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1.
J Pharm Pharmacol ; 72(2): 279-293, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31743450

RESUMO

OBJECTIVES: This study was aimed to explore the mechanism of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats by integrated approaches. METHODS: Effects of ALRP and ZR on cardiac function, serum biochemical indicators and histopathology in rats were analysed. Moreover, UHPLC-Q-TOF/MS was performed to identify the potential metabolites affecting the pathological process of CHF. Metabolomics and network pharmacology analyses were conducted to illustrate the possible pathways and network in CHF treatment. The predicted gene expression levels in heart tissue were verified and assessed by RT-PCR. KEY FINDINGS: ALRP-ZR demonstrated remarkable promotion of hemodynamic indices and alleviated histological damage of heart tissue. Metabolomics analyses showed that the therapeutic effect of ALRP and ZR is mainly associated with the regulation of eight metabolites and ten pathways, which may be responsible for the therapeutic efficacy of ALRP-ZR. Moreover, the results of RT-PCR showed that ALRP-ZR could substantially increase the expression level of energy metabolism-related genes, including PPARδ, PPARγ, Lpl, Scd, Fasn and Pla2g2e. CONCLUSIONS: The results highlighted the role of ALRP-ZR in the treatment of CHF by influencing the metabolites related to energy metabolism pathway via metabolomics and network pharmacology analyses.

2.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(4): 403-407, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31512834

RESUMO

OBJECTIVE: To study the accuracy of 3D printing implant-guided anterior tooth implantation under flap or flapless surgery. METHODS: Twenty-one cases (32 teeth) with missing teeth were divided into two groups: tooth implantation on the maxillary models under flap surgery (FP group) and tooth implantation on the maxillary models under flapless surgery (FPS group). A dental implant guide was designed and used in the two groups. The actual position of the dental implants in the two groups was compared with the preplanned deviation values of implant top, bottom, vertical distance, and angle deviation. SPSS 19.0 software was used for statistical analysis. RESULTS: The deviation values of implant top, bottom, vertical distance, and angle were significantly lower in the FP group than in the FPS group (P<0.05). CONCLUSIONS: High accuracy of tooth implantation can be realized by using the 3D printing implant guide. The different surgical methods influence the precision of tooth implantation. Clinicians can choose the surgery reasonably depending on the actual situation.


Assuntos
Implantes Dentários , Dente , Tomografia Computadorizada de Feixe Cônico , Implantação Dentária Endo-Óssea , Impressão Tridimensional
3.
PeerJ ; 7: e7081, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341726

RESUMO

Background: The objective of this study was to compare the diagnostic value of integrated PET/MRI with PET/CT for assessment of regional lymph node metastasis and deep myometrial invasion detection of endometrial cancer. Methods: Eighty-one patients with biopsy-proven endometrial cancer underwent preoperative PET/CT (n = 37) and integrated PET/MRI (n = 44) for initial staging. The diagnostic performance of PET/CT and integrated PET/MRI for assessing the extent of the primary tumor and metastasis to the regional lymph nodes was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. McNemar's test was employed for statistical analysis. Results: Integrated PET/MRI and PET/CT both detected 100% of the primary tumors. Integrated PET/MRI proved significantly more sensitivity and specificity than PET/CT in regional lymph node metastasis detection (P = 0.015 and P < 0.001, respectively). The overall accuracy of myometrial invasion detection for PET/CT and Integrated PET/MRI was 45.9% and 81.8%, respectively. Integrated PET/MRI proved significantly more accurate than PET/CT (P < 0.001). Conclusion: Integrated PET/MRI, which complements the individual advantages of MRI and PET, is a valuable technique for the assessment of the lymph node metastasis and myometrial invasion in patients with endometrial cancer.

4.
Chin Med J (Engl) ; 132(12): 1400-1405, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31205096

RESUMO

BACKGROUND: Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity. METHODS: A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models. RESULTS: Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04-11.81; P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027; standard error 0.012; P < 0.05). CONCLUSIONS: Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.


