Combination of an allosteric Akt Inhibitor MK-2206 with etoposide or rapamycin enhances the antitumor growth effect in neuroblastoma.

Purpose: Activation of Akt is a marker of decreased event-free or overall survival in neuroblastoma patients. MK-2206, a novel allosteric Akt inhibitor, is now tested in clinical trials in adult cancers. In this study, effect of MK-2206 on tumor growth and murine survival, alone or in combination, with etoposide or rapamycin was evaluated.

Reconstruction of totally degloved fingers with a spiraled parallelogram medial arm free flap.

Purpose: To investigate the results of resurfacing completely degloved digits using a parallelogram free flap from the medial arm in a spiral fashion.

Methods: We reviewed the reconstruction of 26 digits in 21 patients with a parallelogram free flap from the medial arm in a spiral fashion following a non-replantable degloving injury.

Results: The sizable perforator was observed consistently in the medial arm with 13 of 21 (62%) originating from the superior ulnar collateral artery, 6 of 21 (29%) directly from the brachial artery, and 2 of 21 (9%) from the superficial brachial artery.

Genome sequence determination and analysis of a Chinese virulent strain, LMS, of Gallid herpesvirus type 2.

Marek's disease (MD) is a neoplastic and neurodegenerative disease of chickens, which is caused by the Gallid herpesvirus type 2 (GaHV-2). Although vaccination has been used widely in China, MD still occurs frequently. Some molecular epidemiologic studies have shown that Chinese GaHV-2 isolates seem to constitute a separate clade from strains isolated from other regions.

Proteomic alteration of Marc-145 cells and PAMs after infection by porcine reproductive and respiratory syndrome virus.

Viral infections usually result in alterations in the host cell proteome, which determine the fate of infected cells and the progress of pathogenesis. To uncover cellular protein responses in porcine reproductive and respiratory syndrome virus (PRRSV), infected pulmonary alveolar macrophages (PAMs) and Marc-145 cells were subjected to proteomic analysis involving two-dimensional electrophoresis (2-DE) followed by MALDI-TOF-MS/MS identification. Altered expression of 44 protein spots in infected cells was identified in 2D gels, of which the 29 characterised by MALDI-TOF-MS/MS included 17 up-regulated and 12 down-regulated proteins.

EZH2 Mediates epigenetic silencing of neuroblastoma suppressor genes CASZ1, CLU, RUNX3, and NGFR.

Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with an undifferentiated status and generally poor prognosis, but the basis for these characteristics remains unknown. In this study, we show that upregulation of the Polycomb protein histone methyltransferase EZH2, which limits differentiation in many tissues, is critical to maintain the undifferentiated state and poor prognostic status of NB by epigenetic repression of multiple tumor suppressor genes. We identified this role for EZH2 by examining the regulation of CASZ1, a recently identified NB tumor suppressor gene whose ectopic restoration inhibits NB cell growth and induces differentiation.

Comparative full-length sequence analysis of Marek's disease virus vaccine strain 814.

The complete DNA sequence of Marek's disease virus (MDV) serotype 1 vaccine strain 814 was determined. It consisted of 172,541 bp, with an overall gene organization identical to that of the MDV-1 type strains. Comparative genomic analysis of vaccine strains (814 and CVI988) and other strains (CU-2, Md5, and Md11) showed that 814 was most similar to CVI988.

[Effects of Chinese herbal medicine Liuwei Dihuang Pill and its main monomer catalpol on transforming growth factor-β1/Smad pathway in HK-2 cells].

Objective: To observe the effects of sera containing Liuwei Dihuang Pill (LDP), a compound traditional Chinese herbal medicine, and its monomer catalpol on transforming growth factor-β1 (TGF-β1)/Smad pathway in HK-2 cells.

Methods: Wistar rats were intragastrically administered with LDP twice daily for 3 days and then sera were obtained. HK-2 cells were cultured at different concentrations of serum containing LDP.

Perifosine-induced inhibition of Akt attenuates brain-derived neurotrophic factor/TrkB-induced chemoresistance in neuroblastoma in vivo.

