Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-18
·
IF 7.3
Mao Shihui,Lan Ting,Sun Yimei,Li Lin,Jiang Weifeng,Xu Jiadong,Feng Yan,Hu Huiqin,Fang Yan,Xu Lanxi,Chu Lisheng
Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) show therapeutic promise for ischemic stroke (IS). Preconditioning MSCs with drugs can modulate the cargo composition and function of their derived EVs. This study investigated the therapeutic effects and underlying mechanisms of EVs derived from tetramethylpyrazine (TMP)-preconditioned BMSCs (TMP-BMSC-EVs) in IS.Methods EVs were isolated from BMSCs pretreated with or without TMP by differential centrifugation. The therapeutic efficacy of EVs was evaluated in a rat model of middle cerebral artery occlusion (MCAO) through neurological function assessments and infarct volume quantification. The expression of miR-486 and its roles in regulating microglia/macrophage polarization and neurogenesis, as well as the mechanistic targets, were examined by real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, and Western blotting.Results TMP-BMSC-EVs exerted superior therapeutic efficacy compared to BMSC-EVs. Mechanistically, TMP-BMSC-EVs were enriched with miR-486, which promoted microglia/macrophage M2 polarization and neurogenesis, while downregulating phosphatase and tensin homolog (PTEN) and phosphorylated NF-κB (p-NF-κB) protein levels, and upregulating phosphorylated Akt (p-Akt) expression. Transfection with a miR-486 inhibitor abolished the beneficial effects of TMP-BMSC-EVs, which could be counteracted by the PTEN inhibitor bisperoxovanadium (bpV).Conclusion sTMP-BMSC-EVs could significantly promote neural repair by driving microglia/macrophage M2 polarization and enhancing neurogenesis through miR-486-mediated PTEN inhibition, thereby offering a promising treatment strategy for IS.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Dake Huang,Ke Shen,Li Gui,Qiongqiong Cao,Fangmei Yu,Yunxia Lu
Given resveratrol's (RES) potential as an anti-aging agent, this study explored its ability to inhibit the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome through the miR-217/SIRT1 axis in senescent endothelial cells. Male C57BL/6 mice were administered a customized regular diet supplemented with 0.04 % RES for 64 consecutive weeks. Subsequently, the effects of RES on senescent human umbilical vein endothelial cells (HUVECs) induced by H 2 O 2 were evaluated. Gene expression analyses were conducted following SIRT1 knockdown in HUVECs treated with H 2 O 2 and RES, or transfected with miR-217 mimics and inhibitors. The study found that RES reduced body weight, improved endothelial function, enhanced SIRT1 expression, and suppressed the expression of miR-217, NADPH oxidase 4 (NOX4), and NLRP3 in the senescent thoracic aorta. Additionally, RES significantly reduced the expression of NOX4, X-box binding protein 1 spliced (XBP1s), and reactive oxygen species (ROS) production in a dose-dependent manner in senescent HUVECs. SIRT1 knockdown resulted in the activation of the NLRP3 inflammasome by upregulating NOX4 and XBP1s expression, an effect that was partially attenuated by RES pretreatment. RES also suppressed the expression of miR-217 induced by H 2 O 2 . The miR-217 mimic facilitated cellular senescence; however, RES mitigated this effect, which was further amplified by the miR-217 inhibitor.
