Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue.

Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer-surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer-surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane.

Curcuminoids and ω-3 fatty acids with anti-oxidants potentiate cytotoxicity of natural killer cells against pancreatic ductal adenocarcinoma cells and inhibit interferon γ production.

Pancreatic cancer has a poor prognosis attributed in part to immune suppression and deactivation of natural killer (NK) cells. Curcuminoids have a potential for improving the therapy of pancreatic cancer given promising results in cancer models and a clinical trial, but their oral absorption is limited. Our objective in this study is to show curcuminoid anti-oncogenic effects alone and together with human NK cells.

Split anergized Natural Killer cells halt inflammation by inducing stem cell differentiation, resistance to NK cell cytotoxicity and prevention of cytokine and chemokine secretion.

The mechanism of suppression of NK cytotoxicity in cancer patients is not clearly established. In this paper we provide evidence that anergized NK cells induce differentiation of healthy Dental Pulp Stem Cells (DPSCs) or transformed Oral Squamous Cancer Stem Cells (OSCSCs) resulting in cell growth inhibition, resistance to NK cell-mediated cytotoxicity and prevention of inflammatory mediators secretion. Induction of cytotoxicity resistance in differentiated cells correlated with increased CD54 and MHC class I surface expression and mediated by the combination of IFN-γ and TNF-α since antibodies to both, but not each cytokine alone, was able to inhibit resistance.

A method of permeabilization of Drosophila embryos for assays of small molecule activity.

The Drosophila embryo has long been a powerful laboratory model for elucidating molecular and genetic mechanisms that control development. The ease of genetic manipulations with this model has supplanted pharmacological approaches that are commonplace in other animal models and cell-based assays. Here we describe recent advances in a protocol that enables application of small molecules to the developing fruit fly embryo.

Induction of Split Anergy Conditions Natural Killer Cells to Promote Differentiation of Stem Cells through Cell-Cell Contact and Secreted Factors.

In this paper, we provide evidence that anergized NK cells through secreted factors and direct cell-cell contact have the ability to induce differentiation of healthy dental pulp stem cells and stem cell of apical papillae as well as transformed oral squamous cancer stem cell (OSCSC) and Mia-Paca-2, poorly differentiated stem-like pancreatic tumors, resulting in their resistance to NK cell-mediated cytotoxicity. Induction of NK cell resistance and differentiation in the stem cells correlated with the increased expression of CD54, B7H1, and MHC class I, and mediated by the combination of membrane-bound or secreted IFN-γ and TNF-α from the NK cells since antibodies to both cytokines and not each one alone were able to inhibit differentiation or resistance to NK cells. Similarly, antibodies to both TNF-α and IFN-γ were required to prevent NK-mediated inhibition of cell growth, and restored the numbers of the stem cells to the levels obtained when stem cells were cultured in the absence of anergized NK cells.

Heart rate variability in type 2 diabetes mellitus.

Heart rate variability (HRV) is a noninvasive measure of cardiac autonomic modulation. Time and frequency domain measures have primarily been examined in patients with type 2 diabetes mellitus (T2D). Not only do frequency domain HRV parameters tend to be reduced in T2D, but healthy individuals with low HRV are also more likely to develop T2D.

Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing.

Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.

Increased lysis of stem cells but not their differentiated cells by natural killer cells; de-differentiation or reprogramming activates NK cells.

The aims of this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. Increased cytotoxicity and augmented secretion of IFN-gamma were both observed when PBMCs or NK cells were co-incubated with primary UCLA oral squamous carcinoma stem cells (UCLA-OSCSCs) when compared to differentiated UCLA oral squamous carcinoma cells (UCLA-OSCCs). In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells.

Strategies to rescue mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) from NK cell mediated cytotoxicity.

Background: The aim of this paper is to study the function of allogeneic and autologous NK cells against Dental Pulp Stem Cells (DPSCs) and Mesenchymal Stem Cells (MSCs) and to determine the function of NK cells in a three way interaction with monocytes and stem cells.

