Frontiers in Pharmacology
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2026
·
IF 5.4
Yanqing Wu,Xilin Qiao,Shuaiyu Chen,Yalan Lu,Bingyan Mao,Mengdie Zhu,Xinzhi Chen,Nipi Chen,Zhishan Ding,Bo Jin
Introduction MicroRNA-29b-3p (miR-29b-3p) plays a critical role in regulating endothelial apoptosis and autophagy. We previously demonstrated that protocatechualdehyde (PCA), a water-soluble phenolic acid derived from Salvia miltiorrhiza Bge., protects human umbilical vein endothelial cells (HUVECs) against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury. However, whether miR-29b-3p mediates this protective effect remains unclear. Methods Using the OGD/R in vitro model of ischemia-reperfusion injury, we investigated the molecular mechanisms underlying ischemic damage at the cellular level. RT-qPCR was used to measure miR-29b-3p expression, Western blotting to assess autophagy- and apoptosis-related proteins, and MDC staining and flow cytometry to evaluate autophagy and apoptosis, respectively. Results The results showed that miR-29b-3p was downregulated in OGD/R-treated HUVECs, an effect that was reversed by PCA and the ROS inhibitor N-acetylcysteine (NAC). The miR-29b-3p mimic enhanced the promoting effects of PCA and NAC on miR-29b-3p expression, whereas miR-29b-3p inhibitor reversed these effects. Similarly, PCA-induced autophagy and inhibition of apoptosis were enhanced by the miR-29b-3p mimic and reversed by the inhibitor. To determine whether SIRT1 acts downstream of miR-29b-3p, we used EX527 (a SIRT1 inhibitor) and found that it attenuated the PCA-mediated upregulation of miR-29b-3p. The miR-29b-3p mimic enhanced PCA-induced SIRT1 activity and protein expression, while the inhibitor had the opposite effect. Additional experiments revealed that NAC suppressed ROS by upregulating miR-29b-3p, leading to increased SIRT1 expression and reduced apoptosis. Disscussion Collectively, these findings demonstrate that PCA ameliorates OGD/R-induced endothelial injury by promoting autophagy and inhibiting apoptosis via the ROS/miR-29b-3p/SIRT1 regulatory axis.
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高影响因子
ELECTROCHIMICA ACTA
·
2025
·
IF 5.6
Zhikun Zhang,Ying Shi,Zhengjie Li,Jilong Han,Zhiyan Chen,Fangfang Ma,Yanchao Qi,Yumin Liu
MicroRNA-21 (miR-21) has shown great promise as a biomarker for early cancer diagnosis. However, its trace-level abundance in clinical samples complicates point-of-care detection. Herein, we developed a new DNA-modified bimetallic dual-ligand MOF-based electrochemical sensor for highly sensitive and rapid detection of miR-21. The MOF was synthesized using 2,2′-bipyridine-5,5′-dicarboxylic acid (DPDC) and meso‑2,3-dimercaptosuccinic acid (DMSA) as organic linkers, with Ni²⁺/Co²⁺ serving as metal centers. Subsequently, the capture DNA (cDNA) was designed and modified MOF with high porosity and large surface area, significantly enhancing molecular interactions between the cDNA and target miR-21 to boost sensitivity. The developed biosensor exhibits a linear detection range of 10 fM to 100 nM, with a low detection limit of 10 fM and excellent specificity. This method effectively detects miR-21 in blood samples, showcasing strong clinical potential and providing a reliable platform for precision biosensing.
