Effects of Nicotine on Proliferation and Survival in Human Umbilical Cord Mesenchymal Stem Cells

Cigarette smoking is known to have negative effects on tissue repair and healing. The aim of this study is to investigate the effects of nicotine in human umbilical cord mesenchymal stem cells (MSCs). After nicotine treatment, MSCs became pyknotic, vacuoles appeared in the cytoplasm and nucleus, and the nuclear boundary became fuzzy as observed using atomic force microscopy. Cell proliferation was inhibited in a dose‐dependent manner (P < 0.05 for all concentrations). The proportion of apoptotic MSCs was significantly increased in a dose‐dependent manner. The mitochondrial membrane potential was significantly decreased (P < 0.05). Nicotine‐treated MSCs had a significantly higher G0/G1 ratio (P < 0.05). Peptide mass fingerprinting identified 27 proteins that were differentially expressed between MSCs with and without nicotine treatment. These nicotine exerted toxic effects on MSCs are likely related, at least in part, to the altered expression of multiple proteins that are essential to the health and proliferation of these cells.     

Bone Marrow and Adipose‐Derived Mesenchymal Stem Cells Alleviate Methotrexate‐Induced Pulmonary Fibrosis in Rat: Comparison with Dexamethasone

The present study examined the therapeutic effects of bone marrow mesenchymal stem cells (BM‐MSCs) and adipose‐derived mesenchymal stem cells (AD‐MSCs) in methotrexate (MTX)‐induced pulmonary fibrosis in rats as compared with dexamethasone (Dex). MTX (14 mg/kg, as a single dose/week for 2 weeks, p.o.) induced lung fibrosis as marked by elevation of relative lung weight, malondialdehyde, nitrite/nitrate, interleukin‐4, transforming growth factor‐β1, deposited collagen, as well as increased expression of Bax along with the reduction of reduced glutathione content and superoxide dismutase activity. These deleterious effects were antagonized after treatment either with BM‐MSCs or AD‐MSCs (2 × 10⁶ cells/rat) 2 weeks after MTX to even a better extent than Dex (0.5 mg/kg/ for 7 days, p.o.). In conclusion, BM‐MSC and AD‐MSCs possessed antioxidant, antiapoptotic, as well as antifibrotic effects, which will probably introduce them as remarkable candidates for the treatment of pulmonary fibrosis.     

Allogeneic Human Mesenchymal Stem Cells Restore Epithelial Protein Permeability in Cultured Human Alveolar Type II Cells by Secretion of Angiopoietin-1

Acute lung injury is characterized by injury to the lung epithelium that leads to impaired resolution of pulmonary edema and also facilitates accumulation of protein-rich edema fluid and inflammatory cells in the distal airspaces of the lung. Recent in vivo and in vitro studies suggest that mesenchymal stem cells (MSC) may have therapeutic value for the treatment of acute lung injury. Here we tested the ability of human allogeneic mesenchymal stem cells to restore epithelial permeability to protein across primary cultures of polarized human alveolar epithelial type II cells after an inflammatory insult. Alveolar epithelial type II cells were grown on a Transwell plate with an air-liquid interface and injured by cytomix, a combination of IL-1β, TNFα, and IFNγ. Protein permeability measured by ¹³¹I-labeled albumin flux was increased by 5-fold over 24 h after cytokine-induced injury. Co-culture of human MSC restored type II cell epithelial permeability to protein to control levels. Using siRNA knockdown of potential paracrine soluble factors, we found that angiopoietin-1 secretion was responsible for this beneficial effect in part by preventing actin stress fiber formation and claudin 18 disorganization through suppression of NFκB activity. This study provides novel evidence for a beneficial effect of MSC on alveolar epithelial permeability to protein.     

Luminescence properties of novel deep‐red‐emitting Ca3Al2Ge2O10:Cr3+ phosphors

Ca₃Al₂Ge₂O₁₀:Cr³⁺ phosphors were prepared by a high‐temperature solid‐state method, and their luminescence properties were investigated. Under excitation at 550 nm, Ca₃Al₂Ge₂O₁₀:Cr³⁺ phosphors exhibited a broad red emission band at 697 nm in the range 650–750 nm that was caused by the ²E→⁴A₂ transition of Cr³⁺. For the 697 nm emission peak, emission intensity reached a maximum at x = 0.07, and there was concentration quenching of Cr³⁺ in Ca₃Al₂Ge₂O₁₀; the corresponding concentration quenching mechanism was analysed. Under excitation at 262 nm, the Ca₃Al₂Ge₂O₁₀:Cr³⁺ phosphor showed a weakly broad emission band in the range 350–600 nm that was caused by intrinsic defects (V′′_Ca and V′′_O). Copyright © 2016 John Wiley & Sons, Ltd.     

