PM10 promotes an inflammatory cytokine response that may impact SARS-CoV-2 replication in vitro.

Introduction: In the last decades, a decrease in air quality has been observed, mainly associated with anthropogenic activities. Air pollutants, including particulate matter (PM), have been associated with adverse effects on human health, such as exacerbation of respiratory diseases and infections. High levels of PM in the air have recently been associated with increased morbidity and mortality of COVID-19 in some regions of the world. Objective: To evaluate the effect of coarse particulate matter (PM10) on the inflammatory response and viral replication triggered by SARS-CoV-2 using in vitro models. Methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were treated with PM10 and subsequently exposed to SARS-CoV-2 (D614G strain, MOI 0.1). The production of pro-inflammatory cytokines and antiviral factors was quantified by qPCR and ELISA. In addition, using the A549 cell line, previously exposed to PM, the viral replication was evaluated by qPCR and plaque assay. Results: SARS-CoV-2 stimulation increased the production of pro-inflammatory cytokines in PBMC, such as IL-1ß, IL-6 and IL-8, but not antiviral factors. Likewise, PM10 induced significant production of IL-6 in PBMCs stimulated with SARS-CoV-2 and decreased the expression of OAS and PKR. Additionally, PM10 induces the release of IL-1ß in PBMC exposed to SARS-CoV-2 as well as in a co-culture of epithelial cells and PBMCs. Finally, increased viral replication of SARS-CoV-2 was shown in response to PM10. Conclusion: Exposure to coarse particulate matter increases the production of pro-inflammatory cytokines, such as IL-1ß and IL-6, and may alter the expression of antiviral factors, which are relevant for the immune response to SARS-CoV-2. These results suggest that pre-exposure to air particulate matter could have a modest role in the higher production of cytokines and viral replication during COVID-19, which eventually could contribute to severe clinical outcomes.

Chronic resveratrol administration reduces oxidative stress and brain cell loss and improves memory of recognition in old rats.

The cognitive functions of people over 60 years of age have been diminished, due to the structural and functional changes that the brain has during aging. The most evident changes are at the behavioral and cognitive level, with decreased learning capacity, recognition memory, and motor incoordination. The use of exogenous antioxidants has been implemented as a potential pharmacological option to delay the onset of brain aging by attenuating oxidative stress and neurodegeneration. Resveratrol (RSVL) is a polyphenol present in various foods, such as red fruits, and drinks, such as red wine. This compound has shown great antioxidant capacity due to its chemical structure. In this study, we evaluated the effect of chronic RSVL treatment on oxidative stress and cell loss in the prefrontal cortex, hippocampus, and cerebellum of 20-month-old rats, as well as its impact on recognition memory and motor behavior. Rats treated with RSVL showed an improvement in locomotor activity and in short- and long-term recognition memory. Likewise, the concentration of reactive oxygen species and lipid peroxidation decreased significantly in the group with RSVL, coupled with an improvement in the activity of the antioxidant system. Finally, with the help of hematoxylin and eosin staining, it was shown that chronic treatment with RSVL prevented cell loss in the brain regions studied. Our results demonstrate the antioxidant and neuroprotective capacity of RSVL when administered chronically. This strengthens the proposal that RSVL could be an important pharmacological option to reduce the incidence of neurodegenerative diseases that affect older adults.

Impact of the COVID-19 pandemic in the early-onset colorectal cancer.

The COVID19 pandemic has affected the spectrum of cancer care worldwide. Early onset colorectal cancer (EOCRC) is defined as diagnosis below the age of 50. Patients with EOCRC faced multiple challenges during the COVID19 pandemic and in some institutions it jeopardized cancer diagnosis and care delivery. Our study aims to identify the clinicopathological features and outcomes of patients with EOCRC in our Centre during the first wave of the pandemic in comparison with the same period in 2019 and 2021. Patients with EOCRC visited for the first time at Vall d'Hebron University Hospital in Spain from the 1st March to 31st August of 2019, 2020 and 2021 were included in the analysis. 177 patients with EOCRC were visited for the first time between 2019 and 2021, of which 90 patients met the inclusion criteria (2019: 30 patients, 2020: 29 patients, 2021: 31 patients). Neither differences in frequency nor in stage at diagnosis or at first visit during the given periods were observed. Of note, indication of systemic therapy in the adjuvant or metastatic setting was not altered. Days to treatment initiation and enrollment in clinical trials in this subpopulation was not affected due to the COVID-19 outbreak.

