Frontiers in Nutrition
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2022
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IF 6.59
Suwen Liu,Fanna Meng,Dong Zhang,Donglin Shi,Junyi Zhou,Shuo Guo,Xuedong Chang
Exercise fatigue can exert deleterious effects on the body. This study evaluated the effects and mechanisms by which Lonicera caerulea berry polyphenols extract (LCBP) improved the treadmill endurance of mice. Comparison was performed between the effects at 25°C and low temperatures (-5°C). Energy storage, product metabolism, and other biochemical indices were determined using vitamin C (VC) as a positive control. Co-immunoprecipitation was performed to detect the interaction between different proteins. Dietary supplementation with LCBP significantly prolonged the exhaustion time during treadmill exercise by 20.4% (25 °C) and 27.4% (-5 °C). LCBP significantly regulated the expression of antioxidant and inflammatory proteins, Bcl-2 /Bax apoptosis proteins, and the PKCα -NOx2 / Nox4 pathway proteins, and activated the expression of AMPK-PGC1α -NRF1-TFAM proteins in skeletal muscle mitochondria. The gene and protein expression of miRNA-133a/IGF-1/PI3K/Akt/mTOR in skeletal muscle cells was also activated. Molecular docking confirmed that the main components of LCBP such as cyanidin-3-glucoside, catechin, and chlorogenic acid, have strong binding affinity toward AMPKα. LCBP alleviates exercise fatigue in mice by reducing oxidative stress, inflammation, and apoptosis of skeletal muscle cells, enhances mitochondrial biosynthesis and cell proliferation, reduces fatigue, and enhances performance. These effects are also significant in a low-temperature environment (Graphical Abstract). Consequently, these results provide novel insights into the anti- fatigue roles of LCBP in exercise fatigue.
研究领域:
药理学
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生理学
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生物化学
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分子生物学
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运动科学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
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IF 6.1
Siyu Wang,Lutong Wang,Jingwen Xu,Yihai Wang,Limin Xiang,Xiangjiu He
The berries of black nightshade (Solanum nigrum L.) are consumed as a favorite fruit in some regions and have been reported to possess a range of biological activities. Previous studies have found that the steroidal saponins from the berries of S. nigrum (SN) showed potential antileukemic activity, although the underlying mechanism remains to be revealed. This study investigated the effects and mechanisms of SN in combination with adriamycin to reverse leukemia multidrug resistance in vivo and in vitro. The results indicated that the combination of SN and adriamycin displayed enhanced suppression ability both in vitro and in vivo by the modulation of drug efflux proteins. Further study revealed that SN and adriamycin co-treatment induced cell apoptosis in K562/ADR cells through caspase pathways and autophagy through the PI3K/Akt/mTOR and MAPK signaling pathway. This study provides a new prospect of the berries of black nightshade in multidrug resistance therapy of cancer.
研究领域:
药理学
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肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
·
2021
·Vol. 62
·期 9
·25-25
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IF 4.799
Xiaoling Shi,Nuo Dong,Qi Qiu,Shanhua Li,Jiaxing Zhang
Purpose:Retinopathies are associated with the injury of retinal microvascular endothelial cells. Salidroside (SAL) is a medicinal supplement that has antioxidative and cytoprotective properties. We hypothesized that SAL might have a protective function in retinopathies. This research aims to explore the function and mechanism of SAL in hypoxia-induced retinal microvascular endothelial cell injury.Methods:Human retinal microvascular endothelial cells (HRMECs) injury was induced by culturing under hypoxic condition. The function of SAL on HRMECs injury was investigated using cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, Western blotting, and enzyme linked immunosorbent assay. MicroRNA (miR)-138, roundabout 4 (ROBO4), and proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways were examined using quantitative reverse transcription polymerase chain reaction or Western blotting. The target correlation was determined by dual-luciferase reporter analysis and RNA immunoprecipitation.Results:Hypoxia resulted in proliferation inhibition, cycle arrest, apoptosis, inflammatory reaction, and oxidative stress in HRMECs. SAL attenuated hypoxia-induced HRMECs injury via increasing cell proliferation, and mitigating cycle arrest, apoptosis, inflammatory reaction, and oxidative stress. MiR-138 expression was enhanced by hypoxia, and decreased via SAL stimulation. MiR-138 upregulation reversed the influence of SAL on hypoxia-induced HRMECs injury. ROBO4 was targeted via miR-138. ROBO4 overexpression weakened the role of miR-138 in HRMECs injury. The PI3K/AKT/mTOR pathway was inactivated under hypoxic condition, and SAL increased the activation of PI3K/AKT/mTOR pathways by decreasing miR-138.Conclusions:SAL protected against hypoxia-induced HRMECs injury through regulating miR-138/ROBO4 axis, indicating the protective potential of SAL in retinopathies.
