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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 92-96, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950796

RESUMO

Objective: To evaluate the diagnostic value of T-cells enzyme linked immunospot (TSPOT.TB) in the children with tuberculosis. Methods: The clinical data was retrieved from 2 348 children who underwent TSPOT.TB test in the Children's Hospital of Chongqing Medical University from January 2017 to December 2017. The diagnostic value of TSPOT.TB in the children with tuberculosis was analyzed. Results: In the diagnosis of children tuberculosis, the sensitivity of TSPOT.TB was 84.0%, the specificity was 99.1%, the positive predictive value was 93.1%, and the negative predictive value was 97.8%. To the area under receiver operating characteristic (ROC) curve of TSPOT.TB, the area under the curve ( AUC) value of A antigen and B antigen were 0.893 and 0.883, respectively ( P<0.05). When the number of A or B antigens was less than 50, the sensitivity was increased with the increase of puncture number, but there was no clear linear relationship. TSPOT.TB had a highly sensitivity to childhood tuberculosis when the number of A or B antigens was greater than 50. In the true positive groups of TSPOT.TB, the sensitivity of pulmonary tuberculosis group was significantly higher than that of extrapulmonary tuberculosis group ( P<0.05). In addition, the sensitivity to TSPOT.TB increased with age. Conclusion: TSPOT.TB has high diagnostic value in the children with tuberculosis, which can rapidly assist to diagnose pediatric tuberculosis.


Assuntos
ELISPOT , Tuberculose , Criança , Humanos , Curva ROC , Sensibilidade e Especificidade , Linfócitos T/enzimologia , Tuberculose/diagnóstico
2.
Int J Mol Med ; 45(2): 343-352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789424

RESUMO

Oxidative and inflammatory damage has been suggested to play important roles in the pathogenesis of skin photoaging. Andrographolide sodium bisulfate (ASB) is a soluble derivative of andrographolide and has known antioxidant and anti­inflammatory properties. In the present study, cellular experiments were designed to investigate the molecular mechanisms underlying the effect of ASB in relieving ultraviolet (UV)­induced photo­damage. Following ASB pretreatment and UV irradiation, the apoptosis and necrosis of HaCaT cells were investigated by Hoechst 33342/propidium iodide staining. Reactive oxygen species (ROS) production was investigated using a DCFH­DA fluorescence probe. Furthermore, the protein expression levels of p65, NF­κB inhibitor­α, nuclear factor E2­related factor 2 (Nrf2) and kelch­like ECH­associated protein 1 (keap1) were measured via western blotting and immunofluorescence analyses. Furthermore, NF­κB­mediated cytokines were assessed by ELISA, and Nrf2­mediated genes were detected by reverse transcription­quantitative PCR. Pretreatment with ASB markedly increased cell viability, decreased cell apoptosis and decreased UV­induced excess ROS levels. In addition, ASB activated the production of Nrf2 and increased the mRNA expression levels of glutamate­cysteine ligase catalytic subunit and NAD(P)H quinone oxidoreductase 1, while ASB downregulated the protein expression of p65 and decreased the production of interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α. These results suggested that ASB attenuates UV­induced photo­damage by activating the keap1/Nrf2 pathway and downregulating the NF­κB pathway in HaCaT keratinocytes.

3.
Indian J Orthop ; 53(4): 518-524, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303667

RESUMO

Purpose: To evaluate the therapeutic effects of combined atlas fracture with type II (C1-type II) odontoid fractures and to outline a management strategy for it. Patients and Methods: Twenty three patients with C1-type II odontoid fractures were treated according to our management strategy. Nonoperative external immobilization in the form of cervical collar and halo vest was used in 13 patients with stable atlantoaxial joint. Surgical treatment was early performed in 10 patients whose fractures with traumatic transverse atlantal ligament disruption or atlantoaxial instability. The visual analog scale (VAS), neck disability index (NDI) scale, and American Spinal Injury Association (ASIA) scale at each stage of followup were then collected and compared. Results: Compared to pretreatment, the VAS score, NDI score, and ASIA scale were improved among both groups at followup evaluation after treatment. However, in the nonsurgical group, one patient (1/11) developed nonunion which required surgical treatment in later stage and one patient (1/13) with halo vest immobilization had happened pin site infection. Two patients of the surgical group (2/11) had appeared minor complications: occipital cervical pain in one case and cerebrospinal fluid leakage in one case. Two patients (2/23) were excluded from nonsurgical treatment group because their followup period was less than 12 months. Twenty one patients were followed up regularly with an average of 23.9 months (range 15-45 months). Conclusions: We outlined our concluding management principle for the treatment of C1-type II odontoid fractures based on the nature of C1 fracture and atlantoaxial stability. The treatment principle can obtain satisfactory results for the management of C1-type II odontoid fractures.

