Liver X receptors and inflammatory-induced C/EBPb selectively cooperate to control CD38 transcription.

Introduction: Macrophages abundantly express liver X receptors (LXRs), which are ligand-dependent transcription factors and sensors of several cholesterol metabolites. In response to agonists, LXRs induce the expression of key lipid homeostasis regulators. Crosstalk between LXRs and inflammatory signals exist in a cell type- and gene-specific manner.

Immunometabolic Effect of Nitric Oxide on Human Macrophages Challenged With the SARS-CoV2-Induced Cytokine Storm. A Fluxomic Approach.

The cytokine storm associated with SARS-CoV-2 infection is one of the most distinctive pathological signatures in COVID-19 patients. Macrophages respond to this pro-inflammatory challenge by reprogramming their functional and metabolic phenotypes. Interestingly, human macrophages fail to express the inducible form of the NO synthase (NOS2) in response to pro-inflammatory activation and, therefore, NO is not synthesized by these cells.

Water quality trends of streams in Puerto Rico: Evaluating 50 years of the Clean Water Act.

Water quality regulations entail a substantial commitment of resources from governments and private entities. It is important to continually evaluate the effectiveness of these regulations to ensure they are having the intended impact. In this paper, we evaluated nutrient data as indicators of primary productivity and dissolved oxygen (DO) concentrations and pH as response variables to assess historical water quality trends from 55 stations of Puerto Rico.

Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver.

Preclinical and clinical studies suggest that hypothyroidism might cause hepatic endocrine and metabolic disturbances with features that mimic deficiencies of testosterone and/or GH. The absence of physiological interactions between testosterone and GH can be linked to male differentiated liver diseases. Testosterone plays relevant physiological effects on somatotropic-liver axis and liver composition and the liver is a primary organ of interactions between testosterone and GH.

Pore-forming activity of pneumolysin disrupts the paracellular localization of the epithelial adherens junction protein E-cadherin.

a common cause of community-acquired bacterial pneumonia, can cross the respiratory epithelial barrier to cause lethal septicemia and meningitis. pore-forming toxin pneumolysin (PLY) triggers robust neutrophil (PMN) infiltration that promotes bacterial transepithelial migration and disseminated disease in mice. Apical infection of polarized respiratory epithelial monolayers by at a multiplicity of infection (MOI) of 20 resulted in recruitment of PMNs, loss of 50% of the monolayer, and PMN-dependent bacterial translocation.

Regulation of metabolic and transcriptional responses by the thyroid hormone in cellular models of murine macrophages.

Oncogene-immortalized bone marrow-derived macrophages are considered to be a good model for the study of immune cell functions, but the factors required for their survival and proliferation are still unknown. Although the effect of the thyroid hormones on global metabolic and transcriptional responses in macrophages has not yet been examined, there is increasing evidence that they could modulate macrophage functions. We show here that the thyroid hormone T3 is an absolute requirement for the growth of immortal macrophages.

Dynamic Python-Based Method Provides Quantitative Analysis of Intercellular Junction Organization During Infection of the Respiratory Epithelium.

Many respiratory pathogens compromise epithelial barrier function during lung infection by disrupting intercellular junctions, such as adherens junctions and tight junctions, that maintain intercellular integrity. This includes , a leading cause of pneumonia, which can successfully breach the epithelial barrier and cause severe infections such as septicemia and meningitis. Fluorescence microscopy analysis on intercellular junction protein manipulation by respiratory pathogens has yielded major advances in our understanding of their pathogenesis.

Development, Implementation and Initial Results of CDSS Recommendations for Patients at Risk of Hereditary Breast Cancer.

Breast cancer represents 23% of all cancers diagnosed among women each year. BRCA1 and BRCA2 are tumor suppressor genes related to the most frequent form of hereditary breast and ovarian cancer, as well as other types of cancer. The aim of this work is to describe the development of Clinical Decision Support Systems (CDSS) for referral to genetic counseling in patients at increased risk of pathogenic variants in BRCA1 and BRCA2, and to describe results during the pilot study implementation (from January 5, 2021 to March 5, 2021).