研究领域:
生物传感器
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纳米技术
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生物化学
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分子诊断学
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材料科学
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电化学
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肿瘤学
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JOURNAL OF NEUROSCIENCE
·
2025
·
IF 4
Tianyi Yang,Yan Chen,Maolin Wang,Ren Ren,Fang Yan,Peng Xu,Bin Di
Nitrous oxide use Disorder（NUD）has recently received increasing social concern for its sharp rise among young people. However, the underlying mechanisms of NUD remain largely unexplored, which obstructs treatment strategy development and may exacerbate the epidemic of N2O abuse. Thus, specifying the essential mechanisms and targets in NUD are desperately needed. Here we unveiled a series of molecular adaptations regarding N2O reward memory in Nucleus accumbens (NAc) of mice through multi-omics approaches comprising transcriptomics, proteomics, metabolomics approaches. Our miRNA transcriptomics and pull-down proteomics analyzes uncovered that miR-7220-5p regulated N2O-induced conditioned-place preference (CPP) and associated increase of dendritic spine density in NAc of male mice. Our pull-down proteomics and metabolomics analyzes revealed that miR-7220-5p modulated ERK signaling pathway by directly binding with NR2B receptor. In summary, our work confirmed that restoring miR-7220-5p expression in NAc protected against synaptic abnormality via the NR2B/ERK/CREB signaling, thereby attenuating CPP behaviors in NUD. Selective inhibition of NR2B or ERK signaling blocked the reward memory of N2O-CPP via NAc microinjection. Our study proposed a potential therapeutic strategy for NUD and provided comprehensive resources of biological data to support future investigations of NUD treatment.Significance Statement Nitrous oxide Use Disorder (NUD) has recently received tremendously increasing social concern for its sharp rise among young people. Although the neurological consequences and their etiologies of consuming N2O have been well elucidated, the underlying mechanisms of NUD remain largely unexplored, which obstructs the development of clinical treatment strategies and may exacerbate the epidemic of N2O abuse. Our work uncovered the role of miR-7220-5p/NR2B/ERK/CREB signaling against synaptic abnormality/CPP behaviors. Selective inhibition of NR2B or ERK signaling blocked the reward memory of N2O-CPP via NAc microinjection. Our study proposed therapeutic targets for overcoming NUD behaviors and the omics data provided comprehensive biological resources to support future investigations of NUD.
研究领域:
神经科学
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分子生物学
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药理学
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生物信息学
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精神病学
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细胞信号传导
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成瘾研究
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高影响因子
NEUROMOLECULAR MEDICINE
·
2021
·Vol. 24
·期 2
·224-231
·
IF 3.843
Wei Guangxin,Li Shengjun,Wang Pengcheng,Wang Shouxian,Zhao Yujing
Glioma is a kind of brain tumor with low overall survival and treatment success rates in the advanced stage. Evidence has shown microRNA-575 (miR-575) plays an important role in the generation and development of various cancers. This study aimed to explore the function of miR-575 in the prognosis and cell biological behavior of glioma. qRT-PCR was used to evaluate the expression of miR-575 in glioma tissues and cells, Kaplan–Meier survival analysis and Cox regression analysis were used to evaluate the prognostic value. The proliferation ability of glioma cells was determined by MTT assay; the invasion and migration abilities were determined by transwell assays. Compared with normal brain tissues, the expression of miR-575 in glioma tissue cells was significantly up-regulated ( P < 0.001). The survival rate of patients in the miR-575 high expression group was significantly lower than that in the low expression group ( P = 0.020). In addition, the overexpression of miR-575 promoted the proliferation, migration, and invasion of glioma cells. The results of this study suggested that miR-575 may be a new biomarker for the prognosis of glioma.
