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1.
J Sci Food Agric ; 103(13): 6394-6405, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37205788

RESUMEN

BACKGROUND: The present study investigates the physical, chemical, and antibacterial properties of water-soluble chitosan derivatives. Preparation of the water-soluble chitosan derivatives was performed by the Maillard reaction (MR) between chitosan [with the degree of deacetylation (DD) being 50%, 70%, and 90%] and mannose. No organic reagent was used in the process. Systematic evaluations of the effects of chitosan DD on the reaction extent, the structure, the composition, as well as the physicochemical properties, antioxidant properties, and bacterial inhibitory properties of the finished chitosan-mannose MR products (Mc-mrps), were carried out. RESULTS: Based on the experimental data obtained from Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, Pyrolysis-gas chromatography-mass spectrometry analysis, and 1 H-NMR, the Mc-mrps formed from chitosan with different DDs had different structures and components. An increase in the DD of chitosan led to a significant increase in the degree of reaction, color difference (△E), and solubility (P < 0.05). The zeta potential and particle size of the Mc-mrps were also influenced by the DD of chitosan. Additionally, the antimicrobial action against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Salmonella typhimurium), as well as antioxidant activity, were enhanced by the incorporation of mannose. This was also achieved by the increase of the DD of chitosan. CONCLUSION: The results of the present study suggest that chitosan was derived with mannose to yield a novel, water-soluble polysaccharide with better antioxidant and antimicrobial activities. The DD of chitosan had a significant effect on the properties of the Mc-mrp, which can serve as a reference point for the subsequent preparation and application of such derivatives. © 2023 Society of Chemical Industry.


Asunto(s)
Quitosano , Quitosano/farmacología , Quitosano/química , Antioxidantes/farmacología , Antioxidantes/química , Manosa , Antibacterianos/farmacología , Antibacterianos/química , Agua/química , Espectroscopía Infrarroja por Transformada de Fourier
2.
Prostaglandins Other Lipid Mediat ; 163: 106668, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35934213

RESUMEN

Glucocorticoid-induced leucine zipper (GILZ) is a glucocorticoid-responsive protein and is thought to mediate part of the anti-inflammatory effects of glucocorticoid receptors (GRs). Its role in inflammation and immune responses has been widely studied since its discovery in 1997. Recently, increasing studies showed that GILZ might be involved in the differentiation of preadipocytes and adipogenesis. This review aims to provide readers with the latest updates on the biology of GILZ. The role and regulatory mechanism of GILZ in lipid metabolism and preadipocytes differentiation were summarized. In addition, new insights on the regulatory mechanism of GILZ in adipocyte browning was also discussed, which proposes a novel therapeutic target for lipid metabolic disorders in the future. However, research related to the function and regulatory mechanisms of GILZ in lipid metabolism and adipocyte biology is still in its infancy, and there is still much work needs to be done.


Asunto(s)
Glucocorticoides , Factores de Transcripción , Glucocorticoides/metabolismo , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Factores de Transcripción/metabolismo , Metabolismo de los Lípidos , Adipocitos/metabolismo , Biología
3.
Biochem Cell Biol ; 97(4): 397-405, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30475643

RESUMEN

Shikonin, a naphthoquinone derivative isolated from the root of Lithospermum erythrorhizon, exhibits broad-spectrum antitumor activity via different molecular mechanisms. In this study, we investigated the effect of shikonin on mitochondrial dysfunction in hepatocellular carcinoma (HCC). Our results showed that shikonin inhibited the proliferation, migration, and invasiveness of HCCLM3 cells, and promoted cell apoptosis in a dose-dependent manner. More importantly, shikonin affected mitochondrial function by disrupting mitochondrial membrane potential and oxidative stress (OS) status. Furthermore, shikonin decreased the oxygen consumption rate of HCCLM3 cells, as well as the levels of ATP and metabolites involved in the tricarboxylic acid cycle (TCA cycle). We also investigated the molecular mechanisms underlying the regulation of mitochondrial function by shikonin as an inhibitor of PKM2. Shikonin decreased the expression of PKM2 in the mitochondria and affected other metabolic pathways (AMPK and PGC1α pathways), which aggravated the oxidative stress and nutrient deficiency. Our results indicate a novel role of shikonin in triggering mitochondria dysfunction via the PKM2-AMPK-PGC1α signaling pathway and provide a promising therapeutic approach for the treatment of HCC.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Naftoquinonas/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/metabolismo , Antineoplásicos Fitogénicos/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Mitocondrias/metabolismo , Estructura Molecular , Naftoquinonas/química , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/antagonistas & inhibidores , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Relación Estructura-Actividad , Hormonas Tiroideas/metabolismo , Proteínas de Unión a Hormona Tiroide
4.
Biochem Biophys Res Commun ; 462(4): 288-93, 2015 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-25935488

