Food Bioscience
·
2025
·
IF 5.9
Lijiao Zhao,Heyun Zhu,Haoye Li,Shuaihao Guo,Jingchun Wang,Zhaoxin Tang,Jianzhao Liao,Jianying Guo
Nano-copper (nanoCu), a nanoscale form of copper (Cu), has been widely applied in the animal husbandry industry. However, it is of great concern that the Cu exposure to humans and animals can cause toxic damage to multiple organs. Hesperidin (Hes), a flavonoid found in citrus fruits, has shown mitigating effects on various organ damages. In our study, we aimed to investigate the toxic effects of nanoCu exposure on the kidneys of chickens and the therapeutic efficacy of Hes in nanoCu-induced renal injury. Our results indicated that Hes could alleviate endoplasmic reticulum stress (ERS) caused by nanoCu exposure. Intriguingly, nanoCu significantly disrupted endoplasmic reticulum (ER) homeostasis, which manifested as increased levels of key proteins such as GRP78, PERK, and CHOP, as well as elevated H 2 O 2 levels. But Hes treatment exhibited an opposite trend. Furthermore, nanoCu significantly induced autophagy in renal cells, which was accompanied by the activation of the AMPK-AKT/mTOR pathway and a concurrent increase in the protein levels of ATG5, Beclin 1, LC3 Ⅱ/LC3 Ⅰ, and ULK1, along with a decrease in the level of p62. However, it can be reversed by Hes treatment. These findings suggest that Hes could mitigate ER homeostasis disruption and autophagy caused by nanoCu exposure, providing new insights into the pharmacological treatment of Hes in related health issues.
研究领域:
动物医学
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毒理学
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药理学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Jie Zhao,Gai Gao,Jing Ding,Wei Liu,Tao Wang,Liang Zhao,Jiangyan Xu,Zhenqiang Zhang,Xiaowei Zhang,Zhishen Xie
The simultaneous enhancement of lipophagy and mitochondrial biogenesis has emerged as a promising strategy for lipid lowering. The transcription factor EB (TFEB) exhibits a dual role, whereby it facilitates the degradation of lipid droplets (LDs) through the process of lipophagy while simultaneously stimulating mitochondrial biogenesis to support the utilization of lipophagy products. The purpose of this study was to explore the effect of astragaloside I (AS I) on hyperlipidemia and elucidate its underlying mechanism. AS I improved serum total cholesterol and triglyceride levels and reduced hepatic steatosis and lipid accumulation in db/db mice. AS I enhanced the fluorescence colocalization of LDs and autophagosomes and promoted the proteins and genes related to the autolysosome. Moreover, AS I increased the expression of mitochondrial biogenesis-related proteins and genes, indicating that AS I promoted lipophagy and mitochondrial biogenesis. Mechanistically, AS I inhibits the protein level of p-TFEB (ser211) expression and promotes TFEB nuclear translocation. The activation of TFEB by AS I was impeded upon the introduction of the mammalian target of rapamycin (mTOR) agonist MHY1485. The inhibition of p-mTOR by AS I and the activation of TFEB were no longer observed after administration of the Akt agonist SC-79, which indicated that AS I activated TFEB to promote lipophagy-dependent on the Akt/mTOR pathway and may be a potentially effective pharmaceutical and food additive for the treatment of hyperlipidemia.
