POULTRY SCIENCE
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2026
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IF 4.5
Yi Fang,Hongyu Fu,Xuehan Jiang,Hongxue Yang,Yishan Yin,Bo Li,Xiaoxiao Chen,Bendong Shi,Jingzeng Cai,Ziwei Zhang
Deoxynivalenol (DON), as the most prevalent mycotoxin, not only poses a significant threat to animal and human health but also exerts pronounced adverse effects on growth and development. Quercetin (QUE), a naturally occurring antioxidant, is known to promote muscle growth and differentiation. In this study, a DON-exposed broiler model with QUE intervention was established to investigate the protective mechanisms of QUE against DON-induced skeletal muscle toxicity. Eighty broilers were randomly divided into four groups: CON group, DON group, QUE group, and DON+QUE group. Each group received oral administration of 10 mg/kg DON and/or 4 mg/kg QUE. For in vitro experiments, myoblasts were used as experimental subjects to establish intervention models with LY294002, Z-VAD-FMK, and IBS008738. This study demonstrates that DON exposure induces oxidative stress and apoptosis (increased by 329%) in both in vivo muscle tissue and in vitro myoblasts, inhibits the expression of myogenic regulatory factors such as MYH2, and consequently leads to structural muscle damage and developmental impairment. Crucially, we identified that QUE effectively alleviated DON-induced oxidative stress (CAT activity increased by 45.1%), apoptosis (nearly completely inhibited), and muscle developmental disorders (MYH2 increased by 35.2%) by upregulating the transcription and phosphoprotein expression levels of genes associated with the PI3K/Akt/mTOR signaling pathway. The pivotal role of this pathway was further confirmed by the fact that the PI3K inhibitor LY294002 abolished the protective effects of QUE. Moreover, inhibition of apoptosis, but not promotion of myogenesis, directly alleviated DON-induced muscle defects, establishing apoptosis as the causative event. In conclusion, our data demonstrated that QUE alleviated DON-induced apoptosis via the PI3K/Akt/mTOR pathway, thereby mitigating muscle development disorders.
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Journal of Functional Foods
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2026
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IF 3.9
Wei Wei,Shuai Wang,Qiming Wu,Xinyong Zheng,Fuguo Liu
Walnut is a nutrient-rich food resource, yet the utilization of its high-quality plant proteins remains inefficient. Advanced processing strategies are therefore needed to develop walnut-based functional foods. In this study, walnut peptides were prepared by sequential hydrolysis with alcalase and papain, leading to the identification of a novel antioxidant peptide, IRALPEEVL. In vitro , IRALPEEVL increased the viability of PC12 cells under H 2 O 2 -induced oxidative stress. In vivo , it ameliorated cognitive and memory dysfunctions in zebrafish exposed to the environmental toxicant bisphenol AF. Proteomic analysis indicated that the neuroprotective effects of IRALPEEVL were associated with caveolin-1 (Cav1)-dependent penetration of the blood-brain barrier, regulating the AMPK-PI3K/Akt signaling, and inhibiting neuronal apoptosis. These findings highlight the potential of value-added walnut processing and support the application of walnut-derived peptides as functional food ingredients for health promotion.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
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IF 5.2
Zhongting Lv,Xiang Li,Hanning Wu,Xiaowen Zhang,Wangyang Hu,Yong Xu,Jie Zhang,Li Ren
Chronic stress is a major contributor to hippocampal neurotoxicity and cognitive dysfunction. However, mechanism-oriented interventions remain limited. Bilobalide is a chemically defined sesquiterpene lactone from Ginkgo biloba with reported neuroprotective activity. Nevertheless, its effect on chronic stress-induced cognitive injury and its relationship to glucocorticoid receptor (GR) signaling remain unclear. Here, we evaluated bilobalide in chronic restraint stress (CRS) mice and in corticosterone (CORT)-challenged HT22 hippocampal neurons. Bilobalide improved short-term recognition, long-term recognition, and spatial memory in CRS mice, and alleviated neuronal injury in the hippocampal CA1, CA3, and dentate gyrus regions. These effects were accompanied by reduced lipid peroxidation, recovery of antioxidant capacity, attenuation of systemic inflammatory cytokine release and hippocampal inflammatory gene expression, suppression of apoptosis-related signaling, and preservation of dendritic architecture, synaptic ultrastructure, and synaptic proteins. Bilobalide also restored hippocampal BDNF/TrkB/PI3K/Akt signaling. In vivo and in vitro fractionation/immunofluorescence experiments showed that bilobalide restrained stress-enhanced GR nuclear translocation, and GRE-reporter assays showed reduced GR transactivation. Molecular docking and cellular thermal shift assay supported cellular target engagement of GR by bilobalide. Importantly, GR knockdown blunted bilobalide-mediated rescue of oxidative injury and of BDNF/TrkB/PI3K/Akt-associated synaptic signaling in CORT-injured HT22 cells. These data indicate that bilobalide protects against chronic stress-induced hippocampal neurotoxicity and memory impairment, at least in part, by limiting maladaptive GR signaling and preserving neurotrophic-synaptic homeostasis. Bilobalide therefore merits further evaluation as a mechanistically defined lead compound for stress-associated cognitive dysfunction.
