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1.
Front Cell Dev Biol ; 9: 733945, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746130

RESUMO

Disrupted myelin and impaired myelin repair have been observed in the brains of patients and various mouse models of Alzheimer's disease (AD). Clemastine, an H1-antihistamine, shows the capability to induce oligodendrocyte precursor cell (OPC) differentiation and myelin formation under different neuropathological conditions featuring demyelination via the antagonism of M1 muscarinic receptor. In this study, we investigated if aged APPSwe/PS1dE9 mice, a model of AD, can benefit from chronic clemastine treatment. We found the treatment reduced brain amyloid-beta deposition and rescued the short-term memory deficit of the mice. The densities of OPCs, oligodendrocytes, and myelin were enhanced upon the treatment, whereas the levels of degraded MBP were reduced, a marker for degenerated myelin. In addition, we also suggest the role of clemastine in preventing OPCs from entering the state of cellular senescence, which was shown recently as an essential causal factor in AD pathogenesis. Thus, clemastine exhibits therapeutic potential in AD via preventing senescence of OPCs.

2.
Glycoconj J ; 38(5): 573-583, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34515910

RESUMO

To explore effect of the structural properties of porphyra haitanensis polysaccharide on its biological activity, degraded porphyra polysaccharides were separated and purified by Cellulose DEAE-52 and Sephadex G-100 chromatography, obtaining three purified components (P1, P2 and P3). All the three components were sulfate polysaccharides containing the repeating units of → 3) ß-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →, and → 3) ß-D-galactose (1 → 4) α-L-galactose-6-S (1 →, and → 3) 6-O-methyl-ß-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →. The molecular weight of the three fractions was measured to be 300.3, 130.4 and 115.1 kDa, respectively. Their antioxidant activity was investigated by the determination of the free radical scavenging effect and ferric reducing power. It was found that P1, P2 and P3 possessed marked antioxidant activity. It was also found that they appreciably enhanced the proliferation, phagocytic ability and nitric oxide secretion in RAW264.7 cells. Lower molecular weight and higher sulfate content were beneficial to bioactivities of P. haitanensis polysaccharides. Overall, P2 and P3 possess superior immuno-modulatory activity to that of P1 and PHP. Thus, the current work will provide the basis for the better utilization of P. haitanensis to develop the related functional foods.

3.
Neural Regen Res ; 16(11): 2284-2292, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33818514

RESUMO

Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation, the passage of nutrients and oxygen, and the discharge of metabolites. In this study, a porous collagen scaffold with axially-aligned luminal conduits was prepared. In vitro biocompatibility analysis of the collagen scaffold revealed that it enhances the activity of neural stem cells and promotes cell extension, without affecting cell differentiation. The collagen scaffold loaded with neural stem cells improved the hindlimb motor function in the rat model of T8 complete transection and promoted nerve regeneration. The collagen scaffold was completely degraded in vivo within 5 weeks of implantation, exhibiting good biodegradability. Rectal temperature, C-reactive protein expression and CD68 staining demonstrated that rats with spinal cord injury that underwent implantation of the collagen scaffold had no notable inflammatory reaction. These findings suggest that this novel collagen scaffold is a good carrier for neural stem cell transplantation, thereby enhancing spinal cord repair following injury. This study was approved by the Animal Ethics Committee of Nanjing Drum Tower Hospital (the Affiliated Hospital of Nanjing University Medical School), China (approval No. 2019AE02005) on June 15, 2019.

