ABSTRACT
The S100A12 protein was validated as a biomarker of health status in porcine saliva samples using a semi-quantitative approach based on Western blotting in four healthy and sixteen diseased animals, and in four animals with severe respiratory disease during three days of antibiotic therapy. Afterwards, a non-competitive sandwich immunoassay was then developed, validated, and used to quantify S100A12 in clinical porcine samples, using 14 healthy and 25 diseased pigs. Finally, the S100A12 concentrations in the saliva of ten pigs with respiratory disease were monitored during antibiotic therapy. Diseased animals showed higher concentrations of S100A12 than healthy animals, and the high concentrations of S100A12 in pigs with respiratory distress were reduced after antimicrobial therapy. The assay developed showed good precision and accuracy, as well as a low limit of detection of 3.19 ng/mL. It was possible to store saliva samples at -20 °C, or even at 4 °C, for two weeks before analysis without losing the validity of the results. The concentrations of S100A12 observed in serum and saliva samples showed a moderately positive association with a correlation coefficient of 0.48. The concentrations of the new validated biomarker S100A12 are highly associated with the novel salivary biomarker of inflammation, adenosine deaminase, and moderately to highly associated with the total oxidant status. The results reported in this study provide a new way of evaluating inflammatory diseases in pigs using saliva samples, which should be further explored for disease prevention and monitoring in the field.
Subject(s)
Respiratory Tract Diseases , Swine Diseases , Swine , Animals , S100A12 Protein/analysis , S100A12 Protein/metabolism , Saliva/chemistry , Biomarkers/analysis , Anti-Bacterial Agents/metabolism , Respiratory Tract Diseases/veterinary , Swine Diseases/diagnosis , Swine Diseases/metabolismABSTRACT
BACKGROUND: The concentration of biomarkers in saliva could be influenced by several factors not related to the specific condition under analyses, which should be considered for proper clinical interpretation. In the present study, the circadian rhythm of C-reactive protein (CRP), haptoglobin (Hp), Pig-MAP, S100A12, Cu, Zn, Adenosine deaminase (ADA), total protein (TP), total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), cortisol and α-amylase in saliva of 20 female and 20 male pigs was investigated. Moreover, the influence of sex and production phase (post-weaning, fattening and finishing) on the concentrations of biomarkers in a total of 414 healthy pigs was studied and the reference intervals for all salivary biomarkers were calculated accordingly. RESULTS: All parameters except Pig-MAP, OSI and α-amylase varied significantly along the daytime, and most of them peak around early afternoon (13-15 h). The cosinor analysis described the temporal dynamics of circadian rhythms for all parameters. The range values showed differences between male and female pigs in 8 out of the 13 biomarkers, with higher concentrations in females in comparison to male pigs. The influence of the production phase on the salivary concentrations was observed for all the biomarkers. The highest concentrations were observed for Pig-MAP, S100A12 and α-amylase in post-weaning animals, for TP in growing pigs and for OSI in finishing animals. Most of the sex-influenced biomarkers showed the highest concentrations at growing stages with some exceptions such as ADA or Hp that showed the peak at finishing and post-weaning stages respectively. CONCLUSIONS: It is necessary to establish the optimal daytime for routine saliva sampling to avoid circadian variations and for that end, the time interval between 10:00 a.m. to 12:00 a.m. is highly recommended. The factors sex and production phase influence the concentration of biomarkers and should be considered for proper biomarker interpretation. The reference intervals presented here for each salivary biomarker will help to correctly interpret the results of these analytes and contribute to the use of saliva as a non-invasive sample for the diagnosis and monitoring of the health status of swine farms.