Ca2+ Signaling and Cell Death Induced by Protriptyline in HepG2 Human Hepatoma Cells

The effect of protriptyline on Ca²⁺ physiology in human hepatoma is unclear. This study explored the effect of protriptyline on [Ca²⁺]_i and cytotoxicity in HepG2 human hepatoma cells. Protriptyline (50–150 μM) evoked [Ca²⁺]_i rises. The Ca²⁺ entry was inhibited by removal of Ca²⁺. Protriptyline‐induced Ca²⁺ entry was confirmed by Mn²⁺‐induced quench of fura‐2 fluorescence. Except nifedipine, econazole, SKF96365, GF109203X, and phorbol 12‐myristate 13 acetate did not inhibit Ca²⁺ entry. Treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5‐di‐tert‐butylhydroquinone (BHQ) inhibited 40% of protriptyline‐induced response. Treatment with protriptyline abolished BHQ‐induced response. Inhibition of phospholipase C (PLC) suppressed protriptyline‐evoked response by 70%. At 20–40 μM, protriptyline killed cells which was not reversed by the Ca²⁺ chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid‐acetoxymethyl ester (BAPTA/AM). Together, in HepG2 cells, protriptyline induced [Ca²⁺]_i rises that involved Ca²⁺ entry through nifedipine‐sensitive Ca²⁺ channels and PLC‐dependent Ca²⁺ release from endoplasmic reticulum. Protriptyline induced Ca²⁺‐independent cell death.     

Improving green emission of Tb3+ ions in BaO‐B2O3‐P2O5 glasses by means of Al3+ ions

BaO‐B₂O₃‐P₂O₅ glasses doped with a fixed concentration of Tb³⁺ ions and varying concentrations of Al₂O₃ were synthesized, and the influence of the Al³⁺ ion concentration on the luminescence efficiency of the green emission of Tb³⁺ ions was investigated. The optical absorption, excitation, luminescence spectra and fluorescence decay curves of these glasses were recorded at ambient temperature. The emission spectra of terbium ions when excited at 393 nm exhibited two main groups of bands, corresponding to ⁵D₃ → ⁷F_j (blue region) and ⁵D₄ → 7F_j (green region). From these spectra, the radiative parameters, viz., spontaneous emission probability A, total emission probability A_T, radiative lifetime τ and fluorescent branching ratio β, of different transitions originating from the ⁵D₄ level of Tb³⁺ ions were evaluated based on the Judd‐Ofelt theory. A clear increase in the quantum efficiency and luminescence of the green emission of Tb³⁺ ions corresponding to ⁵D₄ → ⁷F₅ transition is observed with increases in the concentration of Al₂O₃ up to 3.0 mol%. The improvement in emission is attributed to the de‐clustering of terbium ions by Al³⁺ ions and also to the possible admixing of wave functions of opposite parities. Copyright © 2016 John Wiley & Sons, Ltd.     

The Role of Hydrogen from ALD‐Al2O3 in Kesterite Cu2ZnSnS4 Solar Cells: Grain Surface Passivation

In this research, a new route of surface passivation is reported by introducing hydrogen from the atomic layer deposited (ALD) Al₂O₃ layer into pure sulfide Cu₂ZnSnS₄ (CZTS) solar cells. Different amounts of hydrogen are incorporated into the Cu₂ZnSnS₄/CdS interface through controlling the thickness of the ALD‐Al₂O₃ layer. The device with three cycles of ALD‐Al₂O₃ yields the highest efficiency of 8.08% (without antireflection coating) with improved open‐circuit voltage of up to 70 mV. With closer examination on the passivation route of ALD‐Al₂O₃, it is revealed by the surface chemisty study that the Al₂O₃ can be etched away by ammonium hydroxide in the CdS buffer deposition process. Instead, the hydrogen is detected within a shallow depth from the CZTS surface, and makes a significant difference in the measured distribution of contact potential difference and device performance. This may be interpreted by the effect of hydrogen passivation of the CZTS surface by curing dangling bonds at the surface of CZTS grains. This work may provide a new direction of further improving the performance of kesterite solar cells.     

