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 Data Integration Reveals the Potential Biomarkers of Circulating MicroRNAs in Osteoarthritis

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 412
Author(s):  
Thuan Duc Lao ◽  
Thuy Ai Huyen Le
Keyword(s):  
Target Genes ◽  
Potential Implication ◽  
Circulating Micrornas ◽  
Abnormal Expression ◽  
Online Databases ◽  
Socioeconomic Burden ◽  
Therapeutic Tools ◽  
Potential Use ◽  
Potential Biomarkers

The abnormal expression of circulating miRNAs (c-miRNAs) has become an emerging field in the development of miRNAs-based diagnostic and therapeutic tools for human diseases, including osteoarthritis (OA). OA is the most common form of arthritis leading to disability and a major socioeconomic burden. The abnormal expression of miRNAs plays important roles in the pathogenesis of OA. Unraveling the role of miRNAs in the pathogenesis of OA will throw light on the potential for the development of miRNAs-based diagnostic and therapeutic tools for OA. This article reviews and highlights recent advances in the study of miRNAs in OA, with specific demonstration of the functions of miRNA, especially c-miRNA, in OA pathogenesis as well as its potential implication in the treatment of OA. Based on a systematic literature search using online databases, we figured out the following main points: (1) the integrative systematic review of c-mRNAs and its target genes related to OA pathogenesis; (2) the potential use of c-miRNAs for OA diagnosis purposes as potential biomarkers; and (3) for therapeutic purposes, and we also highlight certain remedies that regulate microRNA expression based on its target genes.

Abstract 2178: Sonic Hedgehog In Adult Hypoxic Cerebellum

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Giuseppe Straface ◽  
Andrea Flex ◽  
Federico Biscetti ◽  
Eleonora Gaetani ◽  
Giovanni Pecorini ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Target Genes ◽  
Positive Staining ◽  
Lacz Gene ◽  
Downstream Target ◽  
Shh Pathway ◽  
And Migration ◽  
First Time ◽  
Proliferation And Migration

Background: Cerebellar hypoxia is responsible for important aspects of cognitive deterioration and motor disturbances in neurological disorders, such as stroke, vascular dementia, and neurodegeneration. In the cerebellum, VEGF is significantly upregulated after hypoxia and is able to induce angiogenesis, reduce neuronal apoptosis, and regulate neuronal differentiation, proliferation, and migration. But, VEGF is not sufficient to provide neuroprotection. A crucial role is played by growth associated protein-43 (GAP43), for which important activities have been described. The purpose of this study was to investigate the role of the developmental Sonic hedgehog (Shh) signaling pathway in postnatal hypoxic cerebellum and its relationship with VEGF and GAP43 expression. Methods: We used adult C57BL/6J mice, ptc1-lacZ mice, and GAP43−/− mice for these experiments. Ptc1-lacZ mice carry a non-disruptive insertion of the lacZ gene under the control of the ptc1 promoter. Ptc1 is a downstream-transcriptional target of Shh and its upregulation indicates activation of the Shh pathway. Mice were exposed to systemic normobaric hypoxia (6%O 2 ) for 6 hours and the expression of Shh, Ptc1, VEGF, and GAP43 were investigated. Results: After exposure to hypoxia, Shh-positive staining was detected in Purkinje cells (PCs). The same cells were also lacZ(ptc1)-positive, indicating that PCs are both Shh-producing and -responding elements. Also the cells of the internal granular layer (IGL) were lacZ(ptc1)-positive, indicating that these cells are Shh-responsive. LacZ(ptc1)-positive IGL cells were also immunopositive for VEGF and GAP-43. We also found that ptc1 expression is lost in PCs of GAP43−/− mice, indicating that Shh requires GAP43 to activate its downstream target genes in PCs. Finally, when cultures enriched in granular cells were stimulated with Shh recombinant protein, GAP43 phosphorylation was increased. This effect was inhibited by Shh-inhibitor cyclopamine. Conclusions: This is the first time that hypoxia is reported to activate the Shh pathway in the adult. Our data suggest that the Shh pathway might be important for the cerebellar response to hypoxia, through interactions with VEGF and GAP43.

Gender Differences in the Motivations for the Use of Sanctions in Conflicts Within Muslim and Jewish Couples

2020 ◽  
pp. 088626052093549
Author(s):  
Wafaa Sowan-Basheer ◽  
Zeev Winstok
Keyword(s):  
Gender Differences ◽  
Intimate Relationships ◽  
Intimate Partner ◽  
Orthodox Jewish ◽  
Heterosexual Couples ◽  
Preliminary Estimate ◽  
Men And Women ◽  
First Time ◽  
Empirical Implications

This study aimed to examine differences between men and women and between Muslims, secular Jews, and religious Jews in their motivations for using sanctions within their intimate relationships. This work involved heterosexual couples from the general population. The sample included 95 Muslim, 68 secular Jewish, and 70 ultra-orthodox Jewish couples (466 participants). The findings of the study show that sanction use during times of conflict is prevalent among the vast majority of couples. Motivations for the use of sanctions are stronger among women than men. In addition, the strongest motivation expressed by both genders was a motivation for conflict resolution. This is the first time that sanctions, as a tactic to cope with conflict, have been addressed in a scholarly manner. This study provides a preliminary estimate of how commonly these types of behaviors are used in intimate relationships. Theoretical and empirical implications of the theoretical framework and the findings are discussed, including the role of the use of sanction in the escalation of intimate partner conflicts.

