International Journal of Clinical and Experimental Pathology
·
2015
·
IF 1.891
Jing Zhao,Li Li,Ling Peng
The previous studies identify mammalian heart is terminal differentiation organs without regenerative capacity. Recently, there is some evidence point that cardiomyocytes are not terminally differentiated cells and cell proliferation may be stimulated in the pathologic heart. The aim of this study is to discover the possible mechanism which involved in cardiomyocytes proliferation process. In this study, the proliferation assay and cell cycle assay showed the proliferation of cardiomyocytes was inhibited when the cells treated with MAPK1 inhibitor. Moreover, the bioinformatics analysis revealed MAPK1 was positively correlated with MALAT1. Meanwhile, the expression of MALAT1 in H9C2 cells with the treatment of MAPK1 siRNA was obvious lower than scramble siRNA treated group. Finally further study suggested H9C2 cells treated with Wortmannin in combination with LY294002 (PI3K/AKT signaling pathway inhibitor), the expression of MALAT1 was dramatically decreased. These results indicated that MAPK1 was able to increase the proliferation of cardiomyocytes via up-regulating the expression of MALAT1 through PI3K/AKT signaling pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Chaoyu Huang,Chen Qian,Zongxian Li,Yuanyuan Qin,Wuning Mo,Faquan Lin
Ethnopharmacological relevance Rosa roxburghii is an ethnic medicinal herb. Folk medicine collections have documented its nourishing and strengthen effects. It has been used to improve reproductive health, but scientific evidence supporting its efficacy and mechanisms remains limited. Aim of this study Endocrine-disrupting chemicals, such as di-(2-ethylhexyl) phthalate (DEHP), are known to impair male reproductive health. This study aims to investigate the protective effects of raw Rosa roxburghii juice (RRJ) on DEHP-induced reproductive toxicity in mice and elucidates its underlying mechanisms. Materials and methods Using a DEHP-induced murine model of reproductive damage, we evaluated the effects of RRJ on sperm quality, testicular histopathology, reproductive endocrine function, oxidative stress, inflammation, apoptosis, and DNA damage. Network pharmacology analysis was performed to identify the active components, targets, and mechanisms underlying the therapeutic effects of Rosa Roxburghii . Results Our data demonstrated that RRJ significantly improved sperm quality, alleviated testicular atrophy, restored endocrine disorders, and mitigated oxidative stress, inflammation, and apoptosis in testicular tissues. Additionally, RRJ reduced testicular and sperm DNA damage, as evidenced by decreased γ-H2AX expression and DNA fragmentation index. Network pharmacology analysis identified quercetin, apigenin, luteolin, kaempferol, eriodictyol, and ellagic acid as the key bioactive compounds in RRJ, with the PI3K/AKT signaling pathway playing a crucial role in its therapeutic effects. Western blotting confirmed that RRJ reversed DEHP-induced suppression of the PI3K/AKT pathway. Conclusions This study demonstrates that RRJ protects against DEHP-induced reproductive toxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, mediated in part by the PI3K/AKT signaling pathway. This work provides the first comprehensive evidence of the protective effects of Rosa roxburghii against male reproductive system damage and its underlying mechanisms.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2025
·
IF 2.5
Yanru Liu,Ya Hu,Xiaoxia Xie,Gongjun Yang,Fang Feng
Wen-Pi-Tang (WPT), a Traditional Chinese Medicine (TCM) prescription, is commonly used to treat chronic renal failure. However, the material basis and potential mechanisms of WPT against chronic renal failure have not been clarified. UHPLC-Q-Exactive Orbitrap-MS was utilized in this work to investigate the chemical components of WPT and their prototypes or metabolites in vivo. 227 chemical compounds were identified in the WPT. Meanwhile, 56 exogenous components (24 prototype components and 32 metabolic components) were examined in rat plasma. Meanwhile, network pharmacology revealed that liquiritigenin-O-sulfate, 3-keto-18β-glycyrrhetinic acid, 22-hydroxy-18-β-glycyrrhetinic acid, and hydroxyliquiritigenin (B ring)-O-sulfate with related targets AKT1, EGFR, STAT3, ESR1, SRC, MAPK3, MTOR, and PIK3CA were considered as the effective components and core targets. Furthermore, the findings suggested that the therapeutic effects of WPT on chronic renal failure may be substantially influenced by the PI3K-Akt, HIF-1, and FoxO signaling pathways. The outcomes of molecular docking and molecular dynamics simulations indicate that the key targets have strong binding capacities with effective components. Our study offers a comprehensive method for examining the molecular foundation and underlying mechanisms of WPT against chronic renal failure, opening up new therapeutic opportunities.