Tana, a Healthcare Chatbot to Help Patients During the COVID-19 Pandemic at a University Hospital in Argentina.

A Chatbot or Conversational Agent is a computer application that simulates the conversation with a human person (by text or voice), giving automated responses to people's needs. In the healthcare domain, chatbots can be beneficial to help patients, as a complement to care by health personnel, especially in times of high demand or constrained resources such as the COVID-19 Pandemic. In this paper we share the design and implementation of a healthcare chatbot called Tana at the Hospital Italiano de Buenos Aires.

Ecological characterization of a cutaneous leishmaniasis outbreak through remotely sensed land cover changes.

In this work we assessed the environmental factors associated with the spatial distribution of a cutaneous leishmaniasis (CL) outbreak during 2015-2016 in north-eastern Argentina to understand its typical or atypical eco-epidemiological pattern. We combined locations of human CL cases with relevant predictors derived from analysis of remote sensing imagery in the framework of ecological niche modelling and trained MaxEnt models with cross-validation for predictors estimated at different buffer areas relevant to CL vectors (50 and 250 m radii). To account for the timing of biological phenomena, we considered environmental changes occurring in two periods, 2014-2015 and 2015-2016.

Activation of LXR Nuclear Receptors Impairs the Anti-Inflammatory Gene and Functional Profile of M-CSF-Dependent Human Monocyte-Derived Macrophages.

Liver X Receptors (LXR) control cholesterol metabolism and exert anti-inflammatory actions but their contribution to human macrophage polarization remains unclear. The LXR pathway is enriched in pro-inflammatory macrophages from rheumatoid arthritis as well as in tumors-associated macrophages from human tumors. We now report that LXR activation inhibits the anti-inflammatory gene and functional profile of M-CSF-dependent human macrophages, and prompts the acquisition of a pro-inflammatory gene signature, with both effects being blocked by an LXR inverse agonist.

Crosstalk Between LXR and Caveolin-1 Signaling Supports Cholesterol Efflux and Anti-Inflammatory Pathways in Macrophages.

Macrophages are immune cells that play crucial roles in host defense against pathogens by triggering their exceptional phagocytic and inflammatory functions. Macrophages that reside in healthy tissues also accomplish important tasks to preserve organ homeostasis, including lipid uptake/efflux or apoptotic-cell clearance. Both homeostatic and inflammatory functions of macrophages require the precise stability of lipid-rich microdomains located at the cell membrane for the initiation of downstream signaling cascades.

Pharmacologic Activation of LXR Alters the Expression Profile of Tumor-Associated Macrophages and the Abundance of Regulatory T Cells in the Tumor Microenvironment.

Liver X receptors (LXR) are transcription factors from the nuclear receptor family that are activated by oxysterols and synthetic high-affinity agonists. In this study, we assessed the antitumor effects of synthetic LXR agonist TO901317 in a murine model of syngeneic Lewis Lung carcinoma. Treatment with TO901317 inhibited tumor growth in wild-type, but not in LXR-deficient mice, indicating that the antitumor effects of the agonist depends on functional LXR activity in host cells.

Interaction of MDIMP with the Voltage-Gated Calcium Channels.

Amino acid-derived isoindolines are synthetic compounds that were created with the idea of investigating their biological actions. The amino acid moiety was included on the grounds that it may help to avoid toxic effects. Recently, the isoindoline MDIMP was shown to inhibit both cardiac excitation-contraction coupling and voltage-dependent calcium channels.

A comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants.

Background: The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two affected first degree relatives, with an estimated incidence of 4%-10%. The genetic basis is unknown in the majority of families although around 10%-13% of families carry germline mutations in known genes associated with hereditary cancer and pancreatitis syndromes.

Ca Channels Mediate Bidirectional Signaling between Sarcolemma and Sarcoplasmic Reticulum in Muscle Cells.

The skeletal muscle and myocardial cells present highly specialized structures; for example, the close interaction between the sarcoplasmic reticulum (SR) and mitochondria-responsible for excitation-metabolism coupling-and the junction that connects the SR with T-tubules, critical for excitation-contraction (EC) coupling. The mechanisms that underlie EC coupling in these two cell types, however, are fundamentally distinct. They involve the differential expression of Ca channel subtypes: Ca1.

