Clinical Outcomes and Genetic Expression Profile in Human Liver Graft Dysfunction During Ischemia/Reperfusion Injury

Introduction. This study aims to compare the molecular gene expression during ischemia reperfusion injury. Several surgical times were considered: in the beginning of the harvesting (T0), at the end of the cold ischemia period (T1), and after reperfusion (T2) and compared with graft dysfunction after liver transplant (OLT). Methods. We studied 54 patients undergoing OLT. Clinical, laboratory data, and histologic data (Suzuki classification) as well as the Survival Outcomes Following Liver Transplantation (SOFT) score were used and compared with the molecular gene expression of the following genes: Interleukin (IL)-1b, IL-6, tumor necrosis factor-a, perforin, E-selectin (SELE), Fas-ligand, granzyme B, heme oxygenase-1, and nitric oxide synthetase. Results. Fifteen patients presented with graft dysfunction according to SOFT criteria. No relevant data were obtained by comparing the variables graft dysfunction and histologic variables. We observed a statistically significant relation between SELE at T0 (P ¼ .013) and IL-1b at T0 (P ¼ .028) and early graft dysfunction. Conclusions. We conclude that several genetically determined proinflammatory expressions may play a critical role in the development of graft dysfunction after OLT

Microbes as Master Immunomodulators: Immunopathology, Cancer and Personalized Immunotherapies

The intricate interplay between the immune system and microbes is an essential part of the physiological homeostasis in health and disease. Immunological recognition of commensal microbes, such as bacterial species resident in the gut or lung as well as dormant viral species, i.e., cytomegalovirus (CMV) or Epstein-Barr virus (EBV), in combination with a balanced immune regulation, is central to achieve immune-protection. Emerging evidence suggests that immune responses primed to guard against commensal microbes may cause unexpected pathological outcomes, e.g., chronic inflammation and/or malignant transformation. Furthermore, translocation of immune cells from one anatomical compartment to another, i.e., the gut-lung axis via the lymphatics or blood has been identified as an important factor in perpetrating systemic inflammation, tissue destruction, as well as modulating host-protective immune responses. We present in this review immune response patterns to pathogenic as well as non-pathogenic microbes and how these immune-recognition profiles affect local immune responses or malignant transformation. We discuss personalized immunological therapies which, directly or indirectly, target host biological pathways modulated by antimicrobial immune responses

Trained Immunity for Personalized Cancer Immunotherapy: Current Knowledge and Future Opportunities

Memory formation, guided by microbial ligands, has been reported for innate immune cells. Epigenetic imprinting plays an important role herein, involving histone modification after pathogen-/danger-associated molecular patterns (PAMPs/DAMPs) recognition by pattern recognition receptors (PRRs). Such “trained immunity” affects not only the nominal target pathogen, yet also non-related targets that may be encountered later in life. The concept of trained innate immunity warrants further exploration in cancer and how these insights can be implemented in immunotherapeutic approaches. In this review, we discuss our current understanding of innate immune memory and we reference new findings in this field, highlighting the observations of trained immunity in monocytic and natural killer cells. We also provide a brief overview of trained immunity in non-immune cells, such as stromal cells and fibroblasts. Finally, we present possible strategies based on trained innate immunity that may help to devise host-directed immunotherapies focusing on cancer, with possible extension to infectious diseases

IL-10 overexpression predisposes to invasive aspergillosis by suppressing antifungal immunity

© 2017 American Academy of Allergy, Asthma & ImmunologyProinflammatory immune responses are critically required for antimicrobial host defenses; however, excessive inflammation has the potential to damage host tissues thereby paradoxically contributing to the progression of infection. A central negative regulator of inflammatory responses is IL-10, an immunosuppressive cytokine with a wide variety of functions across multiple cell types. Although the role of IL-10 during infection appears to vary for different microorganisms, a largely detrimental role has been attributed to this cytokine during fungal disease. Given the variable risk of infection and its outcome among patients with comparable predisposing factors, susceptibility to invasive aspergillosis (IA) is thought to rely largely on genetic predisposition. The initial investigation of genetic variability at the IL10 locus led to the identification of single nucleotide polymorphisms (SNPs) influencing its transcriptional activity; thus, IL-10 may be a reasonable candidate for the genetic regulation of susceptibility to IA in high-risk patients.Supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (contracts IF/00735/2014 to A.C., IF/01390/2014 to E.T., IF/00021/2014 to R.S., and SFRH/BPD/96176/2013 to C.C.), the Conselho de Reitores das Universidades Portuguesas (CRUP), Portugal (Ações Integradas Luso-Alemãs A-43/16), the Deutscher Akademischer Austauschdienst (DAAD) (project-ID 57212690), the Fondo de Investigaciones Sanitarias (Madrid, Spain) (grant #PI12/02688) and the ERA-NET PathoGenoMics (grant #0315900A).info:eu-repo/semantics/publishedVersio

Avaliação ecológica rápida de indicadores bentônicos de qualidade de água: uma experiência de sucesso na formação de pós-graduandos em ecologia no Brasil

