CELLULAR SIGNALLING
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2025
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IF 3.7
Jianping Wen,Dongxu Wu,Yi Le,Zonghua Yin,Minglong Chen,Yulong Shen,Xia Wu,Kebo Liu,Kun Luo,Zhicheng Shu,Qingxia Shu,Dongsheng Ouyang
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with limited treatment options due to its resistance to temozolomide (TMZ). This study explores a novel therapeutic approach using engineered cell membrane nanovesicles loaded with SERPINE1 inhibitors to combat TMZ resistance. High-throughput sequencing identified pivotal genes associated with resistance, while the nanovesicles demonstrated excellent stability and the ability to cross the blood-brain barrier. Functional assays revealed significant suppression of GBM cell viability, migration, and invasion, accompanied by reduced expression of SERPINE1 and VEGF, suggesting inhibition of angiogenesis and tumor progression. These findings highlight the potential of SERPINE1-targeted nanovesicles as an innovative and effective strategy for overcoming TMZ resistance in GBM.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2025
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IF 6
Wenwu Li,Tingting Xie,Shizhen Gan,Yuanxun Gong,Jiayi Zhang,Qianli Tang,Kai Zhang,Xianjiu Liao
Background Electrochemiluminescence (ECL) biosensors are powerful tools for biomarker detection due to high sensitivity, low background, and programmable signal generation. However, conventional ECL platforms face limitations including reliance on static recognition elements (e.g., antibodies) and susceptibility to denaturation. To address this, we developed a novel β-turn-structured peptide-based ECL biosensor integrating MXene (Ti3C2) nanomaterials with a Ru(dcbpy)32+/AuNPs hybrid. This system targets SERPINE1, a senescence-associated secretory protein and promising early biomarker for lung cancer, leveraging peptide conformational switching for enzyme-free signal amplification. Results The biosensor employs a rationally engineered peptide probe containing: (1) a SERPINE1-specific recognition motif, (2) a central β-turn domain locking the peptide in a catalytically inactive folded state, and (3) a His/Cys-rich tail mimicking peroxidase-like activity. Target binding unfolds the β-turn structure, exposing catalytic residues that accelerate tripropylamine (TPA) oxidation and enhance ECL emission. MXene provides a high-conductivity platform while facilitating efficient peptide immobilization via embedded AuNPs. Under optimized conditions, the sensor achieves ultrasensitive detection of SERPINE1 with a wide linear range (0.05–800 ng/mL), a low detection limit (11.2 pg/mL), and high specificity. It operates without enzymatic amplification and demonstrates excellent reproducibility (RSD = 4.2%) and stability (>85% signal retention after 8 days). Validation in human serum yielded recoveries of 96.3–104.6%. Significance This work introduces the first MXene-assisted ECL biosensor utilizing β-turn peptide conformational switching. The enzyme-free, modular strategy offers clinically adaptable detection of senescence biomarkers for early lung cancer diagnosis. By integrating molecular recognition, structural dynamics, and nanomaterial-enhanced signal transduction, this platform advances programmable biosensing and can be extended to other disease-related targets through peptide redesign, showing broad potential in precision diagnostics.
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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癌症诊断
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电化学
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分子生物学
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PubMed
高影响因子
Urolithiasis
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2026
·Vol. 54
·期 1
·62
·
IF 2.6
Sun Yan,Zhang Xiaoyu,Chen Xiaoyu,Zhao Jiawen,Liu Yunlong,He Weiyang
Paeoniflorin (PF) is a bioactive monoterpene glycoside with well-established anti-inflammatory properties; however, its therapeutic potential and molecular mechanism in nephrolithiasis remain insufficiently defined. In this study, network pharmacology was employed to predict potential targets of PF. In vitro, HK-2 cells exposed to calcium oxalate (CaOx) crystals were treated with PF to evaluate inflammatory responses, crystal adhesion, and NF-κB activation. A glyoxylic acid-induced mouse model was used to assess renal crystal deposition, renal function, and expression of key regulatory targets, supported by transcriptomic profiling. Molecular docking and molecular dynamics simulations were performed to analyze the interaction between PF and Serpine1, and functional relevance was further examined using exogenous Serpine1 rescue experiments. Integrated analyses indicated that PF exerts anti-nephrolithic effects predominantly through modulation of inflammation-associated signaling. PF dose-dependently suppressed CaOx-induced NF-κB phosphorylation and nuclear translocation, reduced the release of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and decreased crystal adhesion in HK-2 cells. In vivo, PF markedly attenuated renal crystal deposition, improved renal functional indices, and downregulated renal Serpine1 and IL-1β expression. Computational simulations supported a stable interaction between PF and Serpine1 (binding energy − 6.22 kcal/mol). Consistently, supplementation with exogenous Serpine1 partially reversed PF-mediated inhibition of NF-κB activation and cytoprotective effects. Collectively, these findings suggest that PF mitigates CaOx-associated renal injury by suppressing inflammation-centered signaling programs involving the Serpine1/NF-κB axis, thereby providing mechanistic insight into PF as a potential multi-target therapeutic candidate for nephrolithiasis.
