ENVIRONMENTAL POLLUTION
·
2022
·
IF 9.988
Wenjing Pu,Xuesheng Chu,Huiling Guo,Gang Huang,Ting Cui,Bingyan Huang,Xueyan Dai,Caiying Zhang
Cadmium (Cd) and excess molybdenum (Mo) have multiple organ toxicity, and testis is one of their important target organs, but the reproductive toxicity of Mo and Cd combined treatment is still unclear. To explore the effects of Mo and Cd co-exposure on DNA damage and autophagy from the insight of ATM/AMPK/mTOR axis in duck testes, we randomly assigned 40 healthy 8-day-old ducks to control, Mo (100 mg/kg Mo), Cd (4 mg/kg Cd), and Mo + Cd groups for 16 weeks. Results found that Mo and/or Cd exposure caused trace elements imbalance, oxidative stress with a decrease in the activities of GSH-Px, CAT , T-SOD and GSH content, an increase in the concentrations of H 2 O 2 and MDA and pathological damage. Additionally, Mo and/or Cd markedly raised DNA damage-related factors expression levels and 8-OHdG content, caused G1/S arrest followed by decreasing CDK2 and Cyclin E protein levels and increasing CDK1 and Cyclin B protein levels, and activated ATM/AMPK/mTOR axis by enhancing p-ATM/ATM, p-AMPK/AMPK and reducing p-mTOR/mTOR protein levels, eventually triggered autophagy by elevating LC3A, LC3B, Atg5, Beclin-1 mRNA levels and LC3II/LC3I, Beclin-1 protein levels and reducing P62, Dynein, mTOR mRNA levels and P62 protein level. Moreover, these changes were most apparent in the combined group. Altogether, the results reveal that autophagy caused by Mo and/or Cd may be associated with activating the DNA damage-mediated ATM/AMPK/mTOR axis in duck testes, and Mo and Cd co-exposure exacerbates these changes.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Sun Xiaowei,Wang Dongyan,Zhang Tingting,Lu Xuejian,Duan Fangfang,Ju Lili,Zhuang Xiaotong,Jiang Xicheng
Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway in vivo and in vitro. In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/P70S6K signaling pathway.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AFFECTIVE DISORDERS
·
2025
·
IF 4.9
Siqi Sun,Jingtong Rong,Chao Wang,Ruiling Li,Honghan Zhang,Wei Wang,Hao Duan,Zhaowen Nie,Dan Xiang,Zhongchun Liu
Background Major depressive disorder (MDD) is a severe, and often treatment-resistant, psychiatric disorder. Mesenchymal stem cell-derived exosomes have been shown to be neuroprotective. Here we employed adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) as a novel therapeutic approach for depressive-like behavior in mice and explored the underlying mechanisms. Methods ADSC-Exos were administered intranasally to mice subjected to chronic restraint stress to assess behavioral changes and neuroprotection in terms of apoptosis, AMPK-mTOR signaling, and NLRP3 pathway activation by western blotting, microglial activation by immunofluorescence, and changes in serum inflammatory factors by ELISA. The effects of ADSC-Exos were also studied in vitro in HT22 cells. Results ADSC-Exos significantly improved depressive-like behavior, anxiety-like behavior, and cognitive function in mice. ADSC-Exos had significant neuroprotective effects, including reducing neuronal apoptosis and promoting autophagy by activating AMPK-mTOR signaling, ultimately reducing neuroinflammation. In vitro, ADSC-Exos inhibited corticosterone-induced apoptosis, activated autophagy in an AMPK pathway-dependent manner, and inhibited NLRP3 inflammasome activation. Conclusion ADSC-Exos may be a potential treatment for MDD by alleviating depressive-like behaviors and protecting against tissue injury, possibly through activation of AMPK-mTOR signaling and inhibition of NLRP3 inflammasome-mediated neuroinflammation.
