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Graphical abstract Solvent-free ionic GO@SiO 2 nanofluids: promising lubricating additive. Highlights • GO@SiO 2 NFs were synthesized by functionalizing hybrid NPs with corona and canopy. • GO@SiO 2 NFs as lubricant additives exhibit extraordinary lubrication performance. • A tribofilm grew in-situ when NFs were fed continuously onto the contact zone. • Graphitized GO and SiO 2 digested in tribofilm enhanced lubricity and robustness. Abstract Solvent-free ionic nanofluids (NFs) of graphene oxide-silica hybrid nanocores (GO@SiO 2) were synthesized for the first time via functionalizing in succession the nanocores with a covalently charged corona and an ionically tethered oligomeric canopy. Being intrinsically one-component materials, GO@SiO 2 NFs display a liquid-like behavior in the absence of any solvent and show excellent dispersion stability in polyethylene glycol (PEG) base oil. Adding even small amount of GO@SiO 2 NFs improved dramatically the lubrication performance of PEG base oil. It was revealed that GO@SiO 2 NFs played an important role in physicochemical actions on the friction interface. This work provided direct evidence that a protective tribofilm grew on the sliding surfaces when molecular species of GO@SiO 2 NFs were fed continuously onto the contact zone. In particular, graphitized GO and SiO 2 nanoparticles digested in the tribofilm enhanced its lubricity and robustness. It is expected that solvent-free ionic GO@SiO 2 NFs open up new opportunities for developing advanced lubricating nanomaterials. [ABSTRACT FROM AUTHOR]

Solid tribofilm plays a vital role in lubricating and separating friction pairs during relative movement especially under mixed/boundary conditions. However, the present of the ultra-low sulfur diesel retrogrades the formation of the high-performance tribofilm on the counter steel. Two-dimensional (2D) transition metal carbides, carbonitrides or nitrides (MXene) with abundant surface functional groups are promising for forming robust tribofilm at the sliding interface when adding it into self-lubricating polymer. Herein, the design of MXene/epoxy (EP) nanocomposites with enhanced tribology performance is reported. Furthermore, we demonstrated an efficient approach for realizing superlubricity and extraordinary low wear rates (97% off) by incorporating 0D Al 2 O 3 and 2D MXenes. Here, we ascribed the splendid tribological properties to the hybrid tribofilm which can effectively avoid direct contact of the friction pairs. This study provides a basis for exploring the structure-properties relationship of tribofilms, also exploring the potentials of MXene for developing advanced functional materials. Image 1 • Tribological mechanisms of EP composites lubricated by ULSD were studied. • MXene is promising for forming robust tribofilm at the sliding interface. • Superlubricity was realized by incorporating MXene, Al 2 O 3 and EP resin. • MXene-Al 2 O 3 has a synergistic effect on reducing wear rate of EP by 97% off. • Hybrid nanostructure tribofilm is crucial on enhancing tribological performance. [ABSTRACT FROM AUTHOR]

Tribological behaviors of carbon fibers (CF) reinforced poly-ether-ether-ketone (PEEK) composites are investigated at low speeds ranging from 0.01 to 0.2 m/s under pressures varying from 1 to 30 MPa. Nano-Bi 2 O 3 , nano-SiO 2 and conventional solid lubricants (graphite and polytetrafluoroethylene) are further added into CF-reinforced PEEK, respectively. It is demonstrated that a small load and relatively high speed are favorable for the wear-reduction role of nano-Bi 2 O 3 , while the positive role of nano-SiO 2 is pronounced at a high load and speed. Friction and wear-reduction roles of the solid lubricants are the most significant at low load and low speed. It turns out that functionalities of the fillers are closely associated with their roles in tribofilm growth governed by complex physical and chemical actions. • Tribological mechanisms of PEEK composites at relatively low speeds were studied. • Nano-Bi 2 O 3 reduces wear of CF/PEEK at speeds higher than 0.05 m/s under 1 MPa. • Nano-SiO 2 enhances wear resistance of CF/PEEK at a high load and 0.1 m/s. • Graphite/PTFE plays an excellent lubrication role at the low speed range studied. • Tribological performance of the materials is closely related to tribofilm growth. [ABSTRACT FROM AUTHOR]

