Biochemistry and Cell Biology
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2017
·Vol. 95
·期 6
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IF 1.895
Xilin Xu,Hang Lv,Xiaodong Li,Hui Su,Xiaofeng Zhang,Jun Yang
Danshen (Salvia miltiorrhiza) is a traditional Chinese medicine herb that can alleviate the symptoms of osteoarthritis (OA) (Söder et al. 2006) in animals. However, the underlying mechanisms remain poorly understood and require further investigation. In this study, rabbits with experimentally induced OA were given an intra-articular injection of danshen (0.7 mL/day) for 5 weeks. In addition to attenuating the cartilage degeneration of OA in the rabbits, danshen decreased the expression and activity of matrix metalloproteinase 9 (MMP-9) and MMP-13, and increased the expression of their natural inhibitors: tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and TIMP-2. Apoptosis in osteoarthritic cartilage tissues was attenuated by danshen, accompanied with increased expression of B cell lymphoma 2 (Bcl-2) and decreased levels of Bcl-2-associated X protein (Bax). Further, danshen inhibited the nuclear accumulation of nuclear factor kappa-B (NF-κB) p65 in osteoarthritic cartilage. The therapeutic effects of danshen in vivo were comparable to that of sodium hyaluronate, which is a drug used clinically for the treatment OA. In vitro, sodium nitroprusside (SNP) was used to stimulate apoptosis in primary rabbit chondrocytes. We found that the SNP-induced apoptosis was mitigated by danshen. BAY11-7028, an inhibitor of the NF-κB pathway, augmented danshen’s anti-apoptotic effects in cells exposed to SNP. When these results are considered together, they indicate that danshen alleviates the cartilage injury in rabbit OA through inhibition of the NF-κB signaling pathway.
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Scientific Reports
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2017
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IF 4.259
Xie Xiaoyun,Han Chaofei,Zeng Weiqi,Chen Chen,Lu Lixia,Liu Queping,Peng Cong,Zhao Shuang,Su Juan,Chen Xiang
The F1F0-ATP synthase, an enzyme complex, is mainly located on the mitochondrial inner membrane or sometimes cytomembrane to generate or hydrolyze ATP, play a role in cell proliferation. This study focused on the role of F1F0-ATP synthase in keratinocyte differentiation, and its relationship with intracellular and extracellular ATP (InATP and ExATP). The F1F0-ATP synthase β subunit (ATP5B) expression in various skin tissues and confluence-dependent HaCaT differentiation models was detected. ATP5B expression increased with keratinocyte and HaCaT cell differentiation in normal skin, some epidermis hyper-proliferative diseases, squamous cell carcinoma, and the HaCaT cell differentiation model. The impact of InATP and ExATP content on HaCaT differentiation was reflected by the expression of the differentiation marker involucrin. Inhibition of F1F0-ATP synthase blocked HaCaT cell differentiation, which was associated with a decrease of InATP content, but not with changes of ExATP. Our results revealed that F1F0-ATP synthase expression is associated with the process of keratinocyte differentiation which may possibly be related to InATP synthesis.
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LANGMUIR
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2016
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IF 3.993
Quan-Xing Mao,Shuang E,Jun-Mei Xia,Ru-Sheng Song,Yang Shu,Xu-Wei Chen,Jian-Hua Wang
Tunable fluorescent emission and applications in both in vitro and in vivo imaging of hydrophobic carbon nanodots (CNDs) with rapid penetration capability are reported. The hydrophobic CNDs are prepared via hydrothermal treatment of ionic liquid 1-ethyl-3-methylimidazolium bromide and exhibit excitation-dependent photoluminescence behavior along with a red-shift in the excitation/emission maxima with concentration. The quantum yields of the as-prepared CNDs are in the range of 2.5–4.8% at an excitation wavelength of 300–600 nm. The rapid penetration behavior (within 1 min) of CNDs into the cell membrane significantly reduces the sample treatment time and avoids potential fluorescence quenching induced by the interaction between CNDs and samples. A co-location study reveals that the hydrophobic CNDs are distributed mainly in the lysosome. The potentials of the hydrophobic CNDs as fluorescent probe in in vitro and in vivo imaging are well demonstrated by the labeling of HeLa cells, MCF-7 cells, A549 cells, and Kunming mice.
