ANALYTICA CHIMICA ACTA
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2018
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IF 5.123
Yajing Liu,Wei Liu,Hongjuan Li,Weixiao Yan,Xinjian Yang,Dandan Liu,Shuxiang Wang,Jinchao Zhang
Hypoxia plays a crucial role in cancer progression, and it has great significance for monitoring hypoxic level in biosystems. Cancer stem cells (CSCs) represent a small population of tumour cells that regard as the key to seed tumours. The survival of CSCs depend on the tumour microenvironment, which is distinct region has the hypoxic property. Therefore, the detection of the hypoxic CSC niche plays a pivotal role in the destructing the ‘soil’ of CSCs, and eliminating CSCs population. Numerous one-photon excited fluorescent probes have been developed to indicate the hypoxic status in tumours through the detection of nitroreductase (NTR) level. However, the biomedical application of one-photon fluorescent probes is limited due to the poor tissue penetration. In the present work, we reported a two-photon fluorescent probe to detect the NTR in CSCs and monitor the hypoxic microenvironment in vivo . The two-photon fluorescent molecular probe with a hypoxic specific response group can be reduced by NTR under hypoxic conditions . We used the two-photon probe to detect the hypoxia status of 3D cultured-CSCs in vitro and in vivo CSCs' microenvironment in tumour. The two-photon absorption cross section extends fluorescent excitation spectra to the near infrared region, which dramatically promotes the tissue penetration for hypoxic microenvironment detection of CSC in vivo .
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ELECTROCHIMICA ACTA
·
2018
·
IF 5.116
Jing Zhao,Yingying Tang,Ya Cao,Tianshu Chen,Xiaoxia Chen,Xiaoxia Mao,Yongmei Yin,Guifang Chen
Cancer stem cells (CSCs) are recognized as an important source of cancers. Surface biomarkers play a critical role for CSCs profiling and also for diagnostic purposes. In this paper, we propose self-assembled supramolecular nanocomposites assisted multiple signal amplification strategy, and successfully apply it in electrochemical detection of an important CSCs biomarker CD44 as well as identification of breast CSCs. A supermolecular composite, consisting of a binding peptide that is able to bind to the target CD44 and a self-assembled diphenylalanine (FF) nanostructure that provides a template for deposition of gold nanoparticles (AuNPs), is elaborately constructed on the surface of an electrode through the linkage of cucurbit[8]urils. In the presence of CD44, this supramolecule is able to provide amplified electrochemical signals from silver-enhancement on AuNPs after target-protection from trypsin-catalyzed digestion. Whereas in the absence of the target, this supramolecular architecture is destroyed, resulting in suppressed signals. Linear sweep voltammetry results present a satisfactory specificity and sensitivity, which also demonstrate a wide linear range with a limit of detection of 2.17 pg/mL toward CD44 protein and a limit of detection of 8 cells/mL toward CD44-positive cancer cells. Therefore, this work provides a promising prospective for further clinic application in the future.
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CELLULAR & MOLECULAR BIOLOGY LETTERS
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2017
·Vol. 22
·期 1
·1-11
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IF 1.26
Li Xican,Xie Hong,Jiang Qian,Wei Gang,Lin Lishan,Li Changying,Ou Xingmei,Yang Lichan,Xie Yulu,Fu Zhen,Liu Yamei,Chen Dongfeng
The natural dihydroflavonol (+) taxifolin was investigated for its protective effect on Fenton reagent-treated bone marrow-derived mesenchymal stem cells (bmMSCs). Various antioxidant assays were used to determine the possible mechanism. These included •OH-scavenging, 2-phenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide radical-scavenging (PTIO•-scavenging), 1, 1-diphenyl-2-picryl-hydrazl radical-scavenging (DPPH•-scavenging), 2, 2′-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) radical-scavenging (ABTS+•-scavenging), Fe3+-reducing, and Cu2+-reducing assays. The Fe2+-binding reaction was also investigated using UV-Vis spectra. The results revealed that cell viability was fully restored, even increasing to 142.9 ± 9.3% after treatment with (+) taxifolin. In the antioxidant assays, (+) taxifolin was observed to efficiently scavenge •OH, DPPH• and ABTS+• radicals, and to increase the relative Cu2+- and Fe3+-reducing levels. In the PTIO•-scavenging assay, its IC50 values varied with pH. In the Fe2+-binding reaction, (+) taxifolin was found to yield a green solution with two UV-Vis absorbance peaks: λmax = 433 nm (ε =5.2 × 102 L mol−1 cm −1) and λmax = 721 nm (ε = 5.1 × 102 L mol−1 cm −1). These results indicate that (+) taxifolin can act as an effective •OH-scavenger, protecting bmMSCs from •OH-induced damage. Its •OH-scavenging action consists of direct and indirect antioxidant effects. Direct antioxidation occurs via multiple pathways, including ET, PCET or HAT. Indirect antioxidation involves binding to Fe2+.
