INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 12
·4126
·
IF 3.687
Guohong Qin,Ji Ma,Qiongshan Huang,Hongli Yin,Jichun Han,Maoru Li,Yang Deng,Bing Wang,Waseem Hassan,Jing Shang
Isoquercetin (IQ), a glucoside derivative of quercetin, has been reported to have beneficial effects in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the potential improvement of IQ in liver lipid accumulation, inflammation, oxidative condition, and activation in Kupffer cells (KCs) on a high-fat diet (HFD) induced NAFLD models. Male Sprague-Dawley (SD) rats were induced by HFD, lipopolysaccharides/free fatty acids (LPS/FFA) induced co-culture cells model between primary hepatocytes and Kupffer cells was used to test the effects and the underlying mechanism of IQ. Molecular docking was performed to predict the potential target of IQ. Significant effects of IQ were found on reduced lipid accumulation, inflammation, and oxidative stress. In addition, AMP-activated protein kinase (AMPK) pathway was activated by IQ, and is plays an important role in lipid regulation. Meanwhile, IQ reversed the increase of activated KCs which caused by lipid overload, and also suppression of Transforming growth factor beta (TGF-β) signaling by TGF-β Recptor-1 and SMAD2/3 signaling. Finally, TGF-βR1 and TGF-βR2 were both found may involve in the mechanism of IQ. IQ can improve hepatic lipid accumulation and decrease inflammation and oxidative stress by its activating AMPK pathway and suppressing TGF-β signaling to alleviate NAFLD.Keywords:isoquercetin;NAFLD;AMPK;TGF-β;Kupffer cell
研究领域:
药理学
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肝病学
·
分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Hua Han,Lu Liu,Jieping Zhang,Meng Zhang,Xinyu Chen,Yuyuan Huang,Wenxiu Ma,Huanlong Qin,Li Shen,Jundong Zhang,Wensheng Yang
Inflammatory bowel disease (IBD), a progressive and unpredictable colorectal inflammatory disease, is a global health problem. Currently, therapeutic strategies for the management of the disease are limited. Results from our previous studies indicated that probiotic Lactobacillus plantarum exhibits therapeutic effects against IBD, and through screening, we obtained an active 61-amino-acid long protein, L. plantarum membrane protein 1 (LpMP-1). Based on druggability-guided strategies, the search for LpMPs with lower molecular weights and better bioactivities contributes to the development of new anti-inflammatory agents to overcome the limitations of existing therapies against IBD. We used amino-acid-truncation strategies to obtain modified LpMPs (LpMP-2 - LpMP-9) using LpMP-1 as the parent template. Furthermore, we systematically evaluated the anti-colitis pharmacodynamics of these LpMPs in terms of symptomatology, histopathology, and cytokine levels in DSS-induced ulcerative colitis mice. Their possible targets of action against IBD was investigated under an iTRAQ-based pharmacoproteomic system and a docking-guided receptor-ligand relationship frame. We found a new active protein, LpMP-8, which had a lower molecular weight than LpMP-1. LpMP-8 was found to exhibit anti-colitis activity following oral administration in vivo (50 μg/kg) by improving symptoms of colitis, colonic ulcerations, and cytokine disorders. TLRs and TGF-β were found to be involved in the action of LpMP-8 against colitis; LpMP-8 was to compete with TLR4-MD2-bound LPS and reverse TGF-β and Smad2/7 disorders. Our probiotic-derived LpMP-8 was shown to elicit oral anti-colitis activity, and its significant efficacy is probably associated with TLR4 and TGF-β.
