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1.
Eur J Pharm Sci ; 141: 105042, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634554

RESUMO

Skin aging affects personal image and health. α - lipoic acid (ALA), with excellent free radical scavenging capacity, was used in this research to prepare W/O emulsion. Considering the instability of ALA, ionic liquid strategy was adopted to heighten the solubility of ALA for dissolving in water phase. The mechanism of different ionic liquids (ILs) on skin retention of ALA was investigated by in vitro skin permeation experiment, emulsion quality characterization, rheological test, ATR - FTIR and molecular simulation. The results showed that ionic liquid strategy had a positive influence on the solubilization of ALA. Different ILs were different in skin retention and regulated by skin layers rather than drug release, in which ALA - triethanolamine (ALA - TEOA) presented the best affinity with both stratum corneum (SC) and viable epidermis and dermis (VED), while ALA - N - (2 - Hydroxyethyl) piperidine (ALA - HEPP) as well as ALA - N - (2 - hydroxyethyl) pyrrolidine (ALA - HEPR) showed affinity with either SC or VED respectively. Finally, the emulsion presented brilliant anti - aging efficacy. This study provided a new method of emulsion research and had great significance for the development of topical formulations.

2.
Food Chem ; 303: 125378, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31450176

RESUMO

This work introduces an inexpensive and user-friendly electrochemical platform for heavy metal determination in liquid food. Smart-phone connectivity, solid-state-microwave flow digestion and nano-Au-modified electrode are synchronously studied. A smart phone is adopted as the information terminal for universal purposes. A solid-state-microwave digestion device is developed to provide programmable digestion for liquid food in a digestion path. Microwave power curve and flow rate in digestion are studied and optimized. A nano-Au-modified electrode, as well as a homemade potentiostat and other electrodes, is used as a tool for electrochemical analyses. Behaviors of this method are evaluated with electrical measurement and stripping voltammetry. This method is used for sensing Cd2+, Pb2+ and Hg2+ in cow milk, orange juice and apple juice. It provides a sensitive response to ≥2 µg L-1 target ion, and shows satisfying stability and good accuracy in a task up to 72 h.


Assuntos
Técnicas Eletroquímicas/métodos , Sucos de Frutas e Vegetais/análise , Metais Pesados/análise , Leite/química , Smartphone , Animais , Cádmio/análise , Bovinos , Eletrodos , Feminino , Ouro/química , Chumbo/análise , Mercúrio/análise , Micro-Ondas
3.
Inflammation ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673976

RESUMO

Luteolin is a natural flavonoid compound derived from vegetables, fruits, and herbs with potent anti-inflammatory activity. Macrophage polarization is important in the development and progression of inflammation. However, whether luteolin can inhibit inflammation by regulating the polarized phenotypes of macrophages remains unknown. The aim of this study was to investigate the effects of luteolin on the inflammatory polarization of macrophages and the underlying mechanisms. RAW264.7 macrophages were induced to M1 polarization by stimulation with lipopolysaccharide plus interferon-γ or to M2 polarization with interleukin 4 (IL-4), simultaneously, accompanied with different concentrations of luteolin. Laser confocal microscopy was used to observe cell morphology; flow cytometry was employed to detect the expression of membrane surface molecule CD86 and CD206; qPCR was performed to examine the mRNA expression of M1 markers (iNOS, IL-1ß, IL-6) and M2 markers (Arg1, CD206, CD163, IL-10, and IL-13), respectively; ELISA was used to examine the levels of IL-6, TNF-α, and IL-10; and Western blotting was used to evaluate the p-STAT3 and p-STAT6 protein pathway. The morphology of activated M1 macrophages changed significantly, developing dendritic characteristics. After luteolin treatment, the expression of M1-type proinflammatory mediators and the surface marker CD86 were decreased evidently, but those of M2-related anti-inflammatory factors and CD206 were increased markedly. Moreover, p-STAT3 was downregulated and p-STAT6 was upregulated in a dose-dependent manner. Conclusion, luteolin can alter the M1/M2 polarization of macrophages, thereby playing an anti-inflammatory role via downregulation of p-STAT3 and upregulation of p-STAT6. Therefore, luteolin may be potentially valuable to inhibit inflammation.