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 The Role of MicroRNAs in Ovarian Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yasuto Kinose ◽  
Kenjiro Sawada ◽  
Koji Nakamura ◽  
Tadashi Kimura
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor Genes ◽  
Target Genes ◽  
Early Stage ◽  
Noncoding Rnas ◽  
Circulating Micrornas ◽  
Gynecological Tumors ◽  
Prevention And Treatment ◽  
Prognostic And Predictive Markers

Ovarian cancer is the most lethal of malignant gynecological tumors. Its lethality may be due to difficulties in detecting it at an early stage and lack of effective treatments for patients with an advanced or recurrent status. Therefore, there is a strong need for prognostic and predictive markers to diagnose it early and to help optimize and personalize treatment. MicroRNAs are noncoding RNAs that regulate target genes posttranscriptionally. They are involved in carcinogenesis, cell cycle, apoptosis, proliferation, invasion, metastasis, and chemoresistance. The dysregulation of microRNAs is involved in the initiation and progression of human cancers including ovarian cancer, and strong evidence that microRNAs can act as oncogenes or tumor suppressor genes has emerged. Several microRNA signatures that are unique to ovarian cancer have been proposed, and serum-circulating microRNAs have the potential to be useful diagnostic and prognostic biomarkers. Various microRNAs such as those in the miR-200 family, the miR-199/214 cluster, or the let-7 paralogs have potential as therapeutic targets for disseminated or chemoresistant ovarian tumors. Although many obstacles need to be overcome, microRNA therapy could be a powerful tool for ovarian cancer prevention and treatment. In this review, we discuss the emerging roles of microRNAs in various aspects of ovarian cancer.

scholarly journals The Gendered Relationship Between (Old and New Forms of) Employment Instability and Union Dissolution

2021 ◽  
Author(s):  
Elena Bastianelli ◽  
Daniele Vignoli
Keyword(s):  
Gender Differences ◽  
Event History ◽  
Limited Time ◽  
Union Dissolution ◽  
Comprehensive Understanding ◽  
The Life Course ◽  
First Time ◽  
Gender Specific ◽  
Employment Instability

AbstractThe present study contributes to a more comprehensive understanding of the relation between employment instability and union dissolution. To address the oversights of previous research, we disentangle the effect of employment instability on union dissolution by: (i) considering not only the effect of joblessness, but also the type of employment contract; (ii) evaluating both status and the accumulation of instability over the life course; and (iii) detecting gender differences. We focus on Italy, applying event-history techniques to the most recent Italian Multipurpose Survey “Families, social subjects and life cycle” of 2016, observing cohorts from 1950 to 1986. Our results suggest that the effect of employment instability on union dissolution is gender-specific: joblessness and limited-time employment are facilitators for men’s dissolution, while, for women, joblessness is an inhibitor for dissolution, and time-limited and permanent employment do not substantially differ. We also highlight the crucial role of the persistence of instability in unpacking the association between employment instability and union dissolution. This paper advances—for the first time for Italy, at least—that men’s time-limited employment arrangements negatively affect a couple’s stability.

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.

Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates

2021 ◽  
Vol 13 (584) ◽  
pp. eabb0202
Author(s):  
Qingju Li ◽  
Yinchuan Xu ◽  
Kaiqi Lv ◽  
Yingchao Wang ◽  
Zhiwei Zhong ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Extracellular Vesicles ◽  
Nonhuman Primates ◽  
Target Genes ◽  
Cardiac Fibroblasts ◽  
Vascular Density ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Stem cell–derived small extracellular vesicles (sEVs) promote angiogenesis after myocardial infarction (MI). However, the components of sEVs that contribute to these effects and the safety and efficiency of engineered sEV treatment for MI remain unresolved. Here, we observed improved cardiac function, enhanced vascular density, and smaller infarct size in mice treated with the sEVs from hypoxia-preconditioned (HP) mesenchymal stem cells (MSCs) (HP-sEVs) than in mice treated with normoxia-preconditioned (N) MSCs (N-sEVs). MicroRNA profiling revealed a higher abundance of miR-486-5p in HP-sEVs than in N-sEVs, and miR-486-5p inactivation abolished the benefit of HP-sEV treatment, whereas miR-486-5p up-regulation enhanced the benefit of N-sEV treatment. Matrix metalloproteinase 19 (MMP19) abundance was lower in HP-sEV–treated than N-sEV–treated mouse hearts but was enriched in cardiac fibroblasts (CFs), and Mmp19 was identified as one of the target genes of miR-486-5p. Conditioned medium from CFs that overexpressed miR-486-5p or silenced MMP19 increased the angiogenic activity of endothelial cells; however, medium from CFs that simultaneously overexpressed Mmp19 and miR-486-5p abolished this effect. Mmp19 silencing in CFs reduced the cleavage of extracellular vascular endothelial growth factor (VEGF). Furthermore, miR-486-5p–overexpressing N-sEV treatment promoted angiogenesis and cardiac recovery without increasing arrhythmia complications in a nonhuman primate (NHP) MI model. Collectively, this study highlights the key role of sEV miR-486-5p in promoting cardiac angiogenesis via fibroblastic MMP19-VEGFA cleavage signaling. Delivery of miR-486-5p–engineered sEVs safely enhanced angiogenesis and cardiac function in an NHP MI model and may promote cardiac repair.

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

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