Estradiol-Induced Epithelial to Mesenchymal Transition and Migration Are Inhibited by Blocking c-Src Kinase in Breast Cancer Cell Lines

Javier E. Jiménez-Salazar,Rene M. Rivera-Escobar,Rebeca Damián-Ferrara,Juan Maldonado-Cubas,Catalina Rincón-Pérez,Rosario Tarragó-Castellanos,Pablo Damián-Matsumura 한국유방암학회 2023 Journal of breast cancer Vol.26 No.5

Purpose: The epithelial-to-mesenchymal transition (EMT) is the main event that favors cell migration and metastasis in breast cancer. Previously, we demonstrated that 1 nM estradiol (E2) promotes EMT, induced by c-Src kinase, causing changes in the localization of proteins that compose the tight junction (TJ) and adherens junction (AJ). Methods: The present work highlights the central role of c-Src in the initiation of metastasis, induced by E2, through increasing the ability of MCF-7 and T47-D cells, which express estrogen receptor alpha (ERα), to migrate and invade before they become metastatic. Results: Treatment with E2 can activate two signaling pathways, the first one by the phosphorylated c-Src (p-Src) which forms the p-Src/E-cadherin complex. This phenomenon was completely prevented by incubation with a selective inhibitor of c-Src (5 μM PP2). p-Src then promotes the downregulation of E-cadherin and occludin, which are epithelial phenotype marker proteins of the AJ and TJ, respectively. In the second pathway, E2 binds to ERα, creating a complex that translocates to the nucleus, inducing the synthesis of SNAIL1 and N-cadherin proteins, markers of the mesenchymal phenotype. Both processes increased the migratory and invasive capacities of both cell lines. Conclusion: The present study demonstrate that E2 enhance EMT and migration, through c-Src activation, in human breast cancer cells that express ERα and become potential therapeutic targets.

Motion-based Optimum Design of a Slender Steel Footbridge and Assessment of Its Dynamic Behaviour

Javier Fernando Jiménez-Alonso,Andres Sáez 한국강구조학회 2017 International Journal of Steel Structures Vol.17 No.4

The improvement of construction materials together with the current aesthetic requirements has led the modern footbridges to a continuous increase in their slenderness. For this reason, the design of their structural systems is mainly conditioned by its dynamic response under pedestrian action. For long-span footbridges, control devices are needed to prevent unacceptable dynamic responses while providing economical designs. However, for medium-span footbridges, it is still possible to control their dynamic response via the modification of their natural frequencies. In this paper, an alternative motion-based design method is first proposed and further implemented for the design of a real footbridge. The main idea of this approach is to optimally determine the structural stiffness distribution to verify an adequate comfort class, while minimizing the self-weight. Furthermore, the uncertainties of its modal parameters are considered during its design. After the construction of the footbridge, its dynamic behaviour was experimentally assessed, with satisfactory results.

Manufacturing design to improve the attainment of functional ingredients from Aloysia citriodora leaves by advanced microwave technology

Francisco Javier Leyva-Jiménez,Jesús Lozano-Sánchez,Isabel Borrás-Linares,David Arráez-Román,Antonio Segura-Carretero 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.79 No.-

A manufacturing design and control of bioactive ingredients from Aloysia citriodora was performedapplying microwave-assisted extraction (MAE). Thus, a Response Surface Methodology based on CentralComposite Design 23 model was performed to monitor the matrix behavior. The factors were extractiontime, percentage of solvent and temperature. The chosen responses were extraction yield andphytochemicals recovery. The design allowed tofind the optimal conditions for each response and tovalidate them in order to attain high quality ingredients. These results pointed out that MAE is a noveltechnique which could be used to improve the new functional ingredient development.

Impact of urban pattern on operating costs of public services: quantification through the economic weight of services ‘to property’

Francisco Javier Garrido-Jiménez,Francesc Magrinyà,María Consuelo del Moral-Ávila 서울시립대학교 도시과학연구원 2022 도시과학국제저널 Vol.26 No.3

Research has shown the existence of strong links between physical configuration of the urban settlements and the economic metabolism of public services. However, this relationship has a different intensity depending on the nature of each service, resting exclusively on the services ‘to property’, that is, those ensuring smooth functionality of the buildings and public spaces. In such services, the operating cost per unit developed area largely depends on representative variables of the urban pattern. For instance, the length of roads per unit developed area impacts the operating costs of linear services, such as street lighting, street cleaning and, together with housing density, on the operating costs of water cycle, waste collection and disposal. Moreover, the maintenance costs of pavements, parks, and gardens are directly proportional to the dimension of the public space. Therefore, the economic weight of services ‘to property’ in the current budget of public administration highlights how vulnerable these budgets are against changes in the urban pattern and determines the expected maximum economic impact of any measure adopted through urban planning. Thus, the main objective of this study is to define, from a theoretical perspective, an indicator representative of the economic weight of the operating cost of the services ‘to property’ upon public administration budgets, capable of delimiting the relationship between the budgets and urban patterns. In addition, to show its utility, this urban-economic indicator has been computed for a sample of medium-sized Spanish cities, showing that, on an average, a quarter of the operating cost of urban public services is directly linked to urban patterns, highlighting the potential impact of urban planning decisions on the economic sustainability of urban settlements.

