JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-11
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IF 9.429
Hsieh Yuan-Chin,Liao Jun-min,Chuang Kuo-Hsiang,Ho Kai-Wen,Hong Shih-Ting,Liu Hui-Ju,Huang Bo-Cheng,Chen I-Ju,Liu Yen-Ling,Wang Jaw-Yuan,Tsai Hsiang-Lin,Su Yu-Cheng,Wang Yen-Tseng,Cheng Tian-Lu
Background Humanization of mouse monoclonal antibodies (mAbs) is crucial for reducing their immunogenicity in humans. However, humanized mAbs often lose their binding affinities. Therefore, an in silico humanization method that can prevent the loss of the binding affinity of mAbs is needed.Methods We developed an in silico V(D)J recombination platform in which we used V(D)J human germline gene sequences to design five humanized candidates of anti-tumor necrosis factor (TNF)-α mAbs (C1–C5) by using different human germline templates. The candidates were subjected to molecular dynamics simulation. In addition, the structural similarities of their complementarity-determining regions (CDRs) to those of original mouse mAbs were estimated to derive the weighted interatomic root mean squared deviation (wRMSDi) value. Subsequently, the correlation of the derived wRMSDi value with the half maximal effective concentration (EC50) and the binding affinity (KD) of the humanized anti-TNF-α candidates was examined. To confirm whether our in silico estimation method can be used for other humanized mAbs, we tested our method using the anti-epidermal growth factor receptor (EGFR) a4.6.1, anti-glypican-3 (GPC3) YP9.1 and anti-α4β1 integrin HP1/2L mAbs.Results The R2 value for the correlation between the wRMSDi and log(EC50) of the recombinant Remicade and those of the humanized anti-TNF-α candidates was 0.901, and the R2 value for the correlation between wRMSDi and log(KD) was 0.9921. The results indicated that our in silico V(D)J recombination platform could predict the binding affinity of humanized candidates and successfully identify the high-affinity humanized anti-TNF-α antibody (Ab) C1 with a binding affinity similar to that of the parental chimeric mAb (5.13 × 10−10). For the anti-EGFR a4.6.1, anti-GPC3 YP9.1, and anti-α4β1 integrin HP1/2L mAbs, the wRMSDi and log(EC50) exhibited strong correlations (R2 = 0.9908, 0.9999, and 0.8907, respectively).Conclusion sOur in silico V(D)J recombination platform can facilitate the development of humanized mAbs with low immunogenicity and high binding affinities. This platform can directly transform numerous mAbs with therapeutic potential to humanized or even human therapeutic Abs for clinical use.Graphical Abstract
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SCIENCE OF THE TOTAL ENVIRONMENT
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2022
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IF 10.753
Hui Tao,Lan Yang,Yiting Qi,Yiyang Chen,Duo Yu,Lingqin Zhou,Tao Lin,Hang Xu,Junlong Song
The mobility of microplastics (MPs) in aqueous media is closely related to their environmental risk. The naturally occurring silica substrate surface in the aquatic environment is easily colonized by microorganisms and forms a biofilm, which may affect the migration and distribution of MPs. Herein, a typical MP, polystyrene (PS), and Pseudomonas fluorescens ( P. fluorescens ) biofilms were selected to study the deposition and release of pristine or ultraviolet (UV)-aged PS MPs on silica and biofilms under different ionic strengths using a quartz crystal microbalance dissipation (QCM-D) system. Statistical analyses of the deposition experiments revealed a significant impact of P. fluorescens biofilms on deposition ( p = 0.0042). The deposition rate of weathered MPs on the biofilms was 4.0 ± 0.1 to 16.3 ± 0.6 times that on silica. A release experiment revealed that the biofilm reduced the release fraction ( f r ) of weathered MPs by 34.5 ± 0.3 % compared to bare silica. In addition, the UV-ageing treatment reduced the deposition mass of MPs on the surface of silica by 27.6 ± 0.21 % compared to pristine microspheres. The analysis of the deposition mechanism revealed that the promotion and inhibition of biofilm or UV-ageing treatment on the deposition of microspheres could be attributed to the non-Derjaguin-Landau-Verwey-Overbeek (DLVO) force and the decreased electrostatic repulsion or the increased hydration repulsion, respectively.
