ABSTRACT
A photo- and electro-thermal film can convert sunlight and electricity into heat to solve icing problems. Combination of them provides an efficient strategy for all-day anti-/de-icing. However, only opaque surfaces have been reported, due to the mutual exclusiveness between photon absorption and transmission. Herein, a highly transparent and scalable solution-processed photo-electro-thermal film is reported, which exhibits an ultra-broadband selective spectrum to separate the visible light from sunlight and a countertrend suppress of emission in longer wavelength. It absorbs ≈ 85% of invisible sunlight (ultraviolet and near-infrared) for light-heat conversion, meanwhile maintains luminous transmittance > 70%. The reflection of mid-infrared leads to low emissivity (0.41), which further preserves heat on the surface for anti-/de-icing purpose. This ultra-broadband selectivity enables temperature elevation > 40 °C under 1-sun illumination and the mutual support between photo-thermal and electro-thermal effects contributes to > 50% saving of electrical consumption under weak solar exposure (0.4-sun) for maintaining unfrozen surfaces at -35 °C environment. The reverberation from photo-electro-thermal and super-hydrophobic effects illustrates a lubricating removal of grown ice in short time (< 120 s). The self-cleaning ability and the durability under mechanical, electrical, optical, and thermal stresses render the film stable for long-term usage in all-day anti-/de-icing applications.
ABSTRACT
Discussions regarding entomophagy in humans have been typically led by entomologists. While anthropologists devote much time to understanding diverse human subsistence practices, historical and cultural variation in insect consumption remains largely unexplained. This review explores the relation between variable ecologies, subsistence strategies, and social norms on insect consumption patterns across past and contemporary human populations. Ecological factors, such as the nutritional contribution of edible insects relative to those of other foraged or farmed resources available, may help explain variation in their consumption. Additionally, our evolved social learning strategies may help propagate social norms that prohibit or prioritize the consumption of some or all edible insects, independent of their profitability. By adopting a behavioral ecological and cultural evolutionary approach, this review aims to resolve current debates on insect consumption and provide directions for future research.
Subject(s)
Insecta , Animals , HumansABSTRACT
Although oral diseases are mostly preventable, they remain a global public health problem. Thus, there is a need for trained personnel to actively intervene in promoting oral health, to prevent and timeously detect oral diseases, and, in turn, to provide comprehensive quality healthcare. The main objective of the study was to evaluate the knowledge, practices and perceptions regarding oral health preventive measures amongst undergraduate dental students. This cross-sectional study was conducted between the period October 2017 and January 2018. The subjects included were undergraduate students of the dental science program at the School of Dentistry, in Leon Guanajuato, Mexico. A validated questionnaire was used to identify knowledge of preventive dentistry and the frequency of oral health preventive actions in the dental school clinics. Besides, perception towards prevention in dentistry was assessed. A total of N=232 undergraduate students participated of whom 65.9% (N=153) were women. More than half of the students 59.5%, (N=138) rated their knowledge on the prevention of oral diseases as good, followed by 32.8% (N=75) of students who rated it as regular. 49% (N=97) of the students performed frequently preventive treatments in their daily clinical practice. 90% (N=217) think that the main reason of low practice of prevention in dentistry is the lack of commitment of the dentist. 72.8% (N=169) mention that there should be professionals dedicated exclusively to preventive dentistry. Students of second grade demonstrated better prevention knowledge and tended to engage more frequently in preventive activities (p<0.05). In conclusion, our study found that, second-year students perform preventive practices more frequently and these practices decrease as their studies progress. It should be sought to create positive attitudes towards prevention not only in the year in preventive dentistry, but also throughout the entire career. This enables students to become trained professionals that can deliver preventive services to their patients.
