INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2017
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IF 3.671
Jing-yi Zhang,Ying Guo,Jin-ping Si,Xiao-bo Sun,Gui-bo Sun,Jing-jing Liu
Dendrobium officinale is one valuable traditional Chinese medicine, which has skyscraping medicinal value. Polysaccharide is the main active ingredient in D. officinale ; its antioxidant activity is a hot research topic nowadays. Oxidative stress plays an important role in the pathological progress of a variety of cardiovascular disease, as one of key factors of cardiomyocyte apoptosis. This research adopts a model of H 2 O 2 induction-H9c2 cardiomyocytes apoptosis, aiming to study the effect of Dendrobium officinale Polysaccharide (DOP-GY) for cardiomyocyte apoptosis caused by oxidative stress and its possible mechanism. Our results showed that pretreatment of DOP-GY (low dose: 6.25 μg/mL, medium dose: 12.5 μg/mL, high dose: 25 μg/mL) followed by a 2 h incubation with 200 μM H 2 O 2 elevated the survival rate, cutted the LDH leakage, reduced lipid peroxidation damage, improved the activity of the endogenous antioxidant enzymes. In addition, the pretreatment of DOP-GY significantly inhibited the production of ROS, declined of the mitochondrial membrane potential, down-regulated pro-apoptosis protein and up-regulated anti-apoptosis protein. The protective effect was correlated with the PI3K/Akt and MAPK signal pathway. Collectively, these observations suggest that DOY-GY has the potential to exert cardioprotective effects against H 2 O 2 -induced H9c2 cardiomyocyte apoptosis.
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ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2023
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IF 3.9
Huaxiang Wang,Minyong Chen,Chengkai Yang,Huanzhang Hu,Yi Jiang,Fang Yang,Lizhi Lv
Background Small nuclear ribonucleoprotein Sm D1 (SNRPD1) has been reported as an oncogene in some solid cancers. Our previous study suggested that SNRPD1 has diagnostic and prognostic value in hepatocellular carcinoma (HCC), but its role in tumor growth and biological behavior remains unknown. In this study, we aimed to unravel the role and mechanism of SNRPD1 in HCC. Methods We investigated the SNRPD1 mRNA level in adjacent normal liver tissues and HCC tissues with different tumor stages in the UALCAN database. The associations between SNRPD1 mRNA expression and HCC prognosis were investigated in TCGA database. Then, 52 pairs of frozen HCC tissues and corresponding adjacent normal liver tissues were collected to perform qPCR and immunohistochemistry assay. Next, we carried out a series of experiments in vitro and in vivo to investigate the effects of SNRPD1 expression on cell invasion, migration, proliferation, autophagy, and the PI3K/AKT/mTOR pathway. Results The bioinformatics analysis and qPCR in our patient cohort demonstrated that the SNRPD1 mRNA level in HCC tissues was higher than in adjacent normal tissues. In addition, the immunohistochemistry assay exhibited an increased SNRPD1 protein level with the tumor stage increase. Survival analysis suggested that higher expression of SNRPD1 was significantly associated with unfavorable prognosis of patients with HCC. The functional experiments in vitro indicated that SNRPD1 knockdown suppressed the cellular proliferation , migration, and invasion capacities. Furthermore, SNRPD1 inhibition induced cellular apoptosis and arrested the HCC cells at the G0/G1 phase of the cell cycle. Mechanistic analyses demonstrated that SNRPD1 knockdown induced the increase of autophagic vacuoles and the expression of autophagy-related genes (ATG5, ATG7 , and ATG12) and blocked the PI3K/AKT/mTOR/4EBP1 pathway in vitro. Moreover, SNRPD1 inhibition suppressed tumor growth and expression of the Ki67 protein in vivo. Conclusions SNRPD1 may serve as an oncogene in HCC and promote tumor proliferation via inhibiting autophagy induced through the PI3K/Akt/mTOR/4EBP1 pathway.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
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IF 5.895
Xiaofei Zhou,Bowei Zhang,Xiuli Zhao,Yongxi Lin,Yuan Zhuang,Jingting Guo,Shuo Wang
Hyperuricemia is an independent hazard factor of renal injury and can induce renal fibrosis, promoting the development of chronic kidney disease (CKD). This study aimed to explore the probability of chlorogenic acid (CGA) as a potential substance for preventing hyperuricemia nephropathy (HN). Pretreatment with CGA downregulated SUA, BUN, and CR levels, relieved oxidative stress and inflammatory response, alleviated kidney fibrosis, and contributed to the prevention of HN. In the gut microbiota, Blautia, Enterococcus, and Faecalibaculum related to trimethylamine N-oxide (TMAO) synthesis were significantly increased in HN rats. In addition, it showed a significant increase in serum TMAO content in HN rats. However, CGA regulated the cascade response of the microbiota-TMAO signaling to reverse the increase of serum TMAO. CGA also decreased the protein expression of protein kinase B (AKT) phosphorylation, phosphatidylinositide 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) by reducing the production of TMAO. CGA delayed kidney fibrosis in HN rats as evidenced by regulating the cascade response of the microbiota-TMAO-PI3K/AKT/mTOR signaling pathway. In summary, CGA can be an excellent candidate for HN prevention.