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CHEMOSPHERE
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2024
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IF 8.1
Huilin Chen,Maomao Xie,Wenjie Li,Lipin Tan,Xiaoming Cai,Mingjing Shen,Ruibin Li
The extensive use of synthetic antioxidants, notably N-(1,3-dimethylbutyl)-N′-phenyl- p -phenylenediamine (6-PPD), in rubber-related products, particularly in tire manufacturing, has induced concerns regarding their environmental impact and potential health hazards. Despite the identification of 6-PPD and its derivative, 6-PPD quinone (6-PPDQ), in various water samples and their lethal effects on certain aquatic species ( e.g. , coho salmon, rainbow trout and brook trout), the levels of airborne 6-PPD/6-PPDQ and their respiratory toxicity remain relatively unexplored. In this study, we aimed to evaluate the respiratory toxicity potential of 6-PPD and its derivatives, with a specific focus on detecting these compounds in airborne particulates and assessing their toxic effects on lung cells. Characterization of four airborne fine particulate (FP) samples revealed spherical morphologies with diameters ranging from 17.7 to 225.7 nm, displaying slight agglomeration and negative surface charge. methanol/acetonitrile extraction followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis confirmed the presence of both 6-PPD and 6-PPDQ on the surfaces of FPs, with significant variations (0.26–1.05 μg g −1 ) in loading capacity observed among the samples. Subsequent exposure of lung cells (THP-1, BEAS-2B, and A549) to 6-PPD and 6-PPDQ revealed dose-dependent declines in mitochondrial metabolic activity induced by 6-PPD, along with severe membrane damage, ATP depletion, and pro-inflammatory cytokine release. Conversely, 6-PPDQ exhibited negligible toxicity in all tested parameters. These findings underscore the potential health risks associated with airborne 6-PPD exposure and emphasize the importance of further research into the respiratory toxicity of 6-PPD derivatives.
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CARBON
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2025
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IF 11.6
Lin Xie,Ruilin Liu,Xiaomeng Jiang,Cui Ni,Baolei Wang,Chuanxin Hou,Di Lan,Wei Du,Xiubo Xie
In order to obtain multiple interfaces of Co/CoO by tuning the oxidation process and simultaneously clarify the interface migration, Co particles loaded on mangosteen shell-derived carbon (MSC) were prepared, and then oxidized under a mixed atmosphere of Ar/O 2 and 300 °C with different oxidation time. Due to the existence of MSC, the Co can completely oxidized in short time of 60 min and low O 2 concentration of 5 %. The oxidation process is: Co→CoO→Co 3 O 4 . A lot of defects in-situ formed in the oxidation process can be clearly detectable. Co/MSC composites oxidized at 300 °C for 10 min exhibits considerable minimum reflection loss of −37.86 dB and an effective absorption bandwidth of 5.28 GHz among the composites with different oxidation times. The Co/CoO, CoO/C, Co/C heterogeneous interfaces are conducive to the depletion of electromagnetic waves through interfacial polarization. The in-situ formed defects are positive for enhancing the dipole prolarization, and the natural resonance is also enhanced due to the presence of Co and its oxides. The positive effects of carbon additive in the oxidation of Co on the in-situ defects formation and multiple interface construction provide a new perspective for designing high performance microwave absorption materials.
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Advanced Science
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2024
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IF 14.3
Dingyuan Guo,Nan Li,Xiaoyan Zhang,Runxin Zhou,Jie He,Xiao-Ping Ding,Weixing Yu,Fuqiang Tong,Sibi Yin,Yu Wang,Xin Xu,Long Wang,Mingzhu Fan,Shan Feng,Ke Liu,Ke Tang,Zhuqing Ouyang,Yusong R Guo,Yugang Wang
N 6 -acetyl- L - lysine residue is abundant in dietary protein but little is known about its potential influences on the diet-consumers. Herein, it is reported that Lysyl-tRNA synthetase (KARS) mediates co-translational deposition of diet-derived N 6 -acetyl- L -lysine (AcK) in nascent proteins to contribute to the acetylome in cells. Acetylated dietary protein is a direct source of AcK that can widely and substantially regulate the acetylome in multiple organs of mice. By analyzing the mechanisms underlying AcK contributing to the acetylome in mammalian cells, it is found that KARS can utilize AcK as an alternative substrate to produce N 6 -acetyl- l -lysyl-tRNA. The crystal structure of KARS in complex with AcK at 2.26 Å resolution shows that AcK shares the same substrate-binding pocket as L -lysine, allowed by a sidechain flip of Tyr499. The generated N 6 -acetyl- L -lysyl-tRNA introduces AcK into growing nascent polypeptide and results in protein acetylation, including the regions buried inside folded proteins that are post-translational modification (PTM)-inaccessible and functionally important. This undocumented protein modification mechanism is inherently different from PTM and termed as co-translational modification (coTM). It is expected to extend the repertoire of acetylome and improve the understanding of protein modification mechanisms in cells.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Lele Wang,Tijie Duan,Yawen Gao,Heqing Liu,Rui Sun,Tong Wu,Jihui Tang