Differential biochemical-inflammatory patterns in the astrocyte-neuron axis of the hippocampus and frontal cortex in Wistar rats with metabolic syndrome induced by high fat or carbohydrate diets.

Metabolic syndrome (MetS) is a public health problem and a risk of developing cardiometabolic and neurodegenerative diseases. The biochemical-inflammatory impairment in brain areas related to learning and memory has not been differentiated between MetS models. We aimed to compare the effect of the MetS generated by consuming high-fat (HFD) or -carbohydrate diets (HCD) on the hippocampus and frontal cortex, related to astrocyte-neuron metabolism and neuroinflammation origin. Sixty male Wistar rats were separated into three groups: 1) control group, 2) HCD group, and 3) HFD group. After 3 months, we evaluated zoometry, a serum bioclinical profile, and in the hippocampus and frontal cortex, we performed biochemical assays (concentration of lactate, glutamate, fatty acids, and ASAT, ALAT, and LDH activity), immunoreactivity tests (GFAP, COX2, CD36, and BDNF), and immunoassays (TNF-α, IL-1ß, IL-6, and PGE2). The bioclinical parameters showed that both diets induce MetS. At the brain level, it is noteworthy that the HCD group had an increase in lactate and glutamate concentration, reactive astrogliosis, immunoreactive COX2 neurons in the CA1 subfield hippocampus and frontal cortex, and high levels of PGE2, TNF-α, IL-1ß, and IL-6, and low BDNF immunoreactivity. Meanwhile, the HFD is highlighted by increased fatty acid levels and CD36 expression in the hippocampus and frontal cortex, strong reactive astrogliosis and COX2 immunoreactivity, and the greatest inflammation with the lowest BDNF immunoreactivity. In conclusion, MetS induction by an HFD or HCD generates different biochemical, cellular, and inflammatory patterns in the hippocampus and frontal cortex.

Semisynthetic Abietic and Dehydroabietic Acid Derivatives and Triptoquinone Epimers Interfere with LPS-Triggered Activation of Dendritic Cells.

Abietic acid (AA), dehydroabietic acid (DHA) and triptoquinones (TQs) are bioactive abietane-type diterpenoids, which are present in many edible vegetables and medicinal herbs with health-promoting properties. Evidence suggests that beneficial effects of diterpenes operate, at least in part, through effects on cells in the immune system. Dendritic cells (DCs) are a key type of leukocyte involved in the initiation and regulation of the immune/inflammatory response and natural or synthetic compounds that modulate DC functions could be potential anti-inflammatory/immunomodulatory agents. Herein, we report the screening of 23 known semisynthetic AA and DHA derivatives, and TQs, synthesized previously by us, in a multi-analyte DC-based assay that detects inhibition of pro-inflammatory cytokine production. Based on the magnitude of the inhibitory effect observed and the number of cytokines inhibited, a variety of activities among compounds were observed, ranging from inactive/weak to very potent inhibitors. Structurally, either alcohol or methyl ester substituents on ring A along with the introduction of aromaticity and oxidation in ring C in the abietane skeleton were found in compounds with higher inhibitory properties. Two DHA derivatives and two TQs exhibited a significant inhibition in all pro-inflammatory cytokines tested and were further investigated. The results confirmed their ability to inhibit, dose dependently, LPS-stimulated expression of the co-stimulatory molecules CD40 and/or CD86 and the production of the pro-inflammatory cytokines IL-1ß, IL-6, IL-12 and TNFα. Our results demonstrate that DC maturation process can be targeted by semisynthetic DHA derivatives and TQ epimers and indicate the potential of these compounds as optimizable anti-inflammatory/immunomodulatory agents.

Effect of cadmium administration on the antioxidant system and neuronal death in the hippocampus of rats.