Assuntos
Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/metabolismo , Plasma/química , Proteína Serina-Treonina Quinases de Interação com Receptores/sangue , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Instável/sangue , Angina Instável/metabolismo , Angina Instável/patologia , Aterosclerose/sangue , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/metabolismo , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
5.
J Cell Physiol ; 234(7): 11451-11462, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30488428

RESUMO

Sphingosylphosphorylcholine (SPC), an important lipid mediator in blood, inhibits the proliferation and migration of various cancer cells. However, its effect as a cell-specific sphingolipid in breast cancer cells is still unknown. Here, we showed that SPC promoted autophagy and apoptosis in triple-negative breast cancer MDA-MB-231 cells. Autophagy worked as a negative regulator of apoptosis-induced by SPC. Mechanistically, SPC mediated apoptosis via activating c-Jun N-terminal kinase (JNK). Meanwhile, p38MAPK (p38) and protein kinase B (PKB or AKT) signaling pathways were also activated to inhibit apoptosis, suggesting that SPC could evoke multiple signaling pathways to modulate cell apoptosis. In addition, the crosstalk between autophagy, p38, AKT and JNK is that autophagy, p38, and AKT attenuated the JNK. AKT and p38 were in the downstream of autophagy, which is autophagy/AKT/p38 signaling evoked by SPC to antagonize JNK signaling and subsequent apoptosis. Although the pathways that antagonize apoptosis were evoked, the cells eventually reached apoptosis by SPC. Therefore, the combination with pharmacological autophagy inhibitors would be a more effective therapeutic strategy for eliminating breast cancer cells by SPC.

7.
Acta Pharmacol Sin ; 39(12): 1830-1836, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30050085

RESUMO

Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid in blood plasma that is metabolized from the hydrolysis of the membrane sphingolipid. SPC maintains low levels in the circulation under normal conditions, which makes studying its origin and action difficult. In recent years, however, it has been revealed that SPC may act as a first messenger through G protein-coupled receptors (S1P1-5, GPR12) or membrane lipid rafts, or as a second messenger mediating intracellular Ca2+ release in diverse human organ systems. SPC is a constituent of lipoproteins, and the activation of platelets promotes the release of SPC into blood, both implying a certain effect of SPC in modulating the pathological process of the heart and vessels. A line of evidence indeed confirms that SPC exerts a pronounced influence on the cardiovascular system through modulation of the functions of myocytes, vein endothelial cells, as well as vascular smooth muscle cells. In this review we summarize the current knowledge of the potential roles of SPC in the development of cardiovascular diseases and discuss the possible underlying mechanisms.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares , Fosforilcolina/análogos & derivados , Esfingosina/análogos & derivados , Animais , Células Endoteliais/fisiologia , Humanos , Células Musculares/fisiologia , Músculo Liso Vascular/fisiologia , Transdução de Sinais/fisiologia , Esfingosina/fisiologia
8.
Front Pharmacol ; 9: 45, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29456506

RESUMO

As a common disorder that accounts for over 70% of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients' life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09-4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28-0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72-2.71; P < 0.00001) and decrease the size of breast lump (MD: -0.67; 95% CI: -0.86 to -0.49; P < 0.00001) to a greater extent, which might provide a possible explanation for the pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH.

9.
Chin J Integr Med ; 24(7): 502-511, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26688180

RESUMO

OBJECTIVE: To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis. METHODS: A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor ß1 (TGF-ß1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase. RESULTS: Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-ß1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01). CONCLUSION: SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-ß1/Smad signaling pathway.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Proteína HMGB1/metabolismo , Cirrose Hepática/tratamento farmacológico , Proteínas Smad/metabolismo , Animais , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(3): 378-383, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-28616910