研究领域:
神经科学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF TOXICOLOGICAL SCIENCES
·
2023
·
IF 2
Haixu Wang,Yan Li,Chuang Liu,Tianxiang Lu,Qian Zhai,Hongna Wang,Jianfang Zhang
Bisphenol A (BPA), one of the main components of industrial products, is clinically associated with the increased male infertility rate. However, the underlying molecular mechanism of the BPA-resulted reproductive toxicity is not fully elucidated. Voltage-dependent anion channel 1 (VDAC1) is a pore protein and located at the outer mitochondrial membrane. As a mitochondrial gatekeeper, VDAC1 controls the release of reactive oxygen species (ROS) and the metabolic and energetic functions of mitochondria, and serves as a critical player in mitochondrial-mediated apoptosis. Herein, we explored the role of VDAC1 in BPA-induced apoptosis of spermatogonia. The results showed that BPA increased spermatogonia cell line GC-1 spg cell apoptosis and intracellular ROS level, and suppressed AMPK/mTOR signaling pathway at a dose of 80 μM for 48 hr. Lentivirus-mediated short hairpin RNA targeting VDAC1 (Lv-shVDAC1) silenced VDAC1 expression and enhanced BPA-restricted cell viability. Knockdown of VDAC1 inhibited the apoptosis of BPA-treated GC-1 spg cells determined by with changes of the expressions of pro-apoptotic and anti-apoptotic proteins. Knockdown of VDAC1 also alleviated the BPA-triggered intracellular ROS generation and oxidative stress. Moreover, silence of VDAC1 increased AMPKα1/2 phosphorylation and suppressed mTOR phosphorylation under BPA exposure. Dorsomorphin, an AMPK inhibitor, partially abolished the effects of VDAC1 gene silencing on BPA-stimulated GC-1 spg cells. In conclusion, inhibition of VDAC1 attenuated the BPA-induced oxidative stress and apoptosis and promoted the cell viability in spermatogonia through modulating AMPK/mTOR signaling pathway.
研究领域:
生殖毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Animal Science and Biotechnology
·
2023
·Vol. 14
·期 1
·1-17
·
IF 7
He Zhaoqi,Zhao Caijun,He Yuhong,Liu Zhuoyu,Fan Guyue,Zhu Kun,Wang Yiqi,Zhang Naisheng,Fu Yunhe,Hu Xiaoyu
Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in ‘gastroenterogenic mastitis’. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that ‘gastroenterogenic mastitis’ can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis.Results First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusion sIn conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
研究领域:
兽医学
·
微生物学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Hongyan Li,Yanzhi Zeng,Guangjun Wang,Kai Zhang,Wangbao Gong,Zhifei Li,Jingjing Tian,Yun Xia,Wenping Xie,Jun Xie,Shouqi Xie,Ermeng Yu
Diets with high carbohydrate (HC) was reported to have influence on appetite and intermediary metabolism in fish. To illustrate whether betaine could improve appetite and glucose-lipid metabolism in aquatic animals, mandarin fish ( Siniperca chuatsi ) were fed with the HC diets with or without betaine for 8 weeks. The results suggested that betaine enhanced feed intake by regulating the hypothalamic appetite genes. The HC diet-induced downregulation of AMPK and appetite genes was also positively correlated with the decreased autophagy genes, suggesting a possible mechanism that AMPK/mTOR signaling might regulate appetite through autophagy. The HC diet remarkably elevated transcriptional levels of genes related to lipogenesis, while betaine alleviated the HC-induced hepatic lipid deposition. Additionally, betaine supplementation tended to store the energy storage as hepatic glycogen. Our findings proposed the possible mechanism for appetite regulation through autophagy via AMPK/mTOR, and demonstrated the feasibility of betaine as an aquafeed additive to regulate appetite and intermediary metabolism in fish.
研究领域:
水产养殖学
·
营养学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2024
·Vol. 2024
·期 1
·4777789
·
IF 4.4
Zheng Liang,Dajin Pi,Jianwei Zhen,Haizhen Yan,Chuiyang Zheng,July Liang Chen,Wen Fan,Qingliang Song,Jinyue Pan,Dongdong Liu,Maoxing Pan,Qinhe Yang,Yupei Zhang
Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine–choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate-activated protein kinase–mammalian target of rapamycin (AMPK–mTOR)-mediated autophagy and ferroptosis markers, such as p-AMPK α /AMPK α , p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH.
研究领域:
药理学
·
肝病学
·
分子生物学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
·
IF 4.06
Zhen Zhang,Dongming Zhu,Xiaobo Zhang,Yun Liu,Jingcheng Wang,Lianqi Yan
Post-surgery arthrofibrosis is one of the most restrictive factors in the development of intra-articular surgery and has presented tremendous obstacles for most orthopaedic surgeons. Tanshinone IIA (Tan IIA), a key active ingredient of Den-shen, has been used to treat fibrosis-related diseases, such as pulmonary, hepatic and myocardial fibrosis. In the present study, we aimed to investigate the effects of Tan IIA on post-surgery arthrofibrosis in vivo and in vitro . Histological analysis indicated that topical application of Tan IIA (10 mg/mL) could significantly alleviate postsurgery arthrofibrosis in rabbits. Immunohistochemistry results showed that proliferating cell nuclear antigen (PCNA) and tubulin protein expression was inhibited, whereas LC3 was activated in vivo . In vitro , EdU and flow cytometry assays demonstrated that Tan IIA could inhibit fibroblast proliferation by arresting cells in G2 phase. Scratch, Transwell and cytoskeleton protein immunofluorescence assays revealed that fibroblast migration was attenuated. Interestingly, LC3 immunofluorescence staining and transmission electron microscopy indicated that autophagy flux could be induced in fibroblasts by Tan IIA. However, the inhibitory effects of Tan IIA against fibroblast proliferation and migration were partially restored when fibroblast autophagy was suppressed after combined treatment with the autophagy inhibitor 3-methyladenine (3-MA). Finally, the expression of p-mTOR was suppressed in a dose-dependent manner after Tan IIA treatment but partially restored when Tan IIA treatment was combined with 3-MA intervention. The inhibitory effect of Tan IIA against fibroblast proliferation and migration may be related to autophagy induction mediated by the PI3K and AMPK-mTOR signaling pathway.
