Biomaterials Science
·
2019
·Vol. 8
·期 1
·201-211
·
IF 5.251
Shuli Man,Miao Li,Jin Zhou,Haiyue Wang,Jinyan Zhang,Long Ma
Fe3O4 magnetic nanoparticles (MNPs), as one of the most intensively researched NPs, have a range of applications in cancer treatments. In current research, we have focused on the influences of MNPs on cancer cells. We chose polyethyleneimine (PEI) coated MNPs (PEI-MNPs) as a model and they are colloidally stable in biological media. It can be proved that PEI-MNPs result in autophagy induction via mTOR-Akt-p70S6 K and ATG7 signaling pathways. For the first time, we have reported that PEI-MNPs activate both NF-κB and TGF-β signaling, two key pro-inflammatory pathways, in cancer cells. More significantly, we have found that autophagy induction and NF-κB and TGF-β activation can be efficiently suppressed through the inhibition of PEI-MNP dependent reactive oxygen species (ROS) over-production. ROS are deemed as a ‘double edge sword’ for cancer cells, owing to the cancer-suppressing and cancer-promoting actions. Our findings would be useful for designing MNPs induced ROS anti-cancer strategies or diminishing long-term toxic effects.
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INTERNATIONAL JOURNAL OF CARDIOLOGY
·
2024
·
IF 3.2
Zihan Wei,Ying Lu,Cheng Qian,Jing Li
Background Atrial fibrosis is associated with the pathogenesis of atrial fibrillation (AF). This study aims to discuss the function of circ_0079480 in atrial fibrosis and its underlying mechanism. Methods In vitro and in vivo models of atrial fibrosis were established by using angiotensin II (Ang II) to treat human atrial fibroblasts (HAFs) and C57/B6J mice. qRT-PCR and western blot were used to examine the mRNA and protein expression levels. CCK-8, EdU, cell strach, and transwell assays were performed to determine the proliferation and migration of HAFs. Dual-luciferase reporter and RIP/RNA pull-down assays were explored to identify the interaction of miR-338-3p and circ_0079480/THBS1. HE and Masson's trichrome staining experiments were performed to analyze the histopathological change in mice atrial tissues. Results Circ_0079480 expression was increased in AF patients' atrial tissues and Ang II-treated HAFs. Silencing circ_0079480 inhibited cell proliferation and migration and reduced fibrosis-associated gene expression in Ang II-treated HAFs. Circ_0079480 could target miR-338-3p to repress its expression. MiR-338-3p inhibitor blocked the inhibitory effects of circ_0079480 knockdown on HAFs proliferation, migration, and fibrosis. Thrombospondin-1 (THBS1) was confirmed as a downstream target of miR-338-3p, and circ_0079480 could sponge miR-338-3p to upregulate THBS1 expression. Moreover, silencing THBS1 suppressed Ang II-induced proliferation, migration, and fibrosis in HAFs. More importantly, depletion of circ_0079480 inactivated the THBS1/TGF-β1/Smad3 signaling by upregulating miR-338-3p. Mice experiments also confirmed the suppression of circ_0079480 knockdown on atrial fibrosis. Conclusion Circ_0079480 acts as a sponge of miR-338-3p to upregulate THBS1 expression and activate the TGF-β1/Smad3 signaling, finally promoting Ang II-induced atrial fibrosis.
