FISH & SHELLFISH IMMUNOLOGY
·
2023
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IF 4.7
Xinyu Wu,Yue Xin,Yeyun Ma,Kaixin Ping,Qiulu Li,Ying Sun,Zunhan Hu,Jingquan Dong
Abamectin (ABM) abuse contaminated aquatic environment and posed a potential threat to fish health as well as public safety. Silybin (SIL), a flavonoid , has been widely used as a novel feed additive to promote fish health. This research was to explore the potential antagonistic mechanism between ABM and SIL on brain and liver toxicity was investigated in common carp . Sixty carp were divided into four groups at random: the Control group, the SIL group, the ABM group, and ABM + SIL group. This experiment lasted for 30 d. According to behavioral observation, the detection of levels of acetylcholinesterase (AchE), iron, and mRNA expression levels of blood-brain barrier (BBB) related tight junction proteins (ZO-1, Claudin7, Occludin , MMP2 , MMP9 , and MMP13) in brain tissues, it was found that SIL relieved neurobehavioral disorders caused by ABM-induced BBB destruction in carp. H&E staining showed SIL mitigated nerve injury and liver injury caused by ABM. Oil Red O staining and liver-related parameters showed that SIL alleviated hepatotoxicity and lipid metabolism disorder caused by ABM exposure. Furthermore, this work also explored the specific molecular mechanism of SIL in liver protection and neuroprotection. It was shown that SIL lowered ROS levels in liver and brain tissues via the GSK-3β/TSC2/TOR pathway. Simultaneously, SIL inhibited NF-κB signaling pathway and played an anti-inflammatory role. In conclusion, we believed that SIL supplementation has a protective effect on the brain and liver by regulating oxidative stress and inflammation.
研究领域:
水生毒理学
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药理学
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分子生物学
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兽医学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Menglong Zhao,Danqing Wu,Weiqian Qiu,Hongchen Zhang,Min Chen,Haixia Zhou,Xiaoxia Ye,Zhong Han,Xiangchao Shi
4-anilinoquinazoline scaffold, a key structure in the development of EGFR-TKI anticancer drugs such as Gefitinib and Erlotinib, continues to drive advancements in non-small cell lung cancer (NSCLC) therapy. In this study, we synthesized a series of novel derivatives ( B3–B11 ). Structure-activity relationship (SAR) analysis revealed that electron-donating groups para-substituted at the 4-anilino position significantly enhanced antiproliferative activity. Notably, B10 incorporating an acrylamide group at the 4-anilino position demonstrated the most potent activity against NSCLC, with an IC 50 of 1.28 μM in A549 cells, nearly six times more effective than Gefitinib (7.81 μM). Acute toxicity studies confirmed that B10 is safe at doses below 50 mg/kg. In vivo studies using an A549 xenograft model showed a 46 % tumor growth inhibition (TGI) with B10 (25 mg/kg), surpassing the 21 % inhibition of Gefitinib at the same dose. Mechanistic studies revealed that B10 inhibited the AKT/GSK-3β/β-catenin signaling pathway, downregulating Wnt target genes (c-Myc, c-Jun), and reduced COX2 expression and IL-8 levels, showcasing its dual anti-inflammatory and antitumor effects. These results position B10 as a promising NSCLC therapeutic candidate, combining potent efficacy with a favorable safety profile, and enhance our understanding of the SAR and mechanism of action of 4-anilinoquinazoline derivatives.
研究领域:
肿瘤学
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药理学
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分子生物学
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药物化学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yue Xiong,Chao He,Xun Lin,Ke Cheng,Fumei He,Jingxin Zhao,Mengjie Yang,Hong Gao,Fangjie He,Xiaopei Zhang,Zeqi Liu,Gan Liu,Wenbin Deng
Black phosphorus nanosheet (BPNS) has recently demonstrated intrinsic anti-tumor bioactivity, but its underlying molecular mechanism remains unclear, limiting its potential applications in biomedicine. In this study, we investigated the impact of BPNS on glioblastoma cells and observed a significant dose-dependent inhibition of invasion and migration. RNA sequencing analysis revealed downregulation of genes associated with the WNT/β-catenin and NOTCH signaling pathways, both linked to invasion and migration. Mechanistically, BPNS directly binds to CSNK2A2, reducing its kinase activity, which indirectly enhances GSK-3β kinase activity. As a result, GSK-3β increases the phosphorylation level of β-catenin, leading to its degradation and subsequent inhibition of downstream molecules in the WNT/β-catenin signaling pathway. Our study uncovers the inherent biological activity of BPNS in hindering glioblastoma invasion and migration and sheds light on the molecular mechanisms, offering new directions for the nanomaterial’s biomedical applications.
