scholarly journals Modulation of RAB7A Protein Expression Determines Resistance to Cisplatin through Late Endocytic Pathway Impairment and Extracellular Vesicular Secretion

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 52 ◽  
Author(s):  
Flora Guerra ◽  
Aurora Paiano ◽  
Danilo Migoni ◽  
Giulia Girolimetti ◽  
Anna Myriam Perrone ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Therapy Response ◽  
Endocytic Pathway ◽  
Endocytic Trafficking ◽  
Chemotherapy Response ◽  
Intracellular Accumulation ◽  
Human Patient ◽  
First Time ◽  
Vesicular Secretion

Background: Cisplatin (CDDP) is widely used in treatment of cancer, yet patients often develop resistance with consequent therapeutical failure. In CDDP-resistant cells alterations of endocytosis and lysosomal functionality have been revealed, although their causes and contribution to therapy response are unclear. Methods: We investigated the role of RAB7A, a key regulator of late endocytic trafficking, in CDDP-resistance by comparing resistant and sensitive cells using western blotting, confocal microscopy and real time PCR. Modulation of RAB7A expression was performed by transfection and RNA interference, while CDDP sensitivity and intracellular accumulation were evaluated by viability assays and chemical approaches, respectively. Also extracellular vesicles were purified and analyzed. Finally, correlations between RAB7A and chemotherapy response was investigated in human patient samples. Results: We demonstrated that down-regulation of RAB7A characterizes the chemoresistant phenotype, and that RAB7A depletion increases CDDP-resistance while RAB7A overexpression decreases it. In addition, increased production of extracellular vesicles is modulated by RAB7A expression levels and correlates with reduction of CDDP intracellular accumulation. Conclusions: We demonstrated, for the first time, that RAB7A regulates CDDP resistance determining alterations in late endocytic trafficking and drug efflux through extracellular vesicles.

scholarly journals Circulating MicroRNAs in Extracellular Vesicles as Potential Biomarkers of Alcohol-Induced Neuroinflammation in Adolescence: Gender Differences

2020 ◽  
Vol 21 (18) ◽  
pp. 6730
Author(s):  
Francesc Ibáñez ◽  
Juan R. Ureña-Peralta ◽  
Pilar Costa-Alba ◽  
Jorge-Luis Torres ◽  
Francisco-Javier Laso ◽  
...  
Keyword(s):  
Gender Differences ◽  
Extracellular Vesicles ◽  
Target Genes ◽  
Alcohol Intoxication ◽  
Peripheral Circulation ◽  
Female Adolescents ◽  
Circulating Micrornas ◽  
Male Adolescents ◽  
First Time

Current studies evidence the role of miRNAs in extracellular vesicles (EVs) as key regulators of pathological processes, including neuroinflammation and neurodegeneration. As EVs can cross the blood–brain barrier, and EV miRNAs are very stable in peripheral circulation, we evaluated the potential gender differences in inflammatory-regulated miRNAs levels in human and murine plasma EVs derived from alcohol-intoxicated female and male adolescents, and whether these miRNAs could be used as biomarkers of neuroinflammation. We demonstrated that while alcohol intoxication lowers anti-inflammatory miRNA (mir-146a-5p, mir-21-5p, mir-182-5p) levels in plasma EVs from human and mice female adolescents, these EV miRNAs increased in males. In mice brain cortices, ethanol treatment lowers mir-146a-5p and mir-21-5p levels, while triggering a higher expression of inflammatory target genes (Traf6, Stat3, and Camk2a) in adolescent female mice. These results indicate, for the first time, that female and male adolescents differ as regards the ethanol effects associated with the inflammatory-related plasma miRNAs EVs profile, and suggest that female adolescents are more vulnerable than males to the inflammatory effects of binge alcohol drinking. These findings also support the view that circulating miRNAs in EVs could be useful biomarkers for screening ethanol-induced neuroinflammation and brain damage in adolescence.

scholarly journals Inhibition of  a v b 3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

2020 ◽  
Author(s):  
Wanessa Altei ◽  
Bianca Pachane ◽  
Patty K. Santos ◽  
Ligia Ribeiro ◽  
Bong Hwan Sung ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Organ Specific ◽  
Breast Cells ◽  
Mediate Cell ◽  
First Time ◽  
Cd63 Expression ◽  
Cell Cell

Abstract Background: Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells.Methods: To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for avb3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments.Results: We find that SEVs secreted from MDA-MB-231 breast cancer cells carry avb3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of avb3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content.Conclusion: In summary, our findings demonstrate for the first time a key role of avb3 integrin in cell-cell communication through SEVs.

scholarly journals Inhibition of  a v b 3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

2020 ◽  
Author(s):  
Wanessa Altei ◽  
Bianca Pachane ◽  
Patty K. Santos ◽  
Ligia Ribeiro ◽  
Bong Hwan Sung ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Αvβ3 Integrin ◽  
Organ Specific ◽  
Breast Cells ◽  
Mediate Cell ◽  
First Time ◽  
Cell Cell

