Seeding Atomic Silver into Internal Lattice Sites of Transition Metal Oxide for Advanced Electrocatalysis.

Transition metal oxides (TMOs) are widely studied for loading of various catalysts due to their low cost and high structure flexibility. However, the prevailing close-packed nature of most TMOs crystals has restricted the available loading sites to surface only, while their internal bulk lattice remains unactuated due to the inaccessible narrow space that blocks out most key reactants and/or particulate catalysts. Herein, using tunnel-structured MnO2, we demonstrate how TMO's internal lattice space can be activated as extra loading sites for atomic Ag in addition to the conventional surface-only loading, via which a dual-form Ag catalyst within MnO2 skeleton is established. In this design, not only faceted Ag nanoparticles are confined onto MnO2 surface by coherent lattice-sharing, Ag atomic strings are also seeded deep into the sub-nanoscale MnO2 tunnel lattice, enriching the catalytically active sites. Tested for electrochemical CO2 reduction reaction (eCO2RR), such dual-form catalyst exhibits a high Faradaic efficiency (94%), yield (67.3 mol/g/h) and durability (∼ 48 h) for CO production, exceeding commercial Ag nanoparticles and most Ag-based electrocatalysts. Theoretical calculations further reveal the concurrent effect of such dual-form catalyst featuring facet-dependent eCO2RR for Ag nanoparticles and lattice-confined eCO2RR for Ag atomic strings, inspiring the future design of catalyst-substrate configuration. This article is protected by copyright. All rights reserved.

Ratiometric Fluorescence Detection of Levofloxacin Based on a Cube-like Zn(II)-Eu(III) Nanocluster: Functionalized Sodium Alginate Film for the Detection in Serum and Medicine.

A cube-like Zn(II)-Eu(III) nanocluster 1 (molecular sizes: 1.8 × 2.0 × 2.0 nm) was constructed by the use of a new long-chain Schiff base ligand. It shows a ratiometric fluorescence response to levofloxacin (LFX) with high sensitivity and selectivity, which can be expressed as I615 nm/I550 nm = A*[LFX]2 + B*[LFX] + C. It is used to quantitatively detect the LFX concentrations in fetal calf serum (FCS) and tablets sold in pharmacy. Filter paper strips bearing 1 can be used to qualitatively detect LFX by a color change to red under a UV lamp. 1 and its hybrid with sodium alginate (SA), 1@SA, display potential applications in the qualitative detection of LFX in FCS and the medicine. The limit of detection of 1 to LFX is as low as 2.1 × 10-2 nM.

A 20-Metal Zn(II)-Cd(II)-Eu(III) Nanocluster with Qualitative and Quantitative Luminescence Detection of Meloxicam (an Anti-Inflammatory Drug).

Meloxicam (MLX) is a novel nonsteroidal anti-inflammatory drug, but on the other hand, it has become one of the common microcontaminants in surface waters and sewage. Herein, we report the preparation of a ternary-metal Zn(II)-Cd(II)-Eu(III) nanocluster 1 for the response of MLX through the enhancement of lanthanide luminescence. The luminescence sensing behavior of 1 is expressed by the equation I615nm = 3060 × [MLX] + 46,604, which can be used in the quantitative analysis of MLX concentrations in meloxicam dispersible tablets. Filter paper strips bearing 1 can be used to qualitatively detect MLX by a color change to red under a UV lamp. The luminescence response time is no more than five s, and the detection limit is as low as 2.31 × 10-2 nM.

Construction of a Zn(II)-Eu(III) Nanoring with Temperature-Dependent Luminescence for the Qualitative and Quantitative Detection of Neopterin as an Inflammatory Marker.

A nine-metal Zn(II)-Eu(III) nanoring 1 with a diameter of about 2.3 nm was constructed by the use of a long-chain Schiff base ligand. It shows a luminescence response to neopterin (Neo) through the enhancement of lanthanide emission with high selectivity and sensitivity, which can be used to quantitatively analyze the concentrations of Neo in fetal calf serum and urine. The luminescence sensing of 1 to Neo is temperature-dependent, and it displays more obvious response behavior at lower temperatures. Filter paper strips bearing 1 can be used to qualitatively detect Neo by the color change from chartreuse to red under a UV lamp. The limit of detection is as low as 3.77 × 10-2 nM.

Injectable and In Situ Formed Dual-Network Hydrogel Reinforced by Mesoporous Silica Nanoparticles and Loaded with BMP-4 for the Closure and Repair of Skull Defects.

