Materials Today Bio
·
2025
·
IF 10.2
Liangyin Wei,Hong Wang,Xietao Ye,Junfan Yue,Hong Guo,Dengxuan Mao,Xia Li,Yeyang Sun,Congyan Liu,Yuping Liu,Yan Chen
The response rate of programmed cell death protein-1 (PD-1) inhibitors in breast cancer remains unsatisfactory, primarily due to the limited infiltration and activity of tumor-infiltrating T lymphocytes (TILs). Previous studies demonstrated that oxymatrine (Om) and astragaloside IV (As) could enhance TIL infiltration and function by inhibiting cancer-associated fibroblasts (CAFs) and promoting mitochondrial activity in TILs, respectively. Thus, combining Om and As may be a promising strategy to improve the antitumor effects of PD-1 inhibitors in breast cancer. However, co-delivery above drugs into breast cancer tissue is challenging due to their low bioavailability and distinct physicochemical properties. This study addresses this challenge by formulating Om and As co-loaded liposomes (Om-As-Lip) and comparing the scale-up production methods: high-pressure homogenization (EP-HPH) and microfluidics. Om-As-Lip prepared via microfluidics demonstrated superior entrapment efficiency (As: 99.03 ± 0.04%, Om: 67.01 ± 0.02%) and a significantly higher production rate (22.12 mL/min) compared to EP-HPH (1.19 mL/min). Additionally, Om-As-Lip produced by microfluidics increased the area under the curve (AUC) (Om: 6.17-fold, As: 2.07-fold) and maximum concentration (Cmax) (Om: 1.58-fold, As: 3.49-fold) compared to the free drugs. Importantly, Om-As-Lip enhanced the antitumor efficacy of α-PD-1 by inhibiting CAF activation and boosting TIL activity, resulting in a tumor inhibition rate of 61.2% and extended survival in mice. This work presents a novel perspective for scaling up co-delivered formulations of drugs with differing polarities to improve breast cancer immunotherapy.
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RSC Advances
·
2017
·Vol. 7
·期 89
·56732-56742
·
IF 3.108
Jun Zhang,Jianan Li,Guoliang Jia,Yikun Jiang,Qinyi Liu,Xiaoyu Yang,Su Pan
To engineer bone tissue, an ideal biodegradable implant should be biocompatible, biodegradable, osteoinductive and osteoconductive. However, the lack of bioactivity has seriously restricted the development of biodegradable implants in bone tissue engineering. In this study, we have developed a three-dimensional porous poly(L-lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) scaffold based on the dual delivery of bone morphogenic protein 2 (BMP-2) and insulin-like growth factor 1 (IGF-1) via polydopamine (PDA) coating. The aim of this study was to improve the osteoinductivity of biodegradable implants for clinical bone repair via a PDA-assisted BMP-2 and IGF-1 surface modification strategy. Our study demonstrated that PDA layer surface modification could more efficiently immobilize BMP-2 and IGF-1 on the scaffold surfaces than physical adsorption, and the immobilized growth factor was released slowly and steadily from the scaffold in a sustained manner. MC3T3-E1 cell attachment and proliferation on IGF-1 and BMP-2-immobilized porous scaffolds were much higher than other groups. According to an in vitro osteogenesis assay, alkaline phosphatase (ALP) activity, the expression of osteogenesis-related genes and the mineralization capacity of MC3T3-E1 cells were increased by the incorporation of BMP-2 and IGF-1. In vivo, digital radiograph evaluation demonstrated that there was the most rapid healing in the defects treated with the IGF-1 and BMP-2 immobilized porous scaffold compared with the other groups eight weeks after implantation. In vitro and in vivo results of this study revealed that the PDA-assisted surface modification method can be a useful tool to graft biomolecules onto biodegradable implants, and the dual release of BMP-2 and IGF-1 could promote cell proliferation and osteogenesis differentiation. Based on the results, the surface modification strategy with growth factors has great potential for the enhancement of osteointegration of biodegradable bone implants.