4.
Appl Opt ; 58(29): 8069-8074, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31674362

RESUMO

The optical properties of symmetric split-ring/ring dimer (SRRD) nanostructures composed of a small nanoring surrounded by an Ag splitting nanoring with a larger diameter are calculated theoretically. The apparent asymmetric Fano line shape in the spectra is related to fast switching of the bonding modes between the split-ring plasmon and ring dipole. The influence of the dimensions of the SRRD nanostructures on the spectral positions and intensity of Fano resonance is studied, and the asymmetric Fano line shape can be flexibly adjusted by varying the geometric parameters. In addition, relatively simple SRRD nanostructures have the same overall sensing figures of merit as conventional nanoparticles, thus rendering them suitable for high-performance optical sensors.

6.
Biosci Rep ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774112

RESUMO

BACKGROUND: Variants in B and T lymphocyte attenuator (BTLA) gene are likely to affect the function of BTLA protein.

Methods: In the present case-control study, we selected BTLA tagging single nucleotide polymorphisms (SNPs) (rs16859629 T>C, rs1982809 G>A, rs2171513 G>A and rs3112270 A>G) and conducted a case-control study to identify the association of BTLA SNPs with risk of esophagogastric junction adenocarcinoma (EGJA). This study involved 1,236 new incident EGJA cases and 1,540 cancer-free controls.

Results: The genotypes of BTLA SNPs were analyzed using a SNPscan Kit. No association was also found between the BTLA SNPs and the susceptibility of EGJA in overall comparsion. In subgroup analyses, the BTLA rs1982809 was found to be associated with an increased susceptibility of EGJA (AA vs. GG: ORadjusted=2.09, 95% CI 1.08-4.07, P=0.030; and AA vs. GA/GG: ORadjusted=1.99, 95% CI 1.04-3.82, P=0.039). In haplotype comparison, we identified that TAAG haplotype with the order of BTLA rs16859629, rs1982809, rs2171513 and rs3112270 SNPs might increase the susceptibility of EGJA (OR=3.07, 95% CI=1.41-6.71; P=0.003).

Conclusion: To conclude, this study suggests that BTLA Trs16859629Ars1982809Ars2171513Grs3112270 haplotype may increase the susceptibility of EGJA. More studies should be conducted to evaluate whether BTLA polymorphisms may influence the susceptibility of cancer in the future.

7.
Cancer Sci ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31778279

RESUMO

Metastasis is a critical determinant for the treatment strategy and prognosis in patient with squamous cell carcinoma of the head and neck (SCCHN). However, mechanisms underlying SCCHN metastasis are poorly understood. Our study sought to find out the key microRNAs and their functional mechanisms involved in SCCHN metastasis. The Cancer Genome Atlas (TCGA) data analysis, qPCR was used to quantify the level of miR-30e-5p in SCCHN and its clinical significance was further analyzed. A series of in vitro and in vivo experiments were applied to determine the effects of miR-30e-5p and its target AEG-1 on SCCHN metastasis. Mechanism investigation further revealed that AEG-1 was implicated in the angiogenesis and metastasis mediated by miR-30e-5p. Overall, our study validates that miR-30e-5p is a valuable predictive biomarker and potential therapeutic target in SCCHN metastasis.

8.
J Diabetes Res ; 2019: 8469739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737686

RESUMO

Objective: To examine the effects of resistance training relative to aerobic training on abdominal adipose tissue and metabolic variables in adults with prediabetes. Methods: 105 participants with prediabetes were randomized into the resistance training group (RT, n = 35), aerobic training group (AT, n = 35), and control group (CG, n = 35). The participants completed supervised 12-month exercise; the control group followed the primary lifestyle without exercise intervention. The primary outcomes were visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) measured by computed tomography (CT). Secondary outcomes were body composition, lipid profile, and metabolic variables. Results: A total of 93 participants completed the study. There were nonsignificant differences between groups before intervention. After training, VAT decreased significantly in AT and RT compared with CG (P = 0.001 and P = 0.014, respectively). Although no significant difference in SAT was found across groups, SAT decreased significantly over time within each exercise group (all P = 0.001). Increase in muscle mass was greater in RT than that in AT and CG (P = 0.031 and P = 0.045, respectively). Compared with CG, fasting plasma glucose (FPG) decreased significantly in RT and AT (P = 0.003 and P = 0.014, respectively). There was a significant difference in the number of prediabetes who converted to diabetes among AT and RT, as compared with the control group (P = 0.031 and P = 0.011, respectively). No significant differences were observed in lipid, waist-to-hip ratio (WHR), body mass index (BMI), fasting insulin (FI), 2-hour postprandial glucose (2hPG), glycosylated hemoglobin (HbA1c), HOMA-IR, and HOMA-ß across groups. Conclusion: Both aerobic training and resistance training are effective in reducing abdominal adipose tissue and fasting plasma glucose in adults with prediabetes. Importantly, resistance training but not aerobic training is effective in augmenting muscle mass. Trial Registration: The trial is registered with NCT02561377 (date of registration: 24/09/2015).