Cadmium (Cd) is a heavy metal classified as a carcinogen whose exposure could affect the function of the central nervous system. Studies suggest that Cd modifies neuronal morphology in the hippocampus and affects cognitive tasks. The oxidative stress pathway is proposed as a mechanism of toxicity. However, this mechanism is not precise yet. This study aimed to evaluate the effect of Cd administration on oxidative stress markers in the male rat's hippocampus. Male Wistar rats were divided into (1) control (drinking water) and (2) treatment with Cd (32.5 ppm of cadmium chloride (CdCl2 ) in water). The Cd was administered for 2, 3, and 4 months. The results show that the oral administration of CdCl2 increased the concentration of Cd in plasma and hippocampus, and this response is time-dependent on its administration. Likewise, it caused an increase in lipid peroxidation and nitrosative stress markers. Moreover, it increased reactive astrogliosis and antioxidant enzyme activity. Consequently, the progression of the oxidative response exacerbated neurodegeneration in hippocampal cells. Our results suggest that Cd exposure induces a severe oxidative response that contributes critically to hippocampal neurodegeneration. It is suggested that exposure to Cd increases the risk of developing neurological diseases, which contributes to a decrease in the quality of life of the human and the environment in which it lives.

Rol de los dispositivos para entrenar caninos empleados para la seguridad y defensa nacional: una revisión sistemática de la literatura de los últimos veinte años / Role of canine training devices used for homeland security and defense: a systematic review of the literature over the past twenty years

El entrenamiento de los caninos de trabajo emplea diversos mecanismos de condicionamiento, los cuales permiten un rendimiento posterior superior, contrarrestando el sistema de drogas ilícitas, las organizaciones criminales, los grupos armados organizados (GAO) y residuales (GAOr), garantizando la seguridad y convivencia ciudadana en Colombia. Por lo anterior, se propone un enfoque cualitativo empleando una revisión sistemática de la literatura, con el objetivo de analizar el rol de la tecnología y aparatos para adiestrar caninos detectores, entre los años 2000 y 2020 dentro de las bases de datos Scopus, Elsevier y Scielo. Como resultados, se observa un aumento en la producción de artículos entre los años 2000 y 2019 (pasando de seis artículos a 86, respectivamente). Además, dentro de las herramientas empleadas en los estudios se encuentran las cajas; clickers; collares electrónicos y carruseles, los cuales discriminan el olor, utilizando sistemas de refuerzo, con diferencias dependiendo del tipo de estudio, el número de animales y el objetivo de entrenamiento. Como conclusión, es necesario desarrollar prototipos adecuados según las necesidades de entrenamiento en cada contexto, continuando con estudios que integren efectivamente los estímulos y los sistemas de recompensa para impactar los resultados en el rendimiento del perro de trabajo.

Identificación documental sobre la COVID-19 y las experiencias en la Fiscalía General de la República de Cuba / Document identification about COVID-19 and experiences at the Office of the Attorney General of the Republic of Cuba

La Fiscalía General de la República ha jugado un rol importante en relación con la COVID-19. Esta institución ha generado un amplio volumen de documentos archivísticos como reflejo de sus actuaciones en el enfrentamiento a la pandemia. El propósito de este trabajo fue mostrar los resultados de una identificación documental realizada sobre las acciones de enfrentamiento y prevención de la COVID-19 en la en la Fiscalía General de la República de Cuba. La identificación se realizó a partir de 11 elementos relacionados con la gestión documental, para lo cual se realizó un análisis de los documentos correspondientes a los meses de abril y mayo del año 2020. Se expusieron las debilidades encontradas en relación con la gestión documental de la Fiscalía, lo que contribuirá a mejorar su trabajo organizacional(AU)

The Office of the Attorney General of the Republic has played an important role in relation to COVID-19. This institution has generated a large number of archival documents reflecting its actions in response to the pandemic. The purpose of the study was to present the results of a document identification effort concerning the response to and prevention of COVID-19 at the Office of the Attorney General of the Republic. The identification started from 11 elements related to document management, for which an analysis was performed of the documents corresponding to the months of April and May 2020. The weaknesses found in relation to document management were revealed, which will contribute to improve organizational work at the Office)

IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule.