Isolation of IgG Antibodies to Toxocara in Ankylosing Spondylitis Patients with Acute Anterior Uveitis

Francisco-Javier Jiménez-Balderas,Janete García-Jaimes,Rita Ríos,Abraham Zonana-Nacach,Raquel Tapia-,Nayeli Villanueva,Patricia Méndez-Samperio,Jorge-Luis de-la-Rosa-Arana 대한안과학회 2014 Korean Journal of Ophthalmology Vol.28 No.3

Purpose: Since few reports had been published on the prevalence of toxocariasis in ankylosing spondylitis (AS)patients with acute non-granulomatous anterior uveitis (ANGAU), the aim of this work was to determine thepresence of antibodies against Toxocara canis in AS patients with ANGAU. Methods: Thirty-six patients (14 female and 22 male) with AS were enrolled in the study. The history of ANGAUwas accepted only if diagnosed by an ophthalmologist. The detection of IgG antibodies to T. canis was determinedby enzyme-linked immunosorbent assay. In addition, antibodies to Ascaris lumbricoides were alsotested to verify non-specific reactions. Results: The prevalence of ANGAU in the AS patients was 58% (21 / 36), and 38% (8 / 21) of the patients withANGAU were positive for antibodies to Toxocara, while 7% (1 / 15) of AS patients without ANGAU were positivefor T. canis (p = 0.038, two tails; mid-p exact). No antibodies were detected to A. lumbricoides antigens inthe serum samples of patients with AS. Conclusions: These data suggest that the seroprevalence of antibodies to T. canis is high in Mexican patientswith AS-associated uveitis, suggesting a chronic asymptomatic toxocariosis, which could be associated withthe pathogenesis of ANGAU; however, further larger-scale studies are needed to confirm this observation.

A plasma circulating miRNAs profile predicts type 2 diabetes mellitus and prediabetes: from the CORDIOPREV study

Rosa Jiménez-Lucena,Antonio Camargo,Juan Francisco Alcalá-Diaz,Cristina Romero-Baldonado,Raúl Miguel Luque,Ben van Ommen,Javier Delgado-Lista,Jose María Ordovás,Pablo Pérez-Martínez,Oriol Alberto Rang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

We aimed to explore whether changes in circulating levels of miRNAs according to type 2 diabetes mellitus (T2DM) or prediabetes status could be used as biomarkers to evaluate the risk of developing the disease. The study included 462 patients without T2DM at baseline from the CORDIOPREV trial. After a median follow-up of 60 months, 107 of the subjects developed T2DM, 30 developed prediabetes, 223 maintained prediabetes and 78 remained disease-free. Plasma levels of four miRNAs related to insulin signaling and beta-cell function were measured by RT-PCR. We analyzed the relationship between miRNAs levels and insulin signaling and release indexes at baseline and after the follow-up period. The risk of developing disease based on tertiles (T1-T2-T3) of baseline miRNAs levels was evaluated by COX analysis. Thus, we observed higher miR-150 and miR-30a-5p and lower miR-15a and miR-375 baseline levels in subjects with T2DM than in disease-free subjects. Patients with high miR-150 and miR-30a-5p baseline levels had lower disposition index (p = 0.047 and p = 0.007, respectively). The higher risk of disease was associated with high levels (T3) of miR-150 and miR-30a-5p (HRT3-T1 = 4.218 and HRT3-T1 = 2.527, respectively) and low levels (T1) of miR-15a and miR- 375 (HRT1-T3 = 3.269 and HRT1-T3 = 1.604, respectively). In conclusion, our study showed that deregulated plasma levels of miR-150, miR-30a-5p, miR-15a, and miR-375 were observed years before the onset of T2DM and pre-DM and could be used to evaluate the risk of developing the disease, which may improve prediction and prevention among individuals at high risk for T2DM.