9.
Islets ; : 1-13, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750757

RESUMO

Curcumin possesses medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2 DM). It has been proposed that pancreatic beta cell dysfunction in T2 DM is promoted by oxidative stress caused by NADPH oxidase over-activity. The aim of the present study was to evaluate the efficacy of curcumin as a protective agent against high glucose/palmitate (HP)-induced islet cell damage and in streptozotocin (STZ)-induced DM rats. INS-1 cells were exposed to HP with or without curcumin. Cell proliferation, islet cell morphological changes, reactive oxygen species production, superoxide dismutase and catalase activity, insulin levels, NADPH oxidase subunit expression, and the expression of apoptotic factors by INS-1 cells were observed. Our results show that curcumin can effectively inhibit the impairment of cell proliferation and activated oxidative stress, increase insulin levels, and reduce the high expression of NADPH oxidase subunits and apoptotic factors induced by HP in INS-1 cells. The STZ-induced DM rat model was also used to determine whether curcumin can protect islets in vivo. Our results show that curcumin significantly reduced pathological damage and increased insulin levels of islets in STZ-induced DM rats. Curcumin also successfully inhibited the high expression of NADPH oxidase subunits and apoptotic factors in STZ-induced DM rats. These results suggest that curcumin is able to attenuate HP-induced oxidative stress in islet cells and protect these cells from apoptosis by modulating the NADPH pathway. In view of its efficiency, curcumin has potential for translation applications in protecting islets from glucolipotoxicity.

10.
J Immunother Cancer ; 7(1): 300, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727135

RESUMO

BACKGROUND: Accumulating studies suggest that targeting epigenetic modifications could improve the efficacy of tumor immunotherapy; however, the mechanisms underlying this phenomenon remain largely unknown. Here, we investigated the ability of the epigenetic modifier, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), to regulate the expression of immune checkpoint inhibitor, programmed death-1 ligand 1 (PD-L1) in hepatocellular carcinoma (HCC). METHODS: Immunohistochemistry and multiplex immunofluorescence staining were performed to analyze the expression and correlation of EZH2 and PD-L1 in HCC tissues. Immunoblotting, quantitative real-time PCR, flow cytometry, chromatin immunoprecipitation, and dual-luciferase reporter gene assays were performed to evaluate the regulatory roles of EZH2 on PD-L1 expression. RESULTS: In vitro cell experiments revealed that EZH2 negatively regulated the PD-L1 expression of hepatoma cell lines in IFNγ-dependent manner. Mechanistic studies demonstrated that EZH2 could suppress PD-L1 expression by upregulating the H3K27me3 levels on the promoters of CD274 (encoding PD-L1) and interferon regulatory factor 1 (IRF1), an essential transcription factor for PD-L1 expression, without affecting the activation of the IFNγ-signal transducer and activator of transcription 1 (STAT1) pathway. Clinical samples from HCC patients with immune-activated microenvironments showed negative correlations between EZH2 and PD-L1 expression in hepatoma cells. Multivariate Cox analysis demonstrated that the combination of EZH2 and PD-L1 was an independent prognostic factor for both OS and RFS for patients with HCC. CONCLUSIONS: The epigenetic modificator EZH2 can suppress the expression of immune checkpoint inhibitor PD-L1 by directly upregulating the promoter H3K27me3 levels of CD274 and IRF1 in hepatoma cells, and might serve as a potential therapeutic target for combination of immunotherapy for immune-activated HCC.