Subject The release rate of hydrophilic gel tablets varies depending on their surface area. In this study, we aimed to develop a sustained-release tablet that maintains a constant release area during drug release. Methods Initially, commercially accessible gliclazide, sinomenine hydrochloride, and trimetazidine hydrochloride tablets were side coated with ethylcellulose to ensure a constant release area. Next, sustained-release gliclazide tablets were prepared by altering their size and thickness to assess the impact of specific surface area on drug release. Then, two types of sustained-release gliclazide tablets were developed and evaluated in vitro. One involved side-coating the tablets with an ethylcellulose solution. The second was a novel three-layer donut-shaped tablet. Finally, these novel sustained-release tablets were evaluated for in vivo drug release and pharmacokinetics in rabbits. Results After lateral coating, commercial tablets altered drug release from first-order to zero-order kinetics. Tablets with the same specific surface area, but different diameters and thicknesses, can have similar release profiles. If the drug release area is unchanged, the tablet typically exhibits zero-order release behavior. Thus, we developed two types of gliclazide sustained-release tablets with a constant release area that achieved zero-order drug release. In vivo, they showed smoother plasma concentration profiles with lower C max , extended T max , and reduced fluctuation, and were bioequivalent to commercial tablets in pharmacokinetic studies. Conclusions Stable drug release can be achieved by maintaining a constant release area. In this study, the novel tablet preparations exhibited consistent drug release both in vivo and in vitro.
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PHYTOMEDICINE
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2024
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IF 6.7
Xin-Rong Wang,Hua Zhong,Shan-Shan Ma,Ya-Hui Huang,Wei-Heng Xu,Yan Wang
Background The incidence of invasive fungal diseases (IFDs), represented by Candida albicans infection, is increasing year by year. However, clinically available antifungal drugs are very limited and encounter challenges such as limited efficacy, drug resistance, high toxicity, and exorbitant cost. Therefore, there is an urgent need for new antifungal drugs. Purpose This study aims to find new antifungal compounds from plants, preferably those with good activity and low toxicity, and reveal their antifungal targets. Methods In vitro antifungal activities of compounds were investigated using broth microdilution method, spot assay, hyphal growth assay and biofilm formation assay. Synergistic effects were assessed using broth microdilution checkerboard technique. In vivo antifungal activities were evaluated using Galleria mellonella and murine candidiasis models. Cytotoxicity of compounds was investigated using Cell Counting Kit-8 (CCK-8). Discovery and validation of antifungal targets of compounds were conducted by using monoallelic knockout library of C. albicans , haploinsufficiency profiling (HIP), thermal shift assay (TSA), enzyme inhibitory effect assay, molecular docking, and in vitro and in vivo antifungal studies. Results 814 plant products were screened, among which petroselinic acid (PeAc) was found as an antifungal molecule. As a rare fatty acid isolated from coriander ( Coriandrum sativum ), carrot ( Daucus carota ) and other plants of the Apiaceae family, PeAc had not previously been found to have antifungal effects. In this study, PeAc was revealed to inhibit the growth of various pathogenic fungi, exhibited synergistic effects with fluconazole (FLC), inhibited the formation of C. albicans hyphae and biofilms, and showed antifungal effects in vivo. PeAc was less toxic to mammalian cells. Fructose-1,6-bisphosphate aldolase (Fba1p) was identified as a target of PeAc by using HIP, TSA, enzyme inhibitory effect assay and molecular docking methods. PeAc exerted antifungal effects more effectively on fba1Δ/FBA1 than wild-type (WT) strain both in vitro and in vivo . Conclusions PeAc is an effective and low toxic antifungal compound. The target of PeAc is Fba1p. Fba1p is a promising target for antifungal drug development.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Maoshan Wang,Yingxue Liu,Houda Gui,Gaoqiang Ma,Binyang Li,Zhanwei Zhang,Gyeonghwi Yu,Ailin Wu,Xin Xu,Dongjiao Zhang
Eldecalcitol (ED-71), a novel active form of vitamin D, shows potential in treating osteoporosis. However, its underlying mechanisms of action remain to be determined. This study aimed to investigate the effect of ED-71 on bone regeneration and to illustrate its mode of action. The in-vitro model was developed using rat primary osteoblasts cultured under high-glucose conditions, and these cells were treated with ED-71. Additionally, an in vivo model of cranial bone defects was established in type 2 diabetic rats, and ED-71 was administered by gavage. The results demonstrated that ED-71 prevented osteoblast cell death, enhanced rat primary osteoblasts' osteogenic capacity, and attenuated the overexpression of hypoxia-inducible factor 1α (HIF1α) induced by high glucose levels. Furthermore, ED-71 increased glutathione peroxidase 4 (GPX4) levels and inhibited ferroptosis in response to hyperglycemic stimulation. Notably, interference with the HIF1α activator and ferroptosis activator Erastin significantly reduced the therapeutic effects of edetate osteolysis. These findings were further tested in vivo experiments. These results suggest that ED-71 activates the HIF1α pathway in vivo and in vitro, effectively relieving the ferroptosis induced by high glucose. Significantly, ED-71 may improve osteogenic disorders caused by diabetes.
