New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

Begoña Alburquerque-González,Manuel Bernabé-García,Silvia Montoro-García,Ángel Bernabé-García,Priscila Campioni Rodrigues,Javier Ruiz Sanz,Fernando F. López-Calderón,Irene Luque,Francisco José Nicolas 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Serrated adenocarcinoma (SAC) is more invasive, has worse outcomes than conventional colorectal carcinoma (CRC), and is characterized by frequent resistance to anti-epidermal growth factor receptor (EGFR) and overexpression of fascin1, a key protein in actin bundling that plays a causative role in tumor invasion and is overexpressed in different cancer types with poor prognosis. In silico screening of 9591 compounds, including 2037 approved by the Food and Drug Administration (FDA), was performed, and selected compounds were analyzed for their fascin1 binding affinity by differential scanning fluorescence. The results were compared with migrastatin as a typical fascin1 inhibitor. In silico screening and differential scanning fluorescence yielded the FDA-approved antidepressant imipramine as the most evident potential fascin1 blocker. Biophysical and different in vitro actin-bundling assays confirm this activity. Subsequent assays investigating lamellipodia formation and migration and invasion of colorectal cancer cells in vitro using 3D human tissue demonstrated anti-fascin1 and anti-invasive activities of imipramine. Furthermore, expression profiling suggests the activity of imipramine on the actin cytoskeleton. Moreover, in vivo studies using a zebrafish invasion model showed that imipramine is tolerated, its anti-invasive and antimetastatic activities are dose-dependent, and it is associated with both constitutive and induced fascin1 expression. This is the first study that demonstrates an antitumoral role of imipramine as a fascin1 inhibitor and constitutes a foundation for a molecular targeted therapy for SAC and other fascin1-overexpressing tumors.

Bioelectronics-on-a-chip for cardio myoblast proliferation enhancement using electric field stimulation

Ángel Aragón,María Cebro-Márquez,Eliseo Perez,Antonio Pazos,Ricardo Lage,José Ramón González-Juanatey,Isabel Moscoso,Carmen Bao-Varela,Daniel Nieto 한국생체재료학회 2020 생체재료학회지 Vol.24 No.3

Background: Cardio myoblast generation from conventional approaches is laborious and time-consuming. We present a bioelectronics on-a-chip for stimulating cells cardio myoblast proliferation during culture. Method: The bioelectronics chip fabrication methodology involves two different process. In the first step, an aluminum layer of 200 nm is deposited over a soda-lime glass substrate using physical vapor deposition and selectively removed using a Q-switched Nd:YVO4 laser to create the electric tracks. To perform the experiments, we developed a biochip composed of a cell culture chamber fabricated with polydimethylsiloxane (PDMS) with a glass coverslip or a cell culture dish placed over the electric circuit tracks. By using such a glass cover slip or cell culture dish we avoid any toxic reactions caused by electrodes in the culture or may be degraded by electrochemical reactions with the cell medium, which is crucial to determine the effective cell-device coupling. Results: The chip was used to study the effect of electric field stimulation of Rat ventricular cardiomyoblasts cells (H9c2). Results shows a remarkable increase in the number of H9c2 cells for the stimulated samples, where after 72 h the cell density double the cell density of control samples. Conclusions: Cell proliferation of Rat ventricular cardiomyoblasts cells (H9c2) using the bioelectronics-on-a-chip was enhanced upon the electrical stimulation. The dependence on the geometrical characteristics of the electric circuit on the peak value and homogeneity of the electric field generated are analyzed and proper parameters to ensure a homogeneous electric field at the cell culture chamber are obtained. It can also be observed a high dependence of the electric field on the geometry of the electrostimulator circuit tracks and envisage the potential applications on electrophysiology studies, monitoring and modulate cellular behavior through the application of electric fields.

Work Ability Index: Psychometric Testing in Aeronautical Industry Workers

González-Domínguez María Eugenia,Fernández-García Elena,Paloma-Castro Olga,González-López Regina María,Rivas Pérez María Paz,López-Molina Luis,García-Jiménez Jesús,Romero-Sánchez José Manuel 한국산업안전보건공단 산업안전보건연구원 2024 Safety and health at work Vol.15 No.1

Background The Work Ability Index (WAI) is an instrument that measures work ability. The wide dispersion of the WAI internationally has led to its adaptation for use in different countries. This study aimed to evaluate the psychometric properties of the Spanish version of the WAI. Methods A methodological design was used over an opportunistic sample of 233 workers in the aeronautical industry in Spain. Reliability was evaluated through internal consistency. Factorial validity, known groups, and convergent validity were tested. Results The Cronbach's alpha and item-total correlation indicated an adequate internal consistency. The confirmatory factor analysis, performed to evaluate the factorial validity, found adequate fit indices for a two-factor solution with a high correlation between the factors. Factor 1, “Subjectively estimated work ability and resources”, was composed of 3 subscales and factor 2, “Ill-health-related”, of 2 subscales. Subscales 4 and 6 had loading in both factors. Workers under 45 years of age obtained higher significant scores than older ones. Convergent validity was also evidenced since WAI was highly correlated with self-assessment of health status. Conclusions The Spanish version of the WAI has shown evidence of reliability and validity in this study, supporting its use in individual and collective health surveillance by occupational health professionals. The factorial solution that was found has previously been reported in another international context. However, further research is needed to resolve the discrepancies detected in the role of some subscales between other national and international studies. Background The Work Ability Index (WAI) is an instrument that measures work ability. The wide dispersion of the WAI internationally has led to its adaptation for use in different countries. This study aimed to evaluate the psychometric properties of the Spanish version of the WAI. Methods A methodological design was used over an opportunistic sample of 233 workers in the aeronautical industry in Spain. Reliability was evaluated through internal consistency. Factorial validity, known groups, and convergent validity were tested. Results The Cronbach's alpha and item-total correlation indicated an adequate internal consistency. The confirmatory factor analysis, performed to evaluate the factorial validity, found adequate fit indices for a two-factor solution with a high correlation between the factors. Factor 1, “Subjectively estimated work ability and resources”, was composed of 3 subscales and factor 2, “Ill-health-related”, of 2 subscales. Subscales 4 and 6 had loading in both factors. Workers under 45 years of age obtained higher significant scores than older ones. Convergent validity was also evidenced since WAI was highly correlated with self-assessment of health status. Conclusions The Spanish version of the WAI has shown evidence of reliability and validity in this study, supporting its use in individual and collective health surveillance by occupational health professionals. The factorial solution that was found has previously been reported in another international context. However, further research is needed to resolve the discrepancies detected in the role of some subscales between other national and international studies.

Effect of Fiber Orientation on the Fatigue Behavior of Steel Fiber-Reinforced Concrete Specimens by Performing Wedge Splitting Tests and Computed Tomography Scanning

Dorys C. González,Álvaro Mena-Alonso,Jesús Mínguez,José A. Martínez,Miguel A. Vicente 한국콘크리트학회 2024 International Journal of Concrete Structures and M Vol.18 No.2

This paper shows the relationship, in steel fiber-reinforced concrete, between fiber orientation and fatigue response through the combined use of computed tomography (CT), digital image processing (DIP) software and wedge splitting test (WST). The WST cubes were extracted from conventional 150 × 150× 600 concrete prisms and a groove and notch were carved on different faces in such a way that in half of the test specimens the fibers are oriented mostly perpendicular to the breaking surface and, in the other half, the fibers are mostly oriented parallel to the breaking surface. Fiber orientation was obtained using a CT device and DIP software from a miniprism extracted from the previously mentioned concrete prisms. The results show that there is a strong correlation between the crack-sewing fiber orientation on the one hand and fatigue life and crack opening rate per cycle on the other hand. Cubes with a higher percentage of fibers perpendicular to the crack surface (i.e., with a higher efficiency index) show a longer fatigue life and a lower crack opening rate per cycle, while cubes with a lower efficiency index show a shorter fatigue life and a higher crack opening rate per cycle.

