SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2019
·
IF 2.931
Lijuan Huang,Xin Zhang,Zhuoyong Zhang
Many endogenous peptides are circulating in bodily fluids at micromole level, and accurate analysis of endogenous peptides at such low level is important. In this study, we presented an extensible, facile and sensitive sensor array based on UV–Vis spectroscopy of the AuNPs combined with chemometric methods for quantitative analysis of binary peptide mixture (Gly-Gly/Ala-Gln) using UV–Vis spectroscopy. High concentration arginine (Arg) and Cr 3+ can induce aggregation of the AuNPs and DNA-AuNPs. However, the glycylglycine (Gly-Gly) and alanyl-glutamine (Ala-Gln) can prevent the AuNPs from aggregation. We investigated the prevention of AuNPs aggregation by using Gly-Gly and Ala-Gln mixtures and constructed sensor arrays for quantitative analyses of Gly-Gly and Ala-Gln mixtures. The color change of the solution is relevant to the dose of the target, and it can be visualized by the naked eyes or monitored by UV–Vis spectrometry. Results showed that the concentrations of Arg and Cr 3+ are the key factors affecting the sensitivity of the sensor array. Whereas when Gly-Gly and Ala-Gln have to be analyzed simultaneously, concentrations of Arg and Cr 3+ both for Gly-Gly and Ala-Gln are difficult to be optimized. Taking the advantages of multivariate analysis and data fusion, PLS models and backward interval PLS (BiPLS) models were built for fused dataset constructed by UV–Vis data obtained at different concentrations of Arg and Cr 3+ . The best results were obtained from the PLS models. The proposed method can be extended to analysis of other peptides in more complex mixture systems.
研究领域:
分析化学
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生物医学工程
·
光谱学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2025
·
IF 4.2
Xiaoqi Wang,Shuang Liu,Di Su,Jiayu Sui,Xiangyu Yan,Jia Yang,Ziqi Zheng,Penghe Wang,Weijun Song,Zexi Jin,Mingyan E,Maomao Zhang,Bo Yu
Background and aims Viral myocarditis is an inflammatory pathology of the myocardium that involves innate immune responses, especially those involving neutrophils. However, strategies targeting neutrophils to alleviate inflammation have not achieved complete success. Alpha lipoic acid (ALA), a natural organosulfur compound, has the capacity to modulate immune cell behavior. This study aimed to investigate whether ALAs can regulate innate immunity to provide protection against coxsackievirus B3 (CVB3)-induced myocarditis. Methods and results Abdominal administration of ALA improved cardiac dysfunction and reduced mortality in a CVB3-induced mouse model of myocarditis (VM). ALA treatment induced neutrophils and inhibited Ly6C hi pro-inflammatory macrophages, favoring a reparatory environment in the myocardium. However, depleting neutrophils with anti-Ly6G antibodies increased Ly6C hi pro-inflammatory macrophage recruitment in blood and heart in ALA-treated VM mice. Further flow cytometry analysis indicated that ALA promoted Ym-1 expression of neutrophils. Blocking Ym-1 significantly reversed ALA-mediated cardiac reparative macrophages infiltration and cardiac function improvement post-VM. Recombinant Ym-1 drives macrophages toward a reparative phenotype and attenuates CVB3-induced viral myocarditis. Mechanistically, ALA reprogrammed neutrophil metabolic patterns, leading to increased production of the metabolite acetyl-CoA, thereby increasing the transcription of Ym-1 by promoting STAT6 acetylation. Conclusions ALA protects against VM by activating metabolic reprogramming/STAT6 acetylation/Ym-1 axis in neutrophils. These results highlight the heterogeneity of neutrophils and suggest that ALA might represent a feasible strategy to improve the prognosis of VM patients.
研究领域:
免疫学
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病毒学
·
心脏病学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2022
·
IF 5.546
Jia-Nan Yan,Yi-Tong Han,Xiao-Yang Liu,Yi-Nan Du,Hai-Tao Wu
The gelation and microstructural behaviors of Ala-Lys dipeptide/iota-carrageenan (AK/IC) mediated by salts were investigated. Obviously, salt addition prominently exaggerated the synergistic gelation between AK and IC, with storage modulus ( G' ) of AK/IC and IC increasing extensively from 1145 to 9516 Pa or 5919 Pa and from 615 to 9981 Pa or 4693 Pa at 0.1 Hz with 0.5 % CaCl 2 or KCl, respectively, in which CaCl 2 revealed superiority over KCl. Additionally, different states of water in AK/IC gels resisted salt interference. Moreover, a honeycomb structure with denser porous networks coupled with rough entanglement morphology of AK/IC was observed, in which the CaCl 2 -treated group exhibited even smaller pore sizes. The conformational changes of AK/IC induced by salts were reflected by the redshift of –OH groups in AK/IC, insinuating salt-mediated H-bonding in AK/IC. The blueshift of amide I bands and water deformation groups of AK/IC in comparison to AK and IC alone illustrated the electrostatic interactions between them. Furthermore, coordination interaction, hydrogen bonds and hydrophobic interactive were highlighted among IC, AK and CaCl 2 /KCl as reflected by molecular docking.
