ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Jinping Fan,Yang Geng,Jinglei Liu,Qixin Huang,Jie Zeng,Huiyuan Cao,Xiaokai Lu,Hao Cheng,Zhili Qi
Deoxynivalenol (DON), a pervasive mycotoxin contaminating crops and soil, poses significant threats to ecological security and intestinal homeostasis. While gut microbiota dysbiosis is implicated in DON-induced enterotoxicity, the engineering-driven mechanisms linking gut-derived extracellular vesicles (EVs) to environmental-host interactions remain unexplored. Here, we isolated and characterized gut-derived EVs (DON-EVs) from DON-exposed mice, employing ultracentrifugation, transmission electron microscope, nanoparticle tracking analysis, and protein marker validation. Functional validation demonstrated that DON-EVs potently attenuated M2 macrophage polarization and downregulated tight junction proteins, thereby exacerbating intestinal barrier dysfunction. miRNA-seq revealed 8 differentially expressed miRNAs in DON-EVs, with 5_19616 exhibiting pronounced pro-inflammatory effects via screening and inhibitor assays. Mechanistically, 5_19616 suppressed peroxisome proliferator-activated receptor gamma (PPAR-γ) expression through direct targeting, inhibiting M2 macrophage polarization and downregulating tight junction proteins, thereby compromising intestinal barrier integrity. Adoptive transfer of 5_19616-transfected macrophages into mice induced systemic inflammation, epithelial damage, and PPAR-γ pathway inhibition, mirroring DON-induced pathology. Crucially, our findings highlight EVs as nanoscale bioengineering vectors mediating environmental-host crosstalk. Collectively, this study pioneers the "gut-EVs-miRNA-macrophage" axis as a novel engineering target, offering miRNA-directed strategies to mitigate mycotoxin-related diseases, with potential applications in nanomedicine and environmental health engineering.
研究领域:
毒理学
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免疫学
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分子生物学
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环境卫生
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纳米医学
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胃肠病学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2020
·
IF 5.115
Shuping Wei,Chaoli Xu,Yidan Zhang,Zhongqing Shi,Min Wu,Bin Yang
Objective To investigate the antifibrotic effect of the combination of a PPARγ agonist-loaded nanoparticle-microbubble complex with ultrasound (US) exposure on renal interstitial fibrosis (RIF). Materials and Methods Polylactide-co-glycolide (PLGA) nanoparticles were used to load PPARγ agonist (rosiglitazone, RSG) and prepare PLGA-RSG nanoparticles (PLNPs-RSG); then, a novel complex between PLNPs-RSG and SonoVue microbubbles (MBs) (PLNPs-RSG-MBs) was prepared. The size distribution, zeta potentials, RSG-loading capacity and entrapment efficiency were measured, and the release of RSG was assessed using a UV-vis spectrophotometer. The in vitro cytotoxicity and in vivo systemic toxicity assays were performed. The cellular uptake assessment was performed using a confocal laser scanning microscope (CLSM). The in vivo biodistribution assessment was performed using fluorescence imaging with a near-infrared (NIR) imaging system. Furthermore, this complex was administered to a unilateral ureteral obstruction (UUO) rat model with the assistance of US exposure to investigate the antifibrotic effect. Results This PLNPs-RSG-MBs complex had a size of 2199.5± 988.1 nm and a drug-loading efficiency of 28.5%. In vitro cytotoxicity and in vivo systemic toxicity assays indicated that the PLNPs-RSG-MBs complex displayed excellent biocompatibility. In addition, the complex showed high cellular uptake efficiency in vitro and kidney-targeting ability in vivo. In a UUO rat model, the combination of the PLNPs-RSG-MBs complex with US exposure significantly reduced collagen deposition and successfully attenuated renal fibrosis. Conclusion The combination of the PLNPs-RSG-MBs complex with US exposure may be a promising approach for the treatment of RIF.
