RESUMEN
The immune system plays a crucial role in controlling colorectal cancer (CRC) development. Natural killer (NK) cells are tumoricidal but undergo exhaustion in CRC patients. The current research aims to understand the role of sirtuin 6 (SIRT6) in CRC-associated NK cell exhaustion in a murine inflammatory colorectal cancer model. To this end, inflammatory CRC was induced by treating mice with azoxymethane plus dextran sulfate sodium. The expression of SIRT6 in NK cells in murine mesenteric lymph nodes (mLNs) and the CRC tissue was characterized by Immunoblotting. SIRT6 knockdown was achieved by lentiviral transduction of murine splenic NK cells, followed by evaluation of NK cell proliferation and the expression of cytotoxic mediators using flow cytometry. NK cell cytotoxicity was measured by cytotoxicity assays. Adoptive transfer of murine NK cells was applied to analyze the effect of SIRT6 knockdown in vivo. We found that SIRT6 was up-regulated in infiltrating NK cells in the murine CRC tissue, especially NK cells with an exhausted phenotype and impaired cytotoxicity. SIRT6 knockdown significantly boosted murine splenic NK cell functionality, as evidenced by accelerated proliferation, increased production of cytotoxic mediators, and higher tumoricidal activity both in vitro and in vivo. Furthermore, the adoptive transfer of SIRT6-knockdown NK cells into CRC-bearing mice effectively suppressed CRC progression. Therefore, SIRT6 up-regulation is essential for murine NK cell exhaustion in CRC because it impedes the tumoricidal activity of murine NK cells. Artificial SIRT6 down-regulation could boost the function of infiltrating NK cells to oppress CRC progression in mice.
Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Sirtuinas , Ratones , Animales , Células Asesinas Naturales , Regulación hacia Abajo , Sirtuinas/metabolismoRESUMEN
Bacterial cellulose (BC) is a kind of high-purity cellulose biomaterial with a unique three-dimensional structure. To improve the mechanical properties and reinforce the BC composite films, in this study, we provide in detail a simple, fast, and environmentally-friendly method to prepare a biodegradable composite film using chitosan (CS) with different molecular weights and BC with excellent dispersion. The water moisture content (MC), water solubility (WS), contact angle (CA), mechanical properties and barrier properties were measured to assess the effect of CSn-OBC composite films. The morphology, structural and thermal properties of the films were evaluated by scanning electron microscopy, spectral analysis, thermogravimetry and X-ray diffraction. Results showed that the biodegradable film prepared by grafting chitosan with high molecular weight and uniformly dispersing bacterial cellulose exhibited superior mechanical properties, water resistance, and thermal stability, which are essential characteristics for commercial applications in complex environments.
Asunto(s)
Celulosa Oxidada , Quitosano , Celulosa/química , Quitosano/química , Solubilidad , TermogravimetríaRESUMEN
Kojic acid (KA) with antibacterial activities produced by fermentation was grafted onto konjac glucomannan oligosaccharide (KGO) composed of glucose and mannose linked by ß-1,4 glycosidic bonds. A novel KGO derivative, konjac glucomannan oligosaccharide kojic acid (KGOK) possessing both moisture retention and antibacterial activities was synthesized. The structure of KGOK was characterized and analyzed by thermogravimetric analysis (TG), XRD, UV-vis absorption, FTIR, and 1H NMR. The analysis results suggest that KA was linked to the KGO molecular chain through a covalent bond, and the reaction site of KA was the methylol group. The studies demonstrate that KGOK maintained the excellent moisture absorption and retention properties of KGO and the good antibacterial activities of KA. The minimum inhibitory concentration (MIC) of KGOK is 2 mg/mL for Staphylococcus aureus, Staphylococcus epidermidis, Shewanella putrefaciens, and Salmonella enterica, while its MIC is 3 mg/mL for Escherichia coli. The multi-functionality of the KGOK synthesized from natural sources provides a theoretical foundation for their potential applications in the preservation of food, beverage, aquatic, and cosmetic products.