Amphiphilic triblock copolymer poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol), enhancement of gene expression and inhibition of lung metastasis by aerosol delivery

Bhattarai, S R,Kim, S Y,Jang, K Y,Yi, H K,Lee, Y H,Bhattarai, N,Nam, S-Y,Lee, D Y,Kim, H Y,Hwang, P H Nature Publishing Group 2007 Gene Therapy Vol.14 No.6

<P>We describe the development of an aerosol system for topical gene delivery to the lungs of C57BL/6 mice. This system is based on the combination of the commercial cationic lipid Lipofectin with a novel amphiphilic triblock copolymer, poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol) (PPDO/PLLA-b-PEG, and abbreviated in the text as polymeric micelles). After optimizing conditions for DNA delivery to the lungs of mice using the combination of polymeric micelles with Lipofectin and LacZ DNA, we used the Lipofectin/polymeric micelle system to deliver the tumor suppressor gene PTEN to the lungs of C57BL/6 mice bearing the B16-F10 melanoma. Lipofectin/PTEN/polymeric micelles significantly improved gene expression of PTEN in the lungs of mice with no evidence of cell toxicity or acute inflammation. Importantly, lung metastasis, as measured by lung weight, was significantly reduced (P<0.001), as were total tumor foci in the lungs (P<0.001) and size of individual tumor nodules in animals treated with Lipofectin/PTEN/polymeric micelles compared with control animals. Survival time was also extended. These results suggest that the Lipofectin/polymeric micelle system is appropriate for enhancing gene delivery in vivo and that it can be applied as a non-invasive gene therapy for lung cancer.</P>

Hydrophilic nanofibrous structure of polylactide; fabrication and cell affinity

Bhattarai, Shanta Raj,Bhattarai, Narayan,Viswanathamurthi, Periasamy,Yi, Ho Keun,Hwang, Pyoung Han,Kim, Hak Yong Wiley Publishers 2006 Journal of Biomedical Materials Research Part A Vol. No.

<P>Microstructure and architecture of the scaffolds along with the surface chemistry exert profound effect on biological activity (cell distribution, proliferation, and differentiation). For the biological activity, scaffolds in tissue engineering have been widely designed. The objective of this study was to develop hydrophilic nanofibrous structure of polylactides (PLLA) polymer in the form of nonwoven mat by electrospinning technique, and further evaluate the fibroblast NIH3T3 cell proliferation, morphology, and cell–matrix interaction. Hydrophilicity of the PLLA fibers was improved by adding small fraction of low molecular weight polyethylene glycol (PEG) into the electrospinning solution. Four different ratio types (100/0, 80/20, 70/30, and 50/50) of PLLA/PEG electrospun matrices were fabricated, and the pore characteristics, tensile properties, contact angle, and hydrolytic degradation were observed. Furthermore, scanning electron microscope (SEM) and fluorescence actin staining images were used for micro-observation of cell–matrix interaction and cell morphology. It was found that the electrospun mat of PLLA/PEG (80/20), composed of fibers with diameters in the range 540–850 nm, majority of pore diameter less than 100 μm, tensile strength 8 MPa, elongation 150%, porosity more than 90%, and improved hydrophilicity with slow hydrolytic degradation, is favorable for biological activity of NIH3T3 fibroblast cell. Based on these results, the correct composition of PLLA and PEG in the porous electrospun matrix (i.e., PLLA/PEG (80/20)) will be a better candidate rather than other compositions of PLLA/PEG as well as hydrophobic PLLA for application in tissue engineering. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006</P>

Effect of long term high altitude exposure on cardiovascular autonomic adjustment during rest and post-exercise recovery

Prem Bhattarai,Bishnu H. Paudel,Dilip Thakur,Balkrishna Bhattarai,Bijay Subedi,Rita Khadka 대한직업환경의학회 2018 대한직업환경의학회지 Vol.30 No.-

Background: Despite the successful adaptation to high altitude, some differences do occur due to long term exposure to the hypoxic environment. The effect of long term high altitude exposure on cardiac autonomic adjustment during basal and post-exercise recovery is less known. Thus we aimed to study the differences in basal cardiac autonomic adjustment and its response to exercise in highlanders and to compare it with lowlanders. Methods: The study was conducted on 29 healthy highlander males who were born and brought up at altitude of 3000 m and above from the sea level, their cardiac autonomic adjustment was compared with age, sex, physical activity and ethnicity-matched 29 healthy lowlanders using Heart Rate Variability (HRV) during rest and recovery from sub-maximal exercise (3 m step test). Intergroup comparison between the highlanders and lowlanders and intragroup comparison between the rest and the postexercise recovery conditions were done. Results: Resting heart rate and HRV during rest was comparable between the groups. However, heart rate recovery after 3 min step test was faster in highlanders (p 〈 0.05) along with significantly higher LF power and total power during the recovery phase. Intragroup comparison of highlanders showed higher SDNN (p 〈 0.05) and lower LF/HF ratio (p〈 0.05) during recovery phase compared to rest which was not significantly different in two phases in lowlanders. Further highlander showed complete recovery of RMSSD, NN50, pNN50 and HF power back to resting level within five minutes, whereas, these parameters failed to return back to resting level in lowlanders within the same time frame. Conclusion: Highlanders completely recovered back to their resting state within five minutes from cessation of step test with parasympathetic reactivation; however, recovery in lowlanders was delayed.