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Biomedical Optics Express
·
2025
·Vol. 16
·期 5
·2033-2046
·
IF 3.2
Binbin Zeng,Huaiwu Fu,Cong Wu,Xudong Zhang,Tianran Li,Qiong Xu,Yayun Qian,Yayun Qian,Ruirui Yang,Ruirui Yang
In this study, we constructed a SERS assay platform that can be used for the ultrasensitive detection of cerebral infarction (CI)-associated miR-106a-5p based on the recognition competition strategy and the highly efficient catalytic activity of Au@Pt NRs nanoenzymes. When the target miR-106a-5p is present in the detection solution, it binds to the nucleic acid aptamer (cDNA), leading to the detachment of its complementary strand (H1) carrying Au@Pt NRs from the surface of AuNHs, and the oxidation of TMB is reduced, resulting in the decrease of SERS signal. In addition, this method enables single-step, ultrasensitive detection of target miRNAs in patient serum with a limit of detection (LOD) of 0.96 fM, which is consistent with the results of real-time quantitative polymerase chain reaction (qRT-PCR) and fluorescence. This method provides a novel approach for the effective detection of miRNAs, which is of great clinical value for the early detection of CI.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Lanxi Xu,Yan Feng,Xintian Zheng,Meiyu Wang,Yan Fang,Lin Li,Jiadong Xu,Yani Zhang,Weiru Jiang,Lisheng Chu
Neuronal loss following ischemic stroke (IS) is a major cause of long-term neurological dysfunction. Neural stem cell (NSC) transplantation holds great potential for neural tissue repair, but exogenous NSCs often over-differentiate into astrocytes, resulting in glial scar formation and poor neuronal maturation, which limits clinical application. Astragaloside IV (AS-IV), a plant-derived monomer, has been shown to regulate the proliferation, migration, and differentiation of endogenous NSCs. This study investigated whether AS-IV preconditioning could promote the neurogenesis of transplanted NSCs and improve functional recovery after IS. Primary NSCs were cultured and exposed to various concentrations of AS-IV, and 100 μM was selected for further use. A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established, and AS-IV-preconditioned or untreated EGFP-labeled NSCs were transplanted into the striatum. Brain injury was assessed histologically. Neurological recovery was evaluated using the modified Neurological Severity Score, grip strength, adhesive removal, and Morris water maze tests. Immunofluorescence staining was used to assess graft survival, differentiation fate, synapse formation, and glial scar area. In vitro experiments explored the involvement of the miR-199a-5p/Caveolin-1 signaling pathway. AS-IV preconditioning significantly improved the survival and neuronal differentiation of grafted NSCs, reduced astrocytic lineage commitment and glial scar formation, and enhanced synaptic reconstruction. These effects were associated with improved sensorimotor and cognitive function. In conclusion, AS-IV pretreatment of NSCs promoted neuronal lineage commitment, inhibited glial scarring, and facilitated functional recovery after ischemic stroke. Targeting the miR-199a-5p/Caveolin-1 axis may offer a novel strategy for optimizing NSC-based therapy in stroke.
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Aggregate
·
2024
·
IF 13.9
Shuqi Wu,Fang Nan,Kewen Zhang,Wan Hao,Di Shi,Yang Li,Wei Deng,Nur Jarhen,Kaixuan Li,Yunyun Xiao,Jun Li,Xiao Lin
Osteoarthritis (OA) is associated with metabolic imbalance of articular cartilage and an increase of intracellular reactive oxygen species (ROS). Synergistic therapy based on the codelivery of ROS scavengers and antisense oligonucleotides (ASO) into chondrocytes has the potential to effectively treat OA. Here, we developed a novel biocompatible metal-organic framework (MOF)-encapsulated nanozyme/ASO delivery platform (miR/IrO 2 @ZIF-8) for OA treatment. IrO 2 nanoparticles with the catalytic activities of superoxide dismutase/catalase were synthesized using a hydrothermal method, resulting in excellent ROS scavenging performance. IrO 2 was further loaded into zeolitic imidazolate framework-8 (ZIF-8) to maintain its catalytic efficacy and regulate its size, surface charge, and biocompatibility to enhance the therapeutic effect of the platform. As an effective ASO delivery carrier, the synthesized IrO 2 @ZIF-8 exhibited high antagomiR-181a loading and lysosomal escape capacity, enabling it to rebalance cartilage metabolism. In vitro experiments showed that miR/IrO 2 @ZIF-8 could restore ROS levels, mitochondrial membrane potential, and lipid peroxidation in chondrocytes. At the same time, the expression levels of proinflammatory markers (IL-1β, IL-6, and COX-2) as well as the extracellular matrix degrading enzymes (ADAMTS-5 and MMP13) were downregulated, indicating effective antioxidant, anti-inflammatory, and anticartilage degradation effects. Notably, miR/IrO 2 @ZIF-8 was able to deliver IrO 2 nanoparticles and antagomiR-181a to the cartilage tissue at a depth of up to 1.5 mm, thus solving the problems of poor permeability and difficult retention of drugs in cartilage tissue. This further improves the synergistic therapeutic effect on OA by inhibiting cartilage degradation. The combination of MOF-encapsulated IrO 2 nanozymes with antagomiR-181a has an excellent therapeutic effect on OA, offering a promising translational medicine paradigm.