Growth Factor Regulation of Prostaglandin-Endoperoxide Synthase 2 (Ptgs2) Expression in Colonic Mesenchymal Stem Cells

We previously found that a population of colonic stromal cells that constitutively express high levels of prostaglandin-endoperoxide synthase 2 (Ptgs2, also known as Cox-2) altered their location in the lamina propria in response to injury in a Myd88-dependent manner (Brown, S. L., Riehl, T. E., Walker, M. R., Geske, M. J., Doherty, J. M., Stenson, W. F., and Stappenbeck, T. S. (2007) J. Clin. Invest. 117, 258–269). At the time of this study, the identity of these cells and the mechanism by which they expressed high levels of Ptgs2 were unknown. Here we found that these colonic stromal cells were mesenchymal stem cells (MSCs). These colonic MSCs expressed high Ptgs2 levels not through interaction with bacterial products but instead as a consequence of mRNA stabilization downstream of Fgf9 (fibroblast growth factor 9), a growth factor that is constitutively expressed by the intestinal epithelium. This stabilization was mediated partially through a mechanism involving endogenous CUG-binding protein 2 (CUGbp2). These studies suggest that Fgf9 is an important factor in the regulation of Ptgs2 in colonic MSCs and may be a factor involved in its constitutive expression in vivo.     

sFRP2 Suppression of Bone Morphogenic Protein (BMP) and Wnt Signaling Mediates Mesenchymal Stem Cell (MSC) Self-renewal Promoting Engraftment and Myocardial Repair

Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for ischemic injury; however, inadequate survival of implanted cells in host tissue is a substantial impediment in the progress of cellular therapy. Secreted Frizzled-related protein 2 (sFRP2) has recently been highlighted as a key mediator of MSC-driven myocardial and wound repair. Notably, sFRP2 mediates significant enhancement of MSC engraftment in vivo. We hypothesized that sFRP2 improves MSC engraftment by modulating self-renewal through increasing stem cell survival and by inhibiting differentiation. In previous studies we demonstrated that sFRP2-expressing MSCs exhibited an increased proliferation rate. In the current study, we show that sFRP2 also decreased MSC apoptosis and inhibited both osteogenic and chondrogenic lineage commitment. sFRP2 activity occurred through the inhibition of both Wnt and bone morphogenic protein (BMP) signaling pathways. sFRP2-mediated inhibition of BMP signaling, as assessed by levels of pSMAD 1/5/8, was independent of its effects on the Wnt pathway. We further hypothesized that sFRP2 inhibition of MSC lineage commitment may reduce heterotopic osteogenic differentiation within the injured myocardium, a reported adverse side effect. Indeed, we found that sFRP2-MSC-treated hearts and wound tissue had less ectopic calcification. This work provides important new insight into the mechanisms by which sFRP2 increases MSC self-renewal leading to superior tissue engraftment and enhanced wound healing.     

Photoluminescence imaging of europium (III)‐doped γ‐Al2O3 nanofiber structures

Aluminium oxide (Al₂O₃) has widely been used for catalysts, insulators, and composite materials for diverse applications. Herein, we demonstrated if γ‐Al₂O₃ was useful as a luminescence support material for europium (Eu) (III) activator ion. The hydrothermal method and post‐thermal treatment at 800°C were employed to synthesize Eu(III)‐doped γ‐Al₂O₃ nanofibre structures. Luminescence characteristics of Eu(III) ions in Al₂O₃ matrix were fully understood by taking 2D and 3D‐photoluminescence imaging profiles. Various sharp emissions between 580 to 720 nm were assigned to the ⁵D₀→⁷F_J (J = 0, 1, 2, 3, 4) transitions of Eu(III) activators. On the basis of X‐ray diffraction crystallography, Auger elemental mapping and the asymmetry ratio, Eu(III) ions were found to be well doped into the γ‐Al₂O₃ matrix at a low (1 mol%) doping level. A broad emission at 460 nm was substantially increased upon higher (2 mol%) Eu(III) doping due to defect creation. The first 3D photoluminescence imaging profiles highlight detailed understanding of emission characteristics of Eu(III) ions in Al oxide‐based phosphor materials and their potential applications.     

