Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications.

Background: Oral squamous cell carcinoma (OSCC) is a malignant oral cavity neoplasm that affects many people, especially in developing countries. Despite several advances that have been made in diagnosis and treatment, the morbidity and mortality rates due to OSCC remain high. Accumulating evidence indicates that aberrant activation of cellular signaling pathways, such as the Notch, Wnt and Hedgehog pathways, occurs during the development and metastasis of OSCC.

1, 25-dihydroxyvitamin D downregulates cytotoxic effector response in pulmonary tuberculosis.

1,25-dihydroxyvitaminD [1,25(OH)D] modulates both the innate and adaptive immunity in tuberculosis. We explored the effect of 1,25(OH)D on cytolytic molecules like perforin, granulysin, and granzyme-B in T-cells and natural killer cells during M. tuberculosis (Mtb) infection.

Hypoxia induced EMT: A review on the mechanism of tumor progression and metastasis in OSCC.

Hypoxia, a condition of low oxygen tension in tissues, has emerged as a crucial factor in tumor pathophysiology. Hypoxic microenvironment gives rise to altered cellular metabolism and triggers varied molecular responses. These responses promote tumor progression and confer radiation resistance and chemo resistance to tumors.

IL-10 Promoter -592 Polymorphism may Influence Susceptibility to HIV Infection in South Indian Population.

Background: Genetic factors play an important role in the development of disease susceptibility or protection. Cytokine gene polymorphisms are reported to be associated with altered levels of cytokine production that can impact disease progression in HIV and TB.

Objective: In this study, we studied IL-10 -592(C/A) and TGF-β -509 (C/T) promoter polymorphisms to understand their role in susceptibility or resistance to HIV and TB in a South Indian population.

Downregulation of Notch4 - a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma.

Introduction: Oral verrucous carcinoma is a special form of well-differentiated squamous cell carcinoma which possesses specific clinical, morphologic and cytokinetic features that differ from other types of oral cancers and hence diagnosis requires immense experience in histopathology. Hence it is certainly important to distinguish such a lesion from other oral tumors as treatment strategies vary widely between them.

Objective: In search of a critical diagnostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma, Notch4 receptor, one of the key regulatory molecules of the Notch signaling family has been aberrantly activated in the progression of several types of tumors.

Influence of Cdx2 and TaqI Gene Variants on Vitamin D Modulated Intracellular Chemokine Positive T-Cell Subsets in Pulmonary Tuberculosis.

Purpose: We studied the effect of 1,25(OH)D (vitamin D) on intracellular chemokine-positive T-cell subsets in whole blood cultures of healthy controls and patients with pulmonary tuberculosis.

Methods: Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. The regulatory role of the Cdx2 and 3'UTR TaqI gene variants on chemokine-positive T-cell subsets was studied from culture filtrate antigen stimulated with or without vitamin D treated whole blood cultures of 60 healthy controls and 50 patients with pulmonary tuberculosis.

Regulatory role of Cdx-2 and Taq I polymorphism of vitamin D receptor gene on chemokine expression in pulmonary tuberculosis.

Vitamin D receptor (VDR) gene variants have been shown to be regulating the immune response in tuberculosis. We studied the regulatory role of VDR promoter Cdx-2 and 3'UTR TaqI gene variants on chemokine levels from culture filtrate antigen (CFA) stimulated with or without 1,25(OH)2D3 treated peripheral blood mononuclear cells of 50 pulmonary tuberculosis patients (PTB) and 51 normal healthy controls (HCs). In CFA with 1,25(OH)2D3 treated cultures, the MIP-1α, MIP-1β, RANTES levels were significantly decreased in Cdx-2 AA genotype compared to GG genotype, while a significantly increased MIG level was observed in Cdx-2 AA genotype (p<0.

Effect of vitamin D3 on chemokine levels and regulatory T-cells in pulmonary tuberculosis.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] the active form of vitamin D3 acts as an immunomodulator in various immune cells. The present study is aimed to study the effect of 1,25(OH)2D3 on chemokine levels and regulatory T-cells in 51 healthy controls (HCs) and 50 pulmonary tuberculosis (PTB) patients. Peripheral blood mononuclear cells were cultured with culture filtrate antigen (CFA) of Mycobacterium tuberculosis in the presence or absence of 1,25(OH)2D3 at 10(-7) M concentration for 72 h and the percentage positive regulatory T-cell subsets were studied using flow cytometry.

