Stem Cells International
·
2021
·
IF 5.443
Yuxin Zhao,Bobo Cai,Weijun Zhu,Jue Shi,Yu Wang,Misi Si
Mesenchymal stem cells (MSCs) have been considered to be a future treatment option for periodontitis due to their excellent regenerative capability. However, it is still a challenge to protect MSCs’ biological properties from multiple bacterial toxins in local inflammatory environment. The present study is aimed at investigating the treatment effect of interleukin-1 receptor antagonist (IL-1ra) on cell proliferation, migration, and osteogenic differentiation of gingival-derived mesenchymal stem cells (GMSCs) under an inflammatory microenvironment induced by Porphyromonas gingivalis lipopolysaccharides (P. gingivalis-LPS). GMSCs derived from Sprague-Dawley (SD) rats’ free gingival tissues were treated with P. gingivalis-LPS (10 μg/mL) to create in vitro inflammatory environment. Different concentrations of IL-1ra (0.01-1 μg/mL) were used to antagonize the negative effect of LPS. Cell behaviors including proliferation, cloning formation unit (CFU), cell migration, osteogenic differentiation, mineral deposition, and cytokine production were assessed to investigate the protection effect of IL-1ra on GMSCs under inflammation. The toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway activated by LPS was evaluated by real-time quantitative polymerase chain reaction (RT-PCR) and western blot. In response to P. gingivalis-LPS treatment, cell numbers, cloning formation rate, cell migration rate, proinflammatory cytokine production, and osteogenic differentiation-associated protein/mRNA expressions as well as mineralized nodules were suppressed in a time-dependent manner. These negative effects were effectively attenuated by IL-1ra administration in a time- and dose-dependent manner. In addition, mRNA expressions of TLR4 and IkBα decreased dramatically when IL-1ra was added into LPS-induced medium. IL-1ra also reversed the LPS-induced TLR4/NF-κB activation as indicated by western blot. The present study revealed that IL-1ra decreased inflammatory cytokine production in a supernatant, so as to protect GMSCs’ osteogenesis capacity and other biological properties under P. gingivalis-LPS-induced inflammatory environment. This might be explained by IL-1ra downregulating TLR4-mediated NF-κB signaling pathway activation.
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JOURNAL OF CHEMICAL AND ENGINEERING DATA
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2020
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IF 2.369
Xiaolin Zhao,Ji Mi,Yitong Dai,Guijin He,Yongsheng Guo,Wenjun Fang
exo-Tetrahydrodicyclopentadiene can serve as both the propellant and coolant in hypersonic vehicles. However, its applications are restricted by the poor properties of ignition and combustion to some extent. Fuel additives such as appropriate alcohols have the ability to overcome these deficits. Research on thermophysical properties of the mixtures composed of exo-tetrahydrodicyclopentadiene and fuel additives can provide important information for the research of fuel additives. In this work, densities and viscosities of the ternary system of exo-tetrahydrodicyclopentadiene (1) + n-decane (2) + iso-butanol (3) and three corresponding binary systems have been measured over the whole composition range in the temperature range from 293.15 to 333.15 K with an interval of 5 K and at pressure p = 0.1 MPa. The values of excess molar volumes (VmE) and viscosity deviations (Δη) of three binary systems and the ternary system were calculated and then fitted to the Redlich–Kister equation and four semi-empirical equations, respectively. The variations of VmE and Δη were explained from the viewpoints of intermolecular forces and structural effects. Furthermore, the Jouyban–Acree model was used to correlate the values of densities (ρ) and viscosities (η) of the studied mixtures with high accuracy.