In this study, we observed a great reduction in the expression of the endogenous long noncoding RNA ROR (lncRNA-ROR) and the stem cell transcription factor Sox2, in contrast to a marked increase in miR-145 expression, during the course of in vitro induced differentiation of human amniotic epithelial stem cells (HuAECs). Bioinformatics analysis and the luciferase reporter assay revealed binding of miR-145 to specific sites in lncRNA-ROR and Sox2, silencing their expression. Overexpression of a lncRNA-ROR-specific siRNA effectively downregulated the expression levels of Sox2 and other stem cell markers in HuAECs while weakening the efficiency of HuAEC differentiation into β islet-like cells. Moreover, the in vitro response of HuAEC-derived β islet-like cells to extracellular stimuli and C-peptide release by these cells were markedly weakened in the siRNA-ROR transfection group. Furthermore, the in vivo expression of β islet-like cell biomarkers was substantially reduced in HuAECs in the siRNA-ROR transfection group, and their in vivo β islet-like cell differentiation and insulin release capacities were reduced in a streptozocin-induced diabetic rat model. The experimental results indicate that lncRNA-ROR effectively maintains Sox2 gene expression through competitive binding to miR-145, achieving pluripotency maintenance in HuAECs and regulation of their directed β islet-like cell differentiation efficiency. [ABSTRACT FROM AUTHOR]

The loss of photoreceptors is a major event of retinal degeneration that accounts for most cases of untreatable blindness globally. To date, there are no efficient therapeutic approaches to treat this condition. In the present study, we aimed to investigate whether human amniotic epithelial stem cells (hAESCs) could serve as a novel seed cell source of photoreceptors for therapy. Here, a two–step treatment with combined Wnt, Nodal, and BMP inhibitors, followed by another cocktail of retinoic acid, taurine, and noggin induced photoreceptor–like cell differentiation of hAESCs. The differentiated cells demonstrated the morphology and signature marker expression of native photoreceptor cells and, intriguingly, bore very low levels of major histocompatibility complex (MHC) class II molecules and a high level of non–classical MHC class I molecule HLA–G. Importantly, subretinal transplantation of the hAESCs–derived PR–like cells leads to partial restoration of visual function and retinal structure in Royal College of Surgeon (RCS) rats, the classic preclinical model of retinal degeneration. Together, our results reveal hAESCs as a potential source of functional photoreceptor cells; the hAESCs–derived photoreceptor–like cells could be a promising cell–replacement candidate for therapy of retinal degeneration diseases. [ABSTRACT FROM AUTHOR]

Xenotransplantation from pigs to human beings is viewed as a potential solution for the acute organ shortage. However, consequent xenorejection induced by Gal alpha 1,3 Gal (a Gal, Gal antigen) prevents xenotransplantation from clinical application. Thus, the most attracting attempt to prevent xenorejection is the elimination of Gal. Our study suggested that compared with the human alpha 1,2 fucosyltransferase (FT) gene and the porcine antisense alpha 1,3 galactosyltransferase gene, sequence-specific siRNA targeting Gal was capable of suppressing Gal expression markedly, and therefore, significantly inhibiting xenoreactivity and the complement activation with human serum in PIEC cells. We also demonstrated the concordant inhibitory effect of siRNA and the human FT gene on Gal and corresponding functions, which implied a practical significance of combined transgenic strategy. The successful application of vector-based dsRNA-GT may extend the list of available modalities in the abrogation of xenorejection in xenotransplantation. [ABSTRACT FROM AUTHOR]

