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1.
Food Res Int ; 137: 109688, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233263

RESUMO

In this study, fruit-zone microclimate was modified by three treatments, including inter-row mulch (M), the combination of leaf removal applied at the onset of veraison and inter-row mulch (MLR-BV), and the combination of leaf removal applied at complete veraison and inter-row mulch (MLR-EV), in a semi-arid climate in three consecutive years (2015-2017). M decreased fruit-zone reflected solar radiation from vineyard floor and low temperature (10-20 °C) duration, whereas it increased soil temperature and high temperature (> 30 °C) duration. MLR-BV and MLR-EV increased fruit-zone incident photosynthetically active radiation while decreased the duration of 20-25 °C compared to M. Notably, M significantly decreased grape total norisoprenoid concentrations in 2015-2017, and total terpenoid concentrations in 2015-2016. Applying leaf removal applied at the onset of veraison could compensate the decreases of total norisoprenoids and terpenoids caused by M when two treatments were applied together. Besides, M significantly increased grape total C6/C9 compound concentrations, besides, (Z)-3-hexen-1-ol concentrations were significantly higher in grapes of M than those of MLR-BV in 2015-2017. Light exposure and high temperature duration after veraison had strong positive correlations with total norisoprenoids and terpenoids, besides, low temperature duration was positively correlated with total norisoprenoids. In addition, light exposure after veraison had strong negative correlations with total C6/C9 compounds. With respect to the volatile compounds in wines, M significantly decreased the concentrations of isopentanol and ethyl acetate, and the concentrations of ethyl cinnamate, phenylacetaldehyde, phenylethyl alcohol and 3-methylthio-1-propanol were significantly lower in MLR-BV and MLR-EV than in M. The outcome of this study can assist winegrowers to properly adjust vineyard managements to optimize the concentrations of desired volatile compounds in grapes and wines.

2.
Food Chem ; 292: 237-246, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054670

RESUMO

The ripeness of a grape is critical to berry composition and to the resultant wine. For wineries with a single cultivar occupying an extensive area, the total soluble solid of grapes can range from 22°Brix to 28°Brix. Accordingly, the influence of different harvest dates (ripeness) on berry compositions and on the resultant wine profile was investigated for Vitis vinifera L. cv. 'Cabernet Sauvignon.' Berry dehydration was observed as berry weight and juice yields decreased. Berry anthocyanins were concentrated and methylated anthocyanin levels fluctuated with increasing delays in harvesting. Hexanal and 2-hexenal levels in must decreased significantly as berries ripened. In the resultant wines, 2,3-butanediol levels increased. Wines harvested earlier were lighter, presented lower color intensity (CI) values and higher yellow% levels, and exhibited richer aroma profiles (compounds). Through a principal component analysis and discriminant analysis, the compounds characterizing each harvest date were identified.


Assuntos
Vitis/química , Vinho/análise , Aldeídos/análise , Antocianinas/análise , Cromatografia Gasosa , Clima , Frutas/química , Frutas/metabolismo , Análise dos Mínimos Quadrados , Análise de Componente Principal , Fatores de Tempo , Vitis/metabolismo , Compostos Orgânicos Voláteis/análise
3.
Liver Int ; 39(8): 1504-1513, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30721562

RESUMO

BACKGROUND & AIMS: Insulin resistance is strongly associated with non-alcoholic fatty liver disease, a chronic, obesity-related liver disease. Increased endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity. METHODS: We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR-30b or inhibit miR-30b rats were injected with lentivirus particles containing PGLV3-miR-30b or PGLV3-miR-30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects. RESULTS: Our data showed that miR-30b was markedly up-regulated in the liver of HFD-treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca2+ -ATPase 2b (SERCA2b), as a novel target of miR-30b. Overexpression of miR-30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR-30b by miR-30b antimiR suppressed ER stress and insulin resistance in HFD-treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR-30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA-IR) in human subjects. CONCLUSIONS: Our findings suggest that miR-30b represents not only a potential target for the treatment of insulin resistance, but also a non-invasive disease biomarker of NAFLD.