研究领域:
药理学
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纳米技术
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医学影像学
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肾脏疾病
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DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2024
·
IF 4.8
Yanqing Wang,Huanying Zhang,Feng Ding,Jianhua Li,Lianyu Li,Zhong Xu,Yan Zhao
Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of β-amyloid (Aβ), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis, and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early-stage AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aβ-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aβ-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aβ in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aβ by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator-activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aβ-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aβ-induced toxicity.
研究领域:
神经生物学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Yuanbiao Ma,Xu Liu,Zhewen Deng,Jiaqi Li,Ruoxi Liu,Shanshan Li,Can Zhang,Yutong Chen,Senqiang Zhu,Qi Zhang,Rui Liu,Bo Ma
CMCSMA/F127/TPGS@α-MG hydrogel promotes infected diabetic wound healing. • F127/TPGS micelles improve the aqueous solubility and sustained release of α-MG. • The composite hydrogel disrupts biofilms and achieves 99.6% wound closure. • α-MG modulates PPAR-γ, attenuating inflammation and promoting angiogenesis. Diabetic wounds pose a major clinical challenge owing to their complex microenvironment and persistent inflammation. To address this issue, we engineered a multifunctional, in situ photocrosslinkable composite hydrogel (CMCSMA/F127/TPGS@α-MG) to promote wound healing. To overcome the hydrophobicity of the antimicrobial agent α-mangostin (α-MG), it was first encapsulated in F127/TPGS nanomicelles. These micelles were then integrated into a methacrylated carboxymethyl chitosan (CMCSMA) matrix, enabling rapid conformal gelation upon 405 nm light irradiation. The resulting hydrogel exhibited a biphasic sustained-release profile, excellent biocompatibility, and potent contact-killing and anti-biofilm activities against Staphylococcus aureus ( S. aureus ). In an S. aureus -infected diabetic wound model, the hydrogel significantly accelerated wound closure, achieving 99.6% closure by day 14, and facilitated high-quality tissue regeneration characterized by complete re-epithelialization and orderly collagen deposition. Furthermore, an integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and experimental validation revealed that the therapeutic efficacy of sustained local α-MG delivery involves the modulation of the PPAR-γ pathway. This regulatory process suppresses the NF-κB/COX-2 inflammatory axis and upregulates pro-angiogenic markers, including VEGF, CD31, and α-SMA. Collectively, this dual-action platform, which synergizes physical barrier protection with targeted molecular modulation, represents a promising translational strategy for refractory diabetic wounds. Schematic illustration of the preparation process and functional attributes of the in situ forming CMCSMA/F127/TPGS@α-MG hydrogel. Download: Download high-res image (67KB) Download: Download full-size image
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高影响因子
Drug Design Development and Therapy
·
2023
·
IF 4.8
Yi-Jin Wu,Sa-Sa Zhang,Qin Yin,Ming Lei,Qi-Hai Wang,Wen-Gang Chen,Ting-Ting Luo,Peng Zhou,Cong-Lan Ji
Background α-Mangostin (MG) showed the potentials in alleviating experimental arthritis, inhibiting inflammatory polarization of macrophages/monocytes, and regulating peroxisome proliferators-activated receptor γ (PPAR-γ) and silent information regulator 1 (SIRT1) signals. The aim of this study was to analyze the correlations among the above-mentioned properties.Methods Antigen-induced arthritis (AIA) was established in mouse, which was treated with MG in combination with SIRT1/PPAR-γ inhibitors to clarify the role of the two signals in the anti-arthritic actions. Pathological changes were systematically investigated. Phenotypes of cells were investigated by flow cytometry. Expression and co-localization of SIRT1 and PPAR-γ proteins in joint tissues were observed by the immunofluorescence method. Finally, clinical implications from the synchronous up-regulation of SIRT1 and PPAR-γ were validated by experiments in vitro.Results SIRT1 and PPAR-γ inhibitors (nicotinamide and T0070097) reduced the therapeutic effects of MG on AIA mice, and abrogated MG-induced up-regulation of SIRT1/PPAR-γ and inhibition of M1 polarization in macrophages/monocytes. MG has a good binding affinity to PPAR-γ, and MG promoted the co-expression of SIRT1 and PPAR-γ in joints. Synchronously activating SIRT1 and PPAR-γ was revealed to be necessary by MG to repress inflammatory responses in THP-1 monocytes.Conclusion MG binds PPAR-γ and excites this signaling to initiate ligand-dependent anti-inflammatory activity. Due to certain unspecified signal transduction crosstalk mechanism, it then promoted SIRT1 expression and further limited inflammatory polarization of macrophages/monocytes in AIA mice.