RESUMEN

TNF-α is a dominant inflammatory mediator in the pathogenesis of inflammatory diseases including rheumatoid arthritis. In our research, we discovered 2-chloro-N-(4-(2-morpholinoethoxy)phenyl)quinazolin-4-amine (9c) exhibited an outstanding anti-inflammatory activity on inhibiting TNF-α production with an IC50 of 8.86 µM in RAW264.7 cells. Interestingly, 9c had no effect on mRNA level of TNF-α but up-regulated the precursor of TNF-α (pro-TNF-α). Then, we studied TNF-α converting enzyme (TACE), which is the most important proteases responsible for the release of TNF-α from pro-TNF-α to soluble TNF-α. The results showed 9c reduced TACE both on the levels of mRNA and protein in a dose-dependent manner. In vivo study, collagen-induced arthritis (CIA) mice were treated by 9c orally. 9c exhibited significant anti-arthritis effect by ameliorating arthritic score, reducing inflammatory cell infiltration, protecting joints from destruction and decreasing the production of systemic TNF-α, IL-6, IL-1ß. The underlying mechanism of 9c on CIA was coincided with the in vitro, which was mediated by TACE. In conclusion, we discovered a novel quinazoline derivative which ameliorates arthritis through inhibiting production of TNF-α mediated by TACE for the first time.


Asunto(s)
Proteínas ADAM/metabolismo , Artritis Experimental/tratamiento farmacológico , Colágeno/administración & dosificación , Quinazolinas/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Proteína ADAM17 , Animales , Línea Celular , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Masculino , Ratones , Ratones Endogámicos DBA , Quinazolinas/farmacología , ARN Mensajero/genética , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genética
5.
J Pharmacol Sci ; 128(3): 116-24, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26220468

RESUMEN

Honokiol (HK), a biphenolic neolignan isolated from Magnolia officinalis, has been reported to possess anti-inflammatory and anti-angiogenic activaties. In this study, our aim was to investigate anti-psoriatic activities of HK and the involved mechanisms. In vitro, the effects of HK on the regulation of Th1/Th2 and TNF-α-induced NF-κB (p65) activation were analyzed by respective FCS and immunofluorescence. Additionally, the K14-VEGF transgenic model was used for the in vivo study. ELISA and Q-PCR were performed to evaluate serum levels of Th1/Th2 cytokines and their corresponding mRNA expressions. Effects on VEGFR-2 and p65 activation, as well as other angiogenic and inflammatory parameters were studied by immunostainings. Importantly, we found that HK significantly decreased the ratio of Th1/Th2-expression CD4(+) T cells and inhibited TNF-α-induced activation of NF-κB. The morphology and histological features of psoriasis were effectively improved by HK treatment. The expression of TNF-α and IFN-γ, and their corresponding mRNA levels were down-regulated and the expression of nuclear p65, VEGFR-2, as well as related phosphorylated proteins (p-VEGFR-2, p-ERK1/2, p-AKT and p-p38) were also suppressed. Overall, these results in our study suggested that HK exhibits anti-psoriatic effects through the inhibition of NF-κB and VEGFR-2.


