Contribution of RAGE axis activation to the association between metabolic syndrome and cancer

Molecular and Cellular Biochemistry - Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of...     

Effects of intensive human management on the taxonomic and functional diversity of ground beetles in a planted forest landscape

The rapid expansion of planted forests harms native biodiversity. Few studies report the effects of replacing wetlands with planted forests on ground beetles. We analyze how the taxonomic and functional diversity of ground beetles are affected by intensive management of a planted forest landscape in the Lower Delta of the Parana River. We defined six habitat types (n?=?3, N?=?18): young and mature willow (YW, MW), young and mature poplar without cattle (YP, MP), young and mature silvopastoral poplar (YS, MS). Using pitfall traps (N?=?1728), we recorded 35 species (1896 individuals). YW and MS reached the highest taxonomic diversity and richness. YW with more vertical heterogeneity showed higher species richness than MW. Hydrophilic species were more abundant in YW. Zoophagous species were more abundant in MS. YS, MS, and YW reached the highest functional evenness, which implies that a large part of the functional niches was used. Cattle dung and freshwater canals for livestock offer more resources for ground beetles. The planted tree species, stand age, and presence of cattle affects taxonomic and functional diversity of ground beetles. Willow and silvopastoral planted forests are the most suitable habitats for hosting wetland species. So, we recommend using willow species rather than poplar species when planted forests replace fluvial wetlands, increasing irrigation of poplar planted forests through ditches and canals, conserving or restoring different strata of understory to increase vertical heterogeneity, and maintaining the landscape heterogeneity. These management measures are essential to prevent the loss of wetland species and conserve ground beetle’s diversity.

     

The Heterogeneity of Early Parkinson’s Disease: A Cluster Analysis on Newly Diagnosed Untreated Patients

Background

The variability in the clinical phenotype of Parkinson’s disease seems to suggest the existence of several subtypes of the disease. To test this hypothesis we performed a cluster analysis using data assessing both motor and non-motor symptoms in a large cohort of newly diagnosed untreated PD patients.

Methods

We collected data on demographic, motor, and the whole complex of non-motor symptoms from 100 consecutive newly diagnosed untreated outpatients. Statistical cluster analysis allowed the identification of different subgroups, which have been subsequently explored.

Results

The data driven approach identified four distinct groups of patients, we have labeled: 1) Benign Pure Motor; 2) Benign mixed Motor-Non-Motor; 3) Non-Motor Dominant; and 4) Motor Dominant.

Conclusion

Our results confirmed the existence of different subgroups of early PD patients. Cluster analysis revealed the presence of distinct subtypes of patients profiled according to the relevance of both motor and non-motor symptoms. Identification of such subtypes may have important implications for generating pathogenetic hypotheses and therapeutic strategies.     

A Kinetic Study of the Rat Liver Adenosine Kinase Reverse Reaction

Adenosine kinase is an enzyme catalyzing the reaction: adenosine + ATP → AMP + ADP. We studied some biochemical properties not hitherto investigated and demonstrated that the reaction can be easily reversed when coupled with adenosine deaminase, which transforms adenosine into inosine and ammonia. The overall reaction is: AMP + ADP → ATP + inosine + NH₃. The exoergonic ADA reaction shifts the equilibrium and fills the energy gap necessary for synthesis of ATP. This reaction could be used by cells under particular conditions of energy deficiency and, together with myokinase activity, may help to restore physiological ATP levels.     

The Predisposition,Infection, Response and Organ Failure (Piro) Sepsis Classification System: Results of Hospital Mortality Using a Novel Concept and Methodological Approach

Introduction

PIRO is a conceptual classification system in which a number of demographic, clinical, biological and laboratory variables are used to stratify patients with sepsis in categories with different outcomes, including mortality rates.

Objectives

To identify variables to be included in each component of PIRO aiming to improve the hospital mortality prediction.

Methods

Patients were selected from the Portuguese ICU-admitted community-acquired sepsis study (SACiUCI). Variables concerning the R and O component included repeated measurements along the first five days in ICU stay. The trends of these variables were summarized as the initial value at day 1 (D1) and the slope of the tendency during the five days, using a linear mixed model. Logistic regression models were built to assess the best set of covariates that predicted hospital mortality.

