Non-Coding RNAs in Breast Cancer: Diagnostic and Therapeutic Implications.

Breast cancer (BC) is one of the most prevalent forms of cancer globally, and has recently become the leading cause of cancer-related mortality in women. BC is a heterogeneous disease comprising various histopathological and molecular subtypes with differing levels of malignancy, and each patient has an individual prognosis. Etiology and pathogenesis are complex and involve a considerable number of genetic alterations and dozens of alterations in non-coding RNA expression.

Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential.

Non-coding RNAs (ncRNAs) are abundant single-stranded RNA molecules in human cells, involved in various cellular processes ranging from DNA replication and mRNA translation regulation to genome stability defense. MicroRNAs are multifunctional ncRNA molecules of 18-24 nt in length, involved in gene silencing through base-pair complementary binding to target mRNA transcripts. piwi-interacting RNAs are an animal-specific class of small ncRNAs sized 26-31 nt, responsible for the defense of genome stability via the epigenetic and post-transcriptional silencing of transposable elements.

Classic and New Markers in Diagnostics and Classification of Breast Cancer.

Breast cancer remains the most frequently diagnosed form of female's cancer, and in recent years it has become the most common cause of cancer death in women worldwide. Like many other tumours, breast cancer is a histologically and biologically heterogeneous disease. In recent years, considerable progress has been made in diagnosis, subtyping, and complex treatment of breast cancer with the aim of providing best suited tumour-specific personalized therapy.

Proteomic analysis of plasma proteins after low-level laser therapy in rats.

The laser radiation absorbed by cells induces production of reactive oxygen species (ROS), followed by the development of oxidative stress. Proteins are major targets for ROS due to their abundance in biological systems. The aim of the present pilot study was to examine the effects of transcutaneous laser blood irradiation (TLBI), i.

Global Longitudinal Strain and Strain Rate in Type Two Diabetes Patients with Chronic Heart Failure: Relevance to Osteoprotegerin.

Background: Biomechanical stress and inflammatory biomarkers relate to global contractility dysfunction; however, adding these biomarkers into a risk model constructed on clinical data does not improve its prediction value in chronic heart failure (CHF).

Aim: The aim of this study was to evaluate whether biomarkers predict declining of left ventricular global contractility function in diabetic patients with ischemia-induced CHF.

Patients And Methods: The study retrospectively evolved 54 diabetic patients who had systolic or diastolic ischemia-induced CHF that was defined as left-ventricular ejection fraction (LVEF) ≤45% or 46-55% respectively assessed by quantitative echocardiography and other conventional criteria according to current clinical guidelines.

Resuscitation and auto resuscitation by airway reflexes in animals.

Various diseases often result in decompensation requiring resuscitation. In infants moderate hypoxia evokes a compensatory augmented breath - sigh and more severe hypoxia results in a solitary gasp. Progressive asphyxia provokes gasping respiration saving the healthy infant - autoresuscitation by gasping.

Reversal of functional disorders by aspiration, expiration, and cough reflexes and their voluntary counterparts.

Agonal gasping provoked by asphyxia can save ~15% of mammals even from untreated ventricular fibrillation (VF), but it fails to revive infants with sudden infant death syndrome (SIDS). Our systematic study of airway reflexes in cats and other animals indicated that in addition to cough, there are two distinct airway reflexes that may contribute to auto-resuscitation. Gasp- and sniff-like spasmodic inspirations (SIs) can be elicited by nasopharyngeal stimulation, strongly activating the brainstem generator for inspiration, which is also involved in the control of gasping.

Multigenerational lifetime low-dose exposure to heavy metals on selected reproductive parameters in rats.

The aim of the present investigation was to evaluate the effects of multigenerational (P, F1 and F2) exposure to low doses of lead, mercury and cadmium dissolved in tap water on the reproductive potency of Wistar rats and the physical health of their progeny. The animals were divided into 4 groups - control (C) and 3 groups intoxicated by metals (Pb, 100 μM; Hg, 1 μM; Cd, 20 μM, respectively). Females gave births from the 13th to the 78th week of experiment.

