BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2012
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IF 2.484
Da-Quan Sun,Ying Wang,Ding-Gan Liu
AU-rich elements are functional motifs in the 3′untranslated region of mRNA and are binding sites for the RNA binding protein HuR, an mRNA stabilizer and translation enhancer implicated in carcinogenesis. It is not clear whether, and, if so, how the AU-rich elements function in cells when they are separated from their mRNA and form an independent RNA species. Here, we show that a short RNA with AU-rich elements derived from C/EBPβ 3′UTR suppressed growth in a human liver cancer cell line. It specifically bound HuR, and it competed with C/EBPβ mRNA in order to bind to HuR. Our results provide evidence that the cancer cell growth suppression by this 62nt RNA containing AU-rich elements may be due to competitive binding to HuR. This work may open new options for the development of novel anti-cancer drugs.
研究领域:
分子生物学
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癌症研究
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RNA生物学
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产品关联
DOI
PubMed
高影响因子
iScience
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2021
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IF 5.458
Jun Ma,Jiajia Lu,Zhibin Zhou,Nan Lu,Jia He,Lei Zhu,Tianwen Ye
Summary The precise effect of estrogen (E2) on osteoclast function is still poorly understood. The aim of this study was to investigate the potential role of transient receptor potential vanilloid 6 (TRPV6) in E2-mediated osteoclast function and to characterize the relevant underlying mechanisms. Here, we found that Trpv6 is drastically decreased in ovariectomy operation animals and the administration of E2 results in an increased expression of Trpv6 in osteoclasts. In contrast, Trpv6 depletion significantly blocked the inhibitory effects of E2 on bone resorption activity, and silencing Trpv6 alleviated E2-induced osteoclast apoptosis. In addition, we found that E2 regulates the transcription of Trpv6 through ERα, by interacting with C/EBPβ and NF-κB. Chip assay analysis indicated that C/EBPβ regulates Trpv6 transcription by binding to Trpv6 promoter fragments −1,866 nt to −1,761 nt and −2,685 nt to −2,580 nt, whereas NF-κB binds to the −953 nt to −851 nt region. We conclude that TRPV6 has a significant effect on E2-mediated osteoclast function.
研究领域:
骨骼生物学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Zhaokun shi,Qinyu Peng,Shangqi Sun,Min Xiong,Xue Zhu,Huijuan Wang,Shiping Liu,Zhenwen Li,Lu Wang,Guang Li,Liying Zhan
Septic encephalopathy (SE), a neurocritical complication with alarmingly high mortality rates, represents a major diagnostic and therapeutic challenge in intensive care units (ICUs). Current diagnostic protocols rely predominantly on nonspecific clinical symptom assessment, while conventional laboratory biomarkers exhibit insufficient sensitivity for early detection. This diagnostic ambiguity contributes to delayed interventions and unfavorable patient prognoses. Mechanistically, prior studies in Alzheimer's disease (AD) have established that genetic ablation of C/EBP β or AEP (asparagine endopeptidase) mitigates neuroinflammation and disease progression. Intriguingly, our investigation reveals a pathophysiological paradox in SE: Conditional AEP knockout significantly attenuated sepsis-induced hippocampal damage, whereas C/EBP β knockdown unexpectedly exacerbated neuronal injury — findings directly opposing AD-related mechanisms. Notably, this study identifies mitochondrial dysfunction in hippocampal neurons as a previously unrecognized hallmark of SE, characterized by cristae fragmentation and mitochondrial membrane potential collapse. Multimodal analyses further demonstrate that AEP inhibition rescues synaptic plasticity through dual modulation of STat3 signaling and oxidative stress cascades. Importantly, our paradoxical findings regarding C/EBP β suggest context-dependent regulation of neuroinflammation, challenging the prevailing assumption of pathway conservation across neuropathologies. These translational insights not only elucidate the C/EBP β/AEP axis as a novel therapeutic target in SE but also warrant caution against extrapolating AD-derived mechanisms to sepsis-related encephalopathies.
研究领域:
神经科学
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重症监护医学
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分子生物学
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免疫学
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病理生理学
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线粒体生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Xiaochang Chen,Peihong Su,Hua Guan,Aoqi Xiang,Lusha Zhang,Zexing Deng,Qi Yu
Obesity is strongly associated with hypertension, hyperglycemia, insulin resistance, and other metabolic syndrome symptoms, emphasizing the urgent need for innovative therapeutic strategies. Physiochemotherapy, which combines the advantages of chemical and physical therapies, has attracted significant research interest. However, the precise outcomes and mechanisms of this integrative approach for obesity treatment remain poorly understood. In this study, we developed a physically photothermal nanocomposite hydrogel (termed SDAR) loaded with chemical resveratrol nanoparticles for obesity mitigation. SDAR was synthesized using polydopamine-functionalized sodium alginate, Zn 2+ , and resveratrol nanoparticles. The resveratrol nanoparticles exhibited a size distribution of 5–15 nm and a minor Zetal potential below 1.3 mV across varying pH conditions. The engineered SDAR hydrogel demonstrated stable photothermal performance with a steady temperature around 44 °C, high biocompatibility, strong antioxidant capacity (antioxidant rate of 93.7 %), and anti-inflammatory properties. In a lipid differentiation model, photothermal SDAR hydrogel administration effectively reduced intracellular reactive oxygen species (ROS) and inflammatory markers by over 50 % in 3T3-L1 preadipocytes. Furthermore, SDAR attenuated CCAAT/enhancer-binding protein beta (C/EBPβ) binding activity to downstream target genes, thereby inhibiting lipogenic differentiation. Collectively, the photothermal-responsive SDAR hydrogel presents a promising physiochemotherapy strategy for obesity treatment by suppressing lipogenesis.
研究领域:
药理学
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生物医学工程
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代谢紊乱
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纳米技术
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肥胖研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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