4.
J Food Biochem ; 45(4): e13661, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33595138

RESUMO

The degraded polysaccharides from Porphyra yezoensis (DPPY) prepared using the H2 O2 -Vc method under optimized conditions were isolated and purified by DEAE Cellulose-52, and Sephadex G-100, providing four pure components, namely, DPPY-0, DPPY-0.1, DPPY-0.3, and DPPY-0.5. Their relative molecular weights were measured to be 10.8, 10.7, 18.7, and 35.5 kDa, respectively. GC-MS analysis revealed that all the four fractions were mainly composed of galactose, together with a small portion of glucose, mannose, xylose, and rhamnose. Structural analysis revealed that the purified polysaccharides mainly possess a backbone of (1 â†’ 3)-ß-D-galactose (1 â†’ 4)-3,6-anhydro-α-L-galactopyranose (G-A) units and (1 â†’ 3)-ß-D-galactose (1 â†’ 4)-α-L-galactose-6-sulfate (G-L6S) units. They were found to promote the proliferation of RAW264.7 macrophages and enhance phagocytosis of the RAW264.7 cells. Antioxidant assays indicated that DPPY-0.5 possessed the most potent reducing power and free radical scavenging ability among the four purified polysaccharides. High sulfate content and proper molecular weight of these fractions are favorable to their immunomodulatory and antioxidant activities. PRACTICAL APPLICATIONS: Porphyra yezoensis, common economic red algae widely distributed in East Asian countries, contains a high content of polysaccharides with a variety of biological activities. However, P. yezoensis polysaccharide (PPY) has not been well utilized due to the relatively low biological activities and lack of understanding of its structure-activity relationship. Thus, it is necessary to improve the bioactivities and elucidate the structure-activity relationship of this polysaccharide for its practical use. In the present work, four purified fractions (DPPY-0, DPPY-0.1, DPPY-0.3, and DPPY-0.5) were isolated from the degraded P. yezoensis polysaccharide, and were investigated for their antioxidant and immunoregulatory activities. The results of the present work will lay a foundation for the application of the degraded P. yezoensis polysaccharide in the food industry as a functional food ingredient.


Assuntos
Porphyra , Animais , Antioxidantes/farmacologia , Camundongos , Peso Molecular , Polissacarídeos/farmacologia , Células RAW 264.7
5.
Neural Regen Res ; 16(2): 382-387, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32859802

RESUMO

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury. This study aimed to decipher the dynamics of systemic immune responses, initiated by spinal cord injury. The spinal cord in mice was completely transected at T8. Changes in the in vivo inflammatory response, between the acute and subacute stages, were observed. A rapid decrease in C-reactive protein levels, circulating leukocytes and lymphocytes, spleen-derived CD4+ interferon-γ+ T-helper cells, and inflammatory cytokines, and a marked increase in neutrophils, monocytes, and CD4+CD25+FOXP3+ regulatory T-cells were observed during the acute phase. These systemic immune alterations were gradually restored to basal levels during the sub-acute phase. During the acute phase of spinal cord injury, systemic immune cells and factors showed significant inhibition; however, this inhibition was transient, and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase. All experiments were performed in accordance with the institutional animal care guidelines, approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital, China (approval No. 2019AE01040) on June 25, 2019.

6.
J Enzyme Inhib Med Chem ; 35(1): 1562-1567, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32746652

RESUMO

In an attempt to synthesise new tyrosinase inhibitors, we designed and synthesised a series of chalcone-hydroxypyridinone hybrids as potential tyrosinase inhibitors adopting strategic modifications of kojic acid. All the newly synthesised compounds were characterised by NMR and mass spectrometry. Initial screening of the target compounds demonstrated that compounds 1a, 1d, and 1n had relatively strong inhibitory activities against tyrosinase monophenolase, with IC50 values of 3.07 ± 0.85, 2.25 ± 0.8 and 2.75 ± 1.19 µM, respectively. The inhibitory activity against monophenolase was 6- to 8-fold higher than that of kojic acid. Compounds 1a, 1d, and 1n also showed inhibition of diphenolase, with IC50 values of 17.05 ± 0.07, 11.70 ± 0.03 and 19.3 ± 0.28 µM, respectively. The inhibition kinetics of diphenolase indicates that compounds 1a and 1d induce reversible inhibition on tyrosinase. Finally, we found that copper coordination should be one of the important inhibitory mechanism of these compounds in tyrosinase.


