INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yingzhu Lian,Guiming Fu,Xinmei Liang,Xinchao He,Jin Xu,Haowei Fan,Yin Wan
Caffeioyl quinic acids and polysaccharides from Artemisia selengensis Turcz are considered potential bioactive substances for hyperuricemia (HUA) treatment. While the mechanism of multi-component combined intervention of polysaccharides and dicaffeoylquinic acids (diCQAs) is not yet clear. In this study, we investigated the effect of A. selengensis Turcz leaves polysaccharides (APS) on the HUA treatment with diCQAs in vitro by direct inhibition of XOD activities and in vivo by using animal model. The results showed that APS had almost no inhibitory effect on XOD activities in vitro , but the inhibitory activity of diCQAs on XOD was affected by changes in inhibition type and inhibition constant. Compared to APS and diCQAs alone, high-dose APS and diCQAs in combination (ADPSh) could significantly reduce the production of uric acid (16.38 % reduction compared to diCQAs group) and oxidative stress damage. Additionally, this combined therapy showed promise in restoring the gut microbiota balance and increasing the short-chain fatty acids levels. The results suggested that APS and diCQAs in combination could be a potential inhibitor for HUA treatment.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
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IF 4.9
Ziwei Yan,Hui Zhang,Jinghao Chen,Qingqing Xu,Shuaipeng Feng,Qinfu Zhao,Siling Wang
Photothermal effect produced in photothermal therapy (PTT) can not only eradicate tumors but also allow the promotion of biological and chemical reactions in tumor tissues, leading to the potential of photothermal-enhanced anti-tumor therapy with desirable outcomes. Biodegradable polydopamine (PDA) nanoparticles exhibit remarkable photothermal conversion efficiency and stability, making them ideal photothermal agents (PTAs) to achieve photothermal-enhanced anti-tumor therapy. The high affinity of PDA to metal ions provides a broad application prospect for the development of multi-functional nanoplatforms to achieve cancer therapy with high efficacy and specificity. In this work, we fabricated Cu(II)-doped mesoporous PDA nanoparticles with polyethylene glycol (PEG) modified (CMP-P), which not only possessed higher photothermal conversion efficacy than mesoporous PDA nanoparticles , but also presented distinctive self-enhanced chemodynamic (CDT) performance. CMP-P mediated CDT was predicated on catalyzing the Fenton-like reaction to generate hydroxyl radicals (·OH). Impressively, CMP-P further triggered glutathione (GSH) depletion intracellular to prevent the consumption of ·OH, and the photothermal effect further improved ·OH generation. Meanwhile, CMP-P exhibited favorable degradability, the process of which was elaborated intuitively by transmission electron microscope (TEM). CMP-P was then employed for doxorubicin (DOX) loading, and enabled the enhanced DOX release in-situ under the stimulation of photothermal effect and tumor micro-environment (TME). The lower IC 50 value of DOX/CMP-P (1.68 μg/mL) than the signal therapy suggested the superior synergistic effect of DOX/CMP-P. Meanwhile, in vivo experiments also revealed the considerably improved anti-tumor efficacy of synergistic therapy mediated by DOX/CMP-P.
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FOOD CONTROL
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2024
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IF 5.6
Jianli Zhou,Junjun Wang,Xiaohuan Huang,Lian Xia,Han Tao,Yuangen Wu
The colorimetric methods for histamine detection still face some challenges in accuracy and stability. Herein, a novel colorimetric aptasensor for sensitive and highly selective detection of histamine was developed based on the enhancement of silver citrate (AgCit) laccase-mimic activity. It has been confirmed that H2 aptamer enhances the affinity of AgCit to the chromogenic substrate, and promotes the generation of semiquinone radical in the laccase-mimic catalytical system. The color change of the sensing solution can be distinguished by the naked eye, and easily converted to the corresponding RGB value by a smartphone for the quantitative and rapid detection of histamine. The aptasensor has a limit of detection (LOD) as low as 27 μg L −1 , and maintains high selectivity for histamine in the presence of other competitive substances. It is strongly believed that the design of a colorimetric aptasensor can provide a simple and versatile platform for histamine detection in food.
