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Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.
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It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.
Assuntos
Isquemia Encefálica , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Ratos , Animais , Microglia/metabolismo , Receptor 4 Toll-Like/metabolismo , Fármacos Neuroprotetores/farmacologia , Isquemia Encefálica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismoRESUMO
The development of chiral alignment media for measuring anisotropic NMR parameters provides an opportunity to determine the absolute configuration of chiral molecules without the need for derivatization. However, chiral alignment media with a high and robust enantiodiscriminating property for a wide range of chiral molecules are still scarce. In this study, we synthesized cholesterol-end-functionalized helical polyisocyanides from a chiral monomer using a cholesterol-based alkyne-Pd(II) initiator. These stereoregular polyisocyanides form stable and weak anisotropic lyotropic liquid crystals (LLCs) in dichloromethane systems, exhibiting highly optical activities in both single left- and right-handed helices. The preparation process of the media was straightforward, and the aligning property of the LLCs could be controlled by adjusting the concentration and temperature. Using the chiral polyisocyanides, we extracted the residual dipolar coupling for an enantiomeric pair of isopinocampheol (IPC), as well as a number of pharmaceutical molecules, demonstrating excellent enantiodiscriminating properties for a broad range of chiral compounds.
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An asymmetric Michael/hemiketalization and Fridel-Crafts reaction has been reported through a one-pot reaction. A number of structurally novel tetrahydrofuran spirooxindoles are synthesized in the presence of a 10 mol % dinuclear zinc catalyst with diastereomer ratios (dr) of 3:1-13:1 and an enantiomeric excess (ee) of 75-99%. The reaction can be performed on a gram scale without impacting its efficiency. The absolute configuration of products is confirmed by X-ray single crystal structure analysis, and a possible mechanism is proposed.
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Transplantation of mesenchymal stem cells (MSCs) into the degenerated intervertebral disc (IVD) has shown promise for decelerating or arresting IVD degeneration. Cellular mechanical properties play crucial roles in regulating cell-matrix interactions, potentially reflecting specific changes that occur based on cellular phenotype and behavior. However, the effect of co-culturing of MSCs with nucleus pulposus cells (NPCs) on the mechanical properties of NPCs remains unknown. In our study, we demonstrated that co-culture of degenerated NPCs with MSCs resulted in significantly decreased mechanical moduli (elastic modulus, relaxed modulus, and instantaneous modulus) and increased biological activity (proliferation and expression of matrix genes) in degenerated NPCs, but not normal NPCs. SDF-1, CXCR4 ligand, was highly expressed in MSCs when co-cultured with degenerated NPCs. Inhibition of SDF-1 using CXCR4 antagonist AMD3100 or knocking-down CXCR4 in degenerated NPCs abolished the MSCs-induced decrease in the mechanical moduli and increased biological activity of degenerated NPCs, suggesting a crucial role for SDF-1/CXCR4 signaling. AKT and FAK inhibition attenuated the MSCs- or SDF-1-induced decrease in the mechanical moduli of degenerated NPCs. In conclusion, it was demonstrated in vitro that MSCs regulate the mechanical properties of degenerated NPCs through SDF-1/CXCR4/AKT signaling. These findings highlight a possible mechanical mechanism for MSCs-induced modulation with degenerated NPCs, which may be applicable to MSCs-based therapy for disc degeneration.