Assuntos
Chalcona/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Piridonas/farmacologia , Chalcona/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Piridonas/química , Relação Estrutura-Atividade
7.
Zhongguo Zhong Yao Za Zhi ; 45(9): 2186-2192, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32495570

RESUMO

Proton nuclear magnetic resonance(~1H-NMR) is used to investigate the effect of Renshenjian Decoction on serum and urine metabolism of type 2 diabetic rats with insulin resistance induced by high-sugar and high-fat diet combined with low-dose streptozotocin(STZ). After the successful establishment of the insulin resistance model of type 2 diabetes, administration for 35 days, the serum and urine of rats were taken. Once the ~1H-NMR data have been collected and processed, PCA and OPLS-DA were used to analyze them. The results show that: compared with the blank group, the contents of methionine, taurine, α-glucose and ß-glucose in the serum of the model group increased significantly(P<0.001), while the contents of 3-hydroxybutyric acid, lactic acid and unsaturated fatty acids decreased significantly(P<0.01). In the model group, the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose, taurine and phosphocholine in urine increased significantly(P<0.05), while the contents of creatine, lactic acid, acetic acid and citric acid decreased significantly(P<0.05). Compared with the model group, the contents of 3-hydroxybutyric acid and unsaturated fatty acids in serum of rats in the treatment group increased significantly(P<0.05), while the contents of taurine, α-glucose and ß-glucose decreased significantly(P<0.01). In the treatment group, the contents of lactic acid, taurine and creatine in urine increased significantly(P<0.05), while the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose and phosphocholine decreased significantly(P<0.01). The results show that Renshenjian Decoction can regulate metabolic disorder and promote the metabolic phenotype to return to the normal range. It displayed therapeutic effect on type 2 diabetic rats with insulin resistance and provided a certain scientific basis for the biological basic research of Renshenjian Decoction by improving insulin resistance in diabetes mellitus.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Glicemia , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ratos Sprague-Dawley
8.
Food Chem ; 322: 126774, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32305876

RESUMO

To explore the potential application of enzymatic degraded polysaccharides from Enteromorpha prolifra (EEP) as antioxidant in fish oils, a stable fish oil emulsion system incorporating EEP was established. Effects of emulsifier (Tween 80, gum arabic and lecithin) and EEP concentration on the physical characteristics of fish oil emulsions were investigated. The results indicated that Tween 80 was the best choice, and 1% (w/w) of EEP was the optimum concentration for the preparation of fish oil emulsions. Influence of EEP on the oxidative stability and physical stability of fish oil emulsions was compared with that of antioxidants VE and TBHQ by determining the physical properties, lipid hydroperoxide formation, secondary reaction products formation, pH and long chain polyunsaturated fatty acid content, during storage at 45 °C. The results indicated that the fish oil emulsion system (5% oil, 1% EEP and 1% Tween 80, w/w) possessed good physical and oxidative stabilities.


Assuntos
Emulsificantes/química , Emulsões/química , Óleos de Peixe/química , Polissacarídeos/química , Ulva/química , Antioxidantes/química , Goma Arábica/química , Lecitinas/química , Oxirredução , Polissorbatos/química , Reologia , Água/química
9.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3187-3194, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602871

RESUMO

Ethnomedicine is the precious wealth left by ethnic minorities in their struggle against diseases. It is similar to traditional Chinese medicine in a narrow sense and has the characteristics of multi-component,multi-target and multi-channel synergy. Under the guidance of the theory of ethnomedicine,the combination of ethnomedicine and network pharmacology will help to understand the essence of the prevention and treatment of ethnomedicines in a dynamic and holistic manner. This paper reviews the research progress of network pharmacology applied in ethnomedicine,analyses the problems and challenges existing in the application of network pharmacology in ethnomedicine research at present,such as inaccurate data and information,lack of network analysis platform for effective analysis of dose-effect relationship of chemical constituents and weak basic research of ethnomedicine,and puts forward corresponding prospects.