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npj Science of Food
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2026
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IF 9.7
Shen Linyuan,Ma Jianfeng,Liang Shuang,Yang Yiting,Liao Tianci,Lei Yuhang,Chen Lei,Wang Yan,Zhao Ye,Niu Lili,Gan Mailin,Zhu Li
Diet derived extracellular vesicles (EV) can be absorbed and influence physiological processes. Herein, this study investigates the potential health impacts of extracellular vesicles in meat products. Experimental results showed the extracellular vesicles derived from cooked red meat (RM-EV) and white meat (WM-EV) were successfully isolated via ultra-high speed centrifugation. The median particle size of RM-EV is 137.5 nm and that of WM-EV is 116.1 nm. RM-EV and WM-EV are added to the drinking water of mice for ten weeks. The mice developed insulin resistance and abnormal lipid metabolism in the liver. The influences of RM-EV are more pronounced for mice than WM-EV. High-throughput sequencing indicated that ssc-miR-1 (52.05%) and scc-miR-133a-3p (14.21%) are the most abundant microRNA in RM-EV. However, the highest content of microRNA is gga-miR-133a-3p (44.16%) in WM-EV, followed by gga-miR-1 (21.58%). Therefore, the most abundant ssc-miR-1 in red meat EV (RM-EV-miR-1) was selected for in vitro studies. In vitro experiments revealed that RM-EV-miR-1 inhibited cell proliferation by targeting IGF1 in NCTC1469 liver cell. Besides, RM-EV-miR-1 exacerbates insulin resistance in NCTC1469 insulin resistance cell model by targeting PI3K/AKT signaling pathway. Our findings show that the differential health impacts of red and white meat may be partially attributed to the presence of EV. These results provide novel insights into dietary health from the perspective of EV.
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BIOCHEMICAL PHARMACOLOGY
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2026
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IF 6.5
Yu-jia Huo,Miao Wei,Xiao Fan,Li-wen Peng,Jing-chang Yuan,Si-si Tan,Xiao-chen Wang,Ruo-tong Ou-yang,Yi-jing Zhou,Yan-yu Pu,Xi Gao,Jun-qin Lei,Hong Li
Glaucoma is a prominent global cause of irreversible vision loss, fundamentally driven by the continuous degeneration and ultimate death of retinal ganglion cells (RGCs), in which persistent oxidative stress plays a pivotal role. While selenium (Se) offers robust endogenous antioxidant defense, the severe toxicity and narrow therapeutic window of inorganic selenium strictly limit its application. To overcome this critical bottleneck, chitosan-functionalized selenium nanoparticles (CS-SeNPs) are engineered. This strategic nanomodification effectively shields the inherent toxicity of free selenium while conferring improved colloidal stability and biocompatibility. Clinically, systemic Se levels in patients with primary open-angle glaucoma (POAG) are found to be significantly diminished compared to healthy controls. Mechanistically, transcriptome sequencing reveals that CS-SeNPs function through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway to upregulate the downstream nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) antioxidant axis, reducing intracellular oxidative stress and apoptosis. In vivo, an intravitreal administration strategy for CS-SeNPs is established. In a rat model of acute ocular hypertension (AOH), this targeted local delivery reduces oxidative damage, preserves retinal hierarchical architecture, and restores visual electrophysiological function. These findings identify systemic Se deficiency as a clinical hallmark of POAG and demonstrate that intravitreal CS-SeNPs offer a promising, intraocular pressure-independent nanotherapeutic strategy for glaucomatous neuroprotection.