Distinct generators for aspiration and expiration reflexes: localization, mechanisms and effects.

Re-evaluation of our earlier c-Fos-like immuno-reactive studies and brainstem transection/lesion experiments in over 40 anaesthetized, non-paralyzed cats allowed comparison of two distinct airway defensive reflexes with the distinct generators for inspiration (I) and expiration (E), described recently in juvenile rats. The spiration reflex (AspR) is characterized by solitary rapid and strong inspiratory effort with a reciprocal inhibition, preventing a subsequent active expiration, while the expiration reflex (ExpR) manifests by rapid and strong expiratory effort, starting without a preceding, inspiration, or reciprocal inhibition of occasional spontaneous inspiration. The retro-trapezoid nucleus/parafacial respiratory group neurones described as the distinct generator for active E in rats, are activated also during the ExpR in adult cats.

The effect of hypoxic myocardial preconditioning is highly dependent on the light-dark cycle in Wistar rats.

Background: Cardioprotective effects by hypoxic preconditioning are well known mainly through in vitro experiments. However, the chronobiological aspects of phenomenon of cardioprotection by hypoxic preconditioning have not been studied in in vitro and in vivo experiments, and there are no consistent data regarding the daytime dependence of preconditioning effects.

Aim: To determine the protective effects of myocardial preconditioning applied during the dark (active) part of the day regimen, and to obtain an understanding concerning chronophysiological aspects of this phenomenon in in vivo rat experiments.

Effect of systemic hypoxia and reoxygenation on electrical stability of the rat myocardium: chronophysiological study.

The aim of the study was to determine the dependence of changes in the electrical stability of the heart on the light-dark cycle (LD cycle) in disorders of pulmonary ventilation. The ventricular arrhythmia threshold (VAT) was measured in female Wistar rats (adaptation to the light regime 12:12 h, ketamine/xylazine anesthesia 100 mg/15 mg/kg, i.m.

Chronophysiological view on changes of the electrical stability of the heart and heart rate under pentobarbital sodium and ketamine/xylazine anesthesia in a hypoventilation-reoxygenation rat model.

Objectives: To determine the effect of the light-dark cycle (LD) and type of anesthetic agent used on changes in the electrical stability of the heart in disorders of pulmonary ventilation.

Methods: The ventricular arrhythmia threshold (VAT) and heart rate (HR) were measured in anesthetized female Wistar rats adapted to an LD regimen of 12 h:12 h (pentobarbital sodium 30 mg/kg, intraperitoneally, or ketamine/xylazine 100 mg/15 mg/kg, intramuscularly; open chest experiments) under artificial normoventilation (tidal volume 1 mL/100 g, respiratory rate 40 breaths/min) and during 20 min of hypoventilation (tidal volume 0.5 mL/100 g, respiratory rate 20 breaths/min) followed by 20 min of reoxygenation.

[Regulation of respiration and its sleep-related disorders].

Four basic control mechanisms of breathing (brainstem respiratory centre, peripheral and central chemoreceptors, intero- and exteroceptive reflexes and suprapontine influences), as well as their sleep-related disorders are analysed. A decrease in central chemoreceptor sensitivity to CO2 and an increase in upper airway resistance during sleep result in hypoventilation and mild hypoxaemia already in physiological conditions. Compensatory increase in ventilatory effort with synchronous inhibition of pharyngeal dilators during sleep reduces the upper airway lumen manifesting with snoring, upper airway resistance syndrome, and OSA.

Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation.

Cardiorespiratory decompensation or even death may result from dysfunction of upper airway reflexes during sleep. This could manifest, for example, as a lack of pharyngeal dilation in obstructive sleep apnoea or failure of autoresuscitation by gasping in sudden infant death syndrome. Data obtained from experiments in anaesthetized cats suggest several clinicophysiological applications for upper airway reflexes possessing important pathogenetic and therapeutic potentials.

Mechanisms and clinicophysiological implications of the sniff- and gasp-like aspiration reflex.

