BMC Complementary Medicine and Therapies
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2020
·Vol. 20
·期 1
·1-10
·
IF 0
Liu Shou Gang,Luo Guang Pu,Qu Yong Bin,Chen Yong Feng
Background Psoriasis is a common inflammatory skin disease. Abnormal proliferation of keratinocytes is one of the psoriatic histopathological features. Indirubin has an essential effect on the proliferation and activation of keratinocytes; however, in psoriasis, the specific mechanism of action of indirubin on keratinocytes is unclear. In the present study, we revealed the effects of indirubin on DNA methyltransferase 1 (DNMT1), wnt inhibitory factor 1 (wif-1), and wnt/β-catenin signal pathway, in the meantime, we explored the effects of indirubin on proliferation, cell cycle and the apoptosis of HaCaT cells.Methods The expression of DNMT1, wif-1, Frizzled2, Frizzled5, and β-catenin in HaCaT cells treated with different concentrations of indirubin were detected by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of DNMT1 and wif-1 were observed after treated with different concentrations of indirubin by enzyme-linked immunosorbent assay (ELISA). The wif-1 promoter methylation status was detected by DNA methylation-specific PCR (MSP). The transcriptional activities of wif-1 and β-catenin were discovered by a luciferase reporter gene system. Cell viability was determined by Cell Counting Kit-8 (CCK8) method. The cell cycle was detected by flow cytometry. The apoptotic cells were surveyed by the apoptosis kit. The expression of Inolucrin, Loricrin, Filaggrin, Keratin 17, and transcriptional activation of transglutaminase 1(TGase1) were detected by Western blotting.Results Indirubin inhibited the expression of DNMT1 and the methylation of the wif-1 promoter. In the wnt signal pathway, indirubin restored the protein expression of wif-1 and inhibited expression of Frizzled2, Frizzled5, and β-catenin. Besides, indirubin inhibited the proliferation of HaCaT cells, induced apoptosis, and arrest cell cycle. We also reported that indirubin could down-regulate the expression of Involucrin, TGase 1, and keratin 17, but the expression of Filaggrin and Loricrin had no significant effect.Conclusion Our research showed that indirubin promoted the demethylation of wif-1 and suppressed the wnt/β-catenin signal pathway, thereby exerted an anti-proliferative effect. This study reveals the anti-proliferation mechanism of indirubin, which may provide an effective option for the treatment of proliferative diseases.
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CANCER LETTERS
·
2020
·
IF 7.36
Huimin Tao,Lu Cheng,Lihua Liu,Hong Wang,Zhijie Jiang,Xu Qiang,Lijun Xing,Yifeng Xu,Xinying Cai,Jing Yao,Min Wang,Zheng Qiu
Antibodies blocking the PD-1/PD-L1 pathway have achieved great success. However, some disadvantages of antibodies have been found, which limit their clinical applications. Peptide antagonists are alternatives to antibodies in PD-1/PD-L1 blockage, but successful studies in this area are limited. A PD-1 targeting peptide, P–F4, was identified using phage display. P–F4 bound PD-1 with an affinity of 0.119 μM, inhibited PD-1/PD-L1 interaction at the cellular level and modulated T cell activity in vitro . We have overcome the poor solubility and rapid degradation problems of this peptide by packaging P–F4 in nanoparticles. In vivo experiments demonstrated that P–F4 nanoparticles could strongly inhibit tumor growth in a CT26 mouse model. Further research revealed that treatment of P–F4 nanoparticles increased CD8+T cells and reduced Tregs in the tumor microenvironment and tumor-draining lymph nodes. It was shown that treatment of P–F4 nanoparticles also increased lymphocytic activities, including proliferation, cytokine secretion and cytolytic activity. Moreover, computer modeling suggested that the P–F4 binding site to PD-1 overlaps with the PD-L1 binding surface. In this study, a peptide candidate for cancer immunotherapy was provided, and its working mechanisms were studied.
