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Background Mast cells play an important role in early immune reactions in the brain by degranulation and the consequent inflammatory response. Our aim of the study is to investigate the effects of rh-relaxin-2 on mast cells and the underlying mechanisms in a germinal matrix hemorrhage (GMH) rat model. Methods One hundred seventy-three P7 rat pups were subjected to GMH by an intraparenchymal injection of bacterial collagenase. Clodronate liposome was administered through intracerebroventricular (i.c.v.) injections 24 h prior to GMH to inhibit microglia. Rh-relaxin-2 was administered intraperitoneally at 1 h and 13 h after GMH. Small interfering RNA of RXFP1 and PI3K inhibitor LY294002 were given by i.c.v. injection. Post-GMH evaluation included neurobehavioral function, Western blot analysis, immunofluorescence, Nissl staining, and toluidine blue staining. Results Our results demonstrated that endogenous relaxin-2 was downregulated and that RXFP1 level peaked on the first day after GMH. Administration of rh-relaxin-2 improved neurological functions, attenuated degranulation of mast cells and neuroinflammation, and ameliorated post-hemorrhagic hydrocephalus (PHH) after GMH. These effects were associated with RXFP1 activation, increased expression of PI3K, phosphorylated AKT and TNFAIP3, and decreased levels of phosphorylated NF-κB, tryptase, chymase, IL-6, and TNF-α. However, knockdown of RXFP1 and PI3K inhibition abolished the protective effects of rh-relaxin-2. Conclusions Our findings showed that rh-relaxin-2 attenuated degranulation of mast cells and neuroinflammation, improved neurological outcomes, and ameliorated hydrocephalus after GMH through RXFP1/PI3K-AKT/TNFAIP3/NF-κB signaling pathway.

Hair follicle stem cells are vital seed cells for hair follicle and tissue engineering skin. However, there is no valid approach to obtain abundant cells within short times in vitro. The purpose of this study was to establish a new medium for culture and expansion of hair follicle outer root sheath (ORS) cells. ORS cells were harvested from human samples and cultured with a medium mixed with keratinocyte serum free medium and mouse embryonic fibroblasts suspension. The proliferation and vitality of ORS cells were evaluated. The cells exhibited typical cobblestone morphology with good adhesion and colony-forming ability. The cells were also characterized through detecting specific markers with immunofluorescent staining and the results showed that partial ORS cells could express hair follicle stem cell markers of CK15, CK19 and FST. At last, ORS cells and fibroblasts were used as seed cells and preliminarily constructed tissue engineering skin successfully. In conclusion, these findings suggested that this new medium could effectively accelerate cell proliferation and maintain the fundamental characteristics of ORS cells.

The paper proposes a novel method which utilizes the garnet to realize the rheological control of the flotation pulp in fine scheelite flotation. The garnet was added in the conditioning operation of the cleaning flotation stage. Sodium oleate and water glass were used as flotation collector and depressant, respectively. Flotation tests on the cleaning flotation with different addition of garnet were conducted, coupled with rheological measurements, flotation rate calculation and optical observations on the corresponding flotation pulp and froth. It is found that there exists strong correlation among the flotation rate, pulp rheology, froth and floc morphology in the cleaning flotation. As the garnet content in the cleaning flotation pulp increases, the viscosity of the flotation pulp decreases and the flotation rate increases; the floc morphology changes from big-branch type to globule-like and the flotation froth becomes cleaner. It is also found that the changes in the fluid properties of the flotation slurry caused by the garnet addition are closely related to the flotation selectivity. As the slurry yield stress decreases and the flotation slurry deviates nearer to the Bingham fluid, the flotation rate increases and the flotation selectivity improves. The results could potentially be used to improve the flotation performance of fine scheelite ore through rheological control of flotation pulp by garnet addition in cleaning flotation operations.

In this paper, the depressant effect of the whey protein, a chelating agent for copper ions, on the flotation of copper-activated marmatite was investigated by micro-flotation, zeta potential, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). The results showed that the formation of a complex through the interaction between the copper ions and the whey protein effectively prevented the activation of marmatite from copper ions, and the flotability of the copper activated marmatite was remarkably decreased. The finding can potentially offer new choices for developing new reagents for depressing the copper-activated marmatite in flotation separation of the polymetallic sulfide ores.