研究领域:
骨科
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Linquan Zhou,Chengcheng Zhang,Tengbin Shi,Dingwei Wu,Huina Chen,Jiaxin Han,Dehui Chen,Jinxin Lin,Wenge Liu
The migration and differentiation of bone marrow mesenchymal stem cells (BMSCs) play crucial roles in bone repair processes. However, conventional scaffolds often lack of effectively inducing and recruiting BMSCs. In our study, we present a novel approach by introducing a 3D-bioprinted scaffold composed of hydrogels, with the addition of laponite to the GelMA solution, aimed at enhancing scaffold performance. Both in vivo and in vitro experiments have confirmed the outstanding biocompatibility of the scaffold. Furthermore, for the first time, Apt19s has been chemically modified onto the surface of the hydrogel scaffold, resulting in a remarkable enhancement in the migration and adhesion of BMSCs. Moreover, the scaffold has demonstrated robust osteogenic differentiation capability in both in vivo and in vitro environments. Additionally, the hydrogel scaffold has shown the ability to induce the polarization of macrophages from M1 to M2, thereby facilitating the osteogenic differentiation of BMSCs via the bone immune pathway. Through RNA-seq analysis, it has been revealed that macrophages regulate the osteogenic differentiation of BMSCs through the AMPK/mTOR signaling pathway. In summary, the functionalized GelMA/Laponite scaffold offers a cost-effective approach for tailored in situ bone regeneration.
研究领域:
组织工程
·
生物材料
·
再生医学
·
骨免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cardiovascular Diabetology
·
2025
·Vol. 24
·期 1
·1-16
·
IF 10.6
Liu Libo,An Ziyu,Zhang Huan,Wan Xueqi,Zhao Xin,Yang Xueyao,Tian Jinfan,Song Xiantao
IntroductionBone marrow-derived mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) are widely used for therapeutic purposes in preclinical studies. However, their utility in treating diabetes-associated atherosclerosis remains largely unexplored. Here, we aimed to characterize BMSC-EV-mediated regulation of autophagy and macrophage polarization.Methods EVs were isolated from the supernatant of cultured BMSCs and characterized with transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. A diabetes-related atherosclerotic ApoE−/− mouse model was established through feeding with a high-fat diet (HFD) and streptozotocin (STZ). Histopathological analyses were carried out using Oil Red O, H&E, and Masson staining of the aorta. TEM and immunohistochemistry (IHC) were applied to evaluate autophagy, and immunofluorescence (IF) was used to identify macrophage polarization. RAW264.7 macrophages were induced with oxidized low-density lipoprotein (ox-LDL) and high glucose (HG), co-cultured with BMSC-EVs, and analyzed for macrophage proliferation, migration, and foam cell formation. RAW264.7 cells were transduced with autophagy marker mRFP-GFP-LC3 lentivirus and analyzed with IF and western blotting.Results Diabetic mice (DA group) had larger aortic plaque areas and lower collagen content than the HFD mice. BMSC-EV treatment significantly reduced blood glucose, LDL levels, and aortic plaque areas while increasing collagen content. BMSC-EV-treated aortas contained a higher number of autophagosomes/autolysosomes, with increased expression of LC3BII correlating with decreased P62 levels and a lower proportion of M1 macrophages. In vitro, BMSC-EVs inhibited proliferation, migration, and foam cell formation in ox-LDL and HG-induced activated RAW264.7 cells. These effects were reversed by the autophagy blocker bafilomycin A1. Consistent with the in vivo findings, BMSC-EVs elevated levels of the autophagy-related protein LC3BII/I and decreased P62 in ox-LDL and HG-induced RAW264.7 cells. These cells also expressed the M1 macrophage markers CD86 and iNOS, but showed reduced expression of the M2 marker Arg-1. Further, BMSC-EVs decreased AMPKα and mTOR phosphorylation levels, which were blocked by the AMPK inhibitor compound C.Conclusion sBMSC-EVs attenuate diabetes-exacerbated atherosclerosis by inhibiting vascular macrophage proliferation, migration, and foam cell formation via AMPK/mTOR signaling-regulated autophagy and macrophage polarization. BMSC-EVs thus hold promise as therapeutic agents for atherosclerosis.Graphical Extracellular vesicles derived from bone marrow mesenchymal stem cells may mitigate diabetes-aggravated atherosclerosis by regulating AMPK/mTOR-mediated autophagy-related macrophage polarization and inhibiting macrophage proliferation, migration, foam cell formation, and cholesterol transport.