Subject(s)
Oral Health , Students, Dental , Attitude of Health Personnel , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Mexico , Perception , Surveys and QuestionnairesABSTRACT
OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Argentina, Chile and Costa Rica. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: A total of 170 S. pneumoniae and 218 H. influenzae isolates were collected at five centres in Argentina, Chile and Costa Rica in 2015-17. Small S. pneumoniae isolate numbers from Costa Rica (n = 2) meant that these could only be included in the penicillin susceptibility analysis; they were excluded from further country analyses. Around one-third of pneumococcal isolates from Argentina and two-thirds from Chile were non-susceptible to penicillin by CLSI oral or EUCAST low-dose IV breakpoints, but most (≥89%) were susceptible by CLSI IV or EUCAST high-dose breakpoints. Amongst pneumococci from Argentina, about 80% or more were susceptible to most other antibiotics except cefaclor (all breakpoints), cefixime (PK/PD breakpoints), cefuroxime (EUCAST breakpoints) and trimethoprim/sulfamethoxazole (CLSI and PK/PD breakpoints). S. pneumoniae isolates from Chile showed significantly lower susceptibility (P < 0.05) using CLSI breakpoints compared with those from Argentina for many of the antibiotics tested. Among isolates of H. influenzae from Latin America, more than 90% were susceptible to amoxicillin/clavulanic acid (high dose), cefixime, cefpodoxime, ceftriaxone and fluoroquinolones, irrespective of the breakpoints used. The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. CONCLUSIONS: Antibiotic susceptibility of H. influenzae isolates was generally high in the Latin American countries studied; however, susceptibility profiles varied for S. pneumoniae by country and depending on the breakpoints used, especially for cefaclor. These factors are important in decision making for empirical therapy of bacterial infections.
Subject(s)
Haemophilus influenzae , Respiratory Tract Infections , Anti-Bacterial Agents/pharmacology , Argentina/epidemiology , Chile/epidemiology , Costa Rica/epidemiology , Drug Resistance, Bacterial , Epidemiological Monitoring , Humans , Latin America/epidemiology , Microbial Sensitivity Tests , Respiratory Tract Infections/epidemiologyABSTRACT
This corrects the article DOI: 10.1038/mp.2017.42.
ABSTRACT
Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.
Subject(s)
Brain/physiopathology , Schizophrenia/genetics , Schizophrenia/physiopathology , Adolescent , Adult , Brain/anatomy & histology , Female , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Gray Matter/physiopathology , Humans , Magnetic Resonance Imaging/methods , Male , Polymorphism, Single Nucleotide/genetics , Risk FactorsABSTRACT
BARD, the BioAssay Research Database (https://bard.nih.gov/) is a public database and suite of tools developed to provide access to bioassay data produced by the NIH Molecular Libraries Program (MLP). Data from 631 MLP projects were migrated to a new structured vocabulary designed to capture bioassay data in a formalized manner, with particular emphasis placed on the description of assay protocols. New data can be submitted to BARD with a user-friendly set of tools that assist in the creation of appropriately formatted datasets and assay definitions. Data published through the BARD application program interface (API) can be accessed by researchers using web-based query tools or a desktop client. Third-party developers wishing to create new tools can use the API to produce stand-alone tools or new plug-ins that can be integrated into BARD. The entire BARD suite of tools therefore supports three classes of researcher: those who wish to publish data, those who wish to mine data for testable hypotheses, and those in the developer community who wish to build tools that leverage this carefully curated chemical biology resource.
Subject(s)
Biological Assay , Databases, Factual , High-Throughput Screening Assays , Data Mining , Internet , Molecular Probes , SoftwareABSTRACT
The aim of the present study was to use a model of simulated human childbirth in rats to determine the damage to genitourinary structures and behavioral signs of urinary dysfunction induced by vaginal distension (VD) in female rats. In experiment 1, the length of the genitourinary tract and the nerves associated with it were measured immediately after simulated human delivery induced by VD or sham (SH) procedures. Electroneurograms of the dorsal nerve of the clitoris (DNC) were also recorded. In experiment 2, histological characteristics of the bladder and major pelvic ganglion of VD and SH rats were evaluated. In experiment 3, urinary parameters were determined in conscious animals during 6 h of dark and 6 h of light before and 3 days after VD or SH procedures. VD significantly increased distal vagina width (P < 0.001) and the length of the motor branch of the sacral plexus (P < 0.05), DNC (P < 0.05), and vesical nerves (P < 0.01) and decreased DNC frequency and amplitude of firing. VD occluded the pelvic urethra, inducing urinary retention, hematomas in the bladder, and thinness of the epithelial (P < 0.05) and detrusor (P < 0.01) layers of the bladder. Major pelvic ganglion parameters were not modified after VD. Rats dripped urine in unusual places to void, without the stereotyped behavior of micturition after VD. The neuroanatomic injuries after VD occur alongside behavioral signs of urinary incontinence as determined by a new behavioral tool for assessing micturition in conscious animals.