Results

A total of 891 patients (age 60±17 years, 64% men, 38% hospital mortality) were studied. Factors significantly associated with mortality for P component were gender, age, chronic liver failure, chronic renal failure and metastatic cancer; for I component were positive blood cultures, guideline concordant antibiotic therapy and health-care associated sepsis; for R component were C-reactive protein slope, D1 heart rate, heart rate slope, D1 neutrophils and neutrophils slope; for O component were D1 serum lactate, serum lactate slope, D1 SOFA and SOFA slope. The relative weight of each component of PIRO was calculated. The combination of these four results into a single-value predictor of hospital mortality presented an AUC-ROC 0.84 (IC_95%:0.81–0.87) and a test of goodness-of-fit (Hosmer and Lemeshow) of p = 0.368.

Conclusions

We identified specific variables associated with each of the four components of PIRO, including biomarkers and a dynamic view of the patient daily clinical course. This novel approach to PIRO concept and overall score can be a better predictor of mortality for patients with community-acquired sepsis admitted to ICUs.     

Polyoxygenated Cholesterol Ester Hydroperoxide Activates TLR4 and SYK Dependent Signaling in Macrophages

Oxidation of low-density lipoprotein (LDL) is one of the major causative mechanisms in the development of atherosclerosis. In previous studies, we showed that minimally oxidized LDL (mmLDL) induced inflammatory responses in macrophages, macropinocytosis and intracellular lipid accumulation and that oxidized cholesterol esters (OxCEs) were biologically active components of mmLDL. Here we identified a specific OxCE molecule responsible for the biological activity of mmLDL and characterized signaling pathways in macrophages in response to this OxCE. Using liquid chromatography – tandem mass spectrometry and biological assays, we identified an oxidized cholesteryl arachidonate with bicyclic endoperoxide and hydroperoxide groups (BEP-CE) as a specific OxCE that activates macrophages in a TLR4/MD-2-dependent manner. BEP-CE induced TLR4/MD-2 binding and TLR4 dimerization, phosphorylation of SYK, ERK1/2, JNK and c-Jun, cell spreading and uptake of dextran and native LDL by macrophages. The enhanced macropinocytosis resulted in intracellular lipid accumulation and macrophage foam cell formation. Bone marrow-derived macrophages isolated from TLR4 and SYK knockout mice did not respond to BEP-CE. The presence of BEP-CE was demonstrated in human plasma and in the human plaque material captured in distal protection devices during percutaneous intervention. Our results suggest that BEP-CE is an endogenous ligand that activates the TLR4/SYK signaling pathway. Because BEP-CE is present in human plasma and human atherosclerotic lesions, BEP-CE-induced and TLR4/SYK-mediated macrophage responses may contribute to chronic inflammation in human atherosclerosis.     

Measuring the Characteristic Topography of Brain Stiffness with Magnetic Resonance Elastography

Purpose

To develop a reliable magnetic resonance elastography (MRE)-based method for measuring regional brain stiffness.

Methods

First, simulation studies were used to demonstrate how stiffness measurements can be biased by changes in brain morphometry, such as those due to atrophy. Adaptive postprocessing methods were created that significantly reduce the spatial extent of edge artifacts and eliminate atrophy-related bias. Second, a pipeline for regional brain stiffness measurement was developed and evaluated for test-retest reliability in 10 healthy control subjects.

Results

This technique indicates high test-retest repeatability with a typical coefficient of variation of less than 1% for global brain stiffness and less than 2% for the lobes of the brain and the cerebellum. Furthermore, this study reveals that the brain possesses a characteristic topography of mechanical properties, and also that lobar stiffness measurements tend to correlate with one another within an individual.

Conclusion

The methods presented in this work are resistant to noise- and edge-related biases that are common in the field of brain MRE, demonstrate high test-retest reliability, and provide independent regional stiffness measurements. This pipeline will allow future investigations to measure changes to the brain’s mechanical properties and how they relate to the characteristic topographies that are typical of many neurologic diseases.