研究领域:
医学
·
分子生物学
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Hongzhou Lin,Huihui Chen,Rengcheng Qian,Guoqi Tang,Yinjuan Ding,Yalan Jiang,Congde Chen,Dexuan Wang,Maoping Chu,Xiaoling Guo
Background Nephrotic syndrome (NS) is a chronic kidney disease mainly caused by impaired podocytes, ultimately resulting in massive proteinuria or even end-stage renal disease (ESRD). Methods The objective of this study was to explore the potential pathogenesis of NS caused by podocyte injury, and further explore the underlying mechanism through data mining , bioinformatics analysis, and experimental verification. The integrated analyses including Seurat, CellChat, gene ontology (GO), and molecular docking were performed based on the single-cell RNA-seq data (scRNA-seq). The adriamycin (ADR)-induced podocyte injury model in vitro was established to conduct the experimental verification for bioinformatics analysis results through western blot and real-time quantitative PCR (RT-qPCR). Results The results of bioinformatics analysis revealed that the bone morphogenetic protein (BMP) signaling pathway was involved in the podocyte-to-podocyte communication, which plays a crucial role in podocyte injury. The expression of BMP7 was significantly increased in ADR-induced podocytes through activating the Adenosine-monophosphate activated-protein kinase/Mammalian target of rapamycin (AMPK/mTOR) mediated autophagy pathway, and these findings were confirmed by in vitro experiments. Conclusion This study first demonstrated that BMP7 participated in ADR-induced podocyte injury. The BMP7/AMPK/mTOR mediated autophagy pathway may play a crucial role in podocyte injury, which may be the potential therapeutic target for NS patients.
研究领域:
肾病学
·
分子生物学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Wu Huilan,Wang Yijia,Tan Pingping,Ran Yuqing,Guan Yuting,Qian Songwei,Feng Xing,Jiang Yalan,Peng Yongmiao,Sheng Ke,Xi Haitao,Ji Weiping,Guo Xiaoling
Background: Kawasaki disease (KD) is a self-limiting and acute systemic vasculitis of unknown etiology, mainly affecting children. Ferulic acid (FA), a natural phenolic substance, has multiple pharmacological properties, including anti-inflammatory, anti-apoptosis, and anti-fibrosis, and so on. So far, the protective effects of FA on KD have not been explored.Methods: In this study, we established Candida albicans water soluble fraction (CAWS)-induced mouse coronary artery vasculitis of KD model and the tumor necrosis factor α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury model to investigate the anti-inflammatory and anti-apoptosis effects of FA on KD, and try to elucidate the underlying mechanism.Results: Our in vivo results demonstrated that FA exerted anti-inflammatory effects on KD by inhibiting the infiltration of CD45-positive leukocytes and fibrosis around the coronary artery. Additionally, FA downregulated the levels of inflammatory and chemotactic cytokines, alleviated splenomegaly, and exhibited anti-apoptotic effects on KD by reducing TUNEL-positive cells, downregulating BAX expression, and upregulating BCL-2 expression. In addition, Our in vitro findings showed that FA could effectively inhibit TNF-α-induced HUVEC inflammation like NF-κB inhibitor QNZ by downregulating the expression of pro-inflammatory cytokines as well as attenuated TNF-α-induced HUVEC apoptosis by reducing apoptotic cell numbers and the BAX/BCL-2 ratio, which could be reversed by the AMPK inhibitor compound c (CC). The further mechanistic study demonstrated that FA could restrain vascular endothelial cell inflammation and apoptosis in KD through activating the AMPK/mTOR/NF-κB pathway. However, FA alone is hard to completely restore KD into normal condition.Conclusion: In conclusion, FA has potential protective effects on KD, suggesting its promising role as an adjuvant for KD therapy in the future.
研究领域:
药理学
·
免疫学
·
血管生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）