One of the interventional strategies to reestablish the immune effector/regulatory balance, that is typically altered in chronic inflammatory diseases (CID), is the reinforcement of endogenous immunomodulatory pathways as the one triggered by interleukin (IL)-10. In a recent work, we demonstrated that the subcutaneous (sc) administration of an IL-10/Treg-inducing small molecule-based formulation, using a repetitive microdose (REMID) treatment strategy to preferentially direct the effects to the regional immune system, delays the progression of atherosclerosis. Here we investigated whether the same approach using other IL-10-inducing small molecule, such as the safe, inexpensive, and widely available polyphenol curcumin, could induce a similar protective effect in two different CID models. We found that, in apolipoprotein E deficient mice, sc treatment with curcumin following the REMID strategy induced atheroprotection that was not consequence of its direct systemic lipid-modifying or antioxidant activity, but instead paralleled immunomodulatory effects, such as reduced proatherogenic IFNγ/TNFα-producing cells and increased atheroprotective FOXP3+ Tregs and IL-10-producing dendritic and B cells. Remarkably, when a similar strategy was used in the neuroinflammatory model of experimental autoimmune encephalomyelitis (EAE), significant clinical and histopathological protective effects were evidenced, and these were related to an improved effector/regulatory cytokine balance in restimulated splenocytes. The essential role of curcumin-induced IL-10 for neuroprotection was confirmed by the complete abrogation of the clinical effects in IL-10-deficient mice. Finally, the translational therapeutic prospection of this strategy was evidenced by the neuroprotection observed in mice starting the treatment one week after disease triggering. Collectively, results demonstrate the power of a simple natural IL-10-inducing small molecule to tackle chronic inflammation, when its classical systemic and direct pharmacological view is shifted towards the targeting of regional immune cells, in order to rationally harness its immunopharmacological potential. This shift implies that many well-known IL-10-inducing small molecules could be easily reformulated and repurposed to develop safe, innovative, and accessible immune-based interventions for CID.

Propuesta de requisitos generales para el sistema de gestión documental de la Universidad de La Habana / Proposal of general requirements for the document management system at the University of Havana

El objetivo de la presente investigación fue proponer una especificación de requisitos generales para el sistema de gestión documental de la Universidad de La Habana consecuente con un ejercicio de gobierno más responsable, abierto, transparente e inclusivo, con un enfoque orientado a la rendición de cuentas y a un mayor control social. La investigación presentó un diseño descriptivo y un enfoque mixto, con predominio cualitativo. Para contribuir al desarrollo de un sistema de información que creara capacidades sobre la base de información de calidad en esta institución, el estudio se basó en la triangulación de dos metodologías: una desde el dominio de la gestión documental y otra desde la ingeniería de requisitos. Como resultado, se presentaron 22 elementos y 201 requisitos, entre funcionales y no funcionales, con un carácter flexible y modular, que deben ser establecidos para el funcionamiento efectivo del sistema de gestión documental de esta Universidad(AU)

The purpose of the study was to propose a general requirements specification for the document management system at the University of Havana, in keeping with more responsible, open, transparent and inclusive governance, an accountability-oriented approach and greater social control. The research had a descriptive design, a mixed approach and qualitative predominance. To contribute to the development of an information system which would build capacities on the basis of quality information in this institution, the study was based on the triangulation of two methodologies: one from the document management domain and the other from requirements engineering. As a result, 22 items and 201 requirements were presented, both functional and non-functional, of a flexible and modular nature, which should be established for the effective operation of the document management system at this university(AU)

Decomposition Residual Odor Volatiles in Soil from a West Texas Environment / Sustancias volátiles de olor por descomposición residual en el suelo en un ambiente del oeste de Texas / Substâncias voláteis de odor de decomposição residual no solo em um ambiente do oeste do Texa

Abstract Knowledge of decomposition residual odor volatiles can improve cadaver dog training and forensic techniques for victim recovery. The purpose of this study is to characterize decomposition VOCs in soils contaminated with decomposing porcine remains throughout various decomposition phases in an outdoor environment. Both a pig-meat simulation model as well as pig carcasses were used in place of human cadavers, allowed to decompose for three distinctive time periods, 14, 17 and 21 days, and then removed from the deposition site. After removal, the headspace of soil samples, taken from under the cadaver decomposition island (CDI), were analyzed once per week for a period of 4 weeks using solid phase micro extraction- gas chromatography/mass spectrometry (SPME-GC/MS) as the instrumental analysis method. While there have been limited studies in terms of volatile residual odor in soil matrices, it is the goal of this work to further expand the analytical knowledge of residual decomposition odor volatiles by adding another geographical location such as the West Texas region characterized by arid and colder climate conditions. Characterization of VOCs of interest was conducted highlighting trends in abundance and presence as a function of remains contact with soil surface as well as post-remains removal soil collection times.

