Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Chem Commun (Camb) ; 58(25): 4056-4059, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35262118

RESUMO

The detection of X-rays has always been a frontier of scientific research. An Eu-MOF with both X-ray-induced photochromic and scintillation properties has been synthesized through the combination of a photochromism-active viologen ligand and rare earth Eu element with high-efficiency absorption of X-rays. In a bright environment, Eu-MOF exhibits different color changes under high-energy X-rays and low-energy X-rays, which can effectively distinguish X-rays. Eu-MOF can also be used for X-ray detection by scintillation properties in dark environments. This work provides a new perspective on the design of multifunctional materials that can perform simple X-ray detection in different environments.

2.
Neurochem Res ; 46(5): 1058-1067, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761044

RESUMO

Albicanol is a natural terpenoid derived from Dryopteris fragrans. Herein, we assessed the ability of Albicanol to protect against oxidative stress-induced senescence. Using a murine model of D-galactose (D-gal)-induced aging, we determined that Albicanol treatment can reverse D-gal-mediated learning impairments and behavioral changes, while also remediating brain tissue damage in treated mice. We found that serum SOD, CAT, GSH-Px, and T-AOC levels were significantly decreased in aging mice, and that Albicanol treatment significantly increased the serum levels of these antioxidant enzymes. We additionally evaluated the impact of Albicanol treatment on the Keap1/Nrf2/ARE signaling pathway, and found that it was able to decrease Keap1 expression while increasing the expression of Nrf2, thereby activating this signaling pathway, suppressing oxidative damage, and enhancing the expression of downstream target genes including SOD, GSH, GST, HO-1, and NQO1 in this murine aging model system. Albicanol treatment also inhibited the secretion of inflammatory TNF-a and IL-1b. Together, these data indicated that Albicanol can activate Nrf2 pathway-related genes, thereby inhibition of delayed aging by alleviating oxidative stress-induced damage.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/uso terapêutico , Galactose/farmacologia , Naftalenos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/patologia , Expressão Gênica/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos
3.
Inflammation ; 44(1): 249-260, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33098521

RESUMO

In order to investigate efficacy of FGF21 combine dexamethasone (Dex) on rheumatoid arthritis (RA) meanwhile reduce side effects of dexamethasone. We used combination therapy (Dex 15 mg/kg + FGF21 0.25 mg/kg, Dex 15 mg/kg + FGF21 0.5 mg/kg or Dex 15 mg/kg + FGF21 1 mg/kg) and monotherapy (Dex 15 mg/kg or FGF21 1 mg/kg) to treat CIA mice induced by chicken type II collagen, respectively. The effects of treatment were determined by arthritis severity score, histological damage, and cytokine production. The levels of oxidative stress parameters, liver functions, and other blood biochemical indexes were detected to determine FGF21 efficiency to side effects of dexamethasone. Oil red O was performed to detect the effects of FGF21 and dexamethasone on fat accumulation in HepG2 cells. The mechanism of FGF21 improves the side effects of dexamethasone which was analyzed by Western blotting. This combination proved to be therapeutically more effective than dexamethasone or FGF21 used singly. FGF21 regulates oxidative stress and lipid metabolism by upregulating dexamethasone-inhibited SIRT-1 and then activating downstream Nrf-2/HO-1and PGC-1. FGF21 and dexamethasone are highly effective in the treatment of arthritis; meanwhile, FGF21 may overcome the limited therapeutic response and Cushing syndrome associated with dexamethasone.


Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Dexametasona/administração & dosagem , Fatores de Crescimento de Fibroblastos/administração & dosagem , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Galinhas , Dexametasona/efeitos adversos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Resultado do Tratamento
4.
Dalton Trans ; 49(22): 7309-7314, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32458956

RESUMO

The synergy of unusual X-aggregation induced luminescent chromophores and heavy Pb(ii) ions has facilitated excellent X-ray scintillation of two structurally similar Pb-SMOFs, which are heat-resistant due to solvent-free lattices. Owing to their higher Pb(ii) contents, Pb-SMOFs with larger X-ray absorption coefficients are more sensitive for X-ray dosage detection than powdered CsPbBr3.

