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2.
JAMA Surg ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39110469
3.
Sci Rep ; 14(1): 18363, 2024 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112724

RESUMO

The combination of anti-angiogenic treatment and immunotherapy presents a promising strategy against colon cancer. Interleukin-17F (IL-17F) emerges as a critical immune cell cytokine expressed in colonic epithelial cells, demonstrating potential in inhibiting angiogenesis. In order to clarify the roles of IL-17F in the colon cancer microenvironment and elucidate its mechanism, we established a mouse colon carcinoma cell line CT26 overexpressing IL-17F and transplanted it subcutaneously into syngeneic BALB/c mice. We also analyzed induced colon tumor in IL-17F knockout and wild type mice. Our results demonstrated that IL-17F could suppress colon tumor growth in vivo with inhibited angiogenesis and enhanced recruitment of cysteine-cysteine motif chemokine receptor 6 (CCR6) positive immune cells. Additionally, IL-17F suppressed the tube formation, cell growth and migration of endothelial cells EOMA in vitro. Comprehensive bioinformatics analysis of transcriptome profiles between EOMA cells and those treated with three different concentrations of IL-17F identified 109 differentially expressed genes. Notably, a potential new target, Caspase 4, showed increased expressions after IL-17F treatment in endothelial cells. Further molecular validation revealed a novel downstream signaling for IL-17F: IL-17F enhanced Caspase 4/GSDMD signaling of endothelial cells, CT26 cells and CT26 transplanted tumors, while IL-17F knockout colon tumors exhibited decreased Caspase 4/GSDMD signaling. The heightened expression of the GSDMD N-terminus, coupled with increased cellular propidium iodide (PI) uptake and lactate dehydrogenase (LDH) release, revealed that IL-17F promoted pyroptosis of endothelial cells. Altogether, IL-17F could modulate the colon tumor microenvironment with inhibited angiogenesis, underscoring its potential as a therapeutic target for colon cancer.


Assuntos
Neoplasias do Colo , Células Endoteliais , Interleucina-17 , Camundongos Endogâmicos BALB C , Piroptose , Animais , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/genética , Interleucina-17/metabolismo , Camundongos , Células Endoteliais/metabolismo , Linhagem Celular Tumoral , Caspases Iniciadoras/metabolismo , Caspases Iniciadoras/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Camundongos Knockout , Microambiente Tumoral , Humanos , Proliferação de Células
4.
Nature ; 629(8011): 286, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38714811
5.
Cell Biochem Biophys ; 82(2): 885-894, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38430410

RESUMO

To investigate the effects and mechanisms of Mycobacterium avium MAV-5183 protein on apoptosis in mouse Ana-1 macrophages. A pET-21a-MAV-5183 recombinant plasmid was constructed. The recombinant MAV-5183 protein was cloned, expressed, purified, and identified using an anti-His-tagged antibody. Rabbits were immunized to obtain antiserum, and its potency and immunoreactivity were assessed through WB. Mouse Ana-1 macrophages were incubated with varying concentrations of MAV-5183 protein. Flow cytometry, following ANNEXIN V-FITC/PI double staining, detected apoptosis. Western Blot analysis was conducted to identify apoptosis-related molecules Caspase-9/8/3 and vesicle-related molecules ASC, NLRP3, and Cleaved-casp1. ELISA measured TNF-α and IL-6 levels in the culture supernatant. LDH activity and ROS levels were analyzed separately. RT-qPCR measured mRNA levels of Caspase-9/8/3, ASC, NLRP3, Caspase-1, IL-1ß, Bax, MAPK-p38, Bcl-2, TNF-α, and IL-6. MAV-5183 protein was successfully cloned, purified, and identified. In in vitro studies on Ana-1 macrophages, MAV-5183 protein increased the expression of Caspase-9/8/3, ASC, NLRP3 (P < 0.01), induced ROS secretion (P < 0.05), and promoted inflammatory cytokine secretion (TNF-α, IL-6, P < 0.0001); however, it did not significantly affect LDH (P > 0.05). MAV-5183 also induced apoptosis in Ana-1 macrophages (P < 0.05). RT-qPCR results indicated a significant increase in mRNA expression of Caspase-9/8/3, ASC, NLRP3, TNF-α, IL-6, MAPK-p38, and pro-apoptotic factor Bax (P < 0.01), with no significant effect on Bcl-2 and IL-1ß mRNA (P > 0.05). The data indicate that MAV-5183 induces macrophage apoptosis through a caspase-dependent pathway and promotes inflammatory cytokine secretion via ROS.