RESUMO

OBJECTIVES: To determine the effects of non-invasive limb ischemic postconditioning (NLIP) on the behavioral performance and the expression and distribution of neural cells in rats with ischemic cortex. METHODS: Rats were randomly divided into 3 groups: sham group (n=10), ischemia/reperfusion (I/R) group (n=50), and NLIP group (n=50). Focal cerebral ischemia was induced by intraluminal MCAO in the rats in the I/R and NLIP groups, while no suture was inserted in the sham-operated rats. NLIP (reperfusion-10 min, ischemia-10 min, ×3 cycles) was conducted immediately after reperfusion on bilateral femoral arteries by modified ischemicelastic bands. Body mass and behavioral performance of the rats were assessed at 3 d, 7 d, 14 d, 21 d and 28 d post-ischemia (n=5-10). Doublecortin (DCX) and glial fibrillary acidic protein (GFAP) in the ischemic cortex were detected by immunohistochemistry.The expression of microtubule associated protein 2 (MAP2) was detected by Western blot. RESULTS: The rats in the sham group showed mild body mass loss and minor neurological deficit 1-3 d post-ischemia and weakened muscle strength 1 d post-ischemia, which were alleviated gradually overtime. Compared with the sham group, neurological deficits were more obvious in the rats in the I/R and NLIP groups, which were alleviated 3-21 d post-ischemia and reached a level close to that of the sham group at 28 d post-ischemia. No significant difference was found betweenthe I/R and NLIP groups in neurologic deficit scores.NLIP significantly alleviated body mass loss 2-7 d post-ischemia (P<0.05) and improved muscle strength 14-28 d post-ischemia (P<0.05).Compared with the sham group, rats in the I/R and NLP groups had increased numbers of DCX and GFAP-labeled cells in the ischemic penumbra over time, increased hypotrophic cell bodies and longer and thickened dendrites, and decreased expression of MAP2 (P>0.05) at 3 d post-ischemia prior to an up-regulation.Higher expression of MAP2 was found 14-21 d post-ischemia (P<0.05) in the I/R group and 7-28 d post-ischemia in the NLIP group(P<0.05). Significant difference in MAP2 was found between the I/R and NLIP groups at 7 d post-ischemia (P<0.05). CONCLUSIONS: NLIP has the potential to improve neurological outcomes and promote increase of neural cells in penumbral cortex after cerebral ischemia.


Assuntos
Isquemia Encefálica/terapia , Proliferação de Células , Ataque Isquêmico Transitório/terapia , Pós-Condicionamento Isquêmico , Traumatismo por Reperfusão/terapia , Animais , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Ratos , Ratos Sprague-Dawley
11.
Acta Pharmacol Sin ; 38(4): 488-497, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28216620

RESUMO

Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg-1·d-1, ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice. The mechanisms underlying ASA's anti-fibrotic effect were further analyzed in neonatal cardiac fibroblasts (CFs) exposed to hypoxia in vitro. ASA (0.5-5 mmol/L) dose-dependently inhibited the proliferation and Akt phosphorylation in the CFs. In addition, ASA significantly inhibited CF apoptosis, and decreased the levels of apoptosis markers (cleaved caspase 3 and Parp1), which might serve as a side effect of anti-fibrotic effect of ASA. Furthermore, ASA dose-dependently inhibited the autophagy in the CFs, as evidenced by the reduced levels of autophagy marker LC3-II. The autophagy inhibitor Pepstatin A (PepA) promoted the inhibitory effect of ASA on CF proliferation, whereas the autophagy inducer rapamycin rescued ASA-caused inhibition of CF proliferation, suggesting an autophagy-dependent anti-proliferative effect of ASA. Both p38 inhibitor SB203580 and ROS scavenger N-acetyl-cysteine (NAC) significantly decreased Akt phosphorylation in CFs in the basal and hypoxic situations, but they both significantly increased LC3-II levels in the CFs. Our results suggest that an autophagy- and p38/ROS-dependent pathway mediates the anti-cardiac fibrosis effect of ASA in CFs. As PepA and SB203580 did not affect ASA-caused inhibition of CF apoptosis, the drug combination will enhance ASA's therapeutic effects.


Assuntos
Aspirina/uso terapêutico , Autofagia/efeitos dos fármacos , Cardiomiopatias/tratamento farmacológico , Cardiotônicos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Aspirina/farmacologia , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Cardiotônicos/farmacologia , Hipóxia Celular , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibrose/tratamento farmacológico , Fibrose/patologia , Imidazóis/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
12.
Amino Acids ; 49(3): 615-623, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27586957

