Role of microbial dysbiosis in carcinogenesis & cancer therapies.

The human body supports a heterogeneous population of microorganisms. Every microorganism has the ability to contribute to the unique microenvironment around it. The aim of this review is to discuss the changes in the microbial population and their relative abundance across different ecosystems of the human body, the interactions within the microbial communities, metabolites they secrete to their external environment, their immunomodulatory functions, their signal transduction pathways and how these respond to environmental stimuli such as various diets, alcohol and drug consumption, smoking and finally suggest new therapeutic approaches. The microbiota may leads to cancer through inflammation mediated mechanisms which modulate immune responses, or produce carcinogenic metabolites and genotoxins, or deregulate cell proliferative signalling pathways. The identification of these molecular mechanisms in carcinogenesis may lead to better treatment strategies. In this review we have tried to explore the changes in microbial composition between cancer and normal tissues and what molecular mechanisms provide a connecting link between microbial dysbiosis and cancer.

MiRNA expression profiling and emergence of new prognostic signature for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome. As deregulated miRNA expression plays a crucial role in malignant transformation and cancer progression, the present study is aimed at profiling the miRNA expression pattern in OSCC and developing a new miRNA prognostic signature for oral cancer. MiRNA expression profiling was performed using MiRNA microarray in 30 tumor and 18 normal samples. MiRNA signature obtained was validated with quantitative real time PCR (qRT-PCR) in 144 tumor and 36 normal samples. The potential targets, clinical implications and prognostic value of the miRNA signature were elucidated by various bioinformatics and statistical analyses. Microarray profiling identified a set of 105 miRNAs to be differentially expressed in OSCC, out of which a subset of 19 most dysregulated miRNAs were validated by qRT-PCR. In silico analysis revealed the signature miRNAs to be involved in various cancer associated pathways. Up-regulation of miR-196a, miR-21, miR-1237 and downregulation of miR-204, miR-144 was associated with poor prognosis of OSCC patients. The mir-196a/miR-204 expression ratio emerged as best predictor for disease recurrence and patient survival. Altogether, our study identified a miRNA signature for OSCC with prognostic significance.

Evaluating Wharton's Jelly-Derived Mesenchymal Stem Cell's Survival, Migration, and Expression of Wound Repair Markers under Conditions of Ischemia-Like Stress.

The efficacy of mesenchymal stem cell (MSC) therapy is currently limited by low retention and poor survival of transplanted cells as demonstrated by clinical studies. This is mainly due to the harsh microenvironment created by oxygen and nutrient deprivation and inflammation at the injured sites. The choice of MSC source could be critical in determining fate and cellular function of MSCs under stress. Our objective here was to investigate the influence of ischemia-like stress on Wharton's jelly MSCs (WJ-MSCs) from human umbilical cord to assess their therapeutic relevance in ischemic diseases. We simulated conditions of ischemia in vitro by culturing WJ-MSCs in 2% oxygen in serum deprived and low glucose medium. Under these conditions, WJ-MSCs retained viable population of greater than 80%. They expressed the characteristic MSC surface antigens at levels comparable to the control WJ-MSCs and were negative for the expression of costimulatory molecules. An upregulation of many ECM and adhesion molecules and growth and angiogenic factors contributing to wound healing and regeneration was noted in the ischemic WJ-MSC population by a PCR array. Their migration ability, however, got impaired. Our findings provide evidence that WJ-MSCs might be therapeutically beneficial and potent in healing wounds under ischemic conditions.