Asunto(s)
Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/uso terapéutico , Lignanos/farmacología , Lignanos/uso terapéutico , Terapia Molecular Dirigida , FN-kappa B/antagonistas & inhibidores , Fitoterapia , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis , Animales , Antiinflamatorios , Compuestos de Bifenilo/aislamiento & purificación , Linfocitos T CD4-Positivos , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Células Endoteliales de la Vena Umbilical Humana , Humanos , Lignanos/aislamiento & purificación , Magnolia , Ratones Transgénicos , FN-kappa B/genética , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Psoriasis/patología , Balance Th1 - Th2/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
6.
Mol Divers ; 19(2): 333-46, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25672287

RESUMEN

Diabetes mellitus, commonly characterized by hyperglycemia, is a group of metabolic diseases. Some oral anti-diabetic drugs show poor tolerability during chronic treatment, and associate with undesired side effects. Recent advances in the understanding of physiological functions of incretins and their degrading enzyme dipeptidyl peptidase DPP-IV have led to the discovery of DPP-IV inhibitors as a new class of oral anti-diabetic drugs. Several DPP-IV inhibitors have different chemical structures of which the xanthine scaffold has specific advantages. Combining previous work with the research strategy of pharmacophore hybridization, we retained this scaffold and synthesized a new series of amino-alcohol or diamino-modified xanthine compounds. Some xanthines exhibited submicromolar inhibitory activities against DPP-IV. The most potent compound 40 [Formula: see text] exhibits a good in vivo efficacy in reducing glucose excursion at a single dose and a better chronic effect in reducing body weight than metformin in DIO mice. In other words, the combined effect improved the pathological state of DIO mice.


Asunto(s)
Dipeptidil Peptidasa 4/química , Inhibidores de la Dipeptidil-Peptidasa IV/química , Diseño de Fármacos , Glucosa/metabolismo , Homeostasis , Xantina/química , Animales , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Homeostasis/efectos de los fármacos , Ratones , Factores de Tiempo , Xantina/farmacología
7.
Chem Pharm Bull (Tokyo) ; 62(9): 883-91, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25177017

RESUMEN

Triglycerides are the main part of fats and half of the lipids in hepatocytes, and play an important role in metabolism as energy sources and transporters of dietary fat. In this study, 33 derivatives based on 3-methyl-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione were synthesized and evaluated for their lipid-lowering activity. Among them, compound 1i was found to exhibit potent triglyceride-lowering potency in 3T3-L1 adipocytes which was comparable to that of the adenosine monophosphate-activated protein kinase (AMPK) agonist Acadesine (AIACR). Furthermore, oral administration of 1i at a dose of 50 mg kg(-1) d(-1) for 5 weeks could reduce the mean body weight and liver weight by 12.02% and 32.00%, respectively, and regulated serum levels of triglycerides in diet-induced obese mice. The results indicate that compound 1i is a potential small-molecule for the treatment of diet-induced obesity and related diseases.


Asunto(s)
Obesidad/tratamiento farmacológico , Hipernutrición , Pirimidinonas/uso terapéutico , Células 3T3-L1 , Animales , Cromatografía Líquida de Alta Presión , Humanos , Ratones , Obesidad/etiología , Espectroscopía de Protones por Resonancia Magnética , Pirimidinonas/síntesis química , Espectrometría de Masa por Ionización de Electrospray
8.
Molecules ; 19(9): 14687-98, 2014 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-25230123

RESUMEN

Mai Tong Fang (MTF), a Chinese herbal combination, has been used for the treatment of diabetic nephropathy in traditional medical clinics in China. However, the anti-adipogenic and anti-hyperglycemic effects of MTF have not been fully elucidated, so this study explored these pharmacological activities in 3T3-L1 adipocytes and ob/ob mice, respectively, of the water fraction of milkvetch root, salviae miltiorrhizae and mulberry as key components of MTF. MTF was found to inhibit adipogenesis and triglyceride accumulation in 3T3-L1 adipocytes. Oral administration of MTF in ob/ob mice for 8 weeks, exhibited positive controls on blood glucose and body weight, and further improved glucose tolerance according to an oral glucose tolerance test. Importantly, MTF extract alleviated fat deposition and ballooning degeneration in liver tissue and blocked the increase of adipocyte size in adipose tissue from treated ob/ob mice. These results indicated that the extract of key components in the traditional Chinese prescription MTF continue a potent anti-adipogenic and glucose-lowering agent.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Obesidad/tratamiento farmacológico , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Animales , Glucemia , China , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Medicamentos Herbarios Chinos/química , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Medicina Tradicional China , Ratones , Obesidad/metabolismo
9.
Membranes (Basel) ; 14(3)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38535276

