Long-term Administration of 3-Di-O-Tolylguanidine Modulates Spatial Learning and Memory in Rats and Causes Transition in the Concentration of Neurotransmitters in the Hippocampus, Prefrontal Cortex and Striatum.

The sigma-1 and sigma-2 (σ and σ) receptors are found in high concentrations in the brain, and their altered expression leads to a variety of neuropsychiatric disorders. 3-di-tolylguanidine (DTG) stimulates the activity of both of these receptors. We assessed the effects of administering DTG to adult male Sprague Dawley rats on learning and memory consolidation processes and on the levels of neurotransmitters in selected brain structures.

The impact of changing the funding model for genetic diagnostics and improved access to personalized medicine in oncology.

Aim: In January 2017, a new funding model for diagnostic genetic testing in cancer was introduced in Poland.

Objectives: The aim of this study was to assess the impact of changing the funding model for genetic diagnosis in oncology on improving access to personalized medicine in Poland between 2017 and 2019.

Methods: The analysis included data on settlements with the National Health Fund for genetic tests in cancer under a contract of the hospital treatment type and under the contract in the type of separately contracted services between 2017 and 2019.

The effects of the recurrent social isolation stress on fear extinction and dopamine D receptors in the amygdala and the hippocampus.

Background: The present study assessed the influence of recurrent social isolation stress on the aversive memory extinction and dopamine D receptors (DR) expression in the amygdala and the hippocampus subnuclei. We also analyzed the expression of epigenetic factors potentially associated with fear extinction: miRNA-128 and miRNA-142 in the amygdala.

Methods: Male adult fear-conditioned rats had three episodes of 48 h social isolation stress before each fear extinction session in weeks intervals.

The role of the dorsal hippocampus in resistance to the development of posttraumatic stress disorder-like behaviours.

This study aimed to determine the activity of the dorsal hippocampus (dHIP) in resistance to the development of posttraumatic stress disorder (PTSD)-like behaviours. Rats were divided into resistant, PTSD(-), and susceptible, PTSD(+) groups based on the time spent in the central area in an open field test and freezing duration during exposure to an aversive context one week after stress experience (electric foot shock). The PTSD(-) rats, compared to the PTSD(+) group, had an increased concentration of corticosterone in plasma and changes in the activity of the dHIP, specifically, increased c-Fos expression in the dentate gyrus (DG) and increased Neuroligin-2 (marker of GABAergic neurotransmission) expression in the DG and CA3 area of the dHIP.

Serum microRNAs in Systemic Sclerosis, Associations with Digital Vasculopathy and Lung Involvement.

Systemic sclerosis (SSc) is an autoimmune, rare multisystem chronic disease that is still not well-understood aetiologically and is challenging diagnostically. In the literature, there are ever-increasing assumptions regarding the epigenetic mechanisms involved in SSc development; one of them is circulating microRNAs. Many of them regulate TLR pathways and are significant in autoimmune balance.

Anticancer efficacy of endo- and exogenous potent ligands acting at dopaminergic receptor-expressing cancer cells.

Cancer is one of the most common and dreaded diseases affecting the vastness of society. Unfortunately, still some people die especially when cancer is not diagnosed and thus caught early enough. On the other hand, using available chemo- or radiotherapy may result in serious side effects.

mTOR and HDAC2 are simultaneously activated during electrically induced kindling of seizures.

Although neurotrophic pathways and epigenetic processes are believed to be significant contributors to epileptogenesis and epilepsy, therapies using modulators of these targets are still lacking. BDNF-TrkB-mTOR signalling and the REST/NRSF-coREST-HDAC2 system are critical pathways responsible for neurotrophic and epigenetic processes, respectively. In our study, we assessed whether these two pathways are activated in a kindling model of seizures.

Association Between the Expression of MicroRNA-125b and Survival in Patients With Acute Coronary Syndrome and Coronary Multivessel Disease.

Background: MicroRNAs (miRNA, miR) have an undeniable physiological and pathophysiological significance and act as promising novel biomarkers. The aim of the study was to investigate blood-derived miRNAs and their association with long-term all-cause mortality in patients with multivessel disease (MVD) suffering from acute coronary syndrome (ACS).

Materials And Methods: This study was an observational prospective study, which included 90 patients with MVD and ACS.

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke.

Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS.

Increased Hippocampal Afterdischarge Threshold in Ketogenic Diet is Accompanied by Enhanced Kynurenine Pathway Activity.

The efficacy of a ketogenic diet (KD) in controlling seizure has been shown in many experimental and clinical studies, however, its mechanism of action still needs further clarification. The major goal of the present study was to investigate the influence of the commercially available KD and caloric restriction (CR) on the hippocampal afterdischarge (AD) threshold in rats, and concomitant biochemical changes, specifically concerning the kynurenine pathway, in plasma and the hippocampus. As expected, the rats on the KD showed higher AD threshold accompanied by increased plasma β-hydroxybutyrate level compared to the control group and the CR rats.

Advanced pharmacodynamics of cangrelor in healthy volunteers: a dose-finding, open-label, pilot trial.

Background: High on-treatment platelet reactivity (HTPR) remains a major problem in the acute management of ST-elevation myocardial infarction (STEMI), leading to higher rates of stent thrombosis and mortality. We aimed to investigate a novel, prehospital treatment strategy using cangrelor and tested its pharmacodynamic effects in a model using healthy volunteers.

