BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Tian Lan,Lihang Zhuang,Shengwen Li,Guizhi Yang,Yuanyuan Xuan,Jiao Guo
Sphingosine kinase 1 (SphK1) plays critical roles in the activation of hepatic stellate cells (HSCs) and liver fibrosis. Our previous study found that polydatin ameliorates chronic liver injury and fibrosis by inhibiting oxidative stress. However, whether polydatin exerts an anti-fibrotic effect on liver fibrosis dependent on SphK1 signaling is unknown. We aimed to investigate the role of polydatin in SphK1, which mediates HSC activation and liver fibrosis. C57BL/6 mice were induced using CCl 4 5 μL g −1 i.p. twice a week for 6 weeks and treated with or without polydatin. Human immortalized HSC line (LX-2) was induced using platelet-derived growth factor-BB (PDGF-BB) or adenovirus-SphK1 and treated with polydatin. Hepatic macrophage filtration, collagen deposition, expression of α-smooth muscle, active caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were markedly increased in mice induced by CCl 4 for 6 weeks. In contrast, polydatin attenuated collagen synthesis and hepatocyte apoptosis. Furthermore, polydatin exhibited significant anti-proliferative activity against PDGF-BB-induced activated hepatic stellate cells (HSCs). SphK1 was strongly induced in mice exposed to CCl 4 , whereas its expression and activity were inhibited by polydatin treatment. Finally, SphK1 overexpression in LX-2 cells promoted proliferation of activated HSCs, which could not be reversed by polydatin treatment. These results demonstrate that polydatin attenuates HSC proliferation and activation through inhibition of SphK1 signaling, contributing to the suppression of liver fibrosis.
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高影响因子
LABORATORY INVESTIGATION
·
2019
·Vol. 100
·期 3
·378-386
·
IF 3.684
Lang Ping-Ping,Bai Jie,Zhang Yun-Long,Yang Xiao-Lei,Xia Yun-Long,Lin Qiu-Yue,Li Hui-Hua
Monocyte and adhesion infiltration into the arterial subendothelium are initial steps in hypertension development. The endothelial intercellular adhesion molecule-1 (ICAM-1) has been implicated in the recruitment and adhesion of leukocytes in several cardiac diseases. However, the role of ICAM-1 in angiotensin II (Ang II)-induced hypertension development remains unknown. Hypertension was induced by administering an infusion of Ang II (1000 ng/kg/min) to wild-type (WT) mice treated with an IgG control or ICAM-1 neutralizing antibody (1 and 2 mg/mouse/day, respectively). Blood pressure was determined using the tail-cuff system. Vascular remodeling was assessed by performing a histological examination. Inflammation and reactive oxygen species (ROS) levels were determined by using immunostaining. Vascular dysfunction was assessed by aortic ring assay. The expression of fibrotic markers, cytokines and NOX was evaluated by quantitative real-time PCR analysis. Our results demonstrate that Ang II infusion markedly increased the ICAM-1 level in the aorta. Blocking ICAM-1 with a neutralizing antibody significantly attenuated Ang II-induced arterial hypertension, vascular hypertrophy, fibrosis, macrophage infiltration, and ROS production and improved vascular relaxation. In conclusion, ICAM-1-mediated monocyte adhesion and migration play a critical role in Ang II-induced arterial hypertension and vascular dysfunction. ICAM-1 inhibitors may represent a new therapeutic strategy for the treatment of this disease.