Bone defects are a common and challenging orthopedic problem with poor self-healing ability and long treatment cycles. The difficult-to-heal bone defects cause a significant burden of medical expenses on patients. Currently, biomaterials with mechanical stability, long-lasting action, and osteogenic activity are considered as a suitable way to effectively heal bone defects. Here, an injectable double network (DN) hydrogel prepared using physical and chemical cross-linking methods is designed. The first rigid network is constructed using methylpropenylated hyaluronic acid (HAMA), while the addition of chitosan oligosaccharide (COS) forms a second flexible network by physical cross-linking. The mesoporous silica nanoparticles (MSN) loaded with bone morphogenetic protein-4 (BMP-4) were embedded into DN hydrogel, which not only enhanced the mechanical stability of the hydrogel, but also slowly released BMP-4 to achieve long-term skull repair. The designed composite hydrogel showed an excellent compression property and deformation resistance. In vitro studies confirmed that the HAMA/COS/MSN@BMP-4 hydrogel had good biocompatibility and showed great potential in supporting proliferation and osteogenic differentiation of mouse embryo osteoblast precursor (MC3T3-E1) cells. Furthermore, in vivo studies confirmed that the DN hydrogel successfully filled and closed irregular skull defect wounds, effectively promoted bone regeneration, and significantly promoted bone repair compared with the control group. In addition, HAMA/COS/MSN@BMP-4 hydrogel precursor solution can quickly form hydrogel in situ at the wound by ultraviolet light, which can be applied to the closure and repair of wounds of different shapes, which provides the new way for the treatment of bone defects.

Construction of a Near-IR-Luminescent Rectangular Yb(III) Complex from a Dodecadentate Schiff Base Ligand for the Excitation-Wavelength-Dependent Detection of Aloe Emodin (a Natural Medicinal Ingredient).

A near-IR-luminescent octanuclear Yb(III) complex 1 was constructed from a new dodecadentate Schiff base ligand, which is used in the rapid and reliable wavelength-dependent detection of aloe emodin (AE) with high sensitivity even in the presence of other interferences.

Atomic Mechanisms of Cation Adsorption/Exchange in Octahedral Molecular Sieves.

Octahedral molecular sieves (OMSs) based on MnO2 have been widely studied in the fields of deionization, geochemistry, and energy storage due to their microporous tunnel framework capable of adsorbing and exchanging various ions, particularly cations. The understanding of cation adsorption/exchange within OMS tunnels demands atomic-scale exploration, which has been scarcely reported. Here, we disclose how various cations (K+/Ag+/Na+) interplay within the OMS tunnel space on an atomic scale. Not only are the lattice sites for each adsorbed cation species pinpointed but the scenario of dual-cation adsorption within single tunnels is also demonstrated, together with the discovery of characteristic concentration-dependent cation ordering. Moreover, compared with the theoretical parent tunnel phase, the heterogeneous tunnels, though sparsely distributed, exhibit a distinct yet orderly cationic accommodation, highlighting the non-negligible role of tunnel heterogeneity in regulating OMS physiochemistry. Our findings clarify the long-existing ambiguities in nano- and atomic-scale science of the ion adsorption process in OMS materials and are expected to inspire their structural/compositional engineering toward functionality enhancement in various fields.

Rapid and reliable triple-emissive detection of 2,6-dichloro-4-nitroaniline as a pesticide based on a high-nuclear Cd(II)-Sm(III) nanocluster.

A luminescent 56-metal Cd(II)-Sm(III) nanocluster (1, molecular sizes: 4.5 × 2.7 × 2.7 nm) was constructed from a flexible Schiff base ligand, and its crystal structure was determined using the X-ray diffraction method. It shows a rapid triple-emissive response to 2,6-dichloro-4-nitroaniline (DCN, a common pesticide) with high sensitivity and selectivity, which can be used to quantitatively analyze the DCN concentrations in fruit extracts. The limits of detection (LODs) of 1 to DCN for the visible ligand-centered and Sm(III) emissions and NIR Sm(III) luminescence are from 0.95 µM to 2.81 µM.

miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1.