Cost-effective, Pt-free catalysts possessing superior electrochemical activity and stability are highly desirable for triiodide reduction reaction in dye-sensitized solar cells (DSCs). Herein, CoSe2 nanoparticles embedded in porous carbon shells (CoSe2/CS) were explored as highly efficient catalysts toward triiodide reduction reaction. The CoSe2/CS composites were fabricated using a soft-template approach involving the carbonization and selenization processes. The CoSe2 nanoparticles were well distributed within highly graphitized nitrogen-doped carbon nanoshells. More importantly, the CoSe2/CS catalysts presented both high catalytic performance and long-term stability, outperforming those of the thermally-deposited Pt electrode. Furthermore, the optimized DSC device with a CoSe2/CS catalyst-based counter electrode showed a power conversion efficiency of 7.54%, exceeding that of the thermally-deposited Pt (7.40%) counterpart. The enhanced catalytic activity, long-term stability and photovoltaic efficiency can be attributed to the much more reaction sites provided by CoSe2 nanoparticles embedded within the porous carbon shells, as well as the better band matching with the potential of the I3−/I− redox couple, revealed by the Kelvin probe force microscope measurement. This work will provide a strategy to construct low-cost, highly efficient and stable non-Pt catalysts for photovoltaic applications.

Background: Angiogenesis is an important process facilitating the growth of glioblastoma (GBM). It also has drawn great attention in the treatment of GBM. GBM angiogenesis is closely related to the function of endothelial cells. microRNAs can affect the activities of endothelial 10 cells directly, or indirectly through the interaction of tumor cells and endothelial cells. However, the mechanism underlying the interaction of GBM cells regulated by specific microRNA with endothelial cells and following angiogenesis requires further research. In published articles, microRNA-16 acted as a tumor suppressor in multiple types of cancers including glioma, but the role in glioma angiogenesis has not been well elucidated. Methods: The expression of microRNA-16 was detected in human GBM samples and normal brain tissues. microRNA-16 was transfected to GBM cell line U87 and A172 then the function of endothelial cells co-cultured with U87/A172 (miR-16 or control) were observed in vitro. Expression of VEGF family in vitro and the effect of microRNA-16 on GBM angiogenesis in vivo were also investigated. Results: microRNA-16 is down-regulated in human GBM samples in contrast to the normal brain tissues. Overexpression of microRNA- 16 in the A172 and U87 GBM cell lines inhibited the activities of co-cultured endothelial cells, including proliferation, migration, extension and tubule formation. Further experiments of dual luciferase assays verified microRNA-16 directly targeting Bmi-1. microRNA-16 down-regulated the expression of vascular endothelial growth factor VEGF-A and VEGF- C which were closely related to the angiogenesis of GBM. Moreover, less vascular formed in the section of neoplasm of the microRNA- transduced group than the control group in vivo. Conclusions: Collectively, these findings indicate that loss of microRNA-16 may favor glioma angiogenesis, on the contrary overexpression of microRNA-16 in GBM cells plays a critical role in repressing endothelial function and angiogenesis by targeting Bmi-1. microRNA-16 may be a potential therapeutic agent in the treatment of GBM.

The depressant effect of sodium alginate on galena flotation in different collector systems was investigated, mainly through micro-flotation tests, zeta potential measurements and molecular dynamics simulations. The micro-flotation results showed that the depressant effect of sodium alginate depended largely on collector type. Galena flotation was effectively and totally depressed by sodium alginate when ammonium dibutyl dithiophosphate acted as collector. When diethyldithiocarbamic acid cyanoethyl ester acted as collector, sodium alginate could only partly inhibit the galena flotation. However, when butyl xanthate acted as collector, sodium alginate could not exhibit any depressant effect on galena flotation. The zeta potential measurement results indicated that these reagents could adsorb on galena surface at different degree of strength and could further result in subsequent different flotation behaviors. The molecular dynamics simulation results demonstrated that the adsorption ability between galena surface and reagents could rank as butyl xanthate > sodium alginate > diethyldithiocarbamic acid cyanoethyl ester > ammonium dibutyl dithiophosphate, which further determined the depressant effect differences. The results could be potentially used for selecting suitable collector type in some sulfide ore flotation plants when sodium alginate acted as galena depressant.

