REDOX REPORT
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2024
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IF 5.2
Hanan M. Hassan,Ahmed M. Hamdan,Abdullah Alattar,Reem Alshaman,Omar Bahattab,Mohammed M. H. Al-Gayyar
Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.
研究领域:
药理学
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肿瘤学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2026
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IF 5
Qi Lou,Rui Bai,Yongwu Liu,Bo Li,Haoran Zhu,Guangzhong Liu
Reports indicate that MARCHF6 can regulate ferroptosis. • The high expression of MARCHF6 alleviates myocardial ischemia-reperfusion injury. • Elevated MARCHF6 expression inhibits ferroptosis in CMECs. • MARCHF6 regulates ferroptosis through the ADAMTS4/SDC-1 pathway. • MARCHF6 is a promising therapeutic target for MIRI. Myocardial ischemia-reperfusion injury is a key factor affecting prognosis after acute myocardial infarction. MARCHF6, as an E3 ubiquitin ligase, is closely implicated in the ferroptosis process. The role of MARCHF6 in MIRI and its mechanism for regulating myocardial cell ferroptosis remained unclear. A mouse model of MIRI overexpressing MARCHF6 was established by tail vein injection of MARCHF6-overexpressing AAV9 virus, followed by left anterior descending coronary artery ligation surgery in mice. High expression of MARCHF6 significantly improved cardiac function and reduced myocardial injury in MIRI mice. Compared with the MIRI mice, the MARCHF6 overexpression mice exhibited a reduction of approximately 14% in myocardial infarction area. Histological damage in the cardiac ischemic penumbra region was markedly alleviated, and the number of cell deaths was significantly decreased. Concurrently, MARCHF6 overexpression substantially reduced serum levels of myocardial injury markers CK-MB, cTnI, and LDH. Mitochondrial morphological alterations and expression of ferroptosis-related indicators in the ischemic penumbra of the heart indicated that MARCHF6 overexpression alleviated ferroptosis in MIRI hearts. In an OGD/R-induced cardiomyocyte microvascular endothelial cell (CMEC) model, MARCHF6 overexpression alleviated lipid peroxidation and inhibited ferroptosis. MARCHF6 overexpression suppressed the upregulation of ACSL4 and 4-HNE while blocking the downregulation of SLC7A11 and GPX4 in vivo and vitro . Mechanistically, MARCHF6 promoted the ubiquitin-mediated degradation of ADAMTS4, thereby upregulating its downstream target SDC-1. This sequence of events inhibits lipid peroxidation, mitigates mitochondrial damage, and ultimately blocks the ferroptosis process in endothelial cells. These findings unveil a novel regulatory pathway involving MARCHF6/ADAMTS4/SDC-1 against MIRI by inhibiting ferroptosis. Download: Download high-res image (104KB) Download: Download full-size image
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF CARDIOLOGY
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2026
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IF 3.2
Qi Lou,Rui Bai,Luyifei Li,Bingqing Lu,Xiaoming Ai,Guangzhong Liu
Background Myocardial ischemia-reperfusion injury (MIRI) is an inevitable consequence of reperfusion therapy and a major determinant of patient prognosis. ADAM Metallopeptidase with Thrombospondin Type 1 Motif 4 (ADAMTS4) is a metalloproteinase that has been implicated in endothelial damage and inflammatory cascades, yet its role in MIRI remains undefined. Methods MIRI was modeled in mice by left coronary artery ligation and subsequently subjected to mRNA sequencing. The role of ADAMTS4 was then dissected in vivo in these MIRI mice and in vitro in cardiac endothelial cells (ECs) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), using both primary murine cardiac ECs and human cardiac microvascular ECs (hCMECs). Results ADAMTS4 was markedly up-regulated in MIRI mouse myocardium and in both primary murine cardiac ECs and hCMECs subjected to OGD/R. ADAMTS4 inhibition preserved cardiac function, shrank infarct size, and attenuated cardiomyocyte damage. At the microvascular level, ADAMTS4 silencing restored CD31 and VE-Cadherin expression, curbed leukocyte adhesion molecules, and lowered tissue myeloperoxidase activity together with pro-inflammatory cytokines. Consequently, endothelial barrier dysfunction and leukocyte transmigration provoked by OGD/R were largely reversed. Mechanistic studies suggested that ADAMTS4 may be transcriptionally regulated by FosB and JunB. Upregulation of FosB or JunB significantly enhanced the transcriptional activity of ADAMTS4. Moreover, overexpression of ADAMTS4 abrogated the protection afforded by FosB/JunB knockdown, establishing ADAMTS4 as the critical downstream executor of activating protein-1 mediated injury in MIRI. Conclusion Overall, we established that FosB and JunB transcriptionally upregulate ADAMTS4, which in turn dismantles the cardiac endothelial barrier and fuels leukocyte infiltration to exacerbate MIRI.
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高影响因子
Materials Today Bio
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2023
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IF 8.2
Zhaowei Yin,Chaoren Qin,Shaowei Pan,Chen Shi,Guanfu Wu,Yan Feng,Jing Zhang,Ziyi Yu,Bin Liang,Jianchao Gui
Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (Exos IPFP ) and ScAT stem cells (Exos ScAT ) in OA treatment. Results suggested that Exos IPFP significantly inhibit the degradation of cartilage extracellular matrix (ECM) than Exos ScAT , following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in Exos ScAT (Exos ScAT−99b−3p ), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in Exos ScAT would enable them to exhibit comparable or even superior effectiveness to Exos IPFP for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.
研究领域:
生物材料
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干细胞治疗
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基因治疗
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骨科
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药学
✓ 已验证
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）