but similar levels of cellular Tim-3 and sCEACAM-1 compared with stable recipients. Correlation analysis revealed that estimated glomerular filtration rate (eGFR) was negatively associated with sTim-3 and sGal-9. Both BPR and non-BPR groups showed comparable levels of Tim-3, Gal-9 and CEACAM-1. Moreover, SRL group showed significantly higher levels of sCEACAM-1 than TAC and HC groups. CONCLUSIONS: sTim-3 and sGal-9 were promising biomarkers for allograft dysfunction, but unable to differentiate allograft rejection from other causes of renal dysfunction in KTRs. Moreover, long-term administration of sirolimus would up-regulate sCEACAM-1 level, while exert similar regulatory effects on Tim-3 and Gal-9 compared to tacrolimus.


Assuntos
Biomarcadores/metabolismo , Proteínas Sanguíneas/metabolismo , Galectinas/metabolismo , Rejeição de Enxerto/diagnóstico , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Nefropatias/diagnóstico , Transplante de Rim , Adulto , Aloenxertos/imunologia , Antígenos CD/metabolismo , Moléculas de Adesão Celular/metabolismo , Estudos Transversais , Diagnóstico Diferencial , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico
15.
J Pharm Pharmacol ; 70(3): 393-403, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29341132

RESUMO

OBJECTIVES: In alcoholic liver disease, alcohol and lipopolysaccharide (LPS) are major stimulation factors of hepatic lipogenesis. Our objective was to determine the protective mechanism of acanthoic acid (AA) in EtOH- and LPS-induced hepatic lipogenesis. METHODS: HSC-T6 cells were treated with ethanol (200 mm) plus LPS (1 µg/ml) for 1 h, followed by AA (10 or 20 µm) for another 6 h. C57BL/6 mice were pretreated with of AA (20 and 40 mg/kg) or equal volume of saline and then exposed to three doses of ethanol (5 g/kg body weight) within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. KEY FINDINGS: Acanthoic acid significantly decreased the expressions of α-SMA, collagen-I, SREBP-1, and lipin1/2 induced, also decreased fat droplets caused by EtOH/LPS. AA treatment decreased the protein expressions of TLR4, CD14, IRAK4, TRAF3, p-TAK1 and NF-κB increased by EtOH/LPS on HSC cells. Results in vivo were consistent with results in vitro. CONCLUSIONS: Our data demonstrated that AA might modulate hepatic fibrosis and lipid deposition in HSC-T6 cell stimulated with ethanol combined with LPS by decreasing lipin1/2 via TLR4 and IRAK4 signalling pathways, and AA might be considered as a potential therapeutic candidate for alcoholic liver disease.


Assuntos
Diterpenos/farmacologia , Lipogênese/efeitos dos fármacos , Hepatopatias Alcoólicas/prevenção & controle , Fosfatidato Fosfatase/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Actinas/biossíntese , Animais , Células Cultivadas , Colágeno/biossíntese , Diterpenos/isolamento & purificação , Etanol , Receptores de Lipopolissacarídeos/biossíntese , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias Alcoólicas/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Camundongos , NF-kappa B/metabolismo , Fosfatidato Fosfatase/biossíntese , Proteínas Serina-Treonina Quinases/biossíntese , Ratos , Proteínas de Ligação a Elemento Regulador de Esterol/biossíntese , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Fator 3 Associado a Receptor de TNF/biossíntese , Receptor 4 Toll-Like/biossíntese
16.
Transpl Immunol ; 46: 1-7, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28974433

RESUMO

BACKGROUND: T follicular helper cells (Tfh) are recently revealed to be vital in antibody-mediated rejection (AMR) in kidney transplant recipients (KTRs). However, the impact of immunosuppressive drugs on Tfh cells is not fully understood. The purpose of this study was to investigate the variation of Tfh cells phenotypically and functionally in KTRs treated with different immunosuppression regimens. METHODS: We recruited 26 KTRs treated with tacrolimus (TAC) -based regimen, 13 with sirolimus (SRL) -based regimen and 10 healthy controls (HC) in this study. The percentage and absolute number of circulating Tfh cells and the co-expression of Tfh related molecules including inducible costimulatory molecule (ICOS), programmed cell death protein 1 (PD-1), interleukin-21 (IL-21) and signal transducer and activator of transcription 3 (STAT3) were analyzed by flow cytometry, while serum IL-6 was detected by electrochemiluminescence immunoassay. RESULTS: The percentage and absolute number of Tfh cells and the co-expression of PD-1, STAT3 in Tfh cells were significantly higher in TAC group than that in SRL group. While no difference was found in regard to IL-21 and ICOS co-expressed with Tfh cells among three groups. Multiple linear regression analysis results showed that pre-transplant PRA level was the significant confounder affecting the absolute numbers of Tfh and CD4+CXCR5+PD-1+ T cells. In addition, correlation analysis showed that CD4+CXCR5+STAT3+ T cells were positively correlated to Tfh cells. CONCLUSIONS: Our study indicates that sirolimus can suppress the quantity of Tfh cells more significantly than tacrolimus. The higher level of circulating Tfh cells in tacrolimus group might be related to STAT3 signaling.