Subject(s)
Disease Models, Animal , Puerperal Disorders/etiology , Urinary Incontinence/etiology , Animals , Female , Ganglion Cysts/pathology , Nerve Crush/adverse effects , Parturition , Puerperal Disorders/pathology , Random Allocation , Rats, Wistar , Urinary Bladder/pathology , Urinary Incontinence/pathology , UrinationABSTRACT
Tissue inhibitor of metalloproteinase-4 (TIMP-4) belongs to a family of extracellular matrix (ECM) metalloproteinases inhibitors that are overexpressed in several cancers. However, the role of TIMP-4 during carcinogenesis is poorly understood. To evaluate TIMP-4 functions in carcinogenesis, stably transfected cells overexpressing this tissue inhibitor were used. Xenograft tumor growth, stem cell enrichment, colony formation, and gene regulation were investigated. Microarrays and in silico analysis were carried out to elucidate TIMP-4 molecular mechanisms. In the present report, we show that in nude mice, cervical cancer cells that overexpress TIMP-4 formed tumors faster than control cell-derived tumors. Furthermore, in vivo limiting dilution assays showed that fewer TIMP-4 overexpressing cells are needed for tumor formation. In vitro analyses demonstrated that TIMP-4 overexpression or exposure to human recombinant TIMP-4 (hrTIMP4) caused an enrichment of the tumor progenitor cell (TPC) population. Accordingly, genome-wide expression and signaling pathway analyses showed that hrTIMP-4 modulated cell survival, cell proliferation, inflammation, and epithelial-mesenchymal transition (EMT) signaling networks. Notably, NFκB signaling pathway appeared to be globally activated upon hrTIMP-4 treatment. Overall, this report provides the first example that TIMP-4 regulates carcinogenesis through enriching the TPC population in cervical cancer cells. Understanding TIMP-4 effects on tumorigenesis may provide clues for future therapies design. © 2015 Wiley Periodicals, Inc.
Subject(s)
Cervix Uteri/pathology , Gene Expression Regulation, Neoplastic , Neoplastic Stem Cells/pathology , Tissue Inhibitor of Metalloproteinases/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Animals , Cervix Uteri/metabolism , Female , HeLa Cells , Humans , Mice , NF-kappa B/metabolism , Neoplastic Stem Cells/metabolism , Signal Transduction , Tissue Inhibitor of Metalloproteinases/metabolism , Up-Regulation , Uterine Cervical Neoplasms/metabolism , Tissue Inhibitor of Metalloproteinase-4ABSTRACT
To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase-mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease.
Subject(s)
Gene Expression Regulation, Neoplastic , Lymphoma, Large B-Cell, Diffuse/genetics , Mutation , Amino Acid Motifs , Cluster Analysis , DNA Mutational Analysis , Exome , Exons , Humans , Models, Genetic , Polymerase Chain Reaction/methods , Sequence Analysis, DNA , Translocation, GeneticABSTRACT
The marsupial blastocyst forms in an entirely different manner from its eutherian counterpart, involving cell-zona rather than cell-cell adhesion during the 8- to-16-cell transition. While the eutherian blastocyst consists of a spherical trophoblast completely enveloping a pluripotent inner cell mass, or pluriblast, the marsupial blastocyst forms initially as a bowl-shaped monolayer of cells lining the zona pellucida at the embryonic pole (ep). This monolayer contains a small patch of centrally positioned pluriblast cells edged with trophoblast cells that later coalesce at the abembryonic pole. Using immunocytochemistry, we examined the localization of the proteins Oct4, Cdx2, Tead4, Sox2, and Yap1 in opossum embryos to determine if their temporal expression pattern differed from that in the mouse, given the important differences in cell behavior preceding blastocyst formation in these mammals. Our results indicate that these proteins are expressed in similar temporal patterns despite the topological differences between mouse and opossum cleavage-stage embryos and blastocysts. That the Hippo-pathway protein Yap1 localized specifically around the approximately 128-cell stage to opossum trophoblast nuclei but remained in the cytoplasm of pluriblast cells suggests that this transcriptional regulator participates in allocating cells to the trophoblast lineage, as it does in mouse. Interestingly, in both mouse and opossum embryos, expression of the pluripotency marker Oct4 persisted after Cdx2, which signals trophoblast specification, began to be expressed in trophoblast cells. This and the observation that Cdx2 is present in opossum embryos well before blastomere-zona adhesion even occurs suggests that the proteins studied may have other roles in early mammalian embryonic development.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Blastocyst/cytology , Homeodomain Proteins/metabolism , Monodelphis/embryology , Octamer Transcription Factor-3/metabolism , Trans-Activators/metabolism , Animals , CDX2 Transcription Factor , Cell Adhesion , Cell Lineage , Cell Nucleus/metabolism , Cytoplasm/metabolism , Female , Gene Expression Regulation, Developmental , Mice , Monodelphis/metabolism , Time Factors , Trophoblasts/metabolismABSTRACT
Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled 156 women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16 (29.4%), HPV31 (21.17%) and HPV18 (15.29%). Next, we evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays in a sub-cohort of 63 women. IL-21 and CXCL9 were significantly upregulated in HPV-positive women (p=0.0002 and p=0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity (p<0.001), and their vaginal microbiota was enriched in bacterial vaginosis-associated anaerobes (Sneathia, Shuttleworthia, Prevotella, and Atopobium) and depleted in Lactobacillus spp. Furthermore, the vaginal microbiota of women with symptomatic cervical ectopy and HPV infection correlated with vaginal inflammation (IL-1ß, rho=0.56, p=0.0004) and increased mucosal homeostatic response (IL-22, rho=0.60, p=0.0001). Taken together, our results suggest that HPV infection and dysbiotic vaginal communities could favor a vaginal microenvironment that might delay the recovery of the cervical epithelium in women with symptomatic cervical ectopy and favor STDs acquisition.
Subject(s)
Alphapapillomavirus , Microbiota , Papillomavirus Infections , Female , Humans , Immunity, Mucosal , Male , Microbiota/genetics , Papillomaviridae/geneticsABSTRACT
Electroporation (EP) is a simple in vivo method to deliver normally impermeable molecules, such as plasmid DNA, to a variety of tissues. Delivery of plasmid DNA by EP to a large surface area is not practical because the distance between the electrode pairs, and therefore the applied voltage, must be increased to effectively permeabilize the cell membrane. The design of the multielectrode array (MEA) incorporates multiple electrode pairs at a fixed distance to allow for delivery of plasmid DNA to the skin, potentially reducing the sensation associated with in vivo EP. In this report, we evaluate the effects of field strength and pulse width on transgene expression and duration using a plasmid encoding the luciferase reporter gene delivered by intradermal injection in a guinea pig model followed by EP with the MEA. As expected, the level of luciferase expression increased with the magnitude and duration of the voltage applied. In addition to adjusting transgene expression levels by altering fielding strength, levels could also be controlled by adjusting the plasmid dose. Our results indicate that the design of the MEA is a viable option for cutaneous plasmid DNA delivery by in vivo EP to a large surface area.
Subject(s)
Electrodes , Electroporation/methods , Gene Transfer Techniques , Plasmids , Administration, Cutaneous , Animals , Female , Gene Expression , Guinea Pigs , Luciferases/genetics , TransgenesABSTRACT
There are two hypotheses that explain tumor progression. The first one, the stochastic hypothesis, assumes that any cell within a tumor has the capacity to form and maintain the tumor mass. The second, the so-called hierarchical hypothesis, suggests the existence of a group of cells with a stem phenotype which, like in normal tissues, preserves tumors through a continuous production of progeny. These stem cells are in a particular niche, have a higher resistance to chemotherapy and radiotherapy, and are also capable of invading and migrating to other tissues. This review describes the cancer stem cells (CSCs), their function inside a tumor and the current knowledge about these cells.
Subject(s)
Neoplastic Stem Cells , Antigens, Differentiation/analysis , Antigens, Neoplasm/analysis , Biomarkers, Tumor , Cell Division , Cell Lineage , Cell Separation , Drug Design , Drug Resistance, Neoplasm , Humans , Models, Biological , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplastic Cells, Circulating , Neoplastic Stem Cells/cytology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/radiation effects , Radiation ToleranceABSTRACT
This is a poetical and historical approach to the last biological stages of the evolutive development of women, namely menopause and old age. It starts with the passages found in Egyptian Papirii such as Ebers or Smith, dated 1500-2000 BC, which describe, among other symptoms, the sweating and hig body temperatures caused by the diminishing hormon secretion of the ovaries. Other important works on the subject, some of them written in the 20th century and some others composed before that date, are also quoted, such as the Edad Crítica (Critical Age) by Dr. Marañon. The final stage of a woman's life, old age, is presented through the famous sonet "Alfa y Omega" (Alpha and Omega) by poet Manuel Machado. Using poetical strokes, the author conveys an image of the many phisiopatological consequences of old age in women: osteoporosis, genital prolapse, urine incontinence and "wrinkles" ("old age is neither shown by white hair nor by wrinkles but by the heart"). The work finishes with the famous statement uttered by Napoleon Bona-parte: "God wanted to be a writer: Man is His prose; His poetry, Women". The same poetry that Dr. Cruz y Hermida has found through the complexities of the evolutive process of feminine biology.