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International Journal of Medical Sciences
·
2024
·Vol. 21
·期 15
·3018
·
IF 3.2
Qi Zhang,Chao Hu,Baoqing Qu,Cuiping Zhang,Longtao He
This work aimed to demonstrate the therapeutic effects of tumor microenvironment-responsive nanotherapeutic drugs targeting PSD95/Discs-large/ZO-1 domain (PDZ)-binding-kinase (PBK) in medulloblastoma Daoy and ONS-76 cells. The objective was to provide critical theoretical and practical foundations for the clinical adoption of tumor microenvironment-responsive nanotherapeutic drugs targeting PBK. The rabies virus glycoprotein (RVG) was utilized as a specific targeting molecule to form a tumor microenvironment-responsive nanocomplex, HPAA/RVG/PBK-siRNA, which incorporated glutathione (GSH) as a microenvironment stimulus factor within a hyperbranched polymer polyamide amine (HPAA). This nanocomplex also carried PBK-small interfering RNA (siRNA) for targeted PBK therapy. Characterization of HPAA, maleimide-polyethylene glycol-N-succinyl ester (MAL-PEG-NHS), HPAA-PEG, RVG, HPAA-RVG, and HPAA/RVG/PBK-siRNA was conducted using nuclear magnetic resonance spectroscopy, high-performance liquid chromatography (HPLC), dynamic light scattering, and transmission electron microscopy (TEM). Flow cytometry was employed to assess endocytosis and cell transfection of HPAA-RVG and HPAA/RVG/PBK-siRNA in Daoy and ONS-76 cells. The two cell lines were treated with HPAA/RVG/PBK-siRNA (HPAA/siRNA group), methoxy-PEG polyethylenimine (PEI-25k)/PBK-siRNA (PEI group), HPAA/RVG nanocarriers without PBK-siRNA (HPAA/RVG group), Dharmacon™ non-targeting siRNA (shNTC group), PBK-siRNA (Control group 1), AChR inhibitor (Control group 2), and GSH inhibitor (Control group 3), and compared with the control group (medium without any substances). Western blot analysis validated PBK expression levels (ELs) in various cell groups. Additionally, cell viability and proliferation were evaluated using methyl tetrazolium (MTT) assays and 5-Bromo-2'-deoxyuridine (BrdU) incorporation assays. The results revealed proton absorption peaks for HPAA at 2.78 ppm, 3.21 ppm, and 3.49 ppm, while RVG and HPAA-RVG exhibited characteristic absorption peaks at 23.653 min and 23.584 min, respectively, with peak areas of 4,856.6 and 6,927.3 for RVG. The nanoparticle sizes were 50-100 nm for HPAA-RVG and 100 nm for HPAA/RVG/PBK-siRNA, displaying spherical morphology and uniform size distribution. The average potential of HPAA-PEG was lower than that of HPAA ( P <0.05), and HPAA-RVG showed dramatically lower potential than HPAA ( P <0.001). At 8 hours, Daoy cells displayed higher endocytosis rates versus ONS-76 cells ( P <0.05). The transfection rates of HPAA-RVG in both ONS-76 and Daoy cells were higher than those of HPAA, with Daoy cells showing higher transfection rates than HPAA ( P <0.05). Under HPAA-RVG treatment, AChR levels in ONS-76 cells were significantly lower than those in Daoy cells ( P < 0.05). Compared to the control group, the PBK protein expression levels, cell survival rates, and the number of cells in the proliferative phase were significantly reduced in Control group 1, the PEI group, and the HPAA/siRNA group in both ONS-76 and Daoy cells, with the ONS-76 cells in the HPAA/siRNA group showing the lowest values among these groups ( P < 0.05). In summary, the findings indicated that the tumor microenvironment-responsive nanocomposite HPAA/RVG/PBK-siRNA selectively inhibited PBK expression in Daoy medulloblastoma cells, showcasing potential applicability in medulloblastoma therapy.
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International Journal of Pharmacology
·
2026
·Vol. 22
·期 6
·
IF 0.7
Yachun Guo,Jiahui Zhang,Yanchao Li
Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, and novel therapeutic strategies are urgently needed to overcome treatment resistance. Cordycepin (Cor), a bioactive nucleoside isolated from Cordyceps militaris, exhibits antitumor activity in multiple malignancies. However, whether Cor induces ferroptosis in NSCLC cells and the underlying mechanisms remain unclear. Therefore, this study aimed to investigate the modulatory effects of Cor on ferroptosis in NSCLC cells and to elucidate the underlying molecular and network pharmacology mechanisms. Methods: Human NSCLC A549 cells were treated with Cor (25, 50, and 100 μM). Cell viability was assessed using Cell Counting Kit-8 assays. Ferroptosis involvement was evaluated using ferroptosis inhibitors (ferrostatin-1, deferoxamine, and liproxstatin-1) and other programmed cell death inhibitors. Intracellular reactive oxygen species (ROS), Fe2+ accumulation, lipid peroxidation, glutathione (GSH) levels, and ferroptosis-related proteins were measured using fluorescence probes, spectrophotometric assays, and western blotting. Network pharmacology, protein-protein interaction analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and molecular docking were performed to identify potential molecular targets. Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expression was further examined by western blotting. Results: Cor inhibited A549 cell viability in a time- and dose-dependent manner (n = 6). Among the tested death inhibitors, only ferroptosis inhibitors significantly reversed Cor-induced cytotoxicity (p < 0.05, n = 3). Cor treatment elevated intracellular ROS levels, Fe2+ accumulation, and lipid peroxidation while reducing GSH content (p < 0.05, n = 3). At the protein level, Cor downregulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression but upregulated transferrin and acyl-CoA synthetase long-chain family member 4 (ACSL4) expression (p < 0.05, n = 3). Database screening identified 28 mutual targets linked to Cor, NSCLC, and ferroptosis. Molecular docking confirmed that Cor spontaneously binds to the Nrf2 and HO-1 proteins encoded by the key pathway genes nuclear factor erythroid 2 like 2 (NFE2L2) and heme oxygenase 1 (HMOX1), which correlated with a significant, dose-dependent downregulation of Nrf2 and HO-1 protein expression (p < 0.05, n = 3). Conclusions: Cordycepin induces ferroptosis in A549 NSCLC cells, characterized by oxidative stress, iron accumulation, lipid peroxidation, and suppression of antioxidant defenses. The Nrf2/HO-1 pathway may contribute to this process and represents a potential therapeutic target for NSCLC.
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高影响因子
Journal of Neuroimmune Pharmacology
·
2024
·Vol. 19
·期 1
·1-17
·
IF 5.2
Lin Yun,Liu Tian,Chen Hong,Zeng Ming,Hu Shunwei,Yu Xiaoning,Chen Yonghua,Xia Chunmei,Wang Jin,Wang Jijiang
The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5’-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5’-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5’-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex. Graphical Abstract
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高影响因子
CELLULAR SIGNALLING
·
2024
·
IF 4.4
Yifeng Fan,Shengyu Kang,Tong Shao,Linhao Xu,Jian Chen
Although doxorubicin (DOX) is a common chemotherapeutic drug, the serious nephrotoxicity caused by DOX-induced renal fibrosis remains a considerable clinical problem. Tanshinone IIA (Tan IIA), a compound extracted from Salvia miltiorrhiza , has been reported to have an anti-fibrotic effect. Therefore, this study investigated the molecular pathway whereby Tan IIA protects the kidneys from DOX administration. DOX (3 mg/kg body weight) was intraperitoneally administered every 3 d for a total of 7 injections (cumulative dose of 21 mg/kg) to induce nephrotoxicity. Then, Tan IIA (5 or 10 mg/kg/d) was administered by intraperitoneal injection for 28 d. In an in vitro study, 293 T cells were cultured and treated with DOX and Tan IIA for 24 h. Tan IIA reduced the blood urea nitrogen levels elevated by DOX while increasing superoxide dismutase activity, down-regulating reactive oxygen species, ameliorating renal-tubule thickening, and rescuing mitochondrial morphology. Additionally, Tan IIA reduced the renal collagen deposition, increased ATP production and complex-I activity, down-regulated transforming growth factor-β1 (TGF-β1) and thrombospondin-1 (TSP-1), and up-regulated sirtuin 3 (SIRT3). Tan IIA significantly increased cell viability. Additionally, RNA interference was employed to silence the expression of SIRT3, which eliminated the effect of Tan IIA in suppressing the expression of TGF-β1 and TSP-1. In conclusion, Tan IIA ameliorated DOX-induced nephrotoxicity by attenuating oxidative injury and fibrosis. The Tan IIA-induced rescue of mitochondrial morphology and function while alleviating renal fibrosis may be associated with the activation of SIRT3 to suppress the TGF-β/TSP-1 pathway.
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高影响因子
APPLIED SURFACE SCIENCE
·
2024
·
IF 6.3
Jialin Zhao,Ting Wu,Youlin Xiong,Wei Zhang,Zian Pan,Shuangfei Cai,Rong Yang
Electrochemical biosensors have shown promise in bioanalysis and diagnosis. However, they suffer from the accumulation and adhesion of biomolecules in biofluids on sensing surfaces, while the hiring of potential antifouling is limited by the cost and complexity of the construction methods. Here, an economical three-dimensional (3D) conductive antifouling coating was prepared. This coating was composed of bovine serum albumin (BSA) crosslinked glutaraldehyde (GA) and copper-gold nanowires (CuAu NWs) with excellent electrical conductivity. Furthermore, a dual-targeted aptamer (D-Apt), with a “3-in-1″ structure of two specific binding sequences and a DNA linker, was designed to specifically recognize BSA and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, affording low nanomolar binding affinity. Importantly, the introduction of the D-Apt greatly simplified the functionalization procedure on the electrode surface and the immobilization of the biorecognition element. Then, a simple electrochemical biosensor based on the CuAu/BSA/GA and D-Apt was constructed for the detection of S protein. This sensor exhibited merits of cost-effectiveness, sensitivity and practicality for detection of S protein. The work could provide a facile avenue to construct electrochemical biosensors with low-cost antifouling for the accurate diagnosis of epidemic antigenic disease markers.
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INDUSTRIAL CROPS AND PRODUCTS
·
2024
·
IF 5.6
Ling Liu,Hong Peng,Ying Shen,Limin Shen,Guiming Fu,Yin Wan,Zhaodi Xu
In-depth understanding the influence of ionic liquid structure on the selective dissolution of the main biopolymers from plant cell walls is necessary for designing ionic liquids that could efficiently pretreat and fractionate lignocellulosic biomass. The current study aimed to investigate the effect of electronegativity of anions of 1-butyl-3-methylimidazolium halide based ionic liquids BmimCl, BmimBr, and BmimI on dissolving bamboo slices. The surface of pretreated bamboo slices and the regenerated carbohydrate-rich fractions were characterized carefully. The results revealed that the ability to damage bamboo cell walls and dissolve bamboo slices followed the order of BmimCl>BmimBr>BmimI, which was consistent with the electronegativity of halogen anions (Cl - >Br - >I - ). The dissolving selectivity for lignin from bamboo cell walls was in the order of BmimBr>BmimI>BmimCl. The ionic liquids performed a greater dissolving selectivity for lignin than carbohydrates (cellulose and hemicellulose). The permeating rate of ionic liquid molecules into bamboo cell walls increased with the enhancement of electronegativity of halogen anions. The regenerated carbohydrate-rich fractions were rich in hemicellulose and cellulose with an amount of lignin. Both temperature and time had also great effect on the dissolution of bamboo slices. On the whole, the electronegativity of halogen anions had a profound impact on the deconstruction of bamboo cell walls and dissolution of bamboo. This study provided important theoretical assistance for designing ionic liquids that could more efficiently pretreat and fractionate lignocellulosic biomass.