RESUMO

Transglutaminases (TGs) comprise a protein family in which the members catalyze the formation of isopeptide bonds between glutamine and lysine residues in various proteins. Expression studies on its three major members, FXIII, TG1, and TG2, have been performed in a relatively large number of mammalian tissues in comparison with those on the other isozymes. We previously identified a highly reactive substrate peptide, including glutamine, for each isozyme from a phage display library and developed a method for detecting isozyme-specific activities by incorporating a labeled substrate peptide into lysine residues of proteins. Here, we describe genetically encoded Förster resonance energy transfer (FRET)-based probes composed of each fluorescence protein (Cerulean and EVenus) fused with substrate peptides. The probe pairs, designated as Trac-MTG (His-CerΔ11-LQ/EV-K-His) containing linker and substrate peptide sequence for microbial TG (MTG), increased the EVenus:Cerulean fluorescence intensity ratio by more than 1.5-fold. Furthermore, we demonstrated that Trac-TG1 (His-CerΔ11-K5) and Trac-TG2 (His-CerΔ11-T26) containing substrate peptide sequence for mammalian TGs successfully detected the isozyme-specific activity of TG1 and TG2, respectively. In this study, we developed a rapid and convenient experimental system for measuring the isozyme-specific activity of TGs. The application of these probes for analyses in cells and tissues will be helpful for elucidating the physiological and pathological functions of TGs.


Assuntos
Proteínas de Bactérias/metabolismo , Bioensaio , Proteínas de Ligação ao GTP/metabolismo , Sondas Moleculares/metabolismo , Peptídeos/metabolismo , Transglutaminases/metabolismo , Animais , Proteínas de Bactérias/química , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Proteínas de Ligação ao GTP/química , Humanos , Isoenzimas/química , Isoenzimas/metabolismo , Cinética , Sondas Moleculares/síntese química , Biblioteca de Peptídeos , Peptídeos/síntese química , Sensibilidade e Especificidade , Especificidade por Substrato , Transglutaminases/química
13.
Front Pharmacol ; 7: 256, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27570511

RESUMO

Increasing evidence has suggested that natural killer (NK) cells contribute to the pathogenesis of human immunological liver injury (ILI). Previous studies have demonstrated that Sophocarpine exerts activity in immune modulation. It also has a therapeutic effect on liver protection in that it can alleviate liver fibrosis by suppressing both the activation of hepatic stellate cells and the proliferation of the activated hepatic stellate cells. However, whether Sophocarpine protects the liver by regulating NK cell activity remains unclear. In this study, the modulating effect of Sophocarpine on NK cells in the liver was investigated. The results showed that Sophocarpine dramatically decreased the production of pro-inflammatory cytokines and attenuated the liver injury induced by Poly I: C/D-GalN in C57BL/6- mice. More importantly, Sophocarpine pre-treatment significantly suppressed NK cell activation and downregulated the expression of NKG2D, a receptor responsible for NK cell activation. Moreover, the protein levels of DAP12, ZAP76 and Syk decreased, as did their corresponding mRNA levels. Overall, our study demonstrates that Sophocarpine inhibits NK cell activity, thus making it a promising therapy for ILI.

14.
Front Pharmacol ; 7: 70, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27065861

RESUMO

BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent medicine approved by the China Food and Drug Administration for the treatment of various types of solid tumors. CKI, combined with transarterial chemoembolization (TACE), is believed to increase the therapeutic efficacy of unresectable hepatocellular carcinoma (HCC). We report an updated and extended meta-analysis with detailed outcomes of both the efficacy and adverse events (AEs) of CKI combined with TACE therapy. MATERIALS AND METHODS: Electronic databases, including PubMed, Embase, the Cochrane Library, the Chinese Biomedical Database (CBM), Wanfang, the VIP medicine information system (VMIS) and the China National Knowledge Infrastructure (CNKI), were examined for relevant articles before November 13, 2015. An odds ratio (OR) was used to estimate tumor response (TR), Karnofsky Performance Scale (KPS) improvement, Child-Pugh (CP) improvement, survival rate (SR) and AEs. A publication bias and a subgroup analysis were also assessed. RESULTS: Eighteen studies, with a total of 1,338 HCC patients who met the criteria for the meta-analysis, were included. TR, KPS improvement and CP improvement were significantly enhanced for the combination therapy compared to TACE alone (OR = 1.84, 95% CI: [1.46, 2.33], P < 0.00001; OR = 2.37, 95% CI: [1.76, 3.18], P < 0.00001; OR = 1.81, 95% CI: [1.08, 3.03], P = 0.02, respectively). The combination therapy was associated with an improvement in 1-year and 2-year SRs but not an improved 3-year SR (OR = 2.40; 95% CI: [1.59, 3.62], P < 0.0001; OR = 2.49, 95% CI: [1.24, 5.00], P = 0.01; OR = 2.49, 95% CI: [0.94, 6.61], P = 0.07, respectively). A safety analysis indicated that AEs (including nausea/vomiting, fever, hepatalgia, increased transaminase, increased bilirubin and leukopenia) were reduced for the combination treatment compared to TACE alone. CONCLUSION: The combination treatment of TACE and CKI was associated with improved TR, KPS and CP improvement and improved 1- and 2-year SRs in patients with unresectable HCC. The 3-year SR was not improved. The combination therapy resulted in a reduction in AEs. The findings of this study should be interpreted with caution because of the small sample size and study limitations.