研究领域:
胃肠病学
·
药理学
·
微生物学
·
免疫学
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DOI
PubMed
高影响因子
Oncology Letters
·
2024
·Vol. 28
·期 3
·1-11
·
IF 2.5
Weimin Hu,Ling Cheng,Jian Zhao,Yonghui Wu,Ying Lin,Jun Yin
Transforming growth factor‑β (TGF‑β) signaling pathway serves a pivotal role in the pathogenesis of colorectal cancer (CRC). However, the specific molecular mechanisms by which the TGF‑β signaling pathway regulates CRC are still not fully understood. In the present study, metabolomics and transcriptomics were used to screen for key metabolites and regulatory genes most related to the regulation of the TGF‑β signaling pathway in CRC. Additionally, reverse transcription‑quantitative PCR, western blotting and Transwell assays were performed to assess the process of epithelial‑mesenchymal transition (EMT). Metabolomics analysis indicated that TGF‑β1 has an impact on purine metabolism, leading to an increase in the purine metabolite inosine. The increase of inosine is essential for facilitating EMT and cell migration in CRC cells. Furthermore, the integrated analysis of metabolomics and transcriptomics data revealed that TGF‑β1 induces the expression of laccase domain‑containing 1 (LACC1), an enzyme involved in the regulation of inosine. Knockdown of LACC1 resulted in a reduction of TGF‑β1‑induced alterations in inosine levels, EMT and cell migration in CRC cells. The results of the present study suggest that the TGF‑β signaling pathway is involved in the regulation of purine metabolism in CRC through the modulation of LACC1 expression. Furthermore, LACC1 appears to influence EMT and cell migration by elevating the levels of the purine metabolite inosine.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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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DOI
PubMed
高影响因子
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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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
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
·
肝病学
·
细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Yuyang Li,Faheem Muhammad,Xiwen Chen,Deao Gu,Wen Li,Jiayi Tang,Mingyue Cheng,Jiang Du,Shuwei Qiao,Yu Deng,Qing Yu,Hui Wei,Leiying Miao
Nanozymes have emerged as promising nanomaterials for the treatment of inflammation-related diseases by eliminating excessive reactive oxide species (ROS) and immunoregulation. However, persistent inflammation invariably causes severe alveolar destruction in periodontitis; and the alleviation of inflammation alone by neglecting the impairment of vascular functions could not effectively realize periodontal regeneration. Herein, a multifunctional copper-ruthenium oxide-based yolk-shell nanozyme (Cu 2 O@RuO 2 , CRNC) is designed to promote effective periodontal regeneration. The ruthenium oxide (RuO 2 ) shell serves to alleviate inflammation by eliminating ROS and triggering macrophage polarization, whereas the cuprous oxide (Cu 2 O) core acts as a responsive Cu 2 + nano-reservoir for promoting angiogenesis and osteogenesis. Results demonstrated that CRNC could activate transforming growth factor β/phosphatidylinositol 3-kinase (TGF-β/PI3K) and hypoxia-inducible factors (HIF-1α) signals, aiding angiogenesis in the human umbilical vein endothelial cells and osteogenesis in periodontal ligament stem cells, respectively. The multifunctional CRNC nanozyme successfully decreased periodontal inflammation and ameliorated alveolar regeneration in a periodontitis model. This study provides promising insights into periodontitis treatment by targeting both angiogenesis and osteogenesis.
研究领域:
牙科学
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纳米医学
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炎症研究
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组织工程
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产品关联
DOI
高影响因子
Advanced Science
·
2026
·
IF 14.1
Peng Dai,Jikuang Zhao,Chang Xue,Kailei Xu,Liang Yong,Zhuangwei Zhang,Yi Huang,Jianwei Shuai,Xianzhen Chen,Sheng Nie,Junpeng Xu
Parkinson's disease (PD) is characterized by progressive dopaminergic neuron loss compounded by oxidative stress and neuroinflammation within a self‐perpetuating pathological brain microenvironment. Here, we report a bioactive injectable self‐healing hydrogel (COPRP) constructed by crosslinking oxidized Polygonati rhizoma polysaccharide (OPRP) with carboxymethyl chitosan via dynamic Schiff base linkages. OPRP is structurally identified as an inulin neoseries‐type fructan with relevance to TGF‐β/Smad pathway regulation. Without levodopa loading, COPRP reduced ROS accumulation and M1‐associated inflammatory markers in LPS‐stimulated microglia. It also improved cell viability, preserved mitochondrial membrane potential, and maintained TH expression in 6‐OHDA‐challenged SH‐SY5Y cells, supporting the intrinsic bioactivity of the hydrogel matrix. In a 6‐OHDA rat PD model, COPRP significantly ameliorated motor deficits and preserved TH‐positive neurons. Incorporating levodopa into COPRP creates a dual‐mechanism platform combining active microenvironmental remodeling with passive dopaminergic supplementation. Proteomic analysis, corroborated by western blotting, identified the TGF‐β/Smad signaling axis as the principal mechanistic mediator. Pharmacological intervention with pirfenidone attenuated TGF‐β2/Smad2/3 activation and partially reduced the behavioral and neuroprotective effects associated with COPRP, supporting the functional involvement of this pathway. This work delineates how a defined polysaccharide structure modulates the intracranial pathological microenvironment, offering insights for the rational design of bioactive biomaterials targeting neurodegenerative disease. An injectable, self‐healing COPRP hydrogel integrates structurally defined oxidized Polygonati rhizoma polysaccharide with carboxymethyl chitosan through dynamic Schiff‐base crosslinking. The bioactive matrix scavenges reactive oxygen species, suppresses neuroinflammation, protects dopaminergic neurons, and supports sustained levodopa release. Its therapeutic effects involve functional activation of TGF‐β2/Smad2/3 signaling within the Parkinsonian brain microenvironment. This design couples intrinsic biomaterial activity with complementary dopaminergic supplementation.
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DOI
PubMed
高影响因子
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
·
药学
·
生物医学工程
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DOI
PubMed
高影响因子
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
·
药学
·
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
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
·
皮肤科学
·
生物医学工程
·
化妆品科学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
·
2021
·Vol. 100
·期 2
·
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
·
细胞生物学
·
糖尿病研究
·
眼科学
✓ 已验证
DOI
PubMed
高影响因子
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