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Drug Design Development and Therapy
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2022
·
IF 4.319
Bozhi Ye,Xudong Chen,Shanshan Dai,Jibo Han,Xiaohe Liang,Shuang Lin,Xueli Cai,Zhouqing Huang,Weijian Huang
Background Emodin has recently been reported to have a powerful antiinflammatory effect, protecting the myocardium against ischemia/reperfusion (I/R) injury. Pyroptosis is a proinflammatory programmed cell death that is related to many diseases. The present study investigated the effect of emodin on pyroptosis in cardiomyocytes.Materials and methods Sprague Dawley rats were randomly divided into sham, I/R, and I/R+Emodin groups. I/R model was subjected to 30 minutes’ ligation of left anterior descending coronary artery, followed by 2 hours of reperfusion. Cardiomyocytes were exposed to hypoxic conditions for 1 hour and normoxic conditions for 2 hours. The level of the pyroptosis was detected by Western blot, real-time PCR analysis, and ELISA.Results The level of gasdermin D-N domains was upregulated in cardiomyocytes during I/R or hypoxia/reoxygenation (H/R) treatment. Moreover, emodin increased the rate of cell survival in vitro and decreased the myocardial infarct size in vivo via suppressing the levels of I/R-induced pyroptosis. Additionally, the expression of TLR4, MyD88, phospho-IκBα, phospho-NF-κB, and the NLRP3 inflammasome was significantly upregulated in cardiomyocytes subjected to H/R treatment, while emodin suppressed the expression of these proteins.Conclusion This study confirms that emodin treatment was able to alleviate myocardial I/R injury and inhibit pyroptosis in vivo and in vitro. The inhibitory effect of emodin on pyroptosis was mediated by suppressing the TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway. Therefore, emodin may provide an alternative treatment for myocardial I/R injury.
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Food Bioscience
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2022
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IF 5.318
Xuan Chen,Jinwen Yu,Liufeng Zheng,Zeyuan Deng,Hongyan Li
Quercetin and lycopene are strong dietary antioxidants that often co-exist in foods . Here, the cardiac and neuroprotective effects of quercetin and lycopene combination were analyzed in d -galactose-induced oxidative stress in mice. ICR mice were divided into control group, d -galactose group (D-GAL), quercetin treatment (Q45: 45 mg kg −1 d −1 quercetin, Q60: 60 mg kg −1 d −1 quercetin), lycopene treatment (15 mg kg −1 d −1 lycopene), and M groups (45 mg kg −1 d −1 quercetin+15 mg kg −1 d −1 lycopene). Mice were given quercetin, lycopene, and their combination through oral gavage for 6 weeks. They were injected with d -galactose (150 mg kg −1 d −1 ) simultaneously except for the control group. Results showed that the quercetin-lycopene combination could ameliorate histopathological injuries in the heart and hippocampus. They significantly decreased the serum and heart malonaldehyde (MDA) levels, heart 4-Hydroxynonenal (4-HNE) levels, and increased the activity of serum and heart superoxide dismutase (SOD), catalase (CAT), and the hippocampal SOD and CAT mRNA level. Quercetin-lycopene combination exhibited anti-inflammation effects by reducing inflammatory genes such as cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β). The heart and hippocampal mRNA level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression was up-regulated, and the antioxidant genes related to Nrf2 including heme oxygenase-1 (HO-1), NAD(P)H Quinone Dehydrogenase 1 (NQO1) were elevated. Quercetin-lycopene combination significantly promoted the mRNA level of deacetylase sirtuin-1 (SIRT1), increased 3.3-fold and 3-fold SIRT1 expression in the heart and hippocampus, respectively. They could bind SIRT1 at the active site predicted by molecular docking . These results suggested that they may interact with SIRT1 to activate Nrf2, inhibit pro-inflammatory factors, and prevent oxidative stress in D-GAL-induced mice.
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PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY
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2021
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IF 2.162
Shu Ye,Fan Zhang,Ying Xu,Yun Sun,Benwei Zhu,Fang Ni,Zhi Zhou,Zhong Yao
In this study, a series of acidic or alkaline polypeptide chains were designed and grafted onto DEG-AM resin using Fmoc solid-phase synthesis to study the relationship between enzyme conformation and carrier surface charge. β-d-glucosidase (βGase) was then immobilized onto these modified carriers by adsorption. Each form of immobilized βGase showed decreasing specific activity compared to that of the free. It could be attributed to both the changes in the enzyme conformation and the decrease in mass transfer efficiency. The optimum temperature of free βGase, DEG@B3-βGase is 55 °C, which of DEG@A3-βGase is 65 °C and they all have the highest activity at pH 5. The Ea values of free βGase, DEG@A3-βGase, and DEG@B3-βGase are 0.546 kJ/mol, 0.224 kJ/mol, and 0.446 kJ/mol, and the Km values were 1.30 mmol/L, 1.44 mmol/L and 2.63 mmol/L, respectively. It shows that free βGase and DEG@A3-βGase are more similar. Meanwhile, the free βGase (1.0 g/L, pH 5.0) stored at 4 °C has a shorter half-life (t1/2), which is only 9 days. However, the half-life of DEG@B3-βGase and DEG@A3-βGase is 20 days and over 60 days, indicating that the negative charged surface was conducive to maintenance of the structure and catalytic property of βGase.