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Biofabrication
·
2025
·
IF 8
Ruoyu Li,Wenfeng Li,Yungshan Teng,Runze Li,Siyi Kong,Xin Chen,Haotian Luo,Danying Chen,Yuqing Guo,Yangqiao Qing,Hio Cheng leong,Bingyan Guo,Meihan Chen,Zixin Pan,Shushuo Zheng,Yihong Deng,Yang Cao,Chen Zhou,Xuenong Zou,Weicai Wang
Craniofacial bone defect healing in periodontitis patients with diabetes background has long been difficult due to increased blood glucose levels which cause overproduction of reactive oxygen species (ROS) and a low pH environment. These conditions negatively affect the function of macrophages, worsen inflammation and oxidative stress, and ultimately, hinder osteoblasts' bone repair potential. In this study, we for the first time found that ANXA1 expression in macrophages was reduced in a diabetic periodontitis environment, with the activation of the NLRP3/Caspase-1/GSDMD signaling pathway, and, eventually, increased macrophage pyroptosis. Next, we have developed a new GPPG intelligent hydrogel system which was ROS and pH responsive, and loaded with Ac2-26, an ANXA1 bioactive peptide, and osteogenic peptide OGP as well. We found that Ac2-26/OGP/GPPG can effectively reduce ROS, mitigates macrophage pyroptosis via the ANXA1/NLRP3/Caspase-1/GSDMD pathway and enhanced osteogenic differentiation. The effect of Ac2-26/OGP/GPPG in regulation of pyroptosis and bone defect repair was also further validated by animal experiments on periodontitis-induced tooth loss model in diabetic rats. To conclude, our study unveils the effect of ANXA1 on macrophage pyroptosis in periodontitis patients with diabetes, based on which we introduced a promising innovative hydrogel system for improvement of bone defects repair in diabetic periodontitis patients via targeting macrophage pyroptosis and enhancing osteogenic potential.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Kunfeng Zhang,Hao Chen,Yunbo Hao,Wensen Li,Yong Li,Wenna Zhang,Yan Chen
We identified Armillariella tabescens polysaccharide (PAT-W), a compound isolated from a Chinese medicinal mushroom , as a potential novel oral ulcer (OU) drug. In treating OU rats with PAT-W, especially in the high-dose group, oral mucous tissue TNF- α , IL-1 β , and IL-6 levels were markedly reduced, and pathological morphology and oxidative stress were effectively improved. Western blot analysis showed that the PAT-W channel ameliorated OU mucous tissue damage, which depends on the activation of the Nrf2/HO-1 antioxidant signaling pathway . Furthermore, high-throughput sequencing results showed that PAT-W regulated the maladjustment of the oral microbiota caused by OU. Therefore, based on the new viewpoint of activating the Nrf2/HO-1 pathway and regulating oral microbiota, PAT-W is expected to become a new natural drug for treating oral ulcers and improving patients' quality of life.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2024
·
IF 8.1
Qunying Sun,Qianxiang Xiao,Qixu Chen,Wen He,Feng He,Hongqing Wang
Efficient and stable photocatalytic materials are urgently needed for the photo-reduction of uranium in wastewater treatment without the addition of external sacrificial agents under air conditions. Herein, we designed and synthesized 1 T@2H MoS 2 QDs (MSQ) modified oxygen-rich defective ZnO photocatalysts 1 T@2H MoS 2 QDs/OV-ZnO (MSQVZO) and systematically investigated its photocatalytic U(VI) activity in various matrices, which exhibited 97 % removal efficiency of uranium after 40 min of visible light irradiation under aerobic conditions, and the order of photocatalytic activity was MSQVZO > OV-ZnO > ZnO. XRD, ESR, XPS, and UV–vis were used for the characterization of the materials. In addition, it was argued using DFT analysis that the introduction of oxygen defects drove the OV-ZnO to interact with the intermediates of the oxygen evolution reaction (OER) reaction more readily than the ZnO, thus improving the activity of the OV-ZnO-based catalysts. More importantly, a new mechanism for photo-reduction of U(VI) was established. It provides an effective strategy for the photo-reduction of U(VI) without a sacrificial agent.
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Small
·
2025
·
IF 12.1
Shufang Zhou,Jintong Xu,Jiayi Wang,Nurimangul Muntiza,Qiliang Deng
The reversible photo-transformation metal–organic framework (MOF) capable of changing properties by surface chemical modification has huge potential in various industrial fields. However, such material is still rare. Herein, a crystalline 3D MOF constructed by 5-boronobenzene-1, 3-dicarboxylic acid, and zinc sulfate (Zn-BBDA) is reported, where the boronic groups are spontaneously change into the hydroxyl groups during the preparation process. The resulted MOF possesses the orderly distributed hydroxyl groups in interlayers. The photo-responsive properties of the resulted MOF are explored. The results indicate that the appearance color and fluorescence emission of the resulted Zn-BBDA can be simultaneously adjusted based on the oxidation-reduction reaction of the hydroxyl group. The transformation degree of the MOF can be quantitatively monitored by fluorescence emission or Red, Green, Blue (RGB) readout. The response mechanism of the resulted Zn-BBDA is revealed. The surface properties of the resulted Zn-BBDA before and after irradiation are also investigated. The present material exhibits a bright future in the field of anti-counterfeiting and antibacterial treatment. The research provides new views in exploring novel photo-response materials.
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高影响因子
危险品化学品经营许可证（带存储）