Expression level of CD117 (KIT) on ovarian cancer extracellular vesicles correlates with tumor aggressiveness.

Ovarian cancer is known to be the most lethal malignancy among all gynecological cancers affecting a large number of women worldwide. The treatment of ovarian cancer is challenging due to the high recurrence rate of the disease and is further complicated by acquired chemoresistance. Most ovarian cancer deaths are the result of the metastatic spread of drug-resistant cells. The theory of cancer stem cells (CSC) suggests that both tumor initiation and progression are driven by a population of undifferentiated capable of self-renewal, tumor initiation and development of chemoresistance. The CD117 mast/stem cell growth factor receptor (KIT) is the most commonly used marker for ovarian CSCs. Here, we analyze the correlation between CD117 expression and histological tumor type in ovarian cancer cell lines (SK-OV-3 and MES-OV) and in small/medium extracellular vesicles (EVs) isolated from the urine of ovarian cancer patients. We have demonstrated that the abundance of CD117 on cells and EVs is correlated with tumor grade and therapy resistance status. Moreover, using small EVs isolated from ovarian cancer ascites, it was shown that recurrent disease is characterized by a much higher abundance of CD117 on EVs than primary tumor.

Directional couplings between the respiration and parasympathetic control of the heart rate during sleep and wakefulness in healthy subjects at different ages.

Cardiorespiratory interactions are important, both for understanding the fundamental processes of functioning of the human body and for development of methods for diagnostics of various pathologies. The properties of cardiorespiratory interaction are determined by the processes of autonomic control of blood circulation, which are modulated by the higher nervous activity. We study the directional couplings between the respiration and the process of parasympathetic control of the heart rate in the awake state and different stages of sleep in 96 healthy subjects from different age groups. The detection of directional couplings is carried out using the method of phase dynamics modeling applied to experimental RR-intervals and the signal of respiration. We reveal the presence of bidirectional couplings between the studied processes in all age groups. Our results show that the coupling from respiration to the process of parasympathetic control of the heart rate is stronger than the coupling in the opposite direction. The difference in the strength of bidirectional couplings between the considered processes is most pronounced in deep sleep.

Directional Couplings Between Electroencephalogram and Interbeat Intervals Signals in Awake State and Different Stages of Sleep.

Purpose of the work is to identify the directional coupling between the structures of the brain and the autonomic control of the heart rate variability, to analyze the changes in these coupling in sleep and in wakefulness. Infra-slow oscillations of the electroencephalograms potential and low-frequency components (0.04-0.15 Hz) of the interbeat intervals signal where analyzed using a sensitive method for identifying the directional coupling. The technique, based on modeling the dynamics of instantaneous phases of oscillations, made it possible to reveal the presence and quantify the directional couplings between the structures of the brain and the autonomic control of the heart rate variability. It was shown that the coupling coefficients in the frequency band of 0.04-0.15 Hz (associated mainly with sympathetic control of blood circulation), on average, decrease with falling asleep. We have also shown the asymmetry of coupling. At the same time, stronger connections were revealed in the direction from the autonomic control of the heart rate variability to the brain structures than in the opposite direction. It has been shown that the strength of such couplings decreases with increasing of sleep depth.

Low-frequency component of photoplethysmogram reflects the autonomic control of blood pressure.

The question of how much information the photoplethysmogram (PPG) signal contains on the autonomic regulation of blood pressure (BP) remains unsolved. This study aims to compare the low-frequency (LF) and high-frequency components of PPG and BP and assess their correlation with oscillations in interbeat (RR) intervals at similar frequencies. The PPG signal from the distal phalanx of the right index finger recorded using a reflective PPG sensor at green light, the BP signal from the left hand recorded using a Finometer, and RR intervals were analyzed. These signals were simultaneously recorded within 15 min in a supine resting condition in 17 healthy subjects (12 males and 5 females) aged 33 ± 9 years (mean ± SD). The study revealed the high coherence of LF components of PPG and BP with the LF component of RR intervals. The high-frequency components of these signals had low coherence. The analysis of the signal instantaneous phases revealed the presence of high-phase coherence between the LF components of PPG and BP. It is shown that the LF component of PPG is determined not only by local myogenic activity but also reflects the processes of autonomic control of BP.

Synchronization of the Processes of Autonomic Control of Blood Circulation in Humans Is Different in the Awake State and in Sleep Stages.