研究领域:
生物医学工程
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癌症生物学
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分子生物学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
COMPOSITES PART B-ENGINEERING
·
2021
·
IF 9.078
Yu Chen,Long Chen,Yitong Wang,Kaili Lin,Jiaqiang Liu
The repair of bone defects in patients with diabetes mellitus (DM) is a challenge in clinical treatment mainly because of inhibited osteogenesis caused by stem cell dysfunction. Our research found that high glucose induced the activation of GSK-3β, which played an important role in this process. Inhibited GSK-3β induced an acceptable osteogenic effect of lithium ions . However, whether lithium-containing biomaterials can exert a good bone-repair effect under the pathological state of DM is still unclear. Therefore, we synthesized a type of lithium-containing mesoporous bioactive glasses (Li-MBG), and explored their in vitro roles in regulating the proliferation, migration and osteogenic differentiation of BMSCs under the high-glucose microenvironment , and the underlying mechanism. Meanwhile, Li-MBG/PLGA composite scaffolds were prepared by 3D printing , followed by investigating their in vivo effects on repairing critical skull defects of DM mice. We found that Li-MBG reversed high glucose-induced suppression in the proliferation, migration and osteogenic differentiation of BMSCs by upregulating Itga3 and activating the β-catenin/Tcf7/Ccn4 signaling pathway. Li-MBG/PLGA composite scaffolds could effectively repair skull defects of DM mice by recruiting stem cells, presenting an excellent osteogenesis effect. Our findings provide references for clinical bone defect repair in DM patients.
研究领域:
生物材料
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组织工程
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糖尿病研究
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骨再生
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Ziyang Liu,Jing Mao,Weiqi Li,Chenci Xu,An Lao,Airi Shin,Jiaqing Wu,Anqi Gu,Zhen Zhang,Lixia Mao,Kaili Lin,Jiaqiang Liu
Diabetic patients often suffer from delayed tissue healing and bone metabolism disorder, presenting a significant clinical challenge in the regeneration of diabetic bone defects. Hyperglycemia weakens osteogenesis and angiogenesis and destroys the balance of homeostasis. To solve this problem, a smart glucose-sensitivity sustained-release Resveratrol-loaded hydrogel platform is proposed to restore the function of mesenchymal stem cells. In this study, phenylboronic acid (PBA), known for its unique glucose sensitivity, is grafted onto the methacrylated gelatin (GelMA) chain, enabling the immobilization of Resveratrol (Res) molecules within the hybrid hydrogel through dynamic borate bond formation. Both in vivo and in vitro findings demonstrate that this hydrogel platform effectively scavenges excessive reactive oxygen species, ameliorates inflammation, modulates macrophage polarization, and enhances osteogenesis by activating the PI3K/AKT/GSK-3β signaling pathway. Collectively, all results suggest that this novel glucose-responsive hydrogel platform may be a potential therapy for diabetic bone regeneration.
