Understanding the Intersection of Environmental Pollution, Pneumonia, and Inflammation: Does Gender Play a Role?

Accumulating evidence indicates that exposure to air pollution is associated with increased mortality from respiratory disease. Exposure to ambient pollutants, such as ozone, particulate matter, sulfur dioxide, nitrogen dioxide, and other agents has been associated with decrease in lung function and immunity, and with increased rates of hospitalization for lung disease, including pneumonia. Furthermore, sex differences in frequency and severity of pulmonary disease and infection have been reported, suggesting a role of sex hormones in mediating these differences. Pneumonia, which is commonly caused by bacterial infection and subsequent lung inflammation leading to hospitalization and death, occurs at different rates in men and women. In this context, male and female hormones can have direct effects on the immunity system by binding to receptors in immune cells, and these responses can be modulated by environmental exposures. This chapter summarizes clinical, animal, and epidemiological studies linking exposure to air pollution and pneumonia in both males and females. Understanding sex-specific mechanisms in pneumonia pathogenesis and environmental responses can help in the development of more effective therapeutics and treatment options to reduce negative health outcomes in men and women

Effect of hypoxia on lung gene expression and proteomic profile: insights into the pulmonary surfactant response

Exposure of lung to hypoxia has been previously reported to be associated with significant alterations in the protein content of bronchoalveolar lavage (BAL) and lung tissue. In the present work we have used a proteomic approach to describe the changes in protein complement induced by moderate long-term hypoxia (rats exposed to 10% O2 for 72h) in BAL and lung tissue, with a special focus on the proteins associated with pulmonary surfactant, which could indicate adaptation of this system to limited oxygen availability. The analysis of the general proteomic profile indicates a hypoxia-induced increase in proteins associated with inflammation both in lavage and lung tissue. Analysis at mRNA and protein levels revealed no significant changes induced by hypoxia on the content in surfactant proteins or their apparent oligomeric state. In contrast, we detected a hypoxia-induced significant increase in the expression and accumulation of hemoglobin in lung tissue, at both mRNA and protein levels, as well as an accumulation of hemoglobin both in BAL and associated with surface-active membranes of the pulmonary surfactant complex. Evaluation of pulmonary surfactant surface activity from hypoxic rats showed no alterations in its spreading ability, ruling out inhibition by increased levels of serum or inflammatory proteins.Ministerio de Ciencia BIO2012-30733Ministerio de Ciencia CSD2007-00010Gobierno de la Comunidad de Madrid S2009MAT-1507National Institutes of Health NIH HL3478

Structural and Functional Determinants of Rodent and Human Surfactant Protein A: A Synthesis of Binding and Computational Data

Surfactant protein A (SP-A) provides surfactant stability, first line host defense, and lung homeostasis by binding surfactant phospholipids, pathogens, alveolar macrophages (AMs), and epithelial cells. Non-primates express one SP-A protein whereas humans express two: SP-A1 and SP-A2 with core intra- and inter-species differences in the collagen-like domain. Here, we used macrophages and solid phase binding assays to discern structural correlates of rat (r) and human (h) SP-A function. Binding assays using recombinant rSP-A expressed in insect cells showed that lack of proline hydroxylation, truncations of amino-terminal oligomerization domains, and site-directed serine (S) or alanine (A) mutagenesis of cysteine 6 (C6S), glutamate 195 (E195A), and glutamate 171 (E171A) in the carbohydrate recognition domain (CRD) all impaired SP-A binding. Replacement of arginine 197 with alanine found in hSP-A (R197A), however, restored the binding of hydroxyproline-deficient rSP-A to the SP-A receptor SP-R210 similar to native rat and human SP-A. In silico calculation of Ca++ coordination bond length and solvent accessibility surface area revealed that the “humanized” R197A substitution alters topology and solvent accessibility of the Ca++ coordination residues of the CRD domain. Binding assays in mouse AMs that were exposed to either endogenous SP-A or hSP-A1 (6A2) and hSP-A2 (1A0) isoforms in vivo revealed that mouse SP-A is a functional hybrid of hSP-A1 and hSP-A2 in regulating SP-A receptor occupancy and binding affinity. Binding assays using neonatal and adult human AMs indicates that the interaction of SP-A1 and SP-A2 with AMs is developmentally regulated. Furthermore, our data indicate that the auxiliary ion coordination loop encompassing the conserved E171 residue may comprise a conserved site of interaction with macrophages, and SP-R210 specifically, that merits further investigation to discern conserved and divergent SP-A functions between species. In summary, our findings support the notion that complex structural adaptation of SP-A regulate conserved and species specific AM functions in vertebrates

