Molecular Medicine Reports
·
2019
·Vol. 19
·期 5
·3707-3713
·
IF 1.851
Shuyu Liang,Jinzhen Cai,Yani Li,Rui Yang
Macrophage polarization serves an important role in immune regulation that is regulated by T‑cell immunoglobulin‑mucin‑3 (Tim‑3). The objective of the present study was to explore the role of 1,25‑dihydroxy‑vitamin D3 [1,25(OH)2D3] in macrophage polarization. Plasmid transfection techniques were applied to prepare RAW264.7 cells with silenced or overexpressed Tim‑3 gene. ELISAs were used to examine the level of inflammatory factors secreted by macrophages. Proteins levels were determined by western blot analysis. mRNAs expression levels were assessed using reverse transcription quantitative polymerase chain reaction. It was identified that 1,25(OH)2D3 upregulated Tim‑3 levels and promoted the secretion of interleukin (IL)‑10. 1,25(OH)2D3 was also observed to increase the level of transforming growth factor‑β and to inhibit tumor necrosis factor‑α and IL‑6. The results also suggested that Tim‑3 gene silencing induced macrophages polarization to classically activated macrophages (M1), and that overexpression of the Tim‑3 gene induced macrophage polarization to alternatively activated macrophages (M2). 1,25(OH)2D3 treatment upregulated the expression level of Tim‑3 in macrophages, which promoted cell polarization to M2 and inhibited polarization to M1. The data from the present study indicated that Tim‑3 may induce macrophage polarization to M2, and that 1,25(OH)2D3 produced immunosuppressive effects by upregulating Tim‑3.
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高影响因子
Experimental and Therapeutic Medicine
·
2017
·Vol. 14
·期 3
·2721-2727
·
IF 1.261
Rui Wu,Li Long,Qiqi Chen,Xiaodan Wu,Jing Zhu,Bin Zhou,Jia Cheng
The objective of the present study was to investigate the effects of Tim‑3 silencing on cell viability and lipopolysaccharide (LPS)‑induced inflammatory reactions in fibroblast‑like synoviocytes (FLS). T‑cell immunoglobulin mucin domain molecule (Tim)‑3 expression in FLS obtained from patients with rheumatoid arthritis (RA) and normal controls were detected by western blot analysis and reverse transcription‑polymerase chain reaction (RT‑PCR). Small interfering (si)RNA was transfected using Lipofectamine® 2000 to decrease Tim‑3 expression. Following transfection, FLS were stimulated by LPS. An MTT assay, RT‑PCR and western blot analysis were performed to measure cell viability, Toll‑like receptor 4 (TLR4) signaling pathway‑related protein expression and inflammatory cytokine release, respectively. The results of the present study indicated that Tim‑3 expression was increased in FLS from patients with RA compared with FLS from healthy controls. Transfection of Tim‑3 siRNA significantly decreased Tim‑3 expression in FLS from patients with RA. Notably, Tim‑3 silencing decreased FLS cell viability. Following stimulation with LPS, cell viability and the expression of TLR4, myeloid differentiation protein gene 88 (MyD88) and nuclear factor‑κB (NF‑κB) p65 were enhanced in FLS. By contrast, Tim‑3 silencing attenuated LPS‑induced cell proliferation and the expression of TLR4, MyD88 and NF‑κB p65. In addition, LPS significantly increased levels of cytokines in the supernatant, including tumor necrosis factor‑α, interferon‑γ and interleukin‑6 (P<0.01). By contrast, Tim‑3 silencing significantly decreased LPS‑induced cytokine release (P<0.01). However, Tim‑3 silencing did not affect TLR4, MyD88 and NF‑κB p65 expression and the release of cytokines in cells that did not undergo treatment with LPS. Therefore, the results of the present study indicate that Tim‑3 silencing decreases the viability of FLS in RA and attenuates the LPS‑induced inflammatory reaction.