Resumen Mediante el conocimiento de las sustancias volátiles de olor por descomposición residual se puede mejorar el adiestramiento de perros de venteo y las técnicas forenses para la recuperación de víctimas. El propósito de este estudio es caracterizar los compuestos orgánicos volátiles (COV) de descomposición en suelos contaminados con restos porcinos en estado de descomposición a lo largo de varias fases en un entorno exterior. Se utilizó un modelo de simulación de carne de cerdo y de cadáveres de cerdos en lugar de cadáveres humanos, los cuales se dejaron descomponer durante tres períodos de tiempo distintos: 14, 17 y 21 días; posteriormente se retiraron del lugar de depósito. Después de la extracción, el espacio vacío de las muestras de suelo, tomadas de debajo de la isla de descomposición cadavérica (CDI, por sus siglas en inglés), se analizaron una vez por semana durante un período de 4 semanas utilizando la microextracción en fase sólida -cromatografía de gases/espectrometría de masas (SPME-GC/MS, por sus siglas en inglés) como método de análisis instrumental. Si bien se han realizado estudios limitados con respecto a los olores residuales volátiles en las matrices del suelo, el objetivo de esta labor es ampliar aún más los conocimientos analíticos acerca de las sustancias volátiles de olor por descomposición residual añadiendo otra ubicación geográfica como la región del oeste de Texas, caracterizada por condiciones climáticas áridas y más frías. Se llevó a cabo la caracterización de los COV de interés, destacando las tendencias en la abundancia y presencia en función del contacto de los restos con la superficie del suelo, así como los tiempos de recolección del suelo después de la eliminación de los restos.

Resumo Através do conhecimento das substâncias odoríferas voláteis devido à decomposição residual, podem ser aprimorados o treinamento dos cães farejadores e as técnicas forenses para a recuperação das vítimas. O objetivo deste estudo é caracterizar compostos orgânicos voláteis de decomposição (COV) em solos contaminados com restos suínos em estado de decomposição ao longo de várias fases em um ambiente externo. Foi utilizado um modelo de simulação de carne de porco e carcaças de suínos em vez de carcaças humanas, que foram deixadas em decomposição por três períodos diferentes: 14, 17 e 21 dias; eles foram posteriormente removidos do local de depósito. Após a extração, o espaço vazio das amostras de solo, retiradas da ilha de decomposição cadavérica (CDI em inglês), foram analisadas uma vez por semana durante um período de 4 semanas usando microextração em fase sólida - cromatografia gasosa / espectrometria de massa (SPME-GC / MS em inglês) como método de análise instrumental. Embora tenham sido realizados estudos limitados sobre odores residuais voláteis em matrizes de solo, o objetivo deste trabalho é expandir ainda mais o conhecimento analítico sobre substâncias voláteis de odor residual de decomposição, adicionando outra localização geográfica, como a região do Oeste do Texas, caracterizado por condições climáticas áridas e frias. Foi realizada a caracterização dos COVs de interesse, destacando as tendências de abundância e presença em função do contato dos restos com a superfície do solo, bem como os tempos de coleta do solo após a remoção dos restos.

Gallic acid improves recognition memory and decreases oxidative-inflammatory damage in the rat hippocampus with metabolic syndrome.

Metabolic syndrome (MS) results from excessive consumption of high-calorie foods and sedentary lifestyles. Clinically, insulin resistance, abdominal obesity, hyperglycemia, dyslipidemia, and hypertension are observed. MS has been considered a risk factor in the development of dementia. In the brain, a metabolically impaired environment generates oxidative stress and excessive production of pro-inflammatory cytokines that deteriorate the morphology and neuronal function in the hippocampus, leading to cognitive impairment. Therapeutic alternatives suggest that phenolic compounds can be part of the treatment for neuropathies and metabolic diseases. In recent years, the use of Gallic Acid (GA) has demonstrated antioxidant and anti-inflammatory effects that contribute to neuroprotection and memory improvement in animal models. However, the effect of GA on hippocampal neurodegeneration and memory impairment under MS conditions is still unclear. In this work, we administered GA (20 mg/kg) for 60 days to rats with MS. The results show that GA treatment improved zoometric and biochemical parameters, as well as the recognition memory, in animals with MS. Additionally, GA administration increased hippocampal dendritic spines and decreased oxidative stress and inflammation. Our results show that GA treatment improves metabolism: reducing the oxidative and inflammatory environment that facilitates the recovery of the neuronal morphology in the hippocampus of rats with MS. Consequently, the recognition of objects by these animals, suggesting that GA could be used therapeutically in metabolic disorders that cause dementia.