The effect of Polygonum multiflorum against hair loss has been widely recognized. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is the main component of Polygonum multiflorum; however, its role in hair regeneration has not been established. To evaluate the hair growth-promoting activity of TSG, depilated C57BL/6J mice were topically treated with normal saline, TSG, Pifithrin-α, Minoxidil for 2 weeks. In this study, we identified that p53, Caspase-3, Active Caspase-3, and Caspase-9 were obviously upregulated in the skin of human and mice with hair loss by western blot analysis. Depilated mice treated with TSG showed markedly hair regrowth. TUNEL+ cells were also reduced in mice with TSG. These changes were accompanied with inhibition of Fas, p53, Bax, Active Caspase-3, and Procaspase-9 activities. These results demonstrated that TSG exerts great hair regrowth effect on hair loss, which was probably mediated by inhibition of p53, Fas, and Bax induced apoptosis.

In this paper, sodium alginate was put forward as a flotation depressant for selectively separating the chalcopyrite from galena. The effects of the sodium alginate on the flotation performance of chalcopyrite and galena were studied using ammonium dibutyl dithiophosphate as the collector. The adsorption behaviors of sodium alginate on the mineral surfaces were investigated through surface analysis including zeta potential, FTIR spectra and XPS spectra analysis. The micro-flotation results showed that sodium alginate exhibited selective and strong depressant effect on the galena flotation while had little influence on the chalcopyrite flotation, whether it was added before or after the collector. The surface analysis results demonstrated that sodium alginate could selectively adsorb on the galena surface and then hinder the subsequent collector adsorption thus resulting in the hydrophilic galena surface. The selective adsorption mainly consisted of the interactions between the Pb2+ on the galena surface and the functional groups in sodium alginate. Sodium alginate did not adsorb on chalcopyrite surface or interfere with the collector coverage on chalcopyrite surface. Based on these findings, a possible adsorption model of the sodium alginate on the water-solid interface of the two minerals was proposed. The paper shows that sodium alginate has the potential to act as an effective, non-toxic depressant in the flotation of Cu-Pb polymetallic sulphide ores.

Tissue-engineered epidermal membranes are useful for clinical wound healing. To facilitate these products in the clinic, optimized storage methods need to be developed. We studied the efficiency of extracellular trehalose at various concentrations for cryopreserving human tissue-engineered epidermal membranes compared with that of dimethyl-sulfoxide (DMSO) used by most organ banks for cryopreserving skin grafts and artificial skin substitutes. Keratinocyte (KC) viability, proliferation and marker expression following cryopreservation in trehalose were examined with similar results to those using DMSO. Trehalose concentration (0.4m) was optimized according to the described cellular activities following cryopreservation. Artificial epidermal substitutes were then cryopreserved in trehalose at the optimized concentration. Cell viability, growth factor secretion and wound healing properties of cryopreserved artificial epidermal substitutes using nude mice were examined and compared with those of DMSO cryopreservation. Cryopreservation with trehalose enhanced human KC viability in suspension and artificial skin substitutes. In addition, trehalose cryopreservation provided fast recovery of EGF and TGF-β1 secretion by KCs after thawing. When transplanted into nude mice, trehalose-cryopreserved artificial skin repaired skin defects in a similar manner to that of a non-cryopreserved control. Moreover, trehalose-cryopreserved artificial skin resulted in engraftment and wound closure that was significantly enhanced compared with that of DMSO-cryopreserved epidermal membranes. The results indicate that the use of trehalose improves cryopreservation of tissue-engineered epithelial sheets.