We explore miR-150-5p in atherosclerosis (AS). The AS model was constructed using Apo E-/- mice with an injection of the miR-150-5p mimic or an inhibitor. Pathological characteristics were assessed using Oil red O staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expressions of microRNA-150-5p (miR-150-5p), STAT1, α-SMA (α-smooth muscle actin) and proliferating cell nuclear antigen (PCNA). Targetscan and dual-luciferase reporter assay were used to analyze the interaction between miR-150-5p and STAT1. The viability, migration, cell cycle and α-SMA and PCNA expressions in oxidized low-density lipoprotein (ox-LDL)-stimulated primary human aortic smooth muscle cells (ASMCs) were assessed using molecular experiments. miR-150-5p was reduced in both AS mice and ox-LDL-stimulated human aortic smooth muscle cells but STAT1 had the opposite effect. The miR-150-5p inhibitor alleviated the increase of lipid plaque and reduced collagen accumulation in the aortas during AS. Upregulation of α-SMA and PCNA was reversed by miR-150-5p upregulation. STAT1 was targeted by miR-150-5p, and overexpressed miR-150-5p weakened the ox-LDL-induced increase of viability and migration abilities and blocked cell cycle in ASMCs, but overexpressed STAT1 blocked the effect of the miR-150-5p mimic. This paper demonstrates that miR-150-5p has potential as a therapeutic target in AS, with plaque stabilization by regulating ASMC proliferation and migration via STAT1.

A mitochondria-targeted ratiometric fluorescent nanoprobe for imaging of peroxynitrite in living cells.

Peroxynitrite (ONOO-) is a series of basic biological oxidants involved in physiological and pathological processes. The detection of ONOO- in biological systems has been challenging due to its extremely short half-life and low steady-state concentration. In this work, a ratiometric fluorescent nanoprobe for ONOO- was constructed by coupling covalently of graphene quantum dots (GQDs) with cyanine 5.5 (Cy5.5). This nanoprobe (GQD-Cy5.5) could selectively accumulate in mitochondrial, appears two strong fluorescence emission peaks at 520 and 694 nm. In the presence of ONOO-, the intensity of fluorescence emission peak at 520 nm increased and the intensity of fluorescence emission peak at 694 nm decreased. The ratio (F520 nm/F694 nm) of fluorescence intensity at two emission peaks had a good linear relationship with the concentration of ONOO- in the range of 0-6.0 µM, and the detection limit was 0.03 µM. The excellent properties of the nanoprobe enable its applications in the ratiometric fluorescence imaging of endogenous ONOO- in cell mitochondria.

O-arm navigation for sacroiliac screw placement in the treatment for posterior pelvic ring injury.

PURPOSE: This study aims to investigate the application value of O-arm navigation system in sacroiliac screw placement for the treatment of unstable pelvic ring injury. METHODS: A total of 40 patients (mean age = 30.75 ± 14.99 years, 25 males, 15 females) were included. From January 2016 to July 2018, 40 patients with posterior pelvic ring injury treated in our hospital were included. Of them, 19 patients underwent O-arm navigation for screw placement (O-arm group) while the other 21 received C-arm fluoroscopy guidance (C-arm group) for sacroiliac screw placement. Intraoperative outcomes and the outcome of screw placement were compared between groups. The quality of radiological images was assessed by Matta's radiological outcome grade. The outcome of complex pelvic fracture treatment was evaluated by Majeed Functional score. RESULTS: All demographic and clinical characteristics were comparable between the two groups. Compared with the C-arm groups, the O-arm group had a shorter surgery time (33.19 ± 3.14 vs. 48.35 ± 4.38 min, P < 0.001), a higher overall good outcome "excellent + good" rate of screw placement (95.45% vs. 73.91%, P < 0.05), and a significantly higher Majeed Functional score better outcome of complex pelvic fracture treatment at 1 and 3 months postoperation (both P < 0.05). CONCLUSION: Our results demonstrated that O-arm navigation system is feasible and safe for the treatment of posterior pelvic ring injury and can effectively improve the accuracy and safety of sacroiliac screw placement, shorten the operation time, and help rapid postoperative functional recovery.

Intrauterine transplantation of autologous menstrual blood stem cells increases endometrial thickness and pregnancy potential in patients with refractory intrauterine adhesion.

