CHEMICAL ENGINEERING JOURNAL
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2023
·
IF 15.1
Shulin Qin,Lichun Ma,Runfeng Li,Pengfei Yuan,Yunfeng Shi,Xin Ji,Wei Xue,Yanli Li,Wen Liu
Although immune checkpoint blockade (ICB) therapy has been widely used for the treatment of a variety of cancers, its therapeutic efficacy is severely impaired by low tumor immunogenicity and the immunosuppressive microenvironment. Herein, we designed multifunctional immunomodulatory calcium nanoparticles to reshape the immunosuppressive tumor microenvironment. Our multifunctional calcium nanoparticles, CD@CaCO 3 P, are designed to release calcium ions and doxorubicin (DOX) into the acidic tumor microenvironment, which synergistically increase the tumor cell calcium ion concentration, while the release of combretastatin A4 phosphate (CA4P) further enhances T cell infiltration. Specifically, CD@CaCO 3 P effectively mediates the immunogenic cell death (ICD) of tumor cells and triggers the activation of nuclear factor kappa-B (NF-κB)/interferon regulatory factor 3 (IRF3), thereby regulating type I interferon (IFN-I) signaling pathways, and ultimately reprogramming the immunosuppressive tumor microenvironment by inducing M1-like macrophage polarization, promoting dendritic cell maturation, and increasing the infiltration of CD8 + T cells. Furthermore, CD@CaCO 3 P significantly increased tumor susceptibility to α-PD-1 checkpoint blocking immunotherapy and enhanced systemic immunotherapy performance against both primary and metastatic tumors. Our work provides new insights for the use functional calcium nanoparticles that modulate the tumor microenvironment to enhance the efficacy of cancer immunotherapy.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
·
IF 5.2
Lanting Wei,Xiang Wang,Junjie Fu,Jian Yin,Jing Hu
The current therapy for muscle injury is facing challenges in tissue self-regeneration and function restoration, which declines steeply with age. Tissue engineering is a promising strategy for treating skeletal muscular disorders. Natural polysaccharides have great potential to support cell growth and attachment as tissue-engineered scaffolds. A three-dimensional (3D) porous hydrogel scaffold has been prepared based on the double network of natural polysaccharide sodium alginate (SA), chitosan (CS) and Ca 2+ ions through the freeze-drying process. The physical, mechanical, and biological properties of the CS/SA/Ca 2+ hydrogel scaffold can be controlled by adjusting the SA/CS ratio. The physically cross-linked double network hydrogel showed good biosafety, high stability and satisfactory degradation rate . When the CS/SA molar ratio was 1:1.2 (H-1.2 group), the pore size and compression modulus of the double network hydrogel were 104.06 ± 2.64 µm and 40.00 ± 2.52 kPa, respectively. The results of in vitro evaluation showed that the 3D structure of the CS/SA/Ca 2+ double network hydrogel could well support adhesion and proliferation of C2C12 murine myoblasts and porcine skeletal muscle stem cells. The best cell growth effect was achieved in the H-1.2 group. The physically cross-linked CS/SA/Ca 2+ double network hydrogel can be a promising printable material as the cell scaffold in applications of skeletal muscle tissue engineering.
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Communications Biology
·
2023
·Vol. 6
·期 1
·1-13
·
IF 5.9
Sun Weijia,Li Yuheng,Li Jianwei,Tan Yingjun,Yuan Xinxin,Meng Haoye,Ye Jianting,Zhong Guohui,Jin XiaoYan,Liu Zizhong,Du Ruikai,Xing Wenjuan,Zhao Dingsheng,Song Jinping,Li Youyou,Pan Junjie,Zhao Yunzhang,Li Qi,Wang Aiyuan,Ling Shukuan,Dai Rongji,Li Yingxian
Mechanical force loading is essential for maintaining bone homeostasis, and unloading exposure can lead to bone loss. Osteoclasts are the only bone resorbing cells and play a crucial role in bone remodeling. The molecular mechanisms underlying mechanical stimulation-induced changes in osteoclast function remain to be fully elucidated. Our previous research found Ca 2+ -activated Cl − channel Anoctamin 1 (Ano1) was an essential regulator for osteoclast function. Here, we report that Ano1 mediates osteoclast responses to mechanical stimulation. In vitro, osteoclast activities are obviously affected by mechanical stress, which is accompanied by the changes of Ano1 levels, intracellular Cl − concentration and Ca 2+ downstream signaling. Ano1 knockout or calcium binding mutants blunts the response of osteoclast to mechanical stimulation. In vivo, Ano1 knockout in osteoclast blunts loading induced osteoclast inhibition and unloading induced bone loss and. These results demonstrate that Ano1 plays an important role in mechanical stimulation induced osteoclast activity changes.
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JOURNAL OF LUMINESCENCE
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2023
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IF 3.6
Shaolian Sun,Shan Shao,Wuyang Fan,Wenhu Zhang,Fan Xu,Haoming Wei,Bingqiang Cao,Yangqing Wu
The synthesis of efficient nano-scintillators is of great significance for the development of X-ray imaging and other applications. Here, X-ray excited afterglow rare earth nanoparticles β-NaLuF 4 :Gd 3+ /Tb 3+ are investigated. The X-ray-induced luminescence intensity and afterglow duration of NaLuF 4 :Gd 3+ /Tb 3+ nanoparticles are effectively improved by Ca 2+ doping. The optimal luminescence and afterglow performance are achieved when Ca 2+ doping ratio reaches 10%. The change of crystal field symmetry is the main reason for the improvement of luminescence performance. According to the thermoluminescence curve, it is proved that Ca 2+ doping increases the trap concentration and further enhances the afterglow. This study provides the research basis for the application of persistent luminescence materials in biomedical and other fields.
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FOOD HYDROCOLLOIDS
·
2023
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IF 10.7
Haifang Liu,Riting Huang,Xinyu Zhao,Shujuan Yang,Furui He,Wenqi Qin,Junhao Huang,Gaobo Yu,Yuhong Feng,Jiacheng Li,Chenghong Liao
The emulsion gels transformed by Pickering emulsions have great potential as a novel platform for oral drug delivery. In this study, an innovative alginate-based fluorescent colloidal particle was synthesized by Ugi reaction with alginate and carbon dots , which can stabilize Pickering emulsion at the present of Ca 2+ . The Pickering emulsions were converted to emulsion gels during gastric digestion. The microstructure of interfacial film was characterized in situ with confocal laser scanning microscopy. In the process of simulated gastrointestinal digestion, phase conversion of the Pickering emulsion was observed directly in situ by an automatic living cell imaging system. The results showed that clear fluorescent interfacial films can be visualized after simulated oral digestion, and fluorescent spheres were appeared after gastrointestinal digestion, indicating that Pickering emulsions were transformed into emulsion gels. Moreover, results on cell viability and cell uptake showed that the Pickering emulsion had good biocompatibility, which could be taken up by Caco-2 cells and could sustain the release of the drug. The formation of emulsion gels delays the digestion rate and improves the stability of encapsulated curcumin (CUR). In particular, in situ visualization technique also has promising applications in the digestion process and cellular uptake.
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2022
·Vol. 29
·期 29
·44794-44805
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IF 5.19
Wu Mingda,Lu Linghong,Zhou Tao,Ma Yi,Weng Zhengsong
Calcium and magnesium ions usually exist in natural water. When Cd 2+ is removed from water by adsorption, it will be inhibited by these two ions. Titanate nanotubes (TNTs) have an effective adsorption capacity for Cd 2+ due to extraordinary ion exchange property. However, TNTs also adsorb Ca 2+ and Mg 2+ in water. In this study, carbon-modified TNT (TNT/C) and TNT/C further treated with acid (TNT/HC) were synthesized by hydrothermal synthesis. The transmission electron microscope (TEM) images show that TNT/C or TNT/HC still keep nanotube morphology. The experimental results show the order of adsorption amount to Cd 2+ is TNT (171.56 mg/g) > TNT/C (166 mg/g) > TNT/HC (159.88 mg/g) when there is no Ca 2+ or Mg 2+ . But when there is 0.1 M Ca 2+ or Mg 2+ in the water, the order of Cd 2+ adsorption capacity becomes TNT/HC (44.28, 49.04 mg/g) > TNT/C (58.84, 69.32 mg/g) > TNT (65.52, 70.6 mg/g). It indicates that the surface carbon modification can alleviate the hindrance of Ca 2+ or Mg 2+ to Cd 2+ removal. This is because the carbon on the surface of TNT captured part of Ca 2+ or Mg 2+ ; it made more Cd 2+ be successfully absorbed by TNT through ion exchange. This mechanism was confirmed by the X-ray photoelectron spectroscopy (XPS) spectra analysis. The results of this paper can provide ideas for the adsorption and removal of Cd 2+ in water in the presence of Ca 2+ or Mg 2+ .
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Journal of Environmental Sciences
·
2021
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IF 5.565
Biran Zhu,Ziniu Wang,Lei Lei,Yongyong Guo,Jian Han,Bingsheng Zhou
Cadmium (Cd), a ubiquitous environmental hazardous heavy metal, poses a significant threat to the health of aquatic organisms, including teleosts. Although the toxic profile of Cd is well recognized, little is known regarding the overall view of toxic responses to varying aquatic environmental parameters (e.g., water hardness) at an individual level. Herein, differences in water hardness were partially mimicked by adjusting Ca 2+ levels in E3 medium. As an in vivo model, zebrafish embryos were exposed to variable Ca 2+ levels (NV, normal Ca 2+ ; LV, low Ca 2+ ; HV, high Ca 2+ ) alone or combined with 30.7 µg/L Cd 2+ (NC, LC, and HC, respectively) until 144 hr post-fertilization. The genome-wide transcriptome revealed differentially expressed genes between groups. Functional enrichment analysis found that biological processes related to metabolism, particularly lipid metabolism, were significantly disrupted in NC and LC treatments, while a remission was observed in the HC group. Biochemical assays confirmed that the decrease in Ca 2+ enhanced synthesis, inhibited mobilization and increased the storage of lipids in Cd 2+ treatments. This study suggests that the toxic effect of Cd on biological pathways will be influenced by Ca 2+ , which will improve the toxicological understanding and facilitate accurate assessment of Cd.
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Scientific Reports
·
2019
·Vol. 9
·期 1
·1-11
·
IF 4.011
Sun Saiwu,He Huijun,Yang Chunping,Cheng Yan,Liu Yongpan
In this study, the adsorption and UV photocatalytic degradation of atrazine using nano-TiO 2 particles were studied systematically, and the colloidal stability of nano-TiO 2 particles in solution was also investigated to reveal the removal mechanism. Experiments which contained the first 6.0 hours darkness and 4.0 hours UV illumination later were conducted at different concentrations of Ca 2+ and/or fulvic acids (FA) at pH = 7.0. Results showed that the adsorption rate of atrazine onto nano-TiO 2 particles decreased with the increase of Ca 2+ and/or FA concentrations, which could be explained well by the colloidal stability of nanoparticles. When the solution contained Ca 2+ or Ca 2+ -FA, the nanoparticles were aggregated together leading to the decrease of the contact surface area. Besides, there existed competitive adsorption between FA and atrazine on the particle surface. During photocatalytic degradation, the increase of Ca 2+ and/or FA concentration accelerated the aggregation of nano-TiO 2 particles and that reduced the degradation efficiency of atrazine. The particle sizes by SEM were in accordance with the aggregation degree of nanoparticles in the solutions. Sedimentation experiments of nano-TiO 2 particles displayed that the fastest sedimentation was happened in the CaCl 2 and FA coexistent system and followed by CaCl 2 alone, and the results well demonstrated the photodegradation efficiency trends of atrazine by nano-TiO 2 particles under the different sedimentation conditions.
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BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Xueying Lei,Lihua Ding,Xiaonan Yang,Feng Xu,Yongjun Wu,Songcheng Yu
The CRISPR/Cas12a system is increasingly used in biosensor development. However, high background signal and low sensitivity for the non-nucleic acid targets detection is challenging. Here, a p adlock activator which could i nhibit the t rans -cleavage activity of CRISPR/Cas12a system in the intact form by steric hindrance effect (PAIT effect) was designed for non-nucleic acid targets detection. The PAIT effect disappeared when padlock activator was separated into two split activators. To verify the feasibility of padlock activator, a Ca 2+ sensor was developed based on PAIT effect with the assistance of DNAzyme, activity of which was Ca 2+ dependent. In the presence of Ca 2+ , DNAzyme was activated to cleave its substrate, a padlock activator modified with adenine ribonucleotide, into split padlock activators which would trigger the trans -cleavage activity of Cas12a to generate fluorescence. There was a mathematical relationship between the fluorescence intensity and the logarithm of Ca 2+ concentration ranging from 10 pM to 1 nM, with a limit of detection of 3.98 pM. The little interference of Mg 2+ , Mn 2+ , Cd 2+ , Cu 2+ , Na + , Al 3+ , K + , Fe 2+ , and Fe 3+ indicated high selectivity. Recovery ranged from 93.32% to 103.28% with RSD s from 1.87% to 12.74% showed a good accuracy and reliability. Furthermore, the proposed sensor could be applied to detect Ca 2+ in mineral water, milk powder and urine. The results were consistent with that of flame atomic absorption spectroscopy. Thus, PAIT effect is valuable for expanding the application boundary of CRISPR/Cas12a system.
研究领域:
生物技术
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生物化学
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分析化学
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分子生物学
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Junjie Li,Yixu Wang,Jiawei Li,Sihan Xu,Shou Wang,Wenjuan Liu,Li Fu,Min Jiang,Gang Bai
Ethnopharmacological relevance Lian Qiao (LQ), the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a well-documented traditional Chinese medicine known for its detoxifying and heat-clearing properties. Clinically, compounds containing LQ are widely used to treat thrombotic diseases, indicating that it may have antithrombotic effects. However, its exact mechanism of action remains unknown. Aim of the study This study aimed to verify the antithrombotic effect of LQ and further explore the material basis and target mechanism of its antithrombotic effect using various biological methods. Materials and methods An epinephrine-collagen-thrombin-induced mouse model of acute pulmonary embolism (APE) was established to study the effects of LQ on thrombus development. A UPLC/Q/TOF-MS screening and identification system based on the inhibition of platelet aggregation and Ca 2+ antagonism was established to determine the pharmacodynamic components of LQ that inhibit platelet activation. The inhibitory effect of active ingredients on platelet activation, and the determination of the target of their inhibitory effect on platelet activation have been studied using chemical proteomics. Furthermore, based on the structure and function of the target protein, a multidisciplinary approach was adopted to analyze the molecular mechanism of active ingredient binding to target proteins and to evaluate the effects of active ingredients on the downstream signaling pathways of target proteins. Results LQ showed significant anticoagulant effects in APE model mice. Phillyrin and phillygenin were the antiplatelet-activating components of LQ. PLCβ3 was identified as a target for inhibiting platelet activation by phillyrin and its metabolites. The mechanism underlying the effect involves phillyrin and its metabolites inhibiting PLCβ3 activity by blocking the binding of PLCβ3 to Gαq through non-covalently targeting the ASN260 of PLCβ3, thus inhibiting the downstream Gαq-PLCβ3-Ca 2+ signaling pathway, effectively hindering platelet activation and therefore playing an anticoagulant role. Conclusion This study not only proposes and validates the antithrombotic effect of LQ for the first time but also finds that phillyrin and phillygenin are the main pharmacological substances through which LQ exerts antithrombotic activity and reveals a novel mechanism by which they exert antiplatelet activity by directly targeting and inhibiting PLCβ3 activity. These findings significantly contribute to our understanding of the therapeutic potential of phillyrin and provide important clues for the discovery and development of new antiplatelet drugs.
