INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 18
·13682
·
IF 5.6
Shiyao Wang,Dongfa Lin,Jiaofei Cao,Liping Wang
Animal studies have proven that 1-acetyl-5-phenyl-1H-pyrrol-3-yl acetate (APPA) is a powerful antioxidant as a novel aldose reductase inhibitor independently synthesized by our laboratory; however, there is no current information on APPA’s anti-aging mechanism. Therefore, this study examined the impact and mechanism of APPA’s anti-aging and anti-oxidation capacity using theCaenorhabditis elegansmodel. The results demonstrated that APPA increasesC. elegans’ longevity without affecting the typical metabolism ofEscherichia coliOP50 (OP50). APPA also had a non-toxic effect onC. elegans, increased locomotor ability, decreased the levels of reactive oxygen species, lipofuscin, and fat, and increased anti-stress capacity. QRT-PCR analysis further revealed that APPA upregulated the expression of antioxidant genes, includingsod-3,gst-4, andhsp-16.2, and the critical downstream transcription factors,daf-16,skn-1, andhsf-1of the insulin/insulin-like growth factor (IGF) receptor,daf-2. In addition,fat-6andnhr-80were upregulated. However, the APPA’s life-prolonging effects were absent on thedaf-2,daf-16,skn-1, andhsf-1mutants implying that the APPA’s life-prolonging mechanism depends on the insulin/IGF-1 signaling system. The transcriptome sequencing also revealed that the mitochondrial route was also strongly associated with the APPA life extension, consistent withmev-1andisp-1mutant life assays. These findings aid in the investigation of APPA’s longevity extension mechanism.Keywords:APPA;lifespan;stress resistant;insulin/IGF-1;Caenorhabditis elegans
研究领域:
衰老研究
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分子生物学
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遗传学
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PubMed
高影响因子
Redox Biology
·
2026
·
IF 16.2
Zhengyi Chen,Xidan Fu,Chao Liu,Wenkang Jiang,Jiurong Liu,Miao Hao,Ling Fu,Wei Huang,Xiujuan Lang,Xijun Liu,Yumei Liu,Hulun Li,Rui Li,Bo Sun
Aging reshapes hematopoiesis toward myelopoiesis, particularly increased output of classical monocytes, contributing to immunosenescence. However, the underlying mechanisms remain unclear. Here, we identify that aging drives hematopoietic stem cells (HSCs) to progressively commit to a CCR2 + monocyte fate along a defined lineage trajectory, which is executed through a redox-sensitive transcriptional cascade. We find that the age-related decline in bone marrow IGF-1 is the upstream niche signal that releases suppression of the oxidative stress/NF-κB/IRF8 axis, allowing this cascade to redirect early progenitors toward a CCR2 + myeloid-primed fate. Functional assays confirm that cells following this CCR2 + trajectory drive myeloid-biased hematopoiesis and directly contribute to age-associated immunosuppression. Our work delineates a hierarchical pathway from niche decay to lineage redirection, establishing the CCR2 + fate trajectory as a key driver of immunosenescence and a potential therapeutic target.
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高影响因子
ANALYTICA CHIMICA ACTA
·
2026
·
IF 6.1
Zimiao Wen,Xinhua Lian,Zihan Zhang,Haiyan Zhao,Na Li,Min Cui,Cong Zhang
Insulin-like growth factor-1 (IGF-1) is a critical biomarker linked to various human diseases, necessitating sensitive and reliable detection methods. Herein, we report a novel sandwich-type ratiometric electrochemical immunosensor with signal on–off capability for the ultrasensitive measurement of IGF-1. The sensor was constructed using gold nanoparticle-engineered carbonized covalent organic frameworks (Au@C-COFs) as the sensing platform and thionine-enriched alkynyl COFs (Thi@aCOFs) as the signal amplification probe. Au@C-COFs exhibited excellent electrocatalytic activity toward hydroquinone (HQ) oxidation, providing a stable internal reference signal, while Thi@aCOFs generated a concentration-dependent reporter signal upon specific recognition of IGF-1 via the immobilized aptamer. The ratiometric strategy effectively eliminated external interferences, significantly enhancing accuracy and reliability. Under optimal conditions, the biosensor displayed a wide linear range from 10 fM to 1 nM, a low detection limit of 0.45 fM (S/N = 3), good specificity, stability, and satisfactory reproducibility. Furthermore, the sensor performed well for measuring IGF-1 in diluted human serum, achieving satisfactory recoveries. This work presents a robust and adaptable platform toward ratiometric electrochemical biosensing, holding great promise to achieve clinical diagnosis and management treatment of IGF-1-related disorders.