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Data
·
2025
·Vol. 11
·期 1
·4
·
IF 2
Nataliya G. Luzgina,Svetlana N. Tarbeeva,Daniil D. Romashin,Konstantin G. Ptitsyn,Svetlana A. Khmeleva,Leonid K. Kurbatov,Sergey P. Radko,Anna S. Kozlova,Polina A. Veselova,Ekaterina V. Ilgisonis,Alexander L. Rusanov
The aryl hydrocarbon receptor (AhR) plays a crucial role in mediating xenobiotic responses, as well as regulating broader metabolic, differentiation, and stress response programs. In this study, we present a comprehensive long-read RNA sequencing dataset that examines transcriptional changes in the HepaRG human cell line during differentiation induced by dimethyl sulfoxide (DMSO) and acute activation of the AhR with 3-methylcholanthrene (3-MC). We identified 946 genes that were differentially expressed between the NonDiff and Diff conditions (303 genes upregulated and 643 genes downregulated), and 1786 genes that showed differential expression between Diff and Ind conditions (961 genes upregulated and 825 genes downregulated). The acute induction of 3-MC produced a robust AhR signature, characterized by the robust induction ofCYP1A1andCYP1B1, along with a coordinated downregulation of several constitutive hepatic genes involved in drug metabolism (e.g.,CYP3A4andCYP2C8). To facilitate further analysis and reuse of our data, we have provided processed gene-level count matrices, transcript per million (TPM) tables, and detailed differential expression results, as well as analysis scripts. This resource supports research into AhR biology, pharmacogene regulation, and the development of methods for long-read transcriptomics in liver models.Dataset:https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1366635Dataset License:CC-BY 4.0
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 4
·1925-1934
·
IF 2.784
Yunfei Ma,Tuo Tang,Lili Sheng,Ziqian Wang,Hong Tao,Qing Zhang,Yao Zhang,Zhilin Qi
The anti‑inflammatory effects of aloin, a bioactive ingredient extracted from Aloe vera, have been described previously. The present study aimed to assess these effects and explore the underlying molecular mechanisms. RAW264.7 cells were incubated with different doses of aloin (100, 150 and 200 µg/ml) and lipopolysaccharide (LPS; 100 ng/ml) for the indicated times. Then, inducible nitric oxide synthase (iNOS) and cyclooxygenase‑2 expression levels were detected by western blot analysis and reverse transcription polymerase chain reaction (RT‑PCR).The concentrations of inflammatory cytokines in the cell culture supernatant were determined by ELISA. Total nitric oxide (NO) assay and reactive oxygen species (ROS) kits were used to detect NO and ROS levels, respectively. Mitogen‑activated protein kinase, nuclear factor κB and Janus kinase‑signal transducer and activator of transcription (JAK‑STAT) pathway activation were verified by western blot analysis. Confocal and nucleocytoplasmic separation experiments were used to detect STAT nuclear translocation. It was identified that aloin decreased the level of LPS‑induced iNOS expression, inhibiting the release of interleukin (IL)‑1β, IL‑6, tumour necrosis factor‑α and NO dose‑dependently. Mechanistically, aloin suppressed LPS‑induced JAK1‑STAT1/3 activation and STAT1/3 nuclear translocation. Additionally, LPS‑induced ROS production was inhibited by aloin. Collectively, these data suggest that aloin attenuated LPS‑induced inflammation by inhibiting ROS‑mediated activation of the JAK1‑STAT1/3 signalling pathway, thereby inhibiting the nuclear translocation of STAT1/3 in RAW264.7 cells. The present study provides an experimental basis for the clinical application of aloin in inflammatory‑associated diseases.