5.
Chem Commun (Camb) ; 55(92): 13816-13819, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31664282

RESUMO

Efficient cathode-ray scintillating metal-organic frameworks are constructed from a π-conjugated luminescent motif and light Ca(ii) ions. The luminescence self-quenching pathway has been effectively hindered through coordination. In situ vacuum ultraviolet fluorescent spectra have shown the excitons recombining in the scintillation process for the first time.

6.
World J Gastroenterol ; 25(20): 2473-2488, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31171891

RESUMO

BACKGROUND: It is challenging to distinguish intestinal tuberculosis from Crohn's disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)-23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM: To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS: We analysed 133 patients with intestinal tuberculosis, 128 with Crohn's disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1ß rs1143627, TGFß rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS: The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION: High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.


Assuntos
Doença de Crohn/diagnóstico , Células Gigantes de Langhans/patologia , Interleucinas/genética , Receptores de Interleucina/metabolismo , Tuberculose Gastrointestinal/diagnóstico , Adulto , Biópsia , Estudos de Casos e Controles , Doença de Crohn/genética , Doença de Crohn/imunologia , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Células Gigantes de Langhans/imunologia , Humanos , Interleucinas/imunologia , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Receptores de Interleucina/imunologia , Fatores de Risco , Tuberculose Gastrointestinal/genética , Tuberculose Gastrointestinal/imunologia , Adulto Jovem
7.
Exp Cell Res ; 382(1): 111457, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31175853

RESUMO

Chronic pancreatitis (CP) is a progressive, irreversible inflammatory and fibrotic disease. The characteristics of this disease are progressive inflammation, acinar atrophy and fibrosis. Numerous factors are involved in CP such as inflammation, and oxidative stress. Recently, it has been noted that fibroblast growth factor 21 (FGF-21) reduced the severity of acute pancreatitis in mice. However, whether FGF-21 has effects on CP remains unclear. Thus, the present study was undertaken to detect the effects of FGF-21 on l-arginine induced chronic pancreatitis/islet fibrosis in mice. We used l-arginine to create a CP model in C57BL/6 mice and treated these mice with FGF-21. Compared to normal mice, blood glucose and intra-peritoneal glucose tolerance test (IPGTT) revealed significant impairment in CP animal model. CP mice also had acinar atrophy, loss of pancreas morphology, inflammatory cells infiltration, extensive deposition of collagen, elevated -SMA expression, collagen I expression, serum amylase activity, MPO activity and MDA level. All these pathological changes were significantly improved by FGF-21 treatment. Moreover, FGF-21 ameliorated inflammatory state in the serum, pancreas and peritoneal macrophages of CP mice. Furthermore, we also found that FGF-21 could regulate differentiation of macrophages so as to improve pancreatic fibrogenesis in CP mice. Taken together, our study identifies the beneficial role of FGF-21 in CP and suggests that FGF-21 improves pancreatic fibrogenesis in CP via the mTOR pathway.


Assuntos
Fatores de Crescimento de Fibroblastos/uso terapêutico , Macrófagos Peritoneais/efeitos dos fármacos , Pancreatite Crônica/tratamento farmacológico , Amilases/sangue , Animais , Arginina/toxicidade , Diferenciação Celular/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/farmacologia , Fibrose , Teste de Tolerância a Glucose , Humanos , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/patologia , Peroxidase/sangue , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Serina-Treonina Quinases TOR/fisiologia
8.
Biomed Res Int ; 2019: 9537050, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31093505