Methods: We conducted a dose-finding, open-label, pilot trial including 12 healthy volunteers and tested three ascending bolus infusions of cangrelor (5 mg, 10 mg and 20 mg) and a bolus infusion followed by a continuous infusion via an intravenous (IV) flow regulator.

High concentration of symmetric dimethylarginine is associated with low platelet reactivity and increased bleeding risk in patients with acute coronary syndrome.

Background: Dual antiplatelet therapy (DAPT) prevents ischemic events in patients with acute coronary syndrome (ACS), but is associated with increased risk of bleeding events. Symmetric dimethylarginine (SDMA) is one of nitric oxide (NO)-related pathway metabolites and stands as a promising biomarker of early chronic kidney disease (CKD) and cardiovascular diseases (CVDs).

Objectives: Our study evaluated the role of SDMA in predicting bleeding events in patients after ACS treated with DAPT.

Pharmacological activity of extracts: pre-clinical research in view of prospective neuroprotection.

Objectives: Rooibos tea, a very popular everyday beverage made of plant material and containing multiple polyphenolic compounds, reveals an expectation to positively affect various processes observed in the pathogenesis of neurodegenerative diseases as in the case of consumption of other polyphenol-abundant food products.

Methods: This review is based on available data from pre-clinical and studies and presents a broad report on the pharmacological activity of the extracts relevant for neurodegenerative diseases.

Results: Flavonoids present in herbal infusions are absorbed from gastro-intestinal tract and may affect the central nervous system.

Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters.

Parasites may significantly affect the functioning of the host organism including immune response and gut-brain-axis ultimately leading to alteration of the host behavior. The impact of intestinal worms on the host central nervous system (CNS) remains unexplored. The aim of this study was to evaluate the effect of intestinal infection by the tapeworm Hymenolepis diminuta on behavior and functions of the CNS in rats.

Antiviral Drugs in Influenza.

Flu is a serious health, medical, and economic problem, but no therapy is yet available that has satisfactory results and reduces the occurrence of these problems. Nearly 20 years after the registration of the previous therapy, baloxavir marboxil, a drug with a new mechanism of action, recently appeared on the market. This is a promising step in the fight against the influenza virus.

COVID-19 research: quality of biostatistics.

Introduction: In recent years, unfortunately, low quality of statistical analyses in medicine has been observed. As it turns out, this also applies to COVID-19 subject matter.

Methods: The study included 2600 medical articles published between the beginning of 2020 and June 2021, in which the authors described the obtained results, i.

Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer.

Breast cancer constitute a common type of oncological disease with a highlighted mortality rate. In recent years, researchers have introduced progranulin (PGRN) as an novel potential biomarker and associated its function with higher risk factor for development of breast cancer. The present review article collects evidence on the association of PGRN with clinicopathological features and drug resistance in the patients with breast cancer.

Flow-Responsive Noncoding RNAs in the Vascular System: Basic Mechanisms for the Clinician.

The vascular system is largely exposed to the effect of changing flow conditions. Vascular cells can sense flow and its changes. Flow sensing is of pivotal importance for vascular remodeling.

Sex-Related Predisposition to Post-Traumatic Stress Disorder Development-The Role of Neuropeptides.

Post-traumatic stress disorder (PTSD) is characterized by re-experiencing a traumatic event, avoidance, negative alterations in cognitions and mood, hyperarousal, and severe functional impairment. Women have a two times higher risk of developing PTSD than men. The neurobiological basis for the sex-specific predisposition to PTSD might be related to differences in the functions of stress-responsive systems due to the interaction between gonadal hormones and stress peptides such as corticotropin-releasing factor (CRF), orexin, oxytocin, and neuropeptide Y.

Electrophoretic Determination of Trimethylamine (TMA) in Biological Samples as a Novel Potential Biomarker of Cardiovascular Diseases Methodological Approach.

In competitive athletes, the differential diagnosis between nonpathological changes in cardiac morphology associated with training (commonly referred to as "athlete's heart") and certain cardiac diseases with the potential for sudden death is an important and not uncommon clinical problem. The use of noninvasive, fast, and cheap analytical techniques can help in making diagnostic differentiation and planning subsequent clinical strategies. Recent studies have demonstrated the role of gut microbiota and their metabolites in the onset and the development of cardiovascular diseases.

The toxic contaminants of plant material as well as herb-drug interactions may constitute the health risk factors in daily rooibos tea consumers.

Rooibos tea is brewed using plant material sensitive to environmental contamination. This review covers the safety data from preclinical experiments as well as human studies and delivers a report on its hepatic activity. tea investigation reveals antioxidative and anti-mutagenic features and ability to modulate microsomal enzymes.

Plasma Trimethylamine-N-Oxide Is an Independent Predictor of Long-Term Cardiovascular Mortality in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome.

To investigate the association of liver metabolite trimethylamine N-oxide (TMAO) with cardiovascular disease (CV)-related and all-cause mortality in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention. Our prospective observational study enrolled 292 patients with ACS. Plasma concentrations of TMAO were measured during the hospitalization for ACS.

Dihydroergotamine affects spatial behavior and neurotransmission in the central nervous system of Wistar rats.

Introduction: Dihydroergotamine (DHE) is a derivative of an ergot alkaloid used as an antimigraine medication. Nowadays, ergot alkaloids may still endanger the safety of humans and animals as food or medicine pollutants, but the outcomes of long-term DHE administration on the behaviour and neurotransmission remain undescribed.

Material And Methods: Adult male Wistar Albino Glaxo rats pre-treated orally with DHE for six weeks were investigated to assess the relationship between concentration of neurotransmitters and behavioural response.