Faculty Publications
Permanent URI for this communityhttps://idr.nitk.ac.in/handle/123456789/18736
Publications by NITK Faculty
Browse
7 results
Search Results
Item Anti-diarrheal potential of Aegle Marmelos Corr. root bark extract in rats(2007) Vrushabendra Swamy, S.B.M.; Nataraj, K.S.; Jayaveera, K.N.; Gopkumar, P.; Nayak, S.; Kumar, G.S.; Umachigi, S.P.A study was undertaken to evaluate the effect of methanolic extract of the rootbark of Aegle marmelos Corr. (MAMC) against several experimental models of diarrhoea in rats. MAMC treated animal's showed significant inhibitory effect against castor-oil induced diarrhea and PGE2 induced enteropooling in rats. The extract also showed a significant reduction in gastrointestinal motility in the charcoal meal test in rats. The results obtained to establish the efficacy and substantiate the folkare claim as an anti-diarrhoeal agent.Item Juglans regia seeds have effects on platelets and peripheral fat deposition in the aorta and heart of C57BL/6J mice fed with normal and high fat simple carbohydrate diet(Bentham Science Publishers B.V. P.O. Box 294 Bussum 1400 AG, 2016) Prabhu, S.G.; Karkala, S.; Roy, N.; D'Souza, S.; Abraham, A.Background: Consumption of nuts particularly walnuts has been widely recommended for lowering the risk of coronary heart disease; however, very few studies have evaluated the potential unfavourable effects that Walnut seeds might have in vivo. Objective: To investigate the long-term effects of Juglans regia seed supplementation in specially formulated feed when fed to developed mice model. Method: C57BL/6J male mice were divided into four groups, labelled, C (control), T (High Fat Simple Carbohydrate-HFSC), Cw (control + walnut) and Tw (HFSC+ walnut) based on diet. Four mice from each group were sacrificed at the end of the first and fifth month respectively. Blood samples were collected every month. Bleeding time, blood platelet number and morphology were studied. Histopathological analysis of heart and aorta were also performed. Results: Groups Cw and Tw showed a significant increase in platelet count; however, platelet activation was not detected. There was a trend to an increase in bleeding time in group Cw. Expanded lumen diameter of the aorta was observed in Cw and Tw mice initially, however, it was found to constrict by the end of the study. A large amount of peripheral fat deposition in the aortas of Cw and Tw was observed, which increased through the course of the experiment. Conclusion: Kashmiri walnut seed supplementation was found to reduce the signs in shape change of platelets as well as increase platelet number with a trend to an increased bleeding time. This observation could be of medical interest. Histopathological analysis of heart and aorta showed lipid sequestration which merits further investigations. © 2016 Bentham Science Publishers.Item Inhibition of Na + /K + - and Ca 2+ -ATPase activities by phosphotetradecavanadate(Elsevier Inc. usjcs@elsevier.com, 2019) Fraqueza, G.; Fuentes, J.; Krivosudský, L.; Dutta, S.; Mal, S.S.; Roller, A.; Giester, G.; Rompel, A.; Aureliano, M.Polyoxometalates (POMs)are promising inorganic inhibitors for P-type ATPases. The experimental models used to study the effects of POMs on these ATPases are usually in vitro models using vesicles from several membrane sources. Very recently, some polyoxotungstates, such as the Dawson anion [P 2 W 18 O 62 ] 6? , were shown to be potent P-type ATPase inhibitors; being active in vitro as well as in ex-vivo. In the present study we broaden the spectrum of highly active inhibitors of Na + /K + -ATPase from basal membrane of epithelial skin to the bi-capped Keggin-type anion phosphotetradecavanadate Cs 5.6 H 3.4 PV 14 O 42 (PV 14 )and we confront the data with activity of other commonly encountered polyoxovanadates, decavanadate (V 10 )and monovanadate (V 1 ). The X-ray crystal structure of PV 14 was solved and contains two trans-bicapped ?