研究领域:
肿瘤学
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分子生物学
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神经科学
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PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Yaru Wang,Yanting Li,Xin Li
Background This study compared the effect of ultrasound microbubble-mediated miR-503–5p downregulation with that of pure liposome-mediated miR-503–5p downregulation on colorectal cancer (CRC) progression and explored the downstream mechanism. Methods Bioinformatics tools were utilized to predict miR-503–5p-targeted genes and CRC progression-associated genes. MiR-503–5p and sal-like 1 (SALL1) expressions in CRC cells and tissues were analyzed by qRT-PCR and/or bioinformatics tools; their correlations with overall survival and clinicopathological features of CRC patients were presented, and their interaction was validated by dual-luciferase reporter assay. CRC cells received ultrasound microbubble-mediated miR-503–5p downregulation and/or liposome-mediated miR-503–5p downregulation or SALL1 silencing. Cell phenotype changes were evaluated by flow cytometry, as well as MTT, Wound healing, Transwell and tube formation assays. E-cadherin, N-cadherin, Vimentin , B-cell lymphoma (Bcl)− 2, Cleaved caspase-3, and SALL1 expressions in cells were analyzed by Western blot . Results Upregulated miR-503–5p in CRC tissues and cells was detected, associated with poorer cell differentiation , easier lymph node metastasis and higher TNM stages, and related to poorer prognoses of CRC patients. Ultrasound microbubble-mediated miR-503–5p downregulation relative to pure liposome-mediated miR-503–5p downregulation better decreased viability, inhibited migration, invasion and tube formation, enhanced apoptosis, upregulated SALL1, E-cadherin and Cleaved caspase-3, and downregulated miR-503–5p, N-cadherin, Vimentin and Bcl-2 in CRC cells. SALL1 was targeted by miR-503–5p, low-expressed in CRC tissues and cells and positively related to CRC patients’ survival. Silencing SALL1 exerted the opposite effects, which reversed the effects of ultrasound microbubble-mediated miR-503–5p downregulation and vice versa. Conclusion Ultrasound microbubble-mediated miR-503–5p downregulation suppressed in vitro CRC progression via promoting SALL1 expression.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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高影响因子
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
·
2022
·
IF 5.763
Min Li,Yanyan Yang,Jinbao Zong,Zhibin Wang,Shaoyan Jiang,Xiuxiu Fu,Xiangqin He,Xiaoxin Li,Qianqian Xue,Jian-Xun Wang,Tao Yu
Background Aortic dissection (AD) is a lethal cardiac disorder and one of the most concerning cardiovascular diseases (CVDs). Increasing evidence indicates that human aortic vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AD, especially related to phenotypic transformation. And notablely, the development of AD is also accompanied by inflammation. Methods By using quantitative real-time PCR and fluorescence in situ hybridization (FISH), we detected the expression levels of miR-564 in vitro and in vivo. The effects of miR-564 proliferation and migration were investigated in VSMCs. The downstream targets of miR-564 were found by bioinformatics analyse, and verified in the regulation on VSMCs. An AD murine model was constructed and clinical evaluation was performed to explore the critical roles of miR-564 in vivo. At the same time, the level of inflammation was detected using quantitative real-time PCR and immunofluorescence. Results Overexpression of miR-564 inhibited cell proliferation and migration, as well as phenotype switch, with or without platelet-derived growth factor BB (PDGF-BB) treatment, whereas downregulation of miR-564 led to opposite results. Mechanistically, miR-564 directly interacted with the target genes proto-oncogene (SKI) and neurogranin (NRGN) to regulate the biological functions of VSMCs. In particular, animal experiments demonstrated that miR-564 can alleviate the progression of AD mainly through mediating phenotypic swithing and inflammation which was consistent with clinical evaluation. Conclusions Our study identified miR-564 as a significant molecule that attenuates AD progression by inhibiting inflammation and VSMCs proliferation, migration and phenotypic transformation, suggesting that it may be a potential therapeutic target for AD.
研究领域:
心血管疾病
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分子生物学
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病理学
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高影响因子
Cell Death & Disease
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2021
·Vol. 12
·期 1
·1-16
·
IF 8.469
Yang Jin,Cao Lu-Lu,Wang Xi-Peng,Guo Wei,Guo Ruo-Bing,Sun Yu-Qin,Xue Teng-Fei,Cai Zhen-Yu,Ji Juan,Cheng Hong,Sun Xiu-Lan
Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.