三种金属氧化物纳米颗粒的水生态毒性

参考国际经济合作与发展组织(OECD)化学品生态毒性测试标准方法,以绿藻(Scenedesmus oblignus)和大型蚤(Daphnia magna)为受试生物,研究了3种金属氧化物纳米颗粒(纳米氧化锌nZnO、纳米二氧化钛nTiO2、纳米氧化铝nAl2O3)水悬浮液的水生生态毒性.结果发现,不同的纳米颗粒具有不同的毒性:nZnO、nTiO2和nAl2O3对斜生栅藻生长的 96 h半效应浓度(EC50)值分别为1.049、15.262、>1000 mg · L-1,而对大型蚤活动抑制的 48 h EC50 值则分别为0.622、35.306 mg · L-1和114.357 mg · L-1.据此可得到3 种金属氧化物纳米颗粒水悬浮液的毒性大小顺序为:nZnO ＞nTiO2 ＞ nAl2O3.此外,不同的生物对金属氧化物纳米颗粒的敏感性也不同,除nTiO2以外,大型蚤对另外2种纳米颗粒的敏感性强于斜生栅藻.实验结果表明,人工纳米材料的生态毒性和环境效应不容忽视,应重视并深入研究此类纳米材料的毒性作用机制和影响因子,以便能对其进行更好的风险管理.     

Role of Wnt-5a in the Determination of Human Mesenchymal Stem Cells into Preadipocytes

Increasing adipocyte size as well as numbers is important in the development of obesity and type 2 diabetes, with adipocytes being generated from mesenchymal precursor cells. This process includes the determination of mesenchymal stem cells (MSC) into preadipocytes (PA) and the differentiation of PA into mature fat cells. Although the process of differentiation has been highly investigated, the determination in humans is poorly understood. In this study, we compared human MSC and human committed PA on a cellular and molecular level to gain further insights into the regulatory mechanisms in the determination process. Both cell types showed similar morphology and expression patterns of common mesenchymal and hematopoietic surface markers. However, although MSC were able to differentiate into adipocytes and osteocytes, PA were only able to undergo adipogenesis, indicating that PA lost their multipotency during determination. WNT-5a expression showed significantly higher levels in MSC compared with PA suggesting that WNT-5a down-regulation might be important in the determination process. Indeed, incubation of human MSC in medium containing neutralizing WNT-5a antibodies abolished their ability to undergo osteogenesis, although adipogenesis was still possible. An opposite effect was achieved using recombinant WNT-5a protein. On a molecular level, WNT-5a was found to promote c-Jun N-terminal kinase-dependent intracellular signaling in MSC. Activation of this noncanonical pathway resulted in the induction of osteopontin expression further indicating pro-osteogenic effects of WNT-5a. Our data suggest that WNT-5a is necessary to maintain osteogenic potential of MSC and that inhibition of WNT-5a signaling therefore plays a role in their determination into PA in humans.     

Luminescence of the near‐ultraviolet blue‐emitting Ba9Al2Si6O24:Ce3+ phosphor

A near‐ultraviolet (NUV) blue‐emitting phosphor Ba₉Al₂Si₆O₂₄:Ce³⁺ (BAS:Ce³⁺) was synthesized using a high‐temperature solid‐state reaction. BAS:Ce³⁺ had an excitation band peak at about 328 nm and showed a blue emission band. The NUV‐blue emission band had a peak at about 386 nm with a band width of about 60 nm, attributed to the 5d–4f transition of Ce³⁺. Fluorescent decay showed an exponential model with a lifetime of 27.2 nsec. At 150°C, the luminescence intensity decreased to 68.7% compared with the intensity at room temperature.     