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Iranian Journal of Biotechnology
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2020
·
IF 0.973
Shuang Feng Li,Huai Wang,Jia Li Chen,Hui Xia Zhu,Ri-Sheng Yao,Huan Wu
Background: Lignin is the largest natural aromatic polymer in nature and is also a unique aromatic-based biopolymer, accountingfor nearly 30% of the earth’s organic carbon. Generally, lignin is regarded as waste and is mainly used as a low- valuefuel that is burned to generate heat and energy to solve the problem of biomass waste; for this obstacle of lignin,highly efficient biodegradation plays a critical role in developing an environmentally friendly technique for lignin biotransformation. Objectives: This study intends to isolate and purify several microbial strains from nature. It also explores how their lignin degradationis able to enhance the biodegradation and recycling of biomass and the reclamation of lignin in wastewater from pulp and paper mills. Materials and Methods: Lignin-degrading microbial strains were isolated from soil using medium containing sodium lignosulphonate as the sole carbonsource. They were then screened by aniline blue and guaiacol plate, and then the best strain was chosen and identified.The conventional one-factor method was used to optimize various parameters that affect lignin’s degradation ability. Results: The strain possessing the highest lignin biodegradation ability was identified and denominated as Aspergillus Flavus F-1. After optimization, the maximum degradation rate of lignin, 44.6% within 3 days, was obtained at pH 7.0, 30 ℃, 2.5 g·L -1 ammoniumsulfate, 2 g·L -1 lignin and 0.5 g·L -1 glucose. The results show the LiP and Lac secreted from Aspergillus Flavus F-1 played the main role in the degradation of lignin. Conclusion: One microbial strain, Aspergillus Flavus F-1, was successfully isolated with a lignin-degrading abilitythat can cut the lignin into fragments. This provides a promising candidate for the transformation and utilization of crop waste biomass for various industrial purposes.
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JOURNAL OF ELECTROANALYTICAL CHEMISTRY
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2020
·
IF 3.807
Lijun Zhou,Xueling Shan,Ding Jiang,Wenchang Wang,Zhidong Chen
Catechol (CC) exists a potential threat to human psychology and physiology. In this research, a novel ultra-sensitive electrochemiluminescence (ECL) sensor was established to detect CC based on carbon dots (CDs) and metal organic framework (HKUST-1) synergy system. The results showed good large specific surface area of HKUST-1 on CDs which could effectively improve the sensitivity of sensor. Under the optimal conditions, the as-fabricated sensor illustrated a wide linear range of 5.0 × 10 −9 –2.5 × 10 −5 mol/L with the detection limit of 3.8 × 10 −9 mol/L(S/N = 3). In addition, owning to its good reproducibility and stability, the sensor had been successfully applied to the actual sample. This work provides an important reference for the application of metal organic framework materials (MOFs) in ECL researches and a novel method for detecting catechol.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2020
·
IF 4.872
Yuliang Xu,Xiaozhou Wang,Na Geng,Yiran Zhu,Shuo Zhang,Yongxia Liu,Jianzhu Liu
Cr (VI), which is a common heavy metal pollutant with strong oxidizing property, exists widely in nature. Organisms can be exposed to Cr (VI) through various means. Cr (VI) causes mitochondrial dysfunction after being absorbed by cells. Whether Cr (VI) induces the selective autophagic degradation of mitochondria, which is a biological process called mitophagy, remains unclear. Mitophagy not only recycles intracellularly damaged mitochondria to compensate for nutrient deprivation but also is involved in mitochondria quality control. Thus, this study investigated whether Cr (VI) could induce mitophagy in DF-1 cells. Carbonyl cyanide m-chlorophenylhydrazone, which is a mitochondrial-uncoupling reagent that induces mitophagy, was used. DF-1 cells were incubated with different doses of Cr (VI) for varying durations. The autophagy-related proteins LC3-II and p62 levels decreased after 6 h of Cr (VI) treatment but recovered within 24 h. The mitochondrial membrane potential, which is an indicator of mitochondrial damage, was detected by flow cytometry. We found that different durations of Cr (VI) treatment induced mitochondrial mass decrease and depolarization. Furthermore, the expression of the protein translocase of outer mitochondrial membrane 20 (TOMM20), which is a mitochondrial outer membrane protein, was decreased significantly in the presence of Cr (VI). Our findings indicate that Cr (VI) may contribute to the mitochondrial morphology and function damage and may therefore lead to the autophagic clearance of mitochondria.