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BIOMATERIALS
·
2025
·
IF 12.9
Wenbo Wu,Zhangrong Cheng,Pengzhi Shi,Haiyang Gao,Yuhang Chen,Anran Zhang,Xianglong Chen,Wang Wu,Yukun Zhang
The progression of intervertebral disc degeneration (IDD) is closely linked to the aging of nucleus pulposus cells (NPCs) caused by oxidative stress and abnormalities in the extracellular matrix (ECM). This study presents an ultrasound-responsive, temperature-sensitive piezoelectric hydrogel (TT@P-Gel) that enables dual therapy combining electrical stimulation (ES) and controlled drug release, achieved by incorporating pyrrole/barium titanate nanoparticles (PB NPs) loaded with tannic acid (TA) and transforming growth factor-β (TGF-β). Experiments have demonstrated that TT@P-Gel can initiate the electrically controlled release of TGF-β and facilitate the gradual release of TA to neutralize reactive oxygen species (ROS) via ultrasound in vitro, while decreasing β-galactosidase expression and restoring the mitochondrial membrane potential ΔΨm in senescent NPCs. Under ultrasound stimulation (US), TT@P-Gel via ES activated the AMPK-FOXO1a signaling pathway and promoted FOXO1a nuclear translocation. Additionally, ES and TA released from the hydrogel enhance SIRT1 expression, which stabilizes nuclear FOXO1a through deacetylation, thereby regulating the expression of downstream genes. Furthermore, TT@P-Gel stimulated the BNIP3-PINK1-Parkin pathway via FOXO1a to augment mitochondrial autophagy, eliminate defective mitochondria, and counteract TBHP-induced cellular senescence. In vivo investigations indicated that TT@P-Gel, in conjunction with ultrasound, markedly enhanced the disc height index and Pfirrmann score while diminishing the expression of p16/p21, a marker of senescence, in a rat model of intervertebral disc degeneration. This study introduces an "electro-chemical synergy" strategy to modulate energy metabolism and mitochondrial autophagy in senescent cells under oxidative stress, utilizing an ultrasound-responsive piezoelectric hydrogel, thereby offering a novel approach for the repair and treatment of intervertebral disc degeneration.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 7
·956-968
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IF 2.571
Wang Youpeng,Jing Weichao,Qu Wanying,Liu Zhiwei,Zhang Di,Qi Xiaoyu,Liu Lujia
ObjectivesThe aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms.MethodsAllergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin.Key findingsHigh dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-β1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase β (p-IKKβ) and NF-κB.ConclusionsTectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-β1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.
研究领域:
药理学
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免疫学
·
呼吸医学
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INFLAMMATION
·
2019
·Vol. 42
·期 5
·1705-1718
·
IF 2.939
Chen Jing,Zhan Changsheng,Zhang Li,Zhang Ligang,Liu Yi,Zhang Yong,Du Hexi,Liang Chaozhao,Chen Xianguo
Treg cells are crucial for maintaining immune homeostasis in CP/CPPS, but the molecular mechanisms underlying the modulation of the function of Treg in CP/CPPS remain unclear. The main purpose of this study is to investigate the relationship between immunosuppressive function of Treg and the methylation level of Foxp3 promoter in experimental autoimmune prostatitis (EAP) mouse model. EAP model was induced by subcutaneous injecting prostate-steroid-binding protein (PSBP) and complete Freund’s adjuvant with NOD mice. Histological analysis revealed that EAP model was successfully induced. The expression of IFN-γ was increased, and TGF-β was decreased in the serum of EAP, respectively. The percentage of Tregs in splenic lymphocyte was increased in EAP. The suppressive ability of Tregs on Teffs was impaired in EAP. The methylation level of Foxp3 promoter was increased, and the expression of Foxp3 was decreased in EAP. By injection AZA which was DNA-methylation inhibitor into EAP mice, prostate inflammation was alleviated, expressions of TGF-β and Foxp3 were increased, and the suppressive function of Tregs was improved in vitro and in vivo . Thus, we concluded that aberrant increased methylation of Foxp3 promoter in Treg cells leads to the impaired suppressive function of Treg cells, exacerbating autoimmune inflammatory injury in EAP.
研究领域:
免疫学
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分子生物学
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自身免疫疾病
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表观遗传学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Yu-Chen Jiang,Jia-Yi Dou,Mei-Yan Xuan,Chong Gao,Zhao-Xu Li,Li-Hua Lian,Zhen-Yu Cui,Ji-Xing Nan,Yan-Ling Wu
Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-β and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial–mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.