ABSTRACT
This work explores the potentially broader contribution of forensic science to preventive public health through the proactive view promoted by forensic intelligence. For that purpose, a new working framework is applied as a strategic tool that channelizes forensic intelligence in a more understandable and didactic way for decision-makers, guiding preventive crime processes. Concretely, the implementation of this operational framework focuses on preventing drug-facilitated sexual assaults in the nightlife context. Through a two-stage research scheme, the working framework is used as a study tool for understanding this violent phenomenon and as a strategic thinking and action platform for overcoming it. Forensic intelligence-guided actions significantly enhanced institutional and direct support facing this specific form of sexual violence. Awareness messages targeting potential assailants, witnesses, and victims reached more than half a thousand students from the university and pre-university education through a preventive intervention within the educational system. Moreover, the inter-professional dialogue between forensic science and other health, security, and education disciplines shows the broader proactive role of forensic science beyond the traditional retroactive view limited to courtrooms and intelligence-led policing. This study demonstrates as forensic intelligence becomes applicable for civilians, who participate as decision-makers in intelligence-led preventive processes, anticipating the need for intervention by police and judicial authorities.
Subject(s)
Forensic Medicine , Sex Offenses , Forensic Sciences , Humans , Intelligence , Police , Sex Offenses/prevention & controlABSTRACT
Introducción y objetivos: La evolución a largo plazo de los pacientes que padecen síncope, una vez descartada su etiología cardiaca, no se ha descrito en profundidad. Se describe la evolución a largo plazo de esta población. Métodos: Durante 147 meses, se estudió a todos los pacientes remitidos a nuestra unidad de síncope tras haberse descartado una causa cardiaca. Resultados: Se incluyó a 589 pacientes consecutivos, 313 de ellos mujeres (53,1%), con una mediana de 52 [34-66] años. A 405 (68,8%) se les diagnosticó síncope vasovagal (SVV); a 65 (11%), síncope por hipotensión ortostática (SHO), y a 119 (20,2%), síncope de etiología desconocida (SED). Durante una mediana de 52 [28-89] meses de seguimiento, 220 (37,4%) tuvieron recurrencias (el 21,7%, 2 o más recurrencias) y se produjeron 39 muertes (6,6%). La recurrencia del síncope se produjo en el 41% de los pacientes con SVV, el 35,4% del grupo con SHO y el 25,2% del de SED (p=0,006). La recurrencia se correlacionó en el análisis multivariado con la edad (p=0,002), el sexo femenino (p<0,0001) y el número de episodios previos (< 5 frente a ≥ 5; p <0,0001). Fallecieron 15 pacientes (3,5%) con SVV, 11 (16,9%) con SHO y 13 (10,9%) con SED (p=0,001), El análisis multivariado asoció edad (p=0,0001), diabetes (p=0,007) y diagnóstico de SHO (p=0,026) y SED (p=0,020) con la muerte. Conclusiones: En los pacientes con síncope de origen no cardiaco, a los 52 meses de seguimiento, la tasa de recurrencias es del 37,4% y la de mortalidad, del 6,6%. Hay más recurrencias en los pacientes con perfil neuromediado y más mortalidad en los pacientes con perfil no neuromediado (AU)
Introduction and objectives: There are no in-depth studies of the long-term outcome of patients with syncope after exclusion of cardiac etiology. We therefore analyzed the long-term outcome of this population. Methods: For 147 months, we included all patients with syncope referred to our syncope unit after exclusion of a cardiac cause. Results: We included 589 consecutive patients. There were 313 (53.1%) women, and the median age was 52 [34-66] years. Of these, 405 (68.8%) were diagnosed with vasovagal syncope (VVS), 65 (11%) with orthostatic hypotension syncope (OHS), and 119 (20.2%) with syncope of unknown etiology (SUE). During a median follow-up of 52 [28-89] months, 220 (37.4%) had recurrences (21.7% ≥ 2 recurrences), and 39 died (6.6%). Syncope recurred in 41% of patients with VVS, 35.4% with OHS, and 25.2% with SUE (P=.006). In the Cox multivariate analysis, recurrence was correlated with age (P=.002), female sex (P <.0001), and the number of