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BIOORGANIC CHEMISTRY
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2024
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IF 4.5
He Liu,Shixi Wang,Meng Xu,Kaiyue Zhang,Qian Gao,Hualei Wang,Dongzhi Wei
( R )-selective transaminases show promise as catalysts for the asymmetric synthesis of chiral amines, which are building blocks of various small molecule drugs. However, their application is limited by poor substrate acceptance and low catalytic efficiency. Here, a potential ( R )-selective transaminase from Fodinicurvata sediminis (FsTA) was identified through a substrate truncating strategy, and used as starting point for enzyme engineering toward catalysis of 4-hydroxy-2-butanone, a substrate that poses challenges in catalysis. Molecular docking and dynamics simulations revealed Y90 as the key residue responsible for poor substrate binding. Starting from the variant (Y90F, mut1) with initial activity, FsTA was systematically modified to improve substrate-binding through active site reshaping and consensus sequence strategy, yielding three variants (H30R, V152K, and Y156F) with improved activity. A quadruple mutation variant H30R/Y90F/V152K/Y156F (mut4) was also found to show a 7.95-fold greater catalytic efficiency ( k cat / K M ) than the initial variant mut1. Furthermore, mut4 also enhanced the thermostability of enzyme significantly, with the T m value increasing by 10 °C. This variant also exhibited significantly improved activity toward a series of ketones that are either not accepted or poorly accepted by the wild-type. This study provides a basis for the rational design of an active to creating variants that can accommodate novel substrates.
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ACS Nano
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2024
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IF 15.8
Hongyan Xu,Bangxun Mao,Shulan Ni,Xiaoling Xie,Sicheng Tang,Yang Wang,Xingjie Zan,Qinxiang Zheng,Wenjuan Huang
Protein drugs have been widely used in treating various clinical diseases because of their high specificity, fewer side effects, and favorable therapeutic effect, but they greatly suffer from their weak permeability through tissue barriers, high sensitivity to microenvironments, degradation by proteases, and rapid clearance by the immune system. Herein, we disrupted the standard protocol where protein drugs must be delivered as the cargo via a delivery system and innovatively developed a free entrapping matrix strategy by simply mixing bevacizumab (Beva) with zinc ions to generate Beva-NPs (Beva-Zn2+), where Beva is coordinatively cross-linked by zinc ions with a loading efficiency as high as 99.2% ± 0.41%. This strategy was universal to generating various protein NPs, with different metal ions (Cu2+, Fe3+, Mg2+, Sr2+). The synthetic conditions of Beva-NPs were optimized, and the generated mechanism was investigated in detail. The entrapment, releasing profile, and the bioactivities of released Beva were thoroughly studied. By using in situ doping of the fourth-generation polyamindoamine dendrimer (G4), the Beva-G4-NPs exhibited extended ocular retention and penetration through biobarriers in the anterior segment through transcellular and paracellular pathways, effectively inhibiting corneal neovascularization (CNV) from 91.6 ± 2.03% to 13.5 ± 1.87% in a rat model of CNV. This study contributes to engineering of protein NPs by using a facile strategy for overcoming the weaknesses of protein drugs and protein NPs, such as weak tissue barrier permeability, low encapsulation efficiency, poor loading capacity, and susceptibility to inactivation.
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LANGMUIR
·
2025
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IF 3.9
Jingke Yao,Xunjie Shang,Nannan Shao,Hao He,Jiayi Wei,Yingying Huang,Tianxi Shen,Limin Chen,Yunlong Zhou,Wei Chen
Bacteria have the potential to exhibit divergent stereochemical preferences for different levels of chiral structures, including from molecule, supramolecule, to nanomicroscale helical structure. Accordingly, the structure–activity relationship between chirality and bactericidal activity remains uncertain. In this study, we seek to understand the multivalent molecular chirality effect of chiral supramolecular polymers on antibacterial activity. Two n-butylazobenzene-modified l- and d-tripeptides (abbreviated C4Azo-l-VKK–OH and C4Azo-d-VKK–OH) were synthesized and subsequently self-assembled in water into chiral supramolecular polymers (designated l-Fiber and d-Fiber, respectively). The l-Fiber and d-Fiber displayed comparable nonhelical nanofiber morphologies but exhibited opposite multivalent molecular chirality. A comparative study demonstrated that the l-Fiber exhibited a markedly higher affinity for bacteria, thereby demonstrating significantly enhanced bactericidal efficiency against methicillin-resistant Staphylococcus aureus (MRSA) in comparison to that of the d-Fiber. Following disassembly into monomers via host–guest chemistry, the bactericidal potency of both the l-Fiber and d-Fiber was found to be almost lost, suggesting the multivalent molecular chirality effect. Of note, the l-Fiber exhibited superior efficacy in curing MRSA-infected keratitis in comparison to the d-Fiber. These findings highlight the importance of multivalent molecular chirality in the design and development of chiral supramolecular polymers for antibacterial applications. This research also presents an effective chiral supramolecular antibacterial strategy for the treatment of drug-resistant bacteria-infected keratitis.