研究领域:
眼科学
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分子生物学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2025
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IF 5.4
Yuxin Huang,Wenya Zhu,Jiaxin Zhang,Yichen Zhang,Yuxin Liu,Guowei Wang,Wuli Yang
Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to its aggressive behavior, lack of therapeutic targets, and poor prognosis. The PI3K/AKT/mTOR pathway is highly activated in TNBC, making it a promising therapeutic target. Conventional PEGylated nanocarriers often face challenges, such as accelerated blood clearance and lysosomal trapping. To overcome these limitations, we developed a zwitterionic block copolymer, poly(2-(N-oxide-dimethylamino)ethyl methacrylate)-block-poly(ε-caprolactone) (OPDMA-PCL), via one-pot living anionic polymerization followed by postmodification. Compared with poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) micelles, the OPDMA-PCL micelles exhibited prolonged systemic circulation, improved tumor targeting, and negligible immunogenicity. OPDMA-PCL micelles exhibited mitochondria-targeting properties in vitro. Loaded with gambogenic acid (GNA), OPDMA-PCL-GNA induces apoptosis in MDA-MB-231 cells by inhibiting the PI3K/AKT/mTOR pathway. In vivo, OPDMA-PCL-GNA achieved 91.2% tumor growth inhibition in xenograft models without systemic toxicity. This work establishes zwitterionic OPDMA-PCL micelles as a promising platform for TNBC therapy, overcoming key limitations of PEGylated systems while enabling organelle-specific drug delivery.
研究领域:
生物医学工程
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药学
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肿瘤学
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聚合物化学
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纳米技术
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细胞生物学
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PubMed
高影响因子
Natural Products and Bioprospecting
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2025
·Vol. 15
·期 1
·1-17
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IF 4.9
Zhao Huimin,Wang Yuyang,Liu Zining,Lin Lin,Xiang Jiasi,Zhu Zihao,Yang Xiongli,Fang Yongsheng,Kong Lingmei,Li Yan
Natural product tanshinone I exhibits weak potency and poor drug-like properties, which have restricted its clinical development as an anticancer agent. Herein, twenty novel tanshinone I-pyridinium salt derivatives and a pyridinium salt precursor were designed and synthesized, and their antitumor activities were evaluated. Among these tanshinone I-pyridinium salts, compound a4 , bearing a 4-bromobenzoylmethyl substituent at the N -1 position of the pyridine ring, showed the most potent cytotoxicity against breast cancer (MDA-MB-231), hepatocellular carcinoma (HepG2), and prostate cancer (22RV1) cell lines, with IC 50 values of 1.40–1.63 μM. Preliminary mechanistic studies suggest that a4 targets PI3Kα with the IC 50 of 9.24 ± 0.20 μM and exerts effective inhibition of the phosphorylation of key PI3K/Akt/mTOR signaling proteins. Besides, a4 significantly downregulates the expression of the immune checkpoint protein PD-L1, indicating its potential to activate tumor immunity. These findings demonstrate that tanshinone I-pyridinium salt derivative a4 is a novel PI3Kα inhibitor, providing a solid foundation for further development of antitumor agents. Graphical
研究领域:
药物化学
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肿瘤学
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药理学
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药物设计
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天然产物研究
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Xi-you Li,Xiao-yuan Gu,Bai-ling Zhou,Bun Tsoi,Wei-xi Li
Eye deformity, a noteworthy embryopathy, is intricately linked with maternal diabetes, frequently resulting in embryonic malformation or even death. In this investigation, a hyperglycemic chick embryo model was established to delve into the protective potential of tamarind shell extract (TSE) on eye development. Chick embryos were administered with TSE (at dosages of 1, 2, and 4 µg/egg) through air sac injection on embryo development day 0 (EDD0) and later exposed to D-glucose (0.4 mmol/egg) on EDD1. To validate our findings, we replicated hyperglycemic environment using D-glucose in ARPE-19 cell model. Our research unveiled that TSE proficiently counters O-GlcNAcylation of proteins in the presence of D-glucose, thereby reinstating levels of key proteins involved in eye development, including Pax6, Daam1, mTOR, and Cdc42. Furthermore, TSE was pinpointed to curtail the D-glucose concentration within the embryo eye, considerably decreasing the accumulation of reactive oxygen species and malondialdehyde accumulation in both the ARPE-19 cells and chick embryos. Beyond its fundamental role in boosting the cellular antioxidative activity, the improved expression of apoptosis-related proteins like Caspase-3, BAX, BCL-2 and other like PI3K and AKT were observed. This suggests a probable activation of the PI3K-AKT-mTOR pathway on ARPE-19 cells by TSE, thereby downregulating apoptotic proteins in ARPE-19 cells during oxidative stress. TSE may become a potent natural countermeasure against D-glucose-induced eye malformation.
