Prognostic Significance of Systemic Inflammation Markers in Testicular and Penile Cancer: A Narrative Review of Current Literature.

In contemporary clinical practice, biomarkers are indispensable in the assessment and management of oncological patients. Although established serum tumor markers (beta human chorionic gonadotropin (bHCG), alpha fetoprotein (AFP), and lactate dehydrogenase (LDH)) have an indisputably important role in the management of patients with testicular cancer (TC), the application of these tumor markers may be accompanied with certain limitations, implying the need for additional biomarkers. Contrary to TC, there is a lack of established serological biomarkers for penile cancer (PC) and the management of this urological malignancy is based on multiple clinicopathological parameters.

The (rs156697) Polymorphism Modifies Diabetic Nephropathy Risk.

Background and Objectives: In the development of type 2 diabetes mellitus (T2DM) and its complications, genetic and environmental factors play important roles. Diabetic nephropathy (DN), one of the major microangiopathic chronic diabetic complications, is associated with an increased risk of major cardiovascular events and all-cause mortality. The present study was designed to investigate the possible modifying effect of glutathione transferase polymorphisms (GSTM1, GSTT1, GSTP1 rs1138272/rs1695, GSTO1 rs4925 and GSTO2 rs156697) in the susceptibility to T2DM and diabetic nephropathy.

Polymorphisms of Antioxidant Enzymes SOD2 (rs4880) and GPX1 (rs1050450) Are Associated with Bladder Cancer Risk or Its Aggressiveness.

Background and Objectives: Oxidative stress induced by increased reactive oxygen species (ROS) production plays an important role in carcinogenesis. The entire urinary tract is continuously exposed to numerous potentially mutagenic environmental agents which generate ROS during their biotransformation. In first line defense against free radicals, antioxidant enzymes superoxide dismutase (SOD2) and glutathione peroxidase (GPX1) both have essential roles.

Effects of metformin and simvastatin treatment on ultrastructural features of liver macrophages in HFD mice.

Type 2 diabetes is a major health burden to the society. Macrophages and liver inflammation emerged as important factors in its development. We investigated ultrastructural changes in the liver, with a special emphasis on macrophages in high fat diet (HFD) fed C57BL/6 J mice treated with metformin or simvastatin, two drugs that are used frequently in diabetes.

Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer.

Chemotherapy resistance of ovarian cancer, regarded as the most lethal malignant gynecological disease, can be explained by several mechanisms, including increased activity of efflux transporters leading to decreased intracellular drug accumulation, increased efflux of the therapeutic agents from the cell by multidrug-resistance-associated protein (MRP1), enhanced DNA repair, altered apoptotic pathways, silencing of a number of genes, as well as drug inactivation, especially by glutathione transferase P1 (GSTP1). Indeed, GSTP1 has been recognized as the major enzyme responsible for the conversion of drugs most commonly used to treat metastatic ovarian cancer into less effective forms. Furthermore, GSTP1 may even be responsible for chemoresistance of non-GST substrate drugs by mechanisms such as interaction with efflux transporters or different signaling molecules involved in regulation of apoptosis.

Therapeutic vs. Suprapharmacological Metformin Concentrations: Different Effects on Energy Metabolism and Mitochondrial Function in Skeletal Muscle Cells .

Metformin is an oral antidiabetic agent that has been widely used in clinical practice for over 60 years, and is currently the most prescribed antidiabetic drug worldwide. However, the molecular mechanisms of metformin action in different tissues are still not completely understood. Although metformin-induced inhibition of mitochondrial respiratory chain Complex I and activation of AMP-activated protein kinase have been observed in many studies, published data is inconsistent.

Correlation Between Proteolytic Activity and Abdominal Aortic Aneurysm Wall Morphology with Intraluminal Thrombus Volume.

Background: The aim of this study was to examine the influence of intraluminal thrombus (ILT) volume on the level of proteolytic activity and the content of abdominal aortic aneurysm (AAA) wall.

Methods: The research was designed as a cross-sectional study at the Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia in the period from April 2017 to February 2018. During this period, a total of 155 patients with asymptomatic AAA underwent open surgical treatment and 50 were included in the study based on inclusion and exclusion criteria.

Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line.

Aims: Many patients with glioblastoma (GBM) suffer from comorbid neurological/psychiatric disorders and, therefore, are treated with psychopharmacological agents. Diazepam (DIA) is widely adopted to treat status epilepticus, alleviate anxiety, and inhibit chemotherapy-associated delayed emesis in GBM patients. Even though temozolomide (TMZ) and DIA could be found as possible combination therapy in clinical practice, there are no reports of their combined effects in GBM.

Interplay between Comprehensive Inflammation Indices and Redox Biomarkers in Testicular Germ-Cell Tumors.

Sustained and dysregulated inflammation, concurrent tumor-induced immune suppression, and oxidative stress are profoundly involved in cancer initiation, presentation, and perpetuation. Within this prospective study, we simultaneously analyzed the preoperative indices of systemic inflammatory response and the representative byproducts of oxidative DNA, protein, and lipid damage with the aim of evaluating their clinical relevance among patients diagnosed with testicular germ-cell tumors (GCT). In the analytical cohort (n = 88, median age 34 years), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and C-reactive protein (CRP) were significantly altered in patients with a higher tumor stage (p < 0.

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID.

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID.

Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells.

