siRNA Versus miRNA as Therapeutics for Gene Silencing

Discovered a little over two decades ago, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are noncoding RNAs with important roles in gene regulation. They have recently been investigated as novel classes of therapeutic agents for the treatment of a wide range of disorders including cancers and infections. Clinical trials of siRNA- and miRNA-based drugs have already been initiated. siRNAs and miRNAs share many similarities, both are short duplex RNA molecules that exert gene silencing effects at the post-transcriptional level by targeting messenger RNA (mRNA), yet their mechanisms of action and clinical applications are distinct. The major difference between siRNAs and miRNAs is that the former are highly specific with only one mRNA target, whereas the latter have multiple targets. The therapeutic approaches of siRNAs and miRNAs are therefore very different. Hence, this review provides a comparison between therapeutic siRNAs and miRNAs in terms of their mechanisms of action, physicochemical properties, delivery, and clinical applications. Moreover, the challenges in developing both classes of RNA as therapeutics are also discussed.published_or_final_versio

Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections

Monoclonal antibodies represent an exciting class of therapeutics against respiratory viral infections. Notwithstanding their specificity and affinity, the conventional parenteral administration is suboptimal in delivering antibodies for neutralizing activity in the airways due to the poor distribution of macromolecules to the respiratory tract. Inhaled therapy is a promising approach to overcome this hurdle in a noninvasive manner, while advances in antibody engineering have led to the development of unique antibody formats which exhibit properties desirable for inhalation. In this Opinion, we examine the major challenges surrounding the development of inhaled antibodies, identify knowledge gaps that need to be addressed and provide strategies from a drug delivery perspective to enhance the efficacy and safety of neutralizing antibodies against respiratory viral infections

The Diurnal Variation on Cardiovascular Endurance Performance of Secondary School Athlete Student

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Design of dry powder formulations of pH responsive peptide/plasmid DNA complexes for pulmonary delivery

Poster Presentation: no. 13PS50Respiratory diseases are substantial public health problems around the world. Recently, nucleic acid was developed as a potential therapeutic strategy to tackle a series of lung diseases. Delivery still poses one of the major challenges for their clinical application. pH responsive peptides containing either histidine or derivatives of 2,3-diaminopropionic acid (Dap) can mediate effective DNA transfection in lung epithelial cells with the latter remaining effective even in the presence of lung surfactant containing bronchoalveolar fluid (BALF), which make them promising vectors for delivering therapeutic nucleic acid to the airways .....published_or_final_versio

Single Cell Transfection through Precise Microinjection with Quantitatively Controlled Injection Volumes

Cell transfection is a technique wherein foreign genetic molecules are delivered into cells. To elucidate distinct responses during cell genetic modification, methods to achieve transfection at the single-cell level are of great value. Herein, we developed an automated micropipette-based quantitative microinjection technology that can deliver precise amounts of materials into cells. The developed microinjection system achieved precise single-cell microinjection by pre-patterning cells in an array and controlling the amount of substance delivered based on injection pressure and time. The precision of the proposed injection technique was examined by comparing the fluorescence intensities of fluorescent dye droplets with a standard concentration and water droplets with a known injection amount of the dye in oil. Injection of synthetic modified mRNA (modRNA) encoding green fluorescence proteins or a cocktail of plasmids encoding green and red fluorescence proteins into human foreskin fibroblast cells demonstrated that the resulting green fluorescence intensity or green/red fluorescence intensity ratio were well correlated with the amount of genetic material injected into the cells. Single-cell transfection via the developed microinjection technique will be of particular use in cases where cell transfection is challenging and genetically modified of selected cells are desiredpublished_or_final_versio

Numerical studies of the Lagrangian approach for reconstruction of the conductivity in a waveguide

We consider an inverse problem of reconstructing the conductivity function in a hyperbolic equation using single space-time domain noisy observations of the solution on the backscattering boundary of the computational domain. We formulate our inverse problem as an optimization problem and use Lagrangian approach to minimize the corresponding Tikhonov functional. We present a theorem of a local strong convexity of our functional and derive error estimates between computed and regularized as well as exact solutions of this functional, correspondingly. In numerical simulations we apply domain decomposition finite element-finite difference method for minimization of the Lagrangian. Our computational study shows efficiency of the proposed method in the reconstruction of the conductivity function in three dimensions

Spray freeze drying of small nucleic acids as inhaled powder for pulmonary delivery

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Use of biologics for inflammatory bowel disease in Hong Kong: consensus statement

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A Novel Liquid Multi-Phytonutrient Supplement Demonstrates DNA-Protective Effects

This study explored the DNA protective (anti-mutagenic) effects of an oral, liquid, multi-phytonutrient dietary supplement containing a proprietary blend of fruits, vegetables and aloe vera concentrated components in addition to a proprietary catechin complex from green tea (VIBE Cardiac & Life, Eniva Nutraceuticals, Anoka, MN; herein described as “VIBE”). This study tested the hypothesis that VIBE would reduce DNA damage in skin cells exposed to UVR. Human epidermal cells, from the cell line A431NS, were treated with 0% (control), 0.125%, 0.5%, 1% and 2% VIBE, and then exposed to 240 J/m2 UVR. The amount of DNA damage was assessed using the COMET assay. At each concentration tested, a significantly smaller amount of DNA damage was measured by the COMET assay for the VIBE treated cells compared to the control cells exposed to UVR without VIBE. The dose response curves showed a maximal response at 0.5% VIBE with a threefold reduction in COMET tail density compared to the control samples without VIBE (p < 0.001). Additional research is warranted in human clinical trials to further explore the results of this study which demonstrated the DNA protective and anti-mutagenic effects of VIBE for human skin cells exposed to UVR-induced DNA damage

Three little pieces for computer and relativity

Numerical relativity has made big strides over the last decade. A number of problems that have plagued the field for years have now been mostly solved. This progress has transformed numerical relativity into a powerful tool to explore fundamental problems in physics and astrophysics, and I present here three representative examples. These "three little pieces" reflect a personal choice and describe work that I am particularly familiar with. However, many more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation: 100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech Republic. To appear in the Proceedings (Edition Open Access). Collects results appeared in journal articles [72,73, 122-124