4.
Biomed Pharmacother ; 114: 108766, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901719

RESUMO

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.


Assuntos
Brucea/química , Doença de Crohn/tratamento farmacológico , Emulsões/farmacologia , NF-kappa B/metabolismo , Óleos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Colo/efeitos dos fármacos , Colo/metabolismo , Doença de Crohn/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley
5.
Med Princ Pract ; 28(3): 256-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30646003

RESUMO

OBJECTIVE: To conduct a meta-analysis of evidence from randomized controlled trails (RCTs) of different doses of intravenous immunoglobulin (IVIG) in children with severe hand, foot and mouth disease (HFMD) to provide the scientific basis for clinical practice. METHODS: A search of PubMed-Medline, CNKI, Wanfang, and VIP database (until June 30, 2017) was performed and Software RevMan5.3 was used to evaluate the effect of different doses of IVIG on HFMD in RCTs. We used random-effects models (or fixed-effects models) and generic inverse variance methods to process quantitative data, followed by a leave-one-out method for sensitivity analysis. RESULTS: From a total of 420 entries identified via searches, 8 RCTs involving 1,450 patients were included in the final analysis. The results of the meta-analysis showed that compared with conventional therapy alone, conventional therapy combined with IVIG had shorter fever clearance time, shorter rash regression time, and shorter clinical cure time. Subgroup analyses showed that the high-dose group (1 g/kg/day) had shorter fever clearance time (p < 0.05), shorter rash regression (p< 0.05), shorter remission time of neurological symptoms (p < 0.05), but longer clinical cure time (p > 0.05). CONCLUSION: The high-dose group has a better prognosis; however, the advantages and disadvantages should be carefully considered when deciding the doses in the treatment of severe HFMD.

6.
Oncogenesis ; 7(9): 77, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30275459

RESUMO

Colorectal cancer stem cells (CSCs), characterized by self-renewal ability and high expression of proliferative genes, contribute to the chemoresistance of colorectal cancer (CRC). We aimed to identify the molecular mechanisms underlying CRC chemoresistance through comprehensive bioinformatics screenings and experimental confirmation of gene functions. We found that high expression of FGF1 intracellular binding protein (FIBP) was correlated with chemoresistance and poor prognosis in CRC patients. Therefore, the chemoresistant CRC cell line HCT116-CSC with high expression of the stem cell markers CD44 and CD133 was established for further phenotypic tests. FIBP knockdown inhibited proliferation, enhanced chemotherapy effects, and attenuated the stemness markers of CRC cells in vivo and in vitro. Through RNA-seq and gene set enrichment analysis, we identified cyclin D1 as a key downstream target in FIBP-regulated cell cycle progression and proliferation. Moreover, FIBP bound to GSK3ß, inhibited its phosphorylation at Tyr216, and activated ß-catenin/TCF/cyclin D1 signaling in HCT116-CSCs. Additional GSK3ß knockdown reversed the FIBP silencing-induced inhibition of proliferation and decreased stemness marker expression in HCT116-CSCs. Furthermore, DNA methylation profiling suggested that FIBP regulated the stemness of CRC cells via methylation activity that was dependent on GSK3ß but independent of ß-catenin signaling. Our data illuminate the potential of FIBP as a novel therapeutic target for treating chemoresistant CRC through inhibition of GSK3ß-related signaling.