previous episodes (< 5 vs ≥ 5; P <.0001). Death occurred in 15 (3.5%) patients with VVS, 11 (16.9%) with OHS, and 13 (10.9%) with SUE (P=.001). In the multivariate analysis, death was associated with age (P=.0001), diabetes (P=.007), and diagnosis of OHS (P=.026) and SUE (P=.020). Conclusions: In patients with noncardiac syncope, the recurrence rate after 52 months of follow-up was 37.4% and mortality was 6.6% per year. Recurrence was higher in patients with a neuromedial profile and mortality was higher in patients with a nonneuromedial profile (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Shock, Cardiogenic/mortality , Syncope, Vasovagal/mortality , Tilt-Table Test , Prospective Studies , Cohort Studies , Time Factors , RecurrenceABSTRACT
Warming trends in Patagonia and severe droughts in recent decades are still poorly understood in terms of their hydrological effects. The effects of climate change on water dynamics in addition to human water management could generate a future water scarcity scenario in one of the regions with the most abundant water resources of Chile. The aim of this work is to focus on assessing the impacts of warming trends on water dynamics in the Patagonian Simpson River watershed during the last two decades. We estimated anomalies in the main components of water balance such as precipitation (P), snow cover (SC), evapotranspiration (ET) and streamflows (Q) as well as surface variables and meteorological forcing (i.e. air temperature - Ta, solar radiation - RS, land surface temperature - LST). The processed data were obtained from remote sensing, reanalysis and in-situ data. We implemented a trend analysis for each variable in the period 2000-2019 at monthly, seasonal and annual scale. Results showed a warming trend in Ta and LST of about 1.2 °C and 2.1 °C, respectively, concentrated mainly in the autumn and winter seasons. Although P showed non-significant trends, Q diminished significantly at rates of more than 9.1 m3/s/decade, representing 36% of its historical mean. However, the decreases in Q are seen only in the maximum (spring) and minimum (summer) seasonal flows. These decreases are explained by significant increases in ET, led by a positive feedback of its drivers (LST, Ta and RS), which is directly linked to the impact of warming and an associated vegetation greenness in the watershed, as well as a decrease in SC during winter that feeds the Simpson River during spring and summer. The decrease in Q is reinforced by the intensification of water withdrawals in recent decades, as shown by an accelerated increase in water rights for agricultural and drinking uses. In a context of water scarcity and increasing and extreme droughts, this work contributes to further understanding water dynamics in western Patagonia, providing support for policy and decision-making when defining sustainable productive practices at watershed scale.
Subject(s)
Environmental Monitoring , Water , Climate Change , Humans , Rivers , SeasonsABSTRACT
Cementum is a bone connective tissue that provides a flexible attachment for the tooth to the alveolar bone in many mammalian species. It does not undergo continuous remodelling, unlike non-dental bone, which combined with its growth pattern of seasonal layering makes this tissue uniquely suitable as a proxy for tracking changes in body repair investment throughout an animal´s life. We tested functional and sexual selection hypotheses on the rate of cementum deposition related to the highly polygynous mating strategy of red deer. We used a sample of 156 first lower molars from wild Scottish red deer of known age between 1 and 17 years old, approximately balanced by sex and age class. Cementum deposition on the inter-radicular pad increased with age at a constant average rate of 0.26 mm per year, with no significant differences between sexes. Cementum deposition was independent of (i) tooth wear, other than that associated with age, and (ii) enamel and dentine micro-hardness. The results partially supported the hypothesis that the main function of cementum is the repositioning of the tooth to maintain opposing teeth in occlusion. However, teeth that had more wear or males´ teeth that had faster rates of tooth wear than those of females did not present the expected higher rates of cementum deposition.
