Objective:The mucosa of Chronic rhinosinusitis with nasal polyps（CRSwNP） is accompanied by tissue remodeling. Epithelial-mesenchymal transition（EMT） plays an important role in tissue remodeling, but the mechanism of EMT is not yet clear. The purpose of this study is to further clarify the pathogenesis of CRSwNP and provide another idea and theoretical basis for the treatment of CRSwNP. Methods:①The expression of NLRP3 and EMT-related protein（E-cadherin, Vimentin） in the nasal mucosa of the CRSwNP group and the normal control group were detected by immunohistochemistry（IHC）. ②Primary human nasal epithelial cells（HNECs） were cultured in vitro, and HNE-intervened cells with different concentrations（0, 10, 25, 50, 100 ng/mL） were used. After stimulation for 24 h, mRNA and protein expressions of E-cadherin, Vimentin, NLRP3 were detected by qRT-PCR and western blotting. ③Cells were collected at 0, 24, 36, 48 and 72 hours later after incubation with HNE with the optimal concentration, and the mRNA and protein expressions of E-cadherin, Vimentin and NLRP3 were detected by qRT-PCR and western blotting. ④Primary human nasal epithelial cells were pretreated with NLRP3 inhibitor MCC950, then stimulated with HNE, and EMT-related proteins（E-cadherin, Vimentin） and NLRP3 expression were detected by qRT-PCR and western blotting. Results:①The expression levels of NLRP3 and Vimentin in nasal polyps of CRSwNP patients were higher than those of control group, and the expression of E-cadherin was lower（P<0.05）. The mRNA and protein expression levels of NLRP3 and Vimentin increased when HNE stimulated primary human nasal epithelial cells, while the expression of E-cadherin decreased. ②The effect was most significant when the HNE stimulated nasal mucosal epithelial cells were exposed to 50 ng/mL（P<0.05）. The primary human nasal epithelial cells were stimulated with 50 ng/ml HNE, and the effect was most significant when the duration of HNE exposure was 36 h（P<0.05）. ③Primary human nasal epithelial cells were pretreated with MCC950 and then stimulated with HNE. The mRNA and protein expression levels of E-cadherin in the NLRP3 inhibitor pretreated group were increased, while the mRNA and protein expression levels of Vimentin and NLRP3 were decreased（P<0.05）. Conclusion:ln CRSwNP, HNE promotes EMT in human nasal mucosal epithelial cells by activating NLRP3.

2025-05-14·ACS Applied Materials & Interfaces

Beta-Sitosterol-Conjugated Sinapic Acid-Engineered Nanoliposome: Biomucoadhesive and Enzyme-Responsive Targeted Oral Therapy in Ulcerative Colitis

Article

作者: Mahajan, Shubham ; Parvez, Suhel ; Rahul ; Kanika ; Ali, Nemat ; Ali, Aneesh ; Kumar, Ajay ; Ahmad, Anas ; Navik, Umashanker ; Khan, Rehan ; Kumar, Bhuvnesh ; kumar, Jattin

Developing oral drug delivery systems is promising for ulcerative colitis (UC). However, the key challenges, including formulation degradation under harsh gastric conditions, poor targeting efficiency, and limited colonic residence, lead to poor therapeutic efficacy that still needs to be tackled. Effective treatment requires a safe, efficacious, enzyme- and pH-responsive, biomucoadhesive oral drug delivery system to overcome these challenges. Therefore, we have developed chitosan-armored 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) nanoliposomes amalgamated with synthesized beta-sitosterol-sinapic acid (Be-S) conjugate, further encapsulated with 3,4-methylenedioxy-β-nitrostyrene (MNS) as NLRP3 inhibitor, termed C@MN@DMBe-S, to overcome the limitation of free MNS and sinapic acid. Formulated by the thin-film hydration method and processed through extrusion, these unilamellar liposomes demonstrated structural stability and mucoadhesive properties due to chitosan coating. This configuration protected the nanoliposomes from the gastric acidic environment and allowed retention in the inflamed colon for 48 h. The enzyme-responsive C@MN@DMBe-S nanoliposome releases sinapic acid at the inflamed colonic site via esterase activity, providing sustained and controlled release of MNS. This synergistic action delivers antioxidant and anti-inflammatory effects while influencing the gut microbiota composition by releasing short-chain fatty acids. Moreover, therapeutic investigations revealed that C@MN@DMBe-S exhibited superior efficacy compared with free MNS when administered orally. The formulation effectively downregulated NF-κB, NLRP3, Caspase-1, and IL-1β expression while upregulating MUC5AC expression, indicating enhanced anti-inflammatory and protective effects and thereby promoting mucosal healing. In addition, C@MN@DMBe-S was found to regulate immune cell expression and effectively downregulate neutrophil infiltration. This armor- and enzyme-responsive strategy elucidates the impact of oral nanomedicines on mitigating UC and is demonstrated as an effective treatment.

2025-02-01·VETERINARY PARASITOLOGY

Interleukin-13 partly induced by the NLRP3 inflammasome promotes Trichinella spiralis encapsulation in infected mice

Article

作者: Liu, Xuanrui ; Shi, Chunwei ; Zhang, Tongxuan ; Zhang, Zhiyuan ; Cao, Xin ; Wang, Chunfeng ; Wang, Xueting ; Zeng, Yan ; Wang, Jianzhong ; Yang, Wentao ; Yang, Guilian ; Wang, Nan ; Jiang, Yanlong ; Huang, Haibin ; Zhang, Bo

Trichinella spiralis infection is a serious parasitic zoonosis in which a collagenous capsule surrounding the larva is developed in the striated muscle cells. However, the mechanism of T. spiralis encapsulation is currently poorly understood. It has been reported that T. spiralis infection can induce the production of IL-13 via the NLRP3 inflammasome, and it has also been suggested IL-13 thus produced may be involved in T. spiralis encapsulation. This research aimed to clarify the involvement of NLRP3 and IL-13 in the T. spiralis capsule formation process. IL-13 and NLRP3 inhibitors were used in a T. spiralis infected mouse model and in C₂C₁₂ cells to analyze the role of IL-13 and NLRP3 in encapsulation. The results showed that T. spiralis infection significantly increased the expression levels of IL-13 and collagen IV and VI. The production of collagen around the T. spiralis encapsulation zone was significantly inhibited when an IL-13 inhibitor was applied. Moreover, the expression levels of IL-13 and collagen IV and VI were significantly decreased by the NLRP3 inhibitor in vitro and in vivo. The above results indicated that NLRP3 can participate in the development of T. spiralis encapsulation by regulating IL-13 expression and stimulating collagen IV and VI synthesis during T. spiralis infection.

100 项与 NLRP3 inhibitor(WuXi AppTec) 相关的药物交易

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