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Materials Today Physics
·
2021
·
IF 9.298
Chengyuan Tang,Xinyu Shen,Siyao Yu,Yuan Zhong,Zhenyu Wang,Junhua Hu,Min Lu,Zhennan Wu,Yu Zhang,William W. Yu,Xue Bai
Inorganic CsPbX 3 (X = Cl, Br, I) perovskite nanocrystals (PNCs) have a great promise for LED applications due to their high brightness and tunable emission. However, the long chain capping ligands such as oleylamine and oleic acid function are electrically insulating layers to hinder the charge carrier injection and transport, limiting the device performances. To overcome the limitations, p -iodo-D-phenylalanine (PIDP) was used in the post-treatment process of PNCs to partially substitute the long insulating ligands to improve the conductivity of CsPbI 3 PNC films. Besides, the surface defects were also passivated by PIDP, increasing the radiative decay rate and decreasing the non-radiative decay rate, thus enhanced the photoluminescence quantum yield of the PNCs. As a result, highly efficient PNC LEDs were obtained with an external quantum efficiency of 12.4% and a peak luminance of 2000 cd m −2 .
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Materials Today Communications
·
2021
·
IF 3.383
Xiangping Hao,Jingzhi Yang,Lei Zhang,Chenhao Ren,Wen Li,Yuntian Lou,Hongchang Qian,Shougang Chen,Dawei Zhang
Bacterial infections, as one of the main reasons for failure of metallic implants, can increase morbidity and mortality. In this study, polydopamine/graphene oxide- d -leucine (PDA/GO-Leu) films that possess pH-responsive antibacterial and anti-adhesion properties were synthesized by the soaking method. Due to the unique features of ampholyte, d -leucine has the same type of charge as the immobilized GO surface when the pH value of the environment is identical to that of the humoral environment. It contributes to the d -leucine release from the GO surface and exerts antibacterial and anti-adhesion effects of such films. The synergistic actions between d -leucine and GO of such films were analyzed by the table colony counting method and dead/live fluorescence. The results indicated that the released d -leucine is the key point within this multilayer system. The PDA/GO-Leu films exhibited both outstanding antibacterial and anti-adhesion properties for E. coli and S. aureus, respectively when pH of the culture medium was 7.4. Meanwhile, the cytotoxicity of the PDA/GO-Leu films was evaluated by CCK-8 and dead/live fluorescence, and the results demonstrated that such films have good biocompatibility.
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JOURNAL OF APPLIED POLYMER SCIENCE
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2021
·Vol. 138
·期 36
·50926
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IF 3.125
Haoran Xu,Yanjun Hou,Rui Li,Lijing Chang,Yang Ma,Shoulei Miao,Haijun Niu
Two donor units (D)-acceptor units (A) type monomers were synthesized by Stille coupling reaction, and then three D-A type hybrid polymers based on 3,4-ethylenedioxythiophene and various benzodiazoles were synthesized by electrochemical polymerization. Spectroelectrochemical and kinetic studies of these polymers showed that all polymer films exhibited excellent electrochromic behavior, obvious optical contrast, and excellent stability. Among them, the response time of P3 film was the shortest ( t c = 1.6 s, t b = 2.2 s), the coloring efficiency of P2 film was the highest ( CE = 333 cm 2 ·C −1 ), and the stability of P1 was the best (the ΔT loss of P1 after 1000 s cycles is only 2.3%). Therefore, these data prove that these new polymers have great potential in applications as electrochromic materials.
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Food Science & Nutrition
·
2021
·Vol. 9
·期 7
·3722-3731
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IF 2.863
Lin Zhu,Yingjuan Liu,Xiaolin Wu,Yuqian Ren,Qinghua Zhang,Leiming Ren,Yunliang Guo
Cerebroprotein hydrolysate-I (CH-I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH-I on brain senescence via JAK2/STAT3 pathway. The results showed that CH-I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence-positive cells induced by D-galactose. In vivo , CH-I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH-I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH-I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH-I in delaying aging.