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JOURNAL OF MOLECULAR LIQUIDS
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2020
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IF 5.065
Jiao Sha,Ruke Zhang,Yuanyuan Zun,Rui Zhao,Yameng Wan,Haixia He,Renren Sun,Gaoliang Jiang,Yu Li,Tao Li,Baozeng Ren
The solubility values of doxifluridine in three mixed solvents of (±)-2-ethyl-1-hexanol + (methanol, ethanol and acetone) ware determined within 278.15–328.15 K under 0.1 MPa using a laser monitoring technique. It can be seen from the solubility profiles that all the solubility of doxifluridine in the mixed solvents increases with the increasing mass fraction of the co-solvent (methanol, ethanol or acetone) and the experimental temperature. The minimum and maximum mole fraction solubility of doxifluridine was found in ethanol + (±)-2-ethyl-1-hexanol (4.981 × 10 −5 at w 1 = 0.1003, T = 278.15 K) and methanol + (±)-2-ethyl-1-hexanol (1.109 × 10 −1 at w 1 = 0.9001, T = 328.15 K), respectively. Through the application of Hansen solubility parameters, the solubility order and miscibility of doxifluridine in the three mixed solvents studied in this work was revealed, and the results showed that the dissolution behavior of doxifluridine was not only determined by a single factor, but also the result of the comprehensive action of various solubility parameters. In addition, three semi-empirical models (λh, Modified Apelblat, and MA) and one activity coefficient model (UNIQUAC) were applied to fit the solubility data of doxifluridine. The minimum average values of ARD (average relative deviation) and 10 4 RMSD (root-mean square deviation) were acquired from Modified Apelblat model, verifying that Modified Apelblat model provides maximum consistency among the four models. Furthermore, Van't Hoff model was used to calculate the apparent thermodynamic parameters (Δ sol G °, Δ sol H °, Δ sol S °) of the dissolution process of doxifluridine. The results demonstrated that the dissolution process of doxifluridine in all the three mixed solvents studied was an entropy-driven endothermic process.
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SEPARATION SCIENCE AND TECHNOLOGY
·
2020
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IF 1.718
Yingying Li,Haoliang Zhao,Weijun Yang,Yong Gao,Liming Wang
Trace cobalt ion in the zinc sulfate electrolyte is the most difficult to be removed among all metallic impurities and has the most detrimental effect on zinc electrowinning. In this study, poly(p-hydroxystyrene) resin was first prepared from polystyrene, and then 1-nitroso-2-naphthol was grafted onto poly(p-hydroxystyrene) resin through -O- group by a series of reactions to obtain the 1-nitroso-2-naphthol-grafted-poly(p-hydroxystyrene) resin. Finally, the grafted resin was supported on SiO2. The supported resin could removal trace cobalt ions with good selectivity and reusability in the zinc sulfate leachate, which can meet the requirements of the industrial electrolytic zinc process.
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Journal of Neuroinflammation
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2019
·Vol. 16
·期 1
·1-13
·
IF 5.7
Wu Xuan,Fu Siming,Liu Yun,Luo Hansheng,Li Feng,Wang Yiying,Gao Meng,Cheng Yuan,Xie Zongyi
Background Neuroinflammation and blood-brain barrier (BBB) disruption are two vital mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Recently, melanocortin-1 receptor (Mc1r) activation by Nle4-D-Phe7-α-MSH (NDP-MSH) was shown to play a neuroprotective role in an experimental autoimmune encephalomyelitis (EAE) mouse model. This study aimed to investigate whether NDP-MSH could alleviate neuroinflammation and BBB disruption after experimental ICH, as well as the potential mechanisms of its neuroprotective roles.Methods Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model. NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult. To further explore the related protective mechanisms, Mc1r small interfering RNA (Mc1r siRNA) and nuclear receptor subfamily 4 group A member 1 (Nr4a1) siRNA were administered via intracerebroventricular (i.c.v) injection before ICH induction. Neurological test, BBB permeability, brain water content, immunofluorescence staining, and Western blot analysis were implemented.Results The Expression of Mc1r was significantly increased after ICH. Mc1r was mainly expressed in microglia, astrocytes, and endothelial cells following ICH. Treatment with NDP-MSH remarkably improved neurological function and reduced BBB disruption, brain water content, and the number of microglia in the peri-hematoma tissue after ICH. Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5. Inversely, the knockdown of Mc1r or Nr4a1 abolished the neuroprotective effects of NDP-MSH.Conclusion sTaken together, NDP-MSH binding Mc1r attenuated neuroinflammation and BBB disruption and improved neurological deficits, at least in part through CREB/Nr4a1/NF-κB pathway after ICH.