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Xiao Zhao,Xinfang Li,Peng Zhang,Jianwei Du,Youxiang Wang
5-Aminolevulinic acid (ALA) based photodynamic therapy (PDT) is a modality for the treatment of cancers. However, due to its hydrophilicity and zwitterionic nature, the transdermal delivery of ALA is limited for the PDT of subcutaneous tumor. To address this problem, tip-loaded fast-dissolving microneedles made of sodium hyaluronate (HA) were fabricated by two casting method. 122 μg of ALA was loaded per microneedle patch and mainly distributed in the tips, which could improve the utilization of drug and avoid the waste of drug residue in the base of microneedle patch after use. The HA microneedles could pierce stratum corneum with insertion depth about 200 μm in isolated skin. After insertion, HA microneedles were rapidly dissolved to release the encapsulated drug to improve patients' convenience and compliance. Importantly, in a subcutaneous mouse tumor model established in BALB/c nude mice, the PDT efficacy of ALA-loaded HA microneedle group was much better than ALA injection group in spite of a relatively lower ALA dose with HA microneedles. The tumor inhibition rate of ALA-loaded HA microneedle group (containing 0.61 mg of ALA) was up to 97%, while the tumor inhibition rate of ALA injection group (containing 1.65 mg of ALA) was just 66%. In addition, microchannels created by microneedle patch were quickly recovered within 3 h after insertion. Overall, the tip-loaded fast-dissolving HA microneedle patch with ALA as drug was promising and might improve topical PDT efficacy of subcutaneous tumor in an efficient and safe manner.
研究领域:
药学
·
肿瘤学
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生物医学工程
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hai-Yun Zhang,Guifang Wang,Yuxin Li,Ying Wen,Yan Zhang,Qiangsong Wang
The combination of multiple anti-tumor methods has shown significant application potential in overcoming the limitations of monotherapy. Photodynamic therapy (PDT) and chemotherapy combination is a promising strategy for reducing drug resistance and side effects. Here, inspired by the acidic environment of tumors, carboxymethyl chitosan-based pH-responsive nanovesicles were developed to co-deliver the chemotherapeutic drug doxorubicin (DOX) and photosensitizer 5-aminolevulinic acid (5-ALA). The in vitro drug release studies revealed that drugs could be responsively released when nanoparticles were triggered by the acidic environment. The controlled-release behavior improved drug retention and reduced the administration time. Our nanoparticles could significantly enhance the killing effect of drugs on tumor cells and increase intracellular levels of reactive oxygen species (ROS) compared to monotherapy, effectively achieving the effects of combined chemotherapy and PDT. The loaded DOX could kill tumor cells and the loaded 5-ALA could enhance the content of protoporphyrin IX (PpIX), resulting in excess ROS production to improve the effects of PDT. In summary, our nanoparticles could co-deliver the drugs and exert synergistical anti-tumor of PDT and chemotherapy by suppressing tumor cell proliferation and facilitating cell apoptosis.
研究领域:
纳米技术
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癌症治疗
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药物递送系统
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2023
·
IF 4.4
Xiaoxuan Cai,Miaoen Huang,Xixiang Huang,Huan Liu,Tianji Wang,Li Li,Weiguang Yang,Hui Luo,Yingnian Lu
The organism Sipunculus nudus L is a good resource for marine peptides because of its rich protein. However, the disadvantage of biological peptides is their short metabolic half-life, therefore, structural modification of peptides is necessary. In this research, the enzymatic hydrolysis of Sipunculus nudus L was performed using trypsin and then peptides were isolated and purified from the hydrolysates, four novel tripeptides were identified by LC-MS-MS as Ser-Arg-Pro (SRP, m/z = 358.39), Pro-Arg-Pro (PRP, m/z = 368.43), Arg-Pro-Ala (RPA, m/z = 342.39), and Lue-Pro-Lys (LPK, m/z = 356.46), their ACE inhibitory activity was investigated with IC 50 value as following 0.046, 0.42, 0.97, and 6.54 mM, respectively. Because of its highest ACE inhibitory activity, SRP was further selected to modify the chemical structure for a sustained release agent DSPE-PEG-SRP. Compared with 7 h of free SRP, the release of DSPE-PEG-SRP in vitro was approximately 120 h. The ACE inhibition rate of SRP released from the synthetic product and the raw material SRP was almost the same, molecular docking demonstrated that ACE inhibitory activity was attributed to the formation of hydrogen bonds between SRP and ACE active sites . In conclusion, DSPE-PEG-SRP, a novel sustained release agent, has great potential and is expected to be further applied to treat hypertension.