AIM: This study was designed to evaluate the effects of intrauterine transplantation of menstrual blood stem cells (MenSCs) on endometrial thickness and pregnancy outcomes in patients with refractory intrauterine adhesion (IUA). METHODS: This study included a group of infertile women (n = 12, age 22-40 years), with refractory IUA. Autologous MenSCs isolated from the women's menstrual blood were expanded in vitro and transplanted into their uteruses, followed by hormone replacement therapy. Transvaginal ultrasound examination was performed to assess the endometrial thickness. Transabdominal ultrasound was conducted to detect pregnancy outcome. RESULTS: Autologous MenSCs were successfully isolated and expanded from menstrual blood and transplanted into the uterus of each patient. A significant improvement of the endometrial thickness was observed from 3.9 ± 0.9 to 7.5 ± 0.6 mm (P < 0.001). No adverse reaction was observed. The duration of menstruation was increased from 2.4 ± 0.7 to 5.3 ± 0.6 days (P < 0.001). Five out of 12 patients achieved clinical pregnancy and the pregnancy rate was 41.7%. CONCLUSIONS: Intrauterine transplantation of autologous MenSCs results in regeneration of endometrium, a prolongation of menstrual duration and an increase rate of pregnancy in patients with refractory IUA.

[Treatment of giant cell tumor of bone around knee joint with three-dimensional printing personalized prosthesis].

OBJECTIVE: To investigate the short-term effectiveness of three-dimensional (3D) printing personalized prosthesis in the treatment of giant cell tumor of bone around knee joint. METHODS: A clinical data of 9 patients with giant cell tumor of bone around knee joints and met the inclusive criteria between May 2014 and August 2017 was retrospectively analysed. There were 4 males and 5 females, with an average age of 35.8 years (range, 24-50 years). The lesion located at the distal femur in 4 cases and at the proximal tibia in 5 cases. The disease duration was 5-25 months (mean, 12.9 months). According to Campanacci grading, there were 2 patients of grade Ⅰ and 7 of grade Ⅱ. The 3D printing personalized prosthesis was designed based on the CT scanning and 3D reconstruction prepared before operation. All patients were treated with the tumor resection and 3D printing personalized prosthesis reconstruction. The radiological examination was taken to observe the tumor recurrence and the Musculoskeletal Tumor Society 1993 (MSTS93) score was used to evaluate the knee function. RESULTS: All operations were successful and all incisions healed by first intention without early complications. All patients were followed up 24-40 months (mean, 31.2 months). At last follow-up, no complication such as pain, pathological fracture, prosthesis loosening, or tumor recurrence occurred. The MSTS93 score was 20-29 (mean, 24.7). The knee function was rated as excellent in 6 cases and good in 3 cases, with the excellent and good rate of 100%. CONCLUSION: For giant cell tumor of bone around knee joint, 3D printing personalized prosthesis has the advantages of bio-fusion with host bone, mechanical stability, good joint function, and ideal short-term effectiveness. But the middle- and long-term effectiveness still need to be further observed.

A multifunctional nanoprobe for targeting tumors and mitochondria with singlet oxygen generation and monitoring mitochondrion pH changes in cancer cells by ratiometric fluorescence imaging.

Mitochondria are the main sites of cell metabolism. Even minor pH changes may lead to mitochondrial dysfunction and promote cell apoptosis. Mitochondrion-targeting photosensitizers can produce singlet oxygen in the mitochondria. In tumor photodynamic therapy (PDT), tumor cells are killed through singlet oxygen generation by photosensitizers, and optimally the process of cell apoptosis can be real-time monitored by monitoring the changes of mitochondrial pH value. To this end, a multifunctional nanoprobe that is not only able to produce singlet oxygen in mitochondria but also able to detect the changes in mitochondrial pH value has been developed in this work. The probe is a single-excited dual-emission biomass quantum dot (BQD-FA) prepared from Osmanthus leaves with folic acid (FA) and polyoxyethylene diamine as modifiers. The BQD-FAs can target tumor cells and mitochondria, and produce singlet oxygen in the mitochondria under near-infrared laser irradiation (λ em = 660 nm). On the other hand, in the pH range of 3-8, the fluorescence intensity ratio of BQD-FAs at wavelengths 490 nm and 650 nm showed a good linear relationship with the pH value of mitochondria. The ratiometric fluorescence imaging of mitochondria using the prepared BQD-FAs showed that when the cells were chemically stimulated with chlorphenizone, the mitochondrial pH dropped from 7.9 to 7.2 within 15 min. Based on these characteristics, we envision that the prepared multifunctional nanoprobe will be of high significance in the biomedical research of mitochondria and PDT of tumors.

A new ratiometric fluorescence assay based on resonance energy transfer between biomass quantum dots and organic dye for the detection of sulfur dioxide derivatives.