Acute toxicity of aqueous extract of Ambrosia arborescens Mill. on biochemical and histopathological parameters in rats

Silva-Correa Carmen R.,Villarreal-La Torre Víctor E.,González-Siccha Anabel D.,Cruzado-Razco José L.,González-Blas María V.,Sagástegui-Guarniz William Antonio,Calderón-Peña Abhel A.,Aspajo-Villalaz Ci 한국독성학회 2022 Toxicological Research Vol.38 No.2

Medicinal plants play an important role in the management of various diseases, so their use has become widespread. However, in some cases the population uses plant species regardless of the toxicity they may possess. The objective of this study was to evaluate the acute toxicity of aqueous extract from the leaves of Ambrosia arborescens Mill. on the biochemical and histopathological parameters of albino Holtzman rats. To do this, the leaves of A. arborescens were collected in the province of Julcan, La Libertad Region—Peru. OECD (Organisation for Economic Cooperation and Development) guideline 423 was conducted, forming experimental groups of 10 animals each one (5 males and 5 females): Group I (Control), which received 2 mL physiological saline solution (SSF 0.9%), Groups II and III (A. arborescens-300 and A. arborescens-2000), which were given the aqueous extract leaves of A. arborescens in a single dose of 300 and 2000 mg/kg/day, respectively. On the 14th day of exposure, biochemical (creatinine, ALT and AST) and histopathological parameters were measured. The results show that the aqueous extract of A. arborescens at the dose of 2000 mg/kg produces an increase in biochemical parameters which is related to histopathological analysis of liver and renal tissue with mild congestion. The study concludes that the aqueous extract leaves of A. arborescens has a LD50 greater than 2000 mg/kg and produces mild congestion in kidneys and liver, but showed no significant toxicological changes in the other albino Holtzman rats organs.

A novel approach for the rigid body guidance synthesis of planar RRPR linkages

Selma J. Rodríguez-González,Henry A. Suárez-Velásquez,J. Jesús Cervantes-Sánchez,José M. Rico-Martínez 대한기계학회 2020 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.34 No.2

This paper demonstrates that the maximum number of poses that can be exactly reached by a planar RRPR linkage is four, while the design for five poses requires the relaxation of displacement constraints at one prescribed pose. To this end, a novel and explicit condition for the synthesis of RP dyads with five prescribed poses is correspondingly introduced. It leads to a new and efficient approach to synthesize planar RRPR linkages, which is equipped with a branching identification procedure. Two successful case studies are provided to validate the applicability of the proposed synthesis approach.

Morphometric and Molecular Data on Two Mitochondrial Genes of a Newly Discovered Chimaeran Fish (Hydrolagus melanophasma, Chondrichthyes)

José De La Cruz-Agüero,Francisco Javier García-Rodríguez,Víctor Manuel Cota-Gómez,Felipe Neri Melo-Barrera,Rogelio González-Armas 한국해양과학기술원 2012 Ocean science journal Vol.47 No.2

Fresh and preserved (type material) specimens of the black ghost chimaera Hydrolagus melanophasma were compared for morphometric characteristics. A molecular comparison was also performed on two mitochondrial gene sequences (12S rRNA and 16S rRNA gene sequences). While significant differences in measurements were found, the differences were not attributable to sexual dimorphism or the quality of the specimens, but to the sample size and the type of statistical tests. The result of the genetic characterization showed that 12S rRNA and 16S rRNA genes represented robust molecular markers that characterized the species.

I Can Not Wear My Sunglasses: An Unusual Sarcoidosis Presentation

José Pablo Miramontes González,Virginia Velasco Tirado,Pablo González García,Marta Sánchez García,Ángeles Fidalgo Fernández 대한가정의학회 2017 Korean Journal of Family Medicine Vol.38 No.4

A 39-year-old Caucasian man was referred to University Hospital Salamanca from a primary care unit due to the presence of an erythematous violaceous nodule at the superior portion of his nose. Physical examination indicated that the firm, fixed erythematous violaceous nodule measured approximately 2 cm in diameter and was located in-ferior to a scar on the nasal bridge. Cutaneous involvement in sarcoidosis occurs in 25% of cases. A wide range of clinical presentations of cutaneous sarcoidosis is recognized. Skin lesions are classified as either non-specific, of which erythema nodosum is the most representative and specific, or as granulomatous, which includes maculo-papular nodules, plaques, infiltrated scars, lupus pernio, ulcerations, warty lesions and erythroderma. Scar sarcoid-osis is a type of cutaneous sarcoidosis.