RESUMEN

Ceramic membranes are applied to remove non-sugar impurities, including proteins, colloids and starch, from glucose-fructose syrup that is dissolved from raw sugar using acid. The performance of ceramic membranes with 0.05 µm pores in clarifying high-fructose syrup was investigated under various operating conditions. The flux decreased rapidly at the start of the experiment and then tended to stabilize at a temperature of 90 °C, a transmembrane pressure of 2.5 bar, and cross-flow velocity of 5 m/s under total reflux operation. Moreover, the steady-state flux was measured at 181.65 Lm-2 h-1, and the turbidity of glucose-fructose syrup was reduced from 92.15 NTU to 0.70 NTU. Although membrane fouling is inevitable, it can be effectively controlled by developing a practical approach to regenerating membranes. Mathematical model predictions, scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy revealed that foulants primarily responsible for fouling are composed of polysaccharides, proteins, sucrose, phenols, and some metal elements, such as calcium, aluminum, and potassium. Due to the removal of suspended colloidal solids, the membrane-filtered glucose-fructose syrup was decolorized using activated carbon; the filtration rate was effectively improved. A linear relationship between volume increase in syrup and time was observed. A decolorization rate of 90% can be obtained by adding 0.6 (w/w) % of activated carbon. The pretreatment of glucose-fructose syrup using a ceramic membrane coupled with activated carbon results in low turbidity and color value. This information is essential for advancing glucose-fructose syrup and crystalline fructose production technology.

10.
Int J Radiat Oncol Biol Phys ; 118(1): 203-217, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37610394

RESUMEN

PURPOSE: Radiation-induced heart fibrosis (RIHF) is a severe consequence of radiation-induced heart damage (RIHD) leading to impaired cardiac function. The involvement of oncostatin M (OSM) and its receptor (OSMR) in RIHD remains unclear. This study aimed to investigate the specific mechanism of OSM/OSMR in RIHF/RIHD. METHODS AND MATERIALS: RNA sequencing was performed on heart tissues from a RIHD mouse model. OSM levels were assessed in serum samples obtained from patients receiving thoracic radiation therapy (RT), as well as in RIHF mouse heart tissues and serum using enzyme-linked immunosorbent assay. Fiber activation was evaluated through costimulation of primary cardiac fibroblasts and NIH3T3 cells with RT and OSM, using Western blotting, immunofluorescence, and quantitative Polymerase Chain Reaction (qPCR). Adeno-associated virus serotype 9-mediated overexpression or silencing of OSM specifically in the heart was performed in vivo to assess cardiac fibrosis levels by transthoracic echocardiography and pathologic examination. The regulatory mechanism of OSM on the transcription level of SMAD4 was further explored in vitro using mass spectrometric analysis, chromatin immunoprecipitation-qPCR, and DNA pull-down. RESULTS: OSM levels were elevated in the serum of patients after thoracic RT as well as in RIHF mouse cardiac endothelial cells and mouse serum. The OSM rate (post-RT/pre-RT) and the heart exposure dose in RT patients showed a positive correlation. Silencing OSMR in RIHF mice reduced fibrosis, while OSMR overexpression increased fibrotic responses. Furthermore, increased OSM promoted histone acetylation (H3K27ac) in the SMAD4 promoter region, influencing SMAD4 transcription and subsequently enhancing fibrotic response. CONCLUSIONS: The findings demonstrated that OSM/OSMR signaling promotes SMAD4 transcription in cardiac fibroblasts through H3K27 hyperacetylation, thereby promoting radiation-induced cardiac fibrosis and manifestations of RIHD.