研究领域:
海洋生物学
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药学
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生物化学
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产品关联
DOI
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Zixian Xia,Xiaoyan Guan,Rui Liu,Yeting Wu,Yingying Li,Mengmeng Liu,Yifeng Ding,Xiaohong Wang,Youyou Lu
Bifidobacterium faces major challenges in the gastrointestinal tract, including inactivation under acidic conditions and insufficient targeted release. In this study, three novel heterologous dual-protein complex systems were constructed by lactoferrin (LF) with α-lactalbumin (ALA), β-lactoglobulin (BLG), casein (CN). Subsequently, sodium alginate (SA) -cross-linked gel microcapsules loaded with these dual-protein complexes and B. animalis F1-7. The optimal preparation conditions for the dual-protein were as follows: ALA/LF = 1.5, 50 °C; BLG/LF = 2, 50 °C; CN/LF = 0.5, 25 °C. Incorporation of SA and endogenous emulsification method enabled efficient encapsulation of B . animalis F1-7, achieving encapsulation efficiency exceeding 90%. B. animalis F1-7@SA-(LF-ALA/BLG/CN) exhibited strong acid resistance, favorable intestinal responsiveness, and significantly improved microbial viability. The microcapsules enhanced gastric acid tolerance primarily through a spatial barrier effect, while the incorporation of dual-protein components contributed to matrix structural reinforcement and digestion-responsive release behavior. This integrated “physical protection-structural modulation” strategy also conferred excellent 28-day storage stability. In vitro experiments by mice/human feces, combined with 16S rRNA and metabolomics analysis, revealed that the composite microcapsules effectively regulated the structure of the microbial community and altered metabolite profiles (e.g. , pathways involved in nitrogen metabolism). Overall, this study provided reproducible preparation parameters and a theoretical basis for SA-based dual-protein composite encapsulation delivery systems, and offered a promising strategy to address the coordinated challenges of activity, controlled release, and storage stability of sensitive food bioactive microorganisms or nutrients.
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DOI
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-14
·
IF 16.6
Fang Fang,Wang Sa,Song Yueyue,Sun Meng,Chen Wen-Cheng,Zhao Dongxu,Zhang Jinfeng
Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe 3+ , and natural bioactive compound curcumin with an ideal API content and pH-responsive release profile for continuous spatiotemporal cancer therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), Fe 2+ , biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe 2+ /BV-BR metabolic pathway, further cooperating with released Fe 3+ and curcumin, ultimately eliciting mitochondria damage, membrane disruption, and intracytoplasmic injury. This work not only provides a paradigm for exploiting diversified metabolites for tumor suppression, but also presents a safe and efficient full-API nanodrug, facilitating the practical translation of nanodrugs.
研究领域:
纳米医学
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癌症研究
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
·
2018
·Vol. 95
·期 4
·1045-1051
·
IF 2.214
Xian Zhang,Longfei Chen,Lvfen Gao,Xuesong Gao,Nan Li,Yuwei Song,Xinke Huang,Shaoqiang Lin,Xiaoyu Wang
Comparison of the fluorescence intensity caused by the accumulation of PpIX in endometrial cancer xenografts in nude mice after low-dose 5-Aminolevulinic acid (ALA) injection combined with siRNA transfection was mediated by ultrasound microbubbles and polyethyleneimine (PEI) to explore the feasibility of the ultrasound microbubble technique as transfection agents. Knockdown of ferrochelatase (FECH) in human endometrial cancer xenografts in nude mice was performed by transfection with FECH-siRNA mediated by PEI and ultrasound microbubbles alone or in combination; then, low-dose ALA was injected. Subsequently, an in vivo animal imaging system was employed to detect the fluorescence intensity in xenografts. Red fluorescence was observed in xenografts given more than 6.25 mg kg −1 of ALA. When the dose of ALA was greater than 50 mg kg −1 , there was a significant difference in the fluorescence between tumor and other tissues. After the nude mice were transfected with siRNA and treated with low-dose ALA (1.0 mg kg −1 ), apparent PpIX fluorescence of the xenografts was observed, and the fluorescence intensity was PEI+ ultrasound microbubbles > PEI > ultrasound microbubbles. Ultrasound microbubbles in combination with PEI could generate a higher fluorescence intensity of PpIX than that obtained with ultrasound microbubbles or PEI alone, and ultrasound microbubbles could wholly or partially replace PEI under certain conditions.