Rapid Ecological Assessment protocols are important tools for the training of postgraduate students, as well as the collection of data on poorly-known and protected areas with the potential for the preservation of water supplies for urban areas. The objective of this study was to perform a survey of water quality and diversity of benthic macroinvertebrates in two sub-basins at the Mata do Junco Wildlife Refuge in the Brazilian state of Sergipe. The collection of data in the field, laboratory processing, and the interpretation and discussion of data were conducted in groups by students from two postgraduate programmes in Ecology and Conservation (UFMG and UFS), personnel of the state environment agency (SEMARH), school teachers from the local town of Capela, and members of the reserve's voluntary fire brigade. The results of the assessment were organised, analysed, and presented at the reserve headquarters in the form of posters, for the development of environmental education activities with pupils from local schools, as well as contributing to a SEMARH seminar. Samples were characterised by distinct taxonomic compositions and diversity, as confirmed by MDS and additive partitioning of diversity analyses. The gravel substrate presented the lower mean taxonomic richness in each sampling unit (a1 = 28%), while the average difference among samples (b1 diversity) was elevated for both substrates (39% for leaf litter, 41% for gravel), reflecting the pronounced variation among samples, even adjacent ones within the same stream. Diversity between streams was lower in the case of leaf litter in comparison with gravel (b2 = 21 and 31%, respectively). A total of 57 fish specimens were collected with a predominance of individuals of the orders Characiformes (62%) and Perciformes (21%). This rapid ecological assessment confirmed the importance of the conservation unit and emphasised the need for its continuation, given its importance for the maintenance of water quality and its other ecological services, such as the conservation of the region's aquatic biodiversity and providing the local town of Capela (circa 20,000 inhabitants) with its water supply, the Mata do Junco being its only source._________________________________________________________________________________ RESUMO: Protocolos de avaliação ecológica rápida são ferramentas importantes para treinamento de pós-graduandos e levantamento de informações em áreas pouco conhecidas. O objetivo deste estudo foi realizar um levantamento de qualidade de água e diversidade de macroinvertebrados bentônicos em duas sub-bacias em uma área protegida. Atividades de campo, processamento em laboratório, interpretação e discussão de dados foram realizados em grupos com a participação de representantes dos Programas de Pós-graduação em Ecologia da UFMG e da UFS, SEMARH, professores do município de Capela e "brigada voluntária de incêndio" do Refúgio de Vida Silvestre (RVS) Mata do Junco em Sergipe. Os resultados foram sintetizados, analisados e disponibilizados na Unidade de Conservação (UC) RVS Mata do Junco na forma de banners de divulgação, atividades de educação ambiental com alunos de escolas locais e em um seminário de recursos hídricos no estado de Sergipe. As amostras de fundo apresentaram composições taxonômicas e diversidade diferentes, como mostraram as análises de ordenação MDS e de partição aditiva da diversidade. O substrato cascalho apresentou menor riqueza taxonômica média em cada unidade amostral (a1 = 28%) e a diferença média entre amostragens (diversidade b1) foi elevada nos dois casos (39% em folhiço, 41% em cascalho), indicando a alta variação que há entre amostras espacialmente próximas em um mesmo riacho. A diversidade entre riachos foi menor em folhiço do que em cascalho (b2 = 21 e 31%, respectivamente). Foram capturados 57 peixes, com predomínio de Characiformes (62%) e Perciformes (21%). Esta avaliação ecológica rápida corrobora a importância da criação e manutenção desta unidade de conservação, a fim de manter a boa qualidade de suas águas e serviços ecológicos, destacando-se a conservação da biodiversidade aquática e o abastecimento do município de Capela, com cerca de 20 mil habitantes que têm no RVS Mata do Junco seu único manancial de abastecimento de água

Challenges Using Extrapolated Family-level Macroinvertebrate Metrics in Moderately Disturbed Tropical Streams: a Case-study From Belize

Family-level biotic metrics were originally designed to rapidly assess gross organic pollution effects, but came to be regarded as general measures of stream degradation. Improvements in water quality in developed countries have reignited debate about the limitations of family-level taxonomy to detect subtle change, and is resulting in a shift back towards generic and species-level analysis to assess smaller effects. Although the scale of pollution characterizing past condition of streams in developed countries persists in many developing regions, some areas are still considered to be only moderately disturbed. We sampled streams in Belize to investigate the ability of family-level macroinvertebrate metrics to detect change in stream catchments where less than 30% of forest had been cleared. Where disturbance did not co-vary with natural gradients of change, and in areas characterized by low intensity activities, none of the metrics tested detected significant change, despite evidence of environmental impacts. We highlight the need for further research to clarify the response of metrics to disturbance over a broader study area that allows replication for confounding sources of natural variation. We also recommend research to develop more detailed understanding of the taxonomy and ecology of Neotropical macroinvertebrates to improve the robustness of metric use

Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity

Background. Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings. Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance. Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF