Journal of Functional Foods
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2023
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IF 5.6
Shangyun Lu,Jiali Xu,Yang Xu,Yang Liu,Dongxing Shi,Jia Wang,Fubin Qiu
Maintaining the integrity and stability of the gut tract is essential for the health of the body. Autophagy is a promising target for balancing gut homeostasis, and numerous studies have focused on regulating autophagy to improve gut health. In this study, we found that glycyrol (GC), a representative coumarin compound isolated from Glycyrrhiza uralensis Fisch (used for medicine and food), can attenuate colon injury by activating autophagy. Specifically, we demonstrated that GC can act on ubiquitin-specific protease 8 (USP8), inhibit the interaction between SQSTM1/p62 and USP8, promote the ubiquitination of p62, and activate autophagy. Collectively, the findings of the present study suggest that GC is a novel and promising colon protector and deserves further investigation.
研究领域:
药理学
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胃肠病学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2026
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IF 11
Junjian Deng,Peiyi Luo,Kejun Li,Miaomiao Zhang,Ruxin Zhang,Zengxing Zhang,Songlin Wang,Yongfa Zheng
Radiotherapy (RT) remains a cornerstone in lung cancer treatment, but its efficacy is often limited by radioresistance and an immunosuppressive tumor microenvironment (TME). Here, we identify the deubiquitinating enzyme USP8 as a key regulator of M2-like tumor-associated macrophages (TAMs) in the irradiated TME. To exploit this finding, we developed a biomimetic nanoparticle, USP8@CPMOF, which co-delivers a USP8 inhibitor and an anti-PD-L1 nanobody-coated membrane. This nanosystem specifically targets both irradiated tumor cells and TAMs, responding to the acidic and high-glutathione TME to trigger ferroptosis and release the USP8 inhibitor. In vitro , USP8@CPMOF enhanced RT-induced apoptosis and ferroptosis, promoted dendritic cell maturation, and reprogrammed M2 macrophages toward an M1 phenotype. In vivo , it improved tumor accumulation, synergized with RT to suppress tumor growth and metastasis, and robustly remodeled the TME by increasing cytotoxic T cell infiltration and reducing immunosuppressive cells. This work presents a promising nanomedicine strategy to overcome radioresistance by simultaneously targeting tumor cells and the immunosuppressive TME.
✓ 已验证
DOI
高影响因子
ACS Nano
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2024
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IF 15.8
Xuantong Zhou,Fene Gao,Wenyan Gao,Qingzhen Wang,Xin Li,Xinyue Li,Wenxin Li,Jing Liu,Huige Zhou,Aiping Luo,Chunying Chen,Zhihua Liu
Despite the superior efficacy of radiotherapy in esophageal squamous cell carcinoma (ESCC), radioresistance by cancer stem cells (CSCs) leads to recurrence, metastasis, and treatment failure. Therefore, it is necessary to develop CSC-based therapies to enhance radiotherapy. miR-339-5p (miR339) is involved in stem cell division and DNA damage checkpoint signaling pathways based on ESCC cohort. miR339 inhibited ESCC cell stemness and enhanced radiation-induced DNA damage by targeting USP8, suggesting that it acts as a potential CSC regulator and radiosensitizer. Considering the limited circulating periods and poor tumor-targeting ability of miRNA, a multifunctional nanoplatform based on bismuth sulfide nanoflower (Bi@PP) is developed to efficiently deliver miR339 and improve radioresistance. Intriguingly, Bi@PP encapsulates more miR339 owing to their flower-shaped structure, delivering more than 1000-fold miR339 into cells, superior to free miR339 alone. Besides being used as a carrier, Bi@PP is advantageous for dynamically monitoring the distribution of delivered miR339 in vivo while simultaneously inhibiting tumor growth. Additionally, Bi@PP/miR339 can significantly enhance radiotherapy efficacy in patient-derived xenograft models. This multifunctional platform, incorporating higher miRNA loading capacity, pH responsiveness, hypoxia relief, and CT imaging, provides another method to promote radiosensitivity and optimize ESCC treatment.
研究领域:
肿瘤学
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分子生物学
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纳米技术
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放射生物学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2023
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IF 7.3
Tingyan Liu,Caiyan Zhang,Jiayun Ying,Yaodong Wang,Gangfeng Yan,Yufeng Zhou,Guoping Lu
Background Notch signaling is critical for regulating the function of vascular endothelial cells (ECs). However, the effect of the intracellular domain of Notch1 (NICD) on EC injury in sepsis remains unclear. Methods We established a cell model of vascular endothelial dysfunction and induced sepsis in a mouse model via lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP). Endothelial barrier function and expression of endothelial-related proteins were determined using CCK-8, permeability, flow cytometry, immunoblot, and immunoprecipitation assays. The effect of NICD inhibition or activation on endothelial barrier function was evaluated in vitro . Melatonin was used for NICD activation in sepsis mice. The survival rate, Evans blue dye of organs, vessel relaxation assay, immunohistochemistry, ELISA, immunoblot were used to explore the specific role of melatonin for sepsis induced vascular dysfunction in vivo . Results We found that LPS, interleukin 6, and serum collected from septic children could inhibit the expression of NICD and its downstream regulator Hes1, which impaired endothelial barrier function and led to EC apoptosis through the AKT pathway. Mechanistically, LPS decreased the stability of NICD by inhibiting the expression of a deubiquitylating enzyme, ubiquitin-specific proteases 8 (USP8). Melatonin, however, upregulated USP8 expression, thus maintaining the stability of NICD and Notch signaling, which ultimately reduced EC injury in our sepsis model and elevated the survival rate of septic mice. Conclusions We found a previously uncharacterized role of Notch1 in mediating vascular permeability during sepsis, and we showed that inhibition of NICD resulted in vascular EC dysfunction in sepsis, which was reversed by melatonin. Thus, the Notch1 signaling pathway is a potential target for the treatment of sepsis.
研究领域:
免疫学
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细胞生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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