Genotoxicity evaluation of metformin and glimepiride by micronucleus assay in exfoliated urothelial cells of type 2 diabetes mellitus patients.

Micronucleus (MN) assay was performed on the exfoliated urothelial cells to detect the genotoxic effects of the anti-hyperglycemic drugs, metformin and glimepiride in T2DM patients and to use it as a biomarker for DNA damage by assessing the frequency of micronuclei in the exfoliated urothelial cells. A total of 201 subjects (147 T2DM patients & 54 Normal cases) were selected from diverse age groups (25-75 years) and the mean MN frequency was examined per 1000 cells in all the subjects. Relative to the control group (5.

Vitamin D: Immuno-modulation and tuberculosis treatment.

Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment.

Effect of 1,25-dihydroxy vitamin D3 on cathelicidin expression in patients with and without cavitary tuberculosis.

1,25-dihydroxy vitamin D3 (1,25(OH)2D3) is a potent immuno-modulator which induces LL-37, the active peptide of cathelicidin, and restricts the growth of Mycobacterium tuberculosis (Mtb) in human macrophages. In the present study, we investigated the effect of 1,25(OH)2D3 on cathelicidin antimicrobial peptide (CAMP) expression in healthy controls (HCs) and pulmonary tuberculosis (PTB) patients. Peripheral blood mononuclear cells (PBMCs) from 50 HCs and 35 PTB patients were cultured for 72 h either with Mtb alone or Mtb with 1,25(OH)2D3 at 10(-7) M concentration.

1,25-Dihydroxy vitamin D3 downregulates pro-inflammatory cytokine response in pulmonary tuberculosis.

1,25-Dihydroxy vitamin D3 [1,25(OH)2D3] is a potent immunomodulator and regulates various immune responses to Mycobacterium tuberculosis (Mtb). The present study aimed to understand the effect of 1,25(OH)2D3 on pro-inflammatory cytokine response to Mtb antigen. Peripheral blood mononuclear cells from 42 healthy controls (HCs) and 42 pulmonary tuberculosis (PTB) patients were cultured with culture filtrate antigen (CFA) of Mtb with and without 1,25(OH)2D3 at 10(-7)M concentration for 72 h.

Molecular cloning, sequencing and structural studies of granulocyte-macrophage colony-stimulating factor (GM-CSF) from Indian water buffalo (Bubalus bubalis).

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is essential for growth and development of progenitors of granulocytes and monocytes/macrophages. In this study, we report molecular cloning, sequencing and characterization of GM-CSF from Indian water buffalo, Bubalus bubalis. In addition, we performed sequence and structural analysis for buffalo GM-CSF.

Efficiency of the intestinal bacteria in the degradation of the toxic pesticide, chlorpyrifos.

Chlorpyrifos (CP) is the most commonly used pesticide throughout the world. Its widespread use in agriculture and its potential toxicity to humans from ingestion of CP contaminated food have raised concerns about its risk to health. Human intestinal microflora has the ability to degrade pesticides, but the exact mechanisms involved and the metabolite end-products formed are not well understood.

Effect of vitamin D3 on chemokine expression in pulmonary tuberculosis.

1,25 Dihydroxy vitamin D(3) (vitamin D(3)) is an immunomodulator and its deficiency has been associated with susceptibility to tuberculosis. We have studied the immunoregulatory role of vitamin D(3) on various chemokine expression in pulmonary tuberculosis. Peripheral blood mononuclear cells obtained from 21 pulmonary tuberculosis (PTB) patients and 24 healthy controls (HCs) were cultured for 48 h with culture filtrate antigen (CFA) of Mycobacterium tuberculosis with or without vitamin D(3) at a concentration 1 × 10(-7)M.

Cloning and sequencing of Indian water buffalo (Bubalus bubalis) interleukin-3 cDNA.

Full-length cDNA (435 bp) of the interleukin-3(IL-3) gene of the Indian water buffalo was amplified by reverse transcriptase-polymerase chain reaction and sequenced. This sequence had 96% nucleotide identity and 92% amino acid identity with bovine IL-3. There are 10 amino acid substitutions in buffalo compared with that of bovine.

Toll-like receptor and TIRAP gene polymorphisms in pulmonary tuberculosis patients of South India.