11.
Sci Rep ; 9(1): 17259, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754201

RESUMO

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Currently, sorafenib is the standard first-line drug for patients with advanced HCC. However, long-term exposure to sorafenib often results in reduced sensitivity of tumour cells to the drug, leading to acquired resistance. Therefore, developing new compounds to treat sorafenib resistance is urgently needed. Although benzimidazole and its derivatives have been reported to exert antimicrobial and antitumour effects, the anti-drug resistance potential of these molecules is still unknown. In this study, we established sorafenib-resistant (SR) cell lines and an acquired sorafenib resistance xenograft model. We showed that treatment with a benzimidazole derivative bearing a pyrrolidine side chain (compound 9a) inhibited the proliferation of SR cells by blocking the phosphorylation of AKT, p70S6 and the downstream molecule RPS6. In addition, caspase 3/PARP-dependent apoptotic signals were induced in 9a-treated cells. Regarding epithelial-mesenchymal transition (EMT) activities, 9a treatment significantly suppressed the migration of SR cells. In particular, the levels of EMT-related transcription factors (snail, slug and twist) and mesenchymal markers (vimentin and N-cadherin) were downregulated. In the acquired sorafenib resistance xenograft model, compound 9a administration decreased the growth of tumours with acquired sorafenib resistance and the expression of the HCC markers α-fetoprotein, glypican 3 and survivin. In conclusion, treatment with this compound may be a novel therapeutic strategy for patients with sorafenib resistance.

12.
Biomaterials ; : 119605, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31740099

RESUMO

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Vascular inflammation is closely related to the pathogenesis of a diverse group of CVDs. Currently, it remains a great challenge to achieve site-specific delivery and controlled release of therapeutics at vascular inflammatory sites. Herein we hypothesize that active targeting nanoparticles (NPs) simultaneously responsive to low pH and high levels of reactive oxygen species (ROS) can serve as an effective nanoplatform for precision delivery of therapeutic cargoes to the sites of vascular inflammation, in view of acidosis and oxidative stress at inflamed sites. The pH/ROS dual-responsive NPs were constructed by combination of a pH-sensitive material (ACD) and an oxidation-responsive material (OCD) that can be facilely synthesized by chemical functionalization of ß-cyclodextrin, a cyclic oligosaccharide. Simply by regulating the weight ratio of ACD and OCD, the pH/ROS responsive capacity can be easily modulated, affording NPs with varied hydrolysis profiles under inflammatory microenvironment. Using rapamycin (RAP) as a candidate drug, we first demonstrated in vitro therapeutic advantages of RAP-containing NPs with optimal dual-responsive capability, i.e. RAP/AOCD NP, and a non-responsive nanotherapy (RAP/PLGA NP) and two single-responsive nanotherapies (RAP/ACD NP and RAP/OCD NP) were used as controls. In an animal model of vascular inflammation in rats subjected to balloon injury in carotid arteries, AOCD NP could accumulate at the diseased site after intravenous (i.v.) injection. Consistently, i. v. treatment with RAP/AOCD NP more effectively inhibited neointimal hyperplasia in rats with induced arterial injuries, compared to RAP/PLGA NP, RAP/ACD NP, and RAP/OCD NP. By surface decoration of AOCD NP with a peptide (KLWVLPKGGGC) targeting type IV collagen (Col-IV), the obtained Col-IV targeting, dual-responsive nanocarrier TAOCD NP showed dramatically increased accumulation at injured carotid arteries. Furthermore, RAP/TAOCD NP exhibited significantly potentiated in vivo efficacy in comparison to the passive targeting nanotherapy RAP/AOCD NP. Importantly, in vitro cell culture experiments and in vivo animal studies in both mice and rats revealed good safety for AOCD NP and RAP/AOCD NP, even after long-term treatment via i. v. injection. Consequently, our results demonstrated that the newly developed Col-IV targeting, pH/ROS dual-responsive NPs may serve as an effective and safe nanovehicle for precision therapy of arterial restenosis and other vascular inflammatory diseases.