研究领域:
肿瘤学
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分子生物学
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基因治疗
·
癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Huihui Liu,Qing Wang,Jingru Guo,Kai Feng,Yiling Ruan,Zhihao Zhang,Xin Ji,Jigang Wang,Tao Zhang,Xiaolian Sun
Cerenkov radiation induced photodynamic therapy (CR-PDT) can tackle the tissue penetration limitation of traditional PDT. However, co-delivery of radionuclides and photosensitizer may cause continuous phototoxicity in normal tissues during the circulation. 5-aminolevulinic acid (ALA) which can intracellularly transform into photosensitive protoporphyrin IX (PpIX) is a cancer-selective photosensitizer with negligible side effect. However, the hydrophilic nature of ALA and the further conversion of PpIX to photoinactive Heme severely hinder the therapeutic benefits of ALA-based PDT. Herein, we developed an 89 Zr-labeled, pH responsive ALA and artemisinin (ART) co-loaded liposome ( 89 Zr-ALA-Liposome-ART) for highly selective cancer therapy. 89 Zr can serve as the internal excitation source to self-activate PpIX for CR-PDT, and the photoinactive Heme can activate the chemotherapeutic effect of ART. The 89 Zr-ALA-Liposome-ART exhibited excellent tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice via CR-PDT and chemotherapy. Combined with anti-PD-L1, the 89 Zr-ALA-Liposome-ART elicited strong antitumor immunity to against tumor recurrence.
研究领域:
药学
·
放射肿瘤学
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纳米技术
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2022
·
IF 10.508
Lei Wang,Jingtao Jiang,Chenghao Dai,Huilan Zeng,Yifan Shang,Yongqi Liu,Qiyan Yin,Gengsheng Weng
The design of materials that can mimic the complex shape-morphing phenomena in nature is important for applications in soft robotics, biomedical devices, and sensors. Yet, morphing a two-dimensional thin plate into a programmed complex three-dimensional (3D) shape is still challenging. Herein, we demonstrate a new paradigm for designing a photothermal shape-transformable Fe3+-containing polymer film (FePF) coated with a patterned inactive black-tape strip layer. The near-infrared (NIR) light-triggered dehydrative shrinkage of the FePF layer drives the bending of the inactive layer toward the FePF layer. Various reversible 3D shapes, including a complex “human face” and gripping-force-tunable soft grippers, are fabricated by the experimental pattern design of the inactive layer with the aid of theoretical simulations. The white-light sensitive dynamic coordination of Fe3+–Alanine (Ala) enables tunability of the deformation degree under white-light irradiation. The deformation rate is also tunable by adjusting the Fe-to-Ala mole ratio, humidity, NIR light intensity, and FePF thickness. These shape transformations are reconfigurable through the simple peeling off and repatterning of the black-tape strip layers. Our simple and scalable design strategy without an intricate heterogeneity design in material properties provides guidance for fabricating new soft robotics and biomimetic systems.
研究领域:
材料科学
·
软机器人
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生物医学工程
·
光学工程
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Xiao Liu,Yuan Zhang,Peng Zhang,Kang Ge,Ruzhi Zhang,Yixin Sun,Yang Sheng,Mark Bradley,Rong Zhang
Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an important approach for the treatment of some skin diseases and cancers. A major defect of this approach is that it is difficult for 5-ALA to accumulate around lesions in deeper regions of tissue, resulting in poor conversion to the active fluorophore and photodynamic efficiencies. Because of their targeting and controlled release abilities, nanogel carriers could solve this problem. In this paper, nanogels were prepared by using micro-emulsion polymerization with various biodegradable polyester crosslinkers ( L -lactide and ε-caprolactone). The swelling and degradation properties and entrapment efficiency, drug loading and drug release ability of the nanogels were investigated. Nanogels co-cultured with skin cancer cells (A2058) allowed the efficiency of the PDT in vitro to be demonstrated. The results showed that the swelling rate of hydrogels reduced with increasing crosslinker levels, which caused a slow-down in the release of 5-ALA, but lipase accelerated degradation of nanogels increased 5-ALA concentrations in tumor cells and leading to higher PDT efficiency. It was proved by in vivo experiment indicating that the development of skin cancer tissues were efficiently inhibited by the 5-ALA loaded nanogels.
研究领域:
药学
·
纳米技术
·
癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）