7.
Int J Nanomedicine ; 13: 5887-5907, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319255

RESUMO

Background: Bruceine D (BD) is a major bioactive component isolated from the traditional Chinese medicinal plant Brucea javanica which has been widely utilized to treat dysentery (also known as ulcerative colitis [UC]). Methods: To improve the water solubility and absolute bioavailability of BD, we developed a self-nanoemulsifying drug delivery system (SNEDDS) composing of MCT (oil), Solutol HS-15 (surfactant), propylene glycol (co-surfactant) and BD. The physicochemical properties and pharmacokinetics of BD-SNEDDS were characterized, and its anti-UC activity and potential mechanism were evaluated in TNBS-induced UC rat model. Results: The prepared nanoemulsion has multiple beneficial aspects including small mean droplet size, low polydispersity index (PDI), high zeta potential (ZP) and excellent stability. Transmission electron microscopy showed that nanoemulsion droplets contained uniform shape and size of globules. Pharmacokinetic studies demonstrated that BD-SNEDDS exhibited enhanced pharmacokinetic parameters as compared with BD-suspension. Moreover, BD-SNEDDS significantly restored the colon length and body weight, reduced disease activity index (DAI) and colon pathology, decreased histological scores, diminished oxidative stress, and suppressed TLR4, MyD88, TRAF6, NF-κB p65 protein expressions in TNBS-induced UC rat model. Conclusion: These results demonstrated that BD-SNEDDS exhibited highly improved oral bioavailability and advanced anti-UC efficacy. In conclusion, our current results provided a foundation for further research of BD-SNEDDS as a potential complementary therapeutic agent for UC treatment.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Quassinas/uso terapêutico , Animais , Disponibilidade Biológica , Colite Ulcerativa/patologia , Liberação Controlada de Fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Nanopartículas/química , Nanopartículas/ultraestrutura , Óleos/química , Tamanho da Partícula , Transição de Fase , Quassinas/química , Quassinas/farmacocinética , Quassinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Solubilidade
8.
PLoS One ; 13(3): e0194069, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29538417

RESUMO

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1ß, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC.


Assuntos
Berberina/análogos & derivados , Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Animais , Berberina/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo
9.
Mol Med Rep ; 17(1): 789-800, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115625

RESUMO

Silymarin has been used in the treatment of a number of liver diseases for a long time, but its efficacy in preventing triptolide induced acute hepatotoxicity has not been reported previously. The present study aimed to assess the protective effect of silymarin against triptolide (TP)-induced hepatotoxicity in rats. Rats were orally administrated with silymarin (50, 100 and 200 mg/kg) for 7 days and received intraperitoneal TP (2 mg/kg) on the day 8. Hepatic injuries were comprehensively evaluated in terms of serum parameters, morphological changes, oxidative damage, inflammation and apoptosis. The results demonstrated that TP-induced increases in serum parameters, including alanine transaminase, aspartate aminotransferase, alkaline phosphatase, total cholesterol and γ-glutamyl transpeptidase, which were determined using a biochemical analyzer, and histopathological alterations and hepatocyte apoptosis as determined by hematoxylin and eosin and TUNEL staining, respectively, were prevented by silymarin pretreatment in a dose-dependent manner. TP-induced depletions in the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione S-transferase and catalase, and glutathione levels, were also significantly reversed by silymarin, as determined using specific kits. Additionally, silymarin dose-dependently exhibited inhibitory effects on malonaldehyde content in the liver. The production of proinflammatory cytokines was investigated using ELISA kits, and the results demonstrated that silymarin dose-dependently inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-1ß in the liver. To determine the mechanism of silymarin, western blot analysis was performed to investigate the protein expression of phosphorylated (p)-p38 and p-c-Jun N-terminal kinase (JNK) of the TNF-α induced inflammatory response and apoptotic pathways. Silymarin significantly blocked p38 and JNK phosphorylation and activation. Additionally, the expression of the proapoptotic proteins cytochrome c, cleaved caspase-3 and Bcl-2-associated X was also reduced following treatment with silymarin, as determined by ELISA, western blotting and immunohistochemistry, respectively. In conclusion, silymarin was demonstrated to dose-dependently protect rat liver from TP-induced acute hepatotoxicity, with the high dose (200 mg/kg) achieving a superior effect. This protective effect may be associated with the improvement of antioxidant and anti-inflammatory status, as well as the prevention of hepatocyte apoptosis. Therefore, silymarin may have the potential to be applied clinically to prevent TP-induced acute hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Diterpenos/toxicidade , Fenantrenos/toxicidade , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Citocinas/metabolismo , Modelos Animais de Doenças , Diterpenos/química , Compostos de Epóxi/química , Compostos de Epóxi/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fenantrenos/química , Substâncias Protetoras/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Silimarina/química
10.
J Sep Sci ; 41(5): 1129-1137, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29227028

