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1.
PLoS Pathog ; 20(9): e1012458, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39241059

RESUMEN

Uropathogenic Escherichia coli (UPEC) can undergo extensive filamentation in the host during acute urinary tract infections (UTIs). It has been hypothesised that this morphological plasticity allows bacteria to avoid host immune responses such as macrophage engulfment. However, it is still unclear what properties of filaments are important in macrophage-bacteria interactions. The aim of this work was to investigate the contribution of bacterial biophysical parameters, such as cell size and shape, and physiological parameters, such as cell surface and the environment, to macrophage engulfment efficiency. Viable, reversible filaments of known lengths and volumes were produced in the UPEC strain UTI89 using a variety of methods, including exposure to cell-wall targeting antibiotics, genetic manipulation and isolation from an in vitro human bladder cell model. Quantification of the engulfment ability of macrophages using gentamicin-protection assays and fluorescence microscopy demonstrated that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, cell surface and external environmental factors. UTI89 filamentation and macrophage engulfment efficiency were also found to occur independently of the SOS-inducible filamentation genes, sulA and ymfM in both in vivo and in vitro models of infection. Compared to filaments formed via antibiotic inhibition of division, the infection-derived filaments were preferentially targeted by macrophages. With several strains of UPEC now resistant to current antibiotics, our work identifies the importance of bacterial physiological and morphological states during infection.


Asunto(s)
Infecciones por Escherichia coli , Macrófagos , Infecciones Urinarias , Escherichia coli Uropatógena , Macrófagos/microbiología , Macrófagos/inmunología , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/inmunología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/inmunología , Fagocitosis , Ratones , Animales
2.
J Nanosci Nanotechnol ; 17(2): 947-53, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29671483

RESUMEN

Hybrid mesoporous materials as carriers for immobilization of D-amino acid oxidase (DAAO) were prepared via three steps: (i) hydrothermal synthesis of nanoporous MCF, SBA-15 and MCM-41 powders, (ii) functionalization with 3-aminopropyltriethoxysilane (APTES) by post-synthesis grafting; and (iii) activation with glutardialdehyde. The resulting mesostructured solids were characterized by various techniques: XRD, IR, TGA-DTA and N2 adsorption­desorption (BET). The characterization results indicated that these materials still maintained their structure after functionalization. IR data and TGA-DTA analysis demonstrated the existence of amine functional groups on the surface of APTES-functionalized samples. The DAAO immobilized on these materials exhibited higher catalytic activity and stability of enzyme for conversion of cephalosporin C (CPC) as compared to those of the non-functionalized ones. The catalytic activity and stability of enzyme decreased in the order MCF > SBA-15 > MCM-41.


Asunto(s)
D-Aminoácido Oxidasa , Enzimas Inmovilizadas , Nanoestructuras/química , Compuestos de Silicona/química , D-Aminoácido Oxidasa/química , D-Aminoácido Oxidasa/metabolismo , Estabilidad de Enzimas , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Porosidad , Dióxido de Silicio/química
3.
Cancer Res ; 84(17): 2761-2775, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-38900938

RESUMEN

Obesity is associated with increased incidence and metastasis of triple-negative breast cancer, an aggressive breast cancer subtype. The extracellular matrix (ECM) is a major component of the tumor microenvironment that drives metastasis. To characterize the temporal effects of age and high-fat diet (HFD)-driven weight gain on the ECM, we injected allograft tumor cells at 4-week intervals into mammary fat pads of mice fed a control or HFD, assessing tumor growth and metastasis and evaluating the ECM composition of the mammary fat pads, lungs, and livers. Tumor growth was increased in obese mice after 12 weeks on HFD. Liver metastasis increased in obese mice only at 4 weeks, and elevated body weight correlated with increased metastasis to the lungs but not the liver. Whole decellularized ECM coupled with proteomics indicated that early stages of obesity were sufficient to induce changes in the ECM composition. Obesity led to an increased abundance of the proinvasive ECM proteins collagen IV and collagen VI in the mammary glands and enhanced the invasive capacity of cancer cells. Cells of stromal vascular fraction and adipose stem and progenitor cells were primarily responsible for secreting collagen IV and collagen VI, not adipocytes. Longer exposure to HFD increased the invasive potential of ECM isolated from the lungs and liver, with significant changes in ECM composition found in the liver with short-term HFD exposure. Together, these data suggest that changes in the breast, lungs, and liver ECM underlie some of the effects of obesity on triple-negative breast cancer incidence and metastasis. Significance: Organ-specific extracellular matrix changes in the primary tumor and metastatic microenvironment are mechanisms by which obesity contributes to breast cancer progression.