Motifs within the CA-repeat-rich region of Surfactant Protein B (SFTPB) intron 4 differentially affect mRNA splicing

The first half of the surfactant protein B (SP-B) gene intron 4 is a CA-repeat-rich region that contains 11 motifs. To study the role of this region on SP-B mRNA splicing, minigenes were generated by systematic removal of motifs from either the 5’ or 3’ end. These were transfected in CHO cells to study their splicing efficiency. The latter was determined as the ratio of completely to incompletely spliced SP-B RNA. Our results indicate that SP-B intron 4 motifs differentially affect splicing. Motifs 8 and 9 significantly enhanced and reduced splicing of intron 4, respectively.  RNA mobility shift assays performed with a Motif 8 sequence that contains a CAUC cis-element and cell extracts resulted in a RNA:protein shift that was lost upon mutation of the element. Furthermore, in silico analysis of mRNA secondary structure stability for minigenes with and without motif 8 indicated a correlation between mRNA stability and splicing ratio.  We conclude that differential loss of specific intron 4 motifs results in one or more of the following: a) altered splicing, b) differences in RNA stability and c)changes in secondary structure. These, in turn, may affect SP-B content in lung health or disease

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Role of Non-Coding RNAs in Lung Cancer

Lung cancer is the most common cancer worldwide, and the leading cancer killer in both men and women. Globally, it accounts for 11.6% of all cancer cases and is responsible for 18.4% of cancer-related deaths. The mechanisms underlying lung cancer development and progression have been widely studied, and roles for non-coding RNAs (ncRNAs) have been identified. Non-coding RNAs are a type of RNA molecules that are not translated into proteins. The main types of ncRNAs include transfer RNAs (tRNAs), microRNAs (miRNAs), small interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), small nucleolar/nuclear RNAs (snoRNAs, snRNAs), extracellular RNAs (exRNAs), tRNA fragments, and long non-coding RNAs (lncRNAs). In the past few years, there has been an increased interest in the role of ncRNAs in oncology, and lung cancer tumorigenesis specifically. Multiple ncRNAs were identified as tumor suppressors: tRNA fragments, snoRNAs, and piRNAs while others were reported to have tumor-promoting functions: circular RNAs (circRNAs), snoRNAs, piRNAs, YRNAs, natural antisense transcripts (NATs) and pseudogene transcripts. In this chapter, we discuss the latest body of knowledge regarding the role of ncRNAs in lung cancer pathogenesis as well as their potential use as biomarkers or therapies against lung cancer

Elaboración y Validación de una Escala de Calidad de Vida para pacientes con cardiopatía

The present is a non experimental study consisting of constructing and validating a diagnostic instrument which evaluates quality of life in people with any kind of cardiovascular disease. Method: The instrument constructed includes sociodemographic and clinical data along with 32 items which constitute the quality of life scale. It was applied to 75 people with a cardiopathy and to 137 members of the general population, using the General Health Questionnaire in its 12 item version as an external criteria, hoping to find consistency among the results thrown by both of the instruments. Results: The quality of life scale for patients with cardiopathy obtained .816 in the analysis of Cronbach’s Alpha, which indicates it is a reliable instrument. The data reduction analysis with varimax rotation proved that most of the items have a factorial weight above 0.40. The rest of the items will be reviewedEl presente es un estudio no experimental de elaboración y validación estadística de un instrumento diagnóstico que evalúa la calidad de vida en personas con algún tipo de enfermedad cardiovascular. Método: Se elaboró un instrumento que incluye datos sociodemográficos y datos clínicos 32 reactivos que conforman la escala de calidad de vida. Se aplicó a 75 personas con cardiopatía y a 137 pertenecientes a la población general, utilizando como criterio externo el Cuestionario General de Salud en su versión de doce reactivos (CGS-12), esperando encontrar consistencia en los resultados obtenidos en los dos instrumentos. Resultados: La escala de calidad de vida para pacientes con cardiopatía posee un Alpha de Cronbach de .816, lo cual indica que es un instrumento confiable. El análisis factorial con rotación Varimax demostró que la mayoría de los reactivos poseen un peso factorial superior a 0.40. Se revisarán los reactivos que no entraron en el análisi