研究领域:
生物医学工程
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组织工程
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糖尿病研究
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再生医学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
PHYSIOLOGY & BEHAVIOR
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2019
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IF 2.635
Hui Wang,Ling Xiao,Huiling Wang,Gaohua Wang
Low-density lipoprotein receptor-related protein 1 (LRP1) and tau play an important role in developing Alzheimer's disease. This study aimed to explore the involvement of LRP1 in microtubule dynamic and depressive-like behavior in a depressive-like rat model. It also investigated whether fluoxetine blocked the change induced by chronic unpredictable mild stress (CUMS). Sprague–Dawley rats (200–250 g) were exposed to CUMS and fluoxetine for 4 weeks respectively. The body weight was determined, and behavior tests, including sucrose preference test, forced swimming test and open field test were performed. Western blot analysis was conducted to determine the protein levels of LRP1, tubulin, Acet-tub, Tyr-tub and PI3K/Akt/GSK-3β. Real-time quantitative polymerase chain reaction was used for mRNA expression levels of LRP1. Immunohistochemical staining was applied for LRP1 and immunofluorescence staining for the co-location of p-tau (404,262) and Acet-tub. The CUMS group presented a decreased body weight and depressive-like behavior, which was improved by fluoxetine. The protein and mRNA expression levels of LRP1 were elevated in the CUMS group. The levels of Acet-tub increased following CUMS, accompanied by elevated levels of p-tau (404,262). The binding of p-tau and Acet-tub significantly decreased in depressive-like rats, and fluoxetine attenuated microtubule instability. Finally, the inhibition of CUMS-induced PI3K/Akt activated GSK-3β, and fluoxetine reversed the change in the signaling pathway. Hence, LRP1 might impair the microtubule dynamics accompanied by depressive-like behavior via the PI3K/ Akt /GSK3β pathway in adult depressive-like rats, and hippocampal LRP1 might be involved in the development of depression.
研究领域:
神经科学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
·
IF 3.118
Man Zhang,Yanqing Wu,Ling Xie,Chen-Huai Teng,Fang-Fang Wu,Ke-Bin Xu,Xiong Chen,Jian Xiao,Hong-Yu Zhang,Da-Qing Chen
Traumatic brain injury (TBI) caused by an external mechanical force acting on the brain is a serious neurological condition. Inflammation plays an important role in prolonging secondary tissue injury after TBI, leading to neuronal cell death and dysfunction. Isoliquiritigenin (ILG) is a flavonoid monomer with anti-inflammatory characteristic. Thus, we had investigated the potential protective effects of ILG on TBI-induced injuries and identified the mechanisms underlying it. Here, we have demonstrated that ILG preserves blood brain barrier (BBB) integrity in vivo, suppresses the activation of microglia and inflammatory responses in mice after TBI, consequently leading to neurofunctional deficits, brain oedema , structural damage, and macrophage infiltration. In vitro, ILG exerts anti-inflammatory effect, and upregulates tight junction proteins 120‑β‑catenin and occludin in SH‑SY5Y cells under oxygen glucose deprivation/reoxygenation (OGD/D) condition. Additionally, we found that PI3K/AKT/GSK‑3β signalling pathway is involved in ILG treatment for TBI. To further confirm it, we had used SC79 (ethyl 2‑amino‑6‑chloro‑4‑(1‑cyano‑2‑ethoxy‑2‑oxoethyl)‑4H‑chromene‑3‑carboxylate), an Akt specific activator, to activate Akt, we found that SC79 partially reduces the protective effect of ILG for TBI. Overall, our current study reveals the neuroprotective role of ILG on TBI-induced BBB damage, downregulated tight junction proteins via PI3K/AKT/GSK‑3β signalling pathway. Furthermore, ILG suppresses the secretion of pro-inflammatory cytokines after TBI through inhibiting the PI3K/AKT/GSK‑3β/NF‑κB signalling pathway. Our findings suggest that GSK‑3β is a key regulatory factor during TBI-induced secretion of inflammatory cytokines, neuronal apoptosis and destruction of BBB.
研究领域:
神经科学
·
药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2021
·
IF 10.041
Maohua Chen,Yan Hu,Yanhua Hou,Yuting Sun,Maowen Chen,Menghuan Li,Lu Tan,Zhong Luo,Kaiyong Cai
By exploiting the high reactive-oxygen-species(ROS) level in osteoporosis fractured sites, a ROS responsive biomimetic multilayer onto titanium(Ti) implant composed of gelatin(Gel)/dextran amine (DA) and α-melanocyte-stimulating hormone (α-MSH) has been constructed using layer-by-layer spin self-assembled technique, which was further cross-linked with 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2) benzyl carbonate (NBC)-grafted-polyethylene glycol (PEG-NBC) for in situ delivery of α-MSH. The PEG-NBC cross-linked Gel/DA multilayer onto Ti substrate (Ti/LBL NBC -MSH) could be broken down when exposed to ROS-rich pathological environment, thus leading to a sustained release of α-MSH from multilayer in a controlled manner. It could maintain the α-MSH concentration at a constant level to promote in situ MSCs differentiation and inhibit osteoclast activity through regulating GSK-3β/β-catenin signal pathways with Runx2 positive feedback regulation loop. Micro-CT analysis, hematoxylin/eosin (HE) staining and Masson's trichrome (MT) staining further confirmed that new bone has fused into mature lamellar bone and trabecularism along the interface of Ti/LBL NBC -MSH in osteoporotic rats. Therefore, this study offers a new perspective on the development of biofunctional Ti implants as supplementary treatment for osteoporotic fracture repair in a clinical context.