Assuntos
Estresse do Retículo Endoplasmático , Resistência à Insulina , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Animais , Gluconeogênese , Glicólise , Lipogênese , Fígado/enzimologia , Masculino , Ratos Sprague-Dawley
4.
Biosci Rep ; 38(6)2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30413613

RESUMO

Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefore, it is of substantial significance to clarify the expression and function of miRNAs in bone endocrine physiology and pathology to improve the potential therapeutic value for metabolism-related bone diseases. We explored the effect of microRNA-182-5p (miR-182-5p) on osteoblast proliferation and differentiation in OP rats after alendronate (ALN) treatment by targeting adenylyl cyclase isoform 6 (ADCY6) through the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway. Rat models of OP were established to observe the effect of ALN on OP, and the expression of miR-182-5p, ADCY6 and the Rap1/MAPK signaling pathway-related genes was determined. To determine the roles of miR-182-5p and ADCY6 in OP after ALN treatment, the relationship between miR-182 and ADCY6 was initially verified. Osteoblasts were subsequently extracted and transfected with a miR-182-5p inhibitor, miR-182-5p mimic, si-ADCY6 and the MAPK signaling pathway inhibitor U0126. Cell proliferation, apoptosis and differentiation were also determined. ALN treatment was able to ease the symptoms of OP. miR-182-5p negatively targeted ADCY6 to inhibit the Rap1/MAPK signaling pathway. Cells transfected with miR-182 inhibitor decreased the expression of ALP, BGP and COL I, which indicated that the down-regulation of miR-182-5p promoted cell differentiation and cell proliferation and inhibited cell apoptosis. In conclusion, the present study shows that down-regulated miR-182-5p promotes the proliferation and differentiation of osteoblasts in OP rats through Rap1/MAPK signaling pathway activation by up-regulating ADCY6, which may represent a novel target for OP treatment.


Assuntos
Adenilil Ciclases/genética , MicroRNAs/genética , Osteoporose/genética , Proteínas de Ligação a Telômeros/genética , Adenilil Ciclases/efeitos dos fármacos , Alendronato/administração & dosagem , Animais , Butadienos/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 1/genética , Nitrilos/administração & dosagem , Osteoblastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos
5.
Neurochem Res ; 43(10): 1927-1937, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30167941

RESUMO

Artificial abnormal microenvironment caused by microperfusion of L-glutamate (Glu) and Ca2+ in the hippocampus results in neuron damage, which is closely related to cerebral ischemia. Ginsenoside Rb1, a compound from Panax notoginseng, was previously used to counter the artificial abnormal hippocampal environment in a microperfusion model. In addition, while the Akt/mTOR/PTEN signaling pathway has been shown to mediate neuronprotection in cerebral ischemia, whether this pathway is involved in the neuroprotection of ginsenoside Rb1 is unknown. Here SH-SY5Y cells exposed to OGD/R injury in treated with LY294002, ginsenoside Rb1, ginsenoside Rb1+ LY294002. Expressions of phosphorylation (P-)Akt/P-mTOR/P-PTEN (24 h after OGD/R) were detected by Western blotting. Effects were examined via the memory function of rats (by Morris water maze test), morphological changes in pyramidal cell (by histology), and mRNA expression (by qRT-PCR) and phosphorylation (P-) (by Western blotting and immunohistochemical staining) of Akt, P-mTOR, and P-PTEN in the hippocampus. The memory deficit of rats and pyramidal cellular necrosis and apoptosis in the CA1 region of hippocampus after microperfusion of Glu and Ca2+ were dose dependently alleviated by ginsenoside Rb1.Moreover,Western blot showed that ginsenoside Rb1 increased the expressions of P-Akt, P-mTOR and reduced P-PTEN in vivo and vitro. Thus, the potent neuroprotection of ginsenoside Rb1 in artificial abnormal microenvironment is, at least partially, related to the activation of P-AKT/P-mTOR signaling pathway and inhibition of P-PTEN protein.


Assuntos
Ginsenosídeos/farmacologia , Hipocampo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Cromonas/farmacologia , Hipocampo/metabolismo , Masculino , Morfolinas/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
6.
J Diabetes Res ; 2018: 9216791, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29977927

