43,819 research outputs found
Seminário sobre aquacultura 14 a 16 de dezembro de 1983
No full textA necessidade de desenvolver a aquacultura em Portugal obriga à escolha das espécies mais indicadas para tal finalidade. A propósito o autor chama a atenção para as graves consequências que podem advir das introduções e/ou transferências de animais aquáticos, quer para as espécies locais e meio ambiente, como para a para a saúde pública.Concerning the need to choose the most convenient species to cultivate in order to implement aquaculture in Portugal, the author draws the attention to the deleterious consequences of introductions and transfers of aquatic animals.Caixa Geral de Depósito
The role of VEGF autocrine signaling in hypoxia and oxidative stress driven "stemness switch": Implications in solid tumor progression and metastasis
No full textFurther investigations suggest that chemotherapeutic drug cisplatin treatment can induce the process of "stemness switch" by VEGF/Flt1 signaling leading to tumorigenicity in an non-tumorigenic osteosarcoma cell line, HOS. Functional inhibition of Flt1 signaling completely reduced cisplatin-induced tumorigenicity by reducing the number of SP cells. Further investigation revealed that both hypoxia and drugs led to increased generation of ROS, oxidative stress and subsequent "stemness switch". To further investigate the role of oxidative stress in hypoxia and drug induced "stemness switch" anti-oxidants squalene and n-acetyl cysteine (NAC) were used to reduce drug-induced stemness. Interestingly, both of these antioxidants were protective against cisplatin-induced toxicity of murine BM stem cell fraction. However, both these agents failed to reduce drug-mediated increased SP cell fraction and VEGF secretion. NAC failed to reduce oxidative stress in the tumor cells, and marginally enhanced the drug-induced tumor cell repopulation in vivo, whereas squalene did not show any significant effects. Further investigations revealed that tumor SP cells have very high endogenous level of oxidants compared to normal BM stem cell fraction. Taken together, here I demonstrate that VEGF autocrine signaling is involved in the oxidative stress induced "stemness switch". Based on these findings I would like to propose a stem cell model of tumor repair and regeneration where following drug-induced hypoxia, TSCs will be mobilized from the quiescent mode to the repair/regeneration mode ("stemness switch") leading to rapid repopulation of tumor cells. During the course of mobilization, TSCs may recruit autocrine growth signaling such as VEGF signaling for the self renewal of TSCs in their hypoxic niche. Tumor hypoxia enhances Vascular endothelial growth factor (VEGF) autocrine/paracrine signaling leading to angiogenic switch, but the role of VEGF in the self-renewal/survival of highly tumorigenic side-population (SP) cells has not been studied. Here I isolated and characterized highly migratory, and tumorigenic fraction of SP cells (SPm(hox)) in several solid tumor cell lines including neuroblastoma, rhabdomyosarcoma, medulloblastoma, and small cell lung carcinoma cell lines and evaluated the role of VEGF in the self-renewal/survival of SPm(hox) during hypoxia in neuroblastoma (SK-N-BE(2)), and rhabdomyosarcoma (RH4) cell lines. Exposure to hypoxia increased the SP fraction by 6-10 fold and SPm(hox) fraction by 2-3 fold in all the cell lines. SPm(hox) cells show very high SDF-1alpha/CXCR4 activity and could be isolated using a modified Boyden Chamber system, migrating in response to a hypoxia/hydrogen peroxide treated bone marrow stromal cell, "injured conditioned medium". In nude mice, significantly fewer (1-5x10 3) SPm(hox) cells form highly angiogenic and rapidly growing subcutaneous tumors and liver metastasis as compared to the original cell line ( sim;5x106). In an in vivo matrigel "stemness" assay, SPm(hox) cells initiate a hypoxic/oxidative-stress condition of repair/regeneration to maintain and enhance the SP-state (stemness). siRNA knockdown of Flt1 reduced the hypoxia-driven SPm(hox) self-renewal by three fold (p=0.03556) and reduced the in vivo homing of SPm(hox) to the "injured bone marrow" by 75% (p=0.0293). In addition, siRNA Flt1 knockdown reduced the hypoxia-induced Oct-4 expressing SPm (hox) cells by five fold (p = 0.0017) suggesting that VEGF/Flt1 signaling may enhance the "stemness" of SPm(hox) during hypoxia. Thus, VEGF/Flt1 signaling may drive the process of a SP cell mediated "stemness switch" during hypoxia.Ph.D
Abstract 923: Human embryonic stem cells exhibit altruistic cell death that release death signals having potent anti-cancer activity
No full textAbstract
Background: We recently described the altruistic stem cell (ASC) phenotype in human embryonic stem cells (hESCs) as well as in mesenchymal stem cells (1, 2). The ASC phenotype was characterized by altered state of p53/MDM2 feedback system that permitted the cells to transiently acquire an unstable state of low p53 allowing the cells to survive in extreme microenvironment (1). Interestingly, we noted that ASCs spontaneously returned to its basal state of high p53 after a period of two weeks (1, 2). In this study, we speculate that this return of p53 levels to basal state could be a safety mechanism to prevent malignant transformation of ASCs. We also speculate that ASCs may release soluble factors like high mobility group protein B1 (HMGB-1) that could selectively target the cells exhibiting abnormal p53 e.g. cancer cells. Here, we further characterized ASC phenotype and its fate.