Subject(s)
Menopause , Poetry as Topic , Female , History, 20th Century , History, Ancient , Humans , Women/historyABSTRACT
Gene therapy approaches delivering fibroblast growth factor-2 (FGF-2) have shown promise as a potential treatment for increasing blood flow to ischemic limbs. Currently, effective noninvasive techniques to deliver plasmids encoding genes of therapeutic interest, such as FGF-2, are limited. We sought to determine if intradermal injection of plasmid DNA encoding FGF-2 (pFGF) followed by noninvasive cutaneous electroporation (pFGFE+) could increase blood flow and angiogenesis in a rat model of hindlimb ischemia. pFGFE+ or control treatments were administered on postoperative day 0. Compared to injection of pFGF alone (pFGFE-), delivery of pFGFE+ significantly increased FGF-2 expression for 10 days. Further, the increase in FGF-2 expression with pFGFE+ was sufficient to significantly increase ischemic limb blood flow, measured by laser Doppler perfusion imaging, beginning on postoperative day 3. Ischemic limb blood flow in the pFGFE+ treatment group remained significantly higher than all control groups through the end point of the study, postoperative day 14. Immunohistochemical staining of gastrocnemius cross sections determined there was a twofold increase in capillary density in the pFGFE+ treatment group. Our results suggest that pFGFE+ is a potential noninvasive, nonviral therapeutic approach to increase perfusion and angiogenesis for the treatment of limb ischemia.
Subject(s)
Fibroblast Growth Factor 2/genetics , Genetic Therapy/methods , Hindlimb/blood supply , Ischemia/therapy , Animals , Disease Models, Animal , Electroporation , Fibroblast Growth Factor 2/biosynthesis , Gene Transfer Techniques , Neovascularization, Physiologic , Peripheral Vascular Diseases/therapy , Rats , Regional Blood FlowABSTRACT
Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly increased cardiac expression of VEGF compared with injection of plasmid alone. This is the first report showing successful intracardiac delivery, through in vivo EP, of a protein expressing plasmid in a large animal.
Subject(s)
Coronary Artery Disease/therapy , DNA/administration & dosage , Electroporation/methods , Gene Transfer Techniques , Genetic Therapy/methods , Vascular Endothelial Growth Factor A/genetics , Animals , DNA/genetics , Genetic Vectors , Heart , Plasmids/administration & dosage , Plasmids/genetics , Protein Biosynthesis/genetics , Swine , Vascular Endothelial Growth Factor A/biosynthesisABSTRACT
(1) Aim: In the present paper we analyzed the transcriptome of CSCs (Cancer Stem Cells), in order to find defining molecular processes of breast cancer. (2) Methods: We performed RNA-Seq from CSCs isolated from the basal cell line MDA-MB-468. Enriched processes and networks were studied using the IPA (Ingenuity Pathway Analysis) tool. Validation was performed with qRT-PCR and the analysis of relevant genes was evaluated by overexpression, flow cytometry and in vivo zebrafish studies. Finally, the clinical relevance of these results was assessed using reported cohorts. (3) Results: We found that CSCs presented marked differences from the non-CSCs, including enrichment in transduction cascades related to stemness, cellular growth, proliferation and apoptosis. Interestingly, CSCs overexpressed a module of co-regulated Chromosomal Passenger Proteins including BIRC5 (survivin), INCENP and AURKB. Overexpression of BIRC5 increased the number of CSCs, as assessed by in vitro and in vivo zebrafish xenotransplant analyses. Analysis of previously published cohorts showed that this co-regulated module was not only overexpressed in basal breast tumors but also associated with relapse-free and overall survival in these patients. (4) Conclusions: These results underline the importance of Cancer Stem Cells in breast cancer progression and point toward the possible use of chromosomal passenger proteins as prognostic factors.