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npj Regenerative Medicine
·
2023
·Vol. 8
·期 1
·1-17
·
IF 7.2
Zhao Chuanrong,Yang Qianru,Tang Runze,Li Wang,Wang Jin,Yang Fangfang,Zhao Jianan,Zhu Juanjuan,Pang Wei,Li Ning,Zhang Xu,Tian Xiao Yu,Yao Weijuan,Zhou Jing
Healing of the cutaneous wound requires macrophage recruitment at the sites of injury, where chemotactic migration of macrophages toward the wound is regulated by local inflammation. Recent studies suggest a positive contribution of DNA methyltransferase 1 (Dnmt1) to macrophage pro-informatory responses; however, its role in regulating macrophage motility remains unknown. In this study, myeloid-specific depletion of Dnmt1 in mice promoted cutaneous wound healing and de-suppressed the lipopolysaccharides (LPS)-inhibited macrophage motility. Dnmt1 inhibition in macrophages eliminated the LPS-stimulated changes in cellular mechanical properties in terms of elasticity and viscoelasticity. LPS increased the cellular accumulation of cholesterol in a Dnmt1-depedent manner; cholesterol content determined cellular stiffness and motility. Lipidomic analysis indicated that Dnmt1 inhibition altered the cellular lipid homeostasis, probably through down-regulating the expression of cluster of differentiation 36 CD36 (facilitating lipid influx) and up-regulating the expression of ATP-binding cassette transporter ABCA1 (mediating lipid efflux) and sterol O-acyltransferase 1 SOAT1 (also named ACAT1, catalyzing the esterification of cholesterol). Our study revealed a Dnmt1-dependent epigenetic mechanism in the control of macrophage mechanical properties and the related chemotactic motility, indicating Dnmt1 as both a marker of diseases and a potential target of therapeutic intervention for wound healing.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Wei Sun,Jing Liu,Renhao Zhao,Teng Yang,Zhichen Zheng,Tongyu Zhang,Guofeng Wang
Background and Purpose: To investigate the biological role of interferon α/β receptor 2 (IFNAR2) in type 1 diabetes (T1D). Methods First, IFNAR2 mRNA and protein expression levels in serum of T1D patients and healthy controls were detected by RT-qPCR and Western blot . For experimental studies, 80 male C57BL/6 mice were randomly divided into 4 groups with 20 mice in each group: the control group, the T1D group, the T1D + ad-con group and the T1D + ad-si-IFNAR2 group. The T1D mouse model was generated by multiple intraperitoneal injections of small doses of streptozotocin (STZ). Body weight and blood glucose levels were measured weekly until 6 weeks. After 6 weeks, all mice were sacrificed and the levels of insulin (Ins), tumor necrosis factor α (TNF-α), interleukin 4 (IL-4), IL-6, and type I interferon γ (IFN-γ), IFNAR2 protein expression, the number of dendritic cells (DCs), and changes in islet β cells were assessed. Results IFNAR2 mRNA and protein expression levels in serum of T1D patients were significantly higher than those in healthy controls ( P < 0.05). Furthermore, IFNAR2 protein expression, number of DCs, and IFNAR2 mRNA, blood glucose, TNF-α, and IFN-γ levels were significantly upregulated in T1D mice compared with the control group ( P < 0.05), while weight, and Ins, IL-6, and IL-4 levels were decreased ( P < 0.05). However, knockdown of IFNAR2 reversed these trends. There was no significant difference in markers between the T1D + ad-con group and the T1D group ( P > 0.05). Conclusions Knockdown of IFNAR2 reduced the inflammatory response and improved islet function of T1D mice.