Abstract Background: Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells. Methods: To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for αvβ3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments. Results: We find that SEVs secreted from MDA-MB-231 breast cancer cells carry αvβ3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of αvβ3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content. Conclusion: In summary, our findings demonstrate for the first time a key role of αvβ3 integrin in cell-cell communication through SEVs.

scholarly journals Inhibition of αvβ3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Wanessa F. Altei ◽  
Bianca C. Pachane ◽  
Patty K. dos Santos ◽  
Lígia N. M. Ribeiro ◽  
Bong Hwan Sung ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Αvβ3 Integrin ◽  
Organ Specific ◽  
Breast Cells ◽  
Mediate Cell ◽  
First Time ◽  
Cell Cell

Abstract Background Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells. Methods To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for αvβ3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments. Results We find that SEVs secreted from MDA-MB-231 breast cancer cells carry αvβ3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of αvβ3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content. Conclusion In summary, our findings demonstrate for the first time a key role of αvβ3 integrin in cell-cell communication through SEVs. Graphical abstract

scholarly journals Proteomic profile of extracellular vesicles released by Lactiplantibacillus plantarum BGAN8 and their internalization by non-polarized HT29 cell line

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Svetlana Sokovic Bajic ◽  
Maria-Alexandra Cañas ◽  
Maja Tolinacki ◽  
Josefa Badia ◽  
Borja Sánchez ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Time Course ◽  
Intestinal Epithelial ◽  
Amino Acid Peptide ◽  
Gram Positive Bacteria ◽  
Ht29 Cells ◽  
Membrane Components ◽  
First Time ◽  
Putative Mechanism

AbstractIn recent years the role of extracellular vesicles (EVs) of Gram-positive bacteria in host-microbe cross-talk has become increasingly appreciated, although the knowledge of their biogenesis, release and host-uptake is still limited. The aim of this study was to characterize the EVs released by the dairy isolate Lactiplantibacillus plantarum BGAN8 and to gain an insight into the putative mechanism of EVs uptake by intestinal epithelial cells. The cryo-TEM observation undoubtedly demonstrated the release of EVs (20 to 140 nm) from the surface of BGAN8, with exopolysaccharides seems to be part of EVs surface. The proteomic analysis revealed that the EVs are enriched in enzymes involved in central metabolic pathways, such as glycolysis, and in membrane components with the most abundant proteins belonging to amino acid/peptide ABC transporters. Putative internalization pathways were evaluated in time-course internalization experiments with non-polarized HT29 cells in the presence of inhibitors of endocytic pathways: chlorpromazine and dynasore (inhibitors of clathrin-mediated endocytosis—CME) and filipin III and nystatin (disrupting lipid rafts). For the first time, our results revealed that the internalization was specifically inhibited by dynasore and chlorpromazine but not by filipin III and nystatin implying that one of the entries of L. plantarum vesicles was through CME pathway.

Psychological Resilience Provides No Independent Protection From Suicidal Risk

Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey
Keyword(s):  
Risk Factors ◽  
Well Being ◽  
Current Status ◽  
Psychological Resilience ◽  
Cross Sectional ◽  
Life Project ◽  
Resilience Factors ◽  
First Time

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.

Synergetic Theory of Document in Evolution of Document Science

2018 ◽  
pp. 1060-1068
Author(s):  
Galina A. Dvoenosova ◽  
Keyword(s):  
Social Role ◽  
Scientific Study ◽  
Self Organization ◽  
Universal Theory ◽  
Social Self ◽  
Social Goal ◽  
The Social ◽  
Synergetic Theory ◽  
First Time

The article assesses synergetic theory of document as a new development in document science. In information society the social role of document grows, as information involves all members of society in the process of documentation. The transformation of document under the influence of modern information technologies increases its interest to representatives of different sciences. Interdisciplinary nature of document as an object of research leads to an ambiguous interpretation of its nature and social role. The article expresses and contends the author's views on this issue. In her opinion, social role of document is incidental to its being a main social tool regulating the life of civilized society. Thus, the study aims to create a scientific theory of document, explaining its nature and social role as a tool of social (goal-oriented) action and social self-organization. Substantiation of this idea is based on application of synergetics (i.e., universal theory of self-organization) to scientific study of document. In the synergetic paradigm, social and historical development is seen as the change of phases of chaos and order, and document is considered a main tool that regulates social relations. Unlike other theories of document, synergetic theory studies document not as a carrier and means of information transfer, but as a unique social phenomenon and universal social tool. For the first time, the study of document steps out of traditional frameworks of office, archive, and library. The document is placed on the scales with society as a global social system with its functional subsystems of politics, economy, culture, and personality. For the first time, the methods of social sciences and modern sociological theories are applied to scientific study of document. This methodology provided a basis for theoretical vindication of nature and social role of document as a tool of social (goal-oriented) action and social self-organization. The study frames a synergetic theory of document with methodological foundations and basic concepts, synergetic model of document, laws of development and effectiveness of document in the social continuum. At the present stage of development of science, it can be considered the highest form of theoretical knowledge of document and its scientific explanatory theory.