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ChemCatChem
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2024
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IF 3.8
Hao Liu,Jian Zhao,Min Zhang
Graphical Utilizing CuPd alloy on C 3 N 4 as catalyst, the photoswitched coupling of alkynes under anaerobic and alkali-free conditions was achieved. The dual photoactive species (coppr phenylacetylide intermediate and the LSPR effect of Cu) and the interface between Cu and Pd is essential for efficiently swtiching the reaction pathway. Various ratios of CuPd alloy are loaded on C 3 N 4 and utilized as efficient photocatalyst for the light-switched homo-coupling of alkynes in anaerobic and base free condition. For the model phenylacetylene reactant, the light-irradiation promotes the reaction rate from 36.9 % to 99.9 % and the selectivity of 1,3-diynes from 0 % to 68.7 %. Different supports, solvents and the induction period of the prepared samples show influence on the activity. The action spectra with different light wavelengths demonstrate that both copper phenylacetylide intermediate formed during the reaction and the localized surface plasmon resonance (LSPR) effect of the copper in CuPd alloy are the photoactive species. Through the control experiments, it confirms that these dual photoactive species and the interface between Cu and Pd are essential for efficient light-switching reaction pathway.
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Antioxidants
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2024
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IF 6
Xiao Xiao,Feiyu Yang,Yuling Huang,Shaohui Liu,Zhenhua Hu,Shanggao Liao,Yuanyuan Li
Numerous approaches targeting hepatic stellate cells (HSCs) have emerged as pivotal therapeutic strategies to mitigate liver fibrosis and are currently undergoing clinical trials. The investigation of herbal drugs or isolated natural active compounds is particularly valuable, due to their multifaceted functions and low risk of side effects. Recent studies have hinted at the potential efficacy of verbascoside (VB) in ameliorating renal and lung fibrosis, yet its impact on hepatic fibrosis remains to be elucidated. This study aims to evaluate the potential effects of VB on liver fibrosis by assessing its ability to inhibit HSC activation. VB demonstrated significant efficacy in suppressing the expression of fibrogenic genes in activated LX-2 cells. Additionally, VB inhibited the migration and proliferation of these activated HSCs by scavenging reactive oxygen species (ROS) and downregulating the AMPK pathway. Furthermore, a biosafe reverse microemulsion loaded with VB (VB-ME) was developed to improve VB’s instability and low bioavailability. The optimal formulation of VB-ME was meticulously characterized, revealing substantial enhancements in cellular uptake, ROS-scavenging capacity, and the suppression of HSC activation.
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ACS ES&T Engineering
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2024
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IF 7.4
Yi Shen,Mingzheng Yang,Chao Zhu,Haizhong Zhang,Renlan Liu,Jun Wang,Qile Fang,Shuang Song,Baoliang Chen
The activation of peroxymonosulfate (PMS) to generate singlet oxygen (1O2) for the removal of emerging organic pollutants (EOPs) from complex aqueous environments has garnered widespread attention. However, the low efficiency and selectivity of current PMS activation for 1O2 generation result in suboptimal EOP degradation. To enhance the selectivity of PMS activation and promote the non-radical pathway, non-metal heteroatoms with varying electronegativities were introduced to disrupt the symmetrical coordination structure of Fe active sites in Fe single-atom catalysts. The results showed that, in the B-Fe1/GLCNs/PMS system, the pseudo-first-order kinetic rate for bisphenol A (BPA) degradation reached 4.435 min–1, which is 7.4 times higher than that of the unmodified control group. Experimental and theoretical calculations demonstrated that the doping of non-metal heteroatoms altered the electron density and distribution at the Fe active sites, thereby modulating the adsorption configuration of HSO5– and increasing the selectivity for PMS activation to generate 1O2. Additionally, the degradation of EOPs by 1O2 produced intermediate products with lower biological toxicity, and 1O2 demonstrated strong anti-interference capability. The change in HSO5– morphology improved the rate of 1O2 generation. This study provides deep insights into designing high-performance PMS activation catalysts via non-metal doping to regulate the electronic structure of active sites for a selective non-radical pathway.
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