Simulation and Model Validation of a Pneumatic Conveying Drying for Wood Dust Particles

Bhattarai, Sujala,Kim, Dae-Hyun,Oh, Jae-Heun Korean Society for Agricultural Machinery 2012 바이오시스템공학 Vol.37 No.2

Purpose: The simulation model of a pneumatic conveying drying (PCD) for sawdust was developed and verified with the experiments. Method: The thermal behavior and mass transfer of a PCD were modeled and investigated by comparing the experimental results given by a reference (Kamei et al. 1952) to validate the model. Momentum, energy and mass balance, one dimensional first order ordinary differential equations, were coded and solved into Matlab V. 7.1.0 (2009). Results: The simulation results showed that the moisture content reduced from 194% to 40% (dry basis), air temperature decreased from $512^{\circ}C$ to $128^{\circ}C$ with the particle residence time of 0.7 seconds. The statistical indicators, root mean square error and R-squared, were calculated to be 0.079, and 0.998, respectively, between the measured and predicted values of moisture content. The relative error between the measured and predicted values of the final pressured drop, air temperature, and air velocity were only 8.96%, 0.39% and 1.05% respectively. Conclusions: The predicted moisture content, final temperature, and pressure drop values were in good agreement with the experimental results. The developed model can be used for design and estimation of PCD system for drying of wood dust particles.

Synthesis and Antibacterial Activity of Novel 2-Oxo-pyrrolidinyl Oxazolidinones

Bhattarai, Deepak,Lee, Sun-Hee,Kim, Hyeong-Kyu,Kang, Soon-Bang,Pae, Ae-Nim,Kim, Eunice Eun-Kyeong,Oh, Taeg-Won,Cho, Sang-Nae,Keum, Gyo-Chang Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.4

Novel antibacterial oxazolidinones bearing pyrrolidinone ring system at the C-5 side chain were synthesized and their in vitro antibacterial activities were evaluated. Most of the synthesized oxazolidinones showed good antibacterial activity against the Gram-positive and Gram-negative bacteria tested.

A controlled surface geometry of polyaniline doped titania nanotubes biointerface for accelerating MC3T3-E1 cells growth in bone tissue engineering

Bhattarai, Deval Prasad,Shrestha, Sita,Shrestha, Bishnu Kumar,Park, Chan Hee,Kim, Cheol Sang Elsevier 2018 CHEMICAL ENGINEERING JOURNAL -LAUSANNE- Vol.350 No.-

<P><B>Abstract</B></P> <P>In this work, titanium oxide nanotubes (TNTs) have been developed via electrochemical anodization process, followed by potentiostatic electropolymerization of aniline monomer to achieve TNTs coated polyaniline (PANI) substrate using cyclic voltammetry method at low temperature. Prior to PANI decoration, crystallinity of titanium oxide nanotubes (TNTs) was obtained by annealing the substrate at 420 °C for two hours. The physicochemical characterization of the as-prepared TNTs and TNTs/PANI were analyzed using FE-SEM, AFM, XRD and FT-IR techniques. A coating of PANI forms a sheath around the nanotubes and protects them from metallic corrosion. Large surface area to volume ratio of TNTs showed improved properties in biocompatibility, thermal stability, electrical conductivity, biomineralization and hydrophilicity after coating with PANI, an electroactive conducting polymer. In addition, the TNTs/PANI exhibited an effective platform to enhance attachment, development and proliferation of preosteoblast (MC3T3-E1) cells which opens a new avenue in the realm of bone tissue engineering. The cells’ morphology to their surrounding topography, development, or proliferation, and osteogenic-related markers (such as ALP increased level, collagen type I secretion) were also analysed. Such types of surface modification tailoring on titanium nanotubes could offer a potential and a promising scaffold material for biomedical implantation in bone tissue engineering.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A uniform surface topography of titanium nanotubes (TNTs) were fabricated through anodization. </LI> <LI> The TNTs were coated with polyaniline (PANI) via cyclic voltammetric technique. </LI> <LI> The bioinspired TNTs/PANI showed an effective antibacterial property. </LI> <LI> Highly biocompatible TNTs/PANI scaffolds enhanced the proliferation of pre-osteoblast cells. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Microwave Drying of Sawdust for Pellet Production: Kinetic Study under Batch Mode

Bhattarai, Sujala,Oh, Jae-Heun,Choi, Yun Sung,Oh, Kwang Cheol,Euh, Seung Hee,Kim, Dae Hyun Korean Society for Agricultural Machinery 2012 바이오시스템공학 Vol.37 No.6

Purpose: Drying characteristics of sawdust was studied under batch mode using lab scale microwave dryer. The objective of this study was to investigate the effect of material load and microwave output power on drying characteristics of sawdust. Methods: Material load and microwave output power were varied from 23 to 186 g and 530 to 370 W respectively. Different kinetic models were tested to fit the drying rates of sawdust. Similarly, the activation energy was calculated by employing the Arrhenius equation. Results: The drying efficiency increased considerably, whereas the specific energy consumption significantly decreased with increase in material load and microwave output power. The cumulative energy efficiency increased by 9%, and the specific energy consumption decreased by 8% when the material load was increased from 23 to 186 g. The effective diffusivity increased with decrease in material load and increase in microwave output power. The previously published model gave the best fit for data points with $R^2$ and RMSE values of 0.999 and 0.01, respectively. Conclusions: The data obtained from this study could be used as a basis for modeling of large scale industrial microwave dryers for the pellet production.