Subject(s)
Dental Cementum/physiology , Animals , Deer , Dentin/physiology , Female , Hardness , Male , Molar/physiology , Tooth/growth & development , Tooth/physiologyABSTRACT
Lionfish (Pterois volitans) is an invasive and predatory species whose proliferation over the Caribbean Sea threatens to cause great damage to coral reefs by negatively affecting the balance of the ecosystem. Control strategies have been the most effective way to reduce the negative impact of the lionfish. The development of diversified food products based on lionfish could support these strategies. The objective of the present study was to investigate the influence of ultrasound and the addition of binders in different concentrations: Egg white liquid (EWL) and corn starch (ST) on texture, microstructure and sensory evaluation properties of patties made of lionfish surimi. Each set of binders was added up to 3% varying proportions. The texture profile, water holding capacity, sensory qualities and fractal dimension of scanning electron microscopy images were analyzed to evaluate the quality of the product based on surimi gel. Results showed that the application of ultrasound and the use of binders enhanced the properties of patties made of lionfish surimi. The addition of EWL (3%) improved the water holding capacity and hardness of the final product. However, the fractal dimension of the images was higher in samples processed using ultrasound and without binder addition.
ABSTRACT
Lanthanide-activated SrF2 nanoparticles with a multishell architecture were investigated as optical thermometers in the biological windows. A ratiometric approach based on the relative changes in the intensities of different lanthanide (Nd3+ and Yb3+) NIR emissions was applied to investigate the thermometric properties of the nanoparticles. It was found that an appropriate doping with Er3+ ions can increase the thermometric properties of the Nd3+-Yb3+ coupled systems. In addition, a core containing Yb3+ and Tm3+ can generate light in the visible and UV regions upon near-infrared (NIR) laser excitation at 980 nm. The multishell structure combined with the rational choice of dopants proves to be particularly important to control and enhance the performance of nanoparticles as NIR nanothermometers.
ABSTRACT
BACKGROUND AND OBJECTIVES: Red blood cell (RBC) transfusion may be justified in iron deficiency anaemia (IDA) when an increase in oxygen delivery is needed, as sometimes occurs in subjects with haemoglobin <8·0 mg/dL, serious comorbidities or at risk of cardiovascular instability. Earlier investigations showed that some patients with severe IDA requiring transfusion had lower than expected post-transfusion haemoglobin levels with poorer clinical outcomes than other patients. After hypothesizing that haemoglobin responses to transfusion were different and that the underlying gastrointestinal (GI) disorders causing IDA could be a confounder explaining this association, these responses were analysed in a prospective cohort of IDA adults referred for outpatient GI investigation. MATERIALS AND METHODS: Transfused patients with proven IDA, baseline haemoglobin at referral <9·0 g/dL and no extraintestinal bleeding were eligible. To assess a homogeneous population, only GI disorders known to cause occult bleeding were considered. Haemoglobin increments per 100 mL of RBCs were investigated. RESULTS: In total, 2818 patients were enrolled over 10·5 years. On multivariable regression, diffuse angiodysplasias and GI cancer independently predicted for reduced increments in post-transfusion haemoglobin [adjusted regression coefficients: -0·082 (95% confidence interval, -0·093 to -0·072) and -0·073 (95% confidence interval, -0·081 to -0·066), respectively, P < 0·001 in both]. Haemoglobin responses in the remaining bleeding disorders were adequate and agreed with the principle that one RBC unit increases the haemoglobin an average of 1 g/dL. CONCLUSION: The potential differential impact of GI disorders on changes in haemoglobin levels after RBC transfusion could be useful for transfusing physicians, especially for diagnostic purposes.