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高影响因子
Translational Cancer Research
·
2025
·Vol. 14
·期 11
·7641
·
IF 1.7
Yuan Cheng,Liu Ruiwen,Xu Xinming,Sun Jun,Zhu Yi,Lu Rongzhu,Liu Yueyu,Chen Jian
Background Because of the high malignancy and subtle early symptoms of hepatocellular carcinoma (HCC), most patients lose the opportunity for surgery and opt for drug therapy. However, the current drugs for HCC treatment remain suboptimal, underscoring the urgent need to develop a novel anti-HCC agent. Curcumin is a natural chemical compound that has anti-cancer effects on various tumor cells, attracting sustained attention from researchers and clinicians. The present study aims to further elucidate curcumin’s anti-HCC mechanisms, thereby offering a promising therapeutic candidate for HCC patients. Methods The viability of HCC cells was evaluated by Cell Counting Kit-8 (CCK-8) assay. The levels of glutathione (GSH), malondialdehyde (MDA), and total iron in the cells were detected by biochemical kits. The levels of reactive oxygen species (ROS) and Fe 2+ in the cells were detected by fluorescent probes. The protein expressions of protein kinase RNA-like endoplasmic reticulum kinase (PERK), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) in the cells were detected by western blotting. Results Curcumin exerted a notably suppressive impact on HCC cells, which could be reversed by ferrostatin-1 (Fer-1) and desferrioxamine (DFO). By detecting cellular metabolic products, we observed an increase in total iron, Fe 2+ , MDA, ROS, and a reduction in GSH levels in HCC cells after treatment with curcumin, and these effects could be attenuated by Fer-1. Western blot analysis showed that curcumin significantly downregulated GPX4 levels in HCC cells while upregulating PERK, Nrf2 and HO-1 expression. Additionally, using PERK inhibitor, HO-1 inhibitor, and endoplasmic reticulum (ER) stress inhibitor could partially reverse the inhibition of HCC cells viability by curcumin and alleviate the reduction of GPX4 expression caused by curcumin. Conclusions Curcumin may induce ferroptosis in HCC cells through the PERK/Nrf2/HO-1 signaling pathway, thereby exerting its anti-cancer effects, suggesting that curcumin could potentially be used as a drug for treating HCC.
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Kidney360
·
2025
·
IF 3
Li Jiachang,Ma Yuhan,Wang Yanni,Chen Yizhi,Wei JiaLi
Plain Language Summary Background: Hyperuricemia is a common metabolic disorder and a risk factor for multiple diseases, including CKD. Hyperuricemic nephropathy (HN) affects many individuals with hyperuricemia, yet its molecular mechanisms are not fully understood, and effective treatments are lacking. Methods: In vitro, human tubular epithelial cells (HK-2) were exposed to uric acid for 36 hours, followed by transfection with microRNA mimic or FIH-1 siRNA. In vivo, HN was induced in mice using potassium oxonate (PO) and adenine (Ad) for two weeks. miR-295 mimic or anti-miR-295 was administered via tail vein injection, and mice were sacrificed for analysis. Results: We demonstrated a significant increase of miR-295 in renal tubular cells in HN mice. Hyperuricemia led to the activation of hypoxia inducible factor-1α (HIF-1α), and inhibition of HIF-1α by YC-1 (a HIF-1α inhibitor) prevented the increase of miR-295. ChIP assay further verified HIF-1α binding to the miR-295 gene promoter directly. Functionally, Inhibition of miR-295 led to increased cell death and tubulointerstitial fibrosis in HN mice, whereas supplementation of miR-295 mimic had kidney protective effects in this model. miR-295 suppressed the expression of factor inhibiting hypoxia-inducible factor-1 (FIH-1) in both in vitro and in vivo models of HN. Luciferase microRNA target reporter assay further verified FIH-1 as a direct target of miR-295.In addition, knockdown of FIH-1 inhibits tubular cell apoptosis and profibrotic cytokines production in HK2 cells during uric acid treatment. Conclusions: This study reveals a HIF-1α/miR-295/FIH-1 positive feedback loop that regulates tubular damage and fibrosis in HN. Plain Language Summary This study explores the molecular mechanisms of hyperuricemic nephropathy (HN), a kidney condition linked to high uric acid levels. Researchers found that in mice with HN, the microRNA miR-295 increased in kidney cells. The study identified a feedback loop involving miR-295, HIF-1α, and FIH-1, where HIF-1α activates miR-295, which then suppresses FIH-1. Inhibition of miR-295 led to increased cell death and fibrosis, while supplementation with miR-295 mimic had protective effects against kidney damage. Inhibiting HIF-1α prevented miR-295 increase. These findings suggest potential therapeutic targets for treating HN by modulating this molecular pathway. Text is machine generated and may contain inaccuracies. FAQ
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高影响因子
CANCER LETTERS
·
2017
·
IF 6.375
Weishan Zhuge,Ruijie Chen,Katanaev Vladimir,Xidan Dong,Khan Zia,Xiangwei Sun,Xuanxuan Dai,Miao Bao,Xian Shen,Guang Liang
Colon cancer is one of the leading causes of cancer-related deaths. A natural sesquiterpene lactone, costunolide (CTD), showed inhibition of cancer development. However, the underlying mechanisms are not known. Here, we have examined the therapeutic activity and novel mechanisms of the anti-cancer activities of CTD in colon cancer cells. Using SPR analysis and enzyme activity assay on recombinant TrxR1 protein, our results show that CTD directly binds and inhibits the activity of TrxR1, which caused enhanced generation of ROS and led to ROS-dependent endoplasmic reticulum stress and cell apoptosis in colon cancer cells. Overexpression of TrxR1 in HCT116 cells reversed CTD-induced cell apoptosis and ROS increase. CTD treatment of mice implanted with colon cancer cells showed tumor growth inhibition and reduced TrxR1 activity and ROS level. In addition, it was observed that TrxR1 was significantly up-regulated in existing colon cancer gene database and clinically obtained colon cancer tissues. Our studies have uncovered the mechanism underlying the biological activity of CTD in colon cancer and suggest that targeting TrxR1 may prove to be beneficial as a treatment option.
