Formulation and characterization of a novel, photoinitiated small intestinal sub-mucosal wound-healing hydrogel

Purpose: To design and characterize a novel 3-D photo-initiated small intestinal sub-mucosal (SIS) hydrogel for use as a scaffold.Methods: Two concentrations of hydrogel were used: 10 mg/mL SIS gel (designated as 1 % hydrogel) and 20 mg/mL SIS gel (designated as 2 % hydrogel). Cross-sections of the hydrogels were examined by scanning electron microscope. In vitro cell culture was carried out on the hydrogels, and cell count was obtained on each hydrogel at different time points. In addition, hematoxylin-eosin (H&E) staining was used to assess in vivo biodegradability of the gels, as well as tissue regeneration.Results: The 1 % hydrogel possessed a larger pore size (143 ± 22 μm) than the 2 % hydrogel (113 ± 17 μm) and showed significantly higher biodegradation rate (22.79 ± 2.47 % of gel left on day 5) than 2% hydrogel (35.37 ± 4.51 % of gel left on day 5) (p < 0.05). However, results from cell culture showed that the 2 % hydrogel had better biocompatibility than 1 % hydrogel. In vivo data revealed that the gels supported cell growth (cell count on days 3 and 5 were 48.33 ± 17.61 and 105.67 ± 21.36, respectively).Conclusion: These results suggest that SIS hydrogels have a high potential for application in tissue regeneration.Keywords: Extracellular matrix, Small intestinal sub-mucosa, Hydrogel, Wound healin

Regulations of the key mediators in inflammation and atherosclerosis by Aspirin in human macrophages

Although its role to prevent secondary cardiovascular complications has been well established, how acetyl salicylic acid (ASA, aspirin) regulates certain key molecules in the atherogenesis is still not known. Considering the role of matrix metalloproteinase-9 (MMP-9) to destabilize the atherosclerotic plaques, the roles of the scavenger receptor class BI (SR-BI) and ATP-binding cassette transporter A1 (ABCA1) to promote cholesterol efflux in the foam cells at the plaques, and the role of NF-κB in the overall inflammation related to the atherosclerosis, we addressed whether these molecules are all related to a common mechanism that may be regulated by acetyl salicylic acid. We investigated the effect of ASA to regulate the expressions and activities of these molecules in THP-1 macrophages. Our results showed that ASA inhibited MMP-9 mRNA expression, and caused the decrease in the MMP-9 activities from the cell culture supernatants. In addition, it inhibited the nuclear translocation of NF-κB p65 subunit, thus the activity of this inflammatory molecule. On the contrary, acetyl salicylic acid induced the expressions of ABCA1 and SR-BI, two molecules known to reduce the progression of atherosclerosis, at both mRNA and protein levels. It also stimulated the cholesterol efflux out of macrophages. These data suggest that acetyl salicylic acid may alleviate symptoms of atherosclerosis by two potential mechanisms: maintaining the plaque stability via inhibiting activities of inflammatory molecules MMP-9 and NF-κB, and increasing the cholesterol efflux through inducing expressions of ABCA1 and SR-BI

Metformin promotes the survival of transplanted cardiosphere-derived cells thereby enhancing their therapeutic effect against myocardial infarction

The CDC differentiation at 4 weeks after transplantation analyzed by immunostaining. A–C: Sections of hearts were immunostained with antibodies to (A) the cardiomyocyte marker tropomyosin, (B) the endothelial cell marker von-Willebrand Factor (vWF), and (C) the smooth muscle cell marker α-smooth muscle actin (α-SMA). Antibody to GFP was used for identifying surviving CDC-derived cells and DAPI was used for identifying nuclei. Scale bars = 20 μm. DAPI 4′,6-diamidino-2-phenylindole. (PDF 178 kb

SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells

Abstract We set out to investigate whether and how SRY (sex-determining region, Y) DNAs in plasma EVs (extracellular vesicles) is involved in the pathogenesis of atherosclerosis. PCR and gene sequencing found the SRY gene fragment in plasma EVs from male, but not female, patients; EVs from male patients with CAD (coronary artery disease) had a higher SRY GCN (gene copy number) than healthy subjects. Additional studies found that leucocytes, the major source of plasma EVs, had higher SRY GCN and mRNA and protein expression in male CAD patients than controls. After incubation with EVs from SRY-transfected HEK (human embryonic kidney)-293 cells, monocytes (THP-1) and HUVECs (human umbilical vein endothelial cells), which do not endogenously express SRY protein, were found to express newly synthesized SRY protein. This resulted in an increase in the adherence factors CD11-a in THP-1 cells and ICAM-1 (intercellular adhesion molecule 1) in HUVECs. EMSA showed that SRY protein increased the promoter activity of CD11-a in THP-1 cells and ICAM-1 in HUVECs. There was an increase in THP-1 cells adherent to HUVECs after incubation with SRY-EVs. SRY DNAs transferred from EVs have pathophysiological significance in vivo; injection of SRY EVs into ApoE −/− (apolipoprotein-knockout) mice accelerated atherosclerosis. The SRY gene in plasma EVs transferred to vascular endothelial cells may play an important role in the pathogenesis of atherosclerosis; this mechanism provides a new approach to the understanding of inheritable CAD in men

NF-κB Hyper-Activation by HTLV-1 Tax Induces Cellular Senescence, but Can Be Alleviated by the Viral Anti-Sense Protein HBZ

