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More than 29 million adults in the United States have been diagnosed with hearing loss. Interestingly, elevated homocysteine (Hcy) levels, known as hyperhomocysteinemia (HHcy), are also associated with impaired hearing. However, the associated mechanism remains obscure. The collagen receptor such as discoidin domain receptor 1 and matrix metalloproteinase (MMP) play a significant role in inner ear structure and function. We hypothesize that HHcy increases hearing thresholds by compromise in inner ear vasculature resulted from impaired Hcy metabolism, increased oxidative stress, collagen IVa and collagen Ia turnover. The treatment with folic acid (FA) protects elevated hearing thresholds and prevents reduction in vessel density by lowering abundant collagen deposition and oxidative stress in inner ear. To test this hypothesis we employed 8 weeks old male wild type (WT), cystathionine-beta-synthase heterozygote knockout (CBS+/-) mice, WT + FA (0.0057 μg/g/day, equivalent to a 400 μg/70 kg/day human dose in drinking water); and CBS(+/-) +FA. The mice were treated for four weeks. The hearing thresholds were determined by recording the auditory brainstem responses. Integrity of vessels was analyzed by perfusion of horseradish peroxidase (HRP) tracer. Endothelial permeability was assessed, which indicated restoration of HRP leakage by FA treatment. A total Hcy level was increased in stria vascularis (SV) and spiral ligament (SL) of CBS+/- mice which was lowered by FA. Interestingly, FA treatment lowered Col IVa Immunostaining by affecting its turnover. The levels of MMP-2, -9, methylenetetrahydrofolate reductase (MTHFR) and cystathione gamma lyase (CSE) were measured by Western blot analysis. The oxidative stress was high in SV and SL of CBS+/- compared to WT however the treatment with FA lowered oxidative stress in CBS+/- mice. These data suggested that hearing loss in CBS+/- mice was primarily due to leakage in inner ear circulation, also partly by induced collagen imbalance, increase in Hcy and oxidative stress in inner ear., (Copyright © 2011 Elsevier B.V. All rights reserved.)

MicroRNAs ( miRNAs) are highly conserved, 19-23 nucleotide long, non-coding, endogenous RNA, which are transcribed from either intergenic, intronic or polycistronic regions and modulate gene expression through mRNA degradation or translational repression. They are fine tuners of biological processes and have recently emerged as biomarkers and therapeutic targets of cardiovascular diseases. Several miRNAs regulate stem cell for differentiation, proliferation and degeneration. Stem cells are pluripotent, self-renewing and clonogenic cells having tremendous potential for regenerative therapy. The current therapeutic approach is unable to cope up with rapidly increasing rates of diabetes and cardiovascular diseases. The empirical and clinical evidences revealed that transplantation of exogenous stem cells can regenerate beta cells in diabetic patients and myocardium in patients with myocardial infarction. Nevertheless, the major limitation of stem cell therapy is unpredictable behavior of exogenous stem cells that incur few reports of teratoma and cancer after transplantation. Therefore, understanding the regulation of newly transplanted stem cells into the foreign body is a major challenge to translational research / clinical trail. Since miRNA plays pivotal role in the fine regulation of proliferation and differentiation of stem cells, investigations on the regulation of miRNA in transplanted stem cells in a specific micro-environment that houses the stem cell is indispensable. Additionally, the inhibition or over expression of specific miRNAs in the niche surrounding the stem cell will be crucial for maintaining the specific lineage of exogenous stem cells. This review embodies major advancement in the field of miRNA biogenesis and its regulatory mechanisms, role of different miRNAs and stem cells as a therapeutic target for diabetes and cardiovascular diseases. It also provides insights into the novel future therapy, where synergistic approach for manipulating miRNAs and stem cells will emerged as a potential treatment for diabetes and cardiovascular diseases.

While there have been a number of international initiatives centred around hydrological sciences and technical approaches, the social, economic, environmental, and legal and institutional aspects of flood management have been dealt with sporadically and in a limited manner. WMO and the Global Water Partnership have established the Associated Programme on Flood Management (APFM) to address these issues and developed a concept of Integrated Flood Management (IFM) in 2002. This article is the result of the integrated flood management approaches through pilot projects and multi-disciplinary approaches launched by the initiative since the establishment of the IFM concept. This approach seeks to integrate land- and water-resources development in a river basin, within the context of Integrated Water Resources Management (IWRM) and aims at maximizing the benefits from floodplains and at the same time reducing loss of life from flooding. This approach identified the key elements of IFM and recommended that these can be put in place by: adopting a basin approach to flood management; adopting a multi-disciplinary approach in flood management; reducing vulnerability to and risks from flooding; enabling community participation; and preserving ecosystems; and addressing climate change and variability, supported by enabling mechanism through appropriate legislation and regulations.