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Ferrochelatase is a therapeutic target for ocular neovascularization
Basavarajappa, Halesha D,Sulaiman, Rania S,Qi, Xiaoping,Shetty, Trupti,Sheik Pran Babu, Sardar,Sishtla, Kamakshi L,Lee, Bit,Quigley, Judith,Alkhairy, Sameerah,Briggs, Christian M,Gupta, Kamna,Tang, Bu John Wiley & Sons Ltd 2017 EMBO molecular medicine Vol.9 No.6
<P><B>Abstract</B></P><P>Ocular neovascularization underlies major blinding eye diseases such as “wet” age‐related macular degeneration (AMD). Despite the successes of treatments targeting the vascular endothelial growth factor (VEGF) pathway, resistant and refractory patient populations necessitate discovery of new therapeutic targets. Using a forward chemical genetic approach, we identified the heme synthesis enzyme ferrochelatase (FECH) as necessary for angiogenesis <I>in vitro</I> and <I>in vivo</I>. FECH is overexpressed in wet AMD eyes and murine choroidal neovascularization; siRNA knockdown of <I>Fech</I> or partial loss of enzymatic function in the <I>Fech</I><SUP>m1Pas</SUP> mouse model reduces choroidal neovascularization. <I>FECH</I> depletion modulates endothelial nitric oxide synthase function and VEGF receptor 2 levels. FECH is inhibited by the oral antifungal drug griseofulvin, and this compound ameliorates choroidal neovascularization in mice when delivered intravitreally or orally. Thus, FECH inhibition could be used therapeutically to block ocular neovascularization.</P>
Basavarajappa Mahanthesh,Nagavangala Shankarappa Shashikumar,Bijjanal Jayanna Gireesha,Isac Lare Animasaun 한국CDE학회 2019 Journal of computational design and engineering Vol.6 No.4
The problem of exponential heat source across a flowing nanofluid (TiO2-EO; titanium oxide-Engine oil) containing tiny dust particles on a deformable planar plate has been an open question in meteorology. In this paper, the boundary layer transient two-phase flow of dusty nanoliquid on an isothermal plate which is deforming with time-dependent velocity in the presence of exponential heat source is studied. The impacts of Hall current, nonlinear radiative heat and an irregular heat source (temperature based heat source and exponential space-based heat source) are also accounted. Dusty nanofluid is the composition of dust particles and nanoliquid (TiO2-EO). Using relevant transformations, the system of PDEs is rehabil-itated to the system of ODEs and then treated numerically. Exploration of the impacts of pertinent param-eters on velocity and temperature fields is performed via graphical illustrations. Numeric data for skin friction factor and the Nusselt number is presented and their characteristics are analyzed/quantified through the slope of linear regression via data points.
Marangoni convection radiative flow of dusty nanoliquid with exponential space dependent heat source
Basavarajappa Mahanthesh,Bijjanal Jayanna Gireesha,Ballajja Chandra PrasannaKumara,Nagavangala Shankarappa Shashikumar 한국원자력학회 2017 Nuclear Engineering and Technology Vol.49 No.8
The flow of liquids submerged with nanoparticles is of significance to industrial applications, specificallyin nuclear reactors and the cooling of nuclear systems to improve energy efficiency. The application ofnanofluids in water-cooled nuclear systems can result in a significant improvement of their economicperformance and/or safety margins. Therefore, in this paper, Marangoni thermal convective boundarylayer dusty nanoliquid flow across a flat surface in the presence of solar radiation is studied. A two phasedusty liquid model is considered. Unlike classical temperature-dependent heat source effects, an exponentialspace-dependent heat source aspect is considered. Stretching variables are utilized to transformthe prevailing partial differential system into a nonlinear ordinary differential system, which is thensolved numerically via the Runge-Kutta-Fehlberg approach coupled with a shooting technique. The rolesof physical parameters are focused in momentum and heat transport distributions. Graphical illustrationsare also used to consider local and average Nusselt numbers. We examined the results under bothlinear and quadratic variation of the surface temperature. Our simulations established that the impact ofMarangoni flow is useful for an enhancement of the heat transfer rate.
Joby Mackolil,Basavarajappa Mahanthesh 한국CDE학회 2019 Journal of computational design and engineering Vol.6 No.4
The statistical and exact analysis of the unsteady radiative flow of Nano and Casson fluids past a vertical plate with Dufour effect is carried out. The heat transport phenomenon is studied under uniform heat flux (UHF) and uniform wall temperature (UWT) conditions. The exact solution to the problem is found using the Laplace transform method (LTM). The effects of various parameters on velocity, temperature and con-centration profiles are examined via graphs. The heat transfer rate and skin friction are analyzed through statistical tools like probable error and regression. The Dufour effect enhances the velocity and temper-ature profiles. It is also observed that the velocity profile is slightly greater in the case of UWT than the UHF case for both nanofluid and Casson fluid. From the regression analysis, it is established that the Dufour number and nanoparticle volume fraction have a negative impact whereas the radiative heat parameter has a positive impact on the rate of heat transfer.