Mechanical stimulation of the pharyngeal mucosa in cats and some other mammals evokes the 'aspiration reflex' (AR) characterized by rapid and strong inspiratory efforts not followed by active expirations. It resembles other spasmodic inspiratory acts such as the sniff, the gasp, and the sigh in several aspects, e.g.

[Disorders of heart rhythm and ECG changes in experimental apneic states].

Background: Apnoeic events are often accompanied by various disturbances in electric cardiac activity, the character and development as well as mechanism of which remain broadly unknown suggesting both direct metabolic defects as well as neurogenous autonomic influences.

Methods: Changes in ECG and heart rate induced by repeated short-lasting inhalation of hypoxic poikilocapnic mixtures (100% N2 and/or 0.5-1% CO2 or 6% CO2 in N2) were analyzed in 17 spontaneously breathing cats anaesthetized with sodium pentobarbitone (40 mg.

Nucleus raphe obscurus evokes 5-HT-1A receptor-mediated modulation of respiratory neurons.

We analysed in vivo the synaptic mechanisms underlying serotonin-mediated depression of expiratory neuronal discharges and phrenic nerve activity. We report that nucleus raphe obscurus stimulation not only abolishes phrenic nerve activity, but also hyperpolarizes the membrane potential, depresses periodic synaptic drive potentials and thus action potential discharges in caudal medullary expiratory neurons. These effects originate from pre- and post-synaptic inhibitory processes that involve 5-HT-1A receptor activation.

Reflex reversal of apnoeic episodes by electrical stimulation of upper airway in cats.

Respiratory effects of electrical stimulation of the upper airways (UAW) before and during apnoeic episodes induced by nitrogen inhalation were studied in 9 anaesthetized cats. In eupnoeic animals these electrically-evoked reflexes comprise rapid and powerful inspiratory efforts characterized by strong maximal airway occlusion pressures (Pmax = 635 +/- 39 mm H2O) and rapid peak inspiratory flow rates (PIF = 536 +/- 36 ml.sec-1) similar to the sniff-like aspiration reflex elicited mechanically.

The sniff-like aspiration reflex evoked by electrical stimulation of the nasopharynx.

Forced inspiratory efforts resembling the sniff-like aspiration reflex (AR) were evoked by single-shocks or trains of electrical impulses to the dorsal pharyngeal and nasal mucosal surfaces in 12 anaesthetized spontaneously breathing cats. The strongest ARs determined by diaphragmatic (DIA) EMG and peak-inspiratory flows were elicited from the dorsolateral nasopharyngeal wall close to the torus tubalis. Highly responsive sites were also detected in the posterolateral nasal cavity and in the rostrolateral oropharynx.

Calcium currents and calcium-dependent potassium currents in mammalian medullary respiratory neurones.

1. Respiratory neurons of mammals are rhythmically active because their membrane potential fluctuates periodically over a voltage range of -70 to -55 mV. These respiratory drive potentials lead to periodic discharges of bursts of action potentials lasting for 1-2 s.

Reversal of apnoea by aspiration reflex in anaesthetized cats.

Various flow and timing characteristics of breathing as well as electrocorticographic (ECoG) records were analysed in a model of reversible respiratory failure induced by N2 inhalation in 27 anaesthetized cats. During the first minute of respiratory arrest, nasopharyngeal stimulation by an elastic nylon fibre elicited a typical sniff- or gasp-like aspiration reflex (in 88.8% of cases), whilst similar tracheobronchial irritation evoked a weak cough reaction in one third of cases (34.

Hypoxic apnoea induced by N2 inhalation can be reversed by the aspiration reflex in anaesthetized cats.

Various cardiorespiratory and electrophysiological parameters were analysed in a model of acute respiratory failure induced by inhalation of pure nitrogen in approximately 150 anaesthetized cats. Initial hyperventilation leading to apnoea was characterized by extreme hypoxaemia, marked bradycardia and flattening of electrocortical (ECoG) activity. Artificial ventilation applied at the stage of marked mydriasis usually spontaneously prevented cardiovascular failure and normalized vital functions.