-Keggin anions H x PV 14 O 42 (9-x)- . The anion is built up from the classical Keggin structure [(PO 4 )@(V 12 O 36 )]capped by two [VO]units. PV 14 (10 ?M)exhibited higher ex-vivo inhibitory effect on Na + /K + -ATPase (78%)than was observed at the same concentrations of V 10 (66%)or V 1 (33%). Moreover, PV 14 is also a potent in vitro inhibitor of the Ca 2+ -ATPase activity (IC 50 5 ?M)exhibiting stronger inhibition than the previously reported activities for V 10 (15 ?M)and V 1 (80 ?M). Putting it all together, when compared both P-typye ATPases it is suggested that PV 14 exibited a high potential to act as an in vivo inhibitor of the Na + /K + -ATPase associated with chloride secretion. © 2019 The AuthorsItem Tailoring solulan C24 based niosomes for transdermal delivery of donepezil: In vitro characterization, evaluation of pH sensitivity, and microneedle-assisted Ex vivo permeation studies(Editions de Sante editions.de.sante@wanadoo.fr, 2020) Nayak, A.S.; Chodisetti, S.; Gadag, S.; Nayak, U.Y.; Srinikethan, S.; Raval, K.The present investigation aims at encapsulating donepezil (DNP) in a niosomes to avert the side effects and to deliver the intact carrier across the skin barrier by modulating its physicochemical properties. The finding conclusively demonstrated that entrapment efficiency and the alteration in the niosome size are associated with the change in the span 60: cholesterol ratio, sonication, and hydration volume. The addition of 5 mM of solulan C24 to the optimized formulation (NSV5SolC24) formed stable niosomes with a mean particle size of 180.1 ± 1.83 nm and entrapment efficiency of 82.15% ± 1.54%. The cryo-SEM image and in vitro drug release profile revealed that the NSV5SolC24 is pH-sensitive. FTIR spectral analysis of NSV5SolC24 suggested that the ether and ester group in the NSV5SolC24 complex undergoes SN2 cleavage and hydrolysis at lower pH, thus enhancing DNP release. The microneedle (MN)-assisted studies with MN1200 showed a 29-fold increase in transdermal permeation of intact NSV5SolC24 against the passive method in porcine skin. The intact NSV5SolC24 carrying DNP was translocated across the skin barrier successfully at a steady flux rate of 9.89 ± 0.923 ?g/cm2/h. Nevertheless, further in vivo studies are recommended to elucidate the pH sensitivity and clinical efficacy of the prepared drug delivery system. © 2020 Elsevier B.V.Item Development and preclinical evaluation of microneedle-assisted resveratrol loaded nanostructured lipid carriers for localized delivery to breast cancer therapy(Elsevier B.V., 2021) Gadag, S.; Narayan, R.; Nayak, A.S.; Catalina Ardila, D.; Sant, S.; Yogendra, Y.; Garg, S.; Nayak, U.Y.Resveratrol (RVT) is one of the potent anticancer phytochemicals which has shown promising potential for breast cancer therapy. However, its short half-life and low bioavailability is a major hurdle in its effective use. In this study, we have developed nanostructured lipid carriers (NLCs) of RVT to enable localized delivery of the drug to the breast tissues using microneedle arrays to improve effectiveness. The NLCs were optimized using the Design of Experiments approach and characterized for their particle size, polydispersity index, zeta potential and entrapment efficiency. The RVT-NLCs delivered using microneedle array 1200 showed a higher permeation of RVT across the skin with lower skin retention compared to pure RVT. Further, RVT-NLCs showed higher anticancer activity on MDA-MB-231 breast cancer cell lines and enhanced internalization compared to pure RVT. Moreover, the RVT-NLCs were found to inhibit the migration of MDA-MB-231 breast cancer cell lines. Preclinical studies in rats showed that RVT-NLCs delivered via microneedles demonstrated a remarkable increase in the Cmax, Tmax and AUC0-inf, and a higher localization in breast tissue compared to pure RVT administered orally. These results suggests that the RVT-NLCs administered by microneedle array system is an effective