Stabilized mixed displacement–pressure finite element formulation for linear hydrodynamic problems with free surfaces

Gonzá,lez, José,A.,Lee, Yeon-Seung,Park, K.C. North-Holland Pub. Co 2017 Computer methods in applied mechanics and engineer Vol.319 No.-

<P><B>Abstract</B></P> <P>A mixed displacement–pressure formulation of the Stokes problem for incompressible fluids with free surfaces is developed for modeling the propagation of gravity waves in liquids and their interaction with structures using a Lagrangian approach. We assume that fluid displacements are small, making convective effects negligible and approximate the fluid velocities from the time derivative of the displacements. The resulting finite element equations are discretized with equal order for both displacement and pressure terms, together with employing stabilization techniques that circumvent the <I>inf–sup</I> requirements. The stability and accuracy of the methodology is finally demonstrated by solving some classical problems of hydrodynamics with free surfaces, comparing the results with known analytical solutions.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Stabilized formulation for hydrodynamic analysis of incompressible fluids with free surfaces. </LI> <LI> Classical stabilization applied to displacement–pressure formulation of hydrodynamics. </LI> <LI> The elimination of spurious in-plane circulation modes is investigated. </LI> <LI> Effective time integration of the equations using the Generalized-alpha algorithm. </LI> <LI> Stability and accuracy demonstrated by solving classical problems of hydrodynamics. </LI> </UL> </P>

Cocoa: a functional food that decreases insulin resistance and oxidative damage in young adults with class II obesity

José Arnold González-Garrido,José Rubén García-Sánchez,Carlos Javier López-Victorio,Adelma Escobar-Ramírez,Ivonne María Olivares-Corichi 한국영양학회 2023 Nutrition Research and Practice Vol.17 No.2

BACKGROUND/OBJECTIVES: Cocoa consumption is associated with health benefits due to its high content of polyphenols. However, the effects of short-term cocoa consumption remain unclear. We aimed to determine the effects generated by cocoa consumption (for 7 days) in young adults in normoweight and class II obesity. SUBJECTS/METHODS: Before-and-after study was carried out in normoweight (NW) (n = 15) and class II obesity (CIIO) (n = 15) young adults. The NW and CIIO participants consumed 25 and 39 g of cocoa, respectively, per day for 7 days. The effect of cocoa consumption was evaluated on the lipid profile, insulin resistance (IR), and inflammation. Oxidative damage was also examined by assessing the biomarkers of oxidative damage in plasma. In addition, recombinant human insulin was incubated with blood obtained from the participants, and the molecular damage to the hormone was analyzed. RESULTS: Cocoa consumption resulted in decreased low-density lipoprotein-cholesterol in both groups (P = 0.04), while the total cholesterol, high-density lipoprotein cholesterol, and triglycerides were maintained at the recommended levels. Initially, IR was detected in the CIIO group (homeostasis model assessment [HOMA] = 4.78 ± 0.4), which is associated with molecular damage to insulin. Interestingly, intervention with cocoa resulted in improved IR (HOMA = 3.14 ± 0.31) (P = 0.0018) as well as molecular damage to insulin. Finally, cocoa consumption significant decreased the arginase activity (P = 0.0249) in the CIIO group; this is a critical enzymatic activity in the inflammatory process associated with obesity. CONCLUSIONS: The short-term consumption of cocoa improves the lipid profile, exerts antiinflammatory effects, and protects against oxidative damage. Results of this study indicate that cocoa consumption can potentially improve IR and restore a healthy redox status.