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CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Xinning Yu,Tengjing Xu,Huimin Shi,Jianqiao Hong,Xiaoqiang Jin,Le Cao,Jiajie Wang,Yunting Lin,Zongyou Pan,Siheng Wang,Jinghua Fang,Kaiwang Xu,Hongyun Song,Zhuxing Zhou,Sunan Zhu,Jun Yin,Yiying Qi,Xuesong Dai
Integration of repair tissue with host cartilage is challenging. The persistent and drastic hypocellular interface resulting from perifocal chondrocyte apoptosis, leads to failure of cartilage repair over time. Recombinant insulin-like growth factor-1 (IGF-1) has been shown to inhibit chondrocyte apoptosis in vitro. However, low bioactivity, limited penetration and short retention are its drawbacks. Herein, a cartilage targeting ionizable lipid nanoparticle (LNP) is developed. Messenger RNA (mRNA) encoding IGF-1 is chemically modified and encapsulated by LNP (mRNA-LNP). CAQK, a peptide previously used for targeted delivery to the central nervous system, is introduced to mRNA-LNP (mRNA-cLNP) to bind aggrecan enriched in cartilage. As a result, mRNA-cLNP exhibits improved penetration of cartilage and prolonged retention in the joint cavity. The mRNA-cLNP also showed robust reversal of chondrocyte apoptosis. In a full-thickness chondral defect plus microfracture model, mRNA-cLNP maintained interfacial cellularity and prevented matrix degradation in cartilage-cartilage interface. This study shows that mRNA-cLNP is a promising therapeutic agent for integrative cartilage repair.
研究领域:
骨科
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生物医学工程
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组织工程
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Xiaojun Yan,Yulin Zhang,Wen Zeng,Yang Li,Chenhui Zhu
Tendon repair remains a major clinical challenge, largely because current strategies often fail to simultaneously achieve early inflammatory control and subsequent matrix remodeling. To address this problem, we developed a dynamically responsive nano-hydrogel, CAPP@IGF-1, composed of 3-carboxyphenylboronic acid-modified chitosan, polyvinyl alcohol, and IGF-1-loaded PLGA microspheres, which were integrated through phenylborate ester crosslinking. The hydrogel exhibited favorable self-healing behavior together with enhanced mechanical properties, with an elastic modulus of 4.5 MPa and a toughness of 15.3 MJ/m³, enabling it to maintain local structural stability under the complex dynamic conditions of tendon repair. Under the acidic inflammatory microenvironment, CAPP@IGF-1 enabled controlled local release of IGF-1 and activated the IGF-1R/AKT signaling pathway, thereby markedly promoting macrophage reprogramming from the pro-inflammatory M1 state to the pro-reparative M2 state. This was accompanied by suppression of IL-6, IL-2, and TNF-α and upregulation of IL-10, leading to the establishment of a local immune microenvironment favorable for repair. On this basis, the hydrogel further promoted tendon stem/progenitor cell migration, proliferation, extracellular matrix remodeling, and more ordered collagen deposition. In a rabbit tendon injury model, CAPP@IGF-1 notably reduced peritendinous adhesion, and enhanced the mechanical recovery of repaired tendons. Collectively, CAPP@IGF-1 achieves stage-specific intervention during tendon healing through the combined effects of a dynamically crosslinked network, enhanced mechanical properties, and intelligent IGF-1 release. This study demonstrates the feasibility of using materials design to connect inflammatory microenvironment regulation with tissue regeneration and provides a new strategic basis for the precise repair of complex tendon injuries.