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BIOCHEMICAL PHARMACOLOGY
·
2020
·
IF 4.96
Yue Liu,Zhuang-Zhuang Tang,Yu-Meng Zhang,Li Kong,Wei-Fen Xiao,Teng-Fei Ma,Yao-Wu Liu
Gestational diabetes mellitus (GDM) is associated with an increased risk of progressing to type 2 DM and cardiovascular disease; however, the pathogenesis is still poorly understood. This study was to investigate roles of thrombin and its receptor protease-activated receptor 1 (PAR-1) and NLRP1 inflammasome in endothelial injury in GDM condition. Umbilical cord and plasma of GDM patients and high glucose (HG) cultured human umbilical vein endothelial cells (HUVECs) were used to examine the pathological changes of these pathways. Meanwhile, ameliorative effects and potential mechanisms of a natural product sarsasapogenin (Sar) were investigated in HUVECs. Thrombin/PAR-1 pathway, advanced glycation endproducts (AGEs) and their receptor (RAGE) axis, and the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome were activated in GDM condition and HG-cultured HUVECs, accompanied by endothelial injury (decreased cell viability and increased lactate dehydrogenase release). Nevertheless, thrombin inhibition or PAR-1 antagonism caused decreases in AGEs formation and RAGE expression in HG-cultured HUVECs, while AGEs inhibition or RAGE antagonism declined PAR-1 expression not thrombin activity. Furthermore, thrombin inhibition or PAR-1 antagonism restrained NLRP1 inflammasome activation in HG-cultured HUVECs; meanwhile, NLRP1 expression and interleukin 18 levels were remarkably reduced in HG-cultured HUVECs after PAR-1 knockdown. Interestingly, Sar co-treatment could suppress thrombin/PAR-1 pathway, NLRP1 inflammasome, and AGEs/RAGE axis. Together, endothelial damages in GDM were likely due to enhanced interaction between AGEs/RAGE axis and thrombin/PAR-1 pathway, followed by NLRP1 inflammasome activation. Moreover, Sar may act as a protective agent against endothelial injury in chronic HG condition.
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JOURNAL OF MEMBRANE SCIENCE
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2020
·
IF 7.183
Jiaqi Li,Mengxiao Zhang,Weilin Feng,Liping Zhu,Lin Zhang
Herein, a novel thin film composite (TFC) membrane pore-filled with polymer of intrinsic microporosity, PIM-1, has been developed for organic solvent nanofiltration (OSN). The TFC membranes were facilely prepared by dip-coating of PIM-1/chloroform solution onto polyacrylonitrile support membranes followed by a solvent vapor annealing (SVA) process. The relationship between preparation conditions, selective layer morphologies and OSN performances of the prepared TFC membranes were studied systematically. It was found PIM-1 was evidently filled into the near surface pores of support membranes due to the infiltration of PIM-1 solution. With the elongation of SVA time, the thickness of the PIM-1 layer decreased and the PIM-1/PAN interface gradually disappeared, which is advantageous to enhance the interfacial bonding. The prepared TFC membranes were used to reject organic molecules in organic solvents and exhibited tunable solvent permeability and solute rejection. Especially, the membranes were suitable for the removal of neutral molecules and anionic dyes from ethanol. The typical membrane demonstrated an ethanol permeance of 4.3 L m −2 h −1 bar −1 with a rejection of 93.7% towards Methyl Orange (327 Da). By comparing the permeance of various solvents, it is found that the closer the Hansen solubility parameter of solvent is to that of PIM-1, the higher the solvent permeance. This indicates the affinity between solvent and membrane plays an important role in solvent permeability. This work offers a novel and convenient strategy to prepare highly permeable membranes with controllable microstructures and tunable permselectivity to meet the diverse demands of molecular separation in organic solvents.