Seroprevalence of spotted fever group rickettsiae in canines along the United States-Mexico border.

Portions of northern Mexico are experiencing a re-emergence of Rocky Mountain spotted fever (RMSF), a tickborne disease caused by Rickettsia rickettsii, a member of the spotted fever group of rickettsiae (SFGR). Infection with R. rickettsii can result in serious and life-threatening illness in people and dogs.

SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity.

Succinate is a signaling metabolite sensed extracellularly by succinate receptor 1 (SUNCR1). The accumulation of succinate in macrophages is known to activate a pro-inflammatory program; however, the contribution of SUCNR1 to macrophage phenotype and function has remained unclear. Here we found that activation of SUCNR1 had a critical role in the anti-inflammatory responses in macrophages.

LXR Signaling Regulates Macrophage Survival and Inflammation in Response to Ionizing Radiation.

Purpose: To evaluate the role of liver X receptor (LXR) nuclear receptors on irradiation-induced cell death and polarization of macrophages and the potential implications in the context of radiation therapy treatment of cancer.

Methods And Materials: Primary and immortalized murine bone marrow-derived macrophages (BMDMs) from wild type or LXR double knock-out mice were exposed to gamma irradiation. Subsequently, analysis of LXR signaling on cell proliferation and cytotoxicity induced by ionizing radiation was determined by time-lapse photomicroscopy.

Analysis of LXR Nuclear Receptor Cistrome Through ChIP-Seq Data Bioinformatics.

Liver X receptors are members of the nuclear receptor superfamily of transcription factors. The LXR genes (NR1H2 and NR1H3) encode for two different proteins referred to as LXRα and LXRβ. Each LXR presents diverse tissue distribution but similar target DNA-binding elements and ligands.

Bone Marrow-Derived Macrophage Immortalization of LXR Nuclear Receptor-Deficient Cells.

Macrophages are professional phagocytic cells that play key roles in innate and adaptive immunity, metabolism, and tissue homeostasis. Lipid metabolism is tightly controlled at the transcriptional level, and one of the key players of this regulation in macrophages and other cell types is the LXR subfamily of nuclear receptors (LXRα and LXRβ). The use of LXR double knockout (LXR-DKO) macrophages in vitro has yielded extensive benefits in metabolism research, but this technique is hindered by primary macrophage cell expansion capability, which diminishes along terminal cell differentiation process.

Common and Differential Transcriptional Actions of Nuclear Receptors Liver X Receptors α and β in Macrophages.

The liver X receptors α and β (LXRα and LXRβ) are oxysterol-activated transcription factors that coordinately regulate gene expression that is important for cholesterol and fatty acid metabolism. In addition to their roles in lipid metabolism, LXRs participate in the transcriptional regulation of macrophage activation and are considered potent regulators of inflammation. LXRs are highly similar, and despite notable exceptions, most of their reported functions are substantially overlapping.

Phenalenone-photodynamic therapy induces apoptosis on human tumor cells mediated by caspase-8 and p38-MAPK activation.

Photodynamic therapy (PDT) is a rising and hopeful treatment for solid tumors and others malignancies. PDT uses harmless visible light to activate a tumor-associated photosensitizer (PS). The excited PS generates cytotoxic reactive oxygen species (ROS) that induce damage and death of tumor cells.

Considerations on the Species Complex of the Cortelezzii series (Diptera: Psychodidae) and Description of Evandromyia chacuensis sp. nov., a New Phlebotomine Species of the Chaco Region, Argentina.

A new species of phlebotomine sand fly is described and illustrated based on male and female specimens collected in rural and semi-urban areas of the Chaco Province, Argentina. A separation of the Cortelezzii series in two species complexes is proposed, as is a species key for its identification. The morphological characters of the new species permit its inclusion in the Cortelezzii series of genus Evandromyia, subgenus Barrettomyia (Diptera: Psychodidae).