15.
J Med Food ; 17(4): 439-46, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24593676

RESUMO

A water soluble extract from the medicinal mushroom Agrocybe aegerita has been shown to stimulate splenocyte proliferation, cytotoxic activity, and tumor rejection effect in tumor-bearing mouse models. In the present study, the crude extract was separated into a protein component fraction (Yp), mainly containing lectins and serine proteinase, and a small molecule component fraction (Ys), mainly containing triethylene glycol, α-bisabolol, n-hexadecanoic acid, and so on. The antitumor activity of the fractions was investigated in a tumor-bearing BALB/c mouse model. Repeat administration of Yp and Ys significantly inhibited tumor growth (P<.001), but little toxicity was observed. Moreover, the protein fraction Yp performed better than Ys in both antitumor and lifespan-prolonging activity. The cytokine expression levels in serum and splenocytes from extract-treated mice were selectively screened by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction, and the results showed that Yp upregulated the mRNA level of Th2 cytokine interleukin-10 (P<.01), and Ys increased the mRNA level of granulocyte-macrophage colony-stimulating factor (P<.01) and anti-inflammatory cytokine transforming growth factor-ß (P<.01). All these data suggest that Yp and Ys can inhibit tumor growth via different mechanisms, which promotes the understanding of antitumor properties of medicinal fungi.


Assuntos
Agrocybe/química , Antineoplásicos Fitogênicos/administração & dosagem , Citocinas/genética , Neoplasias/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Proteínas de Plantas/administração & dosagem , Plantas Medicinais/química , Verduras/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Citocinas/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/genética , Neoplasias/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
16.
Zhonghua Gan Zang Bing Za Zhi ; 21(2): 125-8, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23663885

RESUMO

OBJECTIVE: To characterize the clinical, laboratory, imaging and pathological features of primary sclerosing cholangitis (PSC) and investigate the impact of ursodeoxycholic acid (UDCA) therapy on patient prognosis. METHODS: The medical records of 22 patients diagnosed with PSC between 2002 and 2011 were retrospectively reviewed. The PSC diagnosis had been made in patients with suspect biochemical abnormalities following evaluation by magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). Fibrosis and inflammation were assessed by immunohistochemical analyses of tissue biopsies. Outcome of patients treated with UDCA (13-15 mg/kg/day, oral) were compared to that of patients without UDCA treatment by the X2 or corrected X2 tests. RESULTS: Among the 22 PSC patients, the majority was male (n=15) and presented with fatigue, dark urine, and body weight loss (n=15). Four cases had ulcerative colitis. At admission, all 22 cases showed elevated levels of alkaline phosphatase[ALP: (348+/-184) U/L], 19 cases showed elevated alanine aminotransferase [ALT: (94.0+/-67.0) U/L] and aspartate aminotransferase [AST: (98.0+/-67.0) U/L], and 15 cases showed elevated levels of total bilirubin (99.0+/-115.0) mumol/L and direct bilirubin (74.4+/-92.4 mumol/L. ERCP examination showed segmental intrahepatic bile duct stenosis with expansion, and stiff and enlarged gallbladder bile ducts, but unclear findings for the common bile ducts and pancreatic ducts. MRCP showed beading of the intrahepatic bile duct, stiffness of the bile duct wall, and dilation of the common bile duct. Fibrosis and inflammation were observed in the bile ducts, along with hyperplasia and the typical features of "onion skin" fibrosis and fibrous obliterative cholangitis. Five of the 10 patients treated with UDCA improved, and seven of the 12 patients in the non-UDCA treatment group improved. There was no statistically significant difference in outcome between the groups (paired X2=0.333, corrected X2=0.083, P more than 0.05). CONCLUSION: PSC patients were predominantly male and the common clinical manifestations were fatigue, dark urine, and body weight loss. At admission, serum biochemical indicators of cholangitis were increased significantly and subsequent imaging studies confirmed the suspected diagnosis by showing obvious characteristic changes. UDCA treatment did not significantly improve patient prognosis.