研究领域:
神经科学
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分子生物学
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细胞生物学
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中风研究
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高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2021
·Vol. 476
·期 5
·2061-2073
·
IF 3.396
Wang Gang,Wang Hefeng,Zhang Lijuan,Guo Feng,Wu Xiangyu,Liu Yang
Studies have reported that miR-195-5p plays a role in the Hirschsprung disease (HSCR). Our previous work found GDNF family receptor alpha 4 (GFRA4) is also associated with HSCR. In this study, we focused on whether miR-195-5p induces the absence of enteric neurons and enteric neural crest in HSCR by regulating GFRA4. The expression levels of GFRA4 and miR-195-5p in colon tissues were evaluated by real-time PCR (RT-PCR) assay. We overexpressed GFRA4 or miR-195-5p in SH-SY5Y cells, the cell proliferation, cell cycle, apoptosis and invasion were subsequently investigated by CCK-8 assay, EdU staining, Flow cytometry analysis and Transwell assay, respectively. We also established the xenograft model to detect the effect of miR-195-5p on tumor growth and GFRA4 and p-RET expressions. GFRA4 expression was significantly downregulated in the HSCR colon tissues when compared with that in the control tissues. Overexpression of GFRA4 significantly promoted proliferation, invasion and cell cycle arrest, and inhibited apoptosis of SH-SY5Y cells. We also proved that GFRA4 is a direct target of miR-195-5p, and miR-195-5p inhibited proliferation, invasion, cell cycle arrest and differentiation, and accelerated apoptosis in SH-SY5Y cells which can be reversed by GFRA4 overexpression. Furthermore, we demonstrated that miR-195-5p suppressed tumor growth, and observably decreased GFRA4 and p-RET expressions. Our findings suggest that miR-195-5p plays an important role in the pathogenesis of HSCR. MiR-195-5p inhibited proliferation, invasion and cell cycle arrest, and accelerated apoptosis of nerve cells by targeting GFRA4.
研究领域:
分子生物学
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神经科学
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医学遗传学
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
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IF 3.361
Gao Chao,Xiaoli Li,Yahong Ji,Ying Zhu,Na Li,Nana Zhang,Zunyong Feng,Min Niu
High expression levels of miR-155 are involved in the pathogenesis of inflammatory bowel disease (IBD). We observed an increase in miR-155 in peripheral regulatory T (Treg) cells from IBD patients . Mice that specifically overexpress miR-155 in Foxp3+ Treg cells exhibit spontaneous autoimmunity and more severe dextran sulfate sodium (DSS)-induced intestinal injury . MiR-155 overexpression can lead to a lack of follicular Treg (Tfr) cells and central Treg (cTreg), whereas DSS treatment further depletes the Tfr cells. Furthermore, miR-155 can target the expression of CTLA-4 in cTreg and Tfr, directly inhibiting Tfr cell production and promoting enhanced germinal center (GC) B cell activation and autoantibody overproduction. This outcome may be the cause of severe intestinal injury in patients with autoimmune IBD.
研究领域:
免疫学
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胃肠病学
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分子生物学
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PubMed
高影响因子
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
·
2023
·Vol. 90
·期 5
·e13791
·
IF 3.6
Wenzhi Wang,Jianyong Shi,Lei Zheng
The emerging role of microRNA-935 (miR-935) in modulating cancer progression has been recognized. However, its role in regulating choriocarcinoma (CCA) development and progression remains unknown. The present work aims to reveal the effect of miR-935 on CCA cell tumor properties and the related mechanism. The RNA expression of methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3), miR-935, and gap junction protein alpha 1 (GJA1) was detected by quantitative real-time polymerase chain reaction. Protein expression of GJA1, Ki67, and METTL3 was measured by western blotting and immunohistochemistry assays. CCK-8 and colony formation were used to analyze cell proliferation. Transwell assays were performed to assess cell migration and invasion. Angiogenesis was investigated by tube formation assay. Xenograft mouse model assay was used to determine miR-935-mediated effect on tumor formation in vivo. The luciferase reporter assay and RNA pull-down assay were used to verify the relationship between miR-935 and GJA1. MeRIP assay was used to analyze the m6A methylation of pri-miR-935. MiR-935 expression was significantly upregulated in CCA tissues and cells when compared with control groups. MiR-935 overexpression promoted CCA cell proliferation, migration, invasion, and tube formation and tumor tumorigenesis in vitro and in vivo, but miR-935 knockdown showed the opposite effects. In addition, miR-935 targeted GJA1 and mediated CCA cell tumor properties by negatively regulating GJA1 expression. METTL3 promoted miR-935 maturation by inducing m6A methylation of pri-miR-935, and its overexpression contributed to CCA cell tumor properties through the regulation of miR-935. METTL3 promoted choriocarcinoma progression by m6A-dependently activating the miR-935/GJA1 pathway.