Subject(s)
Anemia, Iron-Deficiency/therapy , Erythrocyte Transfusion , Gastrointestinal Diseases/complications , Adult , Aged , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/etiology , Angiodysplasia/complications , Angiodysplasia/pathology , Erythrocyte Transfusion/adverse effects , Female , Gastrointestinal Diseases/pathology , Hemoglobins/analysis , Humans , Male , Middle Aged , Multivariate Analysis , Prospective StudiesABSTRACT
Resumen ANTECEDENTES: Los estadios clínicos avanzados del cáncer vulvar representan un reto quirúrgico y un abordaje que requiere ser multidisciplinario, con cirugía plástica que provea márgenes quirúrgicos adecuados, con menor tasa de complicaciones, cierre primario de la herida e inicio temprano de la terapia oncológica coadyuvante. OBJETIVOS: Describir y exponer las alternativas de reconstrucción vulvoperineal para pacientes con cáncer vulvar, atendidas en el Instituto Nacional de Cancerología de México. MATERIALES Y MÉTODOS: Análisis descriptivo y retrospectivo de casos de pacientes a quienes se hizo reconstrucción vulvoperineal en el Instituto Nacional de Cancerología, México, entre enero y diciembre de 2015, por el mismo cirujano plástico. Se muestra el algoritmo basado en su experiencia. RESULTADOS: Se analizaron 11 casos de pacientes operadas con diferentes técnicas de reconstrucción vulvoperineal, por defectos quirúrgicos del cáncer vulvar y se expuso el algoritmo utilizado y la experiencia del cirujano. CONCLUSIONES: Se revisaron las diferentes alternativas de reconstrucción para subsanar defectos quirúrgicos en pacientes con cáncer vulvar. Los algoritmos de tratamiento quirúrgico previamente publicados son confusos y complejos, quizá por la baja incidencia del cáncer vulvar y las diversas opciones de procedimientos de reconstrucción.
Abstract BACKGROUND: Vulvar cancer is a relatively infrequent disease, that constitutes 1-5% of all gynecological cancers. Surgery is the mainstay treatment is adequate resection, and lymph node evaluation, often have a high risk of relapse that may reach 65%. ADVANCED: Stages are a surgical challenge and multidisciplinary ap proach with plastic surgery will provide adequate surgical margins, less complications, adequate wound closure, and early adjuvant treat ment starting; as well as excellent cosmetic results, with functional, psychological and sexual morbidity decreased. OBJECTIVES: To describe and present the alternatives of vulvoperineal reconstruction in vulvar cancer at Instituto Nacional de Cancerología, Mexico. METHODS: A retrospective descriptive analysis of eleven cases of vulvoperineal reconstruction in vulvar cancer was performed from January 2015 to December 2015, at Instituto Nacional de Cancerología, Mexico; for one plastic surgeon; and demonstrated the algorithm base don their experience. RESULTS: We performed 11 patients of vulvar reconstruction with different reconstructive techniques, such as gracilis flapping, pudend, with a high success rate. as well as, to propose an algorithm based in our experience with vulvar cancer reconstruction at Instituto Nacional de Cancerología, Mexico. CONCLUSION: The present article aims to review the reconstructive alternatives in Vulvar Cancer, several algorithms for surgical treatment have been published before; but they tend to be complex, in part be cause of the low incidence of Vulvar Cancer and the several options of reconstructive procedures.
ABSTRACT
Real-time polymerase chain reaction (PCR)-based approaches have not been assessed in terms of their ability to detect patients colonized by Acinetobacter baumannii during active surveillance. This prospective, double-blind study demonstrated that a real-time PCR assay had high sensitivity (100%) and specificity (91.2%) compared with conventional culture for detecting A. baumannii in 397 active surveillance samples, and provided results within 3h. Receiver-operator curve analyses demonstrated that the technique has diagnostic accuracy of 97.7% (95% confidence interval 96.0-99.3%). This method could facilitate the rapid implementation of infection control measures for preventing the transmission of A. baumannii.