研究领域:
发育生物学
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药理学
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细胞生物学
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胚胎学
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Jing Li,Qi Huang,Wenfeng Ma,JinYu Yi,Xin Zhong,Rui Hu,Jialing Sun,MengQing Ma,Minling Lv,Zhiyi Han,Wei Zhang,Wenxing Feng,Xinfeng Sun,Xiaozhou Zhou
Ethnopharmacological relevance Acute-on-chronic liver failure (ACLF) progresses rapidly with a high short-term death rate. Although JianPi LiShi YangGan formula (YGF) has been used to treat ACLF by managing inflammatory responses and reducing endotoxemia , hepatocyte injury , and mortality, the underlying mechanisms remain unclear. Aim of the study This study aims to investigate the potential mechanisms underlying the efficacy and protective benefits of YGF in mice with ACLF. Materials and methods YGF composition was determined using high-performance liquid chromatography coupled with mass spectrometry. We constructed a mouse model of ACLF using carbon tetrachloride , lipopolysaccharide (LPS), and D-galactosamine (D-Gal), as well as an in vitro model of D-Gal/LPS-induced hepatocyte injury. The therapeutic effects of YGF in ACLF mice were verified using hematoxylin-eosin, Sirius red, and Masson staining, and by measuring serum alanine transaminase (ALT), aspartate transaminase (AST), and inflammatory cytokine levels. Mitochondrial damage in hepatocytes was evaluated using electron microscopy , while superoxide anion levels in liver tissue were investigated using dihydroethidium . Transcriptome analysis, immunohistochemistry, western blotting , and immunofluorescence assays were performed to explore the mechanisms underlying the ameliorative effects of YGF against ACLF. Results In mice with ACLF, YGF therapy partially decreased serum inflammatory cytokine levels, as well as hepatocyte injury and liver fibrosis . The livers of ACLF mice treated with YGF exhibited decreased mitochondrial damage and reactive oxygen species generation, as well as a decreased number of M1 macrophages and increased number of M2 macrophages. Transcriptome analysis revealed that YGF may regulate biological processes such as autophagy, mitophagy, and PI3K/AKT signaling. In ACLF mice, YGF promoted mitophagy and inhibited PI3K/AKT/mTOR pathway activation in hepatocytes. Meanwhile, the autophagy inhibitor 3M-A reduced the capacity of YGF to induce autophagy and protect against hepatocyte injury in vitro . In contrast, the PI3K agonist 740 Y–P suppressed the ability of YGF to control PI3K/AKT/mTOR pathway activation and induce autophagy. Conclusions Together, our findings suggest that YGF mediates autophagy, tight junctions, cytokine generation, and other biological processes. In addition, YGF inhibits hepatic inflammatory responses and ameliorates hepatocyte injury in mice with ACLF. Mechanistically, YGF can promote mitophagy to ameliorate acute-on-chronic liver failure by inhibiting the PI3K/AKT/mTOR pathway.
研究领域:
药理学
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肝病学
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免疫学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Liya Feng,Yuanxin Wang,Xiangyue Wang,Baochan Li,Yifan Liu,Wanying Zhang,Jianbo Ji,Lijun Shao,Xiuli Guo
In the tumor microenvironment (TME), tumor associated macrophages (TAMs) often exhibit a preference for M2-like phenotype, which supports tumor progression under hypoxia. The underlying mechanisms driving the behavior of hypoxic TAMs are highly complex. Recently, exosomal long non-coding RNAs (lncRNAs) derived from non-cancerous cells within TME have attracted more attention from researchers. In the present study, we investigated the function of exosomal lncRNA MIR210HG derived from hypoxic TAMs in triple negative breast cancer (TNBC). Results showed that MIR210HG was significantly upregulated in hypoxic TAMs, their exosomes, and exosomes-treated TNBC cells. When MIR210HG was suppressed, the expression of M2-polarization markers and proteins associated with the PI3K/Akt/mTOR pathway in hypoxic TAMs was notably inhibited. Moreover, the suppression of TAM-derived exosomal MIR210HG effectively inhibited the migration, invasion and vasculogenic mimicry (VM) formation of TNBC cells. Notably, dual inhibition of both exosomal and endogenous MIR210HG in tumor cells synergistically restricted TNBC metastasis of in vivo . Mechanistically, we elucidated that MIR210HG promoted the malignant phenotypes of TNBC by upregulating the expression of HIF-1α protein, which in turn initiated RASSF7 transcription, resulting in the promotion of epithelial-mesenchymal transition (EMT) process. Collectively, our results identified MIR210HG as a key molecule mediating exosome-based communication from hypoxic TAMs to TNBC cells and revealed its pro-metastatic role, Consequently, MIR210HG emerges as a highly promising therapeutic target of TNBC.