研究领域:
药理学
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代谢学
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分子生物学
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细胞生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2025
·
IF 3.3
Qi Ouyang,Shengye Tian,Hengyu Zhou,Ying Mao,Xiang Li,Feng Yan,Ailong Liu,Xiang Hu,Changqiao You,Jun He
Background Melanomas are caused by the malignant transformation of melanocytes. Numerous studies have demonstrated that the tyrosol components of salidroside inhibit tyrosinase activity. The PI3K/Akt/mTOR signaling pathway plays a crucial role in biological pigment synthesis. However, how salidroside achieves its anti-melanoma effect in melanoma by regulating PI3K/Akt/mTOR remains poorly understood. This study aimed to explore the effect of salidroside on PI3K/Akt/mTOR in melanoma, which plays a role in regulating melanogenesis. Methods Network pharmacology was predicted that salidroside may exert an anti-melanoma effect through modulating melanin synthesis functions and signaling pathways. Zebrafish whole-embryo in situ hybridization, RT-qPCR, melanin synthesis and tumorigenesis assays, and were performed to investigate the therapeutic efficacy of salidroside in melanin synthesis. The mechanism of salidroside in anti-melanoma activity was examined by RT-qPCR, Western blot, immunofluorescence, in vivo imaging, immunohistochemistry. Results We confirmed salidroside may exert an anti-melanoma effect through modulating melanin synthesis-related gene expression and PI3K/Akt pathway by Network pharmacology. Furthermore, salidroside slowed melanin synthesis in zebrafish embryos and H 2 O 2 -induced B16F10 cells by inhibited oxidative stress. Moreover, we determined the effect of salidroside on anti-melanin synthesis via PI3K/Akt/mTOR pathway in vitro , and western blot results showed that salidroside increased the expression of Nrf2 in the nucleus, as well as inhibited the phosphorylation of mTOR and PI3K/Akt pathway. Finally, intratumoral administration showed salidroside suppressed melanoma growth. Conclusion Salidroside inhibits melanin synthesis and melanoma development most likely by its antioxidant properties and downregulating the PI3K/Akt/mTOR pathway. Our results may provide a novel therapeutic strategy for the treatment of melanoma.
研究领域:
肿瘤学
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药理学
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生物化学
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细胞生物学
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分子生物学
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皮肤病学
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生物医学研究
✓ 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
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Agriculture-Basel
·
2022
·Vol. 12
·期 7
·988
·
IF 3.408
Yaojun Liu,Wenqiang Shen,Tao Liu,Rainer Mosenthin,Yinghui Bao,Peng Chen,Wenbo Hao,Lihong Zhao,Jianyun Zhang,Cheng Ji,Qiugang Ma
(1) Background: L-carnosine (β-alanyl-L-histidine), a natural dipeptide, exists at relatively high concentrations in skeletal muscles, and has been shown to protect cells from adverse conditions due to its antioxidant, anti-aging, anti-glycation, and buffering properties. Satellite cells (SCs), residing on the myofiber surface, are crucial for muscle post-growth and regeneration. However, the effects of L-carnosine on muscle development of pigs in vivo, on proliferation and growth of SCs in vitro, and the relationship between SCs and muscle development have not yet been investigated. (2) Methods: The objective of this study was to assess the effect of dietary L-carnosine on growth performance andlongissimus dorsimuscle development of pigs in vivo, and to elaborate its molecular mechanisms in vitro using L-carnosine-treated SCs. (3) Results: It was shown that L-carnosine supplementation (0.2 and 2 mM) increased (p< 0.05) SC proliferation and cell percentage in the synthesis (S) phase and decreased cell percentage in the resting (G0)/first gap (G1)/phase. Moreover, average daily gain (ADG) of pigs fed diets containing 0.1% of L-carnosine was higher (p< 0.05) than that of pigs fed diets without L-carnosine, and thelongissimus dorsimuscle weight of pigs assigned to the L-carnosine treatments was 7.95% higher compared to control pigs. Both in thelongissimus dorsimuscle and cultured SCs of pigs, the Akt/mTOR/S6K signaling pathway was activated (p< 0.05), suggesting that L-carnosine improved muscle growth and SC proliferation of pigs. (4) Conclusions: Considering the important role of SCs in post-natal muscle growth, there is evidence that L-carnosine may improve muscle growth of pigs through promoting SC proliferation via activating the Akt/mTOR/S6K signaling pathway.Keywords:L-carnosine;satellite cells;proliferation;mTOR signaling pathway;muscle growth
研究领域:
动物科学
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
MICROBIOLOGICAL RESEARCH
·
2025
·
IF 6.9
Zheng Jia,Lingdi Niu,Junjie Guo,Jiaqing Wang,Hai Li,Runhang Liu,Ning Liu,Shuhe Zhang,Fang Wang,Junwei Ge
Regulation of the innate immune response may be an effective strategy to enhance Staphylococcus aureus vaccines. Based on our previous findings that the Listeria peptidoglycan skeleton (pBLP) enhances the immune response through an unknown mechanism, we hypothesized that pBLP provides protection by modulating the innate immune response via trained immunity. In vitro, pBLP increased phagocytosis and inflammatory cytokine levels and elevated the anti-inflammatory cytokine TGF-β following secondary stimulation. In an in vivo model, our findings indicate that pBLP, when administered with a vaccine, protects mice from methicillin-resistant S. aureus challenge and also provides protection against S. aureus CMCC26003 in the absence of antigens. Using an ex vivo model, we demonstrated that pBLP increases markers of trained immunity in peritoneal macrophages. Transcriptome analysis of differentially expressed genes and inhibitor experiments revealed that the trained immunity process induced by pBLP depends on mTOR-HIF-1α and hexokinase 2. This study is the first to demonstrate that pBLP can induce trained immunity. Furthermore, we show that the peptidoglycan skeleton induces a distinct trained immunity phenotype compared to β-glucan, enhancing vaccine protection. Our study provides valuable insights for the design of novel vaccines that integrate both specific and innate immune responses.
