Effect of alendronate on bone remodeling around implant in the rat

published_or_final_versio

UV Photofunctionalization Effect on Bone Graft in Critical One-Wall Defect around Implant: A Pilot Study in Beagle Dogs

published_or_final_versio

Intravaginal Administration of Fc-Fused IL7 Suppresses the Cervicovaginal Tumor by Recruiting HPV DNA Vaccine-Induced CD8 T Cells

Purpose: The induction of tissue-localized virus-specific CD8 T-cell response is essential for the development of an effective therapeutic vaccine against genital diseases, such as cervical cancer and genital herpes. Here, we aimed to elucidate the immunologic role of IL7 in the induction of mucosal cellular immunity. Experimental Design: IL7 was engineered through Fc fusion to enhance mucosal delivery across the genital epithelial barrier. The immunomodulatory role of IL7 was evaluated by monitoring the kinetics of various immune cells and measuring the expression of chemokines and cytokines after intravaginal administration of Fc-fused IL7 (IL7-Fc). The antitumor effects of intramuscular human papillomavirus (HPV) DNA vaccine or topical IL7-Fc alone or in a combinational regimen on mice survival were compared using a orthotopic cervical cancer model. Results: Intravaginal treatment of IL7-Fc, but not native IL7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFN-gamma, TNF alpha, IL6, and IL1 beta), and an adhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes, including CD4, CD8, gamma delta T cells, and dendritic cells. Importantly, in this murine cervical cancer model, topical administration of IL7-Fc after intramuscular HPV DNA vaccination increases the number of HPV-specific CD8 T cells in the genital mucosa, but not in the spleen, leading to stronger antitumor activity than the HPV DNA vaccine alone. Conclusions: Our findings provide an important insight into the immunomodulatory role of IL7-Fc via topical application and the design of therapeutic vaccine regimen that induces effective genital-mucosal CD8 T-cell responses.1110Ysciescopu

Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition

We identified the specific role of vaccinia-related kinase 1 (VRK1) in the progression of hepatocellular carcinoma (HCC) and evaluated its therapeutic and prognostic potential. VRK1 levels were significantly higher in HCC cell lines than a normal hepatic cell line, and were higher in HCC than non-tumor tissue. VRK1 knockdown inhibited the proliferation of SK-Hep1, SH-J1 and Hep3B cells; moreover, depletion of VRK1 suppressed HCC tumor growth in vivo. We also showed that VRK1 knockdown increased the number of G1 arrested cells by decreasing cyclin D1 and p-Rb while upregulating p21 and p27, and that VRK1 depletion downregulated phosphorylation of CREB, a transcription factor regulating CCND1. Additionally, we found that luteolin, a VRK1 inhibitor, suppressed HCC growth in vitro and in vivo, and that the aberrant VRK1 expression correlated with poor prognostic features of HCC. High levels of VRK1 were associated with shorter overall and disease-free survival and higher recurrence rates. Taken together, our findings suggest VRK1 may act as a tumor promoter by controlling the level of cell cycle regulators associated with G1/S transition and could potentially serve as a therapeutic target and/or prognostic biomarker for HCC.1110Ysciescopu

Evaporation Mechanism of Sn and SnS from Liquid Fe: Part III. Effect of C on Sn Removal

To understand the effect of C on Sn evaporation from liquid iron in the view of ferrous scrap recycling, the evaporation of Sn from various liquid Fe-C-S-Sn alloys was experimentally investigated. A series of gas-liquid reactions was carried out at 1873 K (1600 degrees C) using an electromagnetic levitation melting technique, where mass transfers in gas phase and liquid phase did not significantly affect the reaction rate. It was found that CS2(g) is a major gas species evaporating from Fe-C-S alloy (initial S content [pct S](0): 0.028 to 0.502 mass pct), and Fe-C-S-Sn alloy ([pct S](0): 0.063 to 0.560 mass pct), thereby competing with SnS for S in the liquid alloy. A model equation for the evaporation rate of CS2(g) was established using the experimental data for the Fe-C-S alloys. The chemical reaction rate constant for the CS2(g) evaporation (k(CS2)(R)) was obtained as 4.24 x 10(-12) m(7) mol(-2) s(-1), and the residual rate constant (k(CS2)(r)) was 4.24 x 10(-16) m(7) mol(-2) s(-1), both at 1873 K (1600 degrees C). Roll of C on the evaporation of Sn in Fe-C-Sn alloy was confirmed to be the increase of activity coefficient of Sn. By taking into account (1) the evaporation of Sn(g), SnS(g), and CS2(g), and (2) the increasing activity coefficient of Sn and S by C, a comprehensive model for the evaporation rate of Sn and S in the Fe-C-Sn-S alloy was developed. The calculation results by the developed model in the present study showed good agreement with the experimental results. Some applications of the current model are presented in the view of increasing the Sn removal rate.open1135Nsciescopu

Evaporation Mechanism of Sn and SnS from Liquid Fe: Part II: Residual Site and Evaporation Kinetics via Sn(g) and SnS(g)