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Quimiocina CXCL12/fisiologia , Degeneração do Disco Intervertebral/patologia , Células-Tronco Mesenquimais/fisiologia , Núcleo Pulposo/patologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Receptores CXCR4/fisiologia , Transdução de Sinais/fisiologia , Agrecanas/biossíntese , Agrecanas/genética , Benzilaminas , Células Cultivadas , Quimiocina CXCL12/antagonistas & inibidores , Técnicas de Cocultura , Colágeno Tipo II/biossíntese , Colágeno Tipo II/genética , Ciclamos , Módulo de Elasticidade , Compostos Heterocíclicos/farmacologia , Humanos , Técnicas In Vitro , Células-Tronco Mesenquimais/metabolismo , Microscopia de Força Atômica , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Receptores CXCR4/antagonistas & inibidoresRESUMO
We aim to develop novel photoresponsive surface molecularly imprinted polymer (SIMP) microspheres, an SiO2 -SIMP, for the photocontrolled extraction of uric acid from biological samples. The SiO2 -SMIP was prepared on silica microspheres by surface polymerization and characterized by using scanning electron microscopy, transmission electron microscopy, FTIR spectroscopy, thermogravimetric analysis, nitrogen adsorption-desorption analysis, and UV-visible spectroscopy. The SiO2 -SMIP microspheres showed a photocontrolled uptake and release of uric acid in NaH2 PO4 buffer upon alternate irradiation at 365 and 440 nm. The SiO2 -SMIP microspheres were able to photocontrollably extract uric acid from complicated biological samples for concentration analysis with no significant interference encountered and it exhibited very good recognition ability and fast binding kinetics toward uric acid.
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Microesferas , Impressão Molecular , Ácido Úrico/isolamento & purificação , Adsorção , Humanos , Polímeros , Dióxido de Silício , Ácido Úrico/urinaRESUMO
In this paper, two types of solid phase 2D and 3D XBOFs were selectively constructed from identical building blocks of tetraphenylmethane tetrapyridine derivative and 1,4-diiodotetrafluorobenzene by changing the crystallization solvent. This 3D XBOF is a novel hybrid supramolecular organic framework with the synergistic control of hydrogen and halogen bonds.
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INTRODUCTION: Cartilage endplate (CEP) degeneration is usually accompanied by loss of cellularity, and this loss may be a crucial key factor in initiation and development of degenerative disc disease. The study of cell types in degenerated CEP could help in understanding CEP etiopathogenesis, and may help in devising new treatments, especially if the presence of progenitor cells could be demonstrated. The aim of this study was to determine if progenitor cells existed in degenerated human CEP. MATERIALS AND METHODS: Cells isolated from CEP were cultured in a three-dimensional agarose suspension to screen for proliferative cell clusters. Cell clusters were then expanded in vitro and the populations were analyzed for colony forming unit, immunophenotype, multilineage induction, and expression of stem cell-related genes. RESULTS: The presence of progenitor cells in degenerated human CEP is indicated by the results of CFU, immunophenotype, multilineage induction, and expression of stem cell-related genes. CONCLUSIONS: We believe that this is the first study which has conclusively shown the presence of progenitor cells in degenerated CEP. The finding of this study may influence the clinical management of degenerative disc disorder.
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Cartilagem/patologia , Degeneração do Disco Intervertebral/patologia , Vértebras Lombares/patologia , Células-Tronco/patologia , Adulto , Células Cultivadas , Discotomia , Feminino , Humanos , Técnicas In Vitro , Degeneração do Disco Intervertebral/etiologia , Degeneração do Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Estenose Espinal/complicações , Estenose Espinal/patologia , Estenose Espinal/cirurgia , Espondilolistese/complicações , Espondilolistese/patologia , Espondilolistese/cirurgiaRESUMO
A novel valine-based isocyanonaphthalene (NpI) was designed and synthesized by using an easy method and enabled the selective fluorescence detection of Hg2+. The chemodosimeter can display an immediate turn-on fluorescence response (500-fold) towards target metal ions upon the Hg2+-mediated conversion of isocyano to amino within NpI. Based on this specific reaction, the fluorescence-enhancement probe revealed a high sensitivity toward Hg2+ over other common metal ions and exhibited excellent aqueous solubility, good antijamming capability, high sensitivity (detection limit: 14.2 nM), and real-time detection. The response mechanism of NpI was supported by NMR spectroscopy, MS analysis and DFT theoretical calculation using various techniques. Moreover, a dipeptidomimetic NpI probe was successfully applied to visualize intracellular Hg2+ in living cells and monitor Hg2+ in real water samples with good recoveries and small relative standard deviations.
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The development of chiral ligands with privileged scaffolds plays an important role in transition-metal-catalyzed asymmetric reactions. Herein we present anthracene-photodimer-derived chiral monophosphine ligand 1, which features dual chirality and a rigid scaffold. This ligand exhibits remarkable efficiency in Pd-catalyzed desymmetric intermolecular C-N coupling under mild conditions with excellent chemo- and enantioselectivity.