RESUMO

Background: Because of the similarity of intestinal tuberculosis and Crohn's disease in disease phenotype, differential diagnosis has always been a clinical problem. Arachidonic acid metabolites play an important role in the inflammatory response of intestinal tuberculosis and Crohn's disease. Recent studies have shown that the polymorphism locus in the promoter region of LTA4H gene affects LTB4 expression level and the susceptibility to extrapulmonary tuberculosis. Thus, we identified a total of 148 patients with intestinal tuberculosis, 145 with Crohn's disease, and 700 normal controls in this study. Methods: All the study participants were local Han people from Jiangxi Province in the past eleven years. DNA was extracted from the paraffin-embedded specimens or the whole blood. The LTA4H promoter SNP (rs17525495) was genotyped with TaqMan assay. Results: The T-alleles frequency was not significantly increased in patients with intestinal tuberculosis compared with healthy control group (p=0.630; OR=1.07; 95%CI=0.81-1.41), while patients with Crohn's disease have significantly increased T allele frequency compared with healthy population (p=0.032; OR=1.34; 95%CI=1.03-1.75). During treatment, the presence of the T allele significantly increased the proportion of Crohn's patients requiring glucocorticoids (p<0.05). Conclusions: The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn's disease instead of intestinal tuberculosis. More importantly, there may be a potential association of the different genotypes of rs17525495 with the treatment efficacy of 5-ASA and glucocorticoids in patients with Crohn's disease. The association between LTA4H polymorphism and drugs therapeutic effects might contribute to the practice of precision medicine and the prediction of clinical outcomes.


Assuntos
/genética , Doença de Crohn/genética , Epóxido Hidrolases/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Tuberculose Gastrointestinal/genética , Adulto , Doença de Crohn/enzimologia , Feminino , Frequência do Gene/genética , Humanos , Masculino , Modelos Genéticos , Tuberculose Gastrointestinal/enzimologia
9.
Obesity (Silver Spring) ; 27(3): 399-408, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30703283

RESUMO

OBJECTIVE: Obesity-related, chronic, low-grade inflammation has been identified as a key factor in the development of many metabolic diseases, such as type 2 diabetes and cardiovascular diseases. Adipocytes, preadipocytes, and macrophages have been implicated in initiating inflammation in adipose tissue. This study aims to investigate the effects of fibroblast growth factor-21 (FGF-21) on obesity-related inflammation and its mechanisms in vivo and in vitro. METHODS: Monosodium glutamate (MSG) was used to induce obesity in mice and subsequently treated the mice with or without FGF-21. Primary adipocytes and stromal vascular fraction cells were isolated from MSG-obesity mice for additional experiments. RESULTS: Results obtained by ELISA and real-time polymerase chain reaction showed that FGF-21 efficiently ameliorated obesity-related inflammation in MSG-obesity mice. This study demonstrated that preadipocytes and adipocytes responded to anti-inflammatory effects of FGF-21. In vitro, 3 T3-L1 preadipocytes lacking ß-klotho did not respond to FGF-21 under glucose uptake. Interestingly, the treatment of 3 T3-L1 preadipocytes with FGF-21 significantly attenuated lipopolysaccharide-induced inflammatory response. CONCLUSIONS: Our study showed that FGF-21-induced glucose uptake and FGF-21-related anti-inflammatory effects are mediated by different signaling pathways. Moreover, FGF-21 showed anti-inflammatory effects on preadipocytes; these effects are mediated by the fibroblast growth factor receptor substrate 2/ERK1/2 signaling pathway.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Fatores de Crescimento de Fibroblastos/uso terapêutico , Inflamação/tratamento farmacológico , Obesidade/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Fatores de Crescimento de Fibroblastos/farmacologia , Humanos , Camundongos
10.
Biomed Pharmacother ; 108: 1825-1834, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372888

RESUMO

Macrophages are paramount to the initiation and procession of atherosclerosis, thus targeting macrophages in the progress of atherosclerosis is indispensable. Therefore, we perform in vitro experiments to investigate the effects of FGF-21 on macrophages in the progress of atherosclerosis. First, we use phorbol-12-myristate-13-acetate (PMA), a phorbol ester, to induce THP-1 cells into macrophages as macrophages model. After that we use Ox-LDL to induce macrophages into foam cells and simultaneously administrate with FGF-21 or not to determine whether FGF-21 has effects on foam cells formation and related inflammatory response. Wound healing results show that FGF-21 can inhibit macrophage migration. Oil Red-O stain, immunofluorescence and flow cytometer results show that FGF-21 can repress cholesterol accumulation in macrophages thereby inhibit foam cells formation and these effects can be abolished by FGFR inhibitor. Moreover, real-time PCR results showed that FGF-21 significantly reduces expression of inflammatory factors including IL-1α, IL-6 and TNF-α and this effect can be abolished by FGFR inhibitor. Furthermore, to determine the mechanism of FGF-21 regulates inflammatory response in Ox-LDL-induced THP-1 macrophages, western blotting results show that after treatment of Ox-LDL in macrophages, NF-κB signaling pathway is activated but FGF-21 can significantly inhibit this pathway. In addition, FGF-21 also regulates some regulators of lipid metabolism after treatment of Ox-LDL in macrophages. Above all, our findings demonstrate that FGF-21 can regulate foam cells formation, macrophage migration, inflammatory response and lipid metabolism in Ox-LDL-induced THP-1 macrophages.


