98 research outputs found
sj-pdf-1-vmj-10.1177_1358863X211035445 – Supplemental material for Temporal dynamics of nitric oxide wave in early vasculogenesis
No full textSupplemental material, sj-pdf-1-vmj-10.1177_1358863X211035445 for Temporal dynamics of nitric oxide wave in early vasculogenesis by Saranya Rajendran, Lakshmikirupa Sundaresan, Geege Venkatachalam, Krithika Rajendran, Jyotirmaya Behera and Suvro Chatterjee in Vascular Medicine</p
Interleukin-1β, lipocalin 2 and nitric oxide synthase 2 are mechano-responsive mediators of mouse and human endothelial cell-osteoblast crosstalk
No full textEndothelial cells are spatially close to osteoblasts and regulate osteogenesis. Moreover, they are sensitive to mechanical stimuli, therefore we hypothesized that they are implicated in the regulation of bone metabolism during unloading. Conditioned media from endothelial cells (EC-CM) subjected to simulated microgravity (0.08g and 0.008g) increased osteoblast proliferation and decreased their differentiation compared to unit gravity (1g) EC-CM. Microgravity-EC-CM increased the expression of osteoblast Rankl and subsequent osteoclastogenesis, and induced the osteoblast de-differentiating factor, Lipocalin 2 (Lcn2), whose downregulation recovered osteoblast activity, decreased Rankl expression and reduced osteoclastogenesis. Microgravity-EC-CM enhanced osteoblast NO-Synthase2 (NOS2) and CycloOXygenase2 (COX2) expression. Inhibition of NOS2 or NO signaling reduced osteoblast proliferation and rescued their differentiation. Nuclear translocation of the Lcn2/NOS2 transcription factor, NF-κB, occurred in microgravity-EC-CM-treated osteoblasts and in microgravity-treated endothelial cells, alongside high expression of the NF-κB activator, IL-1β. IL-1β depletion and NF-κB inhibition reduced osteoblast proliferation and rescued differentiation. Lcn2 and NOS2 were incremented in ex vivo calvarias cultured in microgravity-EC-CM, and in vivo tibias and calvarias injected with microgravity-EC-CM. Furthermore, tibias of botulin A toxin-treated and tail-suspended mice, which featured unloading and decreased bone mass, showed higher expression of IL-1β, Lcn2 and Nos2, suggesting their pathophysiologic involvement in endothelial cell-osteoblast crosstalk
The ‘mover and shaker’: The teacher as a holistic transformative intellectual and creative atypical deviant. A biographical case-study on Suvro Chatterjee: A contemporary Indian teacher
No full textThe qualitative sociological study employs the biographical and case study approach to focus on Suvro Chatterjee, a contemporary Indian teacher. The study identifies the exemplar as a holistic transformative intellectual , and in so doing unpacks the theoretical concept forwarded by Henry A. Giroux (1988) and extends it by exploring in-depth the empirical instance of the real life Indian teacher: his multiple roles and identities, the intimate link amongst his dichotomous but connected ensemble of values, philosophical orientations and self-expressed through his identity and primary aims as a teacher – and his reflections on his work pursued as a calling . In so doing, the study unpacks the levels, the content, and the many-dimensioned creativity of Suvro Chatterjee: a creativity which bridges the knowledge domains and relations domain and is born of a fusion of the four creative types as expounded by Howard Gardner (1993, 1997) as Master and Maker of knowledge, Instrospecter, and Influencer, and self-actualized healer as forwarded by bell hooks (1994). At different levels, the study through the contemporary teacher\u27s varied essay excerpts presents the wider operating social forces and the immediate social context within which the he works and lives. The study thus directly puts into practice the call raised by C. Wright Mills more than half a century ago: the need to apply the sociological imagination (1959) and to engage in empathetic sociological research through the study of individual biography amidst the operating criss-crossing and conflicting social forces. Through a journey that explores the multi-faceted nature of his everyday living, instances of his manner, modes and methods of teaching, his micro-interactions, his musings, and his interconnected writings – reflective, pragmatic, insightful, introspective, humorous, critical, and trenchant – his many-layered identities as teacher, tutor, mentor, father, husband, family-man, friend, guide, modern day guru, master and maker of knowledge domains, philosopher, social thinker, social critic, public intellectual, educator, and writer emerge and sometimes merge. While his essays span divers knowledge areas, the current study focuses especially on those excerpts where he specifically critiques the current goals and values of education while he elaborates upon the intimate connection of holistic education with the multiple 2 arenas and levels of social living. Suvro Chatterjee critiques, among other matters the overwhelming value placed on the narrowly utilitarian goal of education in procuring a job and the over-emphasis upon a restricted and segregated form of technological and technical knowledge which is being promoted through the educational goal and primary values of elite education within the Indian nation (and also worldwide). He points out just why and how this is pernicious connecting it, among other matters, to T. S. Eliot\u27s words on the technological savage to the dwindling value of knowledge and the rapid fragmentation of knowledge in the name of specialization. He systematically notes how at the collective level the goals and values of education are producing a teeming mindless but educated middle-class cognizant of little else other than their identities as consumers. He also elaborates among other aspects of how the education standards within the nation cannot be improved without strenuously improving the quality of the teachers and without a major shift in the collective consciousness, which no longer deems the market to be the sole and final arbiter of what contains value and worth and of what counts as progress and development. As he critiques, Suvro Chatterjee also forwards detailed alternatives of what matter in the making of genuine civilizations, such as …the respect for language as the greatest invention of all time, the love of knowledge in its entirety, good virtues like courtesy, diligence, cleanliness, quietness, punctuality and keeping promises and hating gossip, the importance of the right and power to make up one\u27s own mind, informed concern for the neediest in society, appreciation of art and literature, fascination with history, admiration of justice and contempt for the merely rich… The unfolding study also locates why and how the contemporary Indian teacher is a creative atypical deviant yet cast in a different mould from the social or political activist or the radical social thinker. First, he consistently connects across the micro, meso and macro arenas of social living, and the structural, the collective and the individual while looking constantly at the many sided fluid nature of reality . And secondly, staying away from any single dominant ideological strand or school of thought, he seeks to initiate change that spans the pedestrian and profound levels of social living and one that is directed at the level of ideas, and at the level of the mind, conscience and consciousness from which spring action, and at the level of the individual as a composite being. (Abstract shortened by UMI.