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PubMed
高影响因子
Frontiers in Aging
·
2026
·
IF 4.9
Lipeng Xu,Jinze Li,Anran Li,Jixian Chen,Liping Wang,Yaming Shan,Xianbin Cheng
Introduction Ellagic acid (EA) is a naturally occurring polyphenolic antioxidant speculated to influence aging, but its precise biological mechanisms remain poorly understood. Methods Using Caenorhabditis elegans as a model system, we investigated the anti-aging properties of EA. Lifespan assays were performed at multiple concentrations, and healthspan parameters including locomotor activity, lipofuscin accumulation, and reactive oxygen species (ROS) levels were assessed under thermal and oxidative stress. Genetic requirement was examined using loss-of-function mutants of daf-16, hsf-1, hlh-30, and skn-1. Gene expression was analyzed by qRT-PCR and reporter strains, and global transcriptional changes were mapped by RNA-sequencing. Results EA extended lifespan and preserved key healthspan features, including improved locomotor activity, reduced intestinal lipofuscin accumulation, and decreased ROS levels under stress conditions. The lifespan-extending effects of EA required daf-16, hsf-1, hlh-30, and skn-1, as EA failed to extend lifespan in these mutants. EA also enhanced the expression of downstream cytoprotective genes. Complementary RNA-sequencing revealed broader transcriptional remodeling, including metabolic pathways. Discussion These findings position EA as a modulator of a coordinated transcriptional network—rather than a single pathway—involving the insulin/IGF-1 signaling pathway and interconnected stress-response networks to promote longevity and stress resistance.
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PubMed
高影响因子
AQUACULTURE NUTRITION
·
2026
·Vol. 2026
·期 1
·4395252
·
IF 4.6
Haoran Yin,Lixing Wang,Zexin Lin,Ruilin Li,Qinxiao Cai,Zhiyu Zhou,Xiaoyi Wu
The hybrid grouper ( Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂), a typical carnivorous fish, has a limited ability to utilize dietary carbohydrates (CHOs). This study investigated the effects of different dietary arginine (Arg) levels (2.55 and 3.65%) and CHO-to-lipid ratios (C/L: 3.57, 2.39, 1.61) on the glycometabolism of hybrid grouper. Juvenile hybrid grouper (mean initial body length and weight: 7.8 cm and 13.04 g) were manually fed to fullness two times per day throughout a 7-week growth trial. The results showed that the C/L3.67 diets significantly elevated 2-h postprandial blood glucose concentration, as well as reduced hepatic glycogen level, intraperitoneal fat ratio (IPF), and the whole-body and hepatic lipid contents relative to the C/L2.39 and C/L1.61 diets. Dietary Arg supplementation significantly improved this metabolic disorder. These improvements were associated with enhanced plasma insulin-like growth factor 1 (IGF-1) concentration, hepatic phosphofructokinase (PFK) activity, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) levels. They were also linked to the upregulated expression of key molecules in related pathways, including IGF-1 receptor (igf1r), phosphatidylinositol 3-kinase (pi3k), protein kinase AMP-activated catalytic subunit α (ampk-α), and protein kinase B (Akt) genes, as well as glucose transporter 4 (GLUT4) and mechanistic target of rapamycin (mTOR) proteins. Generally, suitable dietary Arg supplementation can reduce postprandial blood glucose and hepatic glycogen concentrations in hybrid grouper fed high C/L diets by regulating key genes and proteins within the IGF-1 and NO-cGMP pathways. This finding provided a nutritional intervention to enhance CHO utilization in hybrid grouper aquaculture.
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高影响因子
RSC Advances
·
2019
·Vol. 9
·期 15
·8315-8325
·
IF 3.049
Zhiping Qi,Wenlai Guo,Shuang Zheng,Chuan Fu,Yue Ma,Su Pan,Qinyi Liu,Xiaoyu Yang
The mammalian central nervous system has a limited ability for self-repair under injury conditions. The treatment of nerve injuries has been revolutionised with the development of tissue engineering techniques. However, the lack of bioactivity has severely restricted the application of biodegradable implants for neurogenesis. Therefore, surface modification of biomaterials is crucial to improve their bioactivity and promote endogenous repair mechanisms for nerve regeneration. Insulin-like growth factor 1 (IGF-1) is a growth factor for neuroprotection and neurogenesis. In this study, IGF-1 was successfully immobilised on graphene oxide (GO)-incorporated poly(lactic-co-glycolic acid) (PLGA) biodegradable electrospun nanofibres. For the in vitro investigation, neural stem cells (NSCs) were cultured on different nanofibres to observe various cellular activities. GO enhanced NSC survival under H2O2 pre-treatment and neuronal differentiation to some extent. More importantly, the immobilisation of IGF-1 onto the PLGA/GO nanofibres resulted in significantly increased NSC survival, proliferation, and differentiation. Findings from this study revealed that using PLGA/GO electrospun nanofibres to immobilise IGF-1 has excellent potential for the enhancement of the neuroprotective and neurogenic effects of nerve implants.