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ChemSusChem
·
2019
·Vol. 13
·期 4
·803-810
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IF 7.804
Chengyi Zhu,Yannan Zhang,Xiaohua Yu,Peng Dong,Jianguo Duan,Jiaming Liu,Jianxiong Liu,Yingjie Zhang
Graphical Progress towards the positive : A facile strategy through manipulating KMnO 4 concentration is introduced to precisely fabricate 1 D LiMn 2 O 4 nanorods with four distinct diameter gradients. The LiMn 2 O 4 nanorod with a critical diameter of approximately 70–80 nm displays the highest discharge capacity and promising cycling performance. The role of 1 D crystal size in effecting interface chemical species and electrochemical performance is elucidated by comparative characterization methods. The morphology and size of nanoelectrode materials determine their properties. Compared to the bulk structure electrodes, 1 D electrode materials for Li-ion batteries have been intensively studied owing to their excellent Li + diffusion kinetics. It is generally accepted that smaller-sized electrode materials lead to better Li storage kinetics. In this study, this is found to not be the case in 1 D LiMn 2 O 4 positive materials. A facile strategy of manipulating the KMnO 4 concentration is introduced to precisely fabricate 1 D LiMn 2 O 4 nanorods with four distinct diameter gradients from 30 to 170 nm. The role of 1 D crystal size in effecting interface chemical species and electrochemical performance is elucidated by comparative characterization methods. X-ray photoelectron spectroscopy (XPS) Ar-ion etching technology shows that the Mn 2+ is electrochemically inactive on the surface of the sample, which explains the adverse effects observed on LiMn 2 O 4 nanorods with the minimum diameter of 30–40 nm, such as decreased discharge capacity. The LiMn 2 O 4 nanorod with a critical diameter of approximately 70–80 nm displays the highest discharge capacity and promising cycling performance. This work clarifies an important property that has previously been neglected and deepens the understanding for design of Mn-based positive materials.
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FISH & SHELLFISH IMMUNOLOGY
·
2019
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IF 3.298
Hui Li,Guilan Di,Yi Zhang,Rongrong Xue,Jing Zhang,Junping Liang
Cadmium (Cd) is a nonessential metal that is a contaminant in aquatic ecosystems . Cd can accumulate in aquatic animals, leading to detrimental effects in tissues, and Cd exposure can induce immunotoxicity in fish. MicroRNAs (miRNAs) play critical roles in immune responses, yet the participation of miRNAs in Cd-induced immunotoxicity remains poorly understood. The present study evaluated the effects of Cd exposure on the immune responses and the mRNAs and miRNAs expressions of immune-related genes in Cyprinus carpio ( C. carpio ). Then, microRNA-155 (miR-155) was overexpressed and microRNA-181a (miR-181a) was knocked down to determine which miRNA plays a key role in the immune response to Cd. The results showed that 0.5 mg/L Cd 2+ significantly decreased the activity of alkaline phosphatase (AKP) and acid phosphatase (ACP) in the kidneys of C. carpio . Cd exposure upregulated the mRNA expressions of interleukin (IL)-1β, IL-8, nuclear factor-kappa B (NF-κB), tumour necrosis factor-α (TNF-α), and Toll-like receptor 4(TLR-4) and downregulated those of IL-10 and heme oxygenase-1 (HO-1) in C. carpio kidneys. Cd exposure also led to upregulation of miR-155 and miR-181a expressions. Furthermore, AKP and ACP activity in the kidneys was markedly changed after intraperitoneal injection of C. carpio with miR-155 agomir and miR-181a antagomir . All detected mRNA expressions were significantly decreased after injection of miR-155 agomir, and IL-10, NF-κB, TNF-α, and HO-1 mRNA expressions were markedly increased after injection of miR-181a antagomir. The results of this study demonstrate that Cd exposure can immunocompromise C. carpio by targeting HO-1 through miR-155 and miR-181a. This is the first study to reveal that Cd exposure induces immunotoxicity through miR-155 and miR-181a in the kidneys of C. carpio .