Background: Neuroblastoma (NB) tumors expressing high levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB or activated Akt are associated with decreased event-free or overall survival in patients with NB. In the current study, the effect of perifosine, an Akt inhibitor, on the chemosensitivity of TrkB-expressing NB cells or tumors was evaluated.

Methods: A tetracycline-regulated TrkB-expressing isogenic NB cell model system was tested.

[Effect of hirudin on random skin flap survival in rats].

Objective: To investigate the effect of Hirudin on random skin flap survival in rats.

Methods: 24 SD rats were randomly divided into control group and experimental group. The "McFarlane flap (3 cm x 9 cm)" rat models were established on the rat dorsum.

CCL20, γδ T cells, and IL-22 in corneal epithelial healing.

After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6(+) IL-17(+) γδ T cells migrate into the epithelium. γδ T-cell-deficient (TCRδ(-/-)) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mRNA increased 19-fold at 3 h, and protein increased ∼ 16-fold at 6 h after injury.

Indomethacin and SC236 enhance the cytotoxicity of doxorubicin in human hepatocellular carcinoma cells via inhibiting P-glycoprotein and MRP1 expression.

Doxorubicin is a chemotherapeutic drug widely used for the treatment of hepatocellular carcinoma but its efficacy is restricted by multidrug resistance. Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2-selective inhibitors exhibit anti-cancer properties as well as abilities to overcome drug resistance. In the present study, indomethacin (a NSAID) and SC236 (a COX-2-selective inhibitor) enhanced the cytotoxicity of doxorubicin in the hepatocellular carcinoma cell line HepG2 and its drug-resistant sub-line R-HepG2.

IL-17 and VEGF are necessary for efficient corneal nerve regeneration.

The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) γδ T cells, neutrophils, and platelets in the cornea followed by full restoration of the epithelium and ∼19% regeneration of sensory nerves within 96 hours. Mice deficient in γδ T cells (TCRδ(-/-)) or wild-type mice treated systemically with anti-IL-17 had >50% reduction in leukocyte and platelet infiltration and >50% reduction in nerve regeneration.

Colonic mucosal DNA methylation, immune response, and microbiome patterns in Toll-like receptor 2-knockout mice.

The connection between intestinal microbiota and host physiology is increasingly becoming recognized. The details of this dynamic interaction, however, remain to be explored. Toll-like receptor 2 (Tlr2) is important for its role in bacterial recognition, intestinal inflammation, and obesity-related metabolic changes.

Celecoxib antagonizes the cytotoxicity of cisplatin in human esophageal squamous cell carcinoma cells by reducing intracellular cisplatin accumulation.

High cyclooxygenase 2 (COX-2) expression has been reported to be clinically associated with reduced cisplatin-based therapy efficacy in esophageal cancer. However, the benefit of including COX-2-selective inhibitors in therapeutic regimens remains uncertain. Thus, we sought to determine the effects of COX inhibitors on the cytotoxicity of cisplatin and to further explore the mechanism involved in human esophageal squamous cell carcinoma cells.

NGF activation of TrkA induces vascular endothelial growth factor expression via induction of hypoxia-inducible factor-1α.

Communication between the vasculature and nervous system is important during embryogenesis but the molecular mechanisms mediating this are ill-defined. We evaluated the molecular mechanisms by which Nerve Growth Factor (NGF) and Brain-derived neurotrophic factor (BDNF) regulate VEGF production. NGF activation of TrkA causes a marked increase in VEGF secretion by neuronal cells.

The free dorsoradial forearm perforator flap: anatomical study and clinical application in finger reconstruction.

The perforator flaps are characterized by their thinness and the adjustable length of their vascular pedicle. The purpose of this investigation is to refine the anatomy of the perforators in the middorsoradial forearm and present our clinical experience using this free perforator flap in the reconstruction of finger defects. Anatomic study was conducted on 46 cadaver forearms.

ICAM-1 mediates surface contact between neutrophils and keratocytes following corneal epithelial abrasion in the mouse.

Corneal epithelial abrasion elicits an inflammatory response involving neutrophil (PMN) recruitment from the limbal vessels into the corneal stroma. These migrating PMNs make surface contact with collagen and stromal keratocytes. Using mice deficient in PMN integrin CD18, we previously showed that PMN contact with stromal keratocytes is CD18-dependent, while contact with collagen is CD18-independent.

[Clinical significance of MESS scoring system in the treatment of fractures of lower limb combined with vascular injuries].

Objective: To study the clinical significance of MESS scoring system in the treatment of fractures of lower limb combined with vascular injuries, and to evaluate its reliance.

Methods: From March 2006 to March 2008, 28 patients with fractures of lower limb combined with vascular injuries were graded by MESS scoring system. There were 17 patients were male and 11 patients were female, ranging in age from 23 to 53 years, averaged 38 years.

Altered morphology and function of the lacrimal functional unit in protein kinase C{alpha} knockout mice.

Purpose: Protein kinase C (PKC) α plays a major role in the parasympathetic neural stimulation of lacrimal gland (LG) secretion. It also has been reported to have antiapoptotic properties and to promote cell survival. Therefore, the hypothesis for the present study was that PKCα knockout ((-/-)) mice have impaired ocular surface-lacrimal gland signaling, rendering them susceptible to desiccating stress and impaired corneal epithelial wound healing.

In vitro and in vivo inhibition of neuroblastoma tumor cell growth by AKT inhibitor perifosine.

Background: Activated AKT is a marker of decreased event-free or overall survival in neuroblastoma (NB) patients. The aim of this study was to investigate the effect of perifosine, a nontoxic AKT inhibitor, as a single agent on NB cell growth in vitro and in vivo.

Methods: Four human NB cell lines (AS, NGP, BE2, and KCNR) were treated with increasing concentrations of perifosine, and a quantitative analysis of cell death (apoptosis) was performed by using MTS and caspase-3/7 activity assays.

Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells.

As histone deacetylase inhibitors such as romidepsin (depsipeptide, FK228) complete successful Phase I clinical trials in pediatric solid tumors, it is important that their mechanisms of action are delineated in order to inform the development of subsequent clinical trials as single agents or in combination therapies. In this study, we evaluate the effect of romidepsin as a single agent on a number of different neuroblastoma (NB) cell lines. We find that the growth of 6/6 human NB tumor cell lines but not an immortalized fibroblast cell line (NIH3T3) is inhibited by romidepsin (IC(50) = 1-6.

[Suspension with repose system in the treatment of obstructive sleep apnea-hypopnea syndrome].

Objective: To introduce the treatment of severe obstructive sleep apnea-hypopnea syndrome (OSAHS) with Repose bone screw system and to evaluate the treating effect.

Methods: Thirty-two patients with severe OSAHS (Friedman classification II, III) were treated with tongue ablation + uvulopalatopharyngoplasty + hard palate shortening + Repose suspension. All patients were followed-up for 6 months.

Purification, crystallization and preliminary crystallographic analysis of very-long-chain acyl-CoA dehydrogenase from Caenorhabditis elegans.

Acyl-CoA dehydrogenase [acyl-CoA:(acceptor) 2,3-oxidoreductase; EC 1.3.99.

Identification and characterization of Th cell epitopes in MrkD adhesin of Klebsiella pneumoniae.

In this study, we identified the Th epitopes in MrkD of Klebsiella pneumoniae, an excellent vaccine candidate antigen. By using the RANKPEP prediction algorithm, we have identified and characterized three Th epitopes within the MrkD antigen, which can be recognized by CD4+ T cells from BALB/c (H-2(d)) mice. They were M(221-235), M(175-189), and M(264-278).

Antigenic variation between Newcastle disease viruses of goose and chicken origin.

Newcastle disease virus (NDV) is believed to infect only domestic avian species, with waterfowl such as geese either not being infected, even by virulent strains, or developing only inapparent infection. Since the late 1990s, a new infectious disease producing high morbidity and mortality among geese broke out in many provinces of China. This disease was caused by a serotype I avian paramyxovirus known as (APMV-1)-NDV.