Virulence
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2026
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IF 6.8
Xinxian Wang,Shurui Yang,Lichun Xie,Shanshan Qi,Libo Gao,Yongmei Li,Qian Li,Junlong Bi,Jianping Liu,Yongneng Li,Gefen Yin
Classical swine fever virus (CSFV) remains a major threat to the global swine industry, yet the involvement of host miRNAs in its pathogenic mechanisms is not fully understood. In this study, we demonstrate for the first time that miR-17-5p inhibits CSFV replication through an autophagy-dependent mechanism by targeting polycystin-2 (PKD2), a key calcium channel protein that regulates the AMPK/mTOR signaling pathway. Using the PK-15 cell model, we found that CSFV infection significantly upregulates miR-17-5p expression. Functional assays revealed that miR-17-5p exerts antiviral effects by directly binding to the 3’-UTR of PKD2, as confirmed by bioinformatics prediction and dual-luciferase reporter assays. Silencing of PKD2 recapitulated the antiviral effect of miR-17-5p overexpression, while PKD2 reconstitution restored viral replication by activating AMPK signaling and suppressing mTOR activity, thereby significantly enhancing autophagic flux – as evidenced by increased LC3-II/I ratio and decreased p62 levels. Mechanistically, PKD2 regulates intracellular calcium dynamics, modulating the AMPK/mTOR-autophagy axis to promote CSFV proliferation. This work uncovers a novel host antiviral mechanism in which a miRNA controls virus-induced autophagy via calcium signaling. To our knowledge, this is the first report to establish the pivotal role of miRNA-mediated calcium signaling modulation in flavivirus-host interactions. These findings provide a mechanistic framework and potential therapeutic targets for anti-CSFV interventions focused on PKD2 or autophagy regulation.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2026
·Vol. 30
·期 17
·e71359
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IF 4.7
Xuesong Xu,Shichong Qiao
Apoptosis and functional loss of articular chondrocytes serve as initiating events in temporomandibular joint osteoarthritis (TMJOA), and FoxO3 represents a critical molecule for sustaining chondrocyte homeostasis. This study investigates the regulatory mechanism of the lncRNA‐OIP5‐AS1/hsa‐miRNA‐223‐3p/FoxO3 axis in TMJOA, aiming to identify potential therapeutic targets for this disease. Single‐cell database analysis first revealed markedly reduced FoxO3 expression in TMJOA‐derived chondrocytes. A rat TMJOA model was then constructed and assigned to control, model, and FoxO3 overexpression groups; micro‐CT and histological staining, including HE and Safranin O‐fast green staining, were applied to assess articular cartilage injury, while immunohistochemistry was used to detect cartilage‐associated proteins Col2a1, MMP‐13, Aggrecan, and ADAMTS‐5. Further in vitro experiments validated the chondroprotective function of FoxO3 as well as the binding interaction between FoxO3 and rno‐miRNA‐223‐3p. Database screening confirmed significant down‐regulation of FoxO3 in TMJOA cartilage. Animal experiments demonstrated that FoxO3 overexpression mitigated chondrocyte injury in rat TMJOA lesions, increased Col2a1 and Aggrecan levels, and suppressed MMP‐13 and ADAMTS‐5 expression. Cellular assays showed that FoxO3 overexpression enhanced chondrocyte proliferation and matrix synthesis and preserved chondrocyte function. Sequencing and cellular evidence indicated that rno‐miRNA‐223‐3p directly targets FoxO3 mRNA to repress its transcription and negatively modulate FoxO3 abundance, consequently aggravating chondrocyte apoptosis. Collectively, rno‐miRNA‐223‐3p suppresses FoxO3 activity to facilitate TMJOA pathogenesis, and the lncRNA‐OIP5‐AS1/rno‐miRNA‐223‐3p/FoxO3 regulatory cascade may act as a promising molecular target for TMJOA clinical intervention.