Sulfur dioxide (SO2) is considered as the fourth gas signal molecule after nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). It plays important roles in several physiological processes. Therefore, the design and synthesis of nanoprobes for the detection of SO2 derivatives in cells is of great significance. Herein, we report a new ratiometric fluorescence nanoprobe based on resonance energy transfer (RET) between biomass quantum dots (BQDs) and organic dye (DMI) for the detection of SO2 derivatives. The proposed ratiometric fluorescence assay allows the determination of HSO3 - in the range of 1.0 to 225 µM with a detection limit of 0.5 µM. Importantly, the proposed ratiometric fluorescence nanoprobe exhibits a high photostability and good selectivity for HSO3 - over other chemical species including H2S and biological mercaptans. Quantitation of HSO3 - in cell lysates by using the nanoprobe is demonstrated.

[Analysis of anti-fatigue mechanism and potential targets of ginseng].

Ginseng has effects in reinforcing vital energy,invigorating health effectively and relieving fatigue symptoms,and ginsenoside( GS) is the main component of its anti-fatigue effect. Totally 17 active components and 92 drug targets of ginseng compounds were screened from Traditional Chinese Medicine Systems Pharmacology; and 78 intersecting genes of diseases and drug targets were obtained based on R Language Technology. The protein-protein interaction( PPI) network was constructed by STRING 11. 0 software,and Matthews Correlation Coefficient( MCC) algorithm was used to screen core target genes. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the major genes and their roles in regulatory networks. The results indicated that ginseng could regulate the core target genes,including AKT serine/threonine kinase( AKT1),interleukin-1ß,Toll-like receptor binding molecule 1( ICAM1),mitogen-activated protein kinase 8( MAPK8),AP-1 transcription factor subunit( JUN),transducer and activator of transcription 1( STAT1) and prostaglandin peroxidase synthase 2( PTGS2). It could participate in the functions of cytokine receptor binding,cell adhesion molecule binding and tumor necrosis factor receptor superfamily binding,and also regulate the signal pathways of tumor necrosis factor,interleukin 17 and c-type lectin receptor,so as to exert an anti-fatigue effect. Based on the results of network analysis,32 four-week-old male SPFACR mice were randomly divided into control group,low-dose ginsenoside group,middle-dose ginsenoside group and high-dose ginsenoside group. The corresponding drugs were administrated for 3 weeks. The results showed that GS could significantly up-regulate the expressions of STAT1 and AKT1( P<0. 01,P<0. 05),and downregulate the expressions of PTGS2 and JUN( P<0. 01). However,there was no significant effect on MAPK8,IL-1ß and ICAM1. Ginseng's anti-fatigue regulation network was constructed through network pharmacology,and the results were verified by experiments,in order to reveal the anti-fatigue mechanism of ginseng and provide scientific basis for its clinical application.

In Situ Ratiometric Fluorescence Imaging for Tracking Targeted Delivery and Release of Anticancer Drug in Living Tumor Cells.

In situ ratiometric fluorescence tracking the delivery and release of antitumor drugs remains a challenge for targeted treatment of cancer. Herein, we fabricated aptamer-functionalized biomass quantum dots (BQD-Apt) as the nanocarriers and probes for tracking the delivery and release of doxorubicin (DOX) in living cells. The fluorescence resonance energy transfer between BQDs and DOX in the formed BQD-Apt-DOX complex was inhibited after releasing DOX, achieving in situ ratiometric fluorescence imaging of delivery and release of DOX. Because of the good cancer-targeting ability of aptamer and biocompatibility of BQDs, BQD-Apt-DOX holds great potential for improving the efficiency of cancer treatment.

Mapping between HAQ-DI and EQ-5D-5L in a Chinese patient population.

OBJECTIVES: In order to address the current deficiency of health utility evidence relevant for economic evaluations involving treatments for rheumatoid arthritis (RA) in the Chinese setting, this study aims to develop a mapping algorithm linking the Health Assessment Questionnaire (HAQ) and EQ-5D-5L in a Chinese population of patients with RA. METHODS: An estimation sample was obtained from a cross-sectional study that collected HAQ, the pain Visual Analogue Scale, and EQ-5D-5L in RA patients in two tertiary referral hospitals in China. Mapping algorithms were derived in this study using two alternative regression methods: the beta regression and a multivariate ordered probit regression. The internal validity of the mapping algorithms was assessed in each case by calculating predictive performance using a bootstrapping procedure. RESULTS: Of the several algorithms developed using these data, predictive performance was shown to be better when VAS pain was included as a predictor and when the multivariate ordered probit regression method was used, rather than the beta regression method. The algorithms developed were shown to be comparable, in terms of predictive performance, to existing mapping studies despite the small sample size of the estimation data. CONCLUSION: It is hoped that the availability of these algorithms will facilitate the development of cost-effectiveness studies evaluating RA treatments in the Chinese health care setting.