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高影响因子
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
·
2015
·Vol. 53
·期 11
·1305-1309
·
IF 3.113
Yuanyuan Xu,Jinming Sun,Hou Chen,Liangjiu Bai,Qian Tao,Lili Yu,Yating Wang
2-Cyanoprop-2-yl dithionaphthalenoate (CPDN) was successfully used as the chain transfer agent to prepare polyacrylonitrile in combination with manganese(III) acetylacetonate (Mn(acac) 3 ) as the initiator. The novel polymerization exhibited well “living”/controlled characteristics. The polymerization behavior was revealed to comply with features of reversible addition–fragmentation chain transfer polymerization process. Mn(acac) 3 played a key role as the initiator rather than the radical trapping agent in polymerization and exhibited better control performance than azo-initiator. The narrowest molecular weight distribution was 1.31 under the condition of [AN] 0 :[Mn(acac) 3 ] 0 :[CPDN] 0 = 200:1:0.025 and AN:DMF = 1:1 (V/V). Various feed ratios of Mn(acac) 3 and CPDN were also investigated in detail. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53 , 1305–1309
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Anti-Cancer Agents in Medicinal Chemistry
·
2022
·Vol. 22
·期 17
·3009-3024
·
IF 2.527
Zhu Yuting,Wang Huai,Yu Mingjun,Li Chao,Meng Xiaoming,He Meng,Yao Risheng
Background: GRPR is over-expressed in cancer cells and is a potential drug target for the treatment of cancer. PD176252, as the most representative non-peptide inhibitor of GRPR, can inhibit the growth of cancer cells, but its low selectivity to cancer cells and normal cells limits
its further application. Objective: The aim of this study was to design and synthesize novel GRPR inhibitor with stronger anti-cancer activity and higher affinity with GRPR than the lead compound PD176252. Methods: A series of 1, 3, 4-oxadiazole derivatives as PD176252 analogues
(4a-4j, 6a-6q) were synthesized and their cytotoxic activity was investigated on four cancer lines with high expression of GRPR (gastric (HGC-27), colon (HCT- 116), prostate (PC-3), and lung (A549)) and one human cell line (gastric mucosal epithelial (GES-1)) by MTT assay. Flow cytometry analysis
and Western Blot were used to determine whether the compound induced programmed apoptosis of cancer cells. Competitive binding experiment was used to verify the affinity between GRPR and the optimal compound. Results: Compound 6m exhibited significant growth inhibition on all tested cancer
cell lines, especially gastric cancer cells (HGC-27 cellular IC50 0.37 ± 0.04μM). Also, the selectivity of 6m to HGC-27 was much higher than that of PD176252. Flow cytometric analysis and Western Blot proved that 6m significantly promoted the apoptosis of HGC-
27 cells. Moreover, competitive binding experiment confirmed the close binding of 6m with GRPR, which indicated 6m with a higher affinity than lead compound PD176252. Conclusion: Our results suggested that 6m, as a novel GRPR inhibitor, had a higher affinity with GRPR and potential anti-cancer
effect than PD176252, which can be used as a template for further optimization.
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高影响因子
ECS Journal of Solid State Science and Technology
·
2015
·Vol. 4
·期 5
·M25
·
IF 1.558
Vantu Nguyen,Yueli Liu,Yang Li,Shah Abdul Hakim,Xue Yang,Wen Chen
Fe2(MoO4)3/carbon nanotubes (CNTs) nanocomposite was prepared by a precipitation method and used as a cathode for sodium-ion batteries (SIBs). The field emission scanning electron microscopy (FESEM) test showed that the CNTs and Fe2(MoO4)3 nanosheets formed an interpenetrating network structure. The X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis confirmed that the Fe2(MoO4)3 was a monoclinic crystal structure and mixed with element states in the nanocomposite. The electrochemical properties of the Fe2(MoO4)3/CNTs nanocomposite were studies by electrochemical impedance spectroscopy (EIS) and galvanostatic charge-discharge measurement. The results indicated that Fe2(MoO4)3/CNTs nanocomposite had high specific capacity and good cycling stability as a cathode material for SIBs. As the charge/discharge curent density is at 1 C, the initial specific capacity of Fe2(MoO4)3/CNTs nanocomposite is 85 mAhg−1, and it remains 79.81 mAhg−1 after 50 cycles.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Yuehua Li,Shaoxian Li,Weiwei Meng,Lei Dai,Ling Wang
A series of impedancemetric sensors for ammonia detection were fabricated using yttrium stabilized zirconia (YSZ) electrolyte and La n+1 Ni n O 3n+1 (n = 1, 2, and 3) sensing electrodes. The sensing materials with layered perovskite structure were prepared using in-situ impregnation method and well-dispersed in YSZ porous skeleton after calcination at 900 °C. The sensing performances of the sensors with La n+1 Ni n O 3n+1 sensing electrodes were investigated using the impedancemetric modulus |Z| and phase angle Θ as response signals, respectively. The results show that the sensor with La 2 NiO 4+ δ sensing electrode exhibits the higher response values and sensitivity compared to the sensor using La 3 Ni 2 O 7- δ or La 4 Ni 3 O 10- δ sensing electrodes, which is attributed to the largest NH 3 adsorption capacity of La 2 NiO 4+ δ . The response signals |Z| or Θ of the La 2 NiO 4+ δ based sensor linearly depend on NH 3 concentrations. The sensor hardly is insensitive to co-existing gases such as CO 2 , CH 4 , H 2 and relative humidity, but NO or NO 2 causes a positive error.