Toll-like receptors (TLRs) are pattern recognition receptors and play an important role in innate immunity. Changes in TLRs and signaling molecules that result from polymorphisms are often associated with susceptibility to various infectious diseases. In the present study, we investigated whether variants in the TLR-1 1805T/G (Ile602Ser), TLR-2 2258G/A (Arg753Gln), TLR-4 896A/G (Asp299Gly), TLR-4 1196C/T (Thr399Ile), TLR-6 745C/T (Ser249Pro), TIRAP 975C/T (Ser180Leu) genes and TLR-9 promoter region polymorphisms at positions -1237C/T and -1486C/T are associated with susceptibility or resistance to pulmonary tuberculosis (PTB).

Interferon gamma gene +874A/T polymorphism and intracellular interferon gamma expression in pulmonary tuberculosis.

We investigated whether IFN-gamma gene +874(A/T) polymorphism influences intracellular interferon gamma expression in T-cell subsets of normal healthy subjects (NHS) and pulmonary tuberculosis patients (PTB). Peripheral blood mononuclear cells were stimulated with live Mycobacterium tuberculosis (MTB) and the intracellular IFN-gamma expression was studied using flow cytometry. Genotyping of IFN-gamma gene +874(A/T) was done using allele specific polymerase chain reaction.

Plasma 1,25 dihydroxy vitamin D3 level and expression of vitamin d receptor and cathelicidin in pulmonary tuberculosis.

Introduction: Vitamin D(3), which exerts its effect through vitamin D receptor (VDR), is known for its potent immunomodulatory activities. Associations between low serum vitamin D(3) levels and increased risk of tuberculosis have been reported.

Study Subjects And Methods: Plasma 1,25 dihydroxy vitamin D(3) levels (1,25(OH)(2) D(3)) and ex vivo levels of VDR protein from peripheral blood mononuclear cells were studied in 65 pulmonary tuberculosis (PTB) patients and 60 normal healthy subjects (NHS) using enzyme-linked immunosorbent assay-based methods.

CD209 gene polymorphisms in South Indian HIV and HIV-TB patients.

Dendritic-cell-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing non-integrin (DC-SIGN), a pattern recognition receptor, is associated with immune functions and is also exploited by HIV-1 and Mycobacterium tuberculosis as a part of their immune evasion strategy. In the present study we investigated whether variants in the DC-SIGN encoding CD209 gene are associated with susceptibility to or protection against HIV-1 infection as well as development of tuberculosis (TB) among HIV-1 infected south Indian patients. CD209 gene variants in the promoter region (-336 and -139), in the intron and 3'-untranslated regions (In2+11 and 2281) were studied using polymerase chain reaction-based genotyping methods in 131 HIV patients without TB (HIV+TB-) and 107 HIV patients with TB (HIV+TB+), 107 HIV negative pulmonary TB patients (HIV-PTB+) and 157 healthy controls.

Cytokine gene polymorphisms and cytokine levels in pulmonary tuberculosis.

Polymorphisms in the cytokine genes are known to influence cytokine levels and may be associated with outcome of infections. We investigated the polymorphisms in the cytokine genes namely IFN-gamma (+874 and +5644), IL-2 (-330 and +160), IL-4 (VNTR), IL-6 (-174), IL-10 (-1082 and -819) and IL-12B (+1188) in 188 normal healthy subjects (NHS) and 166 pulmonary tuberculosis patients (PTB) using polymerase chain reaction-based methods. To study the influence of cytokine gene polymorphisms on cytokine levels, phytohaemagglutinin and culture filtrate antigen of Mycobacterium tuberculosis-induced cytokine levels were measured by ELISA from 72-h-old peripheral blood mononuclear cell culture supernatants.

Regulatory region polymorphisms of vitamin D receptor gene in pulmonary tuberculosis patients and normal healthy subjects of south India.

Vitamin D receptor (VDR) gene variants are associated with differential susceptibility or resistance to tuberculosis in different ethnic groups. We investigated the polymorphisms in the 5' regulatory region of VDR gene in 206 normal healthy subjects and 166 patients with pulmonary tuberculosis from south India. Cdx-2 polymorphism was studied by polymerase chain reaction (PCR) with allele-specific primers, while genotyping of A1012G was done by PCR-based restriction fragment length polymorphism.

Promoter polymorphism of IL-18 gene in pulmonary tuberculosis in South Indian population.

Interleukin-18 (IL-18) plays a vital role in both innate and acquired immunity. We analysed polymorphisms at -607(C/A) and -137(G/A) in the promoter region of IL-18 gene by allele-specific polymerase chain reaction in normal healthy subjects (n = 173) and patients with pulmonary tuberculosis (n = 165). Allele, genotype and haplotype frequencies did not differ significantly between normal healthy subjects and patients.