Burden of rheumatoid arthritis from a societal perspective: A prevalence-based study on cost of this illness for patients in China.

AIM: To provide a comprehensive estimation of the economic burden of rheumatoid arthritis (RA) in China, especially for patients from less developed areas, and to explore the cost transferability between regions to assist healthcare decision-making. METHODS: The study was conducted in south and north China from May 2013 to December 2013. The burden of RA was investigated by interviewing participants with a questionnaire battery containing socio-demographic, cost of illness (COI) and medical treatments. The COI questionnaire captured direct, indirect and intangible costs. Direct costs included hospitalizations, outpatient visits and medications. Indirect costs were estimated using the human capital approach, and intangible costs valued through the willingness-to-pay approach. All cost data were converted to 2013 US dollars by purchasing power parity, and then summarized descriptively and analyzed with mixed models. RESULTS: Questionnaires were administered to 133 RA patients. The average direct costs were $1917.21 ± $2559.06 per patient year, with medications at $1283.89 ± $1898.15 comprising more than 50% of the total. The average indirect costs were $492.88 ± $1739.74 per patient year, while intangible costs were $20396.30 ± $31145.10. There was no significant difference detected between regions. Recent hospitalization was tested as a significant predictor of the direct costs. Age and income were significantly associated with indirect and intangible costs. CONCLUSIONS: Besides the substantial burden in terms of direct medical costs and productivity lost, there were notable intangible costs, especially among older patients. This conclusion could be potentially expanded to other provinces in China or even other countries through the adjustments for transferability.

Bone marrow-derived mesenchymal stem cells induced by inflammatory cytokines produce angiogenetic factors and promote prostate cancer growth.

BACKGROUND: Prostate is susceptible to infection and pro-inflammatory agents in a man's whole life. Chronic inflammation might play important roles in the development and progression of prostate cancer. Mesenchymal stem cells (MSCs) are often recruited to the tumor microenvironment due to local inflammation. We have asked whether stimulation of MSCs by pro-inflammatory cytokines could promote prostate tumor growth. The current study investigated the possible involvement of MSCs stimulated by pro-inflammatory cytokines in promotion and angiogenesis of prostate cancer through relative pathway in vitro and in vivo. METHODS: A syngeneic mouse model of C57 was established. The murine prostate cancer cells (RM-1) mixing with MSCs treated with tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) or vehicle were subcutaneously injected into C57 mice. Tumor volume of C57 mouse model was estimated and serum level of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) was test by Enzyme-linked Immunosorbent Assay (ELISA). A hen egg test-chorioallantoic membrane (HET-CAM) assay was applied to test the effect of conditioned media of stimulated MSCs in chorioallantoic membrane angiogenesis. Short interfering RNA (siRNA) knocked down either hypoxia-inducible factor-1alpha (HIF-1α) or nuclear factor-erythroid-2-related factor 2 (NRF2) were employed. mRNA of PDGF and VEGF in MSCs, as well as NRF2 and HIF-1α was test by Real time polymerase chain reaction (PCR) analyses. Protein expression levels of PDGF and VEGF from conditioned medium, NRF2, HIF-1α, as well as PDGF and VEGF in MSCs were detected by Western blot analysis. RESULTS: MSCs treated with TNF-α and IFN-γ promote tumor growth in C57 syngeneic mouse model, correlating with increased serum level of PDGF, VEGF. HET-CAM assay shows the angiogenic effect of conditioned medium of MSCs pre-treated with the pro-inflammatory cytokines. mRNA and protein levels of two pro-angiogenic factors (PDGF and VEGF) and key hypoxia regulators (HIF-1α and NRF2) in MSCs were induced after MSCs' pretreatment. siRNA knockdown either HIF-1α or NRF2 results reduction of PDGF and VEGF expression. CONCLUSIONS: MSCs stimulated by pro-inflammatory cytokines increase the expression of PDGF and VEGF via the NRF2-HIF-1α pathway and accelerate prostate cancer growth in mice.