研究领域:
纳米技术
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药学
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生物医学工程
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骨科
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材料科学
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Medical Molecular Morphology
·
2021
·Vol. 54
·期 4
·337-345
·
IF 2.309
Xu Sijia,Dong Wenxin,Shi Yu
The purpose of this study is to explore whether LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, influencing the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation. PICSAR and miR-485-5p expressions were detected by qPCR. Cell proliferation was examined by CCK-8. Protein expressions were determined by western blot. Immunofluorescence detected the Ki-67 expression. Dual-luciferase followed by immunoprecipitation was performed to verify the interaction between PICSAR and miR-485-5p. Interference with PICSAR inhibited the abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and the excessive deposition of ECM. It was also confirmed in our study that MiR-485-5p is a direct target of PICSAR in HSFs. Additionally, inhibition of miR-485-5p reversed the effect of PICSAR knockdown in HSFs. LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, promoting the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation.
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IMMUNOBIOLOGY
·
2023
·
IF 2.8
Zepeng Chen,Qinglong Gu,Ruichao Chen
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Fang Hu,Wancun Zhang,Jiaqi Zhang,Qi Zhang,Tao Sheng,Yueqing Gu
In this study, a simple, economic, and label-free electrochemical biosensor was developed for highly sensitive and selective miR-21 detection based on Fe(CN) 6 3− /Fe(CN) 6 4− electrochemical signal, which relies on DNA structures conjugating with carboxyl multi-wall carbon nanotubes (MWCNTs-COOH)-modified glassy carbon electrode (GCE). High sensitivity and specificity of the biosensor were achieved by taking advantage of the target-recycled non-enzymatic amplification strategy (TRNEAS), which relies on sequence-specific hairpin strand displacement and does not require the addition of environment-susceptible enzymes. Besides, the SP-DNA strictly binds to the cMWCNTs/GCE via amide bonds, which ensure good electrochemical results and excellent stability for target miRNA detection. The developed miR-21 electrochemical biosensor exhibited a broad linear dynamic range of 0.1 fmol to 5 pmol and a detection limit of 56.7 amol for miR-21 detection in vitro . The relative miR-21 expression levels were particularly detected by our developed miR-21 biosensor and were highly consistent with the stem-loop RT-PCR results. In summary, our developed electrochemical biosensor exhibits great potential for further application in biomedical research and early clinical diagnosis.
研究领域:
生物传感器
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电化学
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纳米技术
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分子生物学
·
临床诊断
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Wei Zhang,Hong Lei,Jiachong Li,Xiaoyan Wang,Hui Yan
MicroRNAs are important tumor biomarkers. How to effectively detect them by sensors is a challenge because of their extremely low concentrations. We proposed a dual signal enhancement strategy to develop the fiber optic (FO) localized surface plasmon resonance (LSPR) sensor for the highly sensitive detection of miR-103. It included two stages, one was to obtain the hot-spot by constructing the multimer structure, AuNP-spacer- AuNPs , and another was the combination of capturing miR-103 by the probe and catalytic amplification by Hexagonal star G-quadruplex catalyzing 4-chloro-1-naphthol to generate benzo-4-chlorohexadienone, which deposited on the AuNPs, resulting in the generation of LSPR peak redshift. The parameters of the preparation and detection application were systematically optimized. The redshift values had a good linear relationship with the logarithms of miR-103 concentrations, with high R 2 0.9973, wide detection range 10 2 - 10 7 fM, and low LOD 6.4 fM. The method had high specificity, repeatability, and reproducibility, and was also successfully validated with real samples. Therefore, the dual signal strategy for constructing FO LSPR sensors can achieve the high sensitivity detection of extremely low concentration of MicroRNAs, which will have great application prospects in medicine and life science.
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Food & Function
·
2022
·Vol. 13
·期 5
·2647-2661
·
IF 6.317
Yongfeng Ren,Dongxiao Sun-Waterhouse,Fangxin Ouyang,Xintong Tan,Dapeng Li,Longhua Xu,Bo Li,Yongli Wang,Feng Li
Lead can lead to neurotoxicity and cognitive impairment. In this study, for the first time, the protective effects and working mechanisms of apple phenolic extracts (APEs) against lead acetate (Pb(Ac)2)-induced cognitive impairment and depression- and anxiety-like behavior were examined in vivo. Forty male mice were administered daily (via gastric gavage; 8 weeks) with 0.9% normal saline (control), Pb(Ac)2 (20 ppm), APE (200 ppm) or Pb(Ac)2 (20 ppm) + APE (200 ppm). The APE contained five major phenolic compounds: chlorogenic acid, proanthocyanidin B2, epicatechin, phloridzin and phloretin. Behavioral tests, histopathological examinations and biochemical analyses revealed that Pb(Ac)2-treated mice exhibited cognitive and behavioral deficits (i.e. a reduced percentage of spontaneous alternation, prolonged duration of immobility and decreased open field test scores compared with the control. Pb(Ac)2 exposure significantly increased cellular oxidative damage and the levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), ionized calcium binding adaptor molecule 1 (Iba1) and pro-apoptotic proteins (caspase 3, caspase 9 and Bax), while downregulating the expression of Bcl-2 in the brain. APE administration alleviated these Pb(Ac)2-induced changes through regulating oxidative stress, neuroinflammation and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway. Taken together, the APE has the potential to treat lead-induced neurotoxicity and neurodegenerative disorders via antioxidant, anti-inflammatory and anti-apoptotic actions.
