Beta-defensin index: A functional biomarker for oral cancer detection.

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry.

Predominant factors influencing reactive oxygen species in cancer stem cells.

Reactive oxygen species (ROS) and its related signaling pathways and regulating molecules play a major role in the growth and development of cancer stem cells. The concept of ROS and cancer stem cells (CSCs) has been gaining much attention since the past decade and the evidence show that these CSCs possess robust self-renewal and tumorigenic potential and are resistant to conventional chemo- and radiotherapy and believed to be responsible for tumor progression, metastasis, and recurrence. It seems reasonable to say that cancer can be cured only if the CSCs are eradicated.

The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging.

An increased accumulation of immune-dysfunction-associated CD4Foxp3 regulatory T cells (T) is observed in aging oral mucosa during infection. Here we studied the function of T during oral cancer development in aging mucosa. First, we found heightened proportions of T and myeloid-derived suppressor cells (MDSC) accumulating in mouse and human oral squamous cell carcinoma (OSCC) tissues.

IL-1β-MyD88-mTOR Axis Promotes Immune-Protective IL-17AFoxp3 Cells During Mucosal Infection and Is Dysregulated With Aging.

CD4Foxp3T maintain immune homeostasis, but distinct mechanisms underlying their functional heterogeneity during infections are driven by specific cytokine milieu. Here we show that MyD88 deletion in Foxp3 cells altered their function and resulted in increased fungal burden and immunopathology during oral (CA) challenge. Excessive inflammation due to the absence of MyD88 in T coincided with a reduction of the unique population of IL-17A expressing Foxp3 cells (T17) and an increase in dysfunctional IFN-γ/Foxp3 cells (TIFN-γ) in infected mice.

Microbiome Dependent Regulation of T and Th17 Cells in Mucosa.

Mammals co-exist with resident microbial ecosystem that is composed of an incredible number and diversity of bacteria, viruses and fungi. Owing to direct contact between resident microbes and mucosal surfaces, both parties are in continuous and complex interactions resulting in important functional consequences. These interactions govern immune homeostasis, host response to infection, vaccination and cancer, as well as predisposition to metabolic, inflammatory and neurological disorders.

Role of Short Chain Fatty Acids in Controlling T and Immunopathology During Mucosal Infection.

Interactions between mucosal tissues and commensal microbes control appropriate host immune responses and inflammation, but very little is known about these interactions. Here we show that the depletion of resident bacteria using antibiotics (Abx) causes oral and gut immunopathology during oropharyngeal candidiasis (OPC) infection. Antibiotic treatment causes reduction in the frequency of Foxp3+ regulatory cells (T) and IL-17A producers, with a concomitant increase in oral tissue pathology.

Diosmetin suppresses human prostate cancer cell proliferation through the induction of apoptosis and cell cycle arrest.

Diosmetin, a plant flavonoid, has been shown to exert promising effects on prostate cancer cells as an anti‑proliferative and anticancer agent. In this study, using western blot analysis for protein expression and flow cytometry for cell cycle analysis, we determined that the treatment of the LNCaP and PC‑3 prostate cancer cells with diosmetin resulted in a marked decrease in cyclin D1, Cdk2 and Cdk4 expression levels (these proteins remain active in the G0‑G1 phases of the cell cycle). These changes were accompanied by a decrease in c-Myc and Bcl-2 expression, and by an increase in Bax, p27Kip1 and FOXO3a protein expression, which suggests the potential modulatory effects of diosmetin on protein transcription.

Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell Differentiation, Inflammation, and Immunity.

While T helper (Th) cells play a crucial role in host defense, an imbalance in Th effector subsets due to dysregulation in their differentiation and expansion contribute to inflammatory disorders. Here, we show that Casz1, whose function is previously unknown in CD4 T cells, coordinates Th differentiation and . Casz1 deficiency in CD4 T cells lowers susceptibility to experimental autoimmune encephalomyelitis, consistent with the reduced frequency of Th17 cells, despite an increase in Th1 cells in mice.

Kaposi's sarcoma-associated herpesvirus infection promotes differentiation and polarization of monocytes into tumor-associated macrophages.

Tumor associated macrophages (TAMs) promote angiogenesis, tumor invasion and metastasis, and suppression of anti-tumor immunity. These myeloid cells originate from monocytes, which differentiate into TAMs upon exposure to the local tumor microenvironment. We previously reported that Kaposi's sarcoma-associated herpes virus (KSHV) infection of endothelial cells induces the cytokine angiopoietin-2 (Ang-2) to promote migration of monocytes into tumors.

Mucosal Regulatory T Cells and T Helper 17 Cells in HIV-Associated Immune Activation.

Residual mucosal inflammation along with chronic systemic immune activation is an important feature in individuals infected with human immunodeficiency virus (HIV), and has been linked to a wide range of co-morbidities, including malignancy, opportunistic infections, immunopathology, and cardiovascular complications. Although combined antiretroviral therapy (cART) can reduce plasma viral loads to undetectable levels, reservoirs of virus persist, and increased mortality is associated with immune dysbiosis in mucosal lymphoid tissues. Immune-based therapies are pursued with the goal of improving CD4(+) T-cell restoration, as well as reducing chronic immune activation in cART-treated patients.

Inflammatory Signaling Involved in High-Fat Diet Induced Prostate Diseases.

High-Fat Diet (HFD) has emerged as an important risk factor not only for obesity and diabetes but also for urological disorders. Recent research provides ample evidence that HFD is a putative cause for prostatic diseases including prostate cancer. The mechanisms whereby these diseases develop in the prostate have not been fully elucidated.