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CERAMICS INTERNATIONAL
·
2025
·Vol. 51
·期 30
·65414-65421
·
IF 5.6
Mingyang Chen,Juanjuan Wang,Biao Chen,Fusheng Lai,Zhanhui Peng,Xiaolian Chao,Yanmin Jia
Various industrial dye wastewaters are difficult to treat and have resulted in serious environmental problems. The recent tribocatalytic technology, which degrades dyes by harvesting friction energy, has brought great hope. The ferroelectric property is helpful for enhancing charge transfer and storage, which is expected to result in the strong tribocatalytic performance for dye wastewater treatment. In this study, (1- x )Bi 0.5 Na 0.5 TiO 3 - x SrTiO 3 (abbreviated as (1- x )BNT- x ST, x = 0.2, 0.25, 0.3, 0.35, 0.4) particles are produced employing the traditional solid-state sintering technique. It is found that the 0.7BNT-0.3ST powder catalyst can behave has the maximum tribocatalytic performance with a 96 % degradation ratio for Rhodamine B (RhB) dyes after being stirred for 3.5h. The experiments demonstrate that these primary active substances during the catalytic process are ⋅OH and h + . The 0.7BNT-0.3ST has excellent ferroelectric properties and high dielectric constant, which may contribute to the excellent tribocatalytic performance. Furthermore, degradation ratio of RhB dye by 0.7BNT-0.3ST powder can still reach 89 % after three cycles. The ferroelectric 0.7BNT-0.3ST powder, with its advantages of excellent catalytic performance, simple synthesis route, and low cost, is an ideal option for the water purification by harvesting the friction energy has potential application prospects.
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Foods
·
2025
·Vol. 14
·期 24
·4323
·
IF 5.1
Yazhen Liu,Jiaqi Huang,Ji Yu,Luxin Fu,Ronglong Huang,Jing Liu,Bailin Deng,You-Bao Zhong,Duanyong Liu,Haimei Zhao
(1) Background: Ulcerative colitis (UC) is a persistent inflammatory condition of the intestine, characterized by dysregulated T cell-mediated immune responses. Curcumin (CUR), a common food additive and health supplement, is noted for possessing anti-inflammatory and immunomodulatory properties. Nevertheless, the molecular mechanisms underlying its therapeutic effects remain incompletely elucidated. This research aims to investigate the therapeutic mechanisms of CUR in UC, focusing on its role in restoring T cell homeostasis by modulating TIGIT and Neuropilin-1 (NRP1). (2) Methods: We employed a DSS-induced murine colitis model, combined with network pharmacology, molecular docking, protein–protein interaction docking, molecular dynamics simulations, andinvitroassays with Jurkat T cells. (3) Results: CUR markedly ameliorated clinical manifestations and histopathology in DSS-treated mice, restoring the balance of T cell and memory T cell subsets. Computational predictions and experimental validation showed that CUR downregulated TIGIT and NRP1 expression in inflamed colonic tissue and directly inhibited their expression in activated T cellsinvitro. (4) Conclusions: This study reveals a novel immunoregulatory mechanism of this natural compound. These findings suggest CUR modulates TIGIT/NRP1 to inhibit excessive T cell activation and restore immune homeostasis in UC.