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JOURNAL OF HAZARDOUS MATERIALS
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2026
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IF 10.6
Yan Zhang,Fuqing Yi,Ying He,Yidan Ma,Xinyi Mu,Yanqing Geng,Xin Yin,Rufei Gao,Liping Yan,Xuemei Chen,Junlin He
Dibutyl phthalate (DBP), a common environmental endocrine-disrupting chemical, is known to impair female reproduction, yet its specific effects on ovarian reserve and underlying epigenetic mechanisms are not fully understood. Here, using gestational exposure models ( in vivo ) and fetal ovarian culture models ( in vitro ), we show that gestational DBP exposure disrupts the ovarian reserve through a dual assault: impairing primordial follicle formation ("input") and, more critically, driving primordial follicle premature activation ("output"). Mechanistically, DBP induces METTL14-dependent m⁶A hypermethylation, which activates the PI3K-AKT-FOXO3a signaling axis to promote aberrant follicular activation. Knockdown of Mettl14 rescues this pathway activation and the follicular disruption. Long‑term follow‑up revealed that such precocious activation leads to progressive ovarian reserve depletion, culminating in a premature ovarian insufficiency (POI)-like phenotype with hormonal dysfunction, reduced oocyte quality, and compromised fertility in adult offspring. Collectively, these findings indicate that gestational DBP exposure activates the PI3K-AKT-FOXO3a signaling pathway via METTL14-mediated m⁶A modification, causing impaired follicle formation, follicular over-activation, and ultimately ovarian reserve depletion and a POI-like phenotype in offspring. This study reveals a novel m⁶A‑mediated epigenetic mechanism in plasticizer-induced ovarian toxicity, advancing our understanding of POI etiology and highlighting a significant environmental risk to female fertility.
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EUROPEAN JOURNAL OF MEDICAL RESEARCH
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2025
·Vol. 30
·期 1
·1-11
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IF 3.4
Zhang Zihao,Ren Jiayi,Tang Ke,Hu Xinyi,Liu Jinhui,Li Chunming
Background Oral cancer (OC) is one of the major types of cancer and the most common cause of cancer-related mortality in Asia. In recent years, matrix stiffness in the tumor microenvironment has been found to play an important role in regulating tumor cell behavior. However, the regulatory mechanisms associated with matrix stiffness in OC cells remain unclear. Methods In this study, polyacrylamide gels with different stiffness were prepared to simulate low versus high matrix stiffness environments in tumor tissues by adjusting the acrylamide and cross-linker concentrations. Subsequently, the effects of different stiffness on OC cell survival, migration, invasion and invadopodia formation were explored based on cell counting kit-8 (CCK-8), Transwell and confocal microscopy. Meanwhile, the levels of markers relevant to phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), apoptosis (BAX and BCL2) as well as metastasis (Cadherin-1, CDH1; Cadherin-2, and CDH2) were calculated via western blotting and real-time quantitative PCR. Results According to the results, high matrix stiffness was seen to contribute to the increased number of migrated and invaded cells as well as the enhanced viability of OC cells, along with the aggravated invadopodia formation and the up-regulation in CDH2 and BCL2 levels yet the down-regulation in CDH1 and BAX levels. Elevated PI3K/AKT phosphorylation levels were also seen in high matrix stiffness-mediated OC cells, and the intervention using LY294002 could visibly overturned the effects of high matrix stiffness on the cell migration, invasion and invadopodia formation of OC cells. Conclusions This study reveals that matrix stiffness may enhance the invasiveness and anti-apoptotic ability of OC cells by activating the PI3K/AKT pathway, which provides a new idea for exploring the microenvironmental regulation of tumor mechanics and targeted intervention strategies.