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ACS Nano
·
2023
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IF 17.1
Lang Chen,Chenyan Yu,Wanting Xu,Yuan Xiong,Peng Cheng,Ze Lin,Zhenhe Zhang,Leonard Knoedler,Adriana C. Panayi,Samuel Knoedler,Junqing Wang,Bobin Mi,Guohui Liu
Ongoing research has highlighted the significance of the cross-play of macrophages and mesenchymal stem cells (MSCs). Lysine-specific demethylase 6B (KDM6B) has been shown to control osteogenic differentiation of MSCs by depleting trimethylated histone 3 lysine 27 (H3K27me3). However, to date, the role of KDM6B in bone marrow-derived macrophages (BMDMs) remains controversial. Here, a chromatin immunoprecipitation assay (ChIP) proved that KDM6B derived from osteogenic-induced BMSCs could bind to the promoter region of BMDMs’ brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1) gene in a coculture system and activate BMAL1. Transcriptome sequencing and experiments in vitro showed that the overexpression of BMAL1 in BMDM could inhibit the TLR2/NF-κB signaling pathway, reduce pyroptosis, and decrease the M1/M2 ratio, thereby promoting osteogenic differentiation of BMSCs. Furthermore, bone and macrophage dual-targeted GSK-J4 (KDM6B inhibitor)-loaded nanodiscs were synthesized via binding SDSSD-apoA-1 peptide analogs (APA) peptide, which indirectly proved the critical role of KDM6B in osteogenesis in vivo. Overall, we demonstrated that KDM6B serves as a positive circulation trigger during osteogenic differentiation by decreasing the ratio of M1/M2 both in vitro and in vivo. Collectively, these results provide insight into basic research in the field of osteoporosis and bone repair.
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POULTRY SCIENCE
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2022
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IF 4.014
Zhengtian Lyu,Haifang Li,Xin Li,Hui Wang,Hongchao Jiao,Xiaojuan Wang,Jingpeng Zhao,Hai Lin
ABSTRACT Fibroblast growth factor 23 ( FGF23 ), a bone-derived hormone, is involved in the reabsorption of phosphate ( P ) and the production of vitamin D hormones in the kidney. However, whether and how FGF23 regulates chicken bone metabolism remains largely unknown. In the present study, we investigated the effect of FGF23 on osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells ( BMSCs ). First, we found that the transcription of FGF23 was inhibited by β-glycerophosphate sodium ( GPS , 5 mM, 10 mM, 20 mM) and 10 −9 M 1, 25-dihydroxyvitamin D3 ( 1, 25(OH) 2 D 3 ), but was stimulated by 10 −7 M 1, 25(OH) 2 D 3 and parathyroid hormone ( PTH , 10 −9 M, 10 −8 M, 10 −7 M). Second, overexpression of FGF23 by the FGF23 adenovirus ( Adv-FGF23 ) suppressed the formation of mineralized nodules ( P < 0.001) and alkaline phosphatase ( ALP ) activity ( P < 0.05) in both differentiated and mineralized osteoblasts. Administration of FGF receptor 3 ( FGFR3 ) inhibitor (50 nM) was sufficient to restore the FGF23-decreased ALP activity ( P < 0.05), but not for the formation of mineralized nodules. In addition, the phosphorylation of ERK increased considerably with Adv-FGF23 overexpression ( P < 0.05). Administration of an ERK-specific inhibitor (10 μM) could down-regulate the phosphorylation of ERK ( P-ERK ) ( P < 0.05) and slightly restored the Adv-FGF23-reduction of ALP activity ( P = 0.08). In summary, our data suggest that GPS, 1, 25(OH) 2 D 3 , and PTH could regulate FGF23 mRNA expression in vitro. FGF23 is a negative regulator of bone remodeling. FGF23 not only inhibits BMSCs osteogenesis through the FGFR3-ERK signaling pathway but also suppresses the mineralization of mature osteoblasts.