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Cell Communication and Signaling
·
2022
·Vol. 20
·期 1
·1-11
·
IF 7.525
Yang Jing,Tang Xujiao,Li Baiqiang,Shi Jinsong
In acute pancreatitis, activation of inflammatory signaling, including the nuclear factor-kappa B (NF-κB) pathway, within acinar cells is known to be an early intracellular event occurring in parallel with pathologic trypsinogen activation. Sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in endothelial inflammation, and our previous studies reported that S1PR2 deficiency significantly reduced the inflammatory response in liver injury under cholestasis conditions. However, the role of S1PR2 in inflammatory signaling activation within acinar cells and inflammatory responses during acute pancreatitis has not been elucidated. Here we report that S1PR2 was upregulated in the whole pancreas during acute pancreatitis. Blockade of S1PR2 by pharmacologic inhibition of S1PR2 by JTE-013 or AAV-mediated knockdown of S1PR2 improved the severity of pancreatic injury, as indicated by a significant reduction in inflammation and acinar cells death in acute pancreatitis mice. Moreover, S1PR2 is the predominant S1PRs expressed in pancreatic acinar cells and mediates NF-κB activation and the early inflammatory response within acinar cells under acute pancreatitis conditions via ROCK signaling pathways, not extracellular signal-regulated kinase pathways or p38 mitogen-activated protein kinase pathways. In addition, S1PR2 mediated macrophage NF-κB activation, migration and polarization toward the M1 phenotype. Therefore, these results demonstrated that the S1PR2-mediated early inflammatory response in acinar cells promotes the progression of acute pancreatitis, successfully linking local events to the systematic inflammatory response and leading to a novel therapeutic target for acute pancreatitis aimed at halting the progression of the inflammatory response.
Video Abstract
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JOURNAL OF MEDICINAL CHEMISTRY
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2018
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IF 6.253
Jian Zhang,Vasanthanathan Poongavanam,Dongwei Kang,Chiara Bertagnin,Huamei Lu,Xiujie Kong,Han Ju,Xueyi Lu,Ping Gao,Ye Tian,Haiyong Jia,Samuel Desta,Xiao Ding,Lin Sun,Zengjun Fang,Boshi Huang,Xuewu Liang,Ruifang Jia,Xiuli Ma,Wenfang Xu,Natarajan Arul Murugan,Arianna Loregian,Bing Huang,Peng Zhan,Xinyong Liu
On the basis of our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Among the synthesized compounds, 15b and 15c were exceptionally active against both group-1 and -2 NAs. Especially for 09N1, N2, N6, and N9 subtypes, they showed 6.80–12.47 and 1.20–3.94 times greater activity than oseltamivir carboxylate (OSC). They also showed greater inhibitory activity than OSC toward H274Y and E119V variant. In cellular assays, they exhibited greater potency than OSC toward H5N1, H5N2, H5N6, and H5N8 viruses. 15b demonstrated high metabolic stability, low cytotoxicity in vitro, and low acute toxicity in mice. Computational modeling and molecular dynamics studies provided insights into the role of R group of 15b in improving potency toward group-1 and -2 NAs. We believe the successful exploitation of the 150-cavity of NAs represents an important breakthrough in the development of more potent anti-influenza agents.