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ACTA HISTOCHEMICA
·
2021
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IF 2.479
Dongmin Yu,Jianxian Xiong,Yizhou Gao,Jinghang Li,Dawei Zhu,Xiaowei Shen,Lifu Sun,Xiaowei Wang
Resveratrol is a kind of iPolyphenols widely existing in herbal medicine. Here we aim to investigate whether resveratrol can reduce the degree of myocardial ischemia/reperfusion (IR) injury and inhibit the development of oxidative stress, and elucidate the molecular mechanism of resveratrol in protecting myocardial cells. The primary rat cardiomyocytes were used to establish an ischemia/reperfusion model in vitro, and a series of routine biochemical experiments were conducted to explore the antioxidant and anti-apoptotic effects of resveratrol in myocardial ischemia-reperfusion injury. Compared with that of the simulated ischemia-refusion (SIR) group, cell viability in the SIR and resveratrol co-treatment groups increased significantly (P < 0.001), the release of lactate dehydrogenase (LDH) and creatine kinase MB (CK MB) decreased, the positive rate of reactive oxygen species (ROS) in cardiomyocytes decreased, and the concentration of catalase and glutathione peroxidase increased significantly (P < 0.001). Besides, resveratrol can activate PI3K/AKT signaling pathway. PI3K siRNA can inhibit the PI3K/AKT signaling mediated by resveratrol. The addition of resveratrol can significantly increase the activity of mitochondrial superoxide dismutase (SOD) and reduce the malondialdehyde (MDA), which indicates that the oxidative damage of mitochondria induced by resveratrol was significantly weakened. The mitochondrial functional changes induced by resveratrol can be reversed by PI3K siRNA. In conclusion, our study shows that resveratrol can reduce ROS in cardiomyocytes by PI3K/AKT signaling pathway activation, and effectively inhibit the apoptosis of cardiomyocytes, thus having a direct protective effect on cardiomyocytes under SR.
研究领域:
药理学
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心脏病学
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分子生物学
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 5.4
Bin Yang,Qingqing Xia,Xinyu Ji,Ke Su,Tao Yu,Zihan Xiao,Chen Shi,Zichen Luo,Xuan Wang,Weichen Xu,Yanan Gao,Haibin Hua,Jinjun Shan
Ethnopharmacological relevance Ganjie Decoction (GJD), a traditional Chinese medicine (TCM) formula commonly used for respiratory diseases, has shown therapeutic potential against RSV pneumonia. However, its pharmacological mechanisms against respiratory syncytial virus (RSV) pneumonia are not fully understood. Aim of study This study aimd to characterize the active components of GJD and systematically investigate its therapeutic effects and underlying mechanisms in RSV-induced pneumonia. Materials and methods To evaluate the therapeutic efficacy of GJD in RSV-infected mice, we monitored body weight, performed qPCR, and conducted histopathological examination of lung tissues. The chemical constituents of GJD were characterized using UPLC-MS. Key bioactive compounds and their potential targets were predicted using network pharmacology and molecular docking. The underlying mechanisms were further elucidated using immunohistochemistry and western blotting. The interactions between GJD and the gut microbiota were explored using antibiotic depletion, fecal microbiota transplantation (FMT), metagenomic sequencing, and in vitro co-culture assays. Untargeted metabolomics was employed to assess GJD-induced metabolic alterations. Finally, the role of 4-hydroxyphenylacetic acid (4-HPA) was investigated through cell viability assays, immunofluorescence staining, and western blot analysis in vitro . Results GJD significantly mitigated weight loss, attenuated pulmonary viral load, and suppressed inflammation in RSV-infected mice. Network pharmacology and molecular docking revealed that specific compounds in GJD target the PI3K/AKT signaling pathway. This finding was validated by western blotting and immunohistochemistry, which demonstrated that GJD suppresses PI3K/AKT pathway activation, thereby attenuating apoptosis and ameliorating RSV-induced pneumonia. Notably, these protective effects were markedly attenuated in mice with depleted gut microbiota. Furthermore, the therapeutic effects of GJD against RSV pneumonia were transferable via gut microbiota transplantation. GJD restored RSV-induced dysbiosis of the gut microbiota, with Lactobacillus reuteri emerging as one of the most enriched microbes following treatment. Metabolomics analysis identified 4-HPA as a microbiota-dependent metabolite significantly upregulated by GJD. Remarkably, administration of 4-HPA reproduced GJD’s therapeutic effects in RSV-infected mice and activated the KEAP1/NRF2 antioxidant pathway, suggesting that 4-HPA functions as a key mediator of GJD’s anti-RSV activity. Conclusions These findings suggest that GJD alleviates RSV pneumonia through a synergistic mechanism that modulates the PI3K/AKT–apoptosis pathway, restores gut microbial balance, and normalizes metabolic disturbances. This study systematically elucidates the mechanistic basis underlying the therapeutic effects of GJD against RSV pneumonia.