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Food Bioscience
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2026
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IF 6.2
Donglin Sui,Shugang Li,Chunqing Ai,Shuang Song,Yixuan Li,Shouhao Zhao,Huan Li,Hong Chang,Xiaomeng Ren
Our prior studies have indicated that the isinglass polysaccharide derived from Larimichthys crocea (CIP) can enhance the growth of Ligilactobacillus murinus , which may play a significant role in mitigating colitis. This study investigated the potential of Ligilactobacillus murinus and its derived extracellular vesicles (LM-EVs) as therapeutic and prophylactic agents. LM-EVs demonstrated remarkable ameliorative efficacy in colitis models, substantially mitigating colonic injury, atrophy, and hematochezia, coupled with a significant dampening of inflammatory markers. These beneficial effects are underpinned by significant in vitro antioxidant capacity and a favorable initial safety profile, alongside marked immunomodulatory functions. Mechanistically, we propose a significant role for the miR-146a-5p/TRAF6 signaling axis in LM-EV-mediated immunomodulation, specifically its influence on macrophage polarization. Our findings indicate that LM-EVs modulate the expression level of miR-146a-5p within macrophages. miR-146a-5p subsequently targets and suppresses the TRAF6/NF-κB signaling axis, driving macrophage polarization from the M1 to the M2 phenotype, thereby effectively ameliorating colitis. These insights reveal a promising avenue, potentially utilizing probiotic extracellular vesicles for alleviating colitis and paving the way for new frontiers in gut health modulation.
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JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Mingju Shui,Yi Chen,Miao Guo,Guofeng Zhong,Hongyi Li,Yaqin Xiao,Qin Yuan,Beixin Yuan,Xiaoying Liu,Hefeng Zhou,Zhejie Chen,Shengpeng Wang
Ulcerative Colitis (UC) is a chronic intestinal disease with limited treatment options, where current therapies often suffer from inadequate efficacy and substantial side effects. While polyphenol-based nanocarriers show promise for nucleic acid delivery, a systematic screening approach to identify optimal polyphenols for this purpose remains unexplored. Therefore, we conducted a systematic screening of 110 natural polyphenols to develop an efficient miRNA delivery system for UC intervention. Sinapic acid (SA) was identified as the lead candidate and complexed with miR-124 mimics, followed by sequential encapsulation with a poly(amidoamine) (PAMAM) dendrimer and hyaluronic acid (HA) coating to form HPPR NPs. As expected, HPPR mediated efficient intracellular delivery of miR-124, leading to significant downregulation of the expression of IL-6R , CCL-2 , STAT3 , and their downstream genes in a murine model of dextran sulfate sodium (DSS)-induced acute colitis. HPPR also markedly suppressed the production of pro-inflammatory cytokines and facilitated intestinal mucosal regeneration. Moreover, the system effectively modulated gut microbiota homeostasis by enriching beneficial bacteria ( Akkermansia and norank_f__Muribaculaceae ) while simultaneously suppressing pathogenic bacteria ( Escherichia-Shigella and Helicobacter ). Collectively, this study not only establishes a polyphenol-based strategy for optimizing nucleic acid delivery but also presents a promising nanotherapeutic platform for UC treatment.
研究领域:
纳米医学
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分子生物学
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胃肠病学
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药物递送
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免疫学
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ACS Applied Polymer Materials
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2025
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IF 4.7
Yingqi Wei,Hao Wang,Yaxi Zhu,Guancheng Zhan,Lihuan Zhang,Huichang Gao,Longyang Jin,Ruobing Feng
Peripheral nerve injury frequently occurs alongside vascular injury due to the incorporation of vascular tissue within the nerve bundle. During the repair process of peripheral nerve injuries, the concurrent regeneration of capillaries within the nerve bundles is crucial for facilitating nerve regeneration. However, current studies often overlook the regeneration of blood vessels in nerve bundles when designing nerve repair scaffolds, leading to suboptimal nerve regeneration outcomes. To address this limitation, amino-modified Cu-doped mesoporous bioactive glass (Cu-MBG) was developed as a nanodelivery carrier for miR-29a to construct miR-29a@Cu-MBG nanoparticles, which exhibit dual functionality in promoting nerve regeneration and inducing vascular regeneration. Subsequently, miR-29a@Cu-MBG was incorporated into a CS/GelMA hydrogel to create an engineered multifunctional nerve conduit through the ionic cross-linking of chitosan and the optical cross-linking of GelMA, which demonstrated excellent mechanical properties and biocompatibility. In vitro cell experiments indicated that the sustained release of miR-29a@Cu-MBG from the conduit effectively delivered miR-29a into PC12 cells, leading to the upregulation of nerve regeneration-associated genes (GAP-43 and NF-200) and the outgrowth of neurite. Additionally, Cu-MBG was found to enhance the migration of HUVECs and upregulate genes related to angiogenesis (HIF-α, ANG, eNOS, and KDR), promoting the tube formation of HUVECs. These findings offer a perspective for the design of nerve conduits capable of promoting both nerve and vascular regeneration.