We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well-known reactive oxidative species- (ROS-) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis-like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome-associated LC3-II protein, degradation of p62, and increased expression of beclin-1.

rs4880 and rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort.

Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients' clinical manifestations might be affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms rs6721961, rs4880, rs1050450, rs8177412, and (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters. The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals.

, and Polymorphisms Modify Susceptibility to Developing COVID-19.

Based on the close relationship between dysregulation of redox homeostasis and immune response in SARS-CoV-2 infection, we proposed a possible modifying role of and glutathione transferase omega () polymorphisms in the individual propensity towards the development of clinical manifestations in COVID-19. The distribution of polymorphisms in (rs4646116), (rs4925) and (rs156697) were assessed in 255 COVID-19 patients and 236 matched healthy individuals, emphasizing their individual and haplotype effects on disease development and severity. Polymorphisms were determined by the appropriate qPCR method.

The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor.

The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development of testicular germ cell tumor (GCT), as well as the progression of the disease. (rs6721961), (rs1332018), (rs4880) and (rs8177412) polymorphisms were assessed in 88 patients with testicular GCT (52 with seminoma) and 88 age-matched controls. The plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), thiol groups and the plasma activity of glutathione peroxidase were measured.

and Variant Alleles Affect Susceptibility and Severity of COVID-19.

Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases , , , ( and ), and were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. polymorphisms were determined by appropriate PCR methods.

Association of GSTO1, GSTO2, GSTP1, GPX1 and SOD2 polymorphism with primary open angle glaucoma.

It is becoming increasingly evident that oxidative stress has a supporting role in pathophysiology and progression of primary open angle glaucoma (POAG). The aim of our study was to assess the association between polymorphisms in genes encoding enzymes involved in redox homeostasis, mitochondrial superoxide dismutase (SOD2), glutathione peroxidase (GPX1) and glutathione transferases (GSTs) with susceptibility to POAG. Single nucleotide polymorphisms in GST omega (GSTO1rs4925, GSTO2 rs156697), pi 1 (GSTP1 rs1695), as well as GPX1 (rs1050450) and SOD2 (rs4880) were determined by quantitative polymerase chain reaction (qPCR) in 102 POAG patients and 302 respective controls.

In vitro models of insulin resistance: Mitochondrial coupling is differently affected in liver and muscle cells.

Mitochondrial dysfunction in diabetes is a widely studied topic, but inconsistency in literature data suggests a need for valid and reproducible models that will help to clarify this interaction. We aimed to establish insulin resistance models using chronic high insulin treatment in two cell types: myocytes and hepatocytes, characterise them in terms of mitochondrial function and compare them to the widely used palmitate-induced model of insulin resistance. We found that insulin lowered phosphorylation of Akt while not affecting cell viability, ROS production, mitochondrial morphology or respiration, and caused decrease in mitochondrial coupling only in muscle but not in liver cells.

Selected polyoxopalladates as promising and selective antitumor drug candidates.

Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na[PdAsO(OH)]·42HO (Pd), Na[SrPdO(OH)(PhAsO)(OAc)]·2NaOAc·32HO (SrPd), Na[Pd(AsPh)O]·23HO (PdL), Na[SnOPd(PO)]·43HO (SnPd), and Na[PbOPd(PO)]·38HO (PbPd)), as the largest subset of PONMs. A pure inorganic, Pd, was found as the most potent and selective antineuroblastoma agent with IC values (µM) of 7.

B7 homologue 3 as a prognostic biomarker and potential therapeutic target in gastrointestinal tumors.

The most common digestive system (DS) cancers, including tumors of the gastrointestinal tract (GIT) such as colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC) as well as tumors of DS accessory organs such as pancreatic and liver cancer, are responsible for more than one-third of all cancer-related deaths worldwide, despite the progress that has been achieved in anticancer therapy. Due to these limitations in treatment strategies, oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity. These studies led to new molecular target-driven therapeutic approaches.

Time Course of Redox Biomarkers in COVID-19 Pneumonia: Relation with Inflammatory, Multiorgan Impairment Biomarkers and CT Findings.

Although the original data on systemic oxidative stress in COVID-19 patients have recently started to emerge, we are still far from a complete profile of changes in patients' redox homeostasis. We aimed to assess the extent of oxidative damage of proteins, lipids and DNA during the course of acute disease, as well as their association with CT pulmonary patterns. In order to obtain more insight into the origin of the systemic oxidative stress, the observed parameters were correlated with inflammatory biomarkers and biomarkers of multiorgan impairment.

Glutathione S-Transferase Polymorphisms and Clinical Characteristics in Autism Spectrum Disorders.

Autism spectrum disorders (ASD) are a heterogeneous group of developmental disorders, with different levels of symptoms, functioning, and comorbidities. Recent findings suggested that oxidative stress and genetic variability in glutathione S-transferases (GSTs) might increase the risk of ASD development. We aimed to determine whether GST polymorphisms influence the severity of symptoms as well as the cognitive and adaptive abilities in children with ASD.

Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus.

Early life stress has profound effects on the development of the central nervous system. We exposed 9-day-old rat pups to a 24 h maternal deprivation (MD) and sacrificed them as young adults (60-day-old), with the aim to study the effects of early stress on forebrain circuitry. We estimated numbers of various immunohistochemically defined interneuron subpopulations in several neocortical regions and in the hippocampus.