Search results for "mediat"

Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase

2016

Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (…

The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated trans…

2017

The type I interferon (IFN) response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV) that shuts down signaling following pattern recognition receptor (PRR) sensing. Screening of an MCMV open reading frame (ORF) library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR). Using a series of luciferase-based reporters with specific transcription factor binding sites, …

The Elastin-Derived Peptide VGVAPG Does Not Activate the Inflammatory Process in Mouse Cortical Astrocytes In Vitro.

2019

Abstract During vascular aging or in pathological conditions in humans, elastin is degraded and its by-products, the elastin-derived peptides (EDPs), enter the blood circulation. EDPs may be detected in the serum of healthy subjects or people who suffered a stroke. Moreover, recent evidence suggests a potential role of inflammatory mechanisms in neurological conditions, which are usually not categorized as inflammatory. Therefore, the present in vitro study was conducted to investigate the impact of the VGVAPG peptide on the activation of inflammatory process in mouse primary astrocytes, which were maintained in phenol red-free DMEM/F12 supplemented with 10% fetal bovine serum. The cells we…

Focal Adhesion Genes Refine the Intermediate-Risk Cytogenetic Classification of Acute Myeloid Leukemia

2018

© 2018 by the authors.

Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores

2021

Background & Aims: Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification. Methods: We examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic …

2017

Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of …

Malignant Rhabdoid Tumor in the Gastric Wall of an Aged Orangutan (Pongo pygmaeus)

1994

A 34-year-old female orangutan ( Pongo pygmaeus) developed renal failure and became uremic. At necropsy, large gastric masses were present around the cardia and in the corpus. Abdominal metastases occurred in the liver, pancreas, and right ovary. Light microscopic examination of the tumor revealed polygonal cells with vesicular nuclei and prominent nucleoli. The growth pattern was predominantly solid. Focal areas contained excentric cytoplasmic intermediate filament inclusions, as identified by immunohistochemistry and electron microscopy. Immunohisiochemical procedures demonstrated mainly the vimentin type of intermediate filaments. Except for occasional cytokeratin, other intermediate fil…

In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis

2017

AbstractAutoimmune hypophysitis (AH) is a chronic inflammatory disease characterized by infiltration of T and B lymphocytes in the pituitary gland. The mechanisms through which infiltrating lymphocytes cause disease remain unknown. Using a mouse model of AH we assessed whether T lymphocytes undergo activation in the pituitary gland. Infiltrating T cells co-localized with dendritic cells in the pituitary and produced increased levels of interferon-γ and interleukin-17 upon stimulation in vitro. Assessing proliferation of CD3- and B220-postive lymphocytes by double immunohistochemistry (PCNA-staining) and flow cytometry (BrdU incorporation) revealed that a discrete proportion of infiltrating …

Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity.

2020

The memory CD8 T-cell pool must select for clones that bind immunodominant epitopes with high affinity to efficiently counter reinfection. At the same time, it must retain a level of clonal diversity to allow recognition of pathogens with mutated epitopes. How the level of diversity within the memory pool is controlled is unclear, especially in the context of a selective drive for antigen affinity. We find that preservation of clones that bind the activating antigen with low affinity depends on expression of the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the prosurvival protein…

DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

2019

Background Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. Methods We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring. Results We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10−7) associated with exposure to maternal smoking in adolesc…