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CERAMICS INTERNATIONAL
·
2020
·
IF 3.83
Yunjia Hu,Tengchao Guo,Kangsen Peng,Shujuan Tan,Cheng Xu,Jie Deng
In this study, Ce 1−x Cu x O 2−x (x = 0, 0.01, 0.03, 0.05, 0.07) samples were prepared by hydrothermal method . The structure, microstructure, and elemental composition of the powders were characterized by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy, whereas the electrical conductivity , ultraviolet–visible absorption spectroscopy , and infrared emissivity at 3–5 μm were measured as well. Moreover, the effects of Cu 2+ doping concentration on the microstructure, morphology, bandgap, conductivity, and infrared emissivity of Cu-doped CeO 2 powders were systematically studied. The effects of Cu 2+ doping on infrared reflection and absorption in a 3–5 μm band and their mechanisms were explained based on electromagnetic theory, lattice vibration absorption, and free carrier absorption . Our result indicated that the emissivity of 1% Cu-doped powder reached the lowest emissivity of 0.200 at 800 °C. When the doping concentration was above 1%, the curve of infrared emissivity versus temperature exhibited a “U” shape, with the minimum point shifting towards the low-temperature region with the increase of Cu doping amount. This phenomenon was attributed to the different enhancement amplitude of reflectivity and absorbance of CeO 2 powder by Cu 2+ at different temperatures.
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GENOME BIOLOGY
·
2024
·Vol. 25
·期 1
·1-26
·
IF 10.1
Sun Daming,Bian Gaorui,Zhang Kai,Liu Ning,Yin Yuyang,Hou Yuanlong,Xie Fei,Zhu Weiyun,Mao Shengyong,Liu Junhua
Background The function of diverse ruminal microbes is tightly linked to rumen development and host physiology. The system of ruminal microbes is an excellent model to clarify the fundamental ecological relationships among complex nutrient–microbiome–host interactions. Here, neonatal lambs are introduced to different dietary regimes to investigate the influences of early-life crosstalk between nutrients and microbiome on rumen development. Results We find starchy corn-soybean starter-fed lambs exhibit the thickest ruminal epithelia and fiber-rich alfalfa hay-fed lambs have the thickest rumen muscle. Metabolome and metagenome data reveal that indole-3-carboxaldehyde (3-IAld) and prostaglandin D2 (PGD2) are the top characteristic ruminal metabolites associated with ruminal epithelial and muscular development, which depend on the enhanced ruminal microbial synthesis potential of 3-IAld and PGD2. Moreover, microbial culture experiment first demonstrates that Bifidobacterium pseudolongum is able to convert tryptophan into 3-IAld and Candida albicans is a key producer for PGD2. Transcriptome sequencing of the ruminal epithelia and smooth muscle shows that ruminal epithelial and muscular development is accompanied by Wnt and Ca 2+ signaling pathway activation. Primary cell cultures further confirm that 3-IAld promotes ruminal epithelial cell proliferation depending on AhR-wnt/β-catenin signaling pathway and PGD2 accelerates ruminal smooth muscle cell proliferation via Ca 2+ signaling pathway. Furthermore, we find that 3-IAld and PGD2 infusion promote ruminal epithelial and musculature development in lambs. Conclusions This study demonstrates that early-life ruminal microbiome-derived 3-IAld and PGD2 are effective promoters of rumen development, which enhances our understanding of nutrient–microbiome–host interactions in early life.