研究领域:
免疫学
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微生物学
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疫苗研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Yingjie Wu,Mingxiang Fan,Shixiang Tan,Qiucheng Guo,Hegui Xu
Objective To examine and talk about the mechanism of the Huoxue Jiegu compound capsule's effects on osteoblasts and the PI3K/Akt/mTOR signal pathway in rabbits suffering from tibial fractures. Method In vitro, CCK8 was used to assess the survival rates. Alizarinred staining was used to evaluate mineralized nodules. ALP staining was used to observe the osteoblasts. qRT-PCR was used to determine the mRNA expression of the bone formation-related factors BMP-2, bFGF, and TGF-β. In vivo, three groups of nine male rabbits each were randomly assigned to three groups: the Model group, the Huoxue Jiegu compound capsule group (HXJGC group), and the inhibitor group (HXJGC+3-MA), four weeks following the intervention. HE staining was employed to examine the rabbits' bone histology. immunohistochemistry was employed to examine the relative expression of the proteins VEGF and LC3-II. Western Blot was utilized to examine the relative expression of the proteins Beclin-1, LC3-II/Ⅰ, p62, p-PI3K, p-AKT, and p-mTOR. Results Compared to the control group, the medium- and high-dose groups exhibited considerably higher survival rates ( P < 0.05), as well as enhanced cell proliferation and differentiation ( P < 0.05) and more pronounced mineralized nodules. ( P < 0.05), but the low-dose groups showed no appreciable variation. In the low, medium, and high-dose groups, there was a substantial reduction in the expression of bFGF mRNA, whereas the levels of BMP-2 and TGF-β mRNA were considerably higher than in the control group ( P < 0.05). In vivo, after four weeks of treatment, the model control group and inhibito group had a large amount of fibrous hyperplasia accompanied by bleeding and a small amount of inflammatory cell infiltration. But in the HXJGC group, new cartilage appeared, and the surface of the cartilage was smooth and flat. Beclin-1 and LC3-II/I expression in the HXJGC+3 MA group was significantly lower than in the HXJGC and Model groups ( P < 0.05). The HXJGC group showed lower p62 expression than the HXJGC+3 MA and model groups ( P < 0.05). The HXJGC group exhibited significantly reduced levels of p-PI3K, p-AKT, and p-mTOR expression in comparison to HXJGC+3 MA groups ( P < 0.05). Conclusion Rabbits with tibial fractures can be treated with HXJGC, which can control the expression of the PI3K/Akt/mTOR signal pathway. It can promote the differentiation and maturation of osteoblasts at the fracture end of rabbits, accelerate the recovery of fractures, and achieve the purpose of treating the disease.