RESUMO

We adopted a facile hydrofluoric acid-free hydro-/solvothermal method for the preparation of four magnetic iron(III)-based framework composites (MIL-101@Fe3 O4 -COOH, MIL-101-NH2 @Fe3 O4 -COOH, MIL-53@Fe3 O4 -COOH, and MIL-53-NH2 @Fe3 O4 -COOH). The obtained four magnetic iron(III)-based framework composites were applied to magnetic separation and enrichment of the fungicides (prochloraz, myclobutanil, tebuconazole, and iprodione) from environmental samples before high-performance liquid chromatographic analysis. MIL-101-NH2 @Fe3 O4 -COOH showed more remarkable pre-concentration ability for the fungicides as compared to the other three magnetic iron(III)-based framework composites. The extraction parameters affecting enrichment efficiency including extraction time, sample pH, elution time, and the desorption solvent were investigated and optimized. Under the optimized conditions, the standard curve of correlation coefficients were all above 0.991, the limits of detection were 0.04-0.4 µg/L, and the relative standard deviations were below 10.2%. The recoveries of two real water samples ranged from 71.1-99.1% at the low spiking level (30 µg/L). Therefore, the MIL-101-NH2 @Fe3 O4 -COOH composites are attractive for the rapid and efficient extraction of fungicides from environmental water samples.

11.
Mediators Inflamm ; 2017: 1089028, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28811678

RESUMO

According to the GC-MS analysis, compositional variation was observed between samples of patchouli oil, of which an unknown compound identified as patchoulene epoxide (PAO) was found only in the long-stored oil, whose biological activity still remains unknown. Therefore, the present study aimed to evaluate the potential anti-inflammatory activity with three in vivo inflammatory models: xylene-induced ear edema, acetic acid-induced vascular permeability, and carrageenan-induced paw edema. Further investigation into its underlying mechanism on carrageenan-induced paw edema was conducted. Results demonstrated that PAO significantly inhibited the ear edema induced by xylene, lowered vascular permeability induced by acetic acid and decreased the paw edema induced by carrageenan. Moreover, PAO markedly decreased levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO), but increased levels of interleukin-4 (IL-4) and interleukin-10 (IL-10). PAO was also shown to significantly downregulate the protein and mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS). Western blot analysis revealed that PAO remarkably inhibited p50 and p65 translocation from the cytosol to the nucleus by suppressing IKKß and IκBα phosphorylation. In conclusion, PAO exhibited potent anti-inflammatory activity probably by suppressing the activation of iNOS, COX-2 and NF-κB signaling pathways.


Assuntos
Compostos de Epóxi/uso terapêutico , Inflamação/tratamento farmacológico , Óleos Vegetais/química , Pogostemon/química , Animais , Carragenina/toxicidade , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Compostos de Epóxi/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Inflamação/induzido quimicamente , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
J Chromatogr A ; 1517: 18-25, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-28847581

RESUMO

In this study, we report a facile, environmental friendly fabrication of a type of magnetic metal-organic framework (MOF) MIL-100 that can be used for magnetic solid-phase extraction (MSPE). The magnetic MOF composites were fabricated using in situ calcination method. The as-synthesized materials exhibited both high porosity and magnetic characteristics. They used for the MSPE of polycyclic aromatic hydrocarbons (PAHs) from water samples. Such MOF-based magnetic solid-phase extraction in combination with gas chromatography equipped with a flame ionization detector (GC-FID), exhibited wide linearity (0.02-250µgL-1), low detection limits (4.6-8.9ngL-1), and high enrichment factors (452-907) for PAHs. The relative standard deviations (RSDs) for intra- and inter-day extractions of PAHs were ranging from 1.7% to 9.8% and 3.8% to 9.2%, respectively. The recoveries for spiked PAHs (1µgL-1) in water samples were in the range of 88.5% to 106.6%. The results showed that the special anion-π orbital (electron donor-acceptor) interaction and π-π stacking between magnetic MIL-100 and PAHs play an important role in the adsorption of PAHs.