Methodology/principal Findings: We demonstrate here that freshly isolated untreated or IL-2 treated NK cells are potent inducers of cell death in DPSCs and MSCs, and that anti-CD16 antibody which induces functional split anergy and apoptosis in NK cells inhibits NK cell mediated lysis of DPSCs and MSCs. Monocytes co-cultured with either DPSCs or MSCs decrease lysis of stem cells by untreated or IL-2 treated NK cells.

Xylitol: effects on the acquisition of cariogenic species in infants.

Purpose: The purpose of this study was to examine the effects of xylitol gum (XG) on the acquisition pattern of 39 bacterial species, including mutans streptococci (MS), in infants.

Methods: Ninety-seven mothers (MS counts > 10(5) CFU/ml) were randomly divided into 4 groups and received: (1) XG (4.2 gm/day); (2) XG (6 months after baseline exams); (3) sorbitol gum (4.

N-acetyl cysteine mediates protection from 2-hydroxyethyl methacrylate induced apoptosis via nuclear factor kappa B-dependent and independent pathways: potential involvement of JNK.

The mechanisms by which resin based materials induce adverse effects in patients have not been completely elucidated. Here we show that 2-hydroxyethyl methacrylate (HEMA) induces apoptotic cell death in oral keratinocytes. Functional loss and cell death induced by HEMA was significantly inhibited in the presence of N-acetyl cysteine (NAC) treatment.

Regulation of IGFBP6 gene and protein is mediated by the inverse expression and function of c-jun N-terminal kinase (JNK) and NFkappaB in a model of oral tumor cells.

The aim of this study is to identify potential gene and protein targets when nuclear factor kappa B (NFkappaB) and c-jun N-terminal kinase (JNK) were inversely expressed in oral tumors. To determine which genes were regulated synergistically by the inverse expression of NFkappaB and JNK, a pathway specific microarray analysis was performed. While either inhibition of NFkappaB or activation of JNK alone was unable to affect the IGFBP6 gene expression in microarray analysis, concomitant increase in JNK activation in the presence of NFkappaB inhibition increased the expression of this gene significantly.

N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells.

Resin-based materials are now widely used in dental restorations. Although the use of these materials is aesthetically appealing to patients, it carries the risk of local and systemic adverse effects. The potential risks are direct damage to the cells and induction of immune-based hypersensitivity reactions.

Potent induction of TNF-alpha during interaction of immune effectors with oral tumors as a potential mechanism for the loss of NK cell viability and function.

The inhibitory role of TNF-alpha on survival of naïve and IL-2 treated NK cells has been demonstrated in the past. However, its effect on the function of these cells against tumor cells, in particular against oral tumors has not been established. We investigated the significance of secreted TNF-alpha in death and functional loss of splenocytes and NK cells in ex-vivo cultures with oral tumors.

"All I want for Christmas is my two front teeth" (the story behind the song).

During his long and productive career, Donald Yetter Gardner (1913-2004) played various musical instruments, directed church choirs, wrote contemporary church anthems and led many community-sponsored choral events. Additionally, he penned a number of popular spirituals, including "Man Shall Not Live By Bread Alone," and "O Give Thanks Unto the Lord". He was noted for his varied musical accomplishments, but he was best known for composing what was to become an international childrens holiday favorite, "All I Want For Christmas Is My Two Front Teeth".

Emerging mechanisms of immunosuppression in oral cancers.

Mounting effective anti-tumor immune responses against tumors by both the innate and adaptive immune effectors is important for the clearance of tumors. However, accumulated evidence indicates that immune responses that should otherwise suppress or eliminate transformed cells are themselves suppressed by the function of tumor cells in a variety of cancer patients, including those with oral cancers. Signaling abnormalities, spontaneous apoptosis, and reduced proliferation and function of circulating natural killer cells (NK), T-cells, dendritic cells (DC), and tumor-infiltrating lymphocytes (TILs) have been documented previously in oral cancer patients.