研究领域:
医学
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生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2025
·
IF 5.4
Xiangyun Tan,Yuan Yang,Junjie Hu,Yan Meng,Liang Chen,Guohua Zheng,Han Xiao,Zhenpeng Qiu
Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with insidious onset, limited treatments, and poor prognosis. Recent studies show celecoxib exerts marked cytotoxic effects on cholangiocarcinoma cell lines, suggesting its potential as an iCCA therapy. However, the potential molecular and cellular mechanisms that link celecoxib treatment to its toxicological outcomes remain unclear. In this study, we induced iCCA in mice by overexpressing AKT and YapS127A (hereafter referred to as AKT/YapS127A) and administered celecoxib continuously to evaluate its antitumor effects in vivo . The results demonstrate that celecoxib effectively inhibited tumor growth in AKT/YapS127A-driven iCCA mice. Mechanistically, celecoxib boosted levels of cell cycle inhibitors p21 Waf1/Cip1 and p27 Kip1 , leading to cell cycle arrest. It also promoted apoptosis by downregulating the expression of anti-apoptotic proteins Mcl-1 and Bcl-2. These effects were associated with the modulation of the AKT/mTORC1 signaling pathway. Consistently, celecoxib recapitulated AKT/mTORC1 inhibition and subsequent cell cycle/apoptotic regulator alterations in iCCA cell lines. Collectively, our study elucidates the molecular mechanisms through which celecoxib exerts its anti-tumor effects in iCCA, demonstrating its capacity to induce cytotoxic outcomes via the precise regulation of the AKT/mTORC1 pathway. These findings deepen understanding of the toxicological actions of celecoxib and provide critical insights for developing targeted iCCA therapies.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
肝病学
·
细胞信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2025
·
IF 2.5
Zhao Wenxin,Gong Zelin,Wang Benjie,Wu Zhiyu,Guo Yiyuan,Wang Shurong,Zhai Hao,Zheng Xiaomei,Yang Lu
Autophagy dysfunction plays an influential role in fluoride-induced neurotoxicity, but the mechanism has not yet been clarified. The aim of this study was to investigate the effects of grape seed proanthocyanidin extract (GSPE) on sodium fluoride (NaF)-treated offspring SD rats and SH-SY5Y cells, and to elucidate the mechanism of mTOR/p70s6k-mediated autophagy signaling pathway action. The results of in vivo experiments showed that different doses of GSPE treatment could alleviate NaF-induced neurological damage, centering on the improvement of learning and memory ability, recovery of autonomous exploration ability, reduction of anxiety-like behaviors, restoration of neuronal structure in hippocampal tissues, and reduction of the expression of apoptotic protein cleaved-PARP. Meanwhile, GSPE significantly promoted autophagy in hippocampal tissues, as evidenced by the blockage of mTOR/p70s6k phosphorylation and the upregulation of LC3-II and downregulation of p62 expression. To further explore the mechanistic issues, we conducted cellular experiments, which suggested that GSPE pretreatment significantly increased cell viability and strengthened autophagy compared with the NaF group. These results were evidenced by the inhibition of mTOR/p70s6k phosphorylation and the upregulation of LC3-II protein. To further investigate the effect of GSPE on the mTOR/p70s6k pathway, the mTOR inhibitor rapamycin (RAPA) and activator MHY1485 were incorporated. The results indicated that GSPE inhibited the enhancement of mTOR phosphorylation in combination with MHY1485, and further inhibited the phosphorylation of mTOR in combination with RAPA, and the levels of LC3-II and p62 and immunofluorescence results also confirmed that the pretreatment of GSPE promoted cellular autophagy. Similarly, Hoechst33342 fluorescence intensity and apoptotic protein cleaved-PARP expression were further reduced after GSPE combined with RAPA or MHY1485. In addition, downstream of the mTOR/p70s6k pathway, brain-derived neurotrophic factor (BDNF), which has been widely used in studies of mood disorders, was significantly reduced by GSPE pretreatment, suggesting that GSPE may not only have a role in attenuating neurotoxicity, but also potentially in improving mood. In conclusion, the present study reveals that GSPE may alleviate fluoride-induced neurotoxicity by inhibiting the activation of the mTOR/p70s6k signaling pathway and thereby enhancing cellular autophagy and antagonizing apoptosis.