Asunto(s)
Células Endoteliales , Fibroblastos , Animales , Humanos , Ratones , Fibroblastos/metabolismo , Fibrosis , Células 3T3 NIH , Oncostatina M/genética , Oncostatina M/metabolismo , Oncostatina M/farmacología , Receptores de Oncostatina M/metabolismo , Proteína Smad4
11.
Artículo en Inglés | MEDLINE | ID: mdl-38415967

RESUMEN

An integrated and projected-based laboratory course was described, integrating interconnected knowledge points and biochemistry and molecular biology techniques on a research project-based system. The program, which served as an essential extension of theoretical courses to practice, was conducted with a sophomore of basic medical science who had completed the course in medical biochemistry and molecular biology. This course engaged students in learning "genetic manipulation" and "recombinant DNA technology" to understand the target gene's role in disease mechanics, thus altering evaluation and treatment for clinical disease. Students could master applied and advanced techniques, such as cell culture, transfection, inducing exogenous fusion protein expression, purifying protein and its concentration assay, quantitative polymerase chain reaction, and western bot analysis. This laboratory exercise links laboratory practices with the methods of current basic research. Students need to complete the experimental design report and laboratory report, which could be advantageous for improving their ability to write lab summaries and scientific papers in the future. The reliability and validity analyses were conducted on the questionnaire, and we examined students' satisfaction with the course and their gains from the course. The student feedback was generally positive, indicating that the exercise helped consolidate theoretical knowledge, increase scientific research enthusiasm, and provide a powerful tool to be a better person and make informed decisions.

12.
Carcinogenesis ; 34(7): 1636-43, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23471882

RESUMEN

In this study, we reported millepachine (MIL), a novel chalcone compound for the first time isolated from Millettia pachycarpa Benth (Leguminosae), induced cell cycle arrest and apoptosis in human hepatocarcinoma cells in vitro and in vivo. In in vitro screening experiments, MIL showed strong antiproliferation activity in several human cancer cell lines, especially in HepG2 cells with an IC50 of 1.51 µM. Therefore, we chose HepG2 and SK-HEP-1 cells to study MIL's antitumor mechanism. Flow cytometry showed that MIL induced a G2/M arrest and apoptosis in a dose-dependent manner. Western blot demonstrated that MIL-induced G2/M arrest was correlated with the inhibition of cyclin-dependent kinase 1 activity, including a remarkable decrease in cell division cycle (cdc) 2 synthesis, the accumulation of phosphorylated-Thr14 and decrease of phosphorylation at Thr161 of cdc2. This effect was associated with the downregulation of cdc25C and upmodulation of checkpoint kinase 2 in response to DNA damage. MIL also activated caspase 9 and caspase 3, and significantly increased the ratio of Bax/Bcl-2 and stimulated the release of cytochrome c into cytosol, suggesting MIL induced apoptosis via mitochondrial apoptotic pathway. Associated with those effects, MIL also induced the generation of reactive oxygen species. In HepG2 tumor-bearing mice models, MIL remarkably and dose dependently inhibited tumor growth. Treatment of mice with MIL (20mg/kg intravenous [i.v.]) caused more than 65% tumor inhibition without cardiac damage compared with 47.57% tumor reduction by 5mg/kg i.v. doxorubicin with significant cardiac damage. These effects suggested that MIL and its easily modified structural derivative might be a potential lead compound for antitumor drug.


Asunto(s)
Apoptosis , Proteína Quinasa CDC2/metabolismo , Carcinoma Hepatocelular/patología , Chalconas/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular , Mitocondrias/patología , Animales , Antineoplásicos Fitogénicos/farmacología , Proteína Quinasa CDC2/genética , Carcinoma Hepatocelular/metabolismo , Chalcona/farmacología , Chalconas/química , Ciclina B/genética , Ciclina B/metabolismo , Quinasas Ciclina-Dependientes , Citosol/metabolismo , Daño del ADN , Relación Dosis-Respuesta a Droga , Activación Enzimática , Femenino , Citometría de Flujo , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Neoplasias Hepáticas/patología , Potenciales de la Membrana , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Millettia/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
13.
J Mol Cell Biol ; 15(4)2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37073091