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MICROVASCULAR RESEARCH
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2021
·
IF 3.514
Yi-hua Zhou,Yu-zhi Tang,Liang-yun Guo,Li-li Zheng,Dan Zhang,Can-ying Yang,Wei Wang
Soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein, is involved in the pathogenesis of atherosclerosis (AS), and the underlying mechanism is still unclear. Here, we attempted to investigate the mechanism of action of sFlt-1 in AS. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low density lipoprotein (ox-LDL) to induce cell injury. ox-LDL treatment increased LC3-II/LC3-I ratio, Beclin-1 expression and GFP-LC3 puncta in HUVECs, suggesting that ox-LDL may induce autophagic flux impairment in HUVECs. ox-LDL-treated HUVECs displayed a decrease of sFlt-1 levels. Moreover, ox-LDL treatment reduced cell proliferation and elevated apoptosis in HUVECs, which was abrogated by sFlt-1 overexpression. Up-regulation of sFlt-1 repressed the activity of PI3K/AKT/mTOR signaling pathway and enhanced autophagy in HUVECs following ox-LDL treatment. Additionally, sFlt-1 overexpression-mediated increase of autophagy in ox-LDL-treated HUVECs was abolished by 3-methyladenine (autophagy inhibitor). 3-methyladenine abrogated the impact of sFlt-1 overexpression on proliferation and apoptosis in ox-LDL-treated HUVECs. This work confirmed that overexpression of sFlt-1 activated autophagy by repressing PI3K/Akt/mTOR signaling pathway, and thus alleviated ox-LDL-induced injury of HUVECs. Therefore, this study suggests that sFlt-1 may be a potential target for AS treatment.
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JOURNAL OF NATURAL PRODUCTS
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2019
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IF 4.257
Yong Ling,Yangyang Li,Rui Zhu,Jianqiang Qian,Ji Liu,Weijie Gao,Chi Meng,Jiefei Miao,Biao Xiong,Xiaodong Qiu,Changchun Ling,Hong Dai,Yanan Zhang
Naturally occurring β-carbolines are known to have antitumor activities but with limited effectiveness. In order to improve their efficacy, a series of new hydroxamic-acid-containing β-carbolines connected via a hydroxycinnamic acid moitey (12a–f) were developed to incorporate histone deacetylase (HDAC) inhibition for possible synergistic effects. When evaluated in in vitro assays, most of the analogues showed significant antitumor activities against four human cancer cells. In particular, 12b showed the highest cytotoxic potency of the series, including drug-resistant Bel7402 cells, but had minimal effect on normal hepatic LO2 cells. These compounds also showed excellent inhibitory effects against HDAC1/6, which appear to contribute greatly to their antiproliferative properties. Compound 12b enhanced the acetylation levels of histone H3 and α-tubulin and induced greater cancer cell apoptosis than the FDA-approved HDAC inhibitor SAHA by regulating expression of apoptotic proteins Bax, Bcl-2, and caspase 3. Importantly, 12b also induced a significant amount of autophagic flux activity in Bel7402 cells by increasing the expression of Beclin-1 and LC3-II proteins and decreasing that of LC3-I and p62. Finally, 12b significantly inhibited PI3K/Akt/mTOR signaling, an important cell-growth-promoting pathway aberrantly activated in many cancers. Together, the results suggest that these hydroxamic-acid-containing β-carboline derivatives may be new leads for the discovery of agents for the treatment of human carcinoma cancers.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Mingyuan Cao,Jie Wang,Xueying Jiang,Zhipeng Sun,Liyan Zhao,Guitang Chen
Quinoa is a nutrient-rich pseudocereal with a lower glycemic index and glycemic load. However, its therapeutic potency and underlying mechanism against insulin resistance (IR) have not been fully elucidated. In this work, network pharmacology was applied to screen IR targets and their related pathways. The efficacy and mechanism of black quinoa polyphenols (BQP) on IR improvement were evaluated and uncovered based on the IR model in vitro combined with molecular docking. Ten phenolic constituents of BQP were detected, and the network pharmacology results show that PI3K/Akt pathways are the main pathways in BQP against IR. The in vitro assay proved that BQP increases the glucose consumption and glycogen synthesis via upregulating insulin receptor substrate 1 (IRS1)/PI3K/Akt/glucose transporters (GLUTs) signaling pathways to alleviate IR. Rutin, resveratrol, and catechin show lower binding energy docking with IRS1, PI3K, Akt, and GLUT4 proteins, indicating better interactions. It might be an effective constituent against IR. Hence, BQP could become a potential functional food source for blood glucose management among insulin-resistant people.
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