13.
ACS Nano ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746201

RESUMO

Visual imaging that can extract three-dimensional (3D) space or polarization information on the target is essential in broad sciences and technologies. The simultaneous acquisition of them usually demands expensive equipment and sophisticated operations. Therefore, it is of great significance to exploit convenient approaches for four-dimensional (3D and polarization) visual imaging. Here, we present an efficient solution based on self-assembled asymmetric liquid crystal microlenses, with freely manipulated phase profiles and symmetry-breaking properties. Accordingly, characteristics of multifocal functionality and polarization selectivity are exhibited, along with the underlying mechanisms. Moreover, with a specific sample featured by radially increased unit sizes and azimuthally varied domain orientations, the discriminability of four-dimensional information is extracted in a single snapshot, via referring to the coordinates of the clearest images. Demultiplexing of depth/polarization information is also demonstrated. This work will unlock a variety of revolutionary apparatuses and lighten extensive applications.

14.
Phys Rev Lett ; 123(15): 156801, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31702286

RESUMO

We propose a realization of the lattice-symmetry-assisted second-order topological superconductors with corner Majorana zero modes (MZM) based on two-dimensional topological insulators (2DTI). The lattice symmetry can naturally lead to the anisotropic coupling of edge states along different directions to the in-plane magnetic field and conventional s-wave pairings, thus leading to a single MZM located at the corners for various lattice patterns. In particular, we focus on the 2DTI with D_{3d} lattice symmetry and found different types of gap opening for the edge states along the armchair and zigzag edges in a broad range of parameters. As a consequence, a single MZM exists at the corner between the zigzag and armchair edges, and is robust against weakly broken lattice symmetry. We propose to realize such corner MZMs in a variety of polygon patterns, such as triangles and quadrilaterals. We further show their potentials in building the Majorana network through constructing the Majorana Y junction under an in-plane magnetic field.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31697230

RESUMO

A novel bacterium, designated TRM 44457T, belonging to the genus Streptomyces, was isolated from soil sampled in cotton fields in Xinjiang, PR China. Comparative 16S rRNA gene sequence analysis indicated that strain TRM 44457T was phylogenetically most closely related to Streptomyces laurentii LMG 19959T (99.38 % sequence similarity); however, strain TRM 44457T had a relatively low DNA-DNA relatedness value with S. laurentii LMG 19959T as determined by calculating the average nucleotide identity value (84.42 %). Strain TRM 44457T possessed ll-diaminopimelic acid as the diagnostic cell-wall diamino acid, MK-9 (H6) and MK-9 (H10) as the major menaquinone. The polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphotidylinositol, phosphatidylinositol mannosides and an unidentified phospholipid. The major fatty acids were anteiso-C15:0, iso-C16:0, anteiso-C17:0, iso-C15:0, C16:0, iso-C17:0, cyclo-C17:0 and anteiso-C17:1ω9c. The genomic DNA G+C content was 72.6 mol%. Based on the evidence from this polyphasic study, strain TRM 44457T represents a novel species of the Streptomyces, for which the name Streptomyces roseicoloratus is proposed. The type strain is TRM 44457T (=KCTC 39904T=CCTCC AA 2016040T).

16.
Nucleic Acids Res ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724724

RESUMO

During meiosis, telomere attachment to the inner nuclear envelope is required for proper pairing of homologous chromosomes and recombination. Here, we identified F-box protein 47 (FBXO47) as a regulator of the telomeric shelterin complex that is specifically expressed during meiotic prophase I. Knockout of Fbxo47 in mice leads to infertility in males. We found that the Fbxo47 deficient spermatocytes are unable to form a complete synaptonemal complex. FBXO47 interacts with TRF1/2, and the disruption of Fbxo47 destabilizes TRF2, leading to unstable telomere attachment and slow traversing through the bouquet stage. Our findings uncover a novel mechanism of FBXO47 in telomeric shelterin subunit stabilization during meiosis.

17.
Chem Commun (Camb) ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742267

RESUMO

Newly designed ruthenium(ii) complexes are reported which contain a pyridylpyrrole ligand featuring fast-responsive and reversible proton storage/release on the pyrrole group. The protonated pyrrolium acts as an acidic initiator and is capable of triggering the polymerization of 2,2-dimethyloxirane.