研究领域:
药理学
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肝病学
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细胞生物学
·
分子生物学
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ADVANCED MATERIALS
·
2024
·
IF 27.4
Ying Kong,Xu Chen,Feng Liu,Jiageng Tang,Yijing Zhang,Xiangxiang Zhang,Luyao Zhang,Tong Zhang,Yaqi Wang,Mengxiao Su,Qixin Zhang,Hanxiang Chen,Di Zhou,Fan Yi,Hong Liu,Yi Fu
As a central metabolic molecule, nicotinamide adenine dinucleotide (NAD + ) can potentially treat acute kidney injury (AKI) and chronic kidney disease (CKD); however, its bioavailability is poor due to short half-life, instability, the deficiency of targeting, and difficulties in transmembrane transport. Here we designed a physiologically adaptive gallic acid-NAD + nanoparticle, that had ultrasmall size and pH-responsiveness, passed through the glomerular filtration membrane to reach injured renal tubules, and efficiently delivered NAD + into the kidneys. With an effective accumulation in the kidneys, it restored renal function, immune microenvironment homeostasis, and mitochondrial homeostasis of AKI mice via the NAD + -Sirt1 axis, and exerted strong antifibrotic effects on the AKI-to-CKD transition by inhibiting TGF-β signaling. It also exhibited excellent stability, biodegradable, and biocompatible properties, ensuring its long-term safety, practicality, and clinical translational feasibility. The present study shows a potential modality of mitochondrial repair and immunomodulation through nanoagents for the efficient and safe treatment of AKI and CKD. This article is protected by copyright. All rights reserved
研究领域:
肾病学
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药学
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生物医学工程
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分子生物学
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NEW JOURNAL OF CHEMISTRY
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2025
·
IF 2.5
Yi Yang,Bei Tian,Xinyu Tian,Linyan Yao,Jianxi Xiao
Excessive ultraviolet radiation is one of the most common external factors causing skin photoaging, which leads to collagen degradation, wrinkle formation, pigmentation, and is even associated with skin disorders such as seborrheic keratosis and skin tumors. Although various strategies have been developed to treat photoaging skin; however, they suffer from poor stability, risk of allergic reactions, and prolonged recovery periods. In this study, we develop a novel highly stable and bioactive yak type I collagen-based hydrogels dressing to promote the rejuvenation of photoaged skin. The YIC gel demonstrated excellent stability over a six-month period, and maintained the intact triple-helical structure of collagen. It also displayed shear-thinning behavior and notable ductility. In vitro cell experiments confirmed its favorable biocompatibility and bioactivity.Non-invasive Combo evaluations demonstrated the remarkable ability of YIC gel to restore dermal density, elasticity, hydration, and transepidermal water loss to healthy levels, surpassing the efficacy of the commercial product. Histological analysis revealed YIC gel significantly reduced epidermal thickness, promoted the deposition and regeneration of collagen, demonstrating greater efficacy than the commercial product. Antioxidant indicators further highlighted the antioxidant properties of YIC gel, including reduced MDA content, increased SOD activity and GSH content. Immunofluorescence staining suggested that the YIC gel may enhance collagen synthesis through modulation of the TGF-β/Smad signaling pathway. This YIC gel offers valuable insights into its protective effects against skin photoaging and highlights its promising applications in cosmetic formulations.
研究领域:
生物材料
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皮肤科学
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生物医学工程
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化妆品科学
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分子生物学
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iScience
·
2023
·
IF 5.8
Yi Lin,Wangdu Luo,Bingcai Jiang,Qianyi Lin,Min Tang,Xiangji Li,Lin Xie
Excessive scarring is the main cause of surgical failure in glaucoma filtration surgery. S58 has been shown to have an excellent antifibrotic effect but its duration of action is not sufficient to achieve the desired antiscarring effect. In this study, a light-cured bioadhesive hydrogel composed of GelMA and oxidized dextran (ODex), namely, GelDex, was used to load S58 (GelDex-S58). The microscopic morphology of GelDex-S58 appeared to be a porous structure with good slow-release properties and suitable degradation time. Cell Counting Kit-8, cell scratch and transwell assays showed that GelDex-S58 significantly reduced TGF-β-induced fibroblast proliferation, increased migration and invasion ability. In in vivo studies, GelDex-S58 treatment prolonged follicular retention, reduced mean intraocular pressure, and significantly reduced collagen deposition and α-SMA expression levels in the conjunctival tissue compared to treatment with S58 alone. In conclusion, GelDex-S58 could reduce scar formation after glaucoma filtration surgery.
研究领域:
眼科
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药学
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生物医学工程
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CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
·
2021
·Vol. 100
·期 2
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IF 2.273
Haijing Wang,Zhuolei Feng,Xue Han,Yue Xing,Xiaomei Zhang
The endothelial-mesenchymal transition (EndMT) participates in the progression of diabetic retinopathy (DR), but cell-intrinsic factors modulating this process remain elusive. In this study, we explored the role of lysophosphatidic acid (LPA) – producing enzyme, acylglycerol kinase (AGK), in the EndMT of human retinal microvascular endothelial cells (HRECs) under high-glucose (HG) conditions. We found that AGK was significantly elevated in HG-treated cells. In addition, AGK knockdown reversed the HG-induced EndMT in HRECs, which was evidenced by the increased endothelial markers (CD31 and VE-cadherin) and decreased mesenchymal markers (FSP1 and α-SMA). Furthermore, downregulation of AGK inhibited the HG-induced activation of transforming growth factor β (TGF-β)/Notch pathways, whereas exogenous TGF-β1 (10 ng/mL) impeded the inhibitory effects of AGK knockdown on HG-induced EndMT in HRECs. Additionally, the silencing of AGK abolished the HG-induced upregulation of LPA and its receptor, LPA receptor 1 (LPAR1), and overexpression of LPAR1 further rescued the AGK knockdown-mediated inhibition of the EndMT process. In conclusion, we demonstrate that downregulation of AGK suppresses HG-induced EndMT in HRECs through regulating the LPAR1/TGF-β/Notch signaling pathway, indicating that AGK might be a potential therapeutic target for the treatment of DR.
