Advanced Science
·
2022
·Vol. 9
·期 10
·2105240
·
IF 17.521
Huiming Peng,Jian Shen,Xin Long,Xiaoqi Zhou,Jiaqi Zhang,Xina Xu,Teng Huang,Hui Xu,Shuguo Sun,Chun Li,Ping Lei,Heshui Wu,Jun Zhao
Pancreatic cancer is a deadly disease with little response to standard therapies. Irreversible electroporation (IRE) has emerged as a novel ablative technique for the clinical treatment of pancreatic cancer. Combinations of IRE and immunotherapies, including anti-programmed death 1 ( α PD1) immune checkpoint blockade, have shown promising efficacy in both preclinical and clinical studies. However, tumor recurrence remains an obstacle that needs to be overcome. It herein is shown that IRE induces a substantial infiltration of neutrophils into pancreatic tumors. These neutrophils are then polarized into a protumor phenotype by immunosuppressive cues, in particular transforming growth factor β (TGF- β ). Using glutathione-responsive degradable mesoporous silica nanoparticles loaded with SB525334, an inhibitor of TGF- β 1 receptor, it is demonstrated that local inhibition of TGF- β within the tumor microenvironment promotes neutrophil polarization into an antitumor phenotype, enhances pancreatic cancer response to combined IRE and α PD1 therapy, and induces long-term antitumor memory. The therapeutic efficacy is also attributed to tumor infiltration by CD8 + cytotoxic T cells, depletion of regulatory T cells, and maturation of antigen-presenting dendritic cells. Thus, modulating neutrophil polarization with nanomedicine is a promising strategy for treating pancreatic cancer.
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Nano Energy
·
2025
·
IF 17.1
Xiuzi Che,Huiqing Fan,Jiahao Cao,Yongbo Fan,Yuxin Jia,Yidi Duan,Qinghua Guo,Yafei Feng,Weijia Wang
Piezoelectric biomaterials can convert mechanical energy into electricity, which make them attractive for implant applications, such as sensing, energy harvesting, and medical devices. The β-glycine has excellent piezoelectric performance, but their practical use is hindered by instable crystal phase and water solubility. Here, we present a simple method for preparing poly L-lactide (PLLA) composite fibers encapsulating β-glycine nano crystals via coaxial electrospinning. The formation of β-glycine crystals is the synergistic outcome of the ionization of glycine solution under the electric field and the confinement of external PLLA solution, which enhances the piezoelectric performance of the film. The V oc , I sc , and power density of composite film reach 14 V, 0.94 μA, and 0.92 mW/cm 2 , respectively. In addition, PLLA shell stabilizes β-glycine, leading to a stable piezoelectric performance for device applications. The composite film can be ultrasonically driven to generate electric signals, and therefore functions well in promoting cell proliferation and bone tissue repairing in vivo . Moreover, the film can be naturally degraded after long-term implantation. This study provides a strategy to deal with the instability of β-glycine-based biodegradable piezoelectric films, and promotes the implant applications.
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GENE
·
2024
·
IF 2.6
Wen Zhong,Huanan Jia,Haiyan Zhu,Yuan Tian,Wei Huang,Qiyue Yang
Sarcopenia has become a prominent health problem among the elderly because of its adverse consequence, including physical disabilities and death. Fibro-adipogenic progenitors (FAPs) exhibit adipogenic and fibrogenic potencies and regulate skeletal muscle development, which plays important role in sarcopenia. Mairin, as an ingredient of Astragalus membranaceus, has the effect of anti-fibrosis. Therefore, we predicted that mairin targeted the fibrosis of FAPs and then affected sarcopenia. To verify our ideas, mairin (30 mg/kg/day or 60 mg/kg/day) was given to senescence accelerated mouse-prone 8 (SAMP8) mice by oral administration. Aging led to loss of weight, skeletal muscle mass, strength, and function, and an increase in muscle atrophy and fibrosis, while mairin administration inhibited physiological decline caused by aging. Similarly, mairin (20 μM or 40 μM) treatment enhanced FAP proliferation but blocked the differentiation into fibroblasts. Mechanically, mairin played an anti-fibrotic role via AMP-activated protein kinase-transforming growth factor beta-drosophila mothers against decapentaplegic protein (AMPK-TGF-β-SMAD) axis, as evidenced by increased phosphorylation of AMPKα and decreased TGF-β and phosphorylated-SMAD2/3. In addition, the potential target genes of mairin were explored by mRNA sequencing in our study. In conclusion, mairin may interfere with the AMPK/TGF-β/SMAD pathway to repress the fibrosis of FAPs and eventually ameliorate sarcopenia.
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ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Kuan Cheng,Xiaohong Chen,Yifan Yi,Yue Wang,Mengdie Tian,Jingjing Yu,Yuxin Xia,Jingyi Li,Min Zhang,Cuicui Ding
Collagen, as the principal structural component of the cornea, has emerged as a promising biomaterial for artificial corneal owing to its excellent biocompatibility and degradability. However, the mechanical properties of current collagen membrane cannot match the requirements of artificial corneal materials. Inspired by the hierarchical lamellar organization of native corneal stromal collagen, a biomimetic collagen-based corneal repair material was designed via a “killing two birds with one stone” strategy. In this strategy, carboxymethyl-β-cyclodextrin (CM-β-CD) was incorporated into the collagen, serving dual functions: regulating the in vitro self-assembly process of collagen molecules and establishing multiple covalent cross-linking sites within the network. Concurrently, controlled external shear forces were applied to induce anisotropic alignment of collagen fibers, effectively replicating the highly organized structural hierarchy characteristic of native corneal stromal tissue. The resulting membrane exhibited a 67% enhancement in tensile strength (0.52 MPa) compared to pure collagen membranes. Notably, in vivo lamellar keratoplasty evaluations revealed accelerated tissue regeneration, achieving complete re-epithelialization within 14 days versus 28 days for controls. These findings establish the material’s potential as an advanced artificial corneal for tissue engineering applications.
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Food Analytical Methods
·
2019
·Vol. 12
·期 12
·2777-2784
·
IF 2.413
Li Hong,Zhao Chunxi,Tian Hao,Yang Yaling,Li Wanyi
An uncomplicated, valid, and convenient way for detection of lycopene and β-carotene in fruit juice samples using acid–base-induced deep eutectic solvent (DES) liquid-liquid microextraction (DES-ABLLME) prior to HPLC was developed. The ternary fatty acid DESs were prepared by C 9 :C 10 :C 11 (2:1:1), which serve as hydrogen bond donors and hydrogen bond acceptors synchronously. In extraction procedure, NH 3 ·H 2 O was used as the emulsifier and reacted with DESs with a milk solution, which can significantly increase the extraction efficiency. HCl was used as the de-emulsifier, which could break the state of emulsification. At optimum conditions, the calibration graphs were linear in the concentration range from 0.1 to 100 μg mL −1 for lycopene and from 0.025 to 5.00 μg mL −1 for β-carotene. The limits of detection (LODs) were 0.05 and 0.002 μg mL −1 for lycopene and β-carotene, respectively. The RSD values were varied from 1.3 to 4.1%. Finally, the proposed method was applied to analyze β-carotene and lycopene in fruit juices.
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International Journal of Stem Cells
·
2021
·
IF 2.5
Qiong Li,Lei Huang
Background and Objectives MiR-148a-3p has been reported to regulate the differentiation of marrow stromal cell osteoblast. In this study, whether miR-148a-3p regulated the odontoblastic differentiation of human dental pulp stem cells (hDPSCs) or not was explored. Methods and Results The hDPSCs were isolated and identified via flow cytometry. Targets of miR-148a-3p were identified via bioinformatics and dual-luciferase reporter assay. After the cell was cultured in the odontogenic differentiation medium or infected, cell viability, invasion, and odontoblastic differentiation were detected via MTT, transwell, and Alizarin Red S staining, respectively. The miR-148a-3p, Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions were determined by RT-qPCR and Western blot. The hDPSCs odontoblastic differentiation downregulated the miR-148a-3p expression and upregulated Wnt1 expression. Wnt1 was determined as the target for miR-148a-3p. MiR-148a-3p mimic and siWnt1 suppressed the cell viability, invasion, and odontoblastic differentiation of hDPSCs and inhibited the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. In contrast, miR-148a-3p inhibitor and overexpressed Wnt1 promoted the cell viability, invasion, and odontoblastic differentiation of hDPSCs, and upregulated the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. Also, miR-148a-3p mimic and inhibitor reversed the effects of Wnt1 overexpression and siWnt1. Conclusions MiR-148a-3p modulated the invasion and odontoblastic differentiation of hDPSCs through the Wnt1/β-catenin pathway.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Lichuang Cao,Ran Chen,Xin Huang,Shuifeng Li,Sufang Zhang,Xiangpeng Yang,Zongmin Qin,Wei Kong,Wei Xie,Yuhuan Liu
In this study, a Petri-dish-based double-layer high-throughput screening method was established to improve glucose tolerance of β-glucosidase Bgl15. Two beneficial mutations were identified, and the joint mutant 2R1 improved the half-maximal inhibitory concentration of glucose from 0.04 to 2.1 M. The crystal structure of 2R1 was subsequently determined at 2.7 Å. Structure analysis revealed that enhancement of glucose tolerance may be due to improved transglycosylation activity made possible by a hydrophobic binding site for glucose as an acceptor and more stringent control of a putative water channel. To further ameliorate the application potential of the enzyme, it was engineered to increase the half-life at 50 °C from 0.8 h (Bgl15) to 180 h (mutant 5R1). Furthermore, supplementation of 5R1 to the cellulase cocktail significantly improved glucose production from pretreated sugar cane bagasse by 38%. Consequently, this study provided an efficient approach to enhance glucose tolerance and generated a promising catalyst for cellulose saccharification.
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PHYSIOLOGY & BEHAVIOR
·
2017
·
IF 2.341
Xiaoyu Song,Bo Liu,Lingyu Cui,Biao Zhou,Weiwei Liu,Fanxing Xu,Toshihiko Hayashi,Shunji Hattori,Yuko Ushiki-Kaku,Shin-ichi Tashiro,Takashi Ikejima
Depression is one of the most frequent psychiatric disorders of Alzheimer's disease (AD). Depression and anxiety are associated with increased risk of developing AD. Silibinin , a flavonoid derived from milk thistle ( Silybum marianum ), has been used as a hepato-protectant in the clinical treatment of liver diseases. In this study, the effect of silibinin on Aβ-induced anxiety/depression-like behaviors in rats was investigated. Silibinin significantly attenuated anxiety/depression-like behaviors caused by Aβ1-42-treatment as shown in tail suspension test (TST), elevated plus maze (EPM) and forced swimming tests (FST). Moreover, silibinin was able to attenuate the neuronal damage in the hippocampus of Aβ1-42-injected rats. Silibinin-treatment up-regulated the function through BDNF/TrkB pathway and attenuated autophagy in the hippocampus. Our study provides a new insight into the protective effects of silibinin in the treatment of anxiety/depression.
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CANCER GENE THERAPY
·
2022
·Vol. 30
·期 2
·335-344
·
IF 5.854
Liu Jian,Mai Yumiao,Wang Yingjie,Chen Zhiwei,Wang Fei,Wei Huixia,Yao Qianghua
RAB3D, a small Ras-like GTPase involved in regulating secretory pathway, plays a cancer-promoting role in several solid tumors. However, its role in leukemogenesis remains unknown yet. Acute myeloid leukemia (AML) is a common acute leukemia with a high mortality. Here, we found the higher expression of RAB3D in bone marrow mononuclear cells derived from AML patients ( n = 54) versus healthy participants ( n = 20). The following loss- and gain-of-function experiments demonstrated that RAB3D promoted growth, enhanced colony formation and accelerated G1/S transition of U937, THP-1 and KG-1 AML cells. RAB3D silencing inhibited tumorigenesis of AML cells in vivo and delayed AML cells-induced death of mice. Interestingly, the expression of RAB3D is positively correlated with that of an oncogene mouse double minute 2 (MDM2) in bone marrow mononuclear cells of AML patients ( r = 0.923, p < 0.001). Intracellular MDM2 was conjugated with more ubiquitins and degraded faster when RAB3D was silenced. A commonly therapeutic target of AML, β-catenin signaling, was activated by RAB3D overexpression, but deactivated after MDM2 was silenced. The RAB3D-induced proliferation acceleration and β-catenin activation were abolished by MDM2 knockdown, implying that RAB3D function by stabilizing MDM2. In addition, c-MYC, a β-catenin downstream effector, was recruited directly to the RAB3D gene promoter (-360/-349 and -136/-125 sites) and induced its transcription. Collectively, this study demonstrates that RAB3D may exacerbate the malignant behaviors of AML cells through forming a positive feedback loop with MDM2/β-catenin/c-MYC signaling. RAB3D might be a novel target of clinical AML treatment.