研究领域:
癌症生物学
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分子生物学
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免疫学
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细胞生物学
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遗传学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Xiaomei Liang,Yulu Yang,Chuanqing Huang,Zhibin Ye,Wujiang Lai,Jiamao Luo,Xiaoxuan Li,Xiao Yi,Jun-Bing Fan,Ying Wang,Yifeng Wang
Resistance to the chemotherapeutic agent cisplatin (DDP) is the primary reason for invalid chemotherapy of ovarian cancer. Given the complex mechanisms underlying chemo-resistance, the design of combination therapies based on blocking multiple mechanisms is a rationale to synergistically elevate therapeutic effect for effectively overcoming cancer chemo-resistance. Herein, we demonstrated a multifunctional nanoparticle ( [email protected] ), which could simultaneously co-deliver DDP and Olaparib (Ola, DNA damage repair inhibitor) using targeted ligand cRGD peptide modified with heparin (HR) as nanocarrier, enabling the concurrent tackling of multiple resistance mechanisms to effectively inhibit the growth and metastasis of DDP-resistant ovarian cancer. In combination strategy, heparin could suppress the function of multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein (P-gp) to promote the intracellular accumulation of DDP and Ola by specifically binding with heparanase (HPSE) to down-regulate PI3K/AKT/mTOR signaling pathway, and simultaneously served as a carrier combined with Ola to synergistically enhance the anti-proliferation ability of DDP for resistant ovarian cancer, thus achieving great therapeutic efficacy. Our [email protected] could provide a simple and multifunctional combination strategy to trigger an anticipated cascading effect, thus effectively overcoming the chemo-resistance of ovarian cancer.
研究领域:
药学科学
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癌症研究
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Small Science
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2025
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IF 8.3
Jingyan Huang,Dongheng Lu,Cairong Xiao,Jiezhong Guan,Xiaoshuang Wang,Changhao Li,Peng Yu,Yan Wang
Increasing studies have emphasized the role of implant surface modifications in enhancing osseointegration through the synergistic regulation of osteogenesis and angiogenesis. While both topography and electrical cues have been shown to promote these processes, the interplay between these biophysical characteristics and their combined effects remain unclear. This study employs polarized BaTiO 3 nanorod arrays (NBTP) on titanium surfaces as model substrates to engineer a mechanobiological and piezoelectric microenvironment. Nanotopography improves hydrophilicity, piezoelectric properties, and surface potential due to sharp reduction in Young's modulus. In vitro experiments reveal that topography-mediated mechanobiological remodeling primarily enhances osteogenesis in mesenchymal stem cells (MSCs) and angiogenesis in endothelial cells (ECs) via Piezo2/Piezo1/Ca 2+ signaling. The augmented electric field further amplifies this mechanical stress-driven osteogenic/angiogenic response by activating Ca v1.2 and potentiating Piezo2/Piezo1 signaling. Microarray analysis and blocking experiments identify the PI3K/AKT/mTOR/GSK3β pathway as a key mediator. Together, topography and the built-in electric field activate paracrine crosstalk between MSCs and ECs, indirectly enhancing osteogenesis and angiogenesis. In vivo studies confirm that nanorod topography significantly improves vascularized osseointegration, while the built-in electric field accelerates bone healing by remodeling the peri-implant microenvironment. These findings advance the design of high-performance bone implants by elucidating the mechanobiological–piezoelectric coupling mechanism underlying vascularized osteogenesis.