Subject(s)
Acinetobacter Infections/diagnosis , Acinetobacter baumannii/isolation & purification , Carrier State/diagnosis , Molecular Diagnostic Techniques/methods , Real-Time Polymerase Chain Reaction/methods , Acinetobacter Infections/microbiology , Acinetobacter baumannii/genetics , Bacteriological Techniques/methods , Carrier State/microbiology , Double-Blind Method , Humans , Prospective Studies , ROC Curve , Sensitivity and Specificity , Time FactorsABSTRACT
Background: Over the last decade, evidence suggests the fallopian tubes are the origin of most of the high grade ovarian serous carcinomas. This type of carcinoma represents at least 50% of all the cases of epithelial ovarian cancer. Salpingectomy may lower the risk of high grade serous carcinoma. Removing the two fallopian tubes should be considered a strategy for risk reduction in patients who decide tubal sterilization or in patients with hysterectomy for benign disease. There are ongoing protocols that evaluate the ovarian hormonal production impact after prophilactic salpingectomy. In patients with BRCA1 and BRCA2 mutations, salpingo-oophorectomy is recommended usually between 35 to 40 years of age for BRCA 1 and between 40 and 45 years of age for BRCA 2. The oopherectomy done whithin these decades has the consequences and side effects of premature menopause, some physicians have suggested doing a two step procedure: perform a salpingectomy as soon as the patient has decided to have permanent birth control, and doing the ophoorectomy at the onset of menopause. The oncological safety of this approach is still under evaluation and is not recommended outside a protocol.
Subject(s)
Fallopian Tube Neoplasms/prevention & control , Ovarian Neoplasms/prevention & control , Salpingectomy/methods , Adult , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Fallopian Tubes/surgery , Female , Humans , Ovarian Neoplasms/genetics , Ovariectomy/methodsABSTRACT
La displasia fibrosa es una lesión congénita, lentamente progresiva que puede provocar graves alteraciones morfológicas y funcionales, y estar sujeta a complicaciones de tipo infeccioso. En este reporte de caso se presenta a un paciente masculino de 8 años de edad diagnosticado con una displasia fibrosa madura luego de un hallazgo incidental durante un examen de rutina, el paciente durante el curso de los últimos cinco años ha presentado osteomielitis a repetición en el sitio de biopsia y de exfoliación dentaría, el cuadro clínico se ha tratado mediante curetajes y aseos quirúrgicos y con la indicación antibiótica de clindamicina sin resultados positivos. Se concluye que el manejo de las displasias fibrosas maduras puede ser difícil una vez que se ha instalado un proceso infeccioso crónico sin poder dar de alta al paciente, manteniéndolo permanentemente en control. (AU)
Fibrous dysplasia is a slowly progressive congenital lesion that can cause serious morphological and functional alterations , and complications of infectious type . This case report presents a 8 years old male patient diagnosed with a mature fibrous dysplasia after an incidental finding during a routine examination, the patient during the course of the last five years has been presented recurrent osteomyelitis episodes in the biopsy site and temporal tooth during exfoliation, it has been treated by surgical curettage and clindamycin with no positive results. We conclude that the management of mature fibrous dysplasia can be difficult once a chronic infectious process has been installed without being able to discharge the patient, constantly keeping it in control.(AU)
Subject(s)
Humans , Male , Child , Osteomyelitis/complications , Clindamycin/therapeutic use , Fibrous Dysplasia of Bone/diagnosis , Fibrous Dysplasia of Bone/therapyABSTRACT
La homeostasis de la piel, cuya regulación molecular es aún bastante desconocida, está íntimamente relacionada con la función de las células madre epidérmicas. El programa SkinModel-CM, auspiciado por la Comunidad de Madrid, reúne 5 grupos de investigación con el propósito de desarrollar nuevos modelos experimentales in vitro e in vivo para analizar la función de ADN metiltransferasa 1, la endoglina y la podoplanina en la actividad de las células madre epidérmicas y en la homeostasis y el cáncer cutáneos. Estos nuevos modelos comprenden tanto cultivos organotípicos 3 D, como ratones inmunodeficientes con la piel humanizada y ratones modificados genéticamente. Otro objetivo del programa es el uso de ratones con la piel humanizada como modelo para reconstruir enfermedades cutáneas, tales como el síndrome de Gorlin y el xeroderma pigmentoso, con el objeto de optimizar nuevos protocolos de intervención mediante la terapia fotodinámica (AU)