Assuntos
Monitoramento Ambiental/métodos , Magnetismo , Compostos Organometálicos/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Extração em Fase Sólida/métodos , Poluentes Químicos da Água/análise , Adsorção , Cromatografia Gasosa , Ionização de Chama , Limite de Detecção , Metais/química , Porosidade
13.
Asia Pac J Clin Nutr ; 26(4): 598-605, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28582807

RESUMO

BACKGROUND AND OBJECTIVES: Evidence suggests that dietary fiber benefits patients with chronic kidney disease (CKD); however, this conclusion requires further validation. In this study, we examined the effects of dietary fiber on kidney function, inflammation, indoxyl sulfate, nutritional status, and cardiovascular risk in patients with advanced CKD. METHODS AND STUDY DESIGN: We performed linear regressions to assess the association between dietary fiber intake and CKD parameters. The aforementioned parameters were compared over an 18-month follow- up period. Kaplan-Meier analysis was used to investigate the association between fiber intake and Cardiac vascular disease (CVD). RESULTS: In total, 157 patients were included in this study. Dietary fiber and inflammatory indices were associated (interleukin [IL]-6: ß=-0.024, p=0.035). The differential estimated glomerular filtration rate (ΔeGFR) as well as levels of C-reactive protein, IL-6, indoxyl sulfate, and serum cholesterol in the higher fiber intake (>=25 g/day) group were lower than those in the lower fiber intake (<25 g/day) group (p<0.05). Differences in IL-6 and indoxyl sulfate levels were more significant in patients in the higher protein intake group (p<0.05). Dietary fiber intake may be a protective factor associated with CVD (hazard ratio=0.537 and 0.305- 0.947). The protein nutritional status was not different between the two groups (p>0.05). CONCLUSIONS: Our results suggest that increasing fiber intake can retard the decrease in the eGFR; can reduce the levels of proinflammatory factors, indoxyl sulfate, and serum cholesterol; and is negatively associated with cardiovascular risk, but does not disrupt the nutritional status of patients with CKD.


Assuntos
Doenças Cardiovasculares/etiologia , Fibras na Dieta/administração & dosagem , Fibras na Dieta/farmacologia , Insuficiência Renal Crônica/patologia , Adulto , Estudos de Coortes , Proteínas na Dieta/administração & dosagem , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estado Nutricional
14.
Pharmacol Res ; 121: 70-82, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28456683

RESUMO

Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1ß, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to mice. In summary, the study successfully demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing inflammation, maintaining the integrity of intestinal epithelial barrier, inhibiting cell death signaling, and suppressing tryptophan catabolism. The results provided valuable information and guidance for using PA in treatment of UC.


Assuntos
Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Sulfato de Dextrana , Sesquiterpenos/uso terapêutico , Triptofano/metabolismo , Animais , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Citocinas/análise , Masculino , Camundongos Endogâmicos BALB C , Pogostemon/química , Sesquiterpenos/química
15.
Oncotarget ; 8(25): 40264-40275, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28402965

RESUMO

Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan's effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins. We found that cell viability was inhibited and apoptosis was increased, accompanied by ROS generation and ER stress activation in CRC cells treated with curcumin alone or in combination with irinotecan. Blocking ROS production attenuated the expression of two markers of ER stress: binding of immunoglobulin protein (BIP) and CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP expression using RNA interference also inhibited ROS generation. These results demonstrated that curcumin could enhance the effects of irinotecan on CRC cells by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and that these effects may be mediated, in part, by ROS generation and activation of the ER stress pathway.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Camptotecina/análogos & derivados , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Curcumina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Cálcio/metabolismo , Camptotecina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Proteínas de Choque Térmico/metabolismo , Humanos , Irinotecano , Interferência de RNA , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo
16.
J Ethnopharmacol ; 198: 389-398, 2017 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-28119098