RESUMEN

Recent studies have demonstrated that cancer-associated adipocytes (CAAs) in the tumor microenvironment are involved in the malignant progression of breast cancer. However, the underlying mechanism of CAA formation and its effects on the development of breast cancer are still unknown. Here, we show that CSF2 is highly expressed in both CAAs and breast cancer cells. CSF2 promotes inflammatory phenotypic changes of adipocytes through the Stat3 signaling pathway, leading to the secretion of multiple cytokines and proteases, particularly C-X-C motif chemokine ligand 3 (CXCL3). Adipocyte-derived CXCL3 binds to its specific receptor CXCR2 on breast cancer cells and activates the FAK pathway, enhancing the mesenchymal phenotype, migration, and invasion of breast cancer cells. In addition, a combination treatment targeting CSF2 and CXCR2 shows a synergistic inhibitory effect on adipocyte-induced lung metastasis of mouse 4T1 cells in vivo. These findings elucidate a novel mechanism of breast cancer metastasis and provide a potential therapeutic strategy for breast cancer metastasis.


Asunto(s)
Adipocitos , Transducción de Señal , Animales , Ratones , Línea Celular Tumoral , Fenotipo , Adipocitos/metabolismo , Metástasis de la Neoplasia , Movimiento Celular , Microambiente Tumoral
14.
J Pharmacol Exp Ther ; 341(1): 146-55, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22238210

RESUMEN

Acute liver failure (ALF) is a relatively rare liver disorder that leads to the massive death of hepatocytes. Our previous study reported that a novel small-molecule agent, (E)-5-(2,4-di-tert-butyl-6-((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl)-5'-methyl-7,7'-dimethoxy-4,4'-bibenzo[d][1,3]dioxole-5,5'-dicarboxylate (7k), possessed potent anti-inflammatory activity. In the present study, we further evaluated the therapeutic effects of 7k on lipopolysaccharide (LPS)-induced ALF and investigated the mechanisms of action. Our results demonstrated that 7k inhibited the migration of RAW264.7 macrophages, blocked the activity of nuclear factor-κB protein, and dose-dependently down-regulated the production of interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6 as well as their corresponding mRNAs in RAW264.7 cells. Oral administration of 7k at a dose of 50 mg/kg significantly suppressed the serum level of enzyme activity and prevented the damage of liver tissue in D-galactosamine/LPS-induced ALF. Treatment with 7k also remarkably blocked the increase in the number of CD11b(+)- and CD68(+)-positive cells in the liver, and in vivo nuclear factor-κB activity, known to regulate inflammatory responses in many cell types, was effectively inhibited. The serum concentrations and hepatic mRNA expression of proinflammatory cytokines tumor necrosis factor-α, IL-1ß, and IL-6 were markedly down-regulated in mice by the treatment of 7k. In summary, 7k alleviated the development and progression of D-galactosamine/LPS-induced ALF by inhibiting macrophage infiltration and regulating the expression of cytokines.


Asunto(s)
Inhibición de Migración Celular/efectos de los fármacos , Citocinas/antagonistas & inhibidores , Regulación hacia Abajo/efectos de los fármacos , Galactosamina/toxicidad , Lipopolisacáridos/toxicidad , Fallo Hepático Agudo/patología , Fallo Hepático Agudo/prevención & control , Macrófagos/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/toxicidad , Línea Celular , Movimiento Celular/efectos de los fármacos , Movimiento Celular/inmunología , Citocinas/biosíntesis , Dioxoles/química , Dioxoles/farmacología , Dioxoles/uso terapéutico , Regulación hacia Abajo/fisiología , Femenino , Fallo Hepático Agudo/inducido químicamente , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , Tiazolidinas/química , Tiazolidinas/farmacología , Tiazolidinas/uso terapéutico
15.
J Gastroenterol Hepatol ; 27(5): 966-73, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21913985