研究领域:
中药学
·
药理学
·
代谢组学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Benkai Bao,Dong Gao,Ning Li,Manman Wu,Chengfen Xing
Calmodulin (CaM), as a calcium binding protein involved in the signal pathways of many life activities such as cell proliferation and apoptosis, can be regulated with the near-infrared (NIR) light-based photothermal conversion. Here, we build a conjugated polymer nanoparticle (CPNs-C) by assembling polypyrrole dione and dipalmitoyl phosphatidylethanolamine-polyethylene glycol-maleimide with a calmodulin antibody modified on the surface, which is NIR light-responsive for photothermally inducing apoptosis of cancer cells. Under near-infrared light irradiation, protein kinase B (Akt) and phosphatidylinositol 3-kinase, which bind to CaM, reduce the degree of phosphorylation due to the photothermal effect of CPNs-C, thus inhibiting the recruitment of Akt on the cell membrane. Therefore, the phosphorylation of GSK-3β downstream of the signaling pathway is reduced, and the phosphorylation of FoxO3a is enhanced, which can promote apoptosis of cancer cells. Compared with the photothermal effect of traditional CPNs, CPNs-C exhibits higher efficiency to regulate signaling pathways to promote cancer cells toward apoptosis. This strategy of utilizing NIR light to regulate the tumor apoptotic signaling pathway provides an effective way to enhance cancer cell apoptosis with high efficiency.
研究领域:
生物医学工程
·
癌症生物学
·
纳米技术
·
光疗
✓ 已验证
DOI
PubMed
ACTA HISTOCHEMICA
·
2021
·
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
·
心脏病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2026
·
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2026
·
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.
✓ 已验证
产品关联
DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2026
·
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.
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
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.
✓ 已验证
DOI
高影响因子
npj Science of Food
·
2026
·
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.
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2025
·Vol. 30
·期 1
·1-11
·
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Results in Chemistry
·
2025
·
IF 4.2
Dongqing He,Dongjun Liu,Zhuoyan Wu,Ruiguang Xiao,Wenjie Ruan,Zeqiang Lin,Qiuxia Chen,Chanling Yuan,Qiong Wu,Wenjie Mei
Acne is a chronic inflammatory skin disease that is highly prevalent in adolescents, and its recurrent flare-ups can affect facial aesthetics, severely impacting adolescents' mental health and quality of life. Screening for safer, more effective fruit acid molecules for daily acne treatment is crucial. This work examined potential mandelic acid derivatives. In a zebrafish model, mandelic acid showed a 78.17 % rate of inflammatory cell aggregation, outperforming supramolecular salicylic acid (86.96 % aggregation) at the same concentration. In a P. acnes -induced cell model, MMP9 protein expression was significantly upregulated in the model group. After treatment with mandelic acid, MMP9 expression decreased by 72.84 % compared to the model group, a better effect than that of supramolecular salicylic acid (36.78 %). Further mechanistic investigations indicate that mandelic acid may inhibit the PI3K/AKT signaling pathway activated by P. acnes , thereby blocking MAPK signaling and modulating MMP9 protein production, thereby averting the development of NLRP3 inflammatory vesicles. Mandelic acid has a favourable safety profile and notable anti-inflammatory properties, which can be further harnessed to mitigate acne in sensitive skin demographics, offering a novel approach to acne treatment.
研究领域:
皮肤病学
·
炎症研究
·
分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）