研究领域:
免疫学
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药理学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2026
·
IF 7.5
Weiqi Zhang,Han Yin,Chenchen Wang,Xiaowei Ma,Dazhuang Miao,Guimiao Li,Wei Chen,Zhiyong Hou,Xianda Gao,Yingze Zhang,Di Zhang
Oxidative stress and apoptosis mediated senescence of nucleus pulposus cells (NPCs) and the degradation of extracellular matrix (ECM), which represent a key mechanism underlying intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes hold therapeutic potential for tissue repair; however, their clinical application is limited by rapid clearance, short half-life, and poor target specificity. To overcome these challenges, this study developed poly(lactic-co-glycolic acid) (PLGA) microspheres as a sustained-release carrier for exosomes derived under either normoxic (Exos, 21% O₂) or hypoxic (H-Exos, 1% O₂) conditions. The PLGA microspheres demonstrated high exosome-loading efficiency and provided controlled release for over four weeks. Released hypoxic exosomes activate PPAR-γ pathway, exerting better effects by reducing NPCs SA-β-gal positive rate by 59.8% and elevates Col II and ACAN levels by 30.7% and 25.5%. Animal experiments confirmed that this system effectively attenuated IVDD progression indicating its potential for clinical translation.
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高影响因子
Experimental and Therapeutic Medicine
·
2024
·Vol. 27
·期 6
·1-12
·
IF 2.4
Boyu Tan,Xiaoxu Lan,Yifan Zhang,Pai Liu,Qiyao Jin,Zhiqiang Wang,Zhidong Liang,Wei Song,Ye Xuan,Yunxiao Sun,Youjie Li
The present study aimed to investigate the effect and mechanism of Pulsatilla compounds on lung adenocarcinoma. The representative drug chosen was the compound 23‑HBA. GeneCards, Swiss target prediction, DisGeNET and TCMSP were used to screen out related genes, and MTT and flow cytometry assays were used to verify the inhibitory effect of Pulsatilla compounds on the proliferation of lung adenocarcinoma cells. Subsequently, the optimal target, peroxisome proliferator‑activated receptor (PPAR)‑γ, was selected using bioinformatics analysis, and its properties of low expression in lung adenocarcinoma cells and its role as a tumor suppressor gene were verified by western blot assay. The pathways related to immunity and inflammation, vascular function, cell proliferation, differentiation, development and apoptosis with the highest degree of enrichment and the mechanisms were explored through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Finally, the clinical prognosis in terms of the survival rate of patients in whom the drug is acting on the target was analyzed using the GEPIA database. The results indicated that Pulsatilla compounds can inhibit the proliferation of lung adenocarcinoma cells by blocking the cell cycle at the G1 phase. Subsequently, the related PPAR‑γ gene was verified as a tumor suppressor gene. Further analysis demonstrated that this finding was related to the PPAR signaling pathway and mitochondrial reactive oxygen species (ROS) production. Finally, the clinical prognosis was found to be improved, as the survival rate of patients was increased. In conclusion, Pulsatilla compounds were indicated to inhibit the viability and proliferation of lung adenocarcinoma H1299 cells, and the mechanism of action was related to PPAR‑γ, the PPAR signaling pathway and mitochondrial ROS. The present study provides novel insight to further explore the treatment of lung adenocarcinoma.