Activation of I-κB kinases (IKKs) and NF-κB by the human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, is thought to promote cell proliferation and transformation. Paradoxically, expression of Tax in most cells leads to drastic up-regulation of cyclin-dependent kinase inhibitors, p21CIP1/WAF1 and p27KIP1, which cause p53-/pRb-independent cellular senescence. Here we demonstrate that p21CIP1/WAF1-/p27KIP1-mediated senescence constitutes a checkpoint against IKK/NF-κB hyper-activation. Senescence induced by Tax in HeLa cells is attenuated by mutations in Tax that reduce IKK/NF-κB activation and prevented by blocking NF-κB using a degradation-resistant mutant of I-κBα despite constitutive IKK activation. Small hairpin RNA-mediated knockdown indicates that RelA induces this senescence program by acting upstream of the anaphase promoting complex and RelB to stabilize p27KIP1 protein and p21CIP1/WAF1 mRNA respectively. Finally, we show that down-regulation of NF-κB by the HTLV-1 anti-sense protein, HBZ, delay or prevent the onset of Tax-induced senescence. We propose that the balance between Tax and HBZ expression determines the outcome of HTLV-1 infection. Robust HTLV-1 replication and elevated Tax expression drive IKK/NF-κB hyper-activation and trigger senescence. HBZ, however, modulates Tax-mediated viral replication and NF-κB activation, thus allowing HTLV-1-infected cells to proliferate, persist, and evolve. Finally, inactivation of the senescence checkpoint can facilitate persistent NF-κB activation and leukemogenesis

Establishment of porcine and human expanded potential stem cells.

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine

Hierarchical flower-like titanium phosphate derived from H-titanate nanotubes for photocatalysis

Nanosheet-assembled hierarchical flower-like titanium phosphate (TiP) is synthesized via hydrothermal treatment of H-titanate nanotubes (Ti-NT) at the optimized conditions of 0.1 M of H3PO4 and hydrothermal temperature of 130 A degrees C. A possible formation mechanism for the TiP flowers, involving the disintegration of Ti-NT and the growth and assembling of TiP nanosheets, is proposed. The main compositions of the uncalcined TiP flowers are titanium hydrogen phosphate hydrates (Ti(HPO4)(2)center dot xH(2)O), which can be transformed to titanium phosphate (TiP2O7) after high temperature calcination. The photocatalytic activity of the prepared TiP flowers is increased with the increased calcination temperature, which may be attributed to the better photocatalytic activity of TiP2O7 than Ti(HPO4)(2)center dot xH(2)O and the increased crystallization of TiP2O7

Vehicle Routing and Scheduling of Flex-Route Transit under a Dynamic Operating Environment

To improve the reliability, responsiveness, and productivity of the flex-route transit service, this paper investigates the vehicle scheduling and routing problem under a dynamic operating environment. First, we discuss the new operating polices after the introduction of intelligent transportation systems (ITSs), including automatic vehicle location (AVL) system, mobile data terminal (MDT), and computer-aided dispatch (CAD) system. Second, a mixed integer programming (MIP) formulation is employed to solve the offline routing problem. Third, an online scheduling scheme is presented to tackle different dynamic events, such as dynamic requests, travel time fluctuations, cancellations of requests, and customer no-shows. Finally, simulation experiments based on a real-life flex-route transit service are conducted to assess the influence of different dynamic events. The results demonstrate that the proposed scheduling scheme is reliable for coping with various dynamic events, and our findings can be used to guide the policy making of flex-route transit services

Ultrasound-Assisted Fabrication of AgBr/Ag3PO4/TiO2 Nanorod Heterostructure on Ti Mesh

TiO2 nanorod (TNR) deposited by AgBr/Ag3PO4 nanoparticles was fabricated on Ti mesh substrate through ultrasound-assisted successive ionic layer adsorption and reaction technology. It was revealed that the ultrasound-assisted process is helpful in ensuring uniform deposition of Ag3PO4 on the surface of TNR and in inhibiting the accumulation of Ag3PO4 nanoparticles. The concentration of KBr and the adsorption duration strongly influence the deposition of AgBr. The enhanced photocatalytic activity of Ag3PO4/TNR toward methyl orange compared to that of pure TNR is attributed to the enhanced adsorption ability of visible light and to the efficient charge carrier separation owing to the surface plasmon resonance (SPR) effect of Ag3PO4/Ag/TNR system. The further enhanced photocatalytic activity of the heterostructured AgBr/Ag3PO4/TNR is attributed to the SPR effect resulting from the evolution of AgBr/Ag/Ag3PO4/TNR heterostructures and the synergistic energy band structure of Ag3PO4, AgBr, and TNR. (C) 2015 The Electrochemical Society

Enhanced photocatalytic performance of platinized CdS/TiO2 by optimizing calcination temperature of TiO2 nanotubes

TiO2 nanotubes were prepared by hydrothermal treatment of TiO2 powder in NaOH aqueous solution and then calcined at various temperatures. The post-calcination treated TiO2 nanotubes were decorated with CdS by wetness impregnation and subsequently sulfurization to fabricate CdS/TiO2 composites. The photocatalytic performance of CdS/TiO2 composites toward hydrogen production from water splitting was investigated. The results show that the calcination temperature of TiO2 nanotubes has a significant effect on the photocatalytic performance of CdS/TiO2. With the increase of calcination temperature from 300 to 500 degrees C, the crystallinity of TiO2 nanotubes is increased resulting in the enhanced photocatalytic performance of CdS/TiO2. When the calcination temperature is higher than 500 degrees C, TiO2 nanotubes gradually transform into nanorods and finally completely collapse, which leads to the decrease of photocatalytic performance of CdS/TiO2. The CdS/TiO2 composite with TiO2 nanotubes calcined at 500 degrees C exhibits the highest hydrogen evolution rate, which could be attributed to its 1 D nanotubular structure and good crystallinity. (C) 2014 Elsevier Ltd. All rights reserved