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高影响因子
MATERIALS SCIENCE FORUM
·
2019
·
IF 0
Zhi Min Ou,Jia Ying Pan
In this study, magnetic chitosan microspheres (Fe3O4-CTS) were prepared via chemical co-precipitation and cross-linked with lipase using glutaraldehyde to form Fe3O4-CTS-glutaraldehyde-lipase particles. The textural characteristics of Fe3O4-CTS-glutaraldehyde-lipase particles were assessed by scanning electron microscopy. The optimal immobilization conditions were 2.1 mg/mL lipase, 10 mg/mL Fe3O4-CTS-glutaraldehyde, pH 7.5, 30 °C, 2 h. The loading amount of lipase was 126.0 mg/g carrier, and the specific activity reached to 46.7 U/mg. Fe3O4-CTS-glutaraldehyde-lipase particles was used in resolution of racemic 1-phenylethylamine in a solvent-free system. The conversion and enantiomeric excess of (R)-N-(1-phenylethyl)acetamide reached 33.6% and 97%.
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JOURNAL OF COORDINATION CHEMISTRY
·
2012
·
IF 1.547
Li Zhang,Xiu-Ling Wu,An-Qi Wang,Fei Qin,Da-Wei Meng,Xiao-Yang Liu
A manganese(II) coordination polymer [Mn(TMB)2 · H2O]
n
(1) (HTMB = 3,4,5-trimethoxybenzoic acid) has been synthesized under hydrothermal conditions and characterized by single-crystal X-ray diffraction, elemental analysis, powder X-ray diffraction analysis, spectroscopic (IR, solid state UV-Vis), and thermal methods. The crystal belongs to orthorhombic system, space group P212121, with cell parameters a = 7.3001(8), b = 11.4146(13), c = 27.053(3) Å, α = β = γ = 90°, V = 2254.3(4) Å3, Z = 4. In 1, TMB in two different coordination modes bridges six-coordinate manganese(II) centers forming a 1-D infinite chain coordination framework. The spectral and thermal properties of the complexes have also been studied.
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高影响因子
RSC Advances
·
2015
·Vol. 6
·期 4
·3393-3398
·
IF 3.84
Yusheng Yuan,Xin Huang,Shaopu Liu,Jidong Yang,Ruilin Duan,Xiaoli Hu
In neutral conditions, hypochlorite-assisted oxidative conversion of 1-pyrenylboronic acid into 1-hydroxypyrene, which leads to 1-pyrenylboronic acid fluorescence quenching, was used as the signaling tool. Compared with 1-pyrenylboronic acid, the maximum excitation (λex = 347 nm) and emission (λem = 392 nm) wavelength of 1-hydroxypyrene had no obvious change. The surfactant Triton X-100, as a micellar additive, was not only used to enhance the stability of the fluorescence probe, but also to improve its sensitivity. When using Triton X-100, the signaling of 1-pyrenylboronic acid was markedly enhanced. Herein, a spectrofluorimetric method for highly selective and sensitive hypochlorite determination has been performed. It can be noted that the fluorescence intensities positively correlated with the hypochlorite concentration over the range of 0.69–6.0 μmol L−1. The detection limit was 0.21 μmol L−1, which is lower than for most of the recently published methods. The experimental conditions were optimized and the effects of coexisting substances are evaluated. The results showed excellent priority because a certain amount of ions, including SO32−, NH4+, Cu2+ and other acid radicals, would not interfere with the measurement. The accuracy and reliability of the method was further ensured by recovery studies using the standard-addition method. In addition, the quenching mechanism, which was proven to be static quenching, has been investigated systematically by the linear plots at varying temperatures based on the Stern–Volmer equation, fluorescence lifetime, and UV-visible absorbance spectra. This method was finally used to detect hypochlorite in local water samples.
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