RESUMO

Diabetic retinopathy is the leading cause of blindness, yet its treatment is very limited. Anti-VEGF drug has been widely applied in ocular disease, but its effects on diabetic retinopathy and the underlying mechanism have remained to be fully explored. To elucidate the role of anti-VEGF treatment, we sought to determine the effects of bevacizumab on diabetic neurovascular changes extending from the 3rd to 9th week with induced diabetes in adult rats. The retinal neurovascular changes included increased expression of VEGF, nNOS, iNOS, eNOS, and NO in the course of diabetes progression. In diabetic rats given bevacizumab injection, the ganglion cell loss and alterations of retinal thickness were ameliorated. In this connection, the immunofluorescence labeling of the above biomarkers was noticeably decreased. Along with this, Western blotting confirmed that bevacizumab treatment was associated with a decrease of VEGF, Flk-1, and cAMP response element binding and protein kinase C protein expression. The present results suggest that bevacizumab treatment in the early stage of the retinopathy may ameliorate the lesions of retinopathy, in which VEGF/Flk-1 signaling has been shown here to play an important role.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Animais , Bevacizumab/administração & dosagem , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Injeções Intravítreas , Masculino , Ratos , Ratos Sprague-Dawley , Retina/efeitos dos fármacos , Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Behav Brain Res ; 345: 83-92, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29501622

RESUMO

Panax notoginsenoside saponins Rb1 (PNS-Rb1) is an important active ingredient of panax notoginseng for effective treatment of cerebrovascular diseases. However, the mechanism underlying its actions in the state of cerebral ischemia is still unclear. We asked whether the potential neuroprotection of PNS-Rb1 on the brain is due to, at least partially, its modulation of AkT/mTOR/PTEN signalling pathway along with down-regulation of caspase-3 in rats subjected to phototrombic stroke. To test this hypothesis, rats with induced photothrombotic stroke were treated with PNS-Rb1 (applied in three different doses, 25 mg/kg, 50 mg/kg,100 mg/kg, respectively) or saline, while sham operated rats injected with saline were used as the control. Our results indicate that PNS-Rb1 significantly alleviated the morphological lesion concomitant with improvement of cognitive and sensorimotor deficits induced by ischemic stroke. Moreover, immunohistochemistry and Western blot analyses showed that PNS Rb1 in a dose dependent manner increased the expressions of P-Akt, P-mTOR and reduced P-PTEN and caspase-3. The present study suggests that the improvement of cognitive and sensorimotor deficits by PNS-Rb1 is made, at least partially, by the modulation of the Akt/mTOR/PTEN signalling pathway.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Saponinas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/psicologia , Caspase 3/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Fármacos Neuroprotetores/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Panax notoginseng , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/patologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/psicologia , Serina-Treonina Quinases TOR/metabolismo
8.
Cell Physiol Biochem ; 45(4): 1410-1422, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29462818

RESUMO

BACKGROUND/AIMS: This study aimed to investigate the mechanism by which microRNA-206 (miR-206) affects the proliferation, apoptosis, migration and invasion of osteosarcoma (OS) cells by targeting ANXA2 via the AKT signaling pathway. METHODS: A total of 132 OS tissues and 120 osteochondroma tissues were examined in this study. The targeting relationship between miR-206 and ANXA2 was verified with a dual-luciferase reporter assay. The miR-206 expression and ANXA2, AKT, PARP, FASN, Survivin, Bax, Mcl-1 and Bcl-1 mRNA and protein expression in the above two groups were examined by qRT-PCR and western blotting. The cultured OS cells were divided into 6 groups: a blank group, negative control (NC) group, miR-206 mimic group, miR-206 inhibitor group, si-ANXA2 group and miR-206 inhibitor + si-ANXA2 group. Cell cycle and apoptosis were assessed by flow cytometry, cell migration was examined with a wound-healing assay, and cell invasion was assessed with a Transwell assay. Pearson correlation analysis was used to determine the correlation between ANXA2 mRNA expression and miR-206 expression in OS. RESULTS: OS tissues exhibited increased mRNA and protein expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-2; decreased miR-206 expression; and decreased Bax mRNA and protein expression. ANXA2 mRNA expression was strongly negatively correlated with miR-206 expression in OS. ANXA2 was found to be a miR-206 target gene. In the miR-206 mimic group and the si-ANXA2 group, the mRNA and protein expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-1 decreased markedly, cell proliferation was inhibited, apoptosis was promoted, higher cell growth in G1 phase and decreased growth in S phase was detected, and decreased cell migration and invasion were observed compared with those in the blank group. CONCLUSION: The current results demonstrate that miR-206 overexpression inhibits OS cell proliferation, migration and invasion and promotes apoptosis through targeting ANXA2 by blocking the AKT signaling pathway.


Assuntos
Anexina A2/metabolismo , Neoplasias Ósseas/patologia , MicroRNAs/metabolismo , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Adolescente , Adulto , Anexina A2/antagonistas & inibidores , Anexina A2/genética , Antagomirs/metabolismo , Apoptose , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Criança , Feminino , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Osteossarcoma/genética , Osteossarcoma/metabolismo , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Survivina , Adulto Jovem
9.
Drug Deliv ; 24(1): 1513-1525, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28975813

RESUMO

Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N-vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 ± 0.15 and 82.6 ± 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.


Assuntos
Microesferas , Animais , Diabetes Mellitus Experimental , Glucose , Insulina , Ácido Láctico , Camundongos , Tamanho da Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros
10.
Int J Nanomedicine ; 12: 4037-4057, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28603417

RESUMO

Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid-b-diethylene glycol methyl ether methacrylate); p(AAPBA-b-DEGMA)) were prepared by reversible addition-fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C-47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA-b-DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Insulina/administração & dosagem , Nanopartículas/química , Polímeros/química , Animais , Ácidos Borônicos/química , Cromatografia em Gel , Portadores de Fármacos/química , Feminino , Glucose/química , Glucose/metabolismo , Insulina/química , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Células NIH 3T3 , Nanopartículas/administração & dosagem , Polímeros/síntese química , Temperatura
11.
Mater Sci Eng C Mater Biol Appl ; 76: 845-855, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28482599

RESUMO

A new block polymer named poly 3-acrylamidophenylboronic acid-b-6-O-vinylazeloyl-d-galactose (p(AAPBA-b-OVZG)) was prepared using 3-acrylamidophenylboronic acid (AAPBA) and 6-O-vinylazeloyl-d-galactose (OVZG) via a two-step procedure involving S-1-dodecyl-S-(α', α'-dimethyl-α″-acetic acid) trithiocarbonate (DDATC) as chain transfer agent, 2,2-azobisisobutyronitrile (AIBN) as initiator and dimethyl formamide (DMF) as solvent. The structures of the polymer were examined by Fourier transform infrared spectroscopy (FT-IR) and 1H NMR and the thermal stability was determined by thermal gravimetric analysis (TG/DTG). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were utilized to evaluate the morphology and properties of the p(AAPBA-b-OVZG) nanoparticles. The cell toxicity, animal toxicity and therapeutic efficacy were also investigated. The results indicate the p(AAPBA-b-OVZG) was successfully synthesized and had excellent thermal stability. Moreover, the p(AAPBA-b-OVZG) nanoparticles were submicron in size and glucose-sensitive in phosphate-buffered saline (PBS). In addition, insulin as a model drug had a high encapsulation efficiency and loading capacity and the release of insulin was increased at higher glucose levels. Furthermore, the nanoparticles showed a low-toxicity in cell and animal studies and they were effective at decreasing blood glucose levels of mice over 96h. These p(AAPBA-b-OVZG) nanoparticles show promise for applications in diabetes treatment using insulin or other hypoglycemic proteins.


Assuntos
Nanopartículas , Animais , Ácidos Borônicos , Reagentes para Ligações Cruzadas , Portadores de Fármacos , Galactose , Insulina , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier
12.
Asian Pac J Trop Med ; 8(1): 60-3, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25901926

RESUMO

OBJECTIVE: To explore the effects of gentiana scabra bage on the expression of hepatic collagen proteins in Paragonimus skrjabini rats with liver fibrosis. METHODS: Immunohistochemical technique was used to observe the changes of content of hepatic type I, III collagen proteins in Paragonimus skrjabini rats with liver fibrosis before and after the gentiana scabra bage treatmeat. RESULTS: Comparing with the model group, changes of hepatic type I and type III collagen proteins in gentiana scabra bage treated group were significantly weakened. CONCLUSIONS: Gentiana scabra bage treatment can reduce the content of hepatic type III and type I collagen protein significantly in Paragonimus skrjabini rats with liver fibrosis, thereby, playing the role against hepatic fibrosis.

13.
Dongwuxue Yanjiu ; 35(5): 420-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25297082

RESUMO

Here, we used reverse transcription-PCR (RT-PCR) and western blot to detect protease-activated receptor (PAR) 1, PAR 2 and PAR 4 expression in cancer tissues and cell lines of esophageal squamous cell carcinoma, and investigated the co-relationship between PAR expression and clinic-pathological data for esophageal cancer. The methylation of PAR4 gene promoter involved in esophageal carcinoma was also analyzed. By comparing the mRNA expressions of normal esophageal tissue and human esophageal epithelial cells (HEEpiC), we found that among the 28 cases of esophageal squamous cell carcinoma, PAR1 (60%) and PAR2 (71%) were elevated in 17 and 20 cases, respectively, and PAR4 (68%) expression was lowered in 19 cases. Whereas, in human esophageal squamous cells (TE-1 and TE-10), PAR1 and PAR2 expression was increased but PAR4 was decreased. Combined with clinical data, the expression of PAR1 in poorly differentiated (P=0.016) and middle and lower parts of the esophagus (P=0.016) was higher; expression of PAR4 in poorly differentiated carcinoma was lower (P=0.049). Regarding TE-1 and TE-10 protein expression, we found that in randomized esophageal carcinoma, PAR1 (P=0.027) and PAR2 (P=0.039) expressions were increased, but lowered for PAR4 (P=0.0001). In HEEpiC, TE-1, TE-10, esophageal and normal esophagus tissue samples (case No. 7), the frequency of methylation at the 19 CpG loci of PAR4 was 35.4%, 95.2%, 83.8%, 62.6% and 48.2%, respectively. Our results indicate that the expression of PAR1 and PAR2 in esophageal squamous cell carcinoma is increased but PAR4 is decreased. Hypermethylation of the promoter of the PAR4 gene may contribute to reduced expression of PAR4 in esophageal squamous cell carcinoma.


Assuntos
Neoplasias Esofágicas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Receptor PAR-1/metabolismo , Receptor PAR-2/metabolismo , Receptores de Trombina/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Humanos , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor PAR-1/genética , Receptor PAR-2/genética , Receptores de Trombina/genética
14.
BMC Clin Pathol ; 14: 29, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25057261

RESUMO

BACKGROUND: A higher prevalence of chronic atrophic gastritis (CAG) occurs in younger adults in Asia. We used Stomach Age to examine the different mechanisms of CAG between younger adults and elderly individuals, and established a simple model of cancer risk that can be applied to CAG surveillance. METHODS: Stomach Age was determined by FISH examination of telomere length in stomach biopsies. Δψm was also determined by flow cytometry. Sixty volunteers were used to confirm the linear relationship between telomere length and age while 120 subjects were used to build a mathematical model by a multivariate analysis. Overall, 146 subjects were used to evaluate the validity of the model, and 1,007 subjects were used to evaluate the relationship between prognosis and Δage (calculated from the mathematical model). ROC curves were used to evaluate the relationship between prognosis and Δage and to determine the cut-off point for Δage. RESULTS: We established that a tight linear relationship between the telomere length and the age. The telomere length was obvious different between patients with and without CAG even in the same age. Δψm decreased in individuals whose Stomach Age was greater than real age, especially in younger adults. A mathematical model of Stomach Age (real age + Δage) was successfully constructed which was easy to apply in clinical work. A higher Δage was correlated with a worse outcome. The criterion of Δage >3.11 should be considered as the cut-off to select the subgroup of patients who require endoscopic surveillance. CONCLUSION: Variation in Stomach Age between individuals of the same biological age was confirmed. Attention should be paid to those with a greater Stomach Age, especially in younger adults. The Δage in the Simple Model can be used as a criterion to select CAG patients for gastric cancer surveillance.

15.
Bioorg Med Chem Lett ; 23(3): 630-4, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23290455

RESUMO

In our previous studies, geraniin was reported to have a preventive effect in the rat model of tretinoin-induced osteoporosis. However, whether geraniin exhibits an inhibitory effect on bone resorption or on MMP-9 expression is not yet known. We present here our novel findings from in vitro experiments that geraniin (a) decreases the number of mature osteoclasts and pre-osteoclast in cultures, (b) reduces the osteoclastic fusion index, and (c) inhibits the resorption areas and resorption pits. We also report that geraniin suppresses the mRNA and protein expression levels of MMP-9. These results demonstrate that geraniin has an inhibitory effect on the bone-absorption ability of osteoclasts in vitro, and the mechanisms may be closely associated with the downregulation of mRNA and protein expression of MMP-9.


Assuntos
Reabsorção Óssea , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Osteoclastos/efeitos dos fármacos , Animais , Conservadores da Densidade Óssea/farmacologia , Linhagem Celular , Inibidores Enzimáticos/farmacologia , Glucosídeos/química , Taninos Hidrolisáveis/química , Metaloproteinase 9 da Matriz/genética , Estrutura Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos
16.
J Cell Physiol ; 226(11): 2782-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21935927

RESUMO

Hyperhomocysteinemia (HHcy) has been shown to induce endothelial dysfunction, an early event in the progression of atherosclerosis. However, the underlying mechanism of endothelial cell injury in HHcy has not been clearly elucidated. In this study, we examined the effect of homocysteine on tribbles-related protein 3 (TRB3)-mediated cell-cycle arrest in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with homocysteine (0-250 µmol/L) resulted in inhibition of cell proliferation assessed by [(3)H]-thymidine incorporation into DNA. Homocysteine induced cell-cycle arrest in the G1 phase by up-regulating the protein levels of p27(kip1). Under these conditions, homocysteine did not induce endoplasmic reticulum stress. However, homocysteine up-regulated the expression of TRB3, thus leading to the dephosphorylation of Akt (Thr308). Knock-down of endogenous TRB3 using siRNA significantly suppressed the inhibitory effect of homocysteine on the proliferation of HUVECs. Homocysteine-induced TRB3 expression was mediated by the cAMP/cAMP response element-binding protein (CREB) pathway. These results demonstrate that TRB3 is a critical molecule in the homocysteine-mediated cell-cycle arrest in endothelial cells.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Células Endoteliais/efeitos dos fármacos , Homocisteína/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/metabolismo , Proteínas de Ciclo Celular/genética , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Células Endoteliais/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/genética , Regulação para Cima
17.
J Interv Gastroenterol ; 1(2): 64-69, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21776428

RESUMO

OBJECTIVE: To determine the effect of multidisciplinary team meeting (MDTM) on the success rate and complications of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for hepato-pancreato-biliary diseases. METHODS: All patients undergoing their first therapeutic ERCP over a 21-month period of time in a tertiary care medical center were included. Generally, patients scheduled for ERCP on Friday, Saturday, Sunday, and Monday were subject to MDTM group, and those on Tuesday, Wednesday, and Thursday were allocated to the control group. For each MDTM case, an MDTM was held on the Tuesday prior to the scheduled ERCP. At the meeting, the cases were discussed by a team consisting of chief physicians, radiologists, endoscopists, anesthetists, and surgeons, and a decision was made on the schedule of ERCP. For control cases, a clinical team of one chief physician and two attending physicians made the decision. RESULTS: From April 2006 to December 2007, 912 and 997 ERCP procedures were allocated to the MDTM and control groups, respectively. There was no significant difference in the baseline characteristics and indications between the two groups. Although the success rates were not significantly different between MDTM and control groups (82.9% vs. 84.8%, P=0.321), MDTM was significantly associated with a decreased overall complication rate of (6.9% vs. 12.0%, p<0.001) and severe complication rate (0.4% vs. 2.5%, p=0.035). CONCLUSIONS: Pre-ERCP MDTM decreases the frequency and severity of ERCP-related complications, with similar success rate, compared to routine practice.

18.
Am J Pathol ; 177(5): 2357-65, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20864682

RESUMO

Elevated homocysteine levels are defined as hyperhomocysteinemia (HHcy), a disorder that is associated with cardiovascular and neurodegenerative diseases as well as with hepatic fibrosis. Recent studies have shown that HHcy promotes hepatic injury by increasing oxidative stress. Although homocysteine induces cell cycle arrest in a variety of different cell types, it is not known whether HHcy has a definitive role in hepatocyte proliferation during liver regeneration. In this report, we investigated the effect of homocysteine on liver regeneration. Our results demonstrated that mice with HHcy exhibited an impairment in liver regeneration after partial hepatectomy, as measured by immunohistochemical staining of proliferation cell nuclear antigen and bromodeoxyuridine incorporation. Impaired proliferation was also correlated with reduced cyclin D1 induction and elevated expression levels of both p53 and p21Cip1. In addition, the phosphorylation of Akt, which plays an essential role in normal regeneration responses, was attenuated during the early phases of liver regeneration in HHcy mice. Our results also indicated that the cAMP/protein kinase A pathway mediated the inhibitory effect of homocysteine on liver regeneration. These findings provide evidence that impairment of liver regeneration by HHcy may result in delayed recovery from liver injury induced by homocysteine itself.


Assuntos
Proliferação de Células , Dieta , Hepatócitos/fisiologia , Hiper-Homocisteinemia/fisiopatologia , Regeneração Hepática/fisiologia , Metionina/administração & dosagem , Animais , Células Cultivadas , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Hepatectomia , Hepatócitos/citologia , Humanos , Hiper-Homocisteinemia/etiologia , Fígado/patologia , Fígado/fisiologia , Metionina/efeitos adversos , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismo
19.
Gut ; 59(6): 722-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20551455

RESUMO

OBJECTIVE: Patients with dyspepsia with alarm features are suspected of having upper gastrointestinal (GI) malignancy; however, the true value of alarm features in predicting an underlying malignancy for patients with dyspepsia with high background prevalence of Helicobacter pylori infection and upper GI malignancy is uncertain. The aim of the present study was to determine the diagnostic accuracy of alarm features in predicting upper GI malignancy by reviewing an endoscopic database consisting of >100,000 Chinese patients. METHODS: A retrospective analysis of prospectively collected data was conducted in a single tertiary medical centre. Consecutive patients who underwent oesophagogastroduodenoscopy (OGD) for dyspepsia in 1996-2006 were enrolled. The data including gender, age, symptoms, and endoscopic and pathological findings were analysed. The main outcome measure was the diagnostic accuracy of individual alarm feature. RESULTS: 102,665 patients were included in the final analysis. Among all the 4362 patients with malignancy, 52% (2258/4362) had alarm features. Among 15 235 patients who had alarm features, 2258 (14.8%) were found to have upper GI malignancy. The pooled sensitivity and specificity of the alarm features were 13.4% and 96.6%, respectively. Only the feature of dysphagia in patients between 36 and 74 years old had a positive likelihood ratio (PLR) >10 for malignancy prediction, while all other alarm features in other age groups had a PLR <10. CONCLUSIONS: For uninvestigated Chinese patients with dyspepsia with high background prevalence of H pylori infection and upper GI malignancy, alarm features and age, except for dysphagia in patients between 36 and 74 years old, had limited predictive value for a potential malignancy; therefore, prompt endoscopy may be recommended for these patients. However, less invasive, inexpensive screening methods with high diagnostic yield are still needed to reduce unnecessary endoscopy workload.


Assuntos
Dispepsia/etiologia , Neoplasias Gastrointestinais/diagnóstico , Infecções por Helicobacter/complicações , Helicobacter pylori , Adulto , Fatores Etários , Idoso , China/epidemiologia , Dispepsia/epidemiologia , Endoscopia Gastrointestinal , Feminino , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/epidemiologia , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Neurobiol Aging ; 31(12): 2069-79, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19131143

RESUMO

Epidemiological and experimental studies have correlated hyperhomocysteinemia to a range of neurodegenerative conditions, including Alzheimer's disease, stroke, and Parkinson's disease. Although homocysteine-induced apoptosis in neurons has been extensively studied, little information is available regarding the effect of homocysteine on microglia. In this report, we demonstrated that homocysteine promoted proliferation and up-regulated the expression of CD11b (a marker of microglial activation). Consistent with our in vitro results, a significant increase in the number of CD11b-positive microglia was also observed in brain sections of mice with hyperhomocysteinemia. Homocysteine promoted the activity of NAD(P)H oxidases, resulting in the generation of reactive oxygen species. Up-regulation of NAD(P)H oxidase activity by homocysteine appears to be due to its ability to induce the phosphorylation of p47phox through the p38 MAPK pathway. Furthermore, inhibition of reactive oxygen species significantly blocked cellular proliferation and activation in microglia. Since microglial proliferation and activation play an important role in the development of several neurodegenerative disorders, our results reveal a novel role of homocysteine in the pathogenesis of neurodegenerative diseases.


Assuntos
Proliferação de Células/efeitos dos fármacos , Homocisteína/toxicidade , Microglia/citologia , Microglia/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Células Cultivadas , Replicação do DNA/efeitos dos fármacos , Replicação do DNA/fisiologia , Homocisteína/metabolismo , Hiper-Homocisteinemia/enzimologia , Hiper-Homocisteinemia/metabolismo , Hiper-Homocisteinemia/patologia , Camundongos , Camundongos Endogâmicos BALB C , Microglia/enzimologia , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
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