INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2023
·Vol. 51
·期 6
·1-13
·
IF 5.4
Lin Yang,Chun-Feng Cheng,Zhi-Fang Li,Xiao-Jing Huang,Shao-Qing Cai,Shan-Yu Ye,Li-Jun Zhao,Yi Xiong,Dong-Feng Chen,He-Lu Liu,Zhen-Xing Ren,Hong-Cheng Fang
Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural compound extracted from a Chinese herb, with a clinically reported anti‑DCM effect; however, its molecular mechanisms have not yet been fully elucidated. The present study indicated that BBR markedly alleviated DCM by inhibiting IL‑1β secretion and the expression of gasdermin D (Gsdmd) at the post‑transcriptional level. Considering the importance of microRNAs (miRNAs/miRs) in the regulation of the post‑transcriptional process of specific genes, the ability of BBR to upregulate the expression levels of miR‑18a‑3p by activating its promoter (‑1,000/‑500) was examined. Notably, miR‑18a‑3p targeted Gsdmd and abated pyroptosis in high glucose‑treated H9C2 cells. Moreover, miR‑18a‑3p overexpression inhibited Gsdmd expression and improved biomarkers of cardiac function in a rat model of DCM. On the whole, the findings of the present study indicate that BBR alleviates DCM by inhibiting miR‑18a‑3p‑mediated Gsdmd activation; thus, BBR may be considered a potential therapeutic agent for the treatment of DCM.
研究领域:
心脏病学
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药理学
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分子生物学
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糖尿病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yuan-Fei Lu,Qiao-Mei Zhou,Xiao-Yan Yang,Jia-Ping Zhou,Xiao-Jie Wang,Jie-Ni Yu,Jin-Guo Zhang,Yong-Zhong Du,Ri-Sheng Yu
Immune checkpoint blockade (ICB) therapy for hepatocellular carcinoma (HCC) is limited due to its immunosuppressive tumor microenvironment (TME). Proinflammatory pyroptosis as a new schedule can induce immunogenic cell death (ICD), thereby reversing immunosuppressive TME and improving ICB efficiency. Herein, we report an acid-etched layered double hydroxides nanosheets (E-LDH)-based smart nanoplatforms armed with H 2 O 2 /pH dual “doorkeepers” (denoted as CTEP) targeting HCC to realize membrane-anchored photodynamic therapy (PDT) and evoke potent pyroptosis to effectively improve anti-tumor immunity. The hybrid Hepa1-6 cancer cell membrane (CM) and thylakoid (TK) membrane is cloaked on the surface of pH-(low)-insertion peptide (pHLIP) modified E-LDH to obtain CTEP. Once CTEP nanoplatforms arrive at tumor regions, the dual “doorkeepers” will orderly open to perform PDT precisely. Given the fact that TK membranes have the catalase mimetic function, CTEP is able to respond to high concentrations of H 2 O 2 in TME and rupture the hybrid CM-TK membrane to expose pH-sensitive peptide pHLIP. Membrane-localized PDT can induce gasdermin-D (GSDMD) mediated pyroptosis, effectively stimulating tumor immunogenicity. Pyroptotic cell death releases damage-associated molecular patterns (DAMPs) and consequently robust IaCB ability. CTEP-evoked pyroptosis together with anti-PD-L1 blockade therapy activates adaptive immunity in HCC, successfully inhibiting the progression of primary and distant HCC tumors with mitigation of the side effects. This research has demonstrated that CTEP with excellent biocompatibility and homologous targeting ability can act as a potent pyroptosis inducer to improve immune efficacy. The combination of PDT and immunotherapy via a photo-pyroptosis pathway can be a smart strategy for HCC treatment.
研究领域:
肿瘤学
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免疫治疗
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纳米技术
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-17
·
IF 10.2
Yang Yuxuan,Yang Jia,Zhu Nan,Qiu Haosen,Feng Wenxiang,Chen Ying,Chen Xinhua,Chen Yuehong,Zheng Wenbo,Liang Min,Lin Tian,Yu Jiang,Guo Zhaoze
In recent years, immunotherapy has emerged as a promising strategy for treating solid tumors, although its efficacy remains limited to a subset of patients. Transforming non-responsive “cold” tumor types into immuno-responsive “hot” ones is critical to enhance the efficacy of immune-based cancer treatments. Pyroptosis, a programmed cell death mechanism, not only effectively eliminates tumor cells but also triggers a potent inflammatory response to initiate anti-tumor immune activities. This sheds light on the potential of pyroptosis to sensitize tumors to immune therapy. Hence, it is urgent to explore and develop novel treatments (e.g., nanomedicines) which are capable of inducing pyroptosis. In this study, we constructed tumor-targeting nanoparticles (CS-HAP@ATO NPs) by loading atorvastatin (ATO) onto chondroitin sulfate (CS) modified hydroxyapatite (HAP) nanoparticles (CS-HAP). CS was strategically employed to target tumor cells, while HAP exhibited the capacity to release calcium ions (Ca 2+ ) in response to the tumor microenvironment. Moreover, ATO disrupted the mitochondrial function, leading to intracellular energy depletion and consequential changes in mitochondrial membrane permeability, followed by the influx of Ca 2+ into the cytoplasm and mitochondria. CS and HAP synergetically augmented mitochondrial calcium overload, inciting the production of substantial amount of reactive oxygen species (ROS) and the subsequent liberation of oxidized mitochondrial DNA (OX-mitoDNA). This intricate activation process promoted the assembly of inflammasomes, most notably the NLRP3 inflammasome, followed by triggering caspase-1 activation. The activated caspase-1 was able to induce gasderminD (GSDMD) protein cleavage and present the GSDM-N domain, which interacted with phospholipids in the cell membrane. Then, the cell membrane permeability was raised, cellular swelling was observed, and abundant cell contents and inflammatory mediators were released. Ultimately, this orchestrated sequence of events served to enhance the anti-tumor immunoresponse within the organism.
研究领域:
癌症免疫疗法
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纳米技术
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细胞生物学
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）