Study of the cellular mechanism of Sunitinib mediated inactivation of activated hepatic stellate cells and its implications in angiogenesis
No full textThe development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells (HSC). Inhibition of receptor tyrosine kinase (RTK) signaling showed promise in the treatment of hepatocellular carcinoma. However, there is a lack of knowledge about the effects of RTK inhibitors on the tumor supportive cells. We performed in vitro experiments to study whether Sunitinib, a platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) RTKs' inhibitor, could block both activated HSC functions and angiogenesis and thus prevent the progression of cirrhotic liver to hepatocellular carcinoma. In immortalized human activated HSC LX-2, treatment with Sunitinib 100 nM blocked collagen synthesis by 47%, as assessed by Sirius Red staining, attenuated HSC contraction by 65%, and reduced cell migration by 28% as evaluated using a Boyden's chamber, without affecting cell viability, measured by Trypan blue staining, and apoptosis, measured by propidium iodide (PI) incorporation assay. Our data revealed that Sunitinib treatment blocked the transdifferentiation of primary human HSC (hHSC) to activated myofibroblast-like cells by 65% without affecting hHSC apoptosis and migration. In in vitro angiogenic assays, Sunitinib 100 nM reduced endothelial cells (EC) ring formation by 46% and tube formation by 68%, and decreased vascular sprouting in aorta ring assay and angiogenesis in vascular bed of chick embryo. In conclusion, the present study demonstrates that the RTK inhibitor Sunitinib blocks the activation of HSC and angiogenesis suggesting its potential as a drug candidate in pathological conditions like liver fibrosis and hepatocellular carcinoma
The role of calreticulin transacetylase in the activation of human platelet nitrite reductase by polyphenolic acetates
No full textOur earlier investigations demonstrated the remarkable activation of cytochrome P-450 reductase and nitric oxide synthase by 7,8-diacetoxy-4-methylcoumarin, a model polyphenolic acetate by way of acetylation, catalyzed by the Calreticulin. Protein acetyltransferase action of Calreticulin was hence termed Calreticulin transacetylase (CRTAase). Nitric oxide synthase and nitrite reductase are now considered as parts of nitric oxide cycle. The activation of platelets nitric oxide synthase by 7,8-diacetoxy-4-methylcoumarin has already been demonstrated by us. Also, there are reports that certain proteins such as cytochrome P-450 reductase and cytochrome P-450 are endowed with the nitrite reductase activity in mammalian cells. Keeping these facts in view, we turned our attention to probe whether 7,8-diacetoxy-4-methylcoumarin could alter the levels of nitric oxide independent of the action of nitric oxide synthase in the human platelets model. The incubation of 7,8-diacetoxy-4-methylcoumarin and nitrite with platelets caused significant elevation of nitric oxide and cyclic guanosine monophosphate levels possibly due to the activation of nitrite reductase. Several polyphenolic acetates were similarly found to activate the nitrite reductase in tune with their affinities as substrate to CRTAase. N-omega-Nitro-L-arginine methyl ester, the inhibitor of nitric oxide synthase, failed to reverse such an effect of 7,8-diacetoxy-4-methylcoumarin. Clotrimazole which is known to be an inhibitor of nitrite reductase, effectively abolished the 7,8-diacetoxy-4-methylcoumarin mediated enhancement of nitric oxide levels in platelets as well as the nitric oxide mediated effects; such as cyclic guanosine monophosphate levels as well as adenosine diphospate induced platelets aggregation due to nitrite
Profiling the patterns of miRNAs and transcriptome of human vasculature under micro-gravity: A template study using space science for solving health problems on the Earth
No full textEverolimus is a potent inhibitor of activated hepatic stellate cell functions in vitro and in vivo , while demonstrating anti-angiogenic activities
No full textProgression of liver fibrosis to HCC (hepatocellular carcinoma) is a very complex process which involves several
pathological phenomena, including hepatic stellate cell activation, inflammation, fibrosis and angiogenesis.
Therefore inhibiting multiple pathological processes using a single drug can be an effective choice to curb the
progression of HCC. In the present study, we used the mTOR inhibitor everolimus to observe its effect on the in vitro
activation of hepatic stellate cells and angiogenesis. The results of the present study demonstrated that everolimus
treatment blocked the functions of the immortalized human activated hepatic stellate cell line LX-2 without affecting
the viability and migration of primary human stellate cells. We also observed that treatment with everolimus
(20 nM) inhibited collagen production by activated stellate cells, as well as cell contraction. Everolimus treatment
was also able to attenuate the activation of primary stellate cells to their activated form. Angiogenesis studies
showed that everolimus blocked angiogenesis in a rat aortic ring assay and inhibited the tube formation and
migration of liver sinusoidal endothelial cells. Finally, everolimus treatment reduced the load of tumoral
myofibroblasts in a rat model of HCC. These data suggest that everolimus targets multiple mechanisms, making it a
potent blocker of the progression of HCC from liver fibrosis
Stimulated Microgravity and Induction of Angiogenesis; A New Perspective in Wound Healing
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