Methods: hESC, BG01 cells were exposed to extreme hypoxia followed by reoxygenation and then ABCG2+/SSEA3+ cells were flow cytometry sorted. This specific subpopulation is enriched in ASCs and could be cultured in vitro for two weeks (1). The post- hypoxia treated ABCG2+/SSEA3+ cells were maintained in serum free media, and subjected to apoptosis, and senescence assays. The conditioned media (CM) of these cells and subjected to HMGB-1 measurement by ELISA. To measure bystander apoptosis, teratocarcinoma cells (Tera-2) were treated with the CM followed by measurement of apoptosis.
Results: Here we confirmed that p53 and MDM2 in ABCG2+/SSEA3+ cells exhibited return of oscillation between days 19-24. This was associated increase in apoptosis, and senescence of these cells. Apoptosis/senescence was decreased when treated with either Pifithrin α, an inhibitor of p53, or by siRNA silencing of p53, suggesting p53-dependent apoptosis. Additionally, treatment with Nutlin-3, an inhibitor of MDM2 (1) led to a 10-fold increase in apoptosis indicating that high MDM2 was required to prevent the apoptosis of ASCs. Thus, ASCs underwent spontaneous apoptosis (altruistic cell death) due to the return of p53/MDMD2 oscillation. We suggest that this return of p53 and associated apoptosis could be a safety mechanism to prevent malignant transformation of ASCs. Next, we found that the CM of ABCG2+/SSEA3+ cells contained high levels of HMGB-1 compared to the parental BG01 cells. Importantly, CM treatment led to p53 dependent apoptosis of Tera-2 cells. Furthermore, CM treatment also inhibited the growth of Tera-2 xenografts in NOD/SCID mice.
Conclusion: Our results indicate that ASCs undergoes altruistic cell death, and releases death signal mediated by HMGB1 that can target neighboring cells exhibiting abnormal p53 including cancer cells. We suggest that this unique property of ASCs could be exploited as a novel cancer therapeutic.
1. Das B et al, Stem Cells, 2012; 30(8):1685-95.
2. Pal B et al, Cancer Research, 2016; Volume 76, Issue 14 Supplement, pp. 251
Note: This abstract was not presented at the meeting.
Citation Format: Bidisha Pal, Seema Bhuyan, Jaishree Garhyan, Herman Yeger, Bikul Das. Human embryonic stem cells exhibit altruistic cell death that release death signals having potent anti-cancer activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 923. doi:10.1158/1538-7445.AM2017-923</jats:p
In vitro Culture of Naïve Human Bone Marrow Mesenchymal Stem Cells: A Stemness Based Approach
No full textHuman bone marrow derived mesenchymal stem cells (BM-MSCs) resides in their niches in close proximity to hematopoietic stem cells (HSCs). These naïve MSCs have tremendous potential in regenerative therapeutics, and may also be exploited by cancer and infectious disease agents. Hence, it is important to study the physiological and pathological roles of naïve MSC. However, our knowledge of naïve MSCs is limited by lack of appropriate isolation and in vitro culture methods. Established culture methods use serum rich media, and serial passaging for retrospective isolation of MSCs. These primed MSCs may not reflect the true physiological and pathological roles of naive MSCs (Figure 1). Therefore, there is a strong need for direct isolation and in vitro culture of naïve MSCs to study their stemness (self-renewal and undifferentiated state) and developmental ontogeny. We have taken a niche-based approach on stemness to better maintain naïve MSCs in vitro. In this approach, stemness is broadly divided as niche dependent (extrinsic), niche independent (intrinsic) and niche modulatory (altruistic or competitive). Using this approach, we were able to maintain naïve CD271+/CD133+ BM-MSCs for 2 weeks. Furthermore, this in vitro culture system helped us to identify naïve MSCs as a protective niche site for Mycobacterium tuberculosis, the causative organism of pulmonary tuberculosis. In this review, we discuss the in vitro culture of primed vs. naïve human BM derived MSCs with a special focus on how a stemness based approach could facilitate the study of naïve BM-MSCs
In vitro Culture of Naïve Human Bone Marrow Mesenchymal Stem Cells: A Stemness Based Approach
No full textRedox-Responsive Nanocapsules for the Spatiotemporal Release of Miltefosine in Lysosome: Protection against Leishmania
No full textLeishmaniasis, a vector-borne disease, is caused by intracellular parasite Leishmania donovani. Unlike most intracellular pathogens, Leishmania donovani are lodged in parasitophorous vacuoles and replicate within the phagolysosomes in macrophages. Effective vaccines against this disease are still under development, while the efficacy of the available drugs is being questioned owing to the toxicity for nonspecific distribution in human physiology and the reported drug-resistance developed by Leishmania donovani. Thus, a stimuli-responsive nanocarrier that allows specific localization and release of the drug in the lysosome has been highly sought after for addressing two crucial issues, lower drug toxicity and a higher drug efficacy. We report here a unique lysosome targeting polymeric nanocapsules, formed via inverse mini-emulsion technique, for stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line. A benign polymeric backbone, with a disulfide bonding susceptible to an oxidative cleavage, is utilized for the organelle-specific release of miltefosine. Oxidative rupture of the disulfide bond is induced by intracellular glutathione (GSH) as an endogenous stimulus. Such a stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line over a few hours helped in achieving an improved drug efficacy by 200 times as compared to pure miltefosine. Such a drug formulation could contribute to a new line of treatment for leishmaniasis.A. Das acknowledges SERB (India) Grants (CRG/2020/000492 and JCB/2017/000004) and DBT Grant (BT/PR22251/NNT/28/1274/2017) for supporting this research. N. Mukherjee acknowledges SERB (India) Grant PDF/2016/001437 and K. Das acknowledges the grant EMR/2015/001674 for supporting this research. Financial support from DST (DST/INSPIRE/03/2017/002477) is acknowledged by R.T. This manuscript bears CSMCRI registration no 7/2021.Pramanik, SK (corresponding author), CSIR Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India.