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MACROMOLECULAR BIOSCIENCE
·
2020
·Vol. 20
·期 7
·1900438
·
IF 3.416
Ting Bai,Bobo Zhu,Dongyan Shao,Ziyang Lian,Pei Liu,Junling Shi,Jie Kong
Targeting the distinct cholesterol metabolism of tumor cells is proposed as a novel way to treat tumors. Blocking acyl-CoA cholesterol acyltransferase-1 (ACAT-1) by the inhibitor avasimible (Ava), which elevates intracellular free cholesterol levels, is shown to effectively induce apoptosis. However, Ava faces disadvantages of poor water solubility, a short half-life, and no capability for fluorescence detection, which have greatly limited its application. Herein, a fluorescent hyperstar polymer (FHSP) is developed to encapsulate Ava to improve its ability to inhibit HeLa cells and K562 cells. The results of this study show that the obtained Ava–FHSP micelles possess a high drug loading capacity of 22.7% and bright green fluorescence. Ava and Ava–FHSP are cytotoxic to both HeLa and K562 cells and cause reductions in cell size, nuclear lysis, and chromatin condensation and hindered proliferation of both cell types by causing S phase cell cycle arrest. Further mechanistic analysis indicates that Ava–FHSP reduces the protein and messenger RNA expression of ACAT-1 and significantly increases intracellular free cholesterol levels, which can increase endoplasmic reticulum stress and finally cause cell apoptosis. All these results suggest that this fluorescent hyperstar polymer represents a potential therapeutic tumor strategy by changing the cholesterol metabolism of tumor cells.
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BIOCHEMICAL PHARMACOLOGY
·
2020
·
IF 4.96
Ping Cheng,Huan Liu,Yinchuan Li,Peiling Pi,Yu Jiang,Shaozhen Zang,Xiaorong Li,Ailing Fu,Xiaoyuan Ren,Jianqiang Xu,Arne Holmgren,Jun Lu
Platinum-containing drugs (PtDs; e.g. cisplatin , carboplatin , and oxaliplatin) have been widely used as anticancer reagents against various cancers. However, treatment with these drugs results in undesirable adverse effects with unknown mechanisms. Herein, we found a strong correlation between the inhibitory effects of PtDs on cytosolic thioredoxin reductase (TXNRD1) and tissue injury. Of the PtDs tested, cisplatin was found to be the most effective inhibitory PtD against TXRND1, causing the severest kidney injury . The initial inhibition of TXNRD1 in the kidney resulted from cisplatin-induced transcriptional activation of Nrf2-regulated genes including Txnrd1 . However, the antioxidant responses in the kidney did not reverse the cisplatin-induced oxidation process. Nephrotoxicity was accompanied with an increase of protein glutathionylation and a cellular thiol redox environment oxidation. These results suggest that the changes of the cellular thiol-dependent redox environment regulated by TXNRD1 is a major event in the adverse effects of cisplatin in kidney.