Assuntos
Colangite Esclerosante/diagnóstico por imagem , Colangite Esclerosante/patologia , Adulto , Colangiografia/métodos , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(2): 233-7, 2013 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-23591343

RESUMO

OBJECTIVE: To investigate the autoantibody profile and its clinical implication in the patients with primary biliary cirrhosis. METHODS: During the period of 2008 to 2010,123 patients with primary biliary cirrhosis (PBC) in our hospital were enrolled in this study, of whom, 70 patients were with cirrhosis and 53 without cirrhosis, The autoantibody profile was tested for each patient by using immunoblotting and indirect immunofluorescence. RESULTS: Of the 123 PBC patients with liver cirrhosis, 49% were positive with serum ANA positive; 47%, 51%, 54%, 31% and 49% were positive with serum anti-nuclear antibodies (ANA), anti-mitochondrial antibodies-M2 (AMA-M2), anti-promyelocytic leukemia (anti-PML), anti-sp100 antibodies (anti-sp100), anti-Ro-52 antibody (anti-52KD), respectively. By contrast, of the PBC patients without liver cirrhosis, only 38%, 37%, 51%, 60%, 30% and 51% were positive with serum ANA, AMA, AMA-M2, anti-PML, anti-sp100 and anti-52KD, respectively.There was the statistical difference between the two groups. In addition, it was also found that the anti-gp210 antibody positive group had a higher Mayo risk score,lower serum albumin and severe cholestasis and impaired liver function when compared with anti-gp210 antibody negative patients. CONCLUSION: Our data indicate that serum AMA is helpful for early diagnosis of PBC, and in particular, serum ANA positivity can help make a diagnosis for the AMA-negative patients. These indicate that anti-gp210 antibodies appear in the late course of PBC.Anti-gp210 positive PBC patients have more severe cholestasis and liver dysfunction.


Assuntos
Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Cirrose Hepática Biliar/imunologia , Mitocôndrias Hepáticas/imunologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Estudos Retrospectivos
18.
Artigo em Chinês | MEDLINE | ID: mdl-24809189

RESUMO

By stratified cluster sampling method, 2 urban and 2 rural fields were selected from Shapingha district of Chongqing for survey in December 2009 to February 2010. According to the Administrating Regulations of National Investigation on Important Human Parasitic Diseases, Kato-Katz method was used to examine human intestinal soil-borne nematode eggs, and adhesive cellophane anal swab method was applied to examine Enterobius infection for children under 12 years old. 203 cases were found positive in 2121 subjects, with an infection rate of 9.6% (203/2 121), and the infection rate of hookworms, Ascaris lumbricoides and Trichuris trichiura with mild infection mostly was 9.3% (197/2 121), 0.4% (8/2 121) and 0.1% (2/2 121), respectively. The rate among people over 50 years old was 15.5% (160/1 030), and the farmers was with 22.3%(113/506). The higher the education level, the lower the infection rate (P < 0.01), and there was a significant difference in the prevalence between urban (2.1%) and rural people (17.3%) (chi2 = 140.443 5, P < 0.01). The infection rate of soil-borne nematodes in Shapingba of Chongqing was much lower than the standard of II regions and most infected subjects were with hookworm infection.