Assuntos
Etnofarmacologia , Medicina Tradicional , Medicina Tradicional Chinesa
10.
Cell Commun Signal ; 17(1): 72, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288844

RESUMO

BACKGROUND: Chronic gastritis has been demonstrated to be a key cause of gastric cancer (GC), and control of gastric inflammation is regarded as an effective treatment for the clinical prevention of gastric carcinogenesis. However, there remains an unmet need to identify the dominant regulators of gastric oncogenesis-associated inflammation in vivo. METHODS: The mouse model for the study of inflammation-associated GC was induced by Benzo[a]pyrene (BaP) intragastric administration in Bcl6b-/- and wildtype mice on a C57BL/6 background. 5-Aza-2'-deoxycytidine (5-Aza), the demethylation drug, was intraperitoneally injected to restore Bcl6b expression. Human GC tissue array was used to analyse patient survival based on BCL6B and CD3 protein expression. RESULTS: Bcl6b was gradually downregulated by its own promoter hypermethylation in parallel to an increasing inflammatory response during the progression of BaP-induced gastric carcinogenesis in mice. Moreover, knockout of Bcl6b dramatically worsened the severity of gastric cancer and aggravated the inflammatory response in the BaP-induced mice GC model. Re-activation of Bcl6b by 5-Aza impeded inflammatory amplification and BaP-induced GC development, prolonging survival time in wildtype mice, whereas no notable curative effect occurred in Bcl6b-/- mice with 5-Aza treatment. Finally, significant negative correlations were detected between the mRNA levels of BCL6B and inflammatory cytokines in human GC tissues; patients harbouring BCL6B-negetive and severe-inflammation GC tumours were found to exhibit the shortest survival time. CONCLUSIONS: Epigenetic inactivation of Bcl6b promotes gastric cancer through amplification of the gastric inflammatory response in vivo and offers a new approach for GC treatment and regenerative medicine.


Assuntos
Carcinogênese/genética , Técnicas de Inativação de Genes , Proteínas Repressoras/deficiência , Proteínas Repressoras/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Carcinogênese/efeitos dos fármacos , Decitabina/farmacologia , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Epigênese Genética , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Gástricas/metabolismo , Análise de Sobrevida
11.
Neural Regen Res ; 14(8): 1352-1363, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30964053

RESUMO

Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials can fill cavities, deliver curative drugs, and provide adsorption sites for transplanted or host cells. Some regenerative biomaterials can also inhibit apoptosis, inflammation and glial scar formation, or further promote neurogenesis, axonal growth and angiogenesis. This review summarized a variety of biomaterial scaffolds made of natural, synthetic, and combined materials applied to spinal cord injury repair. Although these biomaterial scaffolds have shown a certain therapeutic effect in spinal cord injury repair, there are still many problems to be resolved, such as product standards and material safety and effectiveness.

12.
Ying Yong Sheng Tai Xue Bao ; 30(4): 1295-1302, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30994291

RESUMO

A field experiment was conducted to examine the effects of controlled-release urea (CRU) application on ammonia (NH3) volatilization, nitrogen (N) use efficiency and fresh ear yield of fresh edible maize. The treatments included one control (CK: no N fertilizer application) and four different band fertilization depths (0, 5, 10, 15 and 20 cm). Results showed that NH3 volatilization from non-fertilization band and planting band mainly occurred in the first two weeks after the fertilization, which lasted for almost a month in the fertilization band. Compared to CK, surface broadcasted CRU (0 cm) significantly increased NH3 volatilization from wide-row non-fertilization band or planting band in field. Soil NH3 volatilization amounts ranged from 3.1 to 25.5 kg N·hm-2 with the different depths of CRU application treatments, accounting for 1.7%-14.2% of total N applied. The cumulative NH3 volatilizations were comparable among the depths of 10, 15 and 20 cm of CRU fertilization treatments, which were significantly decreased by 85.9%-87.8% and 67.0%-71.6% as compared with surface broadcasted CRU and 5 cm of CRU fertilization, respectively. The increases of CRU application depth within a certain extent could increase fresh ear yield, total nitrogen accumulation of plants during milking stage, partial factor productivity, agronomic efficiency and apparent recovery efficiency of nitrogenous fertilizer, and the maximum values of these indices were recorded for 15 cm depth. We concluded that CRU application at 15 cm depth would be the optimal practice in terms of reducing NH3 volatilization and improving N use efficiency of fresh edible maize.