The first synthesis of the antiangiogenic homoisoflavanone, cremastranone
Lee, Bit,Basavarajappa, Halesha D.,Sulaiman, Rania S.,Fei, Xiang,Seo, Seung-Yong,Corson, Timothy W. The Royal Society of Chemistry 2014 Organic & Biomolecular Chemistry Vol.12 No.39
<P>An antiangiogenic homoisoflavanone, cremastranone, was synthesized for the first time. This scalable synthesis, which includes selective demethylation, could be used to develop lead molecules to treat angiogenesis-induced eye diseases. Synthetic cremastranone inhibited the proliferation, migration and tube formation ability of human retinal microvascular endothelial cells, important steps in pathological angiogenesis.</P> <P>Graphic Abstract</P><P>The homoisoflavanone cremastranone is synthesized for the first time and shown to block human retinal endothelial cell angiogenesis <I>in vitro</I>. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4ob01604a'> </P>
Song, Seung-Hee,Kumar, Basavarajappa Mohana,Kang, Eun-Ju,Lee, Yeon-Mi,Kim, Tae-Ho,Ock, Sun-A,Lee, Sung-Lim,Jeon, Byeong-Gyun,Rho, Gyu-Jin Mary Ann Liebert 2011 STEM CELLS AND DEVELOPMENT Vol.20 No.8
<P>The present study evaluated the alkaline phosphatase activity, cell cycle stage, expression of markers and early transcriptional factors, and in vitro differentiation into selected cell lineages of porcine stem/stromal cells (SCs) isolated from skin (SSCs), adipose, and ovarian (OSCs) tissues. Skin and adipose SCs were isolated from a 6-month-old miniature pig, whereas OSCs were isolated from a newly born piglet. Isolated cells exhibited fibroblast-like cell population with significant renewal capacity and formed colonies by cells out-growth. All cells were positive for alkaline phosphatase activity and showed a relatively lower population at G0/G1 phase of the cell cycle. SCs derived from all tissues were strongly positive for cell surface markers, such as CD29, CD44, CD90, and vimentin. Further, relatively lower expression of cytokeratin and immunophenotype markers, such as major histocompatibility complex II (MHCII) and swine leukocyte antigen (SLA), was also observed. SCs derived from all tissues positively expressed the transcription factors, such as Oct-3/4, Nanog, and Sox-2. After induction, all SCs successfully differentiated into osteocytes and adipocytes and expressed the lineage specific marker genes. Further, cells from all tissues exhibited their potential for in vitro oogenesis with morphological changes and expression of markers during the germ-cell formation, namely Oct-4, growth differentiation factor 9b, c-Mos, Vasa, deleted in azoospermia-like gene, zona pellucida C, and follicle stimulating hormone receptor. Apart from basic features and selected lineage potential among all types of cells, OSCs possessed a greater ability to differentiate into the germ cell lineage in vitro.</P>
Jeon, Byeong-Gyun,Kumar, Basavarajappa Mohana,Kang, Eun-Ju,Ock, Sun-A,Lee, Sung-Lim,Kwack, Dae-Oh,Byun, June-Ho,Park, Bong-Wook,Rho, Gyu-Jin Springer 2011 Cell and tissue research Vol.345 No.1
<P>We have characterized and compared the telomere length, telomerase, reverse transcriptase (RT) activity and expression of genes implicated in cancer and in pluripotency, in human mesenchymal stem cells (MSCs) derived from dental papilla tissue, umbilical cord matrix and adipose tissue and in cancer cells (MDA-MB-231, U-87 MG, and MCF-7). MRC-5 fetal fibroblasts and adult muscle cells were used as somatic cell controls. Telomere length was significantly (P<0.05) higher in MSCs and somatic cells (7.2-9.3 kb) than in cancer cell lines (3.9-6 kb). However, the relative telomerase activity (RTA) in the cancer cell lines was significantly (P<0.05) higher than that of MSCs and somatic cells. RTA tended to be slightly higher in MSCs but no significant differences were observed between some cancer cells and MSCs. However, RTA was not detected in somatic cells. Although differentially displayed, the expression of genes related to cancer (BCL-2, p53, NF-κB, TGF-β, VEGF) and transcription and pluripotency (OCT4, NANOG, STAT3, REX1) were commonly observed in MSCs and cancer cells. Thus, endogenous non-telomerase RTA might be a potential biological marker or regulator among MSCs and cancer cells. Further, by sharing the biological and molecular markers of self-renewal and proliferation with cancer cells, MSCs might play a contributory role as tissue resident stem cells in tumor development.</P>
Rai, Narendra Prakash,Divakar, Darshan Devang,Al Kheraif, Abdulaziz Abdullah,Ramakrishnaiah, Ravikumar,Mustafa, Shabil Mohamed,Durgesh, BH,Basavarajappa, Santhosh,Khan, Aftab Ahmed Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16
Background: The treatment selection for the oral squamous cell carcinoma remains controversial. Radiation therapy or surgical excision of the lesion can be applied as the sole treatment or it can be used in combination with other treatment modalities. Radiotherapy is considered to be the safest of all the treatment modalities and can be used in several situations for oral and oropharyngeal cancers. The aim of this study was to evaluate the survival outcome differences in patients treated with radical and palliative radiotherapy as the primary treatment modality. Materials and Methods: The study included a total of 47 patients with oral cancer reporting to our hospital between years 2009 to 2010. The age group for the selected patients was more than 65 years, treated with radical and palliative radiotherapy with no prior surgical interventions. Patients were evaluated till Dec 2013 for overall survival time. Results: Twenty nine patients were treated with radical radiotherapy as main stay of treatment, out of which 21 died during the follow up time with median survival of $352{\pm}281.7$ days with 8 patients alive. All the 16 patients were dead who received palliative radiotherapy with a median survival time of $112{\pm}144.0$ days. Conclusions: This retrospective study showed improved overall survival time, loco regional control rates and reduced morbidity in patients treated with radical radiotherapy when compared to patients treated with palliative radiotherapy.