Assuntos
Fatores de Crescimento de Fibroblastos/farmacologia , Células Espumosas/metabolismo , Células Espumosas/patologia , Inflamação/patologia , Lipoproteínas LDL/farmacologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Movimento Celular/efeitos dos fármacos , Colesterol/metabolismo , Células Espumosas/efeitos dos fármacos , Glucuronidase/metabolismo , Humanos , NF-kappa B/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores Depuradores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células THP-1
11.
Int Immunopharmacol ; 56: 301-309, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29414665

RESUMO

Type 2 diabetes mellitus (T2DM) is accompanied by abnormal glucose metabolism and low-grade chronic inflammation. Fibroblast growth factor 21 (FGF-21) is a novel metabolic regulator and can function as an endocrine hormone to regulate glucose and lipid metabolism. Recently, FGF-21 was found to have anti-inflammatory effect, to our knowledge, the effect of FGF-21 on inflammatory state in diabetes has not been elucidated. Here, we use db/db mice as a Type 2 diabetes model to determine whether FGF-21 alleviates inflammatory state while improves hyperglycemia. Our results demonstrated that FGF-21 not only showed potent long lasting hypoglycemic effect, but also demonstrated strong anti-inflammatory effect in the serum and white adipose tissue. Besides, in vitro experiments, insulin resistance (IR) was induced in 3T3-L1 adipocytes by treating with TNF-α. Our results showed that TNF-α impaired glucose metabolism of 3T3-L1 adipocytes but FGF-21 repressed gene expression of inflammatory factors caused by IR and consequently improved the glucose metabolism in 3T3-L1 adipocytes. Furthermore, FGF-21 ameliorated glucose uptake of TNF-α-induced IR in 3T3-L1 adipocytes by inhibiting NF-κB signaling pathway.


Assuntos
Adipócitos/fisiologia , Tecido Adiposo Branco/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Glucose/metabolismo , Inflamação/metabolismo , Animais , Linhagem Celular , Hiperglicemia , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
12.
Inflammation ; 41(3): 751-759, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29427162

RESUMO

Fibroblast growth factor 21 (FGF-21) has been previously judged as a major metabolic regulator. In this paper, we show that FGF-21 has a potential role in anti-inflammation and immunoregulation. In vivo, treatment with exogenous FGF-21 can alleviate LPS-induced inflammation. In vitro, FGF-21 inhibited LPS-induced IL-1ß expression in THP-1 cells. Furthermore, besides the NF-κB pathway, the mechanism of action of FGF-21 was observed to involve the elevation of IL-10 in the ERK1/2 pathway. This study clearly indicates that FGF21 can be used as an attractive target for the management of inflammatory disorders. This piece of research indicates that FGF-21 could have much value in the management of inflammatory disorders.