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A Brønsted base and Lewis acid cooperatively catalyzed 1,3-dipolar cycloaddition is reported through chiral dinuclear zinc catalysts. An asymmetric exo'-selective [3 + 2] cycloaddition of CF3-containing N-unprotected isatin-derived azomethine ylides is realized. In the presence of 10 mol % of catalyst, azomethine ylides react efficiently with methyleneindolinones, giving a series of trifluoromethyl-substituted 2,3-pyrrolidinyl dispirooxindoles with highly enantio- (up to 99% ee) and exo'-selectivity (>20:1 dr). Up to four contiguous stereogenic centers, including two adjacent spiro quaternary stereocenters, are constructed in one step.
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A series of small-membered heterocycle probes, so-called azaheterocycle-containing diphenylmethanol chiral solvating agents (CSAs), have been developed for NMR enantiodiscrimination. These chiral sensors were readily synthesized were inexpensive and efficiently used for the chiral analysis of alpha-substituted carboxylic acids. The sensing method was operationally simple and the processing was straightforward. Notably, we propose (S)-aziridinyl diphenylmethanol as a promising CSA, which has excellent chiral discriminating properties and offers multiple detectable possibilities pertaining to the 1H NMR signals of diagnostic split protons (including 25 examples, up to 0.194 ppm, 77.6 Hz). Its ability to detect the molecular recognition of fluorinated carboxylic acids were further investigated, with a good level of discrimination via the 19F NMR spectroscopic analysis. In addition, an accurate enantiomeric excess (ee) analysis of the p-methoxyl-mandelic acid with different optical compositions have been calculated based on the integration of well-separated proton signals.
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The application of photoresponsive surface molecularly imprinted polymers based on azobenzene is limited by the UV light source required and their poor water solubility. Reducing the phototoxicity and solvent toxicity of the polymers therefore presents a challenge. In this work, an NIR-light-responsive surface molecularly imprinted polymer was fabricated by atom transfer radical polymerization using up-conversion nanoparticles as the core, a hydrophilic green-light-responsive azobenzene derivative as the functional monomer, and a drug as the template. The up-conversion nanoparticles core emitted green fluorescence in the range of 520-550â¯nm upon NIR irradiation (980â¯nm, 5â¯Wâ¯cm-2), which was absorbed by the azobenzene containing molecularly imprinted polymers layer on the up-conversion nanoparticles surface. This caused the azobenzene chromophores to undergo transâcis isomerization in phosphate buffered solution (pHâ¯=â¯7.4), thus resulting in NIR-light-induced drug release. The up-conversion fluorescence spectra were used to study the interaction mechanism between the azobenzene monomer and NIR light. Compared with structural analogues of the template (antifebrin and phenacetin), the NIR-light-responsive surface molecularly imprinted polymer showed excellent specificity of recognition for the template drug (paracetamol). The maximum adsorption capacity of the NIR-light-responsive surface molecularly imprinted polymer for loading of paracetamol was 16.80⯵molâ¯g-1. The NIR-light-responsive surface molecularly imprinted polymer was applied for NIR-light-induced paracetamol release in phosphate buffered solution (pHâ¯=â¯7.4) through porcine tissue. This work demonstrates the potential of drug delivery systems based on molecularly imprinted polymers for application in deep tissue delivery.
