Functional and phenotypic changes in natural killer cells expressing immune checkpoint receptors PD-1, CTLA-4, LAG-3, and TIGIT in non-small cell lung cancer: the comparative analysis of tumor microenvironment, peripheral venous blood, and tumor-draining veins.

Natural killer (NK) cells are a cytotoxic subset of innate lymphoid cells and have key roles in antitumoral immunity. This study evaluates the roles of immune checkpoint receptors on NK cell phenotype and functions both before and after circulation through tumor tissue. Twenty non-small cell lung cancer patients undergoing surgery and 21 healthy controls were included.

Determination of 16 European Priority Polycyclic Aromatic Hydrocarbons in Doner Kebab Varieties Cooked Under Different Heating Sources.

Doner kebab is a traditional Turkish meat product produced from lamb, beef or poultry meat seasoned with a blend of spices such as salt, black pepper, cumin, thyme and/or sauces. The aim of this study was to determine 16 EU priority polycyclic aromatic hydrocarbons (PAHs) in doner kebabs cooked under four different heating sources (electricity, open gas, wood and charcoal grilling). For this purpose, 200 meat doner and 200 chicken doner kebab samples were obtained randomly from various buffets and restaurants located in Istanbul and analyzed by means of GC-MS.

Macrophage Activation Syndrome in Coinciding Pandemics of Obesity and COVID-19: Worse than Bad.

Epigenetic changes have long-lasting impacts, which influence the epigenome and are maintained during cell division. Thus, human genome changes have required a very long timescale to become a major contributor to the current obesity pandemic. Whereas bidirectional effects of coronavirus disease 2019 (COVID-19) and obesity pandemics have given the opportunity to explore, how the viral microribonucleic acids (miRNAs) use the human's transcriptional machinery that regulate gene expression at a posttranscriptional level.

Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.

Higher body fat content is related to a higher risk of mortality, and obesity-related cancer represents approximately 40% of all cancer patients diagnosed each year. Furthermore, epigenetic mechanisms are involved in cellular metabolic memory and can determine one's predisposition to being overweight. Low-grade chronic inflammation, a well-established characteristic of obesity, is a central component of tumor development and progression.

Targeted Nano-Based Systems for the Anti-Obesity Agent's Delivery.

Obesity is a global health concern and a chronic disease that is accompanied by excessive fat storage in adipose and nonadipose tissues. An increase in the body-mass index (BMI) is directly proportional to the 2- to 3.9-fold increase in all-cause mortality in obesity.

Tryptophan Metabolism in Obesity: The Indoleamine 2,3-Dioxygenase-1 Activity and Therapeutic Options.

Obesity activates both innate and adaptive immune responses in adipose tissue. Adipose tissue macrophages are functional antigen-presenting cells that promote the proliferation of interferon-gamma (IFN-γ)-producing cluster of differentiation (CD)4+ T cells in adipose tissue of obese subjects. The increased formation of neopterin and degradation of tryptophan may result in decreased T-cell responsiveness and lead to immunodeficiency.

MicroRNAs as Epigenetic Regulators of Obesity.

In obesity, the process of adipogenesis largely determines the number of adipocytes in body fat depots. Adipogenesis is regulated by several adipocyte-selective micro-ribonucleic acids (miRNAs) and transcription factors that modulate adipocyte proliferation and differentiation. However, some miRNAs block the expression of master regulators of adipogenesis.

Message Transmission Between Adipocyte and Macrophage in Obesity.

Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction have primary importance in obesity. Large quantity of macrophages is accumulated by different mechanisms in obese adipose tissue.

Mechanism of Obesity-Related Lipotoxicity and Clinical Perspective.

The link between cellular exposure to fatty acid species and toxicity phenotypes remains poorly understood. However, structural characterization and functional profiling of human plasma free fatty acids (FFAs) analysis has revealed that FFAs are located either in the toxic cluster or in the cluster that is transcriptionally responsive to lipotoxic stress and creates genetic risk factors. Genome-wide short hairpin RNA screen has identified more than 350 genes modulating lipotoxicity.

The Checkpoints of Intestinal Fat Absorption in Obesity.

In this chapter, intestinal lipid transport, which plays a central role in fat homeostasis and the development of obesity in addition to the mechanisms of fatty acids and monoacylglycerol absorption in the intestinal lumen and reassembly of these within the enterocyte was described. A part of the resynthesized triglycerides (triacylglycerols; TAG) is repackaged in the intestine to form the hydrophobic core of chylomicrons (CMs). These are delivered as metabolic fuels, essential fatty acids, and other lipid-soluble nutrients, from enterocytes to the peripheral tissues following detachment from the endoplasmic reticulum membrane.

Comparison of Immune Checkpoint Molecule Expression in Different Years of House Dust Mite Subcutaneous Immunotherapy on CD4 T and Treg Cells in Children with Allergic Rhinitis.

Background: Allergen-specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution.

Aims: To investigate how the duration of house dust mite (HDM) subcutaneous immunotherapy (SCIT) affects the expression of major immune checkpoint (ICP) molecules on the surface of CD4 T-helper and regulatory T (Treg) cells.

Study Design: Cross-sectional study.

Mediastinal lymph node removal modulates natural killer cell exhaustion in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death globally. In this study, the effect of complete removal of mediastinal lymph nodes by video-assisted mediastinoscopic lymphadenectomy (VAMLA) on natural killer (NK) cell phenotype and functions in patients with NSCLC was evaluated. The study included 21 NSCLC patients (cIA-IVA) undergoing VAMLA staging and 33 healthy controls.