Assuntos
Infecções por Nematoides/epidemiologia , Infecções por Nematoides/parasitologia , Solo/parasitologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
19.
World J Gastroenterol ; 18(12): 1319-27, 2012 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-22493545

RESUMO

AIM: To investigate whether hepatitis B virus (HBV) could induce a hepatitis B virus core antigen (HBcAg)-specific cytotoxic T lymphocyte (CTL) response in vitro by dendritic cells (DCs) transduced with lentiviral vector-encoding ubiquitinated hepatitis B virus core antigen (LV-Ub-HBcAg). METHODS: Recombinant LV-Ub-HBcAg were transfected into highly susceptible 293 T cells to obtain high virus titres. Bone marrow-derived DCs isolated from BALB/c mice were cultured with recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin (IL)-4. LV-Ub-HBcAg, lentiviral vector-encoding hepatitis B virus core antigen (LV-HBcAg), lentiviral vector (LV) or lipopolysaccharide were added to induce DC maturation, and the DC phenotypes were analyzed by flow cytometry. The level of IL-12 in the supernatant was detected by enzyme-linked immunosorbent assay (ELISA). T lymphocytes were proliferated using Cell Counting Kit-8. DCs were cultured and induced to mature using different LVs, and co-cultured with allogeneic T cells to detect the secretion levels of IL-2, IL-4, IL-10 and interferon-γ in the supernatants of T cells by ELISA. Intracellular cytokines of proliferative T cells were analyzed by flow cytometry, and specific CTL activity was measured by a lactate dehydrogenase release assay. RESULTS: LV-Ub-HBcAg-induced DCs secreted more IL-12 and upregulated the expression of CD80, CD86 and major histocompatibility class II. DCs sensitised by different LVs effectively promoted cytokine secretion; the levels of IL-2 and interferon-γ induced by LV-Ub-HBcAg were higher than those induced by LV-HBcAg. Compared with LV-HBcAg-transduced DCs, LV-Ub-HBcAg-transduced DCs more efficiently stimulated the proliferation of T lymphocytes and generated HBcAg-specific cytotoxic T lymphocytes. CONCLUSION: LV-Ub-HBcAg effectively induced DC maturation. The mature DCs efficiently induced T cell polarisation to Th1 and generated HBcAg-specific CTLs.


Assuntos
Células Dendríticas/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Linfócitos T Citotóxicos/imunologia , Animais , Células Dendríticas/citologia , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Células HEK293 , Antígenos do Núcleo do Vírus da Hepatite B/genética , Humanos , Imunofenotipagem , Interleucina-12/imunologia , Lentivirus/genética , Lentivirus/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Citotóxicos/citologia , Ubiquitinação
20.
Hepat Mon ; 11(8): 620-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22140385

RESUMO

BACKGROUND: Nearly 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Ubiquitin (Ub) is a highly conserved small regulatory protein, ubiquitous in eukaryotes, that usually serves as a signal for the target protein that is recognised and degraded in proteasomes . The Ub-mediated processing of antigens is rapid and efficient and stimulates cell-mediated immune responses. Accordingly, Ub-mediated processing of antigens has been widely used in chronic-infection and cancer studies to improve immune response. OBJECTIVES: Many clinical trials have shown that DNA vaccine potency needs to be greatly enhanced. Here, we report a new strategy for designing an HBV DNA vaccine using the ubiquitin (Ub) sequence. The aim of this study was to investigate a novel DNA vaccination, based on the expression of HBV core antigen (HBcAg), fused to Ub to enhance DNA vaccine potency. MATERIALS AND METHODS: Mouse ubiquitin fused to the HBcAg gene and cloned into the eukaryotic vector pcDNA3.1 (-). BALB/c mice were immunized with recombinant pUb-HBcAg or pHBcAg DNA vaccine. Lymphocyte proliferation assay, intracellular IFN-γ assay, CTL cytotoxicity assay, and antibody assay were performed to analyze the cellular and humoral immune responses to our DNA constructs. RESULTS: HBcAg was expressed effectively in the COS-7 cells that were transiently transfected with pUb-HBcAg. Strong anti-HBc IgG responses were elicited in mice that were immunized with pUb-HBcAg. The endpoint titers of anti-HBc peaked at 1:656100 on the 42nd day after the third immunization. pUb-HBcAg stimulated greater lymphocyte proliferation and induced higher levels of IL-2 and IFN-γ and a greater percentage of HBcAg-specific CD8+ T cells in mice than pHBcAg. In the CTL assay, the specific lysis rate reached 56.5% at an effector:target ratio of 50:1 in mice that were immunized with pUb-HBcAg. CONCLUSIONS: pUb-HBcAg elicits specific anti-HBc responses and induces HBc-specific CTL responses in immunized BALB/c mice. Our results imply that Ub can be used as a molecular adjuvant that enhances the potency of DNA vaccines.

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