Background: This study aims to quantify by intravital microscopy the microhemodynamic response after extracorporeal shock wave application (ESWA) to the physiologic microcirculation of the mouse dorsal skinfold chamber. Materials and Methods: ESWA was carried out using an electrohydraulic shock wave source. Two different shock wave doses of 500 and 1000 pulses at an energy flux rate of 0.08 mJ/mm2 and a frequency of 4 Hz were compared with sham-operated animals. Microcirculatory analyses were performed at baseline (BL) and during a 3 d observation period after ESWA. The expression of caspase-3 (casp-3), proliferating cell nuclear antibody (PCNA), von Willebrand factor (vWF), and endothelial nitric oxide synthase (eNOS) were analyzed semiquantitatively by immunohistochemistry. Results: ESWA provoked a significant and persistent increase of functional capillary density (FCD) throughout the observation period, reaching a maximum (140% ± 5% of BL, P < 0.05 versus sham) after 1 d when animals were treated with 1000 pulses. ESWA induced a slight increase of leukocyte rolling (not, vert, similar2- to not, vert, similar3.5-fold, P < 0.05) and leukocyte adherence (not, vert, similar1.5- to not, vert, similar2-fold, P < 0.05) to the endothelial lining of postcapillary venules. One day following ESWA, we observed enhanced expression of casp-3 (not, vert, similar3- to not, vert, similar4-fold), PCNA (not, vert, similar9- to not, vert, similar14-fold), vWF (not, vert, similar11- to not, vert, similar14-fold), and eNOS (not, vert, similar3-fold), all P < 0.05. Conclusion: This study shows that ESWA provokes a favorable persistent increase of patent capillaries, however accompanied by a transient and slight inflammatory response but also by dose-dependant apoptotic cell death. Our data suggest that ESWA might represent a noninvasive biomechanical tool to treat critically perfused and endangered tissues, but certainly warrants further investigation.

Microglia are the primary immunocompetent cells in brain tissue and microglia-mediated inflammation is associated with the pathogenesis of various neuronal disorders. Recently, many studies have shown that mesenchymal stem cells (MSCs) display a remarkable ability to modulate inflammatory and immune responses through the release of a variety of bioactive molecules, thereby protecting the central nervous system. Previously, we reported that MSCs have the ability to modulate inflammatory responses in a traumatic brain injury model and that the potential mechanisms may be partially attributed to upregulated TNF-α stimulated gene/protein 6 (TSG-6) expression. However, whether TSG-6 exerts an anti-inflammatory effect by affecting microglia is not fully understood. In this study, we investigated the anti-inflammatory effects of MSCs and TSG-6 in an in vitro lipopolysaccharide (LPS)-induced BV2 microglial activation model. We found that MSCs and TSG-6 significantly inhibited the expression of pro-inflammatory mediators in activated microglia. However, MSC effects on microglia were attenuated when TSG-6 expression was silenced. In addition, we found that the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) pathways in LPS-stimulated BV2 microglial cells was significantly inhibited by TSG-6. Furthermore, we found that the presence of CD44 in BV2 microglial cells was essential for MSC- and TSG-6-mediated inhibition of pro-inflammatory gene expression and of NF-κB and MAPK activation in BV2 microglial cells. The results of this study suggest that MSCs can modulate microglia activation through TSG-6 and that TSG-6 attenuates the inflammatory cascade in activated microglia. Our study indicates that novel mechanisms are responsible for the immunomodulatory effect of MSCs on microglia and that MSCs, as well as TSG-6, might be promising therapeutic agents for the treatment of neurotraumatic injuries or neuroinflammatory diseases associated with microglial activation.

Many studies have shown that microglia in the activated state may be neurotoxic. It has been proven that uncontrolled or over-activated microglia play an important role in many neurodegenerative disorders. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown in many animal models to have a therapeutic effect on neural damage. Such a therapeutic effect is attributed to the fact that BMSCs have the ability to differentiate into neurons and to produce trophic factors, but there is little information available in the literature concerning whether BMSCs play a therapeutic role by affecting microglial activity. In this study, we triggered an inflammatory response situation in vitro by stimulating microglia with the bacterial endotoxin lipopolysaccharide (LPS), and then culturing these microglia with BMSC-conditioned medium (BMSC-CM). We found that BMSC-CM significantly inhibited proliferation and secretion of pro-inflammatory factors by activated microglia. Furthermore, we found that the phagocytic capacity of microglia was also inhibited by BMSC-CM. Finally, we investigated whether the induction of apoptosis and the production of nitric oxide (NO) were involved in the inhibition of microglial activation. We found that BMSC-CM significantly induced apoptosis of microglia, while no apoptosis was apparent in the LPS-stimulated microglia. Our study also provides evidence that NO participates in the inhibitory effect of BMSCs. Our experimental results provide evidence that BMSCs have the ability to maintain the resting phenotype of microglia or to control microglial activation through their production of several factors, indicating that BMSCs could be a promising therapeutic tool for treatment of diseases associated with microglial activation.