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ACS Applied Materials & Interfaces
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2022
·
IF 10.383
Qimeng Wang,Ziyan Wang,Difei Zhang,Jieyu Gu,Yongxin Ma,Yan Zhang,Jinghua Chen
As extracellular matrix (ECM) mimetic materials, hydrogels have been widely used for broad biomedical applications. However, with so many physical or chemical cues in the matrix that regulate cell behaviors or functions, it remains challenging to design a customizable hydrogel with the desired properties on demand. In the current study, we aim to establish a circular-patterned hydrogel model with gradient stiffness for screening the most favorable ECM environment for specific cells or certain application purposes. First, six types of hydrogels with a wide stiffness range of 1.2–28.9 kPa were prepared by dynamic covalent cross-linking between gelatin derivatives and oxidized hyaluronic acid. Taking advantage of their instantaneous self-healing property from dynamic chemistry, the hydrogels were further spliced into one whole piece of circular-patterned hydrogel. When rabbit bone marrow mesenchymal stem cells were seeded in the center, the influences of matrix stiffness on the regulation of stem cell adhesion, migration, and differentiation were directly observed and compared under one visual field. In addition, these hydrogels all possessed good biocompatibility, degradability, and injectability, showing great potential for tissue-engineering-related applications.
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Biomaterials Advances
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2022
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IF 0
Shaoshuai Song,Xiaoyun Liu,Jie Huang,Zhijun Zhang
The development of three-dimensional (3D) bioprinting technology opens a door for constructing bionic nerve tissue scaffolds on demand for nerve injury repair. However, the electrical insulation of the current nerve tissue scaffolds fabricated by 3D bioprinting hinders the bioelectrical signal transmission between cells, limiting the therapeutic effect in nerve tissue repair. To address this issue, we have developed a neural stem cell (NSC)-laden 3D bioprinted electroconductive hydrogel (ECH) scaffold, composed of modified poly(3,4-ethylenedioxythiophene) (PEDOT), gelatin methacrylate/polyethylene glycol diacrylate hydrogel matrix, and NSCs, to promote the electron propagation in the scaffold for enhanced nerve regeneration. In our strategy, PEDOT is modified by doping with chondroitin sulfate and tannic acid (TA) to improve its water-solubility and electric property. With moderate mechanical strength and good electroconductivity, the 3D ECH scaffold provides a benign conductive microenvironment for the adhesion, growth, and proliferation of the encapsulated NSCs. Clearly, in the 3D ECH scaffolds, the NSCs not only maintain high cell viability (>90%) after bioprinting, but also tend to differentiate into neurons with extended neurites. This study testifies for the first time the effect of polyphenol structure belonging to TA on neuronal differentiation of NSCs, and offers a new insight into designing electroconductive biomaterials to induce neuronal regeneration for nerve injury repair and neurodegenerative disease therapy.
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ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Jiafeng Wang,Xiaozhang Qu,Chen Xu,Zhimin Zhang,Guohua Qi,Yongdong Jin
Regulating stem cell differentiation in a controllable way is significant for regeneration of tissues. Herein, we report a simple and highly efficient method for accelerating the stem cell differentiation of dental pulp stem cells (DPSCs) based on the synergy of the electromagnetic field and the photothermal (thermoplasmonic) effect of plasmonic nanoparticles. By simple laser irradiation at 50 mW/cm2 (10 min per day, totally for 5 days), the thermoplasmonic effect of Au nanoparticles (AuNPs) can effectively regulate mitochondrial metabolism to induce the increase of mitochondrial membrane potential and further drive energy increase during the DPSC differentiation process. The proposed method can specifically regulate DPSCs’ cell differentiation toward odontoblasts, with the differentiation time reduced to only 5 days. Simultaneously, the molecular profiling change of mitochondria within DPSCs during the cell differentiation process is revealed by in situ surface-enhanced Raman spectroscopy. It clearly demonstrates that the expression of hydroxyproline and glutamate gradually increases with prolonging of the differentiation days. The developed method is simple, robust, and rapid for stem cell differentiation of DPSCs, which would be beneficial to tissue engineering and regenerative medicine.