The Administration of Cadmium for 2, 3 and 4 Months Causes a Loss of Recognition Memory, Promotes Neuronal Hypotrophy and Apoptosis in the Hippocampus of Rats.

Cadmium (Cd) is a toxic metal and classified as a carcinogen whose exposure could affect the function of the central nervous system. There are studies that suggest that Cd promotes neurodegeneration in different regions of the brain, particularly in the hippocampus. It is proposed that its mechanism of toxicity maybe by an oxidative stress pathway, which modifies neuronal morphology and causes the death of neurons and consequently affecting cognitive tasks. However, this mechanism is not yet clear. The aim of the present work was to study the effect of Cd administration on recognition memory for 2, 3 and 4 months, neuronal morphology and immunoreactivity for caspase-3 and 9 in rat hippocampi. The results show that the administration of Cd decreased recognition memory. Likewise, it caused the dendritic morphology of the CA1, CA3 and dentate gyrus regions of the hippocampus to decrease with respect to the time of administration of this heavy metal. In addition, we observed a reduction in the density of dendritic spines as well as an increase in the immunoreactivity of caspase-3 and 9 in the same hippocampal regions of the animals treated with Cd. These results suggest that Cd affects the structure and function of the neurons of the hippocampus, which contribute to the deterioration of recognition memory. Our results suggest that the exposure to Cd represents a critical health problem, which if not addressed quickly, could cause much more serious problems in the quality of life of the human population, as well as in the environment in which they develop.

Integración de los enfoques de gestión documental y gestión de riesgos para el tratamiento de la información como evidencia de actos y transacciones organizacionales / Integration of the approaches of documentary management and risk management for the treatment of the information as evidence of acts and organizational transactions

En el presente artículo se exploran los nexos entre gestión documental y gestión de riesgos. Para esto se analiza cómo la gestión documental ha evolucionado en las últimas décadas hasta enfocarse en los procesos de captura y mantenimiento de evidencias de actos y transacciones de negocios. Se muestra cómo la literatura especializada exploró dicha relación e identificó que los documentos son tanto fuentes de información para la identificación de riesgos, como objetos de riesgos en sí mismos. Se concluye que los sistemas de gestión documental ayudan a las organizaciones a gestionar la incertidumbre en relación con el fracaso en la creación y control de documentos de calidad, por el impacto negativo que esto tiene en la capacidad de la organización para lograr sus objetivos. En este sentido se considera que un sistema de gestión documental es un sistema de gestión de riesgos, en el que es esencial la determinación de requisitos de gestión documental para la identificación y la mitigación de riesgos organizacionales derivados de la información, como evidencia de actos y transacciones de negocios(AU)

In this article the links between records management and risk management are explored. It is exposed how records management has evolved in recent decades to focus on the processes of capture and maintenance of acts evidence and business transactions. It shows how the specialized literature explored this relationship and identified that documents are both information sources for risks identification, and objects of risks in themselves. It is concluded that Records Management Systems help organizations to manage the effect of uncertainty in relation to the failure in the creation and control of quality documents, due to the negative impact that this has on the organization's capacity to achieve its objectives. In that sense a Records Management System is considered to be a Risk Management system, where it is essential the determination of records management requirements for the identification and mitigation of organizational risks derived from information as acts and business transactions evidences(AU)

Increase of Frequency and Modulation of Phenotype of Regulatory T Cells by Atorvastatin Is Associated with Decreased Lung Inflammatory Cell Infiltration in a Murine Model of Acute Allergic Asthma.