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Food Bioscience
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2024
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IF 4.8
Qiang Wang,Feng Zhang,Yuhong Zhang,Yu Zhang,Hongwei Wang,Jiajia Song,Huayi Suo
This study investigated the antifungal effect, mechanism, and potential application in yogurt of Lactiplantibacillus plantarum ( L. plantarum ) LPP95 isolated from Chinese pickles. The L. plantarum LPP95 showed a high inhibitory effect on the growth of five molds , with the strongest inhibitory effect observed on Penicillium sp. The cell-free supernatants (CFS) of L. plantarum LPP95 resulted in the shrinking of Penicillium sp. spores , and destroyed the integrity of the cell wall and membrane of spores, causing the leakage of nucleic acid from cells. The antifungal activity of CFS was not decreased after heat or proteolytic enzyme treatment but was affected by pH change. The inhibitory activity of CFS was associated with organic acids, and 66 organic acids were identified by LC-MS analysis. In addition, the validation experiments showed that trans -cinnamic acid, citric acid , trans -3-indoleacrylic acid, and DL-4-hydroxyphenyllactic acid all exhibited antifungal activity. Moreover, L. plantarum LPP95 effectively inhibited the growth of Penicillium sp. in yogurt. Overall, L. plantarum LPP95 and its CFS have the potential as biological preservatives.
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JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Juntao Hu,Yibing Huang,Hao Hao,Pujing Tian,Yinuo Yin,Yuting He,Fengjie Hao,Wantong Jiang,Yanping Zhang,Youzhong Wan,Quan Luo
Biofilms, protected by their dense, self-produced matrix, pose a significant clinical challenge due to their antibiotic resistance, leading to persistent infections and delayed wound healing, particularly in diabetic patients. Tailored to the biofilm life cycle, a double-layered nanoreactor was developed for rapid and complete antibiofilm therapy. The inner layer, cross-linked with poly(allylamine hydrochloride) (PAH)/phosphate, dimeric indocyanine green (dICG), and bromothymol blue (BTB), shields glucose oxidase (GOx) and β-glucanase (β-DEX) from unfavorable environment. The outer layer is coated with bacteria-targeted gold nanozymes (AuNEs). The healing of biofilm-infected diabetic wounds progresses three spatiotemporal stages activated by light irradiation and pH changes. Initially, the photothermal effect of dICG triggers nitric oxide (NO)-mediated biofilm dispersion and lowers the wound pH via a GOx/AuNEs cascade reaction. The resulting acidic environment then induces nanoreactor disassembly, releasing β-DEX to degrade the biofilm matrix and facilitate deeper penetration. Finally, AuNEs specifically recognize and eliminate planktonic bacteria, further disrupting the biofilms and accelerating wound healing by generating reactive oxygen species (ROS) and more toxic reactive nitrogen species (RNS). The wound status can be monitored in real-time using BTB's colorimetric pH analysis for visual feedback on treatment progress. This multifunctional design offers a programmed antibiofilm strategy for dynamic wound management.
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Advanced Science
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2024
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IF 14.3
Mengmeng Xiong,Ying Zhang,Huan Zhang,Qiaoqiao Shao,Qifan Hu,Junjie Ma,Yiqun Wan,Lan Guo,Xin Wan,Haitao Sun,Zhongyi Yuan,Hao Wan
Aggressive nature of colon cancer and current imprecise therapeutic scenarios simulate the development of precise and effective treatment strategies. To achieve this, a tumor environment-activated photosensitized biomimetic nanoplatform (PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM) is fabricated by encapsulating metal-organic framework loaded with developed photosensitizer PEG 2000 -SiNcTI-Ph and immunoadjuvant CpG oligodeoxynucleotide within fusion cell membrane expressing programmed death protein 1 (PD-1) and cluster of differentiation 47 (CD47). By stumbling across, systematic evaluation, and deciphering with quantum chemical calculations, a unique attribute of tumor environment (low pH plus high concentrations of adenosine 5′-triphosphate (ATP))-activated photodynamic effect sensitized by long-wavelength photons is validated for PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM, advancing the precision of cancer therapy. Moreover, PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM evades immune surveillance to target CT26 colon tumors in mice mediated by CD47/signal regulatory proteins α (SIRPα) interaction and PD-1/programmed death ligand 1 (PD-L1) interaction, respectively. Tumor environment-activated photodynamic therapy realized by PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM induces immunogenic cell death (ICD) to elicit anti-tumor immune response, which is empowered by enhanced dendritic cells (DC) uptake of CpG and PD-L1 blockade contributed by the nanoplatform. The photodynamic immunotherapy efficiently combats primary and distant CT26 tumors, and additionally generates immune memory to inhibit tumor recurrence and metastasis. The nanoplatform developed here provides insights for the development of precise cancer therapeutic strategies.