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Journal of Radiation Research and Applied Sciences
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2025
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IF 2.5
Yu Zhang,Hongbo Lv,Chao Chen,Zixu Li,Zhaoyu Xie,Miaomiao Wu,Zhixu Zhu,Ying Fan,Jing Li,Qiang Gao,Jun Han,Hui Che,Lan Ma
Background Ischemic stroke (IS) is a major global cause of mortality and long-term disability, and effective therapies are urgently needed. Hydrogen sulfide (H 2 S) has shown neuroprotective effects in various neurological disorders, but its mechanisms in IS remain unclear. This study aims to explore the role and mechanism of H 2 S in IS treatment. Methods IS models were established in vivo using middle-cerebral-artery occlusion (MCAO) in rats and in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R) in PC12 cells. These models were treated with H 2 S donors NaHS or GYY4137. Pathological features were evaluated using TTC, FJC, H&E, and Nissl staining. Cell viability was assessed with live/dead staining and CCK-8 assay. RNA sequencing identified gene expression changes after H 2 S treatment under OGD/R conditions. Ferroptosis-related markers, lipid peroxidation (GSH, SOD, MDA), ROS levels, and the expression of SLC7A11 and GPX4 were measured by flow cytometry, Western blot, and immunofluorescence. MiR-27a levels were quantified by qRT-PCR. Results NaHS administration in MCAO rats reduced infarct volume, increased Nissl body density, and decreased degenerating neurons. GYY4137 exhibited similar neuroprotective effects in vitro. RNA sequencing revealed that GYY4137 reversed ferroptosis-related gene changes, including SLC7A11. H 2 S supplementation inhibited neuronal ferroptosis, shown by increased SLC7A11 and GPX4 expression, elevated GSH and SOD levels, and reduced MDA content. Additionally, MCAO or OGD/R induced miR-27a expression, which negatively regulated SLC7A11. H 2 S reversed this induction, and miR-27a overexpression partially blocked the anti-ferroptotic effect of H 2 S. Conclusion H 2 S alleviated IS-induced brain injury by suppressing ferroptosis, partially through miR-27a-dependent regulation of SLC7A11. These findings suggest H 2 S as a promising therapeutic agent for IS, warranting further clinical exploration.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Congna Zi,Ying Zhu,Xian Ma,Yulei Wei
Apoptosis is a main cause of myocardial injury in myocardial ischemia/reperfusion injury (MIRI). Brain abundant membrane attached signal protein 1 (BASP1) was an apoptosis regulator that may be involved in the myocardial apoptosis during MIRI. In this study, we established the MIRI mouse model by ligating the left anterior descending coronary artery of mice for 30 min followed by reperfusion for 24 h. BASP1 was upregulated in the MIRI model. The adenoviruses carrying shRNA that specifically targets BSAP1 were used to downregulate BASP1 expression in myocardium. BASP1 silencing alleviated myocardial infarction and improved cardiac function. Furthermore, BASP1 silencing inhibited MIRI-induced myocardial apoptosis as evidenced by decreased TUNEL-positive cells and reduced caspase-3 and caspase-9 activities. Meanwhile, cell model was also established by culturing mouse HL-1 cells in a hypoxic (H) environment for 8 h, followed by reoxygenation (R) for 12 h. H/R upregulated BASP1 expression and BASP1 knockdown reduced H/R-induced apoptosis. Besides, the mRNA-sequencing analysis was conducted to explore the underlying mechanism by which BASP1 functions. HtrA serine peptidase 2 (HTRA2), one of the 1975 differentially expressed genes ( p < 0.05, |log 2 FC| > 1.5), was identified as candidates of molecular targets of BASP1 through gene ontology annotation and enrichment analysis. Introduction of HTRA2 to HL-1 cells counteracted the impact of BASP1 knockdown. MiR-7a-5p was found to target the 3′-untranslated regions of BASP1 and inhibit its expression through dual luciferase reporter assay. Collectively, BASP1/HTRA2 axis, regulated by miR-7a-5p, may be the promoter of MIRI process, indicating that BASP1/HTRA2 axis is a potential target for treating MIRI.