• Rheological properties of composite hydrogels were studied systematically for printing. • High printing precision (151 ± 13.04 μm) and structural fidelity were achieved. • A low temperature (4 °C) chamber was responsible for rapid solidification for complex constructs. • Human AECs and WJMSCs were bioprinted as seed cells to form bilayered skin-like constructs. Extrusion-based 3D bioprinting of cell-laden hydrogels is a potential technology for regenerative medicine, which enables the fabrication of constructs with spatially defined cell distribution. However, the limited assessment of rheological behaviors of hydrogel before printing is still a major issue for the advancement of 3D bioprinting. In this work, we systematically investigated the rheological behaviors (i.e. viscosity, storage modulus (G'), and loss modulus (G")) of alginate/gelatin composite hydrogels first for 3D printing complex constructs. The rheological studies revealed that viscosity of alginate/gelatin hydrogels is temperature-dependent and shear thinning. Sol-gel transition (intersection of G' and G") study provided indication for printing temperature, which are in the range of 18.8 °C (H2/7.5) to 24.5 °C (H2/24.5). The alginate (2 wt%) /gelatin (15 wt%) composite hydrogel sample was chosen to print the constructs and subsequent bioprinting. Complex constructs (i.e. nose and ear) were obtained with high printing resolution (151 ± 13.04 μm) in a low temperature (4 °C) chamber and crosslinking with 2 wt% CaCl 2 subsequently without extra supports. Human amniotic epithelial cells (AECs) showed superior potential to differentiate into epithelial cells, while Wharton's jelly derived mesenchymal stem cells (WJMSCs) showed a superior angiogenic potential and fibroblastic phenotype. For the in vitro study, AECs and WJMSCs as seed cells, encapsulated in alginate/gelatin composite hydrogels, were bioprinted to form biomimetic bilayered membranous construct. High cell viability (> 95%) were observed up to 6 days after printing. The presented 3D bioprinting of human AECs and WJMSCs-laden alginate/gelatin composite hydrogels provides promising potentials for future skin tissue engineering. [ABSTRACT FROM AUTHOR]

Polymer nanocomposites are key materials in the development of flexible microelectronic devices based on polymer engineering and technology. In this work, CCTO/ABS and CCTO/ABS/PVDF nanocomposites were prepared by solution blending method using acrylonitrile(A)-butadiene(B)-styrene(S) (ABS) and polyvinylidene fluoride (PVDF) with low cost and low dielectric loss as the polymer matrix, and the one-dimensional nano ceramic CaCu 3 Ti 4 O 12 (CCTO) with ultrahigh dielectric constant as the filler. The morphology of nanocomposites were analyzed and the dielectric properties were studied based on the percolation theory. The scanning electron microscope showed that the CCTO filler had strong compatibility with the polymer matrix, most fillers can be uniformly distributed in the polymer matrix. When the volume fraction of CCTO reaches the percolation threshold of 23 vol%, the dielectric constant of the composite reaches the maximum. The dielectric constant of CCTO/ABS and CCTO/ABS/PVDF is 15.7 and 35.2, respectively, at 102 Hz with the corresponding dielectric loss is 0.07 and 0.23. The addition of ABS can effectively reduce the dielectric loss of composites by 50 % compared to CCTO/PVDF at the same dielectric constants. Introducing PVDF appropriately in CCTO/ABS can obtain a higher dielectric constant and also improve the flexibility of the composite. The research results indicate that CCTO/ABS/PVDF composites with excellent performance can provide reference for the preparation of thin film capacitors. [Display omitted] • One-dimensional nanowires with high aspect ratio have significant advantages in improving the dielectric properties of polymer matrix composite. • The ABS can effectively reduce the dielectric loss of composites by 50 % compared to CCTO/PVDF at the same dielectric constants. • The CCTO/ABS/PVDF composite materials can be prepared on a large scale, which is beneficial for practical applications. [ABSTRACT FROM AUTHOR]