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高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
MinChao Feng,BaiJun Qin,Fang Luo,Hui Li,KunRong Liu,Kai Li,DongYang Wu,XiPing Tang,Guozhong Chen
Background Safer and more effective drugs are needed for the treatment of acute pancreatitis (AP). Qingjie Huagong decoction (QJHGD) has been applied to treat AP for many years and has shown good clinical effects. However, the potential mechanism has not yet been determined. Purpose To investigate the role and underlying mechanism of the effects of QJHGD on AP both in vitro and in vivo . Methods QJHGD was characterized by UHPLC-Q-Orbitrap-MS. The protective effect of QJHDG and the underlying mechanism were investigated in MPC-83 cells in vitro . A caerulein-induced AP model was established to evaluate the protective effect of QJHGD in mice. CCK-8 assays were used to detect cell viability. The contents of inflammatory mediators were determined by ELISA. Expression levels of circRNA, miRNA and mRNA were determined by qRT-PCR. Protein expression was determined using Western blot . Pancreatic tissues were assessed by hematoxylin and eosin staining as well as immunohistochemical and immunofluorescence analyses. Pull-down and luciferase activity assays were performed to determine the regulatory relationships of circHipk3, miR-193a-5p and NLRP3. Results Our results confirmed that mmu-miR-193a-5p was sponged by mmu-circHipk3, and NLRP3 was a target of miR-193a-5p. In vitro experiments showed that QJHGD enhanced MPC-83 cell viability by regulating circHipk3 sponging mir-193a-5 targeting NLRP3 and inhibiting pyroptosis-related factors. Finally, we showed that QJHGD ameliorated pancreatic tissue injury in AP mice via this pathway. Conclusion This study demonstrate that QJHDG exerted its anti-AP effects via the circHipk3/miR-193a-5p/NLRP3 pathway, revealing a novel mechanism for the therapeutic effect of QJHDG on AP.
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高影响因子
ANALYTICAL BIOCHEMISTRY
·
2023
·
IF 2.9
Jianhua Yan,Jiayu Wang,Hongjie Liu,Liwei Wang,Kefu Yu,Li Deng,Junyou Su,Hongfei Chen
Gestational diabetes mellitus (GDM) is a severe perinatal condition with serious consequences for the growth and development of the mother and baby. MicroRNA-29b (miR-29b) is essential to the pathogenesis of GDM and can be used as a molecular biomarker for diagnosis. Given the limitations of current GDM screening technologies, there is a pressing need for a sensitive detection approach to evaluate serum miR-29b in GDM patients, thus aiding in disease treatment. In this study, an electrochemical biosensor Co 7 Fe 3 –CN nanoparticles (NPs) was developed. Using a duplex-specific nuclease (DSN) signal amplification strategy with a linear range of 1–10 4 pM and a low detection limit of 0.79 pM, the ultra-sensitive detection and quantification of miR-29b were accomplished. The dependability and applicability of the developed biosensor were validated by the standard method of qRT-PCR, and the content of serum miR-29b in GDM patients was shown to be significantly lower than that in the control group ( P = 0.03). Specifically, miR-29b concentrations could be detected from 2.0 to 7.5 and 2.4 to 7.3 pM using qRT-PCR and the biosensor, respectively. These similar results indicated that a biosensor based on miR-29b detection has the potential to be used in the point-of-care testing of GDM patients in clinical practice.
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高影响因子
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