Assuntos
Agricultura/métodos , Amônia/análise , Fertilizantes , Nitrogênio , Preparações de Ação Retardada , Solo , Ureia , Volatilização , Zea mays/crescimento & desenvolvimento
13.
Eur J Pharmacol ; 844: 165-174, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30550742

RESUMO

Previous research showed N1-(quinolin-2-ylmethy) butane-1, 4-diamine (QMA), a polyamine analogue, was efficacious in the prevention of oxidative injury in models of cerebral ischemia. The present study manifested that pretreatment with QMA attenuated ischemic damage accompanying up regulation of Nuclear factor erythroid 2­related factor (Nrf2), Heme oxygenase­1 (HO­1), p-ERK and p-Akt in cerebral cortex tissues of middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation (OGD)-treated PC12 cells. Further more, treatment with LY294002 (specific PI3K inhibitor), PD98059 (specific ERK inhibitor), brusatol (specific Nrf2 inhibitor) and SnPP (specific HO-1 inhibitor) deprived almost all the effects of QMA in MCAO rats and OGD-treated PC12 cells. These data suggested that the protective actions of QMA on the cerebral ischemia may be related to activation of endogenous cytoprotective mechanism via ERK and Akt activated Nrf2/HO-1 signaling pathway.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Poliaminas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinolinas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Células PC12 , Poliaminas/farmacologia , Quinolinas/farmacologia , Ratos , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Diabetes ; 67(12): 2569-2584, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30279163

RESUMO

Wnt/ß-catenin signaling plays a key role in regulating adipogenesis through indirectly inhibiting the expression of C/EBPα and peroxisome proliferator-activated receptor γ (PPARγ); however, the detailed molecular mechanism remains poorly understood. Moreover, the factor(s) that determines the Wnt/ß-catenin output level during adipogenesis is also not completely defined. In this study, we showed that Pygo2 exhibited a declined expression pattern during adipocyte differentiation, resulting in an attenuated Wnt/ß-catenin output level. The mechanism study indicated that Pygo2 inhibition led to the downregulation of Axin2, a constitutive Wnt target, in the cytoplasm. Consequently, Axin2-bound GSK3ß was released and translocated into the nucleus to phosphorylate C/EBPß and Snail, resulting in an increase in the DNA binding activity of C/EBPß and decreased protein stability of Snail, which subsequently activated the expression of C/EBPα and PPARγ. Consistent with this, embryonic fibroblasts from Pygo2-/- mice exhibited spontaneous adipocyte differentiation, and adipocyte precursor-specific Pygo2-deficient mice exhibited increased adiposity with decreased energy expenditure. We further showed impaired glucose tolerance and decreased systemic insulin sensitivity in Pygo2-deficient mice. Our study revealed an association between Pygo2 function and obesity or diabetes.