The influence of higher nervous activity on the processes of autonomic control of the cardiovascular system and baroreflex regulation is of considerable interest, both for understanding the fundamental laws of the functioning of the human body and for developing methods for diagnostics and treatment of pathologies. The complexity of the analyzed systems limits the possibilities of research in this area and requires the development of new tools. Earlier we propose a method for studying the collective dynamics of the processes of autonomic control of blood circulation in the awake state and in different stages of sleep. The method is based on estimating a quantitative measure representing the total percentage of phase synchronization between the low-frequency oscillations in heart rate and blood pressure. Analysis of electrocardiogram and invasive blood pressure signals in apnea patients in the awake state and in different sleep stages showed a high sensitivity of the proposed measure. It is shown that in slow-wave sleep the degree of synchronization of the studied rhythms is higher than in the awake state and lower than in sleep with rapid eye movement. The results reflect the modulation of the processes of autonomic control of blood circulation by higher nervous activity and can be used for the quantitative assessment of this modulation.

Low-frequency variability in photoplethysmographic waveform and heart rate during on-pump cardiac surgery with or without cardioplegia.

We studied the properties of low-frequency (LF) heart rate variability (HRV) and photoplethysmographic waveform variability (PPGV) and their interaction under conditions where the hemodynamic connection between them is obviously absent, as well as the LF regulation of PPGV in the absence of heart function. The parameters of HRV and finger PPGV were evaluated in 10 patients during cardiac surgery under cardiopulmonary bypass (on-pump cardiac surgery) with or without cardioplegia. The following spectral indices of PPGV and HRV were ertimated: the total spectral power (TP), the high-frequency (HF) and the LF ranges of TP in percents (HF% and LF%), and the LF/HF ratio. We assessed also the index S of synchronization between the LF oscillations in finger photoplethysmogram (PPG) and heart rate (HR) signals. The analysis of directional couplings was carried out using the methods of phase dynamics modeling. It is shown that the mechanisms leading to the occurrence of oscillations in the LF range of PPGV are independent of the mechanisms causing oscillations in the LF range of HRV. At the same time, the both above-mentioned LF oscillations retain their activity under conditions of artificial blood circulation and cardioplegia (the latter case applies only to LF oscillations in PPG). In artificial blood circulation, there was a coupling from the LF oscillations in PPG to those in HR, whereas the coupling in the opposite direction was absent. The coupling from the LF oscillations in PPG to those in HR has probably a neurogenic nature, whereas the opposite coupling has a hemodynamic nature (due to cardiac output).

Comparative study of short-term cardiovascular autonomic control in cardiac surgery patients who underwent coronary artery bypass grafting or correction of valvular heart disease.

Introduction: Our aim was to perform a comparative study of short-term cardiovascular autonomic control in cardiac surgery patients who underwent coronary artery bypass grafting (CABG) or surgical correction of valvular heart disease (SCVHD ). Methods: The synchronous 15 minutes records of heart rate variability (HRV) and finger's photoplethysmographic waveform variability (PPGV) were performed in 42 cardiac surgery patients (12 women) aged 61.8 ± 8.6 years (mean ± standard deviation), who underwent CABG, and 36 patients (16 women) aged 54.2 ± 14.9 years, who underwent SCVHD , before surgery and in 5-7 days after surgery. Conventional time and frequency domain measures of HRV and index S of synchronization between the slow oscillations in PPGV and HRV were analyzed. We also calculated personal dynamics of these indices after surgery. Results: We found no differences (Р > 0.05) in all studied autonomic indices (preoperative and post-surgery) between studied patients' groups, except for the preoperative heart rate, which was higher in patients who underwent SCVHD (P = 0.013). We have shown a pronounced preoperative and post-surgery variability (magnitude of inter-quartile ranges) of all autonomic indices in studied patients. In the cluster analysis based on cardiovascular autonomic indices (preoperative and post-surgery), we divided all patients into two clusters (38 and 40 subjects) which did not differ in all clinical characteristics (except for the preoperative hematocrit, P = 0.038), index S, and all post-surgery HRV indices. First cluster (38 patients) had higher preoperative values of the HR, TP, HF, and HF%, and lower preoperative values of the LF% and LF/HF. Conclusion: The variability of cardiovascular autonomic indices in on-pump cardiac surgery patients (two characteristic clusters were identified based on preoperative indices) was not associated with their clinical characteristics and features of surgical procedure (including cardioplegia).