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Brucea javanica is an important traditional medicinal herb used for the treatment of dysentery, malaria, inflammation and cancer in southeast Asia for many years. However, the anti-inflammatory mechanism of Brucea javanica in the treatment of dysentery (also known as ulcerative colitis, UC) has not been fully illuminated. Brucea javanica oil emulsion (BJOE) is the major active and most common application form of Brucea javanica oil (BJO), which has a variety of pharmacological activities. The aim of this study was to investigate the potential anti-inflammatory effect of BJOE and possible mechanism of action on dextran sulfate sodium (DSS)-induced UC in mice. MATERIALS AND METHODS: The components of BJOE were determined by gas chromatography-mass spectrometry (GC-MS). Balb/C mice with dextran sulfate sodium (DSS, 30mg/mL) induced colitis were treated with BJOE (0.5, 1 and 2g/kg) and two positive drugs (sulfasalazine, SASP, 200mg/kg; and azathioprine, AZA, 13mg/kg) once daily by gavage for 7 days. Mice in normal control group and DSS group were orally given the same volume of distilled water and soybean lecithin suspension (0.15g/kg) respectively. The effects of BJOE on DSS-induced UC were assessed by determination of body weight loss, disease activity index (DAI), colon length, histological analysis, as well as levels of pro-inflammatory cytokines. The mRNA expression of MPO, iNOS and COX-2 in colon tissues was detected by qRT-PCR. In addition, NF-κB p65, p-p65 and IκB-α, p-IκBα protein expression levels in colon tissues were investigated using Western blotting. RESULTS: The major components of BJOE were found to be oleic acid (62.68%) and linoleic acid (19.53%) as detected by GC-MS. Our results indicated that BJOE, SASP and AZA showed beneficial effect on DSS-induced colitis in mice, and significantly reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, decreased histological scores, and decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-8, IL-17 and IFN-γ) as compared with the DSS group. In addition, the mRNA expression of MPO, iNOS and COX-2 induced by DSS treatment was remarkably inhibited by BJOE, SASP or AZA treatments. Furthermore, when compared with DSS-treated mice, the activation of NF-κB was significantly inhibited by AZA and BJOE treatment. CONCLUSIONS: Our study shows that BJOE possessed appreciable anti-inflammatory effect against murine experimental UC induced by DSS. The protective mechanism of BJOE may involve inhibition of NF-κB signal transduction pathways and subsequent down-regulation of inflammatory mediators. These findings suggest that BJOE might be an efficacious and promising therapeutic approach for the treatment of UC. Our investigation might also provide experimental evidence for the traditional application of Brucea javanica in the treatment of dysentery and might add new dimension to the clinical indications for BJOE.


Assuntos
Anti-Inflamatórios/farmacologia , Brucea/química , Colite Ulcerativa/tratamento farmacológico , Óleos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Azatioprina/farmacologia , Colite Ulcerativa/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Emulsões , Cromatografia Gasosa-Espectrometria de Massas , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfassalazina/farmacologia
17.
Anal Bioanal Chem ; 409(7): 1895-1904, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28012110

RESUMO

Highly efficient extraction of peptides from serum is critical for finding serum biomarkers using mass spectrometry, which still remains a great challenge. Currently, a bottom-up proteomics approach has been applied to discover serum biomarkers. However, the approach was labor intensive, time and cost consuming, and cannot meet the requirements for clinical application. In this work, Fe3O4/C@MIL-100 composites were synthesized to efficiently capture peptides from microwave-assisted formic acid digests of BSA and human serum prior to MALDI-TOF MS analysis. Fe3O4/C@MIL-100 composites exhibited size-selective adsorption performance, thus providing a rapid and convenient approach to enrich low-abundance peptides. Notably, the peptides' mass fingerprinting of serum digestions between type 2 diabetes mellitus (T2DM) and healthy persons were distinguishable, which indicated the potential ability of this technique for T2DM diagnosis and rapid biomarker discovery. Graphical Abstract Efficient extraction and identification of serum biomarkers using Fe3O4/C@MIL-100 composites from acid hydrolysate.