The "canary incident" in W.C. Field's 1928 Earl Carroll's vanities stage dental skit.

W.C. Fields (1880-1946), a gifted writer, director and performer, became one of the greatest comedians, jugglers and pantomimes of all time.

Notch signaling in the regulation of tumor angiogenesis.

The Notch signaling pathway is conserved in vertebrates and invertebrates and is involved in many developmental processes. Notch receptors and ligands are expressed on the cell surface enabling interactions between adjacent cells upon receptor-ligand binding. Notch signaling molecules have an important well-documented role in vascular development, differentiation, proliferation, apoptosis and tumorigenesis.

Myasthenia gravis and pregnancy.

Treatment considerations for women who have MG and are of childbearing age are complicated. When possible, before pregnancy, establishing a plan for therapy is ideal, recognizing the potential concerns for the patient and the fetus. Decisions about treatment during pregnancy must balance the potential complications for the fetus, the patient, and even the integrity of the pregnancy.

Hepatocyte growth factor inhibits anoikis by induction of activator protein 1-dependent cyclooxygenase-2. Implication in head and neck squamous cell carcinoma progression.

Anoikis, also called suspension-induced apoptosis, plays an important role in tumor development, progression, and metastasis. Recently we found that hepatocyte growth factor (HGF) inhibited anoikis of human head and neck squamous cell carcinoma (HNSCC) cells by activating the extracellular signal-regulated kinase (ERK)-signaling pathway. However, the anti-apoptotic effectors that were regulated by the ERK-signaling pathway were unknown.

Nitric oxide synthase/PGE(2) cross-talk in rat submandibular gland.

It is known that nitric oxide modulates the prostaglandin generation. However, little is known about the regulatory action of prostaglandin on nitric oxide production. There is a molecular cross-talk between nitric oxide and prostaglandin.

Do we need clinical trials to test the ability of transdermal HRT to prevent coronary heart disease?

Postmenopausal hormone replacement therapy (HRT) with oral oestrogen was predicted to reduce coronary heart disease (CHD) risk by 50%. Randomized controlled trials show no such benefit, however, pointing instead to an initial increase in CHD events. Although the cardiovascular effects of transdermal HRT are largely unknown, improvements in arterial function are maintained when oestrogen is administered transdermally.

Autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor in children with congenital heart block.

Isolated congenital heart block may be associated with autoimmune disorder such as Sjögren Syndrome and systemic lupus erythematosus. In this work we demonstrate circulating autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor (mAChR) in the sera of children with congenital heart block. This antibody were able to react with the second extracellular loop of the human M1 mAChR as demonstrated using a synthetic peptide in enzyme immune assay and binding assay.

Effect of tea polyphenols on growth of oral squamous carcinoma cells in vitro.

Epidemiologic evidence indicates that both black and green tea is a rich source of flavonoids and other polyphenolic antioxidants which protects against heart disease and cancer. In the current investigation, utilizing human oral squamous carcinoma cell line SCC-25, we have evaluated the effect of three major tea constituents, (-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate (ECG) and (-)-epigallocatechin (EGC) on cell growth and DNA synthesis. Test agents in concentrations of 50, 80, 100 and 200 microM were incubated in triplicates in DMEM-HAM's F-12 (50: 50) supplemented with 10% calf serum and antibiotics in an atmosphere of 5% CO2 in air for 72 hrs.

A Role for Inflammation in Chronic Pain.

Recent studies indicate that inflammatory events induced by nerve injury play a central role in the pathogenesis of neuropathic pain. These involve inflammatory cells (eg, macrophages), the production of molecules that mediate inflammation (cytokines/interleukins), and the production of nerve growth factor (NGF). However, in many instances, neuropathic pain is associated with nerve inflammation, neuritis, in the absence of nerve injury.