Assuntos
Fatores de Crescimento de Fibroblastos/farmacologia , Inflamação/tratamento farmacológico , Interleucina-10/metabolismo , Linhagem Celular , Fatores de Crescimento de Fibroblastos/fisiologia , Humanos , Inflamação/induzido quimicamente , Interleucina-10/farmacologia , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
13.
Inflammation ; 41(1): 73-80, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28965199

RESUMO

Monocytes display a gradual change in metabolism during inflammation. When activated, the increase in glucose utilization is important for monocytes to participate in immune and inflammatory responses. Further studies on the mechanism underlying this biological phenomenon may provide a new understanding of the relationship between immune response and metabolism. The THP-1 cells were used as a monocyte model. The cells were activated with lipopolysaccharide (LPS). Glucose uptake was measured using flow cytometry. The expression of fibroblast growth factor 21 (FGF-21), glucose transporter 1 (GLUT-1), and other FGF-21 signaling pathway-related factor mRNAs was determined by real-time polymerase chain reaction. Further, the relationship between FGF-21 expression in monocytes and phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway was determined by Western blotting. LPS elevated FGF-21 expression in monocytic THP-1 cells in vitro. Functional assays showed that the phenomenon in which LPS and FGF-21 stimulated glucose uptake in monocytic THP-1 cells could be inhibited by FGFR inhibitor. The mechanism of elevation of FGF-21 was found to involve the PI3K/Akt signaling pathway. This study indicated that FGF-21 could regulate the immune response indirectly by influencing the glucose uptake of activated monocytes cells.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Glucose/metabolismo , Monócitos/metabolismo , Transporte Biológico , Transportador de Glucose Tipo 1/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Proteínas de Membrana/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Células THP-1 , Fatores de Tempo
14.
Asian Pac J Cancer Prev ; 17(4): 1823-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27221859

RESUMO

BACKGROUND: Biological and pharmacological activities of dryocrassin ABBA, a phloroglucinol derivative extracted from Dryopteris crassirhizoma, have attracted attention. In this study, the apoptotic effect of dryocrassin ABBA on human hepatocellular carcinoma HepG2 cells was investigated. MATERIALS AND METHODS: We tested the effects of dryocrassin ABBA on HepG2 in vitro by MTT, flow cytometry, real-time PCR, and Western blotting. KM male mice were used to detect the effect of dryocrassin ABBA on H22 cells in vivo. RESULTS: Dryocrassin ABBA inhibited the growth of HepG2 cells in a concentration-dependent manner. After treatment with 25, 50, and 75 µg/mL dryocrassin ABBA, the cell viability was 68%, 60% and 49%, respectively. Dryocrassin ABBA was able to induce apoptosis, measured by propidium iodide (PI)/annexin V-FITC double staining. The results of real-time PCR and Western ting showed that dryocrassin ABBA up-regulated p53 and Bax expression and inhibited Bcl-2 expression which led to an activation of caspase-3 and caspase-7 in the cytosol, and then induction of cell apoptosis. In vivo experiments also showed that dryocrassin ABBA treatment significantly suppressed tumor growth, without major side effects. CONCLUSIONS: Overall, these findings provide evidence that dryocrassin ABBA may induce apoptosis in human hepatocellular carcinoma cells through a caspase-mediated mitochondrial pathway.


Assuntos
Apoptose/efeitos dos fármacos , Compostos de Benzilideno/farmacologia , Carcinoma Hepatocelular/patologia , Caspases/metabolismo , Cicloexanonas/farmacologia , Neoplasias Hepáticas/patologia , Mitocôndrias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Caspases/genética , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Inflammation ; 39(1): 309-319, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26424095

RESUMO

Recently, FGF21 was reported to play an important role in anti-inflammation. The aim of the study is to explore the mechanism for FGF21 alleviating inflammation of CIA. CIA mice were injected with FGF21 once a day for 28 days after first booster immunization. The results showed that FGF21 alleviates arthritis severity and decreases serum anti-CII antibodies levels in CIA mice. Compared with CIA model, the number of the splenic TH17 cells was significantly decreased in FGF21-treated mice. FGF21 treatment reduced the mRNA expression of IL-17, TNF-α, IL-1ß, IL-6, IL-8, and MMP3 and increased level of IL-10 in the spleen tissue. The expression of STAT3 and phosphorylated STAT3 was suppressed in FGF21-treated group. The mRNA expression of RORγt and IL-23 also decreased. In conclusion, these findings suggest that the beneficial effects of FGF21 on CIA mice were achieved by down-regulating Th17-IL-17 axis through STAT3/RORγt pathway. Modulating of Th17-mediated inflammatory response may be one of the mechanisms for FGF21 attenuating inflammation in CIA.