研究领域:
肿瘤学
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药理学
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生物信息学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
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IF 4.4
Yu Wenjing,Luo Rongsiqing,He Chunxiang,Li Ze,Yang Miao,Zhou Jinyong,He Jiawei,Chen Qi,Song Zhenyan,Cheng Shaowu
Background: The escalating global burden of diabetes and its associated cognitive impairment underscores the urgency for effective interventions. Bergenin shows promise in regulating glucose metabolism, mitigating inflammation, and improving cognitive function. Zebrafish models offer a unique platform for assessing drug efficacy and exploring pharmacological mechanisms, complemented by subsequent investigations in cell and rat models.Methods: The experimental subjects included zebrafish larvae (CZ98:Tg (mpeg1:EGFP)ihb20Tg/+), adult zebrafish (immersed in 2% glucose), BV2 cell line (50 mM glucose + 10 μm Aβ1-42), and a streptozotocin (STZ) bilateral intracerebroventricular injection rat model. Bergenin’s effects on the toxicity, behavior, and cognitive function of zebrafish larvae and adults were evaluated. The Morris water maze assessed cognitive function in rats. Neuronal histopathological changes were evaluated using HE and Nissl staining. qPCR and Western blot detected the expression of glycolysis enzymes, inflammatory factors, and Bergenin’s regulation of PPAR/NF-κB pathway in these three models.Results: 1) In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased ins expression and increased expression of irs1, irs2a, and irs2b, suggesting a reduction in insulin resistance. It also altered the expression of pparg and rela. 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1β, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus.Conclusion: Bergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.
研究领域:
药理学
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神经科学
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糖尿病
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炎症
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代谢
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行为科学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
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IF 10.723
Pengchao Xie,Yan Peng,Liyan Qiu
To explore effective therapeutic strategy on nonalcoholic fatty liver disease (NAFLD), the amphiphilic oligochitosan derivative containing ursodeoxycholic acid (UDCA) was synthesized and named as UBC, which could self-assemble and encapsulate exenatide (Exe) to obtain Exe-UBC nano-vesicle. Exe-UBC could be uptaken by fatty-acid cultured cells and release UDCA and Exe responsive to the high esterase concentration. In vitro experiments demonstrated that Exe-UBC activated the expression level of SIRT1 with inhibited expression of PGC-1β and PPAR-γ and consequently exerted synergistic bioaction immediately on reducing lipidosis. After a month of Exe-UBC treated through intravenous injection, the body weight of high-fat diet feeding C57BL/6 mice recovered to ordinary level, and their lipid contents in the liver declined significantly. The recovery in hepatic function indexes like TG , AST , and ALT further revealed the superiority of Exe-UBC vesicles. These results suggested that the co-delivery of UDCA and Exe via Exe-UBC could be a potent platform for NAFLD treatment.
研究领域:
药学
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生物技术
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 8
·期 9
·3259-3270
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IF 3.247
Xiaozhou Zhou,Shiguo Chen,Xingqian Ye
The anti-obesity effects of different proanthocyanidin extracts (PE) from Chinese bayberry (Myrica rubra Sieb.et Zucc.) leaves were evaluated in a high-fat (HF) diet-induced obese rat model. The leaves of Chinese bayberry (LCB), a non-desaccharified proanthocyanidin extract (NDPE), and a desaccharified proanthocyanidin extract (DPE) were compared with orlistat, a conventional anti-obesity drug used as a positive control. The rats from all of the PE-treated groups showed obvious weight loss, with the greatest weight loss in the DPE group (P < 0.05). Compared to the HF group, almost all of the PE-treated groups showed significantly reduced levels of serum TC, TG, AST, ALT, ALP, LDL-C, ADP and a LEP/ADP ratio, and increased levels of HDL-C and LEP. Furthermore, the expression levels of SIRT1, PPAR-γ, C/EBP-α, BMP4 and UCP1 were investigated in the liver, kidney, epididymis and abdominal adipose tissue. Compared to the HF group, PPAR-γ and C/EBP-α levels were significantly reduced and SIRT1, BMP4 and UCP1 levels were significantly upregulated in the DPE-treated group. Our results suggested that PE exerted its anti-obesity effects by upregulating the expression of SIRT1, thus inducing the deacetylation of PPAR-γ and downregulating the expression of C/EBP-α, and also upregulating the expression of BMP4 to boost the levels of brown fat.