Assuntos
Centro Germinativo/imunologia , Rejeição de Enxerto/imunologia , Imunossupressores/uso terapêutico , Transplante de Rim , Sirolimo/uso terapêutico , Linfócitos T Auxiliares-Indutores/imunologia , Tacrolimo/uso terapêutico , Adulto , Citotoxicidade Celular Dependente de Anticorpos , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Isoanticorpos/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Receptor de Morte Celular Programada 1/metabolismo , Receptores CXCR5/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
17.
Biomed Res Int ; 2018: 3486864, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30598992

RESUMO

Penthorum chinense Pursh (PCP) is a kind of functional food or medicine for liver protection. In the present work, Plackett-Burman design, steepest ascent method, and response surface methodology (RSM) were employed to obtain maximum total sugar yield. The experimental yield of 6.91% indicated a close agreement with the predicted yield of 7.00% of the model under optimized conditions. The major polysaccharide fraction (PCPP-1a) from PCPP was purified and identified as acidic polysaccharides with a high content of uronic acid (FT-IR, UV, HPGPC). PCPP had similar monosaccharide profile with PCPP-1a but was rich in galacturonic acid (HPLC). Both of PCPP and PCPP-1a possessed strong hydroxyl radical scavenging, DPPH radical scavenging, and Fe2+ chelating activities. Moreover, they were revealed to show strong anti-inflammatory activities by inhibiting NO, TNF-α, and IL-1ß release compared to LPS treatment in RAW264.7 cells. These data suggest that the polysaccharides from PCP could be potential natural products for treating ROS and inflammatory-related diseases.


Assuntos
Anti-Inflamatórios/química , Antioxidantes/química , Magnoliopsida/química , Polissacarídeos/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Alimento Funcional , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacologia , Radical Hidroxila/química , Camundongos , Polissacarídeos/farmacologia , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Ácidos Urônicos/química , Ácidos Urônicos/farmacologia
18.
Zhongguo Zhong Yao Za Zhi ; 43(23): 4645-4651, 2018 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-30717553

RESUMO

Prunellae Spica is a perennial edible and medicinal plant, rich in antioxidant substances. Total flavonoids (TFC), Phenolics (TPC), triterpenoids (TSC), polysaccharides (PC) and their antioxidant capacities (by the FRAP, DPPH and ABTS⁺ methods) of ethyl acetate fraction, n-butanol fraction and other fractions of aqueous extract from Prunellae Spica were investigated in this study. Then the multivariate statistical method was adopted to analyze the relationship between the multiple pharmaceutical ingredients and antioxidant capacities of Prunellae Spica. The results showed that ethyl acetate fraction had relatively high concentration of TFC (0.61±0.10) g·g⁻¹DW, TPC (0.52±0.09) g·g⁻¹DW, and TSC (0.21±0.03) g·g⁻¹DW, with high scavenging capacity of DPPH (3.1±0.38) mmol·L⁻¹·g⁻¹DW and FRAP (2.56±0.35) mmol·L⁻¹·g⁻¹DW. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) results indicated the information from chemical compositions and antioxidant capacity can represent the "differences" of different fractions. Canonical correlation analysis (CCorA) revealed a high positive correlation between the amounts of multiple chemical compositions and the antioxidant capacities (r=0.970 0), and the first canonical variate had been reached. Moreover, ABTS⁺ method showed a low response to the compositions of different fractions, so this method may not be suitable for evaluation of Prunellae Spica antioxidant capacities, while DPPH evaluation method was more suitable for TSC and TPC. The results of this study have important reference significance for the evaluation method on antioxidant activity of Prunellae Spica in the field of food or medicine as well as for the development of related extracts.


Assuntos
Antioxidantes/análise , Extratos Vegetais , Flavonoides , Fenóis
20.
Toxicol Lett ; 281: 127-138, 2017 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-28964808

RESUMO

The aim of this study was to investigate the effects of acanthoic acid (AA) on the regulation of inflammatory response, lipid accumulation, and fibrosis via AMPK- IRAK4 signaling against chronic alcohol consumption in mice. Ethanol-induced liver injury was induced in male mice by Lieber-DeCarli diet for 28d. And mice in AA groups were gavaged with AA (20 or 40mg/kg) for 28d. AA treatment significantly decreased serum AST and TG, hepatic TG levels, serum ethanol and LPS levels compared with chronic ethanol administration. AA ameliorated histological changes, lipid droplets, hepatic fibrosis, and inflammation induced by ethanol. AA significantly increased the expressions of p-LKB1, p-AMPK, and SIRT1 caused by chronic ethanol administration, and attenuated the increasing protein expressions of IRAK1 and IRAK4.siRNA against AMPKα1 blocked AMPKα1 and increased IRAK4 protein expressions, compared with control-siRNA-transfected group, while AA treatment significantly decreased IRAK4 expressions compared with AMPKα1-siRNA-transfected group. AMPK-siRNA also blocked the decreased effect of AA on inflammatory factors. AA decreased over-expression of IRAK4 and inflammation under ethanol plus LPS challenge. AA recruited LKB1-AMPK phosphorylation and activated SIRT1 to regulate alcoholic liver injury, especially, inhibited IRAK1/4 signaling pathway to regulate lipid metabolism, hepatic fibrosis and inflammation caused by alcohol consumption.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diterpenos/farmacologia , Etanol/toxicidade , Fígado Gorduroso Alcoólico/tratamento farmacológico , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Aspartato Aminotransferases/sangue , Células Cultivadas , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Triglicerídeos/sangue
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