Mukherjee, N (corresponding author), CSIR Indian Inst Chem Biol, Canc Biol & Inflammatory Disorder Div, Kolkata 700032, India.
Chattopadhy, S (corresponding author), BITS Pilani, Pilani 403726, Goa, India.
Das, A (corresponding author), Indian Inst Sci Educ & Res Kolkata, Mohanpur 741246, W Bengal, India.
[email protected]; [email protected]; [email protected]
Interview with Indra Das
No full textIndra Das is most well-recognized as the author of The Devourers (2015), a novel that won the Lambda Literary Award for straddling the genres of sci-fi, speculative, and fantasy fiction alongside LGBT themes. Das’s short fiction is widely published is horror and sci-fi anthologies, as well as magazines like Tor.com, Strange Horizons, and Asimov’s Science Fiction. He spoke candidly with Alok Amatya over email about the current literary landscape, the work of writing transgressive genre fiction, and his own experiences as an upcoming global author
"PULS." - Ein Blog als Online-Magazin für Medizinstudierende der Goethe-Universität Frankfurt
No full textIm Herbst 2009 forderten Studierende im Rahmen landesweiter Proteste auch am Fachbereich Medizin/Zahnmedizin der Goethe-Universität Frankfurt mehr Transparenz und Kommunikation zu Angelegenheiten ihres Studiums. Einen innovativen Lösungsansatz, um diesen Forderungen nachzukommen, bietet eines der Web 2.0 Werkzeuge: ein auf einer Blog-Software basierendes Online-Magazin für Studierende und andere Mitglieder des Fachbereichs.
Das öffentlich zugängliche Online-Magazin "PULS." (https://newsmagazin.puls.med.uni-frankfurt.de/wp/) wird mit einer freien Blog-Software (wordpress Version 3.1.3.) realisiert und von einer Online-Redakteurin konzipiert und geschrieben. Die Beiträge entstehen nach eigenen Recherchen sowie aus Anregungen und Gesprächen mit verschiedenen Personengruppen des Fachbereichs. Die datenschutzkonforme Auswertung der Zugriffe erfolgt über eine open-source Webanalyse-Software (Piwik). Zusätzlich werden jährlich mit dem Online-Umfrage-Tool Survey Monkey die Nutzer anonym befragt.
"PULS." ist seit dem 14.02.2010 ununterbrochen online und hat seitdem 806 Beiträge (Stand: 27.11.2012) publiziert und wird von ca. 2400 Besuchern monatlich gelesen. Das Themenspektrum ist zentriert auf die Anliegen der Frankfurter Medizin- und Zahnmedizinstudierenden. Die enge Zusammenarbeit mit verschiedenen Gruppierungen des Fachbereichs – Dekanat, Studierende und Lehrende – garantiert darüber hinaus ein fachbereichs-relevantes Themenspektrum. Das Online-Magazin begleitet komplexe Projekte und Entscheidungen mit Hintergrundinformationen und kommuniziert sie verständlich. Eine jährliche Nutzer-Evaluierung zeigt eine wachsende Leserzahl und eine sehr hohe Zustimmung für das Online-Magazin, seine Inhalte und seinen Stil. Das Web 2.0-Medium "Blog" und seine web-typische Sprache entsprechen dem Medienverhalten der Zielgruppe, d.h. den Studierenden des Fachbereichs Medizin.
"PULS." hat sich als ein geeignetes und strategisches Instrument erwiesen, um größere Transparenz, mehr Kommunikation und letztendlich eine stärkere Identifikation der Studierenden mit ihrem Fachbereich voranzutreiben
- …