研究领域:
药理学
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营养学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2025
·Vol. 24
·期 1
·1-16
·
IF 4.2
Li Lishuang,Ren Xing,Gao Xinyu,Zhao Yujia,Ma Yuman,Gong Junxiao,Yang Shuo,Sun Yanan,Wang Yi
Objective This study aimed to investigate the regulatory role and mechanisms of chenodeoxycholic acid (CDCA) on lipid metabolism, and to evaluate its therapeutic potential in lipid metabolism-related diseases such as acne, seborrheic alopecia, and prostate cancer, with the aim of identifying safer and more sustainable treatment alternatives. Methods Lipid-overproduction models were established using RM-1 (murine prostate cancer cells) and primary sebaceous gland cells, stimulated by linoleic acid (LA) and dihydrotestosterone (DHT), respectively. CDCA’s mechanisms were explored using transcriptomics, proteomics, and fatty acid-targeted metabolomics. In vivo validation was conducted via intradermal injection of CDCA into the sebaceous gland area of golden hamsters to assess its effect on sebaceous lipid metabolism. Results CDCA significantly reduced intracellular lipid accumulation in both murine prostate cancer cells (RM-1) and primary sebaceous gland cells, and suppressed the expression of the androgen receptor (AR), along with the downregulation of key lipogenic enzymes (SREBF1, FASN, FADS2). Mitochondrial membrane potential was restored in CDCA-treated cells. Multi-omics analyses revealed that CDCA modulated fatty acid biosynthesis and degradation, energy metabolism, mitochondrial function, and Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) signaling. Lipidomic profiling demonstrated a shift from saturated to unsaturated fatty acid dominance after CDCA treatment. In vivo, CDCA decreased sebaceous lipid accumulation and downregulated PPAR-γ expression in golden hamsters. Conclusion CDCA exerted multifaceted regulatory effects on lipid metabolism, hormone signaling, and mitochondrial dynamics. These effects contributed to the maintenance of sebaceous gland homeostasis and supported the development of innovative and potentially more biocompatible therapies for lipid-related disorders.
研究领域:
生物化学
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分子生物学
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药理学
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皮肤科学
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肿瘤学
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内分泌学
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系统生物学
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代谢组学
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转录组学
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蛋白质组学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Danlei Hu,Dongmei Chen,Aoxue Zhang,Kuiyu Meng,Min Chen,Raja Mubbashar,Wei Qu,Shuyu Xie
Current IBD therapies face limitations such as systemic toxicity, off-target effects, and microbiota dysbiosis. We developed an oral multifunctional gel bead integrating three innovations: (1) a butyrate–apigenin synergy that inhibits NF-κB via CK2/p65 phosphorylation suppression, activates a PPAR-γ-mediated metabolic shift to β-oxidation, and modulates the microbiota by enhancing Bacteroidetes/suppressing Enterobacteriaceae; (2) an apigenin–butyrate ester prodrug overcoming organoleptic issues while enabling CK2 targeting; and (3) a pH/enzyme–responsive delivery system using the FDA-approved ascorbyl palmitate/alginate, achieving gastric protection, charge–mediated colitis targeting, and esterase–triggered release. In colitis model mice, gel beads restore clinical parameters, intestinal integrity, and microbial balance, outperforming apigenin-butyrate ester and 5-ASA at half-doses with extended intervals. It significantly downregulated colon CK2 expression (4.07-fold) and the phospho-P65/total P65 ratio (3.04-fold). This integrated strategy combining multimodal drug actions and precision delivery establishes a new paradigm for efficient and alternative IBD therapeutics with reduced dosing requirements.
研究领域:
药学
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胃肠病学
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药物递送
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分子医学
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微生物组研究
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DOI
PubMed
高影响因子
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