TLR-2 Signaling Promotes IL-17A Production in CD4+CD25+Foxp3+ Regulatory Cells during Oropharyngeal Candidiasis.

Recent studies show that CD4+CD25+Foxp3+ regulatory cells (Tregs) produce effector cytokines under inflammatory conditions. However, the direct role of microbial agents that serve as toll-like receptor (TLR) ligands in the induction of effector cytokines in Tregs is less clear. Here we show that CD4+Foxp3+Tregs produce the effector cytokine IL-17A during oropharyngeal candidiasis (OPC) and inflammatory bowel disease in a TLR-2/Myd88 signaling dependent manner.

Th17 inflammation model of oropharyngeal candidiasis in immunodeficient mice.

Oropharyngeal Candidiasis (OPC) disease is caused not only due to the lack of host immune resistance, but also the absence of appropriate regulation of infection-induced immunopathology. Although Th17 cells are implicated in antifungal defense, their role in immunopathology is unclear. This study presents a method for establishing oral Th17 immunopathology associated with oral candidal infection in immunodeficient mice.

Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells.

Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it's binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells.

Isolation of T cells from mouse oral tissues.

Background: Utilizing mouse models provides excellent immunological and experimental tools to study oral immune responses. However for functional assays, isolating T lymphocytes from the oral tissues has proved to be challenging due to the absence of reliable methods that yield viable cells with consistency. To study adaptive immune cell interactions in the oral mucosal tissues, it is necessary to isolate T cells with a good viability and study them at the single cell level.

Comparative Evaluation of Anti-Inflammatory Activity of Curcuminoids, Turmerones, and Aqueous Extract of Curcuma longa.

Curcuma longa is widely known for its anti-inflammatory activity in traditional system of medicine for centuries and has been scientifically validated extensively. The present study was conducted to evaluate the anti-inflammatory activity of curcuminoids and oil-free aqueous extract (COFAE) of C. longa and compare it with that of curcuminoids and turmerones (volatile oil), the bioactive components of C.

Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K/Akt/FoxO pathway.

Forkhead box O (FoxO) transcription factors play an important role as tumor suppressor in several human malignancies. Disruption of FoxO activity due to loss of phosphatase and tensin homolog and activation of phosphatidylinositol-3 kinase (PI3K)/Akt are frequently observed in prostate cancer. Apigenin, a naturally occurring plant flavone, exhibits antiproliferative and anticarcinogenic activities through mechanisms, which are not fully defined.

Deregulation of FoxO3a accelerates prostate cancer progression in TRAMP mice.

Background: Forkhead box, class "O" (FoxO) transcription factors are involved in multiple signaling pathways and possess tumor suppressor functions. Loss of PTEN and activation of PI3K/Akt is frequently observed in prostate cancer, which may potentially inactivate FoxO activity. We therefore investigated the role of FoxO transcription factors in prostate cancer progression, in particular FoxO3a, in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which mimics progressive forms of human disease.

Green tea polyphenols induce p53-dependent and p53-independent apoptosis in prostate cancer cells through two distinct mechanisms.

Inactivation of the tumor suppressor gene p53 is commonly observed in human prostate cancer and is associated with therapeutic resistance. We have previously demonstrated that green tea polyphenols (GTP) induce apoptosis in prostate cancer cells irrespective of p53 status. However, the molecular mechanisms underlying these observations remain elusive.

Protection against oxidative DNA damage and stress in human prostate by glutathione S-transferase P1.

The pi-class glutathione S-transferase (GSTP1) actively protect cells from carcinogens and electrophilic compounds. Loss of GSTP1 expression via promoter hypermethylation is the most common epigenetic alteration observed in human prostate cancer. Silencing of GSTP1 can increase generation of reactive oxygen species (ROS) and DNA damage in cells.

Induction of heme oxygenase-1 by chamomile protects murine macrophages against oxidative stress.

Aims: Protection of cells from oxidative insult may be possible through direct scavenging of reactive oxygen species, or through stimulation of intracellular antioxidant defense mechanisms by induction of antioxidant gene expression. In this study we investigated the cytoprotective effect of chamomile and elucidated the underlying mechanisms.

Main Methods: The cytoprotective effect of chamomile was examined on H(2)O(2)-induced cellular stress in RAW 264.

Chamomile confers protection against hydrogen peroxide-induced toxicity through activation of Nrf2-mediated defense response.

Oxidative stress plays an important role in the development of various human diseases. Aqueous chamomile extract is used as herbal medicine, in the form of tea, demonstrated to possess antiinflammatory and antioxidant properties. We demonstrate the cytoprotective effects of chamomile on hydrogen peroxide (H₂O₂)-induced cellular damage in macrophage RAW 264.

High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-κB.

Background: Signal transducer and activator of transcription (Stat)-3 and nuclear factor-kappa B (NF-κB) are important signaling pathways constitutively activated during inflammation. We previously reported that high-fat diet (HFD) intake induces oxidative stress in the prostate through elevated expression of NADPH oxidase subunits causing NF-κB activation. We sought to determine whether Stat-3 is involved in the activation of NF-κB in the prostate as a result of HFD feeding, leading to inflammation.

Anti-ulcer and antioxidant activity of GutGard.

The present study was undertaken to determine the anti-ulcer and antioxidant potential of GutGard, a standardized extract of Glycyrrhiza glabra commonly known as licorice. Effect of various doses (12.5, 25, and 50 mg/kg, po) of GutGard was studied on gastric ulcers in pylorus ligation-, cold-restraint stress- and indomethacin induced gastric mucosal injury in rats.