Application of CE-QUAL-W2 [v3.2] to Andong Reservoir:Part II: Simulations of Chlorophyll a and Total Phosphorus Dynamics

Bhattarai Prasid Ram,김윤희,김범철,허우명 한국하천호수학회 2008 생태와 환경 Vol.41 No.4

The calibrated Andong Reservoir hydro-dynamic module (PART I) of the 2-dimensional hydrodynamic and water quality model, CE-QUAL-W2 [v3.2], was applied to examine the dynamics of total phosphorus, and chlorophyll a concentration within Andong Reservoir. The modeling effort was supported with the data collected in the field for a five year period. In general, the model achieved a good accuracy throughout the calibration period for both chlorophyll a and total phosphorus concentration. The greatest deviation in algal concentration occurred on 10th October, starting at the layer just beneath the surface layer and extending up to the depth of 35 m. This deviation is principally attributed to the effect of temperature on the algal growth rate. Also, on the same date, the model over-predicts hypolimnion and epilimnion total phosphorus concentration but under-predicts the high concentrated plume in the metalimnion. The large amount of upwelling of finer suspended solid particles, and re-suspension of the sediments laden with phosphorus, are thought to have caused high concentration in the epilimnion and hypolimnion, respectively. Nevertheless, the model well reproduced the seasonal dynamics of both chlorophyll a and total phosphorus concentration. Also, the model tracked the interflow of high phosphorus concentration plume brought by the turbid discharge during the Asian summer monsoon season. Two different hypothetical discharge scenarios (discharge from epilimnetic, and hypolimnetic layers) were analyzed to understand the response of total phosphorus interflow plume on the basis of differential discharge gate location. The simulated results showed that the hypolimnetic discharge gate operation (103~113 m) was the most effective reservoir structural control method in quickly discharging the total phosphorus plume (decrease of in-reservoir concentration by 219% than present level).

Homology Modeling and Docking Studies of Streptomyces peucetius CYP147F1 as Limonene Hydroxylase

( Bhattarai Saurabh ),( Kwangkyoung Liou ),( Tae Jin Oh ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.7

Homology modeling of Streptomyces peucetius CYP147F1 was constructed using three cytochrome P450 structures, CYP107L1, CYPVdh, and CYPeryF, as templates. The lowest energy SPCYP147F1 model was then assessed for stereochemical quality and side-chain environment by Accelrys Discovery Studio 3.1 software. Further activesite optimization of the SPCYP147F1 was performed by molecular dynamics to generate the final SPCYP147F1 model. The substrate limonene was then docked into the model. The model-limonene complex was used to validate the active-site architecture, and functionally important residues within the substrate recognition site were identified by subsequent characterization of the secondary structure. The docking of limonene suggested that SPCYP147F1 would have broad specificity with the ligand based on the two different orientations of limonene within the active site facing to the heme. Limonene with C7 facing the heme with distance of 3.4 A from the Fe was predominant.

Gene Delivery of c-myb Increases Bone Formation Surrounding Oral Implants

Bhattarai, G.,Lee, Y.H.,Lee, M.H.,Yi, H.K. SAGE Publications 2013 Journal of dental research Vol.92 No.9

<P>Bone regeneration around titanium (Ti) implants is a relatively slow process. The c-myb transcription factor has been associated with high proliferation and differentiation rates in bone. This study analyzed whether c-myb can enhance new bone surrounding the implant. <I>In vitro</I> overexpressed chitosan-gold nanoparticles conjugated with plasmid DNA/c-myb (Ch-GNPs/c-myb)-coated Ti surfaces were associated with enhanced expression of the osteogenic molecules osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), and bone morphogenetic proteins (BMP2/7) in MC-3T3E1 osteoblast cells. Further, to determine its <I>in vivo</I> effect, we inserted Ch-GNPs/c-myb-coated Ti implants into rat mandibles. One and 4 wks post-implantation, mandibles were examined by microcomputed tomography, immunohistochemistry, and hematoxylin & eosin staining. The microcomputed tomography analysis demonstrated that c-myb overexpression increased the density and volume of newly formed bone surrounding the implants, compared with those in controls (<I>p</I> < .05). Further, c-myb increased the number of cells expressing BMP2/7 and aided in the increase of new bone (<I>p</I> < .05). These results support the view that c-myb overexpression accelerates new bone surrounding implants and can serve as a potent molecule in promoting tissue regeneration around dental implants. The recipient rat used in this system provides an excellent <I>in vivo</I> model for studies of bone regeneration.</P>