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Cells
·
2022
·Vol. 11
·期 17
·2642
·
IF 7.666
Chunyan Yang,Zixuan Guan,Xincheng Pang,Zengqi Tan,Xiaomin Yang,Xiang Li,Feng Guan
Hepatocellular carcinoma (HCC) is one of the dominating causes of cancer-related death throughout the world. Treatment options for patients with HCC vary, however, the lack of effective targeted drugs is the major reason for death in advanced HCC patients. In this study, a delivery system based on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) loaded with doxorubicin (Dox) was developed. In this system, we initially erased terminal linked α2–3 and α2–6 sialic acids on the surface of EVs by neuraminidase. The exhibition of galactose (Gal) and N-acetylgalactosamine (GalNAc) residues in treated MSC-EVs can specifically be recognized by asialoglycoprotein receptor (ASGPR) of hepatoma cells. Compared to free Dox and Dox-loaded EVs, desialylated EVs loaded with Dox significantly presented the improved cellular uptake, prioritized targeting efficacy, and had a better inhibiting effect in vitro and in vivo. Overall, the results of the present study of the demonstrated delivery system using desialylated MSC-EVs suggest its therapeutic potential for HCC.Keywords:extracellular vesicles;drug delivery;desialylation;ASGPR;liver targeting
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Materials Today Advances
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2022
·
IF 9.918
Longfei Li,Tong Wang,Kelly Van,Xiaodi Zhang,Xindan Zhang,Jian Song,Rui Shi,Liqun Zhang,Jiajia Xue
The construction of gradient scaffolds to mimic the in vivo microenvironment for promoting tissue regeneration is attractive, especially by incorporating biochemical cues with physical guidance to manipulate cell behavior. Here, we report a general method to generate dual concentration-gradient of two types of bioactive components on scaffolds composed of uniaxially aligned electrospun nanofibers through layer-by-layer self-assembly. Different layers of collagen (COL) and chondroitin sulfate (CS) are sequentially coated onto the specific positions of uniaxially aligned electrospun polycaprolactone (PCL) nanofibers upon electrostatic attraction. In this case, dual stepwise gradients of COL and CS are generated along the fiber alignment. In demonstrating the potential application, the dual gradients can effectively promote the migration and proliferation of bone marrow stem cells (BMSCs) and spatially control their osteogenic differentiation. This simple strategy for generating dual gradients can be easily extended to different types of gradient scaffolds for bone regeneration and related applications involving cell migration, stem cell differentiation, and tissue interface.
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EXPERIMENTAL ANIMALS
·
2022
·
IF 1.798
Kai KANG,Lukuan CUI,Qian ZHANG,Shijun GAO
Although many surgical or non-operative therapies have been developed to treat Achilles tendon injuries, the prognosis of which is often unsatisfactory. Recently, biologic approaches using multipotent stem cells like tendon-derived stem cells (TDSCs) pose a possible treatment option. To evaluate whether the Leucine rich repeat containing 32 (Lrrc32) affects the tenogenic differentiation of TDSCs and thus promotes Achilles tendon healing. TDSCs were infected with the recombinant Lrrc32-overexpressing lentivirus (LV-Lrrc32) and then locally injected into the injured site of rat. Four weeks after surgery, the Achilles tendon tissue (~0.5 cm) around the injured area was harvested for analysis. Pathological results showed that Lrrc32-overexpressing TDSCs significantly improved the morphological changes of the injured tendons. Specifically, the increased collagen-I expression and hydroxyproline content in extracellular matrix, and more orderly arrangement of the regenerated collagen fibers were observed in the Lrrc32 overexpression group. Moreover, 4 weeks after injection of Lrrc32-overexpressing TDSCs, the expression of tenocyte-related genes such as tenomodulin (Tnmd), scleraxis (Scx) and decorin (Dcn) were upregulated in the area of the healing tendon. These findings indicated that Lrrc32 promoted the tenogenic differentiation of TDSCs in vivo. Additionally, Lrrc32 overexpression also increased the expression of TGF-β1 and p-SMAD2/3, suggesting that the beneficial effects of Lrrc32 on tendon repair might be associated with the expression of TGF-β1 and p-SMAD2/3. Our findings collectively revealed that Lrrc32-overexpressed TDSCs promoted tendon healing more effectively than TDSCs alone.
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CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Penghui Wang,Yajie Pu,Yanhan Ren,Rong Yang,Wenjie Zhang,Xiaoyan Tan,Wenliang Xue,Shuai Liu,Shuang Li,Bo Chi
Traditional hydrogels often fail to match the dynamic interactions between mechanical and cellular behaviors exhibited by the natural cartilage extracellular matrix. In this research, we constructed a novel hybrid hydrogels system based on sodium alginate and polyglutamic acid. By controlling the grafting rate and concentration of polymer, the gelation time and mechanical strength can be adjusted between range of 8–28 s and 60–144 kPa. By adding microcrystalline cellulose into the system, so that the degradation time was prolonged (125%) and the swelling rate was reduced (470%). Additionally, the presence of hydrazone bonds gives the system some dynamic response characteristics, and the hydrogel exhibits excellent self healing and injectable ability. It was found that the system had positive cytocompatibility (80%), which accelerated regulatory gene expression in cartilage tissue. In conclusion, this injectable hydrogel with self-healing and customizable mechanical strength will have broad application prospects in future biomedical engineering.
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