Abstract Background aims The chronic inflammation of autoimmune diseases develops repetitive localized destruction or systemic disorders, represented by Hashimoto's thyroiditis (HT) and Systemic lupus erythematosus (SLE) respectively. Currently, there are no efficient ways to treat these autoimmune diseases. Therefore, it is critically important to explore new therapeutic strategies. The aim of this study was to investigate the therapeutic efficacy of human amniotic epithelial cells (hAECs) in murine models of HT and SLE. Methods Experimental autoimmune thyroiditis (EAT) was induced in female CBA/J mice by immunization with porcine thyroglobulin (pTg). hAECs were intravenously administered at different time points during the disease course. MRL-Fas lpr mice, a strain with spontaneously occurring SLE, were intravenously administered hAECs when their sera were positive for both anti-nuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies. Two weeks after the last cell transplantation, blood and tissue samples were collected for histological examination and immune system analysis. Results hAECs prevented lymphocytes infiltration into the thyroid and improved the damage of thyroid follicular in EAT mice. Correspondingly, hAECs administration reduced anti-thyroglobulin antibodies (TGAb), anti-thyroid peroxidase antibodies (TPOAb) and thyroid stimulating hormone (TSH) levels. SLE mice injected with hAECs appeared negative for ANAs and anti-dsDNA antibodies and showed reduced immunoglobulin profiles. Mechanically, hAECs modulated the immune cells balance in EAT and SLE mice, by downregulating the ratios of Th17/Treg cells in both EAT and SLE mice and upregulating the proportion of B10 cells in EAT mice. This was confirmed by in vitro assay, in which hAECs inhibited the activation of EAT mice-derived splenocytes. Moreover, hAECs improved the cytokine environment in both EAT and SLE mice, by suppressing the levels of IL-17A and IFN-γ and enhancing TGF-β. Conclusion These results demonstrated the immunoregulatory effect of hAECs for inflammation inhibition and injury recovery in HT and SLE murine models. The current study may provide a novel therapeutic strategy for these autoimmune diseases in clinic. [ABSTRACT FROM AUTHOR]

In the pathogenesis of acute kidney injury (AKI), the release of multiple interleukins can lead to increased kidney damage. Human amniotic epithelial cells (HuAECs) can inhibit immune cell activation in vivo and in vitro. We hypothesized that HuAECs could weaken patient-derived peripheral blood CD4+ T-cell activation and decreasing the ability of these cells to express and release IL-2. −Cell proliferation assay revealed that under the same culture conditions, activated AKI patient-derived CD4+ T cells had a significantly reduced proliferation rate when were co-cultured with HuAECs. And the level of IL-2 released was also significantly reduced. Western blot and qRT-PCR assays showed that the expression of c-Rel in the CD4+ T cells was also significantly reduced. However, the expression level of endogenous miR-101 in the CD4+ T cells co-cultured with HuAECs was significantly increased. Luciferase reporter assay results suggested that miR-101 could bind to a specific site in the c-Rel 3′ UTR and induce the post-transcriptional silencing of c-Rel. Subsequently, we over-expressed miR-101 in AKI patient-derived CD4+ T cells. The qRT-PCR and western blot assay results revealed that the expression of endogenous c-Rel was significantly reduced, while the ELISA results indicated that the level of IL-2 released was also significantly decreased. Finally, ChIP-PCR assay results showed that the miR-101-overexpressing CD4+ T-cell group and the HuAEC co-culture CD4+ T-cell group exhibited significantly decreased binding capacities between the ‘c-Rel-NFκB’ complex and the IL-2 gene promoter, and the transcriptional activity of IL-2 was also significantly decreased. Therefore, we confirmed that HuAECs can stimulate miR-101 expression in AKI patient-derived peripheral blood CD4+ T cells, thus inhibiting the expression of the miR-101 target gene c-Rel and leading to a reduction in IL-2 expression and release. [ABSTRACT FROM AUTHOR]