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JOURNAL OF MOLECULAR HISTOLOGY
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2026
·Vol. 57
·期 1
·30
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IF 2.2
Xiang Shouyu,Liu Wei,Tang Cheng,Xie Chuhai,Hu Hailan,Zhou Jianhui,Cao Yanming,Ling Long
Bone marrow mesenchymal stem cells (BMSCs) play a significant role in bone defect repair. Currently, the limited survival and function of transplanted BMSCs pose major obstacles to tissue repair mediated by these cells. Therefore, the exploration of BMSCs transplantation activity has become an urgent clinical problem. In this experiment, we constructed lentiviral vectors with overexpression and silencing of miR-19b-3p and utilized a rat fracture model. The effects of BMSCs proliferation were examined using CCK-8, the Annexin V-FITC apoptosis kit and TUNEL assay, the effects of BMSCs osteogenic differentiation were detected using ALP and Alizarin red staining. Furthermore, Western blotting and qRT-PCR were employed to examine the expression of key proteins in the PTEN/Akt/mTOR signaling pathway and autophagy-related proteins. Moreover, the impact of miR-19b-3p on bone microstructure was assessed using Micro CT, HE, Safranin O/Fast Green, as well as Masson staining, and Immunohistochemistry analysis examined PTEN, p62 and Runx2 expression levels on fracture site. By constructing lentiviral vectors with overexpression and silencing of miR-19b-3p, we found that silencing miR-19b-3p significantly promoted the proliferation as well as the osteogenic differentiation of BMSCs under hypoxia. Western blotting and qRT-PCR results showed that silencing miR-19b-3p significantly increased PTEN, LC3, and Beclin1 expression while decreasing p-Akt, p-mTOR, and p62 expression. Furthermore, by constructing the fracture rats and administering hypoxia-treated BMSCs transfected with miR-19b-3p via tail vein injection, we found that silencing miR-19b-3p obviously increased the formation of trabecular and promoted the healing of the fractures. Immunohistochemistry analysis showed that silencing miR-19b-3p upregulated PTEN and Runx2 expression levels and suppressed p62 expression with statistical significance. In summary, these findings suggest that miR-19b-3p may regulate BMSCs’ autophagy and osteogenic differentiation under hypoxia via the PTEN/Akt/mTOR signaling pathway, thereby promoting fracture healing and providing a potential target for the treatment of fractures.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2026
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IF 4.8
Tingting Guo,Chang Zuo,Ping Bai,Lingjing Hu
A novel multi-functional DNA tetrahedron-based target-induced cascaded cyclic catalytic amplification (TICA) assay was developed for the sensitive detection of microRNA-21 (miR-21) in prostate cancer. This strategy ingeniously integrates two distinct DNA tetrahedron with specific functions (catalytic tetrahedron (Cat-DT) and signal DNA tetrahedron (Sig-DT)) to create a self-sustaining amplification circuit. The process is initiated when miR-21 triggers the release of a DNAzyme enzymatic strand (E-DNA), which converts Cat-DT into tri-branched DNA nanostructures (TB-DNA). Critically, each TB-DNA acts as a cascaded amplifier, bearing three E-DNA units that drive the exponential generation of more catalytic sites. Furthermore, the system employs an ingenious feedback loop: the TB-DNA/Sig-DT interaction produces a fluorescent signal while regenerating a miR-21-mimetic strand to perpetuate the catalytic cycle. This “target → catalyst → new target” paradigm enables ultra-efficient amplification, achieving a wide linear range from 600 fM to 100 nM and a low detection limit of 400 fM for miR-21. Notably, the TICA strategy significantly shortens the total reaction time to 80 min, demonstrating great potential for rapid and sensitive clinical diagnostics.