RESUMEN

BACKGROUND AND AIM: (Z)2-(5-(4-methoxybenzylidene)-2, 4-dioxothiazolidin-3-yl) acetic acid (MDA) is an aldose reductase (AR) inhibitor. Recent studies suggest that AR contributes to the pathogenesis of inflammation by affecting the nuclear factor κB (NF-κB)-dependent expression of cytokines and chemokines and therefore could be a novel therapeutic target for inflammatory pathology. The current study evaluated the in vivo role of MDA in protecting the liver against injury and fibrogenesis caused by CCl(4) in rats, and the underlying mechanisms. METHODS: A single injection of CCl(4) induced acute hepatitis, and repeated injections were used to induce hepatic fibrosis in rats. Therapeutic efficacy was assessed by comparison of the severity of hepatic injury and fibrosis in MDA-treated rats versus untreated controls. RESULTS: MDA significantly protected the liver from injury by reducing the activity of serum alanine aminotransferase, and improving the histological architecture of the liver. MDA modulated NF-κB-dependent activation of inflammatory cytokines by reducing hepatic mRNA levels of tumor necrosis factor-α, interleukin-1ß, inducible nitric oxide (NO) synthase and transforming growth factor-ß. In addition, MDA attenuated oxidative stress by increasing the content of hepatic glutathione. These favorable changes were associated with suppressed hepatic NF-κB activation by MDA. MDA treatment improved liver fibrosis in rats that received repeated CCl(4) injections. In vitro, MDA attenuated phosphorylation of IκB and activation of NF-κB, and thus prevented biosynthesis of NO in lipopolysaccharide-activated RAW264.7 cells. CONCLUSIONS: The present study suggests that AR is a novel therapeutic anti-inflammatory target for the treatment of hepatitis and liver fibrosis.


Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/prevención & control , Tiazolidinedionas/uso terapéutico , Alanina Transaminasa/sangre , Animales , Tetracloruro de Carbono , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Inhibidores Enzimáticos/farmacología , Glutatión/metabolismo , Proteínas I-kappa B/metabolismo , Interleucina-1beta/metabolismo , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Experimental/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Tiazolidinedionas/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
16.
Front Nutr ; 9: 914416, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35719160

RESUMEN

Glycosylation is considered to be an effective way to improve the performance of protein emulsification. This study focused on the effects of the molecular structure and emulsifying properties of ovalbumin (OVA) by wet heating Maillard reaction with three types of monosaccharides (i.e., xylose, glucose, and galactose). Results showed that increasing reaction temperature from 55°C to 95°C could significantly improve the degree of grafting (DG), while glycosylated OVA conjugate with xylose at 95°C processed the highest DG of 28.46%. This reaction was further confirmed by the browning intensity determination. Analysis of Fourier transform infrared spectrophotometer, circular dichroism, and fluorescence spectra indicated that there were slight changes in the subunits and the conversion of α-helices to ß-sheets, as well as the unfolded structures, thereby increasing the surface hydrophobicity and absolute zeta potential of obtained glycosylated OVA. Glycosylation endowed OVA with better emulsifying properties, especially the xylose glycosylated OVA was superior to that of glucose and galactose glycosylated OVA, which was mainly due to its shorter molecular chains with smaller steric hindrance for reaction. Furthermore, the enhancement of emulsifying properties may be attributed to the synergistic effect of stronger electrostatic repulsion of larger absolute zeta potential and the steric hindrance from thicker adsorbed layer, thereby inhibiting aggregation and flocculation of emulsion droplet.

17.
Foods ; 11(14)2022 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-35885414

RESUMEN

The clarification of sugarcane juice is a crucial stage in the sugar manufacturing process, as it affects evaporator performance, sugar quality and yield. The emergence of environmentally friendly and efficient adsorption technology has resulted in widespread interest in carbon-based materials. However, their low adsorption capacity and reusability make them unsuitable for processing sugarcane juice. Here, we provide a cost-effective and sustainable method to dope hydroxyapatite (HAP) nanoparticles on porous carbon (BBC) derived from sugarcane bagasse (BBC-HAP). The composite shows excellent adsorption capacity for color extract from sugarcane juice of 313.33 mg/g, far more effective than the commercially available carbon-based adsorbents. Isotherm studies show that the adsorption of BBC-HAP composite to the colorants is a monolayer process. The pseudo-first-order (PFO) and pseudo-second-order (PSO) kinetic models demonstrate that the adsorption process is dominated by chemisorption and supplemented by physical adsorption.