Does lithium attenuate the liver damage due to oxidative stress and liver glycogen depletion in experimental common bile duct obstruction?

In extrahepatic cholestasis, the molecular mechanisms of liver damage due to bile acid accumulation remain elusive. In this study, the activation of glutamatergic receptors was hypothesized to be responsible for bile acid-induced oxidative stress and liver damage. Recent evidence showed that lithium, as an N-methyl-d-aspartate receptor (NMDAR) GluN2B subunit inhibitor, may act on the glutamate/NMDAR signaling axis.

Effects of co-selection of antibiotic-resistance and metal-resistance genes on antibiotic-resistance potency of environmental bacteria and related ecological risk factors.

The inadequate elimination of micropollutants in wastewater treatment plants (WWTP), cause to increase in the incidence of antibiotic resistant bacterial strains. Growth of microbial pathogens in WWTP is one of the serious public health problems. The widespread and simultaneous emergence of antibiotic resistance genes (ARGs) and heavy metal resistance genes (HMRGs) in the environment with heavy metals create persistent and selective pressure for co-selection of both genes on environmental microorganisms.

Can iron, zinc, copper and selenium status be a prognostic determinant in COVID-19 patients?

In severe COVID-19, the levels of iron (Fe), copper (Cu), zinc (Zn) and selenium (Se), do not only regulate host immune responses, but modify the viral genome, as well. While low serum Fe concentration is an independent risk factor for the increased death rate, Zn controls oxidative stress, synthesis of inflammatory cytokines and viral replication. Therefore, Zn deficiency associates with a worse prognosis.

Mediastinal lymph node removal ameliorates cytotoxic T-lymphocyte functions in patients with non-small cell lung cancer.

Introduction: Mediastinal lymph node (MLN) removal by video-assisted mediastinoscopic lymphadenectomy (VAMLA) for preoperative cancer staging was reported to be associated with increased survival. The aim of this study was to evaluate the immunologic effects of complete MLN removal by VAMLA on cytotoxic T lymphocyte (CTL) phenotype and function.

Methods: Seventeen patients with non-small cell lung cancer (NSCLC) (stage cT1-4N0-3M0-1A) and 20 healthy participants were included in this study.

The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice.

Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy.

The effect of environmental diesel exhaust pollution on SARS-CoV-2 infection: The mechanism of pulmonary ground glass opacity.

Diesel exhaust particles (DEP) are the major components of atmospheric particulate matter (PM) and chronic exposure is recognized to enhance respiratory system complications. Although the spread of SARS-CoV-2 was found to be associated with the PMs, the mechanism by which exposure to DEP increases the risk of SARS-CoV-2 infection is still under discussion. However, diesel fine PM (dPM) elevate the probability of SARS-CoV-2 infection, as it coincides with the increase in the number of ACE2 receptors.

Current opinion in neurological manifestations of SARS-CoV-2 infection.

Neurological symptoms occur in approximately one-third of hospitalized patients with coronavirus disease 2019 (COVID-19). Among these symptoms, hypoxic encephalopathy develops in one-fifth of severe cases, while ischemic strokes due to thrombotic complications are common in one-third of COVID-19 intensive care patients. Brain involvement of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is eventuated by several routes, including hematogenous spread, transsynaptic entry through infected neurons, olfactory nerve, ocular epithelium, vascular endothelium, and impaired blood-brain barrier.

Indoleamine 2,3-Dioxygenase Activity-Induced Acceleration of Tumor Growth, and Protein Kinases-Related Novel Therapeutics Regimens.

Indoleamine 2,3-dioxygenase (IDO) is overexpressed in response to interferon-gamma (IFN-γ). IDO-mediated degradation of tryptophan (Trp) along the kynurenine (Kyn) pathway by immune cells is associated with the anti-microbial, and anti-tumor defense mechanisms. In contrast, IDO is constitutively expressed by various tumors and creates an immunosuppressive microenvironment around the tumor tissue both by depletion of the essential amino acid Trp and by formation of Kyn, which is immunosuppressive metabolite of Trp.

Alzheimer's Disease and Protein Kinases.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and accounts for more than 60-80% of all cases of dementia. Loss of pyramidal neurons, extracellular amyloid beta (Abeta) accumulated senile plaques, and neurofibrillary tangles that contain hyperphosphorylated tau constitute the main pathological alterations in AD.Synaptic dysfunction and extrasynaptic N-methyl-D-aspartate receptor (NMDAR) hyperactivation contributes to excitotoxicity in patients with AD.

N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia.

Although stroke is very often the cause of death worldwide, the burden of ischemic and hemorrhagic stroke varies between regions and over time regarding differences in prognosis, prevalence of risk factors, and treatment strategies. Excitotoxicity, oxidative stress, dysfunction of the blood-brain barrier, neuroinflammation, and lysosomal membrane permeabilization, sequentially lead to the progressive death of neurons. In this process, protein kinases-related checkpoints tightly regulate N-methyl-D-aspartate (NMDA) receptor signaling pathways.

Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.

Type 2 diabetes (T2D) is a worldwide serious public health problem. Insulin resistance and β-cell failure are the two major components of T2D pathology. In addition to defective endoplasmic reticulum (ER) stress signaling due to glucolipotoxicity, β-cell dysfunction or β-cell death initiates the deleterious vicious cycle observed in T2D.