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DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2026
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IF 4.5
Dan Wang,Liran Xu,Yangang Sun,Jingyu Yue,Liangping Li
Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition resulting from varicella-zoster virus reactivation, yet remains inadequately treated. Here, we elucidate a pathogenic function of Serpin Family E Member 1 (SERPINE1) in neuropathic pain using a resiniferatoxin (RTX)-induced neuropathic pain to simulate PHN. RTX administration triggered sustained mechanical allodynia and thermal hyposensitivity, accompanied by damage in the dorsal root ganglion (DRG) and sciatic nerve. Transcriptomic analysis identified SERPINE1 as a prominently upregulated gene in DRG following RTX challenge. Pharmacological inhibition of SERPINE1 with TM5441 alleviated pain-related behaviors in a dose-dependent manner, restored vanilloid 1 (TRPV1)-positive neuronal populations, and mitigated ultrastructural nerve pathology. Mechanistically, SERPINE1 suppression attenuated neuronal apoptosis (lowered caspase‑3) in the DRG. This anti‑apoptotic effect was associated with inhibition of the AKT pathway, evidenced by decreased AKT phosphorylation in both DRG tissues from RTX‑treated rats and RTX‑stimulated SH‑SY5Y cells. Our findings demonstrate that SERPINE1 drives neuropathic pain in the RTX model and highlight its pharmacological inhibition as a promising therapeutic strategy.
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PubMed
高影响因子
ACS Nano
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2026
·
IF 17.3
Xue-Wu Chen,Jun Long,Xiao-Peng Zheng,Bang-Xian Yu,Guang-Zhao Wang,Wen-Qi Wu,Yong-Da Liu,Guo-Hua Zeng,Ling-Hong Huang,Xin-Yuan Sun
Crystalline nephropathy is driven by a self-perpetuating cycle in which crystal-induced tubular injury promotes further nucleation, growth, and aggregation, transforming the kidney into a pathological mineralization niche. Conventional therapies fail to disrupt this vicious loop, while nanomedicines are hindered by the glomerular filtration barrier (<10 nm), and natural antioxidants like protocatechuic acid (PCA) suffer from poor bioavailability. Here, we report a 7.3 nm mitochondria-targeted metal−polyphenol network (Fe-PCA@TPP) that overcomes both delivery and targeting challenges to directly intervene at sites of redox imbalance. Formed via PCA−Fe3+ coordination and functionalized with triphenylphosphonium (TPP), Fe-PCA@TPP efficiently traverses the glomerular barrier, accumulates selectively in mitochondria, scavenges free radicals broadly, restores redox homeostasis, and potently inhibits calcium oxalate (CaOx) crystal nucleation, growth, and aggregation. In vitro, Fe-PCA@TPP protects renal tubular epithelial cells from oxalate-induced oxidative stress by preserving mitochondrial bioenergetics and preventing apoptosis. In vivo, it preferentially accumulates in the kidney, reduces CaOx deposition, improves renal function, and downregulates markers of injury and inflammation. Mechanistically, Fe-PCA@TPP targets Plasminogen Activator Inhibitor Type 1 (SerpinE1) to block oxidative stress−apoptosis cascades, thereby remodeling the intrarenal pathological microenvironment. This work presents a size-compatible, mitochondria-targeted, and SerpinE1-specific nanoplatform that integrates crystal inhibition, redox regulation, and efficient renal clearance, offering a promising therapeutic strategy for crystalline nephropathy.