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Stem Cells International
·
2025
·Vol. 2025
·期 1
·5243270
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IF 3.3
Bei Li,Qiongni Wang,Linru Shi,Qifeng Liu,Hui Qian,Lixia Yu,Cheng Ji
Diabetic kidney disease (DKD) is characterized by a continuous decline in renal function and progressive fibrosis, making it a leading cause of end-stage kidney disease with limited therapeutic options. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown great potential in tissue regeneration and repair, offering a new avenue for the treatment of DKD. The purpose of this study is to explore the function and mechanism of action of EVs derived from human umbilical cord MSCs (hucMSC-EVs) in the development of DKD. Our findings show that under high-glucose (HG) conditions, miR-146b-5p is highly expressed in glomerular mesangial cells, downregulating the target protein Merlin, which promotes the activation of the YAP signaling pathway and induces mesangial cell fibrotic-like changes, leading to a significant deposition of collagen and interstitial fibrosis in the kidney. In vivo and in vitro experimental findings reveal that hucMSC-EVs can significantly inhibit miR-146b-5p, upregulate Merlin expression, prevent the nuclear translocation of YAP, improve renal function, and reduce collagen deposition, demonstrating a significant antifibrotic effect. The findings of this study emphasize the central role of the miR-146b-5p/Merlin/YAP axis in hucMSC-EVs-mediated inhibition of renal fibrosis and highlight the potential of MSC-EVs as a targeted nanotherapeutic strategy for DKD.
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JOURNAL OF HAZARDOUS MATERIALS
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2022
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IF 14.224
Wenqi Diao,Jin Yan,Xuedong Wang,Qiuhui Qian,Huili Wang
Although triclosan (TCS) is ubiquitously detected in environmental media and organisms, little information is available on its cardiotoxicity and underlying mechanisms. Herein, acute TCS exposure (0.69–1.73 μM) to zebrafish from embryos (6 hpf) to larvae (72 hpf) resulted in cardiac development defects, including increased angle between atrium and ventricle, prolonged SV-BA distance, linearized heart and pericardial cyst in 72-hpf larvae. These malformations resulted from interfered oxidative-stress pathways, reflecting in accumulated ROS and MDA and inhibited SOD and CAT activities. By RT-qPCR, the transcription levels of four cardiac development-related marker genes were significantly up-regulated except for gata4 . Besides, miR-144 was identified as a regulatory molecule of TCS-induced cardiac defects by integrating analyses of artificial intervene expression and RNA-Seq data. Interestingly, the target genes of miR-144 were found and interacted with the above marker genes through constructing protein-protein interaction networks. After intervening the expression of miR-144 by microinjecting and activating Wnt pathway by an agonist BML-284, we confirmed that up-regulated miR-144 suppressed the expression of angiogenesis-related genes and negatively regulated Wnt pathway, further triggering angiogenesis disorders and cardiac phenotypic malformation. These findings unravel the underlying molecular mechanisms regarding TCS-induced cardiac development toxicity, and contribute to early warning and risk management of TCS.
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DRUG DEVELOPMENT RESEARCH
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2022
·Vol. 83
·期 8
·1758-1765
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IF 5.004
Longxue Cai,Renqing Zeng,Qi Huang,Xianfa Liu,Zuohong Cao,Qicai Guo
Neuropathic pain affects millions of people in the worldwide, but the major therapeutics perform limited effectiveness. Paeonol (PAE) is widely distributed in Paeonis albiflora , and has manifested anti-inflammatory and antioxidative effects in multiple diseases. The present study aims to elucidate the effect of Paeonol (PAE) on neuropathic pain (NP) and the potential targets. Chronic constriction injury model was established to mimic NP in vivo in rats. The expression of GFAP, HDAC2, AHDAC3, Ac-H3K9, Histone-H3, Ac-H4K12, Histone-H4, TNF-α, IL-1β, and IL-6 was assessed by real-time polymerase chain reaction, western blot, and/or enzyme-linked immunosorbent assay kits. Ultimately, results indicated that intervention of PAE significantly blocked neuroinflammation and astrocytic activation via blocking HDAC/miR-15a signaling in CCI rats. These data revealed PAE is a novel therapeutic target for the treatment of neuropathic pain.
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