Physical Warmth Attenuates Ethnocentric Bias under Mortality Salience: An Embodied Terror Management Perspective

2020 ◽  
Author(s):  
Armand Chatard ◽  
Margaux Renoux ◽  
Jean Monéger ◽  
Leila Selimbegovic
Keyword(s):  
Mortality Salience ◽  
Terror Management ◽  
Negative Consequences ◽  
Defensive Reaction ◽  
Worldview Defense ◽  
Management Perspective ◽  
Physical Warmth ◽  
Alternative Means ◽  
First Time

Research indicates that individuals often deal with mortality salience by affirming beliefs in national or cultural superiority (worldview defense). Because worldview defense may be associated with negative consequences (discrimination), it is important to identify alternative means to deal with death-related thoughts. In line with an embodied terror management perspective, we evaluate for the first time the role of physical warmth in reducing defensive reaction to mortality salience. We predicted that, like social affiliation (social warmth), physical warmth could reduce worldview defense when mortality is salient. In this exploratory (preregistered) study, 202 French participants were primed with death-related thoughts, or an aversive control topic, in a heated room or a non-heated room. The main outcome was worldview defense (ethnocentric bias). We found no main effect of mortality salience on worldview defense. However, physical warmth reduced worldview defense when mortality was salient. Implications for an embodied terror management perspective are discussed.

Relationship between big five personality model and abusive supervision

2019 ◽  
Vol 12 (2) ◽  
Author(s):  
Bibi Tahira ◽  
Naveed Saif ◽  
Muhammad Haroon ◽  
Sadaqat Ali
Keyword(s):  
Big Five ◽  
Abusive Supervision ◽  
State Universities ◽  
Big Five Personality ◽  
Big Five Model ◽  
The Impact ◽  
First Time ◽  
Supervisor Behavior ◽  
Moderating Role

The current study tries to understand the diverse nature of relationship between personality Big Five Model (PBFM) and student's perception of abusive supervision in higher education institutions of Khyber Pakhtoonkhwa Pakistan. Data was collected in dyads i.e. (supervisors were asked to rate their personality attributes while student were asked to rate the supervisor behavior) through adopted construct. For this purpose, data was collected from three government state universities and one Private Sector University. The focus was on MS/M.Phill and PhD student and their supervisors of the mentioned universities. After measuring normality and validity regression analysis was conducted to assess the impact of supervisor personality characteristics that leads to abusive supervision. Findings indicate interestingly that except agreeableness other four attributes of (PBFM) are play their role for abusive supervision. The results are novel in the nature as for the first time Neuroticism, openness to experience, extraversion and conscientiousness are held responsible for the abusive supervision. The study did not explore the demographic characteristics, and moderating role of organizational culture, justice and interpersonal deviances to understand the strength of relationship in more detail way. Keywords: Personality big five model, abusive supervision, HEIs

Smolensk Proper Names in A.T. Tvardovsky’s Poems

2020 ◽  
pp. 54-62
Author(s):  
Inna A. Koroleva ◽  
Keyword(s):  
Proper Names ◽  
Personal Characteristics ◽  
Entire Body ◽  
Literary Works ◽  
Thematic Content ◽  
Home Town ◽  
Birthday Anniversary ◽  
Long Poems ◽  
First Time

This article is dedicated to the 110th birthday anniversary of a great Russian poet, native of Smolensk, one of the founders of the Smolensk Poetic School Aleksandr Tvardovsky (1910–1971). It examines how Smolensk motifs and Tvardovsky’s love for his home town are reflected in his works at the onomastic level. Smolensk-onyms reflected in long poems are analysed here, the focus being on anthroponyms and toponyms naming the characters and indicating the locations associated with Smolensk region. A close connection between the choice of proper names and Tvardovsky’s biography is established. An attempt is made to demonstrate how, using onomastic units introduced by the author into the storyline of his artistic text, the general principles of autobiography and chronotopy are realized, which have been noted earlier in critiques of Tvardovsky’s literary works. The onomastic component of the poems is analysed thoroughly and comprehensively, which helps us to decode the conceptual chain writer – name – text – reader and identify the author’s attitude to the characters and the ideological and thematic content of the works, as well as some of the author’s personal characteristics, tastes and passions. At the onomastic level, the thesis about the role of Smolensk motifs in Tvardovsky’s literary works is once more substantiated. A review is presented of onomastic studies analysing proper names of different categories in Tvardovsky’s poems (mainly conducted by the representatives of the Voronezh Onomastic School and the author of this article). It should be noted that Smolensk proper names in the entire body of Tvardovsky’s poetry are analysed for the first time.

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