strategy for the local delivery of RVT for breast cancer therapy. © 2021 Elsevier B.V.Item An Enhancer-Driven Stem Cell–Like Program Mediated by SOX9 Blocks Intestinal Differentiation in Colorectal Cancer(W.B. Saunders, 2022) Liang, X.; Duronio, G.N.; Yang, Y.; Bala, P.; Hebbar, P.; Spisák, S.; Sahgal, P.; Singh, H.; Zhang, Y.; Xie, Y.; Cejas, P.; Long, H.W.; Bass, A.J.; Sethi, N.S.Background and Aims: Genomic alterations that encourage stem cell activity and hinder proper maturation are central to the development of colorectal cancer (CRC). Key molecular mediators that promote these malignant properties require further elucidation to galvanize translational advances. We therefore aimed to characterize a key factor that blocks intestinal differentiation, define its transcriptional and epigenetic program, and provide preclinical evidence for therapeutic targeting in CRC. Methods: Intestinal tissue from transgenic mice and patients were analyzed by means of histopathology and immunostaining. Human CRC cells and neoplastic murine organoids were genetically manipulated for functional studies. Gene expression profiling was obtained through RNA sequencing. Histone modifications and transcription factor binding were determined with the use of chromatin immunoprecipitation sequencing. Results: We demonstrate that SRY-box transcription factor 9 (SOX9) promotes CRC by activating a stem cell–like program that hinders intestinal differentiation. Intestinal adenomas and colorectal adenocarcinomas from mouse models and patients demonstrate ectopic and elevated expression of SOX9. Functional experiments indicate a requirement for SOX9 in human CRC cell lines and engineered neoplastic organoids. Disrupting SOX9 activity impairs primary CRC tumor growth by inducing intestinal differentiation. By binding to genome wide enhancers, SOX9 directly activates genes associated with Paneth and stem cell activity, including prominin 1 (PROM1). SOX9 up-regulates PROM1 via a Wnt-responsive intronic enhancer. A pentaspan transmembrane protein, PROM1 uses its first intracellular domain to support stem cell signaling, at least in part through SOX9, reinforcing a PROM1-SOX9 positive feedback loop. Conclusions: These studies establish SOX9 as a central regulator of an enhancer-driven stem cell–like program and carry important implications for developing therapeutics directed at overcoming differentiation defects in CRC. © 2022Item Experimentally Induced Hyperglycemia in Prepubertal Phase Impairs Oocyte Quality and Functionality in Adult Mice(Endocrine Society, 2022) Predheepan, D.; Daddangadi, A.; Uppangala, S.; Koulmane Laxminarayana, S.L.K.; Raval, K.; Kalthur, G.; Kovaĉiĉ, B.; Kumar Adiga, S.Reproductive abnormalities in women with a history of childhood diabetes are believed to be partially attributed to hyperglycemia. Prolonged hyperglycemia can negatively affect ovarian function and fertility during reproductive life. To address this in an experimental setting, the present study used streptozotocin-induced hyperglycemic prepubertal mouse model. The impact of prolonged hyperglycemic exposure during prepubertal life on ovarian function, oocyte quality, and functional competence was assessed in adult mice. The ovarian reserve was not significantly altered; however, the in vitro maturation potential (P<0.001), mitochondrial integrity (P<0.01), and meiotic spindle assembly (P<0.05-0.001) in oocytes were significantly affected in hyperglycemic animals in comparison to control groups. The results from the study suggest that prepubertal hyperglycemia can have adverse effects on the oocyte functional competence and spindle integrity during the reproductive phase of life. Because these changes can have a significant impact on the genetic integrity and developmental potential of the embryos and fetus, the observation warrants further research both in experimental and clinical settings. © 2022 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.