Evaporation of Sn from molten steel was experimentally investigated for Fe-Sn-S alloy with low initial S (0.0007<[pct S] 0< 0.05) or with high initial S (0.55<[pct S](0) < 0.894) at 1873 K (1600 degrees C) using an electromagnetic levitation melting technique, in order to clarify the role of S on the evaporation mechanism of Sn. It was found that increasing initial S concentration, [pct S](0), decreased the second-order evaporation rate constant of Sn (k(SnS)), but there was a residual rate for the evaporation even at high [pct S](0). The obtained residual rate constant, k(SnS)(r) , was 1.4 x 10(-9) m(4) mol(-1) s(-1) at 1873 K (1600 degrees C). Evaporation of Sn under virtually no S condition ([pct S](0) = 0.0007) was also measured and corresponding first-order rate constant was determined to be 3.49 x 10(-7) m s(-1) at 1873 K (1600 degrees C). A comprehensive model for the Sn evaporation from molten Fe-Sn-S alloy was developed in the present study, under the condition where mass transfer in gas and liquid phases were fast and interfacial chemical reaction controlled the evaporation of Sn. The model equation is able to represent the evaporation of Sn in the forms of Sn(g) and SnS(g) simultaneously, from very low S melt (when there is no S) to very high S melt investigated in the present study up to similar to 0.9 mass pct. Gradual transition of major evaporation species from SnS(g) to Sn(g) was well accounted for by the developed model.open1146Nsciescopu

Oral immunization of haemaggulutinin H5 expressed in plant endoplasmic reticulum with adjuvant saponin protects mice against highly pathogenic avian influenza A virus infection

Pandemics in poultry caused by the highly pathogenic avian influenza (HPAI) A virus occur too frequently globally, and there is growing concern about the HPAI A virus due to the possibility of a pandemic among humans. Thus, it is important to develop a vaccine against HPAI suitable for both humans and animals. Various approaches are underway to develop such vaccines. In particular, an edible vaccine would be a convenient way to vaccinate poultry because of the behaviour of the animals. However, an edible vaccine is still not available. In this study, we developed a strategy of effective vaccination of mice by the oral administration of transgenic Arabidopsis plants (HA-TG) expressing haemagglutinin (HA) in the endoplasmic reticulum (ER). Expression of HA in the ER resulted in its high-level accumulation, N-glycosylation, protection from proteolytic degradation and long-term stability. Oral administration of HA-TG with saponin elicited high levels of HA-specific systemic IgG and mucosal IgA responses in mice, which resulted in protection against a lethal influenza virus infection with attenuated inflammatory symptoms. Based on these results, we propose that oral administration of freeze-dried leaf powders from transgenic plants expressing HA in the ER together with saponin is an attractive strategy for vaccination against influenza A virus.X111411Ysciescopu

SUMO-Specific Protease 2 (SENP2) Is an Important Regulator of Fatty Acid Metabolism in Skeletal Muscle

Small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) that reverse protein modification by SUMO are involved in the control of numerous cellular processes, including transcription, cell division, and cancer development. However, the physiological function of SENPs in energy metabolism remains unclear. Here, we investigated the role of SENP2 in fatty acid metabolism in C2C12 myotubes and in vivo. In C2C12 myotubes, treatment with saturated fatty acids, like palmitate, led to nuclear factor-B-mediated increase in the expression of SENP2. This increase promoted the recruitment of peroxisome proliferator-activated receptor (PPAR) and PPAR, through desumoylation of PPARs, to the promoters of the genes involved in fatty acid oxidation (FAO), such as carnitine-palmitoyl transferase-1 (CPT1b) and long-chain acyl-CoA synthetase 1 (ACSL1). In addition, SENP2 overexpression substantially increased FAO in C2C12 myotubes. Consistent with the cell culture system, muscle-specific SENP2 overexpression led to a marked increase in the mRNA levels of CPT1b and ACSL1 and thereby in FAO in the skeletal muscle, which ultimately alleviated high-fat diet-induced obesity and insulin resistance. Collectively, these data identify SENP2 as an important regulator of fatty acid metabolism in skeletal muscle and further implicate that muscle SENP2 could be a novel therapeutic target for the treatment of obesity-linked metabolic disorders.11116Ysciescopu

Dopamine Regulation of Amygdala Inhibitory Circuits for Expression of Learned Fear.

GABAergic signaling in the amygdala controls learned fear, and its dysfunction potentially contributes to posttraumatic stress disorder (PTSD). We find that sub-threshold fear conditioning leads to dopamine receptor D4-dependent long-term depression (LTD) of glutamatergic excitatory synapses by increasing inhibitory inputs onto neurons of the dorsal intercalated cell mass (ITC) in the amygdala. Pharmacological, genetic, and optogenetic manipulations of the amygdala regions centered on the dorsal ITC reveal that this LTD limits less salient experiences from forming persistent memories. In further support of the idea that LTD has preventive and discriminative roles, we find that LTD at the dorsal ITC is impaired in mice exhibiting PTSD-like behaviors. These findings reveal a novel role of inhibitory circuits in the amygdala, which serves to dampen and restrict the level of fear expression. This mechanism is interfered with by stimuli that give rise to PTSD and may also be recruited for fear-related psychiatric diseases.1110Ysciescopu

Shortcuts to adiabaticity in a time-dependent box

A method is proposed to drive an ultrafast non-adiabatic dynamics of an ultracold gas trapped in a box potential. The resulting state is free from spurious excitations associated with the breakdown of adiabaticity, and preserves the quantum correlations of the initial state up to a scaling factor. The process relies on the existence of an adiabatic invariant and the inversion of the dynamical self-similar scaling law dictated by it. Its physical implementation generally requires the use of an auxiliary expulsive potential analogous to those used in soliton control. The method is extended to a broad family of many-body systems. As illustrative examples we consider the ultrafast expansion of a Tonks-Girardeau gas and of Bose-Einstein condensates in different dimensions, where the method exhibits an excellent robustness against different regimes of interactions and the features of an experimentally realizable box potential.Comment: 6 pp, 4 figures, typo in Eq. (6) fixe