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Science China-Materials
·
2021
·
IF 8.273
Li Yue,Liu Liqiang,Xu Chuanlai,Kuang Hua,Sun Li
A novel lateral flow immunoassay biosensor, combining the receptor-ligand reaction and antigen-antibody reaction was developed for the detection of β-lactam antibiotics in milk. The receptor protein, the carboxy-terminal domain of β-lactam sensor-transducer mutant from Bacillus. licheniformis , served as the recognition element. Colloidal gold (CG)-labelled receptor antibody-receptor ternary complex was applied as a signal transducer probe. The presence of β-lactams was identified through a color change in the test zone, where the reaction between the complex of CG/anti-receptor antibody/receptor and β-lactam antigen on the test line could be inhibited by β-lactam residues in the sample, thus leading to a reduction in color signal. Based on the indirect labeling of the receptor with an antibody as a linker, the ability to detect 33 β-lactams was below or near the corresponding maximum residue limit. The proposed lateral flow immunoassay biosensor appears to be an excellent field-based screening tool for the qualitative screening of β-lactams in milk.
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JOURNAL OF BIOMATERIALS APPLICATIONS
·
2016
·
IF 1.988
Yantian Chen,Fengli Zhang,Qiang Fu,Yong Liu,Zejian Wang,Nianmin Qi
Injectable thermo-sensitive hydrogels have a potential application in bone tissue engineering for their sensitivities and minimal invasive properties. Human dental pulp stem cells have been considered a promising tool for tissue reconstruction. The objective of this study was to investigate the proliferation and osteogenic differentiation of dental pulp stem cells in injectable thermo-sensitive chitosan/β-glycerophosphate/hydroxyapatite hydrogel in vitro. The chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel were prepared using the sol-gel method. The injectability of chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel was measured using a commercial disposable syringe. Scanning electron microscopy was used to observe the inner structure of hydrogels. Then dental pulp stem cells were seeded in chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel, respectively. The growth of dental pulp stem cells was periodically observed under an inverted microscope. The proliferation of dental pulp stem cells was detected by using an Alamar Blue kit, while cell apoptosis was determined by using a Live/Dead Viability/Cytotoxicity kit. The osteogenic differentiations of dental pulp stem cells in chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel were evaluated by alkaline phosphatase activity assay and mRNA expression of osteogenesis gene for 21 days in osteogenic medium. The results indicated that there was no significant difference between chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel in injectability. Cells within the chitosan/β-glycerophosphate/hydroxyapatite hydrogel displayed a typical adherent cell morphology and rapid proliferation with high cellular viability after 14 days of culture. Dental pulp stem cells seeded in chitosan/β-glycerophosphate/hydroxyapatite hydrogels had a higher alkaline phosphatase activity and better up-regulation of gene expression levels of Runx-2, Collagen I, alkaline phosphatase and osteocalcin than in chitosan /β-glycerophosphate hydrogels after osteogenic differentiation. These results demonstrated that the chitosan/β-glycerophosphate/hydroxyapatite hydrogel had excellent cellular compatibility and the superiority in promoting dental pulp stem cells osteogenic differentiation in vitro, showing that the combination of dental pulp stem cells and chitosan/β-glycerophosphate/hydroxyapatite hydrogel has the potential to be used for bone tissue engineering.
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MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 2
·1-11
·
IF 5.833
Wang Xiaoying,Li Linyu,Gu Xuan,Yu Bingjia,Jiang Meng
The aggregation of amyloid-β oligomers (AβOs) with extremely strong neurotoxicity has been proved to be the main pathogenesis of Alzheimer’s disease (AD). For sensitive quantification of AβOs, a switchable electrochemical aptasensor is proposed. Metal organic framework carrying Au nanoparticles (AuNPs@CuMOF) has been used to label signaling displaced-probe (SD), which formed triple helix switch (THS) by hybridizing with label-free anti-AβOs aptamer (Apt) on the electrodeposited palladium electrode (EPd). Thus, a relatively strong response of differential pulse voltammetry (DPV) was produced (switch on). With the specific binding between AβOs and Apt, the DPV response obviously decreased, owing to destroyed structure of THS and the separation of AuNPs@CuMOF/SD from the EPd (switch off). The mode of “switch on-off” can dramatically enhance the AβOs-dependent DPV intensity change. As a result, the switchable EA exhibited excellent selectivity and sensitivity with the linear range from 0.5 fM to 500 fM and the detection limit of 0.25 fM. When evaluating the AβOs of artificial cerebrospinal fluid (aCSF) samples, the switchable EA exhibited desirable feasibility, and the results are basically consistent with the enzyme linked immunosorbent assay (ELISA). The work could provide a potential tool of the AD diagnosis and a bright future in clinical applications.
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