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Advanced Healthcare Materials
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2024
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IF 10
Meng-Meng Chen,Han-Wen Tian,Yuan-Qiu Cheng,Yu-Xin Yue,Yu-Chen Pan,Dong-Sheng Guo
Snakebite is a medical emergency that often leads to high mortality and morbidity in tropical and subtropical regions. The diversity in venom composition between various types of snakes necessitates the use of different specific antivenom treatments, which presents clinical and financial challenges in the management of snakebites. Therefore, developing a broad-spectrum antidote to neutralize complex and diverse snake venoms has assumed critical importance. Herein, a broad-spectrum antidote is developed through molecular recognition and coassembly to neutralize four kinds of snake venom toxins, those are three-finger toxin (3FTx), snake venom metalloproteinase (SVMP), phospholipase A 2 (PLA 2 ), and snake venom serine protease (SVSP), which have high abundance and toxicity. The coassembly of sulfonate-modified amphiphilic calixarene (SCA) and amphiphilic cyclodextrin (CD) is employed to neutralize the toxicity of 3FTx, 1,2-dodecanedithiol (DDT) and thioetheramide phosphorylcholine (TEAPC) are introduced through coassembly to neutralize toxicity of SVMP and PLA 2 , respectively, and the nafamostat (NT), which can be loaded through the host-guest complexation, is employed to neutralize toxicity of SVSP. The broad-spectrum antidote, NT@SCA/CD/DDT/TEAPC, effectively neutralizes key toxins from the most medically important cobra and vipers, significantly improving survival rates of poisoned mice. This study conceptually validated the feasibility of broad-spectrum detoxification and also offers a conveniently integrated supramolecular strategy.
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Heliyon
·
2024
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IF 3.4
Yu Yang,Xingyan Bao,Jiangyue Ning,Ruiyan Huang,Yuan Liang,Zelong Yan,Haotian Chen,Li Ding,Chang Shu
The investigation of peptide drugs has become essential in the development of innovative medications for hypertension. In this study, a sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the plasma concentration and stability of the antihypertensive peptide FR-6 in rats. An isotopically labeled peptide (with an unchanged sequence) was utilized as an internal standard (IS) for validation purposes. Subsequently, this assay was employed to examine the pharmacokinetics of different administration methods (tail vein and gavage) in Sprague Dawley (SD) rats. Extracted plasma samples underwent sample preparation through methanol protein precipitation, followed by elution of FR-6 on Wondasil C18 Superb column (4.6 × 150 mm, 5 μm), using a mobile phase consisting of formic acid (0.1%) in water (A) and formic acid (0.125%)-ammonium formate (2 mM) in methanol (B). Ion pairs corresponding to FR-6 and IS were monitored via multiple reaction monitoring (MRM) under positive ion mode: m / z 400.7 → 285.1 for FR-6 and m / z 406.1 → 295.1 for IS detection respectively. The method exhibited excellent linearity with respect to FR-6 concentrations. In addition, the inter-day and intra-day precision were 0.61–6.85% and 1.76–11.75%; the inter-day and intra-day accuracy were −7.28–0.13% and −7.20–2.28%, respectively. In conclusion, the matrix effect, extraction recovery, and stability data were validated according to FDA recommended acceptance criteria for bioanalytical methods. This validated method serves as a reliable tool for determining the concentration of antihypertensive peptide FR-6, and has been successfully applied in pharmacokinetic studies involving rats.
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Heliyon
·
2024
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IF 3.4
Hongyan Li,Yanzhi Zeng,Guangjun Wang,Kai Zhang,Wangbao Gong,Zhifei Li,Jingjing Tian,Yun Xia,Wenping Xie,Jun Xie,Shouqi Xie,Ermeng Yu
Diets with high carbohydrate (HC) was reported to have influence on appetite and intermediary metabolism in fish. To illustrate whether betaine could improve appetite and glucose-lipid metabolism in aquatic animals, mandarin fish ( Siniperca chuatsi ) were fed with the HC diets with or without betaine for 8 weeks. The results suggested that betaine enhanced feed intake by regulating the hypothalamic appetite genes. The HC diet-induced downregulation of AMPK and appetite genes was also positively correlated with the decreased autophagy genes, suggesting a possible mechanism that AMPK/mTOR signaling might regulate appetite through autophagy. The HC diet remarkably elevated transcriptional levels of genes related to lipogenesis, while betaine alleviated the HC-induced hepatic lipid deposition. Additionally, betaine supplementation tended to store the energy storage as hepatic glycogen. Our findings proposed the possible mechanism for appetite regulation through autophagy via AMPK/mTOR, and demonstrated the feasibility of betaine as an aquafeed additive to regulate appetite and intermediary metabolism in fish.
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危险品化学品经营许可证（带存储）