Assuntos
Artrite Experimental/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/uso terapêutico , Interleucina-17/biossíntese , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Fator de Transcrição STAT3/metabolismo , Células Th17/imunologia , Animais , Regulação para Baixo , Fatores de Crescimento de Fibroblastos/genética , Inflamação/imunologia , Interleucina-10/biossíntese , Interleucina-1beta/biossíntese , Subunidade p19 da Interleucina-23/genética , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Masculino , Metaloproteinase 3 da Matriz/biossíntese , Camundongos , Camundongos Endogâmicos DBA , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Fosforilação , RNA Mensageiro/biossíntese , Fator de Transcrição STAT3/biossíntese , Baço/imunologia , Fator de Necrose Tumoral alfa/biossíntese
16.
Endocrine ; 49(2): 385-95, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25542183

RESUMO

Fibroblast growth factor 21 (FGF-21) is a major paracrine and endocrine regulator of metabolic homeostasis. Here we demonstrate that FGF-21 is also a potent mediator of innate immunity. Double-staining flow cytometry identified neutrophils and monocytes as the main sources of FGF-21 among circulating leukocytes. Functional assays showed that FGF-21 stimulates phagocytosis and production of reactive oxygen species in neutrophil-like HL-60 cells and monocytic THP-1 cells. The mechanism of action of FGF-21 was observed to involve FGF receptor activation, signal transduction through the PI3K/Akt pathway, and stimulation of NADPH oxidase activity. This study indicates that FGF-21 could be an attractive target for the management of inflammatory disorders.


Assuntos
Fatores de Crescimento de Fibroblastos/fisiologia , Imunidade Inata/fisiologia , NADPH Oxidases/metabolismo , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Monócitos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Adulto Jovem
17.
Endocrine ; 48(2): 519-27, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24895044

RESUMO

Fibroblast growth factor 21 (FGF21), a recently discovered regulatory factor, plays an important role in glucose and lipid metabolism. In this study, we firstly found the FGF21 expression in white blood cells (WBCs). Then, we enrolled 51 women with gestational diabetes mellitus (GDM) and 50 pregnant women with normal blood glucose levels to determine the FGF21 levels in the WBCs and the sera at the 28th week of pregnancy, and tracked the dynamic changes of FGF21 in these women until the 7th day postpartum. Repeated Measures analysis of variance (ANOVA) revealed that there was a significant interaction effect between group and time on FGF21 levels (P < 0.05). FGF21 levels were significantly higher in the GDM patients than those in the controls at the 28th week of pregnancy. The 7th day after the delivery, the FGF21 levels decreased in the WBCs and the sera in both groups. The D values (the difference between pregnancy and postpartum) for FGF21 levels were significantly higher in the GDM group (P < 0.05). Serum FGF21 level during gestation positively correlated with leptin, triglyceride, and HDL-cholesterol, and FGF21 may act as a glucose and lipid metabolism compensatory regulatory factor to improve glucose and lipid metabolism during the period of pregnancy. Further, FGF21 level in the WBCs (during pregnancy and the D values for FGF21) was chiefly influenced by GDM.


Assuntos
Diabetes Gestacional/sangue , Fatores de Crescimento de Fibroblastos/metabolismo , Leucócitos/metabolismo , Período Pós-Parto/sangue , Soro/metabolismo , Adulto , Feminino , Humanos , Gravidez , RNA Mensageiro/metabolismo
18.
Endocrine ; 49(1): 119-29, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25306889