研究领域:
生物材料工程
·
组织工程
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骨科
·
药剂学
·
材料科学
✓ 已验证
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2023
·
IF 8.1
Qiannan Zhao,Jinyi Yang,Jiahui Li,Lei Zhang,Xiaohai Yan,Tianli Yue,Yahong Yuan
Phenolics of mulberry ( Morus alba L.) leaves (MLs) have potential anti-diabetic effects, but they may be chemically modified during gastrointestinal digestion so affect their biological activity. In this study, an in vitro digestion model coupled with Caco-2 monolayer and Caco-2/insulin-resistant HepG2 coculture model were used to study the transport and hypoglycemic effects of phenolics in raw MLs (U-MLs) and solid-fermented MLs (F-MLs). The results of LC-MS/MS analysis showed that the Papp (apparent permeability coefficient, 10 –6 cm/s) of phenolics in digested MLs ranged from 0.002 ± 0.00 (quercetin 3- O -glucoside) to 60.19 ± 0.67 (ferulic acid), indicating higher phenolic acids absorbability and poor flavonoids absorbability. The Papp values of phenolic extracts of F-MLs in Caco-2 monolayer were significantly higher (p > 0.05) than that of U-MLs. Digested phenolic extracts inhibited the activities of sucrase (60.13 ± 2.03%) and maltase (82.35 ± 0.78%) and decreased 9.28 ± 0.84% of glucose uptake in Caco-2 monolayer. Furthermore, a decrease in the mRNA expression of glucose transporters SGLT1 (0.64 ± 0.18), GLUT2 (0.14 ± 0.02) and the sucrase-isomaltase (0.59 ± 0.00) was observed. In Caco-2/insulin-resistant HepG2 co-culture model, phenolic extracts regulated glucose metabolism by up-regulating the mRNA expressions of IRS1 (9.32-fold), Akt (17.07-fold) and GYS2 (1.5-fold), and down-regulating the GSK-3β (0.22-fold), PEPCK (0.49-fold) and FOXO1 (0.10-fold) mRNA levels. Both U-MLs and F-MLs could improve glucose metabolism, and the partial least squares (PLS) analysis showed that luteoforol and p -coumaric acid were the primary phenolics that strongly correlated with the hypoglycemic ability of MLs. Results suggested that phenolics of MLs can be used as dietary supplements to regulate glucose metabolism.