Expression of Vascular Endothelial Growth Factor-C (VEGF-C) and Its Receptor (VEGFR-3) in the Glial Reaction Elicited by Human Mesenchymal Stem Cell Engraftment in the Normal Rat Brain

To determine whether vascular endothelial growth factor-C (VEGF-C) and its receptor (VEGFR-3) are involved in the glial reaction elicited by transplanted mesenchymal stem cells (MSCs), we examined the cellular localization of VEGF-C and VEGFR-3 proteins in the striatum of adult normal rats that received bone marrow-derived human MSCs. The MSC grafts were infiltrated with activated microglia/macrophages and astrocytes over a 2-week period post-transplantation, which appeared to parallel the loss of transplanted MSCs. VEGF-C/VEGFR-3 was expressed in activated microglia/macrophages recruited to the graft site, where the induction of VEGF-C protein was rather late compared with that of its receptor. VEGF-C protein was absent or very weak on day 3, whereas VEGFR-3 immunoreactivity was evident within the first three days. Furthermore, within three days, VEGF-C could be detected in the brain macrophages localized immediately adjacent to the needle track. At the same time, almost all the brain macrophages in both regions expressed VEGFR-3. Reactive astrocytes at the graft site expressed VEGFR-3, but not VEGF-C. These data demonstrated the characteristic time- and cell-dependent expression patterns for VEGF-C and VEGFR-3 within the engrafted brain tissue, suggesting that they may contribute to neuroinflammation in MSC transplantation, possibly through the recruitment and/or activation of microglia/macrophages and astrogliosis.     

Deactivating Defects in Graphenes with Al2O3 Nanoclusters to Produce Long‐Life and High‐Rate Sodium‐Ion Batteries

Carbon materials are the most promising anodes for sodium‐ion batteries (SIBs), but low initial Coulombic efficiency (ICE) and poor cyclic stability hinder their practical use. It is shown herein, that an effective but simple remedy for these problems can be achieved by deactivating defects in the carbon with Al₂O₃ nanocluster coverage. A 3D porous graphene monolith (PGM) is used as the model material and Al₂O₃ nanoclusters around 1 nm are grown on the defects of graphene. It is shown that these Al₂O₃ nanoclusters suppress the decomposition of conductive sodium salt in the electrolyte, resulting in the formation of a thin and homogenous solid electrolyte interphase (SEI). In addition, Al₂O₃ nanoclusters appear to reduce the detrimental etching of the SEI by hydrogen fluoride (HF) and improve its stability. Therefore, after the introduction of Al₂O₃ nanoclusters, the ICE, cyclic stability, and rate capability of the PGM are greatly improved. A higher ICE (70.2%) and capacity retention (82.9% after 500 cycles at 0.5 A g^?1) than those of normally reported for large surface area carbons are achieved. This work indicates a new way to deactivate defects and modify the SEI of carbon materials, and hopefully accelerate the commercialization of carbon materials as anode materials for SIBs.     

Inverted Tandem Polymer Solar Cells with Polyethylenimine‐Modified MoOX/Al2O3:ZnO Nanolaminate as the Charge Recombination Layers

A new charge recombination layer for inverted tandem polymer solar cells is reported. A bilayer of MoO_X/Al₂O₃:ZnO nanolaminate is shown to enable efficient charge recombination in inverted tandem cells. A polymer surface modification on the MoO_X/Al₂O₃:ZnO nanolaminate bilayer increases the work function contrast between the two outward surfaces of the charge recombination layer, further improving the performance of tandem solar cells. An analysis of the electrical, optical, and surface properties of the charge recombination layer is presented. Inverted tandem polymer solar cells, with two photoactive layers comprising poly (3‐hexylthiophene) (P3HT):indene‐C₆₀ bisadduct (IC₆₀BA) for the bottom cell and poly[(4,8‐bis‐(2‐ethylhexyloxy)‐benzo[1,2‐b:4,5‐b']dithiophene)‐2,6‐diyl‐alt‐(4‐(2‐ethylhexanoyl)‐thieno[3,4‐b]thiophene))‐2,6‐diyl] (PBDTTT‐C):[6,6]‐phenyl C₆₁ butyric acid methyl ester (PC₆₀BM) for the top cell, yield an open‐circuit voltage of 1481 mV ± 15 mV, a short‐circuit current density of 7.1 mA cm^?2 ± 0.1 mA cm^?2, and a fill factor of 0.62 ± 0.01, resulting in a power conversion efficiency of 6.5% ± 0.1% under simulated AM 1.5G, 100 mW cm^?2 illumination.