研究领域:
药理学
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传统中药
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分子生物学
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生物化学
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血栓研究
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FOOD HYDROCOLLOIDS
·
2024
·
IF 11
Qingmei Zhu,Xiaona Su,Keyang Mai,Riting Huang,Shujuan Yang,Haifang Liu,Furui He,Yu Bao,Gaobo Yu,Yuhong Feng,Jiacheng Li
The agar (AG) film exhibited poor mechanical and water-resistant properties which limited its application for food packaging. The structural modification of AG nanocomposite film greatly impacts their macroscopic properties. In this paper, edible AG nanocomposite films were achieved by incorporating colloidal particles based on conjugates of whey protein isolate (WPI) and alginate oligosaccharides (AOS) as the nanofiller to obtain the micro-phase separation structure and the multiple cross-linking network with the synergistic interactions of the Ca 2+ crosslinking. Firstly, WPI-AOS colloidal particles were synthesized through the Wet-heating Maillard reaction. Good compatibility between WPI-AOS colloidal particles and AG was exhibited, resulting in improved mechanical and water-resistant properties of AG composite films. Compared to pure AG film, the tensile strength (TS) of the agar composite film with 10% WPI-AOS colloidal particles increased significantly to 81.87 MPa from 24.02 MPa, and the elongation at break (EAB) also improved to 46.25% from 18.65%. The moisture content (MC), water solubility (WS), and water vapor permeability (WVP) of the AG composite film decreased by 33.1%, 18.0%, and 22.4% respectively. In addition, the multiple cross-linking network hindered the relative sliding between the AG molecular chain, which resulted in improved thermal stability of the composite film. Using soft colloidal particles as nanofillers to fabricate edible films for improving their properties is an effective and promising strategy.
研究领域:
食品科学
·
材料科学
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2024
·Vol. 53
·期 4
·1-16
·
IF 5.7
Zailin Fu,Dingsheng Wang,Caiyun Zheng,Minghua Xie,Yifang Chen,Yi Zhou,Yan Huang,Ying Song,Weiyong Hong
Calcium overload, a notable instigator of acute pancreatitis (AP), induces oxidative stress and an inflammatory cascade, subsequently activating both endogenous and exogenous apoptotic pathways. However, there is currently lack of available pharmaceutical interventions to alleviate AP by addressing calcium overload. In the present study, the potential clinical application of liposome nanoparticles (LNs) loaded with 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA‑AM), a cell‑permeant calcium chelator, was investigated as a therapeutic approach for the management of AP. To establish the experimental models in vitro, AR42J cells were exposed to high glucose/sodium oleate (HGO) to induce necrosis, and in vivo, intra‑ductal taurocholate (TC) infusion was used to induce AP. The findings of the present study indicated that the use of BAPTA‑AM‑loaded LN (BLN) effectively and rapidly eliminated excessive Ca2+ and reactive oxygen species, suppressed mononuclear macrophage activation and the release of inflammatory cytokines, and mitigated pancreatic acinar cell apoptosis and necrosis induced by HGO. Furthermore, the systemic administration of BLN demonstrated promising therapeutic potential in the rat model of AP. Notably, BLN significantly enhanced the survival rates of rats subjected to the TC challenge, increasing from 37.5 to 75%. This improvement was attributed to the restoration of pancreatic function, as indicated by improved blood biochemistry indices and alleviation of pancreatic lesions. The potential therapeutic efficacy of BLN in rescuing patients with AP is likely attributed to its capacity to inhibit oxidative stress, prevent premature activation of zymogens and downregulate the expression of TNF‑α, IL‑6 and cathepsin B. Thus, BLN demonstrated promising value as a novel therapeutic approach for promptly alleviating the burden of intracellular Ca2+ overload in patients with AP.
研究领域:
药理学
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医学
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纳米技术
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细胞生物学
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炎症
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胃肠病学
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