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Bioresources and Bioprocessing
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2021
·Vol. 8
·期 1
·1-15
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IF 4.578
Tan Xu,Zhang Sheng,Song Wei,Liu Jia,Gao Cong,Chen Xiulai,Liu Liming,Wu Jing
In this study, a four-enzyme cascade pathway was developed and reconstructed in vivo for the production of d - p -hydroxyphenylglycine (D-HPG), a valuable intermediate used to produce β-lactam antibiotics and in fine-chemical synthesis, from l -tyrosine. In this pathway, catalytic conversion of the intermediate 4-hydroxyphenylglyoxalate by meso -diaminopimelate dehydrogenase from Corynebacterium glutamicum ( Cg DAPDH) was identified as the rate-limiting step, followed by application of a mechanism-guided “conformation rotation” strategy to decrease the hydride-transfer distance d (C6HDAP−C4NNADP) and increase Cg DAPDH activity. Introduction of the best variant generated by protein engineering ( Cg DAPDH BC621/D120S/W144S/I169P with 5.32 ± 0.85 U·mg −1 specific activity) into the designed pathway resulted in a D-HPG titer of 42.69 g/L from 50-g/L l -tyrosine in 24 h, with 92.5% conversion, 71.5% isolated yield, and > 99% enantiomeric excess in a 3-L fermenter. This four-enzyme cascade provides an efficient enzymatic approach for the industrial production of D-HPG from cheap amino acids.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
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IF 5.279
Pengfei Liu,Jiaojiao Zhang,Yan Qiao,Xianglin Hou,Yu Liu,Yingxiong Wang
Using environment-friendly catalysts to convert biomass into compounds with high values is one of the central topics of green chemistry. In this work, [Ch][Pro] (cholinium as the cation and l-proline as the anion) ionic liquid was synthesized and applied as a model catalyst in the production of deoxyfructosazine (DOF) and fructosazine (FZ) from d-glucosamine (GlcNH2). The 13C NMR chemical shift titration experiments and the diffusion-ordered NMR spectroscopy (DOSY) measurements showed that, when the [Ch][Pro] interacted with GlcNH2, the l-proline anion ([Pro]−) played a major catalytic role instead of cholinium cation ([Ch]+). The effects of the reaction temperature and the amount of [Ch][Pro] on the product yields were surveyed. The experimental results showed that the highest DOF yield (33.78%) was obtained after 30 min at 100 °C when the molar ratio of [Ch][Pro]/GlcNH2 was 1. Moreover, in situ1H NMR and in situ13C NMR experiments were applied to monitor the reaction process with [Ch][Pro] as the catalyst. The reactive intermediate, dihydrofructosazine, was clearly detected by these in situ techniques. Accordingly, a possible reaction pathway was proposed. By applying other amino acids as the anions, we also prepared five other [Ch][AA] ionic liquids, and they showed different catalytic activities and selectivity in the GlcNH2 self-condensation reaction.
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BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2020
·Vol. 128
·期 5
·661-668
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IF 2.651
Hongfang Li,Yunyan Tang,Weipeng Wei,Chengchen Yin,Fushan Tang
Saikosaponin-d (SSd) is a major bioactive triterpenoid saponin extracted from Bupleurum , which has anti-inflammatory, anticancer, antioxidative and anti-hepatic fibrosis effects. Due to the effects of Bupleurum -related formulations on cytochrome P450 (CYPs) expression still remain unclear, the combination therapies involved formulations containing Bupleurum may sometimes lead to unexpected drug-drug interactions in clinical practice. These interactions can limit the clinical applications of related formulations. In this study, we tried to explore the effects of SSd on CYP3A4 mRNA, protein expression and the enzyme activity in HepaRG cells by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blot (WB) and HPLC method, respectively. The interaction between SSd and CYP3A4 was analysed by molecular docking. HepaRG cells were cultured with different concentrations of SSd (0.5, 1, 5 and 10 μmol/L) for 72 hours. It is revealed that SSd can inhibit CYP3A4 mRNA and its protein expression, and also the enzyme activity. Molecular docking study demonstrated that SSd can bind to several key active sites of amino acid residues of CYP3A4 protein with hydrogen bonds and hydrophobic interactions. Thus, drug-drug interactions resulted by SSd inhibiting CYP3A4 need attention when formulations containing SSd or Bupleurum are co-administrated with drugs metabolized by CYP3A4.
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