Biomarkers for Bronchopulmonary Dysplasia in the Preterm Infant

Bronchopulmonary dysplasia (BPD) is a chronic inflammatory lung disease of very-low-birth-weight (VLBW) preterm infants, associated with arrested lung development and a need for supplemental oxygen. Over the past few decades, the incidence of BPD has significantly raised as a result of improved survival of VLBW infants requiring mechanical ventilation. While early disease detection is critical to prevent chronic lung remodeling and complications later in life, BPD is often difficult to diagnose and prevent due to the lack of good biomarkers for identification of infants at risk, and overlapping symptoms with other diseases, such as pulmonary hypertension (PH). Due to the current lack of effective treatment available for BPD and PH, research is currently focused on primary prevention strategies, and identification of biomarkers for early diagnosis, that could also represent potential therapeutic targets. In addition, novel histopathological, biochemical, and molecular factors have been identified in the lung tissue and in biological fluids of BPD and PH patients that could associate with the disease phenotype. In this review, we provide an overview of biomarkers for pediatric BPD and PH that have been identified in clinical studies using various biological fluids. We also present a brief summary of the information available on current strategies and guidelines to prevent and diagnose BPD and PH, as well as their pathophysiology, risk factors, and experimental therapies currently available.Fil: Rivera, Lidys. State University of Pennsylvania; Estados UnidosFil: Siddaiah, Roopa. State University of Pennsylvania; Estados UnidosFil: Oji Mmuo, Christiana. State University of Pennsylvania; Estados UnidosFil: Silveyra, Gabriela Romina. State University of Pennsylvania; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Silveyra, Patricia. State University of Pennsylvania; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Effects of atrazine on vitellogenesis, steroid levels and lipid peroxidation, in female red swamp crayfish Procambarus clarkii

Atrazine, a widely use herbicide, has been classified as a potential endocrine disruptor, especially for freshwater species. In this study, we tested the hypothesis that atrazine can affect reproduction in crayfish through dysregulation of vitellogenin expression and hormone synthesis. Adult female crayfish (Procambarus clarkii) were exposed during one month to atrazine at concentrations of either 1 or 5 mg/L. At the end of the exposure, ovaries, hepatopancreas, and hemolymph samples were harvested for analysis of vitellogenin expression and steroid hormone levels. Ovarian tissue was also sampled for both biochemical and histological analyses. Our results show that atrazine-exposed crayfish had a lower expression of vitellogenin in the ovary and hepatopancreas, as well as smaller oocytes, and reduced vitellogenin content in the ovary. Despite these effects, circulating levels of estradiol increased in females exposed to 5 mg/L of atrazine, showing that the inhibiting effect of atrazine on vitellogenin production was not related to a lower secretion of sexual steroids. Instead, some early stimulating effects of estradiol on vitellogenesis could have occurred, particularly in the hepatopancreas. On the other hand, atrazine caused a higher metabolic effort, in terms of lactate production, presumably triggered to provide the energy needed to face the unspecific stress produced by the herbicide. Lipid peroxidation was not affected by atrazine, but glutathione levels were significantly increased.Fil: Silveyra, Gabriela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Silveyra, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Penn State College of Medicine; Estados UnidosFil: Vatnick, Itzick. Widener University; Estados UnidosFil: Medesani, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Rodriguez, Enrique Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; Argentin