研究领域:
生物材料
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生物医学工程
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细胞生物学
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力学生物学
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组织工程
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信号转导
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纳米技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2021
·Vol. 42
·期 2
·230-243
·
IF 3.446
Yan-ping Liu,Xiao-yan Yuan,Xun-ya Li,Ye Wang,Zhan-bing Sun,Wei-hua Deng,Yuan-di Lei,Lian Huang,Tian-yi Jiang,Zhao-hui Zhang
Beryllium and its compounds are systemic toxicants that are widely applied in many industries. Hydrogen sulfide has been found to protect cells. The present study aimed to determine the protective mechanisms involved in hydrogen sulfide treatment of 16HBE cells following beryllium sulfate-induced injury. 16HBE cells were treated with beryllium sulfate doses ranging between 0 and 300 μM BeSO 4 . Additionally, 16HBE cells were subjected to pretreatment with either a 300 μM dose of sodium hydrosulfide (a hydrogen sulfide donor) or 10 mM DL-propargylglycine (a cystathionine- γ -lyase inhibitor) for 6 hr before then being treated with 150 μM beryllium sulfate for 48 hr. This study illustrates that beryllium sulfate induces a reduction in cell viability, increases lactate dehydrogenase (LDH) release, and increases cellular apoptosis and autophagy in 16HBE cells. Interestingly, pretreating 16HBE cells with sodium hydrosulfide significantly reduced the beryllium sulfate-induced apoptosis and autophagy. Moreover, it increased the mitochondrial membrane potential and alleviated the G2/M-phase cell cycle arrest. However, pretreatment with 10 mM DL-propargylglycine promoted the opposite effects. PI3K/Akt/mTOR and Nrf2/ARE signaling pathways are also activated following pretreatment with sodium hydrosulfide. These results indicate the protection provided by hydrogen sulfide in 16HBE cells against beryllium sulfate-induced injury is associated with the inhibition of apoptosis and autophagy through the activation of the PI3K/Akt/mTOR and Nrf2/ARE signaling pathways. Therefore, hydrogen sulfide has the potential to be a promising candidate in the treatment against beryllium disease.
研究领域:
毒理学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Immunity Inflammation and Disease
·
2024
·Vol. 12
·期 2
·e1177
·
IF 3.1
Nannan Pang,Shabaaiti Tudahong,Yuejie Zhu,Jiang He,Chunxia Han,Gang Chen,Weiguo Wang,Jing Wang,Jianbing Ding
Background Acute graft-versus-host disease (aGVHD) arises from the imbalance of host T cells. Galectin-9 negatively regulates CD4 effector T cell (Th1 and Th17) function by binding to Tim-3. However, the relationship between Galectin-9/Tim-3 and CD4 + T subsets in patients with aGVHD after Haplo-HSCT (haploidentical peripheral blood hematopoietic stem cell transplantation) has not been fully elucidated. Here, we investigated the role of Galectin-9 and CD4 + T subsets in aGVHD after haplo-HSCT. Methods Forty-two patients underwent Haplo-HSCT (26 without aGVHD and 16 with aGVHD), and 20 healthy controls were included. The concentrations of Galectin-9, interferon-gamma (IFN-γ), interleukin (IL)-4, transforming growth factor (TGF)-β, and IL-17 in the serum and culture supernatant were measured using enzyme-linked immunosorbent assay or cytometric bead array. The expression levels of Galectin-9, PI3K, p-PI3K, and p-mTOR protein were detected by western blot analysis. Flow cytometry was used to analyze the proportions of CD4 + T cell subsets. Bioinformatics analysis was performed. Results In patients with aGVHD, regulatory T (Treg) cells and Galectin-9 decreased, and the Th1, Th17, and Treg cells were significantly imbalanced. Moreover, Treg and Galectin-9 were rapidly reconstituted in the early stage of patients without aGVHD after Haplo-HSCT, but Th17 cells were reconstituted slowly. Furthermore, Tim-3 upregulation on Th17 and Th1 cells was associated with excessive activation of the PI3K/AKT pathway in patients with aGVHD. Specifically, in vitro treatment with Galectin-9 reduced IFN-γ and IL-17 production while augmenting TGF-β secretion. Bioinformatics analysis suggested the potential involvement of the PI3K/AKT/mTOR pathway in aGVHD. Mechanistically, exogenous Galectin-9 was found to mitigate aGVHD by restoring the Treg/Teffs (effector T cells) balance and suppressing PI3K. Conclusion Galectin-9 may ameliorate aGVHD after haplo-HSCT by modulating Treg/Teffs balance and regulating the PI3K/AKT/mTOR pathway. Targeting Galectin-9 may hold potential value for the treatment of aGVHD.
研究领域:
免疫学
·
血液学
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移植学
·
分子生物学
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DOI
PubMed
高影响因子
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