18.
Mol Cell ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31668930

RESUMO

High-resolution Cas9 structures have yet to reveal catalytic conformations due to HNH nuclease domain positioning away from the cleavage site. Nme1Cas9 and Nme2Cas9 are compact nucleases for in vivo genome editing. Here, we report structures of meningococcal Cas9 homologs in complex with sgRNA, dsDNA, or the AcrIIC3 anti-CRISPR protein. DNA-bound structures represent an early step of target recognition, a later HNH pre-catalytic state, the HNH catalytic state, and a cleaved-target-DNA-bound state. In the HNH catalytic state of Nme1Cas9, the active site is seen poised at the scissile phosphodiester linkage of the target strand, providing a high-resolution view of the active conformation. The HNH active conformation activates the RuvC domain. Our structures explain how Nme1Cas9 and Nme2Cas9 read distinct PAM sequences and how AcrIIC3 inhibits Nme1Cas9 activity. These structures provide insights into Cas9 domain rearrangements, guide-target engagement, cleavage mechanism, and anti-CRISPR inhibition, facilitating the optimization of these genome-editing platforms.

19.
Int J Pharm ; : 118831, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715344

RESUMO

Increasing the dissolution rate of water insoluble drugs by decreasing the particle size of the drugs into nano-size is a well-known strategy. However, continuous production of drug nanoparticles with uniform particle size is critical for clinical application of the strategy. Here we report a simple microfluidic mixing method that can achieve continuous production of celecoxib nanoparticles with uniform particle size and high dissolution rate. A three-dimensional (3D) coaxial-flow microfluidic device was fabricated by assembling two coaxial aligned borosilicate glass capillaries on a glass slide, and a tapered glass capillary was inserted into another bigger cylindrical one with coaxial alignment. Celecoxib nanoparticles were prepared by the microfluidic device under the turbulent jet regime. The 3D-coaxial-flow pattern and high Reynolds number ensured the extremely short mixing time, consequently, resulted in the high throughput production of drug nanoparticles with uniform particle size. The obtained nanoparticles were spherical in shape, and showed superior dissolution rate compared with the coarse powder both in sink and non-sink conditions. The bioavailability of the water insoluble drug was also significantly improved by the reduction of particle size into nano-size.

20.
Stem Cells ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721356

RESUMO

Mesenchymal stem cells (MSCs), which are undifferentiated stem cells with the property of stemness and the potential to differentiate into multiple lineages, including osteoblasts, have attracted a great deal of attention in bone tissue engineering. Consistent with the heterogeneity of MSCs, various surface markers have been used. However, it is still unclear which markers of MSCs are best for cell amplification in vitro and later bone regeneration in vivo. Krüppel-like Factor 2 (KLF2) is an important indicator of the stemness of hMSCs [1], and as early vascularization is also critical for bone regeneration, we used KLF2 as a novel in vitro marker for MSCs and investigated the angiogenesis and osteogenesis between KLF2+ MSCs and endothelial cells (ECs). We found a synergistic interaction between hMSCs and human umbilical vein ECs (HUVECs) in that KLF2+ stemness-maintained hMSCs initially promoted the angiogenesis of HUVECs, which in turn more efficiently stimulated the osteogenesis of hMSCs. In fact, KLF2+ hMSCs secreted angiogenic factors initially, with some of the cells then differentiating into pericytes through the PDGF-BB/PDGFR-ß signaling pathway, which improved blood-vessel formation. The matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through upregulated vascular endothelial growth factor (VEGF). A three-dimensional (3D) coculture model using cell-laden GelMA hydrogel further confirmed these results. This study provides insight into the stemness-directed synergistic interaction between hMSCs and HUVECs, and our results will have a profound impact on further strategies involving the application of KLF2+ hMSC/HUVEC-laden GelMA hydrogel in vascular network bioengineering and bone regeneration. © AlphaMed Press 2019 SIGNIFICANCE STATEMENT: KLF2 was creatively put forward as a novel marker in vitro for MSCs to investigate the osteogenesis and angiogenesis between KLF2+ MSCs and ECs. We demonstrated there was a synergistic strategy to help readers understand the process of intercellular interaction between hMSCs and HUVECs, which KLF2+ hMSCs secreted angiogenic factors like ANG1 initially, and some of hMSCs then differentiated into pericytes through PDGF-BB/PDGFR-ß signaling pathway. Both of which improved the formation of blood vessels. Matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through the up-regulated VEGF more efficiently. This work therefore focuses on the synergistic strategy between KLF2+ hMSCs and HUVECs and will have a profound impact on further vascular network bioengineering and bone regeneration.

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