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Impressão Molecular/métodos , Polímeros/química , Animais , Compostos Azo/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Microscopia Eletroquímica de Varredura , Polimerização , SuínosRESUMO
Lycium barbarum polysaccharides (LBP) are derived from Wolfberry and have antioxidant activities. This study aimed to evaluate the efficacy of LBP for kidney injury in a rat model of sepsis. Male rats were divided randomly to control group (Con), LPS group (LPS), ulinastatin group (ULI), low dose LBP group (LBP-1), middle dose LBP group (LBP-2) and high dose LBP group (LBP-3). After intraperitoneal injection of LPS (5 mg/kg) to make sepsis model (LPS group), 10,000 U/kg ulinastatin were given in ULI group, and 200, 400 and 800 mg/kg LBP was given in LBP-1, -2, -3 group, respectively. Serum IL-1ß, IL-6, IL-8, TNF-α and NF-κB levels were measured by ELISA. Nrf2, Keap1, NF-κB, HO-1 and NQO1 expression levels were detected by PCR and Western blot analysis. We found that LBP decreased the levels of NF-κB and pro-inflammatory cytokines while attenuated kidney injury. In addition, LBP regulated Keap1-Nrf2/ARE signaling pathway in the kidney. In conclusion, LBP attenuates inflammation injury in the kidney via possible regulation of Keap1-Nrf2/ARE signaling.
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Injúria Renal Aguda/prevenção & controle , Elementos de Resposta Antioxidante/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sepse/complicações , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The trans to cis isomerization of the azobenzene chromophore in most azobenzene-based photoresponsive molecularly imprinted polymers (MIPs) is initiated by UV irradiation. This limits the application of these materials in cases where UV light toxicity is an issue, such as in biological systems, food monitoring, and drug delivery. Herein we report a tetra-ortho-methyl substituted azobenzene, (4-[(4-methacryloyloxy)-2,6-dimethyl phenylazo]-3,5-dimethyl benzenesulfonic acid (MADPADSA). The photoswitching of MADPADSA could be induced by visible-light irradiation (550â¯nm for trans to cis and 475â¯nm for cis to trans) in 4-hydroxyethylpiperazineethanesulfonic acid (HEPES) buffer-ethanol (4:1, v/v) at pHâ¯7.0, however, the photoisomerization was slow. With the use of MADPADSA as a functional monomer, NaYF4:Yb3+,Er3+ as a substrate, 4-ethylphenol (4-EP) as a template, a novel photoresponsive surface molecularly imprinted polymer NaYF4:Yb3+,Er3+@MIP was obtained. The NaYF4:Yb3+,Er3+@MIP displayed rapid visible-light-induced photoswitching. The NaYF4:Yb3+,Er3+ substrate could efficiently increase the trans to cis isomerization rate of the photoresponsive MIP on its surface, which was faster than that of the corresponding azobenzene monomer MADPADSA. Possible reasons for this effect were investigated by fluorescence spectroscopy. NaYF4:Yb3+,Er3+@MIP displayed good specificity toward 4-EP with a specific binding constant (Kd) of 3.67â¯×â¯10-6â¯molâ¯L-1 and an apparent maximum adsorption capacity (Qmax) of 10.73⯵molâ¯g-1, respectively. NaYF4:Yb3+,Er3+@MIP was applied to determine the concentration of 4-EP in red wine with good efficiency and a limit of detection lower than the value that could cause an unpleasant off-flavor.
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Fenóis/análise , Processos Fotoquímicos , Raios Ultravioleta , Vinho/análise , Espectrometria de FluorescênciaRESUMO
A new photoresponsive surface molecularly imprinted polymer shell (PMIPS) was developed for determination of trace griseofulvin from milk. The PMIPS was prepared by surface imprinting technique using poly(styrene-co-methacrylic acid) (PS-co-PMMA) microspheres as the sacrificial substrate, griseofulvin as the template, a photoresponsive azobenzene derivative 4-((4-(methacryloyloxy)phenyl)diazenyl)-3,5-dimethyl benzenesulfonic acid as the functional monomer, and triethanolamine trimethacrylate as the cross-linker. The PMIPS was obtained after the removal of the sacrificial PS-co-PMMA core from the surface imprinted core-shell microspheres, PS-co-PMAA@PMIP. Compared with PS-co-PMAA@PMIP, PMIPS displayed better properties such as higher surface area and pore volume, rapid photo-isomerization rate, and higher adsorption capacities, specific binding constant and binding density. The PMIPS could efficiently detect griseofulvin in complex samples such as milk.