Regulatory T cells (Tregs) play an important role by controlling allergic inflammation of airways. Recently, it has been shown that statins have immunomodulatory properties, probably mediated by their effects on Tregs. Therefore, we evaluated the in vivo effect of atorvastatin (ATV) on Tregs and its association with the inflammatory process in a model of allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with intranasal OVA. ATV (40 mg/kg) was delivered by daily intraperitoneal injection for 7 or 15 days before each OVA challenge. ATV treatment for 7 days increased the frequency of Tregs in mediastinal lymph nodes (MLN) and the interleukin (IL)-10 in lungs. After 15 days of treatment, ATV increased the percentage of glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR+) and programmed cell death protein 1 (PD-1+) Tregs in the lung, without enhancing their suppressive activity, but also increased the percentage of conventional T cells expressing GITR+, PD1+, and OX-40 (tumor necrosis factor receptor superfamily member 4). Although no significant changes were observed in the number of inflammatory cells in the bronchoalveolar lavage (BAL), OVA-specific immunoglobulin E in the serum, and type 2 helper (Th2) cytokines in the lungs, there was a significant decrease of peribronchial inflammation that negatively correlated with the Tregs in MLN and the concentration of IL-10 in the lung. These results suggest that ATV has an immunomodulatory role possibly mediated by their effects on Tregs, which could contribute to the control of inflammation during allergic asthma. Further studies are necessary to elucidate the contribution of Treg to immunomodulatory action of statins in the context of allergic asthma.

A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats.

A high calorie intake can induce the appearance of the metabolic syndrome (MS), which is a serious public health problem because it affects glucose levels and triglycerides in the blood. Recently, it has been suggested that MS can cause complications in the brain, since chronic hyperglycemia and insulin resistance are risk factors for triggering neuronal death by inducing a state of oxidative stress and inflammatory response that affect cognitive processes. This process, however, is not clear. In this study, we evaluated the effect of the consumption of a high-calorie diet (HCD) on both neurodegeneration and spatial memory impairment in rats. Our results demonstrated that HCD (90 day consumption) induces an alteration of the main energy metabolism markers, indicating the development of MS in rats. Moreover, an impairment of spatial memory was observed. Subsequently, the brains of these animals showed activation of an inflammatory response (increase in reactive astrocytes and interleukin1-ß as well as tumor necrosis factor-α) and oxidative stress (reactive oxygen species and lipid peroxidation), causing a reduction in the number of neurons in the temporal cortex and hippocampus. Altogether, these results suggest that a HCD promotes the development of MS and contributes to the development of a neurodegenerative process and cognitive failure. In this regard, it is important to understand the relationship between MS and neuronal damage in order to prevent the onset of neurodegenerative disorders.

Amyloid-ß(25-35) induces a permanent phosphorylation of HSF-1, but a transitory and inflammation-independent overexpression of Hsp-70 in C6 astrocytoma cells.

Two hallmarks of Alzheimer diseases are the continuous inflammatory process, and the brain deposit of Amyloid b (Aß), a cytotoxic protein. The intracellular accumulation of Aß(25-35) fractions, in the absence of Heat Shock proteins (Hsps), could be responsible for its cytotoxic activity. As, pro-inflammatory mediators and nitric oxide control the expression of Hsps, our aim was to investigate the effect of Aß(25-35) on the concentration of IL-1ß, TNF-α and nitrite levels, and their relation to pHSF-1, Hsp-60, -70 and -90 expressions, in the rat C6 astrocyte cells. Interleukin-specific ELISA kits, immunohistochemistry with monoclonal anti-Hsp and anti pHSF-1 antibodies, and histochemistry techniques, were used. Our results showed that Aß25-35 treatment of C6 cells increased, significantly and consistently the concentration of IL-1ß, TNF-α and nitrite 3 days after initiating treatment. The immunoreactivity of C6 cells to Hsp-70 reached its peak after 3 days of treatment followed by an abrupt decrease, as opposed to Hsp-60 and -90 expressions that showed an initial and progressive increase after 3 days of Aß(25-35) treatment. pHSF-1 was identified throughout the experimental period. Nevertheless, progressive and sustained cell death was observed during all the treatment times and it was not caspase-3 dependent. Our results suggest that Hsp-70 temporary expression serves as a trigger to inhibit casapase-3 pathway and allow the expression of Hsp-60 and -90 in C6 astrocytoma cells stimulated with Aß(25-35).

