In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17α-hydroxylase), 3β-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.

Glycidyl azide polymer (GAP), an energetic binder, is the focus of this review. We briefly introduce the key properties of this well-known polymer, the difference between energetic and non-energetic binders in propellant and explosive formulations, the fundamentals for producing GAP and its copolymers, as well as for curing GAP using different types of curing agents. We use recent works as examples to illustrate the general approaches to curing GAP and its derivatives, while indicating a number of recently investigated curing agents. Next, we demonstrate that the properties of GAP can be modified either through internal (structural) alterations or through the introduction of external (plasticizers) additives and provide a summary of recent progress in this area, tying it in with studies on the properties of such modifications of GAP. Further on, we discuss relevant works dedicated to the applications of GAP as a binder for propellants and plastic-bonded explosives. Lastly, we indicate other, emerging applications of GAP and provide a summary of its mechanical and energetic properties.

The gonadal steroids, including androgens, estrogens and progestogens, are involved in the control of body fat distribution in humans. Nevertheless, not only the size and localization of the fat depots depend on the sex steroids levels, but they can also highly affect the functioning of adipose tissue. Namely, the gonadocorticoids can directly influence insulin signaling, lipid metabolism, fatty acid uptake and adipokine production. They may also alter energy balance and glucose homeostasis in adipocytes in an indirect way, e.g., by changing the expression level of aquaglyceroporins. This work presents the recent advances in understanding the molecular mechanism of how the gonadal steroids influence the functioning of adipose tissue leading to a set of detrimental metabolic consequences. Special attention is given here to highlighting the sexual dimorphism of adipocyte functioning in terms of health and disease. Particularly, we discuss the molecular background of metabolic disturbances occurring in consequence of hormonal imbalance which is characteristic of some common endocrinopathies such as the polycystic ovary syndrome. From this perspective, we highlight the potential drug targets and the active substances which can be used in personalized sex-specific management of metabolic diseases, in accord with the patient’s hormonal status.

Potassium channels play an important physiological role in glioma cells. In particular, voltage- and Ca 2+ -activated large-conductance BK channels (gBK in gliomas) are involved in the intensive growth and extensive migrating behavior of the mentioned tumor cells; thus, they may be considered as a drug target for the therapeutic treatment of glioblastoma. To enable appropriate drug design, molecular mechanisms of gBK channel activation by diverse stimuli should be unraveled as well as the way that the specific conformational states of the channel relate to its functional properties (conducting/nonconducting). There is an open debate about the actual mechanism of BK channel gating, including the question of how the channel proteins undergo a range of conformational transitions when they flicker between nonconducting (functionally closed) and conducting (open) states. The details of channel conformational diffusion ought to have its representation in the properties of the experimental signal that describes the ion-channel activity. Nonlinear methods of analysis of experimental nonstationary series can be useful for observing the changes in the number of channel substates available from geometrical and energetic points of view at given external conditions. In this work, we analyze whether the multifractal properties of the activity of glioblastoma BK channels depend on membrane potential, and which states, conducting or nonconducting, affect the total signal to a larger extent. With this aim, we carried out patch-clamp experiments at different levels of membrane hyper- and depolarization. The obtained time series of single channel currents were analyzed using the multifractal detrended fluctuation analysis (MFDFA) method in a standard form and incorporating focus-based multifractal (FMF) formalism. Thus, we show the applicability of a modified MFDFA technique in the analysis of an experimental patch-clamp time series. The obtained results suggest that membrane potential strongly affects the conformational space of the gBK channel proteins and the considered process has nonlinear multifractal characteristics. These properties are the inherent features of the analyzed signals due to the fact that the main tendencies vanish after shuffling the data.

BK channels are potassium selective and exhibit large single-channel conductance. They play an important physiological role in glioma cells: they are involved in cell growth and extensive migrating behavior. Due to the fact that these processes are accompanied by changes in membrane stress, here, we examine mechanosensitive properties of BK channels from human glioblastoma cells (gBK channels). Experiments were performed by the use of patch-clamp method on excised patches under membrane suction (0–40 mmHg) at membrane hyper- and depolarization. We have also checked whether channel’s activity is affected by possible changes of membrane morphology after a series of long impulses of suction. Unconventionally, we also analyzed internal structure of the experimental signal to make inferences about conformational dynamics of the channel in stressed membranes. We examined the fractal long-range memory effect (by R/S Hurst analysis), the rate of changes in information by sample entropy, or correlation dimension, and characterize its complexity over a range of scales by the use of Multiscale Entropy method. The obtained results indicate that gBK channels are mechanosensitive at membrane depolarization and hyperpolarization. Prolonged suction of membrane also influences open–closed fluctuations—it decreases channel’s activity at membrane hyperpolarization and, in contrary, increases channel’s activity at high voltages. Both membrane strain and its “fatigue” reduce dynamical complexity of channel gating, which suggest decrease in the number of available open conformations of channel protein in stressed membranes.