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JOURNAL OF MEDICINAL CHEMISTRY
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2019
·
IF 6.054
Yao-Ling Wang,Sha Liu,Zhu-Jun Yu,Yuan Lei,Meng-Yi Huang,Yu-Hang Yan,Qiang Ma,Yang Zheng,Hui Deng,Ying Sun,Chengyong Wu,Yamei Yu,Qiang Chen,Zhenling Wang,Yong Wu,Guo-Bo Li
The emergence and spread of bacterial pathogens acquired metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) medicated β-lactam resistance gives rise to an urgent need for the development of new dual-action MBL/SBL inhibitors. Application of a pharmacophore fusion strategy led to the identification of (2′S)-(1-(3′-mercapto-2′-methylpropanamido)methyl)boronic acid (MS01) as a new dual-action inhibitor, which manifests broad-spectrum inhibition to representative MBL/SBL enzymes, including the widespread VIM-2 and KPC-2. Guided by the VIM-2:MS01 and KPC-2:MS01 complex structures, further structural optimization yielded new, more potent dual-action inhibitors. Selectivity studies indicated that the inhibitors had no apparent inhibition to human angiotensin-converting enzyme-2 and showed selectivity across serine hydrolyases in E. coli and human HEK293T cells labeled by the activity-based probe TAMRA-FP. Moreover, the inhibitors displayed potentiation of meropenem efficacy against MBL- or SBL-positive clinical isolates without apparent cytotoxicity. This work will aid efforts to develop new types of clinically useful dual-action inhibitors targeting MBL/SBL enzymes.
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ChemistrySelect
·
2023
·Vol. 8
·期 45
·e202303025
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IF 2.1
Sida Hu,Xiuqin Dong,Jianhang Tian,Lingtao Wang,Yifei Chen,Haoxi Jiang
Graphical We prepared the Co-based materials via the pyrolysis of ZIF-67 at low temperature, and obtained the optimum catalyst ZIF-67-Sg-350-10 with the conversion of 1-butene, aldehyde selectivity and n/i ratio of 94.9 %, 77.1 % and 2.2, respectively. We prepared the Co-based materials via the pyrolysis of ZIF-67 at low temperature (250 °C~350 °C), and obtained the optimum catalyst ZIF-67-Sg-350-10 with the conversion of 1-butene, aldehyde selectivity and n/i ratio of 94.9 %, 77.1 % and 2.2, respectively. The conversion of 1-butene and aldehyde selectivity obviously increased with the increasing pyrolysis temperature and pyrolysis time. It was found that the interaction between the Co cluster and N-doped carbon composites could improve the hydroformylation activity. Different catalyst models were built to investigate the active centers (Co) in the derived materials. The Co-N4 surface was the best catalyst model with the lowest hydrogen insertion reaction energy barrier (0.37 eV).
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ACS Nano
·
2023
·
IF 17.1
Hong Guo,Yuping Liu,Xia Li,Hong Wang,Dengxuan Mao,Liangyin Wei,Xietao Ye,Ding Qu,Jiege Huo,Yan Chen
Programmed cell death protein 1 (PD-1) inhibitors are the most common immune-checkpoint inhibitors and considered promising drugs for hepatocellular carcinoma (HCC). However, in clinical settings, they have a low objective response rate (15%–20%) for patients with HCC; this is because of the insufficient level and activity of tumor-infiltrating T lymphocytes (TILs). The combined administration of oxymatrine (Om) and astragaloside IV (As) can increase the levels of TILs by inhibiting the activation of cancer-associated fibroblasts (CAFs) and improve the activity of TILs by enhancing their mitochondrial function. In the present study, we constructed a magnetic metal–organic framework (MOF)-based nanoplatform with platelet membrane (Pm) coating (PmMN@Om&As) to simultaneously deliver Om and As into the HCC microenvironment. We observed that PmMN@Om&As exhibited a high total drug-loading capacity (33.77 wt %) and good immune escape. Furthermore, it can target HCC tissues in a magnetic field and exert long-lasting effects. The HCC microenvironment accelerated the disintegration of PmMN@Om&As and the release of Om&As, thereby increasing the level and activity of TILs by regulating CAFs and the mitochondrial function of TILs. In addition, the carrier could synergize with Om&As by enhancing the oxygen consumption rate and proton efflux rate of TILs, thereby upregulating the mitochondrial function of TILs. Combination therapy with PmMN@Om&As and α-PD-1 resulted in a tumor suppression rate of 84.15% and prolonged the survival time of mice. Our study provides a promising approach to improving the antitumor effect of immunotherapy in HCC.
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