研究领域:
神经毒理学
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药理学
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行为神经科学
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分子生物学
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高影响因子
Bioengineered
·
2021
·
IF 3.269
Xinyue Zhou,Zhenyu Chen,Lipeng Pei,Jingli Sun
Emerging evidence has exhibited an obvious decreased expression of miR-106a-5p in the ectopic endometrial tissue of endometriosis (EMS) patients. Thus far, the pathophysiological function of miR-106a-5p in EMS is unknown. A previous study showed an increased FOXC1 expression in the ectopic endometrial tissue of patients with EMS. Moreover, we found that there was a binding site of miR-106a-5p on the 3ʹUTR of FOXC1 through bioinformatics predictions. Hence, we speculated that miR-106a-5p might affect the development of EMS via targeting FOXC1. We first showed a decreased level of miR-106a-5p and an increased level of FOXC1 mRNA in ectopic endometrial tissues compared with normal tissues. Functionally, we transfected ectopic endometrial stromal cells (ESCs) with miR-106a-5p mimics or NC mimics and indicated an inhibitory role of miR-106a-5p on ESC proliferation, invasion, and migration. Mechanistically, FOXC1 was found to be a target gene of miR-106a-5p. To confirm whether miR-106a-5p exerted an inhibitory activity in ESCs via targeting FOXC1, miR-106a-5p mimic was co-transfected into ESCs with the FOXC1-plasmid or vector. We found that FOXC1 overexpression evidently reversed the results caused by a miR-106a-5p mimic in ESCs. Additionally, our results demonstrated that miR-106a-5p mimic inhibited the expression of p-Akt and p-PI3K. Collectively, these results revealed that miR-106a-5p inhibited the proliferative, migratory, and invasive ability of ESCs via directly binding to FOXC1, likely through the suppression of the PI3K and its downstream signaling pathway, which offered a potential and novel therapeutic strategy for EMS treatment.
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Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Hechen Wang,Xudan Shen,Xinlan Zhu,Su Zeng,Sheng Cai
Hepatocellular carcinoma (HCC) shows the highest morbidity among liver cancers and accounts for a major factor inducing cancer-associated mortality globally. It is characterized by genetic mutations in hepatocytes, leading to uncontrolled cell growth and proliferation. Treatment options for HCC include surgery, chemotherapy, and immunotherapy. But chemotherapeutics, which focus on single-targeted drug therapy, are still associated with certain limitations and may affect the treatment outcomes. Compared with chemotherapy drugs, natural products also show the anticancer effect of HCC and hypotoxicity, but overall low activity of natural products limits their further application. MiRNAs can modulate post-transcriptional functions of target genes. An increasing body of evidence has demonstrated that miRNAs are the key regulators in HCC by targeting different molecules in different signaling pathways. However, miRNAs are fragile and liable to catabolism by RNases in serum and other body fluids and small molecules separated from natural products may have limited bio-availability. According to this background, a chitosan based, targeted sustained-release nanoparticle delivery miR-128-3p agomir (NA-miR-128-3p) was developed in this work. This nanoparticle was prepared by pentasodium tripolyphosphate (TPP), chitosan hydrochloride, and miR-128-3p agomir with target aptamer which was loaded into the chitosan nanoparticle by self-assembly. It can intervene in HCC progress by affecting AKT1 expression. Based on this, a novel, efficient, long-acting, multi-mechanism, low-dosage combination drug delivery strategy was proposed in this work and showed a prominent anti-tumor effect. NA-miR-128-3p combined with natural product Oroxin B significantly affected HCC progression by the interference with VEGF and PI3K-AKT pathways, better than using NA-miR-128-3p and Oroxin B alone. Taken together, this nanoparticle and combinative administration compensate for the shortcomings of the fragile RNA drugs and the low activity of natural products, with high prospects in HCC treatment.
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