Overexpression of glycosylated proteins in cervical cancer recognized by the Machaerocereus eruca agglutinin.

In cervical cancer, glycosylation has been suggested as being involved in both its carcinogenesis and invasive capacity. In this work, we analyzed mucin type O-glycosylation in biopsies of invasive cervical cancer in FIGO stage II B through histochemistry using lectins specific for O-glycosidically linked glycans. Our results reveal that the lectin Machaerocereus eruca (MeA, specific for Gal in a Fucα1,2 (GalNAcα1,3) Galß1,4) showed increased recognition of tumoral cells and tumoral stroma tissue compared to other lectins with similar specificity; healthy cervical tissue was negative for MeA. Trypsin treatment of recognized tissues abolished MeA's recognition;moreover, interaction of MeA was inhibited with oligosaccharides from mucin. As demonstrated by Western blot of 2-D electrophoresis, MeA recognized ten glycoproteins in the range from 122 to 42 kDa in cervical cancer lysates. The LC-ESI-MS/MS analysis of the MeAs' recognized peptides revealed that the latter matched mainly with the amino acid sequences of lamin A/C, vimentin, elongation factor 2, keratin 1, and beta actin. Our results suggest that MeA recognizes a complex of over-expressed O-glycosidically-linked proteins that play a relevant role in cervical cancer's invasive capacity. O-glycosylation participates in the disassembly of intercellular junctions favoring cancer progression.

Proatherogenic macrophage activities are targeted by the flavonoid quercetin.

Many studies have demonstrated that the flavonoid quercetin protects against cardiovascular disease (CVD) and related risk factors. Atherosclerosis, the underlying cause of CVD, is also attenuated by oral quercetin administration in animal models. Although macrophages are key players during fatty streak formation and plaque progression and aggravation, little is known about the effects of quercetin on atherogenic macrophages. Here, we report that primary bone marrow-derived macrophages internalized less oxidized low-density lipoprotein (oxLDL) and accumulated less intracellular cholesterol in the presence of quercetin. This reduction of foam cell formation correlated with reduced surface expression of the oxLDL receptor CD36. Quercetin also targeted the lipopolysaccharide-dependent, oxLDL-independent pathway of lipid droplet formation in macrophages. In oxLDL-stimulated macrophages, quercetin inhibited reactive oxygen species production and interleukin (IL)-6 secretion. In a system that evaluated cholesterol crystal-induced IL-1ß secretion via nucleotide-binding domain and leucine-rich repeat containing protein 3 inflammasome activation, quercetin also exhibited an inhibitory effect. Dyslipidemic apolipoprotein E-deficient mice chronically treated with intraperitoneal quercetin injections had smaller atheromatous lesions, reduced lipid deposition, and less macrophage and T cell inflammatory infiltrate in the aortic roots than vehicle-treated animals. Serum levels of total cholesterol and the lipid peroxidation product malondialdehyde were also reduced in these mice. Our results demonstrate that quercetin interferes with both key proatherogenic activities of macrophages, namely foam cell formation and pro-oxidant/proinflammatory responses, and these effects may explain the atheroprotective properties of this common flavonoid.

La gestión de documentos de archivo en el actual contexto organizacional y la introducción a la Norma ISO 15489 / The archive documents management in the current organizational context and introduction to ISO 15489 Standard

Se aborda la gestión documental en el contexto organizacional actual. Se examina el concepto de documento de archivo y las complejidades de su manejo en el ambiente digital que afectan su capacidad de constituir evidencia veraz de los procesos de negocios organizacionales. Finalmente se presenta la Norma ISO 15489 Información y documentación Gestión de Documentos como una metodología útil para la adecuada gestión de documentación archivística, independientemente de su soporte, en el contexto organizacional. Se ofrecen consideraciones finales y recomendaciones

The documentary management in the current organizational context is approached. The concept of archive document and the complexity of its management in the digital environment affecting its ability to create a truthful evidence of processes of organizational business are examined. Finally, the ISO 15489 Standard is presented: Information and documentation document management as a useful methodology for a appropriate management of archives documents, independently of its support in the organizational context. Final considerations and recommendations are offered