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PubMed
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 106
·期 6
·e70214
·
IF 3.3
Guihua Jia,Jiayi Li,Abbas Khan,Aman Chandra Kaushik,Diyi Wu,Hongyu Chen,Rongpei Li,Jian Wang,Chen Zhang,Adil Farooq,Xueying Mao,Aamir Mehmood,Weidong Zhang,Heng Wang,Dong-Qing Wei
WGX-50, a previously reported drug candidate for Alzheimer's disease, is derived from Zanthoxylum bungeanum Maxim commonly called Sichuan pepper. Its pharmacological actions for the long run benefit of human health have been extensively investigated. However, in terms of its anti-aging effect, it totally remains unexplored. In this work, WGX-50 was first reported to promote healthy aging in Caenorhabditis elegans with insights from drug target prediction and molecular dynamics simulations. Further investigations have experimentally demonstrated that: Firstly, both daf-16 and skn-1 genes are causative to WGX-50 mediated longevity. WGX-50 failed to extend lifespan upon depletion of these genes in transgenic worms. Their orthologs Foxo1 and Nrf2 were also activated even in D-galactose (D-gal) induced aging and Zmpste24 −/− progeria mice intestines. Secondly, WGX-50 inhibits IIS signaling via downregulating daf-2 , and activating daf-16 and skn-1 genes, which thus enable downstream pro-longevity effectors increasing stress resistance and promoting healthier aging. WGX-50 increased expression levels of sod-3 , ctl-1 , gst-7/8/12/33 , gsto-1 , and heat shock protein genes such as hsp-12.2 , hsp-90 , F44E5.4/0.5 , T05E11.9 and their inducer hsf-1 . In addition, the accumulation of lipofuscin, fat, and reactive oxygen species levels with age was decreased significantly upon WGX-50 supplementation without physiological impairments. Thirdly, in progeria, D-gal and naturally aged mice, WGX-50 is incapable of inducing aging. Senescent genes and SASP factors were not produced at higher levels in livers and small intensities. No impact was observed on key organ indices, blood biochemistry parameters, and bone histomorphometry. WGX-50 perhaps prolongs lifespan through other mechanisms such as reducing fertility, inducing dietary restriction, and improving proteostasis with lowered levels of polyQ35 aggregates. Our findings thus provide primary insights for the potential medical use of WGX-50 in anti-aging and long-term healthcare.
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PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 3
·376
·
IF 5.5
Yuxing Zhang,Xixi Zou,Qiran Du,Xiaotao Dong,Uday Kumar Chinta,Ruyue Yu,Fei Wu,Tuo Jin
Objectives: Thermo-gelling hydrophilic polymers like PLGA–PEG–PLGA are known as injectable sustained-release depots for biologics, but they face challenges due to the occurrence of severe burst release. This study aimed to develop a strategy to avoid the initial burst release by pre-encapsulating proteins in polysaccharide microparticles through an aqueous–aqueous emulsion mechanism, thereby enhancing therapeutic retention and linear release kinetics.Methods: Five model proteins (G-CSF, GM-CSF, IGF-1, FVIII, BSA) were encapsulated in dextran microparticles, using an organic solvent-free aqueous–aqueous emulsion method. These particles were dispersed in a 23% (w/w) PLGA–PEG–PLGA solution and injected into a 37 °C release buffer to form a gel depot. The in vitro release profiles were quantified using ELISA and MicroBCA assays over 9–42 days. The bioactivity of the proteins was validated using cell proliferation assays (NFS-60, TF-1, MCF-7) and chromogenic kits. The in vivo pharmacokinetics of the FVIII-loaded formulations were evaluated in Sprague–Dawley rats (n = 5/group) over 28 days.Results: Protein-loaded dextran particles retained their structural integrity within the hydrogel and exhibited minimal burst release (≤5% within 30 min vs. >25% for free proteins). Sustained near-linear release profiles were observed for all the proteins, with complete release by day 9 (G-CSF, GM-CSF, BSA) or day 42 (FVIII). Rats administered with the thermal gel with FVIII–dextran particles showed a significantly lower peak plasma concentration (Cmax: 88.25 ± 30.21 vs. 132.63 ± 66.67 ng/mL) and prolonged therapeutic coverage (>18 days vs. 15 days) compared to those administered with the thermal gel with the FVIII solution. The bioactivity of the released proteins remained at ≥90% of the native forms.Conclusions: Pre-encapsulation in dextran microparticles effectively mitigates burst release from thermosensitive hydrogels, while preserving protein functionality.