Assuntos
Biomarcadores/sangue , Óxido Ferroso-Férrico/química , Magnetismo , Diabetes Mellitus Tipo 2/sangue , Humanos , Microscopia Eletrônica de Varredura , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(12): 1277-1281, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-27974122

RESUMO

OBJECTIVE: To study the association between the single nucleotide polymorphisms (SNP) of interleukin (IL)-19 and susceptibility to hepatitis B virus (HBV) infection in children. METHODS: A case-control study was performed, and 136 children with positive HBsAg(case group) and 297 healthy children with negative HBsAg(control group) were enrolled. PCR and DNA sequencing were used for genotyping. RESULTS: There were significant differences in the frequencies of genotypes of IL-19 rs1798 between the case and control groups. The case group also had a significantly higher proportion of children with CG genotype than the control group (p<0.05). There were significant differences in the frequencies of genotypes and alleles of IL-19 rs2243191 between the HBV infection and non-infection groups among children who born to HBV-positive mothers. The infection group had significantly higher proportions of children with TC and CC genotypes and C allele than the non-infection group (p<0.05). CONCLUSIONS: The SNP of IL-19 rs1798 may be associated with susceptibility to hepatitis B in children, and the SNP of IL-19 rs2243191 may be associated with susceptibility to breakthrough HBV infection in children at a high risk of HBV infection.


Assuntos
Predisposição Genética para Doença , Hepatite B/genética , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Pré-Escolar , Feminino , Genótipo , Hepatite B/etiologia , Humanos , Lactente , Masculino
19.
J Ethnopharmacol ; 186: 125-135, 2016 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-27049295

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Existing evidences suggest that Radix Astragali and its polysaccharides composition (APS) can improve muscle mass, but the mechanisms need more research. AIM OF THE STUDY: In this study, we aimed to examine the effects of APS on muscle wasting at molecular level in 5/6 nephrectomised rats. MATERIALS AND METHODS: We performed 5/6 nephrectomy or sham operation in 160 6-week-old Sprague-Dawley rats, and feed animals with or without 2% APS for 155 days. After treatment, we compared the change of weight, muscle fibre, protein metabolism, pro-inflammatory factors (TNF-α, IL-15, CRP) and oxidative factors (MDA, SOD) among each group. In addition, we detected the Akt/mTOR, ubiquitin proteasome, autophagy signalling and AA transporters in vivo and in vitro. RESULTS: Data in vivo show 2% APS could alleviate weight loss and improve protein metabolism in nephrectomised rats. The levels of serum pro-inflammatory factors and oxidative factors were restored by APS treatment. In molecular levels, APS restored Akt/mTOR, MAFbx, MuRF1, Atg7, LC3B-II/LC3B-I and SLC38A2 which changed in nephrectomised rats. Data in vitro show the optimal dose of APS is 0.2mg/mL, and SLC38A2 siRNA attenuated the effects of 0.2mg/mL APS on atrophy and autophagy. CONCLUSIONS: Our results suggested APS could improve muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling, and SLC38A2 may be one of potential targets.


Assuntos
Astrágalo (Planta)/química , Nefrectomia , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina/metabolismo , Animais , Autofagia/fisiologia , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Masculino , Músculo Esquelético/patologia , Mioblastos/efeitos dos fármacos , Polissacarídeos/química , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/genética , Ubiquitina/genética
20.
Exp Gerontol ; 77: 76-86, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26929999

RESUMO

Pogostone, a chemical constituent of patchouli oil, has been confirmed to possess favorable anti-inflammatory property. In the present study, we investigated the possible anti-photoaging potential of pogostone and the underlying mechanism against UV-induced skin damage in mice. The macroscopic and histopathological lesions were significantly ameliorated by pretreatment of pogostone as compared to the VC group. Furthermore, topical application of pogostone markedly increased the activities of the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observably decreased malonaldehyde (MDA) level. Analysis of inflammatory cytokines showed obvious down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) in the pogostone groups. In addition, pogostone pretreatment evidently inhibited the abnormal expression of matrix metalloproteinases (MMP-1 and MMP-3). Taken together, pogostone exhibited prominent photo-protective activity mainly by its antioxidative and anti-inflammatory properties, promising it as an effective alternative pharmaceutical therapy for photoaging.


Assuntos
Óleos Voláteis/uso terapêutico , Envelhecimento da Pele/efeitos dos fármacos , Pele/patologia , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Feminino , Hiperplasia/tratamento farmacológico , Malondialdeído/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Camundongos , Óleos Voláteis/farmacologia , Pele/enzimologia , Raios Ultravioleta
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