protein expression is reduced in high grade astrocytomas which is not caused by the methylation of its promoter.

Introduction: Epigenetics play a vital role in stratifying CNS tumors and gliomas. The importance of studying Secreted frizzled-related protein 4 (SFRP4) in gliomas is to improve diffuse glioma methylation profiling. Here we examined the methylation status of promoter and the level of its protein expression in diffuse gliomas WHO grades 2-4.

Overview of the Lipid Peroxidation Measurements in Patients by the Enzyme-Linked Immunosorbent Assay Specific for the 4-Hydroxynonenal-Protein Adducts (4-HNE-ELISA).

Oxidative stress often affects the structure and metabolism of lipids, which in the case of polyunsaturated free fatty acids (PUFAs) leads to a self-catalysed chain reaction of lipid peroxidation (LPO). The LPO of PUFAs leads to the formation of various aldehydes, such as malondialdehyde, 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal, and 4-oxo-2-nonenal. Among the reactive aldehydes, 4-HNE is the major bioactive product of LPO, which has a high affinity for binding to proteins.

The 4-Hydroxynonenal-Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?

It is well known that oxidative stress and lipid peroxidation (LPO) play a role in physiology and pathology. The most studied LPO product with pleiotropic capabilities is 4-hydroxynonenal (4-HNE). It is considered as an important mediator of cellular signaling processes and a second messenger of reactive oxygen species.

Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer.

An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated with prostate cancer progression a few decades ago, the knowledge of the involvement of 4-HNE in prostate cancer tumorigenesis is limited. This study investigated the appearance of 4-HNE-protein adducts in prostate cancer tissue by immunohistochemistry using a genuine 4-HNE monoclonal antibody.

Papillary tumor of the pineal region in pediatric patient - A case report.

Background: Papillary tumor of the pineal region (PTPR) represents a rare and histologically distinct subgroup of tumors originating in the pineal region. Few pediatric cases have been reported so far in the literature; therefore, clinical data are scarce.

Case Description: We describe a case of PTPR in a 9-year-old girl who presented with a 5-month history of excessive appetite and weight gain.

4-Hydroxynonenal Modulates Blood-Brain Barrier Permeability In Vitro through Changes in Lipid Composition and Oxidative Status of Endothelial Cells and Astrocytes.

Blood brain barrier (BBB) is a dynamic interface responsible for proper functioning of brain, but also a major obstacle for effective treatment of neurological diseases. Increased levels of free radicals, in high ferrous and high lipid content surrounding, induce lipid peroxidation, leading to production of 4-hydroxynonenal (HNE). HNE modifies all key proteins responsible for proper brain functioning thus playing a major role in the onset of neurological diseases.

Spontaneous Regression of Cancer: Revealing Granulocytes and Oxidative Stress as the Crucial Double-edge Sword.

Background: It is commonly believed that cancer development is irreversible, organ-specific as well as systemic malignant disorder, often associated with harmful oxidative stress and inflammation. However, there are also well-documented cases of spontaneous cancer regression, the causative mechanisms of which are not understood. It is known that inflammation is a negative pathophysiological process that may support the development of cancer, but it is also believed that the immune system as well as oxidative stress play important roles in prevention of cancer development and defense against tumor progression.

Case Report: Advanced Skeletal Muscle Imaging in S-Adenosylhomocysteine Hydrolase Deficiency and Further Insight Into Muscle Pathology.

Introduction: S-Adenosylhomocysteine hydrolase deficiency (SAHHD) is a rare inherited multisystemic disease with muscle involvement as one of the most prominent and poorly understood features. To get better insight into muscle involvement, skeletal muscles were analyzed by magnetic resonance imaging (MRI) and MR spectroscopy (MRS) in three brothers with SAHHD in the different age group.

Method: The study was based on analysis of MRI and MRS of skeletal muscles of the lower and the proximal muscle groups of the upper extremities in three SAHHD patients.

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19.

A recent comparison of clinical and inflammatory parameters, together with biomarkers of oxidative stress, in patients who died from aggressive COVID-19 and survivors suggested that the lipid peroxidation product 4-hydroxynonenal (4-HNE) might be detrimental in lethal SARS-CoV-2 infection. The current study further explores the involvement of inflammatory cells, systemic vascular stress, and 4-HNE in lethal COVID-19 using specific immunohistochemical analyses of the inflammatory cells within the vital organs obtained by autopsy of nine patients who died from aggressive SAR-CoV-2 infection. Besides 4-HNE, myeloperoxidase (MPO) and mitochondrial superoxide dismutase (SOD2) were analyzed alongside standard leukocyte biomarkers (CDs).

Oxidative stress and regeneration.

Regeneration is the process of replacing/restoring a damaged cell/tissue/organ to its full function and is limited respecting complexity of specific organ structures and the level of differentiation of the cells. Unlike physiological cell turnover, this tissue replacement form is activated upon pathological stimuli such as injury and/or disease that usually involves inflammatory response. To which extent will tissue repair itself depends on many factors and involves different mechanisms.

Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19.

Major findings of the pilot study involving 21 critically ill patients during the week after admission to the critical care unit specialized for COVID-19 are presented. Fourteen patients have recovered, while seven passed away. There were no differences between them in respect to clinical or laboratory parameters monitored.

Lipid peroxidation in brain tumors.

There is a lot of evidence showing that lipid peroxidation plays very important role in development of various diseases, including neurodegenerative diseases and brain tumors. Lipid peroxidation is achieved by two main pathways, by enzymatic or by non-enzymatic oxidation, respectively. In this paper, we focus on non-enzymatic, self-catalyzed chain reaction of poly-unsaturated fatty acid (PUFA) peroxidation generating reactive aldehydes, notably 4-hydroxynonenal (4-HNE), which acts as second messenger of free radicals and as growth regulating factor.

