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1.
J Cancer ; 12(22): 6629-6639, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659553

RESUMO

Cancer stem cells (CSCs) are characterized by self-renewal and unlimited proliferation, providing a basis for tumor occurrence, metastasis, and recurrence. Because CSCs are highly resistant to conventional chemotherapy and radiotherapy, various immunotherapies, particularly chimeric antigen receptor T cell (CAR-T) therapy and dendritic cell (DC)-based vaccine therapy, are currently being developed. Accordingly, in this study, we evaluated programmed cell death ligand-1 (PD-L1) expression in colorectal CSCs (CCSCs) and non-CCSCs and designed a combination immunotherapy synchronously utilizing PD-L1-CAR-T cells together with CCSC-DC vaccine-sensitized T cells for the treatment of colorectal cancer. PD-L1-CAR-T cells specifically recognized the PD-L1 molecule on CCSCs by binding to the extracellular domain of programmed cell death-1. The CCSC-DC vaccine was prepared using CCSC lysates. We found that aldehyde dehydrogenase 1 (ALDH1)-positive CCSCs were abundant in samples from patient tumor tissues and cancer cell lines. Moreover, PD-L1 was highly expressed in ALDH1-positive CCSCs compared with that in non-CCSCs. Monotherapy with PD-L1-CAR-T cells or CCSC-DC vaccine only elicited moderate tumor remission both in vitro and in vivo. However, combination therapy markedly killed cancer cells and relieved the tumor burden in mice. Our findings may provide a novel strategy for the clinical treatment of colorectal malignancy.

2.
J Food Sci Technol ; 58(8): 3199-3204, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34294982

RESUMO

The Bacillus subtilis natto fermented soy protein isolate (FSPI) exhibited concentration-dependent scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS+·) and hydroxyl (·OH) free-radicals. In addition, FSPI administration significantly increased superoxide dismutase activity in mice liver and serum by 20.2% and 86.2%, and suppressed the production of malondialdehyde by 51.3% and 35.1%, respectively, compared to high-fat control (HFC) group. Notably, the movement of mice treated with FSPI was livelier and more active, and its weight gain was significantly lower than that of both NC and HFC groups. The production and accumulation of perirenal fat was also significantly inhibited by FSPI, however, no significant difference in TG and TC levels were observed between FSPI and HFC groups. The results revealed the great potential of FSPI applying in the development of health food or sports food.

3.
Mol Nutr Food Res ; 65(20): e2100167, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34268878

RESUMO

SCOPE: Adiponectin (ADPN), a kind of adipokines, plays an important role in the regulation of lipid metabolism. The objective of this study is focused on the ADPN to investigate the functional mechanisms of pectin oligosaccharide (POS) from hawthorn fruit in the improvement of hepatic fatty acid oxidation. METHOD AND RESULTS: High-fat fed mice are used in this experiment. POS is administrated with the doses of 0.25, 0.75, and 1.5 g kg-1 diet, respectively. The results demonstrate that gene and protein expressions of ADPN synthesis regulators involved in PKA/ERK/CREB and C/EBPα/PPARγ pathways are upregulated by POS administration. POS also activates the AdiopR1/AMPKα/PGC1 and AdipoR2/PPARα signaling pathways to improve the fatty acid oxidation in the liver, which is further accelerated by the enhancement of mitochondrial functions. CONCLUSION: POS can act as an ADPN activator to improve lipid metabolism, leading it to the applications of biomedical and functional foods for ameliorating chronic liver diseases resulted from a high-energy diet.

4.
Arch Microbiol ; 202(5): 1251-1256, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32112121

RESUMO

Clostridium butyricum, an anaerobic spore-forming bacillus, is a common human and animal gut commensal bacterium. Spore is an important structure for C. butyricum to tolerate environmental stress. However, it is not easy to form in common fermentation process of C. butyricum. In this study, the parameters for optimizing the spore formation of C. butyricum NN-2 were defined. The results showed that the pH value was a crucial factor that significantly affected the spore formation of C. butyricum NN-2. Down-regulation steps of pH value from 6.5 to 5.5 over time during the cultural process significantly (p < 0.05) promoted spore formation of C. butyricum NN-2, allowing for the sporulation rate of > 90%. In addition, the duration of pH regulation also had significant effects on the spore formation of C. butyricum NN-2. The results revealed a highly effective strategy for enhancing the spore production of C. butyricum.


Assuntos
Clostridium butyricum/efeitos dos fármacos , Fermentação , Esporos Bacterianos , Meios de Cultura/química , Concentração de Íons de Hidrogênio , Esporos Bacterianos/fisiologia
5.
PLoS One ; 10(7): e0133736, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26208355

RESUMO

OBJECTIVE: To investigate the epidemic characteristics of human cutaneous anthrax (CA) in China, detect the spatiotemporal clusters at the county level for preemptive public health interventions, and evaluate the differences in the epidemiological characteristics within and outside clusters. METHODS: CA cases reported during 2005-2012 from the national surveillance system were evaluated at the county level using space-time scan statistic. Comparative analysis of the epidemic characteristics within and outside identified clusters was performed using using the χ2 test or Kruskal-Wallis test. RESULTS: The group of 30-39 years had the highest incidence of CA, and the fatality rate increased with age, with persons ≥70 years showing a fatality rate of 4.04%. Seasonality analysis showed that most of CA cases occurred between May/June and September/October of each year. The primary spatiotemporal cluster contained 19 counties from June 2006 to May 2010, and it was mainly located straddling the borders of Sichuan, Gansu, and Qinghai provinces. In these high-risk areas, CA cases were predominantly found among younger, local, males, shepherds, who were living on agriculture and stockbreeding and characterized with high morbidity, low mortality and a shorter period from illness onset to diagnosis. CONCLUSION: CA was geographically and persistently clustered in the Southwestern China during 2005-2012, with notable differences in the epidemic characteristics within and outside spatiotemporal clusters; this demonstrates the necessity for CA interventions such as enhanced surveillance, health education, mandatory and standard decontamination or disinfection procedures to be geographically targeted to the areas identified in this study.


Assuntos
Antraz/epidemiologia , Dermatopatias Bacterianas/epidemiologia , Antraz/história , China/epidemiologia , Análise por Conglomerados , Feminino , História do Século XXI , Humanos , Masculino , Vigilância da População , Medição de Risco , Estações do Ano , Dermatopatias Bacterianas/história , Análise Espaço-Temporal
6.
Gene ; 569(1): 60-5, 2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-25979673

RESUMO

In this study, we aimed to assess the neuroprotective effect of sevoflurane preconditioning in a cerebral focal ischemia-reperfusion rat model. Sixty Sprague Dawley rats were divided into six groups: sham operated group, cerebral focal ischemia-reperfusion (CIR) group, CIR+sevoflurane preconditioning (SP) (2%) group, CIR+sevoflurane preconditioning (2.5%) group, CIR+sevoflurane preconditioning (3%) group, and CIR+sevoflurane preconditioning (3.5%) group. All subjects were euthanized 2days post-surgery and their hippocampus tissues were removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus tissue samples were examined histopathologically. Results showed that significant difference in antioxidant, immunity indexes, and apoptosis-related protein expression was detected in hippocampus tissue between sham-operated control and CIR groups. Sevoflurane preconditioning significantly dose-dependently reduced MDA, IL-1ß, IL-6, IL-10 and TNF-α levels and enhanced antioxidant enzyme activities in hippocampus tissue of CIR+SP groups compared to CIR group. In addition, sevoflurane preconditioning significantly dose-dependently upregulated PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded that sevoflurane preconditioning demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane preconditioning are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of PI3K and p-Akt signal activation.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Éteres Metílicos/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Isquemia Encefálica/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Traumatismo por Reperfusão/patologia , Sevoflurano , Transdução de Sinais/efeitos dos fármacos
8.
Gene ; 542(1): 46-51, 2014 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-24630969

RESUMO

Tea polyphenols (TP) was investigated in rats for its protective effect on renal ischemia/reperfusion injury (RIRI). Rats were randomized into groups as follows: (I) sham group (n=10); (II) RIRI group (n=10); (III) RIRI+TP (100mg/kg) group (n=5); (IV) RIRI+TP (200mg/kg) group (n=5); (V) RIRI+TP+ Astragalus mongholicus aqueous extract (AMAE) (300 mg/kg+100mg/kg) group (n=5). For the IRI+TP groups, rats were orally given with tea polyphenols (100, 200 and 300 mg/kg body weight) once daily 10 days before induction of ischemia, followed by renal IRI. For the sham group and RIRI group, rats were orally given with equal volume of saline once daily 10 days before induction of ischemia, followed by renal IRI. Results showed that tea polyphenol pretreatment significantly suppressed ROS level and MDA release. On the other hand, in rats subjected to ischemia-reperfusion, the activities of endogenous antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) showed recovery, whereas the levels of urea nitrogen and serum creatinine were reduced by administration of tea polyphenols orally for 10 days prior to ischemia-reperfusion. Moreover, tea polyphenol pretreatment significantly decreased TLR4 and NF-κB p65 protein expression levels in RIRI rats. At the same time, tea polyphenol pretreatment attenuated the increased level of serum IL-1ß, IL-6, ICAM-1 and TNF-α, and enhanced IL-10 production in RIRI rats. Furthermore, tea polyphenol pretreatment significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that tea polyphenol pretreatment could suppress the TLR4/NF-κB p65 signaling pathway, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by TLR4/NF-κB p65 signal pathway. Moreover, supplement of AMAE can increased renal protection effect of TP.


Assuntos
Apoptose/efeitos dos fármacos , Camellia sinensis/química , Rim/irrigação sanguínea , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes/uso terapêutico , Nitrogênio da Ureia Sanguínea , Catalase/metabolismo , Creatinina/sangue , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Molécula 1 de Adesão Intercelular/sangue , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Rim/efeitos dos fármacos , Túbulos Renais/irrigação sanguínea , Túbulos Renais/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/biossíntese , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/biossíntese , Fator de Necrose Tumoral alfa/sangue
9.
Mol Biol Rep ; 40(12): 6997-7006, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24190484

RESUMO

Tumor necrosis factor (TNF) and the TNF receptor (TNFR) superfamily play very important roles for cell death as well as normal immune regulation. Previous studies have strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in ischemic brain injury. The purpose of this investigation was to examine the protective effect of remifentanil preconditioning in cerebral ischemia/reperfusion injury (CIR) and its possible molecular mechanism. Results showed that Remifentanil pretreatment significantly decreased the CD4(+) and increased the CD8(+) in cerebral tissues. Additionally, CD4(+)/CD8(+) in CIR + Remifentanil group was markedly lower than that in CIR group. TNF-α and TNFR1 in CIR + Remifentanil group rats was found to be significant lower than that in CIR group rats. The expression levels of Cyt-c, caspase-3, caspase-9 and pJNK proteins in brain of CIR + Remifentanil group rats were found to significantly decreased compared to CIR group rats. In addition, decreased ROS level indirectly inhibit JNK activation and cell death in CIR rat receiving Remifentanil preconditioning. From current experiment results, at least two signal pathways involve into the process of Remifentanil preconditioning inhibiting cerebral damage induced by ischemia reperfusion. The inhibitory effects of Remifentanil preconditioning on the brain damage are achieved probably through blocking the activation of TNF-α/TNFR1, JNK signal transduction pathways, which implies that Remifentanil preconditioning may be a potential and effective way for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by TNF-α/TNFR1, JNK signal pathways. Taken together, this study indicated that regulation of the TNF-α/TNFR1 and JNK signal pathways may provide a new therapy for cerebral damage induced by ischemia and reperfusion.


Assuntos
Isquemia Encefálica/prevenção & controle , Encéfalo/patologia , Precondicionamento Isquêmico , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Piperidinas/farmacologia , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo , Animais , Encéfalo/enzimologia , Encéfalo/fisiopatologia , Isquemia Encefálica/enzimologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Modelos Biológicos , Ratos , Ratos Sprague-Dawley , Remifentanil , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Superóxido Dismutase/metabolismo
10.
Folia Histochem Cytobiol ; 49(3): 389-97, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22038216

RESUMO

The aim of this study was to evaluate the expression of COX-2 and Bcl-2 in primary fallopian tube carcinoma (PFTC), as well as their correlations with clinicopathologic features. We studied a cohort of 33 patients with a pathological diagnosis of PFTC. Thirty normal tubal tissues used for controls were obtained from patients diagnosed with uterine myomas. Expression analysis for COX-2 and Bcl-2 was performed using the immunohistochemical technique. The rate of preoperative diagnosis was 18.2%. With a median survival of 61.0 months (95% CI: 43.2 to 78.8 months), the estimated five-year overall survival rate in the 33 patients was 39.0%. Increased expression of COX-2 and Bcl-2 was observed in tumor specimens compared to normal controls (p = 0.026; p = 0.003). The expression rate of COX-2 in node-positive tumors was significantly higher than that of node-negative tumors (p = 0.024). Moreover, the expression rate of COX-2 was statistically significantly higher in patients with infiltration through the serosa (p = 0.019). Positive significant associations were observed between Bcl-2 staining index and FIGO stage (p = 0.015), and between Bcl-2 staining and lymph node metastasis (p = 0.010). There was a significant correlation between COX-2 expression and Bcl-2 staining index (r = 0.517, p = 0.002). We conclude that COX-2 and Bcl-2 may potentially be useful prognostic markers for PFTC. The exact molecular mechanism for correlations between COX-2 and Bcl-2 remains to be elucidated.


Assuntos
Biomarcadores Tumorais/metabolismo , Ciclo-Oxigenase 2/metabolismo , Neoplasias das Tubas Uterinas/metabolismo , Tubas Uterinas/metabolismo , Tubas Uterinas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Adulto , Idoso , Estudos de Coortes , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/citologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida
11.
Molecules ; 17(1): 341-54, 2011 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-22210172

RESUMO

The volatile anesthetic sevoflurane is capable of inducing preconditioning and postconditioning effects in the brain. In this study, we investigated the effects of sevoflurane postconditioning on antioxidant and immunity indexes in cerebral ischemia reperfusion (CIR) rats. Rats were randomly assigned to five separate experimental groups I-V. In the sham group (I), rats were subjected to the same surgery procedures except for occlusion of the middle cerebral artery and exposed to 1.0 MAC sevoflurane 90 min after surgery for 30 min. IR control rats (group II) were subjected to middle cerebral artery occlusion (MCAO) for 90 min and exposed to O2 for 30 min at the beginning of reperfusion. Sevoflurane 0.5, 1.0 and 1.5 groups (III, IV, V) were all subjected to MCAO for 90 min, but at the beginning of reperfusion exposed to 0.5 MAC, 1.0 MAC or 1.5 MAC sevoflurane for 30 min, respectively. Results showed that sevoflurane postconditioning can decrease serum tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), nitric oxide (NO), nitric oxide synthase (NOS) and increase serum interleukin-10 (IL-10) levels in cerebral ischemia reperfusion rats. In addition, sevoflurane postconditioning can still decrease blood lipid, malondialdehyde (MDA) levels, infarct volume and increase antioxidant enzymes activities, normal pyramidal neurons density in cerebral ischemia reperfusion rats. It can be concluded that sevoflurane postconditioning may decrease blood and brain oxidative injury and enhance immunity indexes in cerebral ischemia reperfusion rats.


Assuntos
Encéfalo/irrigação sanguínea , Infarto da Artéria Cerebral Média/tratamento farmacológico , Pós-Condicionamento Isquêmico , Éteres Metílicos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Glutationa/sangue , Infarto da Artéria Cerebral Média/sangue , Infarto da Artéria Cerebral Média/patologia , Mediadores da Inflamação/sangue , Interleucina-10/sangue , Interleucina-1beta/sangue , Lipídeos/sangue , Masculino , Malondialdeído/sangue , Éteres Metílicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/sangue , Estresse Oxidativo , Oxirredutases/sangue , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologia , Sevoflurano , Fator de Necrose Tumoral alfa/sangue
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