研究领域:
神经毒理学
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分子生物学
·
药理学
·
发育神经科学
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细胞自噬
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2017
·
IF 2.466
Menglu Zhou,Shuying Shen,Xin Zhao,Xingguo Gong
Autophagy has attracted a great deal of interest in tumour therapy research in recent years. However, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, on autophagy remains poorly understood in human lung cells. In the present study, we have investigated the anticancer effects of luteoloside on non-small cell lung cancer (NSCLC) cells and demonstrated that luteoloside effectively inhibited cancer cell proliferation , inducing G 0 /G 1 phase arrest associated with reduced expression of CyclinE, CyclinD1 and CDK4; we further found that treatment with luteoloside did not strongly result in apoptotic cell death in NSCLC (A549 and H292) cells. Interestingly, luteoloside induced autophagy in lung cancer cells, which was correlated with the formation of autophagic vacuoles, breakdown of p62, and the overexpression of Beclin-1 and LC3-II, but not in a human bronchial epithelial cell line (BEAS-2B). Notably, pretreatment of cancer cells with 3-MA, an autophagy inhibitor, protected against autophagy and promoted cell viability but not apoptosis. To further clarify whether luteoloside-induced autophagy depended on the PI3K/AKT/mTOR/p70S6K signalling pathway , a major autophagy-suppressive cascade, cells were treated with a combination of AKT inhibitor (LY294002) and mTOR inhibitor (Rap). These results demonstrated that luteoloside induced autophagy in lung cancer cell lines by inhibiting the pathway at p -Akt (Ser473), p -mTOR and p-p70S6K (Thr389). Moreover, we observed that luteoloside-induced cell autophagy was correlated with production of reactive oxygen species (ROS). NAC-mediated protection against ROS clearly implicated ROS in the activation of autophagy and cell death. In addition, the results showed that ROS served as an upstream effector of the PI3K/AKT/mTOR/p70S6K pathway. Taken together, the present study provides new insights into the molecular mechanisms underlying luteoloside-mediated cell death in NSCLC cells and supports luteoloside as a potential anti-cancer agent for targeting NSCLC through the induction of autophagy, inhibition of proliferation and PI3K/AKT/mTOR/p70S6K signalling.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Jianyu Xia,Pengju Guo,Jing Yang,Tao Zhang,Kejian Pan,He Wei
Background Colorectal cancer (CRC) is a prevalent malignancy and poses a significant clinical challenge. Piperine, an alkaloid molecule extracted from Piper nigrum and Piper longum, has emerged as a promising anticancer agent. However, the molecular mechanisms of piperine’ antitumor effects in CRC need to be further elucidated. Methods Human colorectal cancer cells were treated with piperine in vitro . CCK-8 and clone formation assays were adopted to detect cell viability. The accumulation of autophagosomes was assessed by Western blotting and immunofluorescence. Apoptosis and reactive oxygen species (ROS) levels were analyzed by flow. In vivo , a xenograft tumor mouse model was constructed using CT26 cells. Results Piperine inhibited CRC cell viability and suppressed tumor weight and volume in a mouse model. Additionally, piperine treatment induced the accumulation of autophagosomes in CRC cells. This effect was attributed to the inhibition of the AKT/mTOR pathway and the accumulation of ROS. activation of AKT or clearance of ROS attenuated piperine-mediated tumor suppression. Conclusion This study shows that piperine induces autophagy-dependent cell death in CRC cells by increasing ROS production and inhibiting Akt/mTOR signaling.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2019
·
IF 4.868
Qiang Chu,Xin Yu,Ruoyi Jia,Yaxuan Wang,Yiru Zhang,Shuang Zhang,Yangyang Liu,Yonglu Li,Wen Chen,Xiang Ye,Xiaodong Zheng
Apios americana Medikus was once widely accepted as staple food in India for a long time, and the tuber of which possesses high nutrients. During the past decades, most of the research has focused on the biological activity in the tubers of Apios americana Medikus whereas the leaves were ignored. In this study, the Apios americana Medikus leaf extract (ALE) was obtained and seven compounds were identified. LPS-induced RAW264.7 cells were used to study the anti-inflammation activity of ALE. As expected, ALE reduced the secretion of nitric oxide (NO) and inflammatory cytokines via inhibition of NF-κB and MAPK signaling together with activation of Nrf2-Keap1 and FOXO pathways, as well as alleviating the oxidative stress and mitochondrial dysfunction. In addition, ALE could activate HMGB1-Beclin1 and Sirt1-FoxO1 pathways and inhibit the Akt-mTOR signaling pathway to activate autophagy, protecting RAW264.7 cells from inflammation. In summary, our results suggested that ALE might help activate the anti-inflammation system, resulting in the prevention of LPS-induced damage in RAW264.7 cells.
研究领域:
药理学
·
免疫学
·
分子生物学
✓ 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）