Improving thermal conductivity is critical for tribological performance but remains a challenge. Here, a 3D structure with layered features is fabricated by electrostatic assembly of h - BN and GO nanosheets. The strategy for structural adjustment from macro to microscopic is beneficial for efficient phonon transport by reducing interfacial thermal resistance, which in turn promotes friction-reduction and wear resistance performance based on "synergistic lubrication". The superiority of the strategy is directly reflected in the excellent self-lubricating, wear-resistance properties, and outstanding thermal conductivity enhancement (1039.16 %) of the composite. Significantly, the comprehensive properties of epoxy-based composites are closely related to macro- and microgeometry of GO and h -BN, helping to reveal the relation between the structural design of multicomponent 2D fillers and tribology-based multifunctionality. [Display omitted] [ABSTRACT FROM AUTHOR]

Emerging evidence suggests amniotic epithelial cells (AECs) as a promising source of progenitor cells in regenerative medicine and bone tissue engineering. However, investigations comparing the regenerative properties of AECs with other sources of stem cells are particularly needed before the feasibility of AECs in bone tissue engineering can be determined. This study aimed to compare human amniotic epithelial cells (hAECs), human bone marrow mesenchymal stem cells (hBMSCs), and human amniotic fluid derived mesenchymal stem cells (hAFMSCs) in terms of their morphology, proliferation, immunophenotype profile, and osteogenic capacity in vitro and in vivo. Not only greatly distinguished by cell morphology and proliferation, hAECs, hAFMSCs, and hBMSCs exhibited remarkably different signature regarding immunophenotypical profile. Microarray analysis revealed a different expression profile of genes involved in ossification along the three cell sources, highlighting the impact of different anatomical origin and molecular response to osteogenic induction on the final tissue-forming potential. Furthermore, our data indicated a potential role of FOXC2 in early osteogenic commitment. [ABSTRACT FROM AUTHOR]

The effects of proton irradiation on the tribological performance of polyimide (PI) composites filled with carbon nanotubes (CNTs) were explored. The results demonstrate that incorporating CNTs into PI decreased the friction coefficients of the composites after they were exposed to proton irradiation. In particular, the addition of 1.0 wt% CNT reduces the friction coefficient by up to 58.8%, which is attributed to the generation of a protective tribofilm. Further analysis of FIB-TEM images demonstrates that polymers and hydrogenated amorphous carbon promote the tribofilm growth, and improve the lubrication properties of the composites. Whereas, the proton radiation-induced mechanical changes result in the poor wear resistance of the PI composites. • Proton irradiation improved the nano-mechanical properties of polyimide samples. • Adding carbon nanotubes reduced the friction coefficient of irradiated composites. • Proton irradiation benefited to the formation of a uniform tribofilm. [ABSTRACT FROM AUTHOR]

The friction coefficients of composites prepared by traditional fillers and structure design are usually uncontrollable, which gradually cannot meet the requirements of intelligent response behavior in the modern manufacturing industry. Hence, an epoxy, graphene oxide, and paraffin wax composite (GPEP@ PW) with a network-like sandwich structure was prepared by a four-step method (template method-vacuum impregnation-de-template-vacuum impregnation). Due to sensitive photothermal conversion of GO and excellent ability to control heat (absorption and release) of paraffin wax, GPEP@ PW can respond to near-infrared light to realize the real-time conversion of friction coefficient (0.052 and 0.062), while the wear rate was reduced by two orders of magnitude rate (10−4 to 10−6 mm3/N·m). The light response behavior of tribology under different near-infrared intensities was studied. This strategy is simple and versatile, providing a new idea for the design and preparation of light stimulus-responsive materials to achieve smart tribological properties. [Display omitted] • Ternary hybrid composite with 3D sandwich structure was prepared by a four-step method. • Real-time controllable friction was achieving by structural functionalized photothermal conversion of GO. • The COF changed between 0.052 and 0.062 with NIR switching on and off. • Extremely low wear rate (3.33 × 10−6 mm3/N.m) was got by synergy in GO and paraffin wax. [ABSTRACT FROM AUTHOR]