Asunto(s)
Dieta Alta en Grasa , Matriz Extracelular , Obesidad , Microambiente Tumoral , Animales , Obesidad/metabolismo , Obesidad/patología , Obesidad/complicaciones , Femenino , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Ratones , Humanos , Dieta Alta en Grasa/efectos adversos , Invasividad Neoplásica , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metástasis de la Neoplasia , Colágeno Tipo IV/metabolismo
4.
bioRxiv ; 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37662270

RESUMEN

Younger age and obesity increase the incidence and metastasis of triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer. The extracellular matrix (ECM) promotes tumor invasion and metastasis. We characterized the effect of age and obesity on the ECM of mammary fat pads, lungs, and liver using a diet-induced obesity (DIO) model. At 4 week intervals, we either injected the mammary fat pads with allograft tumor cells to characterize tumor growth and metastasis or isolated the mammary fat pads and livers to characterize the ECM. Age had no effect on tumor growth but increased lung and liver metastasis after 16 weeks. Obesity increased tumor growth starting at 12 weeks, increased liver metastasis only at 4 weeks, and weight gain correlated to increased lung but not liver metastasis. Utilizing whole decellularized ECM coupled with proteomics, we found that early stages of obesity were sufficient to induce changes in the ECM composition and invasive potential of mammary fat pads with increased abundance of pro-invasive ECM proteins Collagen IV and Collagen VI. We identified cells of stromal vascular fraction and adipose stem and progenitor cells as primarily responsible for secreting Collagen IV and VI, not adipocytes. We characterized the changes in ECM in the lungs and liver, and determined that older age decreases the metastatic potential of lung and liver ECM while later-stage obesity increases the metastatic potential. These data implicate ECM changes in the primary tumor and metastatic microenvironment as mechanisms by which age and obesity contribute to breast cancer progression.

5.
J Hazard Mater ; 420: 126560, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34274809

RESUMEN

Agx-Zn100-x-BTC/GO composites (BTC: benzene-1,3,5-tricarboxylic, GO: graphene oxide) with different Ag/Zn molar ratios were synthesized using microwave-assisted hydrothermal treatment. The Agx-Zn100-x-BTC/GO exhibited excellent photocatalytic performance in the reactive yellow 145 dye (RY-145) degradation under irradiation of visible light with nearly 100% of RY-145 removal after 35 min, as compared to Zn-BTC/GO and Ag-BTC/GO. Reactive oxygen species scavenging assays have shown that the holes (h+) and superoxide radical anion (O2-•) play a primary role in RY-145 degradation. Based on the band structure of materials, the Z-scheme photocatalytic mechanism was suggested. The effect of catalyst dosage, pH and dye concentration on the efficiency of photocatalytic activity of bimetallic Ag50-Zn50-BTC/GO was also investigated. The improvement in photocatalytic activity of bimetallic Ag50-Zn50-BTC/GO could be given by the synergism of (i) absorption of visible light confirmed by UV-Vis diffuse reflectance spectra; (ii) the increased lifetime as evidenced by photoluminescence spectra and transient photocurrent response; (iii) the increased oxygen vacancy defects as confirmed by X-ray photoelectron spectroscopy results. The degradation pathway of RY-145 dye was also predicted based on liquid chromatography-mass spectrometer analysis. The removed chemical oxygen demand, biological oxygen demand, total organic carbon outcomes indicated the high mineralization ability for RY-145 degradation over Ag50-Zn50-BTC/GO.


Asunto(s)
Luz , Agua , Catálisis , Zinc
6.
Chemosphere ; 265: 129062, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33250232

RESUMEN

The modified Al-MCM-41 solid acids with turning Si/Al molar ratio were successfully fabricated through a hydrothermal route and utilized as a suitable catalyst in the cellulose conversion into 5-hydroxylmethylfurfural (5-HMF). The crystal structure, composition, morphologies and porosity of as-synthesized acids were characterized by XRD, FT-IR, N2 adsorption-desorption, TEM and EDS. The 27Al MAS NMR and 29Si-MAS NMR results revealed the existence of both Al framework and Al extra framework. Besides, the existence of medium-weak and strong acid sites, according to Brønsted and Lewis acidity, in Al-MCM-41 acids was confirmed by NH3-TPD and FTIR-pyridine adsorption. The 30Al-MCM-41 solid acid (Si/Al molar ratio = 30) exhibited excellent activity with the highest 5-HMF yield of 40.56% compared to other samples. We also discovered that 5-HMF production, as well as cellulose conversion, strongly depended on the total acid, strong/medium-weak acid ratio, as well as Brønsted/Lewis acid ratio. Therefore, these parameters have been considered as essential factors for the design of solid acid for 5-HMF production.


Asunto(s)
Celulosa , Ácidos de Lewis , Dióxido de Silicio , Espectroscopía Infrarroja por Transformada de Fourier
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