The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

Javier Gayarre,Marta M. Kamieniak,Alicia Cazorla-Jiménez,Ivan Muñoz-Repeto,Salud Borrego,Jesús García-Donas,Susana Hernando,Luis Robles-Díaz,José M. García-Bueno,Ivan Márquez-Rodas,María José Echarri 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.1

Objective: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. Methods: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low- GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and logrank test were used to estimate patients’ survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Results: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5- silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. Conclusion: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.

Association between cigarette smoking and the prevalence of post-endodontic periapical pathology: a systematic review and meta-analysis

Ríos-Osorio Néstor,Muñoz-Alvear Hernan Darío,Jiménez-Castellanos Fabio Andrés,Quijano-Guauque Sara,Jiménez-Peña Oscar,García-Perdomo Herney Andrés,Caviedes-Bucheli Javier 대한치과보존학회 2022 Restorative Dentistry & Endodontics Vol.47 No.3

Objectives This systematic review and meta-analysis aimed to assess the association of cigarette smoking with the prevalence of post-endodontic apical periodontitis in humans. Materials and Methods We searched through PubMed/Medline, Web of Science, and Scopus from inception to December 2020. Risk of bias was performed by using the Newcastle-Ottawa Scale for cross-sectional, cohort, and case-control studies. We performed the statistical analysis in Review Manager 5.3 (RevMan 5.3). Results 6 studies met the inclusion criteria for qualitative and quantitative synthesis. Statistical analysis of these studies suggests that there were no differences in the prevalence of post endodontic apical periodontitis (AP) when comparing non-smokers vs smoker subjects regarding patients (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.31–1.49; I2 = 58%) and teeth (OR, 1.71; 95% CI, 0.99–2.93; I2 = 72%). Conclusions Our findings suggest that there was no association between cigarette smoking and post-endodontic apical periodontitis, as we did not find statistical differences in the prevalence of post-endodontic AP when comparing non-smokers vs smoker subjects. Therefore, smoking should not be considered a risk factor associated with endodontic failure. Objectives This systematic review and meta-analysis aimed to assess the association of cigarette smoking with the prevalence of post-endodontic apical periodontitis in humans. Materials and Methods We searched through PubMed/Medline, Web of Science, and Scopus from inception to December 2020. Risk of bias was performed by using the Newcastle-Ottawa Scale for cross-sectional, cohort, and case-control studies. We performed the statistical analysis in Review Manager 5.3 (RevMan 5.3). Results 6 studies met the inclusion criteria for qualitative and quantitative synthesis. Statistical analysis of these studies suggests that there were no differences in the prevalence of post endodontic apical periodontitis (AP) when comparing non-smokers vs smoker subjects regarding patients (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.31–1.49; I2 = 58%) and teeth (OR, 1.71; 95% CI, 0.99–2.93; I2 = 72%). Conclusions Our findings suggest that there was no association between cigarette smoking and post-endodontic apical periodontitis, as we did not find statistical differences in the prevalence of post-endodontic AP when comparing non-smokers vs smoker subjects. Therefore, smoking should not be considered a risk factor associated with endodontic failure.

Phosphoregulation of the oncogenic protein regulator of cytokinesis 1 (PRC1) by the atypical CDK16/CCNY complex

Sara Hernández-Ortega,Abril Sánchez-Botet,Eva Quandt,Núria Masip,Laura Gasa,Gaetano Verde,Javier Jiménez,Rebecca S. Levin,Florentine U. Rutaganira,Alma L. Burlingame,Don Wolfgeher,Mariana P. C. Ribeir 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

CDK16 (also known as PCTAIRE1 or PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family that forms an active complex with cyclin Y (CCNY). Although both proteins have been recently implicated in cancer pathogenesis, it is still unclear how the CDK16/CCNY complex exerts its biological activity. To understand the CDK16/ CCNY network, we used complementary proteomic approaches to identify potential substrates of this complex. We identified several candidates implicating the CDK16/CCNY complex in cytoskeletal dynamics, and we focused on the microtubule-associated protein regulator of cytokinesis (PRC1), an essential protein for cell division that organizes antiparallel microtubules and whose deregulation may drive genomic instability in cancer. Using analog-sensitive (AS) CDK16 generated by CRISPR-Cas9 mutagenesis in 293T cells, we found that specific inhibition of CDK16 induces PRC1 dephosphorylation at Thr481 and delocalization to the nucleus during interphase. The observation that CDK16 inhibition and PRC1 downregulation exhibit epistatic effects on cell viability confirms that these proteins can act through a single pathway. In conclusion, we identified PRC1 as the first substrate of the CDK16/CCNY complex and demonstrated that the proliferative function of CDK16 is mediated by PRC1 phosphorylation. As CDK16 is emerging as a critical node in cancer, our study reveals novel potential therapeutic targets.