研究领域:
药理学
·
营养学
·
生物化学
·
分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Biology-Basel
·
2024
·Vol. 13
·期 8
·597
·
IF 3.6
Pengyu Wang,Qing Lan,Qi Huang,Ruyi Zhang,Shuo Zhang,Leiming Yang,Yan Song,Tong Wang,Guandi Ma,Xiufen Liu,Xiying Guo,Youzhi Zhang,Chao Liu
Simple SummaryEnd-stage renal disease is mainly caused by diabetic nephropathy, which has a complex pathogenesis and currently has no effective treatment. Schisandrin A has a wide range of pharmacological activities, including antioxidant, apoptosis inhibition, and immune regulation, but its pharmacological mechanism of action on diabetic nephropathy is still unclear. This study aimed to explore the pharmacological mechanism of Schisandrin A in the treatment of diabetic nephropathy using a network pharmacology approach. Through in vivo experiments, hub genes and related signaling pathways were verified based on the results of network analysis. The results showed that Schisandrin A had a protective effect on diabetic nephropathy, EGFR might be a potential therapeutic target, and AKT/GSK-3β might be involved in this process. This will provide a certain theoretical basis for the further clinical application of Schisandrin A in the treatment of diabetic nephropathy.AbstractDiabetic nephropathy (DN) is one of the common complications of diabetes and the main cause of end-stage renal disease (ESRD) in clinical practice. Schisandrin A (Sch A) has multiple pharmacological activities, including inhibiting fibrosis, reducing apoptosis and oxidative stress, and regulating immunity, but its pharmacological mechanism for the treatment of DN is still unclear. In vivo, streptozotocin (STZ) and a high-fat diet were used to induce type 2 diabetic rats, and Sch A was administered for 4 weeks. At the same time, protein–protein interaction (PPI) networks were established to analyze the overlapping genes of DN and Sch A. Subsequently, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to determine the hub pathway. In addition, molecular docking was used to preliminarily verify the affinity of hub proteins and Sch A. Further, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, and western blot analysis were used to detect the location and expression of related proteins in DN. This study revealed the multi-target and multi-pathway characteristics of Sch A in the treatment of DN. First, Sch A could effectively improve glucose tolerance, reduce urine microprotein and urine creatinine levels, and alleviate renal pathological damage in DN rats. Second, EGFR was the hub gene screened in overlapping genes (43) of Sch A (100) and DN (2524). Finally, it was revealed that Sch A could inhibit the protein expression levels of EGFR and PTRF and reduced the expression of apoptosis-related proteins, and this effect was related to the modulation of the AKT/GSK-3β signaling pathway. In summary, Sch A has a protective effect in DN rats, EGFR may be a potential therapeutic target, throughout modulating AKT/GSK-3β pathway.
研究领域:
药理学
·
内分泌学
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肾病学
·
分子生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Fei Gao,Jing Zhao,Ping Liu,Dongsheng Ji,Litao Zhang,Mengxiao Zhang,Yuqin Li,Yuliang Xiao
The purpose of this study was to ascertain the effect of selenium-chondroitin sulfate nanoparticles ( [email protected] ) on multi-target-directed therapy for the treatment of Alzheimer's disease (AD). [email protected] nanoparticles were successfully synthesized, and their therapeutic effects were studied in in vitro AD models. [email protected] effectively inhibited amyloid-β (Aβ) aggregation and protected SH-SY5Y cells from Aβ 1–42 -induced cytotoxicity. Moreover, [email protected] significantly decreased okadaic acid-induced actin cytoskeleton instability in SH-SY5Y cells. In addition, [email protected] decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the levels of glutathione peroxidase (GSH-Px). The Western blot results indicated that [email protected] attenuated the hyperphosphorylation of tau (Ser396/Ser404) by regulating the expression of GSK-3β. In summary, this study demonstrated that [email protected] could inhibit the aggregation of Aβ, reduce damage to the cytoskeleton, mitigate oxidative stress and attenuate the hyperphosphorylation of tau protein. [email protected] might be a potent multi-functional agent for the treatment of AD and thus warrants further research and evaluation.
研究领域:
神经科学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 10
·2306
·
IF 4.2
Danyang Zhang,Xiaoshi He,Ting Wang,Yan Xing,Zhilong Xiu,Yongming Bao,Yuesheng Dong
Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the nervous system. In this study, flavonoids were found to enhance the protective effect of metformin when added at a molar concentration of 0.5%. The structure–activity relationship (SAR) analysis indicated that ortho- substitution in the B ring, and the absence of double bonds between the 2 and 3 position combined with the gallate substitution with R configuration at the 3 position in the C ring played crucial roles in the synergistic effects, which could be beneficial for designing a combination of the compounds. Additionally, the mechanism study revealed that a typical flavonoid, EGCG, enhanced ROS scavenging and anti-apoptotic ability via the BCL2/Bax/Cyto C/Caspase-3 pathway, and synergistically inhibited the expression of GSK-3β, BACE-1, and APP in PC-12 cells when used in combination with metformin. The dose of metformin used in the combination was only 1/4 of the conventional dose when used alone. These results suggested that ROS-mediated apoptosis and the pathways related to amyloid plaques (Aβ) formation can be the targets for the synergistic neuroprotective effects of flavonoids and metformin.
研究领域:
药理学
·
神经科学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）