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COLLOID AND POLYMER SCIENCE
·
2021
·Vol. 299
·期 9
·1459-1468
·
IF 1.931
Guan Peiwen,Ren Cong,Shan Houchao,Cai Di,Zhao Peimian,Ma Dongze,Qin Peiyong,Li Shufeng,Si Zhihao
To meet the increasing requirements toward biobutanol, pervaporation membrane with high separation performance needs to be developed. In this work, a hydrophobic MAF-6 (RHO-[Zn(eim) 2 ]) was synthesized and its adsorption properties for 1-butanol was systematically studied, which are supposed to benefit the separation performance of polydimethylsiloxane (PDMS) membrane. The hydrophobic MAF-6 particles were therefore doped into PDMS to fabricate mixed matrix membrane. The morphology, chemical structure, and other properties of particles and hybrid membrane were fully studied by SEM, PXRD, FT-IR, TGA, and BET. Results demonstrate that the hydrophobicity of PDMS membrane is improved with the water contact angle increasing from 112.7° to 118.1° after being doped with MAF-6, as well as enhanced adsorption ability toward 1-butanol. More importantly, when doping MAF-6 into PDMS layer, the enhancements of 23.30% and 41.93% are separately observed in the separation factor and total flux to separate 1.5 wt% 1-butanol solution, compared with the PDMS membrane. In addition, the heat energy consumption of pervaporation process is decreased from 4.27 to 3.71 kJ g −1 via the doping of MAF-6. Overall, this work confirms that the hydrophobic particle such as MAF-6 is not only conductive to enhance the separation performance of PDMS membrane but also helpful to decrease the energy consumption.
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JOURNAL OF ALLOYS AND COMPOUNDS
·
2021
·
IF 5.316
Zhe Hu,Hanqing Dai,Wenjie Zhou,Jinxin Wei,Hongbin Zhang,Zhaoqi Ye,Yi Qiu,Yuanyuan Chen,Zhongtao Duan,Jing Wang,Wanlu Zhang,Fengxian Xie,Ruiqian Guo
The aggregation-induced quenching (AIQ) properties of the solid-state carbon dots (CDs) limit their wide-scale actual applications. Herein, a novel corrosion resistant solid-state CDs@Silicalite-1 (CDs@S-1) composite was synthesized via in situ embedding CDs into the S-1 matrix. Owing to the confinement effect, CDs are immobilized into the interrupted defects of the three-dimensional S-1 matrix. The as-prepared composite possesses high photoluminescence quantum yield (63%) and extra-high stability in common organic solvents and various pH solutions (pH=2–14). Moreover, the feasibility of the CDs@S-1 composite as a fluorescent label on various substrates was investigated. The results demonstrate the images with well-defined papillary ridges under ultraviolet (UV) light and show great potential for latent fingerprints detection in forensic science.
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ACS Sustainable Chemistry & Engineering
·
2019
·
IF 6.97
Mingjie Chen,Rui-Min Li,Troy Runge,Jin Feng,Jing Feng,Songnan Hu,Qing-Shan Shi
Cellulose acetate is one of the oldest synthetic thermoplastic polymers and has various applications including usage as films, fibers, and membrane products. Traditionally, cellulose acetate is prepared by reacting cellulose with acetic anhydride in acetic acid using sulfuric acid as a catalyst. This process suffers from extensive depolymerization of the cellulose molecules and corrosion of the equipment from the use of the acidic solvent and catalyst. Herein we present an acid-free cellulose acetylation process using vinyl acetate as both the reactant and reaction medium and 1-ethyl-3-methylimidazolium acetate as the catalyst. The obtained cellulose acetate was confirmed by FTIR, NMR, and XRD studies. Additionally, the reaction kinetics, mechanism of the process, and properties of the obtained cellulose acetate were studied. Cellulose triacetate was obtained by our process within 2 h at 90 °C. The reaction kinetics was described with the classical pseudo-first-order rate expression of heterogeneous cellulose acetylation. The reaction mechanism was shown to be a peel-off mechanism similar to that of cellulose acetylation by the traditional acetic acid process. The molecular weight of the cellulose acetate produced by this new process was significantly higher than that from the traditional acetic acid process because of the absence of strong acids, which can depolymerize cellulose. In summary, we describe a new acid-free process to produce cellulose acetate that limits cellulose depolymerization and avoids the use of corrosive chemicals.
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