研究领域:
药剂学
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生物医学工程
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药物递送系统
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蛋白质工程
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PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Song Wang,Chenyu Jiang,Shitong Yu,Qianru Fan,Kai Yang,Jianqin Huang,Yan Li
Background Hickory ( Carya cathayensis ) nuts, renowned for their health benefits and delightful taste, contain abundant bioactive compounds, particularly polyphenols. However, the specific mechanisms underlying their antioxidant properties and anti-aging effects remain elusive. Purpose This study aims to investigate the effects of hickory nut polyphenols (HNP) on oxidative stress mitigation and aging modulation. Methods The innovative integration of medium-pressure liquid chromatography (MPLC) with in vitro bioactive screening was employed to discover an optimized HNP fraction (HNP3–2). Anti-aging effects of HNP3–2 on Caenorhabditis elegans ( C. elegans ) were determined through lifespan analysis, lipofuscin accumulation quantification, and motility assessments. Oxidative stress resistance was further evaluated by detecting the reactive oxygen species (ROS) contents, lipid peroxidation, and antioxidase activities. Integrative approaches combining transcriptomic, qRT-PCR, GFP reporter strains, and gene knockout mutants were utilized to explore the potential regulatory mechanisms. Non-targeted metabolomics was employed to conduct a comprehensive profiling analysis of HNP and their bioactive fractions. Results HNP3–2 significantly decreased ROS production, lipofuscin accumulation, and lipid peroxidation, while enhanced the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). It also conferred robust protection against oxidative stress induced by H 2 O 2 and juglone. HNP3–2 regulated lifespan extension mainly via the DAF-16/-2 insulin/IGF-1 signaling (IIS), which was further validated using loss- and gain-of-function mutants including age-1, akt-1/2, daf-2 , and daf-16 , as well as worms overexpressing SOD-3, GST-4, and DAF-16. Metabolomic analysis identified 31 kinds of polyphenol compounds displaying abundance patterns congruent with the overall antioxidant potency in vitro. Conclusion This study first reveals the efficacy of HNP as a promising antioxidant and anti-aging intervention. Notably, the screened bioactive fraction HNP3–2 acts primarily by modulating the DAF-16/DAF-2 insulin/IGF-1 signaling cascade, operating through a mechanism independent of dietary restriction. Collectively, these findings position HNP as a breakthrough candidate for next-generation gerotherapeutics, with translational potential for advancing human aging research.
研究领域:
生物化学
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分子生物学
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衰老研究
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PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2015
·Vol. 15
·期 8
·1070-1080
·
IF 3.851
Tianlin Gao,Ning Zhang,Zongliang Wang,Yu Wang,Ya Liu,Yoshihiro Ito,Peibiao Zhang
In this study, insulin-like growth factor 1 (IGF-1) was successfully immobilized on the poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and pure PLGA microcarriers via polydopamine (pDA). The results demonstrated that the pDA layer facilitated simple and highly efficient immobilization of peptides on the microcarriers within 20 min. Mouse adipose-derived stem cells (ADSCs) attachment and proliferation on IGF-1-immobilized microcarriers were much higher than non-immobilized ones. More importantly, the IGF-1-immobilized PLGA/HA microcarriers significantly increased alkaline phosphatase (ALP) activity and expression of osteogenesis-related genes of ADSCs. Therefore, it is considered that the IGF-1-decorated PLGA/HA microcarriers will be of great value in the bone tissue engineering.
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高影响因子
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