研究领域:
分子生物学
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细胞生物学
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糖尿病研究
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眼科学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 7
·6172
·
IF 5.6
Tianxiao Sun,Haihua Li,Yan Zhang,Guixin Xiong,Yuerun Liang,Fang Lu,Rong Zheng,Qi Zou,Jiejie Hao
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by lung inflammation and excessive deposition of extracellular matrix components. Transforming growth factor-β1 (TGF-β1) induced epithelial–mesenchymal transformation of type 2 lung epithelial cells leads to excessive extracellular matrix deposition, which plays an important role in fibrosis. Our objective was to evaluate the effects of 3-cyclopropylmethoxy-4-(difluoromethoxy) benzoic acid (DGM) on pulmonary fibrosis and aimed to determine whether EMT plays a key role in the pathogenesis of pulmonary fibrosis and whether EMT can be used as a therapeutic target for DGM therapy to reduce IPF. Firstly, stimulation of in vitro cultured A549 cells to construct EMTs with TGF-β1. DGM treatment inhibited the expression of proteins such as α-SMA, vimentin, and collagen Ⅰ and increased the expression of E-cadherin. Accordingly, Smad2/3 phosphorylation levels were significantly reduced by DGM treatment. Secondly, models of tracheal instillation of bleomycin and DGM were used to treat rats to demonstrate their therapeutic effects, such as improving lung function, reducing lung inflammation and fibrosis, reducing collagen deposition, and reducing the expression of E-cadherin. In conclusion, DGM attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in rats.Keywords:IPF;A549;EMT;TGF-β1/Smad;ECM
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Cell and Bioscience
·
2019
·Vol. 9
·期 1
·1-15
·
IF 3.355
Tan Jianxin,Wang Yajun,Wang Siliang,Wu Simeng,Yuan Zhe,Zhu Xike
Background Adipocyte accumulation is a predominant feature of age-related thymic involution, but the mechanisms responsible for thymic adipogenesis remain to be elucidated. The aim of this study was to identify key regulators in thymic adipogenesis. We used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation of OP9-DL1 cells, and investigated the differentially expressed proteins during adipogenic differentiation by using label-free quantitative proteomics. Furthermore, the effects of transforming growth factor β1 (TGF-β1) on rosiglitazone-induced adipogenic differentiation of OP9-DL1 cells as well as the underlying mechanisms were also investigated. Results Proteomic analysis identified 139 proteins differed significantly in rosiglitazone-treated cells compared with dimethyl sulphoxide (DMSO)-treated cells. Rosiglitazone-induced adipogenic differentiation was inhibited by TGF-β1 treatment in OP9-DL1 cells and primary thymic stromal cells. Real-time PCR analysis showed significant increases in PPARγ and fatty acid binding protein 4 mRNA levels in rosiglitazone-treated cells, which were inhibited by TGF-β1 treatment. TGF-β1 down-regulated PPARγ expression at both mRNA and protein levels in OP9-DL1 cells. Chromatin immunoprecipitation analysis demonstrated that TGF-β1 enhanced the binding of Smad2/3 and histone deacetylase 1, but reduced the binding of H3K14ac to the promoter of PPARγ gene. TGF-β1 partially reversed the inhibitory effects of rosiglitazone on the expression of Axin2 and β-catenin protein levels. TGF-β1 inhibited rosiglitazone-induced adipogenic transformation in OP9-DL1 cells by down-regulation of PPARγ and activation of the canonical Wnt/β-catenin signaling pathway. Conclusion Taken together, activation of TGF-β pathway may serve as a useful strategy to prevent thymic adiposity in age-related thymic involution.
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