Assuntos
Adiposidade/genética , Glicemia/metabolismo , Homeostase/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Via de Sinalização Wnt/fisiologia , Adipócitos/metabolismo , Adipogenia/genética , Tecido Adiposo Branco/metabolismo , Animais , Proteína Axina/metabolismo , Composição Corporal/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Knockout , beta Catenina/metabolismo
15.
Curr Med Sci ; 38(2): 236-244, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30074181

RESUMO

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect. Nevertheless, the mechanism is not completely identified. This study was conducted to investigate the effects of melatonin on TGF-ß1/Smad signaling pathway in liver fibrosis in rats. The liver fibrosis model was made by the subcutaneous injection of CCl4. The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer. Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry. Expression levels of TGF-ß1, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis. Results showed that melatonin suppressed CCl4-induced liver fibrosis, along with an improvement in histological changes, significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver. Melatonin improved liver function indicated by decreased serum ALT and AST activities. In addition, melatonin exerted its anti-oxidant effects, as supported by decreased MDA levels and increased GPx activities in liver. Furthermore, melatonin inhibited TGF-ß1/Smad pathway, as evidenced by decreased TGF-ß1, Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver. In conclusion, melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-ß1/Smad pathway. It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.


Assuntos
Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Melatonina/uso terapêutico , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/metabolismo , Tetracloreto de Carbono , Hidroxiprolina/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Malondialdeído/metabolismo , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Extratos de Tecidos
16.
Int J Biol Macromol ; 118(Pt B): 1550-1557, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29981327

RESUMO

In order to improve the bioactivity of the polysaccharide from Sargassum fusiforme (PSF), the degraded polysaccharide (DPSF) was modified by carboxymethylation, yielding carboxymethylated degraded polysaccharides (CDPSF), which were further modified to generate hydroxamated derivatives (HCDPSF). Both CDPSF and HCDPSF were characterized by Fourier transform infrared spectroscopy. The molecular weight of CDPSF and HCDPSF was found to be 354 kDa and 375 kDa, respectively. The in vitro antioxidant activity of CDPSF and HCDPSF was evaluated by determining the radical scavenging ability and total antioxidant activity. The results indicated that the antioxidant activity of CDPSF and HCDPSF was significantly improved when compared to those of DPSF. Antimicrobial assays indicated that both CDPSF and HCDPSF possessed a marked antimicrobial ability, while DPSF did not exhibit such effects under the same conditions. Such polysaccharide derivatives have potentials in the pharmaceutical and food industries.


Assuntos
Ácidos Hidroxâmicos/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Sargassum/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Radicais Livres/química , Metilação , Testes de Sensibilidade Microbiana , Peso Molecular
17.
Bioorg Med Chem Lett ; 28(14): 2504-2512, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29886020

RESUMO

Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron(III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric chelators were synthesized using a convergent strategy. Their iron chelating ability was demonstrated by UV/Visible spectrometry and high resolution mass spectrometry (HRMS). The iron binding affinities were also investigated by the competition with a fluorescent iron chelator CP691. The result indicated that these dendrimers possesses a high affinity for iron with a very high pFe3+ value, which is close to that of an isolated hexadentate unit. These dendrimeric chelators were found to exhibit inhibitory effect on the growth of both Gram-positive and Gram-negative bacteria.


Assuntos
Antibacterianos/farmacologia , Dendrímeros/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Quelantes de Ferro/farmacologia , Piridonas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Dendrímeros/síntese química , Dendrímeros/química , Relação Dose-Resposta a Droga , Quelantes de Ferro/síntese química , Quelantes de Ferro/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piridonas/síntese química , Piridonas/química , Relação Estrutura-Atividade
18.
Oncotarget ; 8(24): 39401-39416, 2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28455959