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Griseofulvina/análise , Luz , Leite/química , Impressão Molecular , Polímeros/química , Adsorção , Animais , Isomerismo , Cinética , Nitrogênio/química , Polímeros/síntese química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaRESUMO
This paper reports a photoresponsive hollow molecularly imprinted polymer for the determination of trace triamterene in biological sample. The photoresponsive hollow molecularly imprinted polymer was prepared on sacrificial silica microspheres via surface imprinting technique through atom transfer radical polymerization using a novel water-soluble azobenzene derivative, 4-[(4-methacryloyloxy)phenylazo]-3,5-dimethyl benzenesulfonic acid, as the functional monomer, and the sacrificial silica core was subsequently removed using HF etching method with 1.25vol.% HF ethanolic solution. The morphologies and properties of the photoresponsive hollow molecularly imprinted polymer were further characterized and compared systematically with the corresponding photoresponsive surface molecularly imprinted polymer. Compared with surface imprinted polymer, the hollow material displayed higher binding capacity, better recognition ability, faster mass-transfer rate, and larger isomerization rate constants toward triamterene. The static binding properties of the imprinted materials were investigated under three irradiation conditions. The photoresponsive hollow molecularly imprinted polymer showed better specificity toward triamterene than its structural analogues (folic acid and caffeine) as examined by UV-vis and HPLC. The photoresponsive hollow molecularly imprinted polymer was utilized for the determination of trace triamterene in biological samples (human urine and serum) with advantages of simple sample pre-treatment, good recovery and good sensitivity.
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Polímeros/química , Humanos , Microesferas , Impressão Molecular , Polimerização , TrianterenoRESUMO
A photoresponsive surface molecularly imprinted polymer for uric acid in physiological fluids was fabricated through a facile and effective method using bio-safe and biocompatible ZnO nanorods as a support. The strategy was carried out by introducing double bonds on the surface of the ZnO nanorods with 3-methacryloxypropyltrimethoxysilane. The surface molecularly imprinted polymer on ZnO nanorods was then prepared by surface polymerization using uric acid as template, water-soluble 5-[(4-(methacryloyloxy)phenyl)diazenyl]isophthalic acid as functional monomer, and triethanolamine trimethacryl ester as cross-linker. The surface molecularly imprinted polymer on ZnO nanorods showed good photoresponsive properties, high recognition ability, and fast binding kinetics toward uric acid, with a dissociation constant of 3.22×10(-5)M in aqueous NaH2PO4 buffer at pH=7.0 and a maximal adsorption capacity of 1.45µmolg(-1). Upon alternate irradiation at 365 and 440nm, the surface molecularly imprinted polymer on ZnO nanorods can quantitatively uptake and release uric acid.
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Impressão Molecular , Nanotubos/química , Polímeros/química , Ácido Úrico/análise , Óxido de Zinco/química , Adsorção , Cinética , Metacrilatos/química , Silanos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Água/químicaRESUMO
In a general view of anatomy, intervertebral disc is composed of three parts: annulus fibrosus (AF), nucleus pulposus (NP), and cartilage endplate (CEP). Recently, several types of stem cells were successfully isolated from these corresponding regions, but up to now, no research was performed about which kind of stem cells is the most efficient candidate for NP tissue engineering or for stem cell-based disc regeneration therapy. In this study, we compared the regenerative potentials of the above-mentioned three kinds of disc-derived stem cells with that of the classic bone marrow (BM)-mesenchymal stem cells (MSCs) in a rabbit disc degeneration model. By magnetic resonance imaging (MRI), X-ray, histology, etc. evaluations, we found that cartilage endplate-derived stem cells (CESCs) showed superior capacity compared with the annulus fibrosus-derived stem cells (AFSCs), nucleus pulposus-derived stem cells (NPSCs), and BM-MSCs (p<0.05); additionally, when comparing the CESC group with the normal control group, there existed no statistical difference in X-ray (p>0.05). Those results demonstrated that the CESC-seeded alginate construct performed the most powerful ability for NP regeneration, while AFSCs showed the most inferior potency, NPSCs and BM-MSCs had similar regenerative capacity and located in the middle. All in all, our study showed that CESCs might act as an efficient seed cell source for NP tissue engineering, which paved a new way for the biological solution of disc degeneration diseases.