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FREE RADICAL BIOLOGY AND MEDICINE
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2026
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IF 8
Bin Lu,Yuhui Shi,Xingzhi Chen,Yongheng Huang,Jie Ding,Mingxing Xu,Yuan Feng,Nan Lin
BPA induces liver injury in mice and mitochondrial dysfunction in cultured cells. • Transcriptomics identifies LAMP3 as the most upregulated autophagy-related gene. • BPA produces a pattern consistent with impaired late-stage mitophagic processing. • LAMP3 knockdown attenuates and overexpression aggravates BPA-associated injury. • LAMP3-related changes accompany reduced PI3K-AKT-mTOR phosphorylation. Bisphenol A (BPA) is a ubiquitous environmental toxicant, but the mechanisms underlying BPA-associated hepatic injury remain incompletely understood. This study investigated the involvement of lysosome-associated membrane protein 3 (LAMP3) in mitophagy-related alterations and downstream survival signaling. Human hepatocellular carcinoma-derived Huh7 and PLC5 cells and a mouse model of 4-week BPA exposure were used. Cell proliferation and apoptosis were assessed using CCK-8, EdU, TUNEL, and flow cytometry; mitochondrial function and morphology were evaluated using JC-1, MitoTracker, reactive oxygen species detection, and transmission electron microscopy. RNA sequencing identified BPA-responsive genes, followed by LAMP3 loss- and gain-of-function experiments and chloroquine (CQ) treatment. BPA exposure was associated with proliferative arrest, apoptosis, mitochondrial dysfunction, increased oxidative stress, accumulation of acidic vesicular organelles, an increased LC3B-II/I ratio, and p62 accumulation—a pattern consistent with impaired late-stage mitophagic processing. LAMP3 was strongly upregulated after BPA exposure. LAMP3 silencing attenuated mitochondrial and cellular injury, reduced p62, increased LysoTracker signal, and increased PI3K-AKT-mTOR phosphorylation; CQ attenuated these protective changes. Conversely, LAMP3 overexpression aggravated BPA-associated injury and produced marker changes consistent with impaired autophagic processing. Together, these findings support LAMP3 as a contributor to BPA-associated cellular injury in the Huh7 and PLC5 models studied and suggest an association between LAMP3-related lysosomal alterations, impaired mitophagic processing, and reduced PI3K-AKT-mTOR signaling. Because dynamic mitophagic flux was not directly measured and LAMP3 was not targeted in vivo, the proposed pathway requires confirmation using tandem flux reporters, primary human hepatocytes, and in vivo genetic models. Download: Download high-res image (371KB) Download: Download full-size image
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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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JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Xiang Chen,Mengting Li,Miaomiao Xia,Yumeng Yang,Rui Liu,Ling Ma,Mao Luo
Ethnopharmacological relevance Cassiae Semen, the dried seeds of Cassia obtusifolia L., has traditionally been used in East Asian medicine to manage metabolic disorders, including hyperglycemia and dyslipidemia. Aurantio-obtusin (AO), a bioactive anthraquinone compound, exhibits diverse pharmacological activities, derived from Cassiae Semen, a traditional herb used for metabolic disorders; however, its protective efficacy against prediabetes remains poorly understood. Aim of the study This study aimed to investigate the effects of AO on prediabetes and to elucidate the underlying mechanisms, with particular emphasis on gut microbiota-mediated regulation of metabolic homeostasis. Materials and methods Mice were subjected to prediabetes by a combination of a high-fat diet and streptozotocin. Metabolic parameters, liver function, oxidative stress, inflammatory responses, insulin signaling, and gut microbiota composition were assessed. Fecal microbiota transfer and models simulating antibiotic-induced germ-free conditions were utilized to investigate the function of gut microbiota. Results AO exhibited a marked improvement in glucose tolerance, lipid profiles, and insulin sensitivity among prediabetic mice. Furthermore, AO demonstrated a protective effect against liver damage, as suggested by the notable reductions in serum levels of alanine aminotransferase and aspartate aminotransferase. Oxidative stress was markedly suppressed, as indicated by decreased malondialdehyde levels, along with enhanced antioxidant defenses, including superoxide dismutase, catalase, and reduced glutathione. Additionally, AO preserved intestinal barrier integrity, reduced endotoxemia, and suppressed Toll-like receptor 4-mediated inflammatory signaling, accompanied by restoration of the PI3K/Akt/GLUT4 pathway. Notably, depletion of gut microbiota completely abolished the metabolic benefits of AO. Conclusion Collectively, this study substantiates the ethnomedical value of Cassiae Semen, demonstrating that AO improves prediabetes through the regulation of intestinal barrier function, oxidative stress, inflammation, and insulin signaling, which is dependent on gut microbiota.
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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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