RESUMO

The aim of this study is to investigate the role of FGF21 in obesity-related inflammation in livers of monosodium glutamate (MSG)-induced obesity rats. The MSG rats were injected with recombinant murine fibroblast growth factor 21(FGF21) or equal volumes of vehicle. Metabolic parameters including body weight, Lee's index, food intake, visceral fat and liver weight, intraperitoneal glucose tolerance, glucose, and lipid levels were dynamically measured at specific time points. Liver function and routine blood test were also analyzed. Further, systemic inflammatory cytokines such as glucose transporter 1 (GLUT-1), leptin, TNF-α, and IL-6 mRNAs were determined by real-time PCR. FGF21 independently decreased body weight and whole-body fat mass without reducing food intake in the MSG rats. FGF21 reduced blood glucose level, Lee's index, visceral fat, and liver weight, and improved glucose tolerance, lipid metabolic spectrum, and hepatic steatosis in the MSG-obesity rats. Liver function parameters including AST, ALT, ALP, TP, T.Bili, and D.Bili levels significantly reduced in the FGF21-treated obesity rats compared to the controls. Further, FGF21 ameliorated the total and differential white blood cell (WBC) count, serum C-reactive protein (CRP), IL-6, and TNF-α levels in adipose tissues of the obesity rats, suggesting inflammation amelioration in the in the obesity rats by FGF21. FGF21 improves multiple metabolic disorders and ameliorates obesity-related inflammation in the MSG-induced obesity rats.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/farmacologia , Aromatizantes/farmacologia , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Animais , Modelos Animais de Doenças , Fígado Gorduroso/induzido quimicamente , Inflamação/induzido quimicamente , Camundongos , Obesidade/induzido quimicamente , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Glutamato de Sódio/farmacologia
19.
Yao Xue Xue Bao ; 50(9): 1101-6, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26757545

RESUMO

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on type 2 diabetic mice model and to provide mechanistic insights into its therapeutic effect. Type 2 diabetic animal model was established with high calorie fat diet and low dose streptozotocin (STZ) injection. Mice were then randomized into 5 groups: model control, FGF21 0.25 and 0.05 µmol x kg(-1) x d(-1) groups, insulin treatment group. Ten age-matched normal KM mouse administered with saline were used as normal controls. Serum glucose, insulin, lipid products and the change of serum and liver tissue inflammation factor levels between five groups of mouse were determined. The results showed that blood glucose, insulin, free fatty acids (FFAs), triglycerides, and inflammatory factor average FGF-21 of type 2 diabetes model group and normal control group were significantly higher (P < 0.01), while compared with insulin group, no difference was significant. Average blood glucose, insulin, blood lipid and inflammatory factor of FGF-21 treatment group compared with type 2 diabetes group was significantly lower (P < 0.01) and insulin group has no difference with the model control group. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF-21 significantly remits type 2 diabetic mice model's insulin resistance state and participates in the regulation of inflammatory factor levels and type 2 diabetes metabolic disorders.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/farmacologia , Resistência à Insulina , Animais , Glicemia , Dieta Hiperlipídica , Ácidos Graxos não Esterificados/sangue , Insulina/sangue , Camundongos , Estreptozocina , Triglicerídeos/sangue
20.
Ying Yong Sheng Tai Xue Bao ; 25(8): 2385-9, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25509093

RESUMO

To explore the alleviation effect of silicon on wheat growth under copper stress, cultivar Aikang 58 was chosen as the experimental material. The growth, root activities and root tip ultrastructures of wheat seedlings, which were cultured in Hoagland nutrient solution with five different treatments (control, 15 mg x L(-1) Cu2+, 30 mg x L(-1) Cu2+, 15 mg x L(-1) Cu2+ and 50 mg x L(-1) silicon, 30 mg x L(-1) Cu2+ and 50 mg x L(-1) silicon), were fully analyzed. The results showed that root length, plant height and root activities of wheat seedlings were significantly restrained under the copper treatments compared with the control (P < 0.01), while these restraining effects were alleviated after adding silicon to copper-stress Hoagland nutrient solution. Under copper stress, the cell wall and cell membrane of wheat seedling root tips suffered to varying degrees of destruction, which caused the increase of intercellular space and the disappearance of some organelles. After adding silicon, the cell structure was maintained intact, although some cells and organelles were still slightly deformed compared with the control. In conclusion, exogenous silicon could alleviate the copper stress damages on wheat seedlings and cellular components to some extent.


Assuntos
Membrana Celular/ultraestrutura , Parede Celular/ultraestrutura , Cobre/química , Silício/química , Triticum/citologia , Raízes de Plantas/citologia , Plântula/citologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...