Ovarian cancer comprises a small population of cancer stem cells (CSCs) that are responsible for tumor maintenance and resistant to cancer therapies, it would be desirable to develop a therapy that could selectively target ovarian CSCs. Recently, cellular immune-based therapies have improved the prognosis of cancer patients clinically. In this study, we isolated a subset of ovarian cancer sphere cells that possess CSC properties and explored the cell cytotoxicity of γδ T cells to ovarian cancer sphere cells using a transwell cocultured cell system. The proliferation rate of the cancer sphere cells decreased to 40% after cocultured with γδ T cells. The γδ T cells increased the sensitivity of SK-OV-3 sphere cells to chemotherapeutic drugs. After the treatment of γδ T cells, the expression of stem cell marker genes decreased in sphere cells, while the expression of HLA-DR antigen on tumor cells was increased in a time-dependent manner. Further, γδ T cells induced G2/M phase cell cycle arrest and subsequent apoptosis in SK-OV-3 sphere cells. Xenograft mouse models demonstrated that γδ T cells dramatically reduced the tumor burden. Notably, the level of IL-17 production significantly increased after cocultured with γδ T cells. We conclude that γδ T cells may efficiently kill ovarian CSCs through IL-17 production and represent a promising immunotherapy for ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. [Copyright &y& Elsevier]

Abstract: Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene. Methods: HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay. Results: HepG2/NTG cells concentrated 125I− up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T 1/2eff of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or 131I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%±2.5%, 43.4%±2.8% and 8.6%±1.2% after exposure to 131I, GCV and combined therapy, respectively. Conclusion: We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings. [Copyright &y& Elsevier]

Abstract: Luteolin, 5,7-dihydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one, has been proposed and proved to be a novel dopamine transporter (DAT) activator. In order to develop this potential of luteolin, a series of novel luteolin derivatives were designed, synthesized, and evaluated for their DAT agonistic activities, utilizing constructed Chinese hamster ovary (CHO) cell lines stably expressing rat DAT. Biological screening results demonstrated that luteolin derivatives 1d, 1e, and 4c carry great DAT agonistic potency (EC50 =0.046, 0.869, and 1.375μM, respectively) compared with luteolin 8 (EC50 =1.45±0.29μM). Luteolin derivative 1d, notably, exhibited a 32-fold-higher DAT agonistic potency than luteolin. These luteolin derivatives represent a novel DAT agonist class, from which lead compounds useful for exploration of additional novel DAT agonists could be drawn. [ABSTRACT FROM AUTHOR]

We explored the effects on brain oedema and neurological functional recovery after transplantation of hAECs (human amniotic epithelial cells) into the lateral ventricle of rats with ICH (intracerebral haemorrhage). hAECs were isolated from human term placenta and seeded for primary culture. We delivered hAECs labelled with Hoechst33258 and transfected with EGFP (enhanced green fluorescent protein) gene using lentiviral vectors into ICH rat models. The behaviour of the animals and brain oedema were evaluated after 28 days, and brain sections were made for morphological and immunohistochemical analyses with fluorescence microscopy. Our results were as follows. Transplanted hAECs were observed along the lateral wall and survived for at least 4 weeks. Some of the cells were stained with human specific antibody to vimentin and nestin. Around the injury site, activated microglia stained with OX42 were reduced. The water content of ICH rats decreased in the treatment group. The behaviour test scores were improved in the treatment group compared with those in the control groups. In conclusion, hAECs cannot only survive in the lateral ventricle of ICH rats after transplantation, but also express vimentin and nestin. hAEC transplantation reduced brain oedema and improved the motor deficits of ICH rats. [ABSTRACT FROM AUTHOR]