Methylation Patterns of , and Are Accompanied with Different Expression Levels in Human Astrocytoma.

In the present study, we investigated genetic and epigenetic changes and protein expression levels of negative regulators of Wnt signaling, , , and as well as glycogen synthase kinase 3 (GSK3β) and β-catenin in 64 human astrocytomas of grades II-IV. Methylation-specific PCR revealed promoter methylation of , , and in 38%, 43%, and 18% of samples, respectively. Grade IV comprised the lowest number of methylated cases and highest of .

Lowe syndrome - Old and new evidence of secondary mitochondrial dysfunction.

The oculocerebrorenal syndrome of Lowe (LS) is a rare, progressive, multisystemic X-linked disorder caused by mutations in OCRL gene. Patients classically present with ocular abnormalities including bilateral congenital cataracts and glaucoma, intellectual delay, severe generalized hypotonia with absent tendon reflexes, and proximal renal tubular dysfunction. Congenital bilateral cataracts and hypotonia are present at birth in almost all patients, while other classical symptoms develop gradually with variable severity.

The Appearance of 4-Hydroxy-2-Nonenal (HNE) in Squamous Cell Carcinoma of the Oropharynx.

Tumor growth is associated with oxidative stress, which causes lipid peroxidation. The most intensively studied product of lipid peroxidation is 4-hydroxy-2-nonenal (HNE), which is considered as a "second messenger of free radicals" that binds to proteins and acts as a growth-regulating signaling factor. The incidence of squamous cell carcinoma of the oropharynx is associated with smoking, alcohol and infection of human papilloma virus (HPV), with increasing incidence world-wide.

The relevance of pathophysiological alterations in redox signaling of 4-hydroxynonenal for pharmacological therapies of major stress-associated diseases.

Modern analytical methods combined with the modern concepts of redox signaling revealed 4-hydroxy-2-nonenal (4-HNE) as particular growth regulating factor involved in redox signaling under physiological and pathophysiological circumstances. In this review current knowledge of the relevance of 4-HNE as "the second messenger of reactive oxygen species" (ROS) in redox signaling of representative major stress-associated diseases is briefly summarized. The findings presented allow for 4-HNE to be considered not only as second messenger of ROS, but also as one of fundamental factors of the stress- and age-associated diseases.

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation.

Key regulators of the Wnt signalling, DVL1, DVL2 and DVL3, in astrocytomas of different malignancy grades were investigated. Markers for DVL1, DVL2 and DVL3 were used to detect microsatellite instability (MSI) and gross deletions (LOH), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three DVL proteins and transcription factors of the pathway, TCF1 and LEF1. Our findings demonstrated that MSI at all three DVL loci was constantly found across tumour grades with the highest number in grade II (P = 0.

Hypogammaglobulinemia and imaging features in a patient with infantile free sialic acid storage disease (ISSD) and a novel mutation in the SLC17A5 gene.

Background Infantile free sialic acid storage disease (ISSD) is a severe multisystemic disorder characterized by the accumulation of free sialic acid in lysosomes. Case presentation The patient presented prenatally with fetal ascites and large scrotal hernias, without pleural or pericardial effusion. During the infantile period, he was diagnosed with permanent isolated immunoglobulin G (IgG) hypogammaglobulinemia, which thus far has rarely been associated with ISSD.

Development of a novel monoclonal antibody against 4-hydroxy-2E,6Z-dodecadienal (4-HDDE)-protein adducts: Immunochemical application in quantitative and qualitative analyses of lipid peroxidation in vitro and ex vivo.

Non-enzymatic peroxidation of polyunsaturated fatty acids (PUFA) results in the formation of various α,β-unsaturated aldehydes, of which 4-hydroxyalkenals are abundant. The propensity of n-6 PUFA, such as linoleic acid, γ-linolenic acid and arachidonic acid, to undergo radical-induced peroxidation and generate 4-hydroxy-2E-nonenal (4-HNE) has been widely demonstrated. The ability of the latter to form covalent adducts with macromolecules and modify cellular functions has been linked to numerous pathological processes.

Nivolumab-induced synchronous occurrence of myositis and hypothyroidism in a patient with squamous cell lung cancer.

Aim: Alongside the proven efficacy, immunotherapy in treatment of malignant diseases can cause immune-related adverse events different from commonly known chemotherapy-related toxicities.

Case Presentation: During nivolumab treatment of metastatic squamous cell lung cancer, the patient developed a symptomatic inflammatory myositis confirmed with muscle biopsy and primary hypothyroidism. After initiation of corticosteroids and thyroid hormone replacement, the clinical and laboratory improvement occurred.

Amaranth oil reduces accumulation of 4-hydroxynonenal-histidine adducts in gastric mucosa and improves heart rate variability in duodenal peptic ulcer patients undergoing Helicobacter pylori eradication.

Helicobacter pylori-induced oxidative stress in gastric mucosa (GM) is a milieu for the development of chronic gastritis, duodenal peptic ulcer (DPU), gastric cancer, and a number of extragastric diseases. Because our previous study revealed the accumulation of the protein adducts of lipid peroxidation product 4-hydroxynonenal (HNE) in GM, which persists after eradication of H. pylori, the aim of the study was to test whether Amaranth oil supplementation in addition to standard anti-Helicobacter treatment could prevent such accumulation of HNE in GM in H.

Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients.

Objective: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype.

Methods: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery.

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies.

Unlabelled: The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue.

Methods: Nineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer.