Hemodynamic study of the ICA aneurysm evolution to attain the cerebral aneurysm rupture risk.

The influence of the aneurysm evolution on the hemodynamic characteristic of the blood flow inside the sac region is comprehensively investigated. By using the computational method, the blood flow through the vessel and aneurysm of the sac region is examined to find the role of aneurysm evolution on the wall shear stress, pressure, and risk of aneurysm rupture. Three different models of ICA aneurysms are chosen for the investigation of the aneurysm evolution at risk of rupture.

Impact of surgical strategies on the survival of gallbladder cancer patients: analysis of 715 cases.

Objective: The aim of the study is to evaluate the impact of application of surgical strategies at different cancer stages on the survival of gallbladder cancer (GBC) patients.

Methods: The patients with GBC were divided into 3 groups according to their received surgical strategies: simple resection (full-thickness cholecystectomy for removal of primary tumor site), radical resection (gallbladder bed removal combined with partial hepatectomy), and palliative surgery (treatment at advanced stages). The overall survival (OS) of GBC patients who were received different surgical strategies was compared.

An oncogenic gene, SNRPA1, regulates PIK3R1, VEGFC, MKI67, CDK1 and other genes in colorectal cancer.

Purpose: Colorectal cancer (CRC) caused more than 65,000 mortalities worldwide per year. It is a result of one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. SNRPA1 (small nuclear ribonucleoprotein polypeptide A) is a subunit of spliceosome complex that is involved in the RNA processing.

IDH mutant gliomas escape natural killer cell immune surveillance by downregulation of NKG2D ligand expression.

Background: Diffuse gliomas are poorly immunogenic, fatal brain tumors. The basis for insufficient antitumor immunity in diffuse gliomas is unknown. Gain-of-function mutations in isocitrate dehydrogenases (IDH1 and IDH2) promote diffuse glioma formation through epigenetic reprogramming of a number of genes, including immune-related genes.

Phospho-BAD BH3 mimicry protects β cells and restores functional β cell mass in diabetes.

Strategies that simultaneously enhance the survival and glucose responsiveness of insulin-producing β cells will greatly augment β cell replacement therapies in type 1 diabetes (T1D). We show that genetic and pharmacologic mimetics of the phosphorylated BCL-2 homology 3 (BH3) domain of BAD impart β-cell-autonomous protective effects in the face of stress stimuli relevant to β cell demise in T1D. Importantly, these benefits translate into improved engraftment of donor islets in transplanted diabetic mice, increased β cell viability in islet grafts, restoration of insulin release, and diabetes reversal.

Sequence variation in promoter of Ica1 gene, which encodes protein implicated in type 1 diabetes, causes transcription factor autoimmune regulator (AIRE) to increase its binding and down-regulate expression.

ICA69 (islet cell autoantigen 69 kDa) is a protein implicated in type 1 diabetes mellitus in both the non-obese diabetic (NOD) mouse model and humans. ICA69 is encoded by the Ica1 gene on mouse chromosome 6 A1-A2. We previously reported reduced ICA69 expression in the thymus of NOD mice compared with thymus of several non-diabetic mouse strains.

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane KATP channels.

Understanding mechanisms by which glibenclamide stimulates insulin release is important, particularly given recent promising treatment by glibenclamide of permanent neonatal diabetic subjects. Antidiabetic sulfonylureas are thought to stimulate insulin secretion solely by inhibiting their high-affinity ATP-sensitive potassium (K(ATP)) channel receptors at the plasma membrane of beta-cells. This normally occurs during glucose stimulation, where ATP inhibition of plasmalemmal K(ATP) channels leads to voltage activation of L-type calcium channels for rapidly switching on and off calcium influx, governing the duration of insulin secretion.

In vivo immune modulatory activity of hepatic stellate cells in mice.

Accumulating data suggest that hepatic tolerance, initially demonstrated by spontaneous acceptance of liver allografts in many species, results from an immune regulatory activity occurring in the liver. However, the responsible cellular and molecular components have not been completely understood. We have recently described profound T cell inhibitory activity of hepatic stellate cells (HSCs) in vitro.

Protective regulatory T cell generation in autoimmune diabetes by DNA covaccination with islet antigens and a selective CTLA-4 ligand.

DNA vaccination of autoimmune diabetes-prone NOD mice with unmodified target islet antigens, i.e., preproinsulin (PPIns) or glutamic acid decarboxylase 65 (GAD65), is poorly protective.

A mutant B7-1/Ig fusion protein that selectively binds to CTLA-4 ameliorates anti-tumor DNA vaccination and counters regulatory T cell activity.

We have shown that a plasmid encoding a B7-1/Ig fusion protein enhanced DNA vaccination against human carcinoembryonic antigen (CEA) more effectively than the plasmid encoding membrane-bound B7-1. However, it was not known if B7-1/Ig acted only by binding CD28 (amplifying a stimulatory signal) or by blocking CTLA-4 on T cells (removing inhibitory signals). Here, we aimed to determine this using a plasmid encoding mutant B7-1/Ig (B7-1wa/Ig), which binds only to CTLA-4 but not to CD28.

Plasmids encoding membrane-bound IL-4 or IL-12 strongly costimulate DNA vaccination against carcinoembryonic antigen (CEA).

Vaccination with plasmids encoding an antigen of interest (DNA vaccination) is a new strategy to achieve effective immunization against many agents. DNA vaccination can be ameliorated by co-administration of plasmids encoding a cytokine. Thus far, only plasmids encoding soluble cytokines have been used for this purpose.

Flexible management of enzymatic digestion improves human islet isolation outcome from sub-optimal donor pancreata.

Worldwide growing interest in reproducing the result of the Edmonton protocol in islet transplantation trials poses the problem of paucity of donors to supply sufficient amount of islets for clinical use. Improved outcomes include finding better ways to obtain higher yields from every donor organ processed and the possibility of extending islet isolation processing to glands of suboptimal quality. In order to optimize enzymatic digestion of marginal donor organs, we have modified the technique of tissue collection following enzymatic digestion of human pancreatic organs, allowing for reduced time of exposure of free islets to warm Liberase trade mark solution.

Intramuscular gene transfer of soluble B7.1/IgG(1) fusion cDNA induces potent antitumor immunity as an adjuvant for DNA vaccination.

Soluble B7.1/IgG Fc fusion protein, which has costimulatory effects, is an effective molecular adjuvant in tumor immune therapy. Here, we describe a nonviral intramuscular (i.

Immunoinhibitory DNA vaccine protects against autoimmune diabetes through cDNA encoding a selective CTLA-4 (CD152) ligand.

Cytotoxic T lymphocyte antigen 4 (CTLA-4 or CD152) is a strong negative regulator of T cell activity. Like CD28 (a positive regulator) it binds to B7-1 and B7-2, and there is no known natural selective ligand. Monoclonal antibodies to CTLA-4 generally have a masking effect, enhancing rather than suppressing responses.