Homeostasis, whose regulation at the molecular level is still poorly understood, is intimately related to the functions of epidermal stem cells. Five research groups have been brought together to work on new in vitro and in vivo skin models through the SkinModel-CM program, under the auspices of the Spanish Autonomous Community of Madrid. This project aims to analyze the functions of DNA methyltransferase 1, endoglin, and podoplanin in epidermal stem cell activity, homeostasis, and skin cancer. These new models include 3-dimensional organotypic cultures, immunodeficient skin-humanized mice, and genetically modified mice. Another aim of the program is to use skin-humanized mice to model dermatoses such as Gorlin syndrome and xeroderma pigmentosum in order to optimize new protocols for photodynamic therapy (AU)
Subject(s)
Humans , Homeostasis/physiology , Skin Diseases/physiopathology , DNA Modification Methylases/physiology , Stem Cells/physiology , Disease Models, Animal , Phototherapy , Hair Follicle/physiology , Models, Genetic , Bioengineering/methodsABSTRACT
Invadopodia are actin-rich cell membrane projections used by invasive cells to penetrate the basement membrane. Control of invadopodia stability is critical for efficient degradation of the extracellular matrix (ECM); however, the underlying molecular mechanisms remain poorly understood. Here, we uncover a new role for podoplanin, a transmembrane glycoprotein closely associated with malignant progression of squamous cell carcinomas (SCCs), in the regulation of invadopodia-mediated matrix degradation. Podoplanin downregulation in SCC cells impairs invadopodia stability, thereby reducing the efficiency of ECM degradation. We report podoplanin as a novel component of invadopodia-associated adhesion rings, where it clusters prior to matrix degradation. Early podoplanin recruitment to invadopodia is dependent on lipid rafts, whereas ezrin/moesin proteins mediate podoplanin ring assembly. Finally, we demonstrate that podoplanin regulates invadopodia maturation by acting upstream of the ROCK-LIMK-Cofilin pathway through the control of RhoC GTPase activity. Thus, podoplanin has a key role in the regulation of invadopodia function in SCC cells, controlling the initial steps of cancer cell invasion.
Subject(s)
Carcinoma, Squamous Cell/pathology , Cell Surface Extensions/physiology , Extracellular Matrix/metabolism , Membrane Glycoproteins/physiology , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Humans , Lim Kinases/physiology , Membrane Microdomains/physiology , Signal Transduction , rho GTP-Binding Proteins/physiology , rho-Associated Kinases/physiology , rhoC GTP-Binding ProteinABSTRACT
Homeostasis, whose regulation at the molecular level is still poorly understood, is intimately related to the functions of epidermal stem cells. Five research groups have been brought together to work on new in vitro and in vivo skin models through the SkinModel-CM program, under the auspices of the Spanish Autonomous Community of Madrid. This project aims to analyze the functions of DNA methyltransferase 1, endoglin, and podoplanin in epidermal stem cell activity, homeostasis, and skin cancer. These new models include 3-dimensional organotypic cultures, immunodeficient skin-humanized mice, and genetically modified mice. Another aim of the program is to use skin-humanized mice to model dermatoses such as Gorlin syndrome and xeroderma pigmentosum in order to optimize new protocols for photodynamic therapy.
Subject(s)
Homeostasis , Skin Diseases/physiopathology , Skin Physiological Phenomena , Animals , Biomedical Research , Disease Models, Animal , Hair Follicle , Humans , Mice , Models, Animal , Models, Genetic , Photochemotherapy , Skin Diseases/genetics , Skin Diseases/therapy , Stem CellsABSTRACT
Tribbles pseudokinase-3 (TRIB3) has been proposed to act as an inhibitor of AKT although the precise molecular basis of this activity and whether the loss of TRIB3 contributes to cancer initiation and progression remain to be clarified. In this study, by using a wide array of in vitro and in vivo approaches, including a Trib3 knockout mouse, we demonstrate that TRIB3 has a tumor-suppressing role. We also find that the mechanism by which TRIB3 loss enhances tumorigenesis relies on the dysregulation of the phosphorylation of AKT by the mTORC2 complex, which leads to an enhanced phosphorylation of AKT on Ser473 and the subsequent hyperphosphorylation and inactivation of the transcription factor FOXO3. These observations support the notion that loss of TRIB3 is associated with a more aggressive phenotype in various types of tumors by enhancing the activity of the mTORC2/AKT/FOXO axis.