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PubMed
高影响因子
BIOMACROMOLECULES
·
2022
·
IF 6.978
Zhaoyue Li,Yilin Qian,Yihuan Lai,Fu-Sheng Du,Zi-Chen Li
Poly(α-methylene ester)s are an attractive type of functional aliphatic polyesters that represent a platform for the fabrication of various biodegradable and biomedical polymers. Herein, we report the controlled ring-opening polymerization (ROP) of a seven-membered α-methylene lactone (3-methylene-1,5-dioxepan-2-one, MDXO) that was synthesized based on the Baylis–Hillman reaction. The chemoselective ROP of MDXO was catalyzed by diphenyl phosphate (DPP) at 60 °C or stannous octoate (Sn(Oct)2) at 130 °C, generating α-methylene-containing polyester (PMDXO) with a linear structure and easily tunable molar mass. The ring-opening copolymerization of MDXO with ε-caprolactone or 1,5-dioxepan-2-one was also performed under the catalysis of DPP or Sn(Oct)2 to afford copolymers with different compositions and sequence structures that are influenced by the kinds of monomers and catalysts. PMDXO is a slowly crystallizable polymer with a glass transition temperature of ca. −33 °C, and its melting temperature and enthalpy are significantly influenced by the thermal history. The thermal properties of the copolymers are dependent on their composition and sequence structure. Finally, the post-modification of PMDXO based on the thiol-Michael addition reaction was briefly explored using triethylamine as a catalyst. Given the optimized condition, PMDXO could be dually modified to afford biodegradable polyesters with different functionalities.
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高影响因子
CURRENT DRUG METABOLISM
·
2024
·Vol. 25
·期 10
·754-768
·
IF 2.1
Xiaoyun Liu,Dafang Zhong,Chongzhuang Tang,Xiaofeng Xu,Hong Lan,Xingxing Diao
Background BPI-460372 is an orally available, covalent, irreversible small molecule inhibitor of the transcriptional enhanced associate domain (TEAD) 1/3/4, which is currently in clinical development for the treatment of cancers with Hippo pathway alterations. Objectives This study aimed to determine the cytochrome P450 (CYP) phenotyping, metabolic stability, and in vitro and in vivo metabolic profile of BPI-460372. Methods The CYP phenotyping and metabolic stability were assessed by measuring the depletion of substrate. The metabolic profile in hepatocytes and rat and dog plasma was analyzed using ultra-high-performance liquid chromatography combined with Orbitrap tandem mass spectrometry (UHPLC-Orbitrap-HRMS). Results BPI-460372 was mainly metabolized by CYP2D6, CYP3A4, and CYP1A2. BPI-460372 exhibited low clearance in human, monkey, and rat hepatocytes, while moderate clearance in dog and mouse hepatocytes. A total of 10 metabolites were identified in five species of hepatocytes, and no human-unique metabolite was detected. In rat plasma and dog plasma, the primary metabolites were M407 (BPI-460430) and M423 (BPI-460456), respectively. The two metabolites were quantitatively determined in rat and dog plasma in pharmacokinetic and toxicological studies. The major metabolic site was 2-fluoro-acrylamide, and major metabolic pathways in hepatocytes, and rat and dog plasma involved oxidative defluorination, hydration, glutathione (GSH) conjugation, hydrolysis, cysteine conjugation, and N-acetyl cysteine conjugation. β-lyase pathway contributed to the metabolism of BPI-460372 in rats to a certain degree. Conclusion This study elucidated the metabolism of BPI-460372 and provided a basis for pharmacokinetic and toxicological species selection, human pharmacokinetics prediction, and assessment of clinical co-administration limitations and possible metabolic pathways in humans.
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