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DOI
PubMed
高影响因子
HUMAN MUTATION
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2026
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IF 1.8
Xiaomei Nie,Gang Su,Ran Zhang,Han Wang,Mingbo Li,Qian Liang
Background Diabetic retinopathy is caused by chronic hyperglycemia, which damages the retina′s blood vessels and neurons. This study is aimed at identifying potential therapeutic targets for DR. Methods Transcriptomic and proteomic data were obtained from the Gene Expression Omnibus (GEO) and ProteomeXchange databases, respectively. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were intersected. An enrichment analysis of the overlapping genes was performed based on the DAVID database. A protein–protein interaction (PPI) network (STRING) was analyzed via Cytoscape/cytoHubba to identify key genes. Single‐cell RNA‐sequencing (scRNA‐seq) data were processed using Seurat. Gene set enrichment analysis (GSEA) (clusterProfiler) and molecular docking (EnrichR) were performed. High glucose‐induced retinal microvascular endothelial cells (RMECs) were used for functional assays. Results The intersection of DEGs and DEPs yielded shared genes, enriched in the PI3K–Akt signaling pathway, AGE–RAGE signaling pathway in diabetic complications, complement and coagulation cascades, and ECM–receptor interaction; a PPI network incorporating these genes revealed two key DR‐associated highly expressed genes, COL1A1 and SERPINE1. GSEA showed that samples with high expression of these key genes were enriched in pathways such as reactome signaling by TGFB family members, inflammatory response, TGF‐ β signaling, and reactome cell extracellular matrix interactions. Single‐cell and molecular docking analyses revealed high expression of the two key genes in fibroblasts and binding between SERPINE1 and paricalcitol, and HG induction increased their levels in RMECs, whereas knockdown of SERPINE1 repressed RMEC proliferation, migration, and invasion in vitro. Conclusion This study identifies SERPINE1 and COL1A1 as possible DR therapeutic targets, providing new insights into relevant therapeutic development.
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高影响因子
HUMAN MUTATION
·
2025
·Vol. 2025
·期 1
·5319444
·
IF 3.7
Xin Wu,Linde Sun,Peifa Liu,Qiong Wang,Yu Wang
Background PANoptosis, as an inflammatory programmed cell death, is involved in tumor development. This study set out to discover novel PANoptosis-correlated prognostic signatures in stomach adenocarcinoma (STAD), a prevalent malignancy of the digestive system. Methods STAD samples were derived from a public database, and PANoptosis-related genes (PRGs) were acquired from existing reports. Prognosis-related PRGs were screened by univariate Cox regression analysis. Molecular subtypes of STAD were identified by the “ConsensusClusterPlus” package. The “Limma” package was employed to filter differentially expressed genes (DEGs) between different subtypes. PANoptosis-related prognostic signatures in STAD were identified to establish the RiskScore model. The RiskScore and some of the clinical features were integrated to establish a nomogram. Immune cell infiltration and TIDE score in different risk groups were compared. Correlation between immune checkpoint genes, drug sensitivity, and RiskScore was analyzed by the Spearman method. The biological function of PANoptosis-related signature genes in STAD was preliminarily explored by in vitro cell experiments. Results Based on 18 prognosis-related PRGs, two molecular subtypes of STAD were recognized, and the C1 subtype showed a lower overall survival (OS) rate than the C2 subtype. Further, three PANoptosis-related signature genes ( APOD , GPC3 , and SERPINE1 ) were determined to establish a RiskScore model that could accurately assess the prognostic outcomes for STAD patients. Then, by integrating RiskScore with clinical features, a nomogram was established. The high-risk group had higher immune cell infiltration and TIDE score and lower OS rate than those with a low risk. RiskScore was positively correlated with nine immune checkpoint genes. Besides, we screened 23 drugs that significantly correlated with RiskScore. In vitro cell experiments showed that the mRNA and protein levels of APOD , GPC3 , and SERPINE1 were upregulated in the STAD cell line and that APOD knockout significantly reduced cancer cell proliferation, migration, and invasion levels and increased the apoptotic capacity of the STAD cell line. Conclusion This study established a PANoptosis-related RiskScore model for assessing STAD patient prognosis, which could contribute to the personalized treatment of STAD.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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免疫治疗
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精准医学
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DOI
PubMed
高影响因子
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