The present study was carried out to identify GABA (γ-aminobutyric acid) transport protein I (GAT1) in male reproductive organs and to study the effect of GAT1 overexpression on the male reproductive system in GAT1 transgenic mice (TG). Expression and location of GAT1 in testes, epididymis, and sperm of wild-type (WT) mice were identified by immunohistochemistry and western-blot. Histological changes of testes, epididymis, and sperm of transgenic mice overexpressing GAT1 were detected by immunofluorenscent staining and haematoxylin and eosin (HE) staining. GAT1 expression was detected in the testes, epididymis, and sperm of non-transgenic mice. Vacuolization and deformity of spermatogenic cells were observed in the transgenic mice, but the epididymis was unremarkable. Immunofluorenscent staining showed that the number of diastrophic and decapitated sperm increased significantly in transgenic mice to 46.9% from 7.3% in nontransgenic mice. These results suggest that abnormal expression of GAT1 could result in spermiogenesis function injury, sperm paramorphia and dysgenesis. [ABSTRACT FROM AUTHOR]

Abstract: Preparation for the N-alkylated derivatives of enantiomerically pure (2S)-4-fluoroproline and (2S)-4-fluoropyrrolidine-2-acetic acid is described. The final compounds were evaluated as potential GAT-1 uptake inhibitors via cultured cell lines expressing mouse GAT-1. Compared with their corresponding 4-hydroxy compounds, these derivatives exhibited slight improvement on their inhibitory potency, but still much weaker than their corresponding compounds with no substituents at the C-4 of the pyrrolidine moiety, with the most potent affinity being about 1/15 fold as that of Tiagabine. The drastic decrease of their affinity may arise from sharp reduction of their basicity due to strong inductive effect of the 4-fluorine. However the configuration of the C-4 linking fluorine did not have much influence on their affinity for GAT-1. [Copyright &y& Elsevier]

Abstract: Hyperproliferation of synovial fibroblasts is considered to be a pivotal event in the pathogenesis of rheumatoid arthritis (RA). Luteolin, a flavonoid, inhibits the proliferation of synovial fibroblasts in collagen-induced arthritic rats. Treatment with luteolin also decreases the secretion of matrix metalloprotease-1 and -3 and the expression of IL-6, IL-8, IL-15, and TGF-β. Luteolin treatment caused a delay of cells in the G2/M phase. Interestingly, combination treatment with luteolin and TNF-α exhibited a synergistic inhibitory effect in all experiments. Western blotting demonstrated that treatment with luteolin alone or combined with TNF-α inhibited the MAPK/ERKs and PI3K-Akt pathways. These results indicate that luteolin inhibits the proliferation and partially blocks the pathogenic function of synovial fibroblasts in rheumatoid arthritis. [Copyright &y& Elsevier]

Abstract: The deficits due to global cerebral ischemia show a close correlation with hippocampal CA1 neurons damage. Here we presented that galantamine showed effective protection against ischemic insults. In a transient brain global ischemic model conducted in gerbils, we investigated the alterations of performance in passive avoidance test and the histological changes between sham-operated animals (as controls) and those received post-ischemic continuous administration of saline (vehicle) or galantamine. Compared to the controls, gerbils received ischemic insults with saline treatment showed significant impairment in performance in passive avoidance test and dramatic loss of cells in hippocampal CA1 region. However, gerbils that received the same insults with galantamine (2mg/kg/day) treatment performed similarly to the controls. Consistently, most of the cells in hippocampal CA1 region which were vulnerable to ischemic insults, survived after galantamine treatment. Our results suggested that continuous application of galantamine might be effective in treatment of ischemic injury. [Copyright &y& Elsevier]

The excitatory amino acid transporter EAAC1 is an electrogenic Na+- and K+-gradient-driven transporter. In addition, the transporter mediates in the presence of Na+ and glutamate an anion conductance uncoupled from the transport of the glutamate. The first two N-terminal domains, important for forming the conductance mode, are extracellularly bordered by positively charged arginine residues, R39 and R61, being completely conserved throughout the transporter family. Also the conserved tyrosine residue Y98 could be important for Cl− conductance. We have investigated, by measurements of glutamate uptake and glutamate-induced currents, the effects of mutation of the arginines and the tyrosine to alanine. The mutation R39A hardly affects transport and channel mode. The mutation R61A, on the other hand, reduces the activity of transport but stimulates the channel conductance. In addition, the apparent Km values for glutamate uptake and for the glutamate-activated current are reduced. Glutamate stimulation of current seems to be associated with a voltage-dependent step, and the apparent valence of charge moved during binding is reduced in the R61A mutant. The mutation Y98A leads to reduced function with reduced apparent Km value for glutamate, and with strong reduction of the selectivity ration between NO3− and Cl− of the conductance mode. [Copyright &y& Elsevier]

Abstract: Twenty novel N-diarylalkenyl-piperidinecarboxylic acid derivatives were synthesized and evaluated as γ-aminobutyric acid uptake inhibitors. The biological assay showed that (R)-1-[4,4-bis(3-phenoxymethyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic hydrochloride (4e) possessed almost as strong GAT1 inhibitory activity as tiagabine. The synthesis and structure–activity relationships are discussed. [Copyright &y& Elsevier]

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and communication and stereotypical patterns of behaviors, interests, or activities. Even with the increased prevalence of ASD, there is no defined standard drug treatment for ASD patients. Currently, stem cells, including human amniotic epithelial cell (hAEC) transplantation, seem to be a promising treatment for ASD, but the effectiveness needs to be verified, and the mechanism has not been clarified. Methods: We intraventricularly transplanted hAECs into a 2-month-old BTBR T+tf/J (BTBR) mouse model of ASD. Behavior tests were detected 1 month later; hippocampal neurogenesis, neuroprogenitor cell (NPC) pool, and microglia activation were analyzed with immunohistochemistry and immunofluorescence; the levels of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were determined by real-time PCR or western blotting. Results: After intraventricular injection of hAECs into adult males, social deficits in BTBR mice were significantly ameliorated. In addition, hAEC transplantation restored the decline of neurogenesis and NPCs in the hippocampus of BTBR mice by expanding the stem cell pool, and the decreased levels of BDNF and TrkB were also rescued in the hippocampus of the hAEC-injected BTBR mice. Meanwhile, the transplantation of hAECs did not induce microglial overactivation or excessive production of pro-inflammatory cytokines in the hippocampus of BTBR mice. Conclusions: Based on these results, we found that hAEC transplantation ameliorated social deficits and promoted hippocampal neurogenesis in BTBR mice. Our study indicates a promising therapeutic option that could be applied to ASD patients in the future. [ABSTRACT FROM AUTHOR]

Culture conditions that support the growth of undifferentiated human embryonic stem cells (hESCs) have already been established using primary human amnion epithelial cells (hAECs) as an alternative to traditional mitotically inactivated mouse embryonic fibroblasts (MEFs). In the present work, inner cell masses (ICM) were isolated from frozen embryos obtained as donations from couples undergoing in vitro fertilization (IVF) treatment and four new hESC lines were derived using hAECs as feeder cells. This feeder system was able to support continuous growth of what were, according to their domed shape and markers, undifferentiated naïve-like hESCs. Their pluripotent potential were also demonstrated by embryoid bodies developing to the expected three germ layers in vitro and the productions of teratoma in vivo. The cell lines retained their karyotypic integrity for over 35 passages. Transmission electron microscopy (TEM) indicated that these newly derived hESCs consisted mostly of undifferentiated cells with large nuclei and scanty cytoplasm. The new hESCs cultured on hAECs showed distinct undifferentiated characteristics in comparison to hESCs of the same passage maintained on MEFs. This type of optimized culture system may provide a useful platform for establishing clinical-grade hESCs and assessing the undifferentiated potential of hESCs. [ABSTRACT FROM AUTHOR]