Subject(s)
Cell Cycle Proteins/metabolism , Forkhead Transcription Factors/metabolism , Neoplasms/metabolism , Protein Serine-Threonine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Repressor Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Animals , Cell Cycle Proteins/genetics , Cell Line, Tumor , Forkhead Box Protein O3 , Forkhead Transcription Factors/genetics , Humans , Mechanistic Target of Rapamycin Complex 2 , Mice , Mice, Knockout , Mice, Nude , Multiprotein Complexes/genetics , Multiprotein Complexes/metabolism , Neoplasms/genetics , Neoplasms/pathology , Phosphorylation/genetics , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Repressor Proteins/genetics , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Tumor Suppressor Proteins/geneticsABSTRACT
The Ca-Looping (CaL) process, based on the multicyclic carbonation/calcination of CaO at high temperatures, is a viable technology to achieve high CO2 capture efficiencies in both precombustion and postcombustion applications. In this paper we show an experimental study on the multicyclic CO2 capture of a natural limestone in a fixed bed at CaL conditions as affected by the application of a high-intensity acoustic field. Our results indicate that sound promotes the efficiency of CO2 sorption in the fast carbonation phase by enhancing the gas-solids mass transfer. The fundamentals of the physical mechanism responsible for this effect (acoustic streaming) as well as the technical feasibility of the proposed technique allows envisaging that sonoprocessing will be beneficial to enhance multicyclic CO2 capture in large-scale applications.
Subject(s)
Calcium Carbonate/radiation effects , Carbon Dioxide/radiation effects , Sound , Calcium Carbonate/chemistry , Carbon Dioxide/chemistryABSTRACT
BACKGROUND: HIF-1alpha plays a key role in the development and progression of cancer. Its polymorphic variants C1772T and G1790A have been associated with greater susceptibility to cancer and increased tumor progression. METHODS: We determined the distribution of these polymorphisms among 121 patients with glottic cancer and 154 healthy volunteers by PCR-RFLP. We also analyzed the relationship between the presence of these polymorphisms and various clinicopathologic variables. RESULTS: Advanced tumors (T3-T4) were associated with the TT variant (p = 0.036), which was present in 75 % of T4 tumors (p = 0.008). Among patients with nodal metastasis (N+), 41.7 and 22 % were carrying the TT and GA variants, respectively, compared with 9.4 and 2 % of the patients with no metastasis (N0), (p = 0.006 and p = 0.032). CONCLUSIONS: The presence of the TT and GA variants were associated with lymph node metastasis, while the presence of the TT variant can be associated with larger tumor size (AU)
Subject(s)
Humans , Male , Female , Glottis/metabolism , Glottis/pathology , Glottis , Glottis/radiation effects , Neoplasm Metastasis/genetics , Lymph Nodes/radiation effectsABSTRACT
BACKGROUND: HIF-1alpha plays a key role in the development and progression of cancer. Its polymorphic variants C1772T and G1790A have been associated with greater susceptibility to cancer and increased tumor progression. METHODS: We determined the distribution of these polymorphisms among 121 patients with glottic cancer and 154 healthy volunteers by PCR-RFLP. We also analyzed the relationship between the presence of these polymorphisms and various clinicopathologic variables. RESULTS: Advanced tumors (T3-T4) were associated with the TT variant (p = 0.036), which was present in 75 % of T4 tumors (p = 0.008). Among patients with nodal metastasis (N+), 41.7 and 22 % were carrying the TT and GA variants, respectively, compared with 9.4 and 2 % of the patients with no metastasis (N0), (p = 0.006 and p = 0.032). CONCLUSIONS: The presence of the TT and GA variants were associated with lymph node metastasis, while the presence of the TT variant can be associated with larger tumor size.