Assuntos
Apoptose , Macrófagos , Mycobacterium avium , Animais , Camundongos , Macrófagos/metabolismo , Macrófagos/citologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Coelhos , Interleucina-6/metabolismo , Interleucina-6/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Linhagem Celular , Proteínas Recombinantes/farmacologia
6.
Food Chem ; 444: 138602, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38310778

RESUMO

In this work, the MeJA-loaded gelatin/pullulan/chitosan composite biofilm was prepared to inhibit the chilling lignification of the loquat fruit during storage at 0 °C. The firmness and lignin content were decreased by 89 % and 81.77 % after MeJA-loaded biofilm treatment. Malondialdehyde (MDA) production was almost completely suppressed and chilling injury of loquat fruit was significantly reduced. Enzyme activity results show that the biofilm alleviated chilling lignification mainly by inhibiting peroxidase (POD) activity in the phenylpropanoid pathway (PCCs = 0.715, with lignin content). Also, the conventional MeJA vapor treatment only alleviated lignification on day 3, but the biofilm treatment had a better and more sustained effect throughout the whole storage due to its sustained release ability. Besides, the biofilm had good mechanical properties, transparency and water vapor transmission rate. This work indicates that loading preservatives into biofilms has a promising application prospect for inhibiting the postharvest quality deterioration of fruit and vegetables.


Assuntos
Acetatos , Antioxidantes , Ciclopentanos , Eriobotrya , Lignina , Oxilipinas , Extratos Vegetais , Lignina/metabolismo , Antioxidantes/metabolismo , Frutas/metabolismo
7.
Food Chem ; 444: 138632, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38330606

RESUMO

Green food packaging plays an important role in environmental protection and sustainable development. Therefore, it is advisable to employ low-energy consumption manufacturing techniques, select environmentally friendly materials, and focus on cost-effectiveness with high production yields during the production process. In this study, an amphiphilic polyquaternium called PBzCl was proposed and synthesized by free radical polymerization of cost-efficient quaternary ammonium salts and methacrylate monomers. Then, biodegradable PCL and PVP were used to rapidly prepare the PBzCl@PCL/PVP nanofiber films via environmentally friendly microfluidic-blow-spinning (MBS). The best antibacterial effect was observed at a PBzCl loading concentration of 13.5%, and the PBzCl@PCL/PVP nanofiber films had 91% and 100% antibacterial rates against Escherichia coli and Staphylococcus aureus, respectively. Besides, the loading of PBzCl improved the water stability of the PCL/PVP nanofiber films, and the films also showed excellent biocompatibility. Overall, PBzCl@PCL/PVP nanofibre films have promising food packaging potential.


Assuntos
Embalagem de Alimentos , Nanofibras , Embalagem de Alimentos/métodos , Microfluídica , Antibacterianos/farmacologia , Compostos de Amônio Quaternário
8.
Food Chem ; 442: 138436, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38244441

RESUMO

Fruit is susceptible to various postharvest pathogens; thus, the development of multifunctional preservation materials that can achieve the broad-spectrum inhibition of different pathogens is a current research hotspot. Here, microfluidic blow spinning was used to create a biodegradable polycaprolactone/ethyl cellulose (PCL/EC) nanofibrous film that incorporated two naturally-sourced compounds, natamycin and trans-cinnamic acid, resulting in multi-microbial inhibition. The PCL/EC-based film had a smooth and even morphology, indicating the favorable integration of PCL and EC. After the incorporation of ingredients, the film exhibited good inhibitory activity against Escherichia coli, Staphylococcus aureus, and Botrytis cinerea, and it had finer fiber diameters, higher permeability, and antioxidant properties. We further demonstrated that strawberries that were padded with the film had good resistance to Botrytis cinerea. Also, the film did not interference with the qualities of the strawberries during storage. The study demonstrates a promising application for multi-antimicrobial and bio-friendly packaging materials in postharvest fruit preservation.


Assuntos
Anti-Infecciosos , Botrytis , Celulose/análogos & derivados , Cinamatos , Nanofibras , Poliésteres , Natamicina , Frutas , Microfluídica , Anti-Infecciosos/farmacologia
10.
Mater Today Bio ; 12: 100161, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34870140

RESUMO

Acellular adipose matrix (AAM) has emerged as an important biomaterial for adipose tissue regeneration. Current decellularization methods damage the bioactive components of the extracellular matrix (ECM), and the residual immunogenic antigens may induce adverse immune responses. Here, we adopted a modified decellularization method which can protect more bioactive components with less immune reaction by methoxy polyethylene glycol (mPEG). Then, we determined the adipogenic mechanisms of mPEG-modified AAM after xenogeneic transplantation. AAM transplantation caused significantly lesser adipogenesis in the wild-type group than in the immune-deficient group. The mPEG-modified AAM showed significantly lower immunogenicity and higher adipogenesis than the AAM alone after xenogeneic transplantation. Furthermore, mPEG modification increased regulatory T (Treg) cell numbers in the AAM grafts, which in turn enhanced the M2/M1 macrophage ratio by secreting IL-10, IL-13, and TGF-ß1. These findings suggest that mPEG modification effectively reduces the immunogenicity of xenogeneic AAM and promotes adipogenesis in the AAM grafts. Hence, mPEG-modified AAM can serve as an ideal biomaterial for xenogeneic adipose tissue engineering.

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