BIO-MEDICAL MATERIALS AND ENGINEERING
·
2024
·Vol. 35
·期 5
·475-485
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IF 1
Bao Ronghua,Mao Yifan,Zhang Yuliang,Chai Junlei,Zhang Yuanbin,Luo Cheng,Zhang Kailong,Jiang Guohua,He Xiaodan
BACKGROUND:Osteoarthritis (OA) is a chronic and degenerative joint disease that remains a great challenge in treatment due to the lack of effective therapies. 4-octyl itaconate (4-OI) is a novel and potent modulator of inflammation for the treatment of inflammatory disease. However, the clinical usage of 4-OI is limited due to its poor solubility and low bioavailability. As a promising drug delivery strategy, injectable hydrogels offers an effective approach to address these limitations of 4-OI. OBJECTIVE:The aim of the study was to verify that the composite 4-OI/SA hydrogels could achieve a controlled release of 4-OI and reduce damage to articular cartilage in the group of osteoarthritic rats treated with the system. METHODS:In this study, an injectable composite hydrogel containing sodium alginate (SA) and 4-octyl itaconate (4-OI) has been developed for continuous intra-articular administration in the treatment of OA. RESULTS:After intra-articular injection in arthritic rats, the as-prepared 4-OI/SA hydrogel containing of 62.5 μM 4-OI effectively significantly reduced the expression of TNF-α, IL-1β, IL-6 and MMP3 in the ankle fluid. Most importantly, the as-prepared 4-OI/SA hydrogel system restored the morphological parameters of the ankle joints close to normal. CONCLUSION:4-OI/SA hydrogel shows a good anti-inflammatory activity and reverse cartilage disruption, which provide a new strategy for the clinical treatment of OA.
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PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Wenying Li,Dong Chen,Yanmei Zhu,Qiange Ye,Yang Hua,Ping Jiang,Ying Xiang,Yuejie Xu,Yinya Pan,Hua Yang,Yichun Ma,Hang Xu,Cheng Zhao,Chang Zheng,Changrong Chen,Yun Zhu,Guifang Xu
Current therapies primarily targeting inflammation often fail to address the root relationship between intestinal mucosal integrity and the resulting dysregulated cell death and ensuing inflammation in ulcerative colitis (UC). First, UC tissues from human and mice models in this article both emphasize the crucial role of Gasdermin E (GSDME)-mediated pyroptosis in intestinal epithelial cells (IECs) as it contributes to colitis by releasing proinflammatory cytokines, thereby compromising the intestinal barrier. Then, 4-octyl-itaconate (4-OI), exhibiting potential for anti-inflammatory activity in inhibiting pyroptosis, was encapsulated by butyrate-modified liposome (4-OI/BLipo) to target delivery for IECs. In brief, 4-OI/BLipo exhibited preferential accumulation in inflamed colonic epithelium, attributed to over 95% of butyrate being produced and absorbed in the colon. As expected, epithelium barriers were restored significantly by alleviating GSDME-mediated pyroptosis in colitis. Accordingly, the permeability of IECs was restored, and the resulting inflammation, mucosal epithelium, and balance of gut flora were reprogrammed, which offers a hopeful approach to the effective management of UC.
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PubMed
高影响因子
Hematology
·
2025
·
IF 1.6
Yuying Chang,Yinglan Jin,Xi Chen,Xiaomin Zhang,Yaoyao Tian,Xinyu Gao,Xiushuai Dong,Wei Wang
Objective: This study aimed to investigate the effects of 4-Octyl itaconate (4-OI) on immune thrombocytopenia (ITP) mice model and elucidate the underlying mechanism.Methods: An ITP mouse model was established by intraperitoneal injection of the monoclonal antibody MWReg30 and treated by 4-OI with/without chloroquine (CQ). The mice were divided into four groups: Control, ITP, ITP+4-OI and ITP+4-OI + CQ. Platelet (PLT) content was detected and bone marrow megakaryocytes were quantified using Giemsa staining. Apoptosis was evaluated by TUNEL staining, protein expression of Bax and Bcl-2 in bone marrow tissues was detected by western blotting, and megakaryocyte apoptosis ratio was assessed by flow cytometry detection of CD61+ cells. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood, and the mRNA expression of LC3II, Becin-1, and SQSTM1 were detected by qRT-PCR; Immunofluorescence evaluated LC3II, Beclin-1, and SQSTM1 expression in bone marrow, as well as the ratios of CD41+Beclin-1+ and CD41+LC3II+ megakaryocytes.Results: Compared to the ITP group, 4-OI treatment significantly increased PLT counts, while reduced the spleen index and bone marrow megakaryocyte numbers. 4-OI also increased the apoptosis rate of megakaryocytes by increasing Bax protein expression and reducing Bcl-2 expression in the bone marrow. LC3II and Beclin-1 expression increased in PBMCs and bone marrow tissues, whereas SQSTM1 expression decreased. Megakaryocytes exhibited reduced LC3II and Beclin-1. The autophagy inhibitor chloroquine (CQ) suppressed all the 4-OI-induced effects.Conclusion: 4-OI ameliorated ITP-induced thrombocytopenia by modulating autophagy-related proteins in megakaryocytes, inducing autophagy, and promoting apoptosis.
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