RESUMO

Great progress has been achieved in the study of the role of TGF-ß signaling in triggering epithelial-mesenchymal transition (EMT) in a variety of cancers; however, the regulation of TGF-ß signaling during EMT in mammary tumor metastasis has not been completely defined. In the present study, we demonstrated that OVOL2, a zinc finger transcription factor, inhibits TGF-ß signaling-induced EMT in mouse and human mammary tumor cells, as well as in mouse tumor models. Data from the Oncomine databases indicated a strong negative relationship between OVOL2 expression and breast cancer progression. Moreover, our experiments revealed that OVOL2 inhibits TGF-ß signaling at multiple levels, including inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the binding between Smad4 and target DNA, and interfering with complex formation between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls the TGF-ß signaling output level in vitro and in vivo. The modulation of these molecular processes may represent a strategy for inhibiting breast cancer invasion by restoring OVOL2 expression.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal , Transdução de Sinais , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Biomarcadores , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Camundongos , Metástase Neoplásica , Prognóstico , Ligação Proteica , Proteína Smad4/genética , Proteína Smad4/metabolismo , Proteína Smad7/genética , Proteína Smad7/metabolismo , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
19.
Hepatology ; 65(4): 1206-1221, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27809333

RESUMO

Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between Yes-associated protein/TEA domain family member (YAP-TEAD) and hepatocyte nuclear factor 4-alpha (HNF4α) in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells by a ubiquitin proteasome pathway. By contrast, HNF4α was found to directly associate with TEAD4 to compete with YAP1 for binding to TEAD4, thus inhibiting the transcriptional activity of YAP-TEAD and expression of their target genes. Moreover, overexpression of HNF4α was found to significantly compromise YAP-TEAD-induced HCC cell proliferation and stem cell expansion. Finally, we documented the regulatory mechanism between YAP-TEAD and HNF4α in rat and mouse tumor models, which confirmed our in vitro results. CONCLUSION: There is a double-negative feedback mechanism that controls TEAD-YAP and HNF4α expression in vitro and in vivo, thereby regulating cellular proliferation and differentiation. Given that YAP acts as a dominant oncogene in HCC and plays a crucial role in stem cell homeostasis and tissue regeneration, manipulating the interaction between YAP, TEADs, and HNF4α may provide a new approach for HCC treatment and regenerative medicine. (Hepatology 2017;65:1206-1221).


Assuntos
Carcinoma Hepatocelular/genética , Fator 4 Nuclear de Hepatócito/genética , Neoplasias Hepáticas/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Biópsia por Agulha , Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfoproteínas/genética , Distribuição Aleatória , Ratos , Ratos Wistar , Sensibilidade e Especificidade , Transdução de Sinais , Fatores de Transcrição/genética
20.
Tissue Eng Part C Methods ; 23(2): 61-71, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27981878

RESUMO

Women younger than 40 years may face early menopause because of premature ovarian failure (POF). The cause of POF can be idiopathic or iatrogenic, especially the cancer-induced oophorectomy and chemo- or radiation therapy. The current treatments, including hormone replacement therapy (HRT) and cryopreservation techniques, have increased risk of ovarian cancer and may reintroduce malignant cells after autografting. Decellularization technique has been regarded as a novel regenerative medicine strategy for organ replacement, wherein the living cells of an organ are removed, leaving the extracellular matrix (ECM) for cellular seeding. This study aimed to produce a xenogeneic decellularized ovary (D-ovary) scaffold as a platform for ovary regeneration and transplantation. We have developed a novel decellularization protocol for porcine ovary by treatment with physical, chemical, and enzymatic methods. Using hematoxylin and eosin (H&E) staining, DAPI staining, scanning electron microscopy (SEM), and quantitative analysis, this approach proved effective in removing cellular components and preserving ECM. Furthermore, the results of biological safety evaluation demonstrated that the D-ovary tissues were noncytotoxic for rat ovarian cells in vitro and caused only a minimal immunogenic response in vivo. In addition, the D-ovary tissues successfully supported rat granulosa cell penetration ex vivo and showed an improvement in estradiol (E2) hormone secretion.


Assuntos
Matriz Extracelular/metabolismo , Ovário/citologia , Regeneração/fisiologia , Engenharia Tecidual/métodos , Tecidos Suporte , Animais , Sobrevivência Celular , Células Cultivadas , Estradiol/metabolismo , Feminino , Ratos , Medicina Regenerativa , Suínos
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