18.
RSC Adv ; 12(3): 1885-1896, 2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-35425169

RESUMEN

Activated-hydrochar (AHC) derived from sugarcane bagasse was synthesized by hydrothermal carbonization (HTC) using phosphoric acid and sodium hydroxide (NaOH) as activators. The properties of AHC were systematically characterized by elemental analysis, BET, SEM, FTIR, XPS and zeta potential, and applied to evaluate the adsorption ability of methylene blue (MB) by batch adsorption tests. The MB adsorption isotherm and kinetics of AHC were well described by the Langmuir model and pseudo-second-order kinetic model. Characteristic analysis suggested electrostatic attraction, hydrogen bonding and π-π interactions were the main contributors to MB adsorption. Analysis of mass transfer mechanisms demonstrated the adsorption process towards MB by AHC involved intra-particle diffusion to some extent. Thermodynamic studies indicated MB adsorption was an endothermic, spontaneous process associated with a disorder increase at the solid-liquid interface. The maximum adsorption capacity of AHC for MB was 357.14 mg g-1 at 303 K. Thus, the combination of HTC in phosphoric acid and NaOH activation offered a facile, green and economical alternative for conversion of sugarcane bagasse into efficient adsorbents used in wastewater treatment.

19.
RSC Adv ; 13(1): 1-13, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36545289

RESUMEN

In this study, a novel polyethyleneimine (PEI) modified MOF-derived carbon adsorbent (PEI@MDC) was proposed, which exhibited significant adsorption capacity for Congo Red (CR) in aqueous solutions. FT-IR and XPS results showed that PEI was successfully grafted onto MDC, increasing the content of amine groups on the surface of MDC. The adsorption process conformed to the Langmuir isotherm adsorption model and pseudo-second-order kinetic equation, indicating that the adsorption of CR on PEI@MDC was covered by a single layer, and the adsorption process was controlled by chemical processes. According to the Langmuir model, the maximum adsorption capacity at 30 °C was 1723.86 mg g-1. Hydrogen bonding and electrostatic interactions between CR and PEI@MDC surface functional groups were the main mechanisms controlling the adsorption process. After five adsorption-desorption cycles, PEI@MDC still showed a high adsorption capacity for CR, indicating that the adsorbent had an excellent regeneration ability.

20.
Front Nutr ; 9: 1110706, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36712504

RESUMEN

Bagasse is one of major by-product of sugar mills, but its utilization is limited by the high concentration of lignin. In this study, the optimal alkaline hydrogen peroxide (AHP) treatment conditions were determined by the response surface optimization method. The results showed that the lignin removal rate was 62.23% and the solid recovery rate was 53.76% when bagasse was prepared under optimal conditions (1.2% H2O2, 0.9% NaOH, and 46°C for 12.3 h), while higher purity of bagasse insoluble dietary fiber (BIDF) was obtained. To further investigate the modification effect, AHP assisted with high-temperature-pressure cooking (A-H) and enzymatic hydrolysis (A-E) were used to modify bagasse, respectively. The results showed that the water holding capacity (WHC), oil holding capacity (OHC), bile salt adsorption capacity (BSAC), and nitrite ion adsorption capacity (NIAC) were significantly improved after A-H treatment. With the A-E treatment, cation exchange capacity (CEC) and BSAC were significantly increased, while WHC, OHC, and glucose adsorption capacity (GAC) were decreased. Especially, the highest WHC, OHC, BSAC and NIAC were gained by A-H treatment compared to the A-E treatment. These changes in the physicochemical and functional properties of bagasse fiber were in agreement with the microscopic surface wrinkles and pore structure, crystallinity and functional groups. In summary, the A-H modification can effectively improve the functional properties of bagasse fiber, which potentially can be applied further in the food industry.

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