Determination of Ozone Concentration and Its Effect on Degradation of Materials

The ongoing Covid-19 pandemics showed the need for the effective decontamination of environment and surfaces. One of the options could be the use of gas ozone. Ozone has been well known for its disinfection properties, which were in the past used to decontaminate water. In this article, we present a development of an easy-made and ready-to-use portable detector of ozone, which could be used to easily detect ozone in the environment. In addition, we studied degradation impact of ozone on different materials, which normally occur in households or at working places. Ozone is well detectable and does not cause any damage to materials at concentrations needed for decontamination of the environment

Mitotic Poisons in Research and Medicine

Cancer is one of the greatest challenges of the modern medicine. Although much effort has been made in the development of novel cancer therapeutics, it still remains one of the most common causes of human death in the world, mainly in low and middle-income countries. According to the World Health Organization (WHO), cancer treatment services are not available in more then 70% of low-income countries (90% of high-income countries have them available), and also approximately 70% of cancer deaths are reported in low-income countries. Various approaches on how to combat cancer diseases have since been described, targeting cell division being among them. The so-called mitotic poisons are one of the cornerstones in cancer therapies. The idea that cancer cells usually divide almost uncontrolled and far more rapidly than normal cells have led us to think about such compounds that would take advantage of this difference and target the division of such cells. Many groups of such compounds with different modes of action have been reported so far. In this review article, the main approaches on how to target cancer cell mitosis are described, involving microtubule inhibition, targeting aurora and polo-like kinases and kinesins inhibition. The main representatives of all groups of compounds are discussed and attention has also been paid to the presence and future of the clinical use of these compounds as well as their novel derivatives, reviewing the finished and ongoing clinical trials

Cardiac Glycosides as Immune System Modulators

Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na+/K+-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds

Advances in Purpurin 18 Research: On Cancer Therapy

How to make cancer treatment more efficient and enhance the patient’s outcome? By multimodal therapy, theranostics, or personalized medicine? These are questions asked by scientists and doctors worldwide. However, finding new unique approaches and options for cancer treatment as well as new selective therapeutics is very challenging. More frequently, researchers “go back in time” and use already known and well-described compounds/drugs, the structure of which further derivatize to “improve” their properties, extend the use of existing drugs to new indications, or even to obtain a completely novel drug. Natural substances, especially marine products, are a great inspiration in the discovery and development of novel anticancer drugs. These can be used in many modern approaches, either as photo- and sonosensitizers in photodynamic and sonodynamic cancer therapy, respectively, or in tumor imaging and diagnosis. This review is focused on a very potent natural product, the chlorophyll metabolite purpurin 18, and its derivatives, which is well suitable for all the mentioned applications. Purpurin 18 can be easily isolated from green plants of all kinds ranging from seaweed to spinach leaves and, thus, it presents an economically feasible source for a very promising anticancer drug

Current Perspectives on Taxanes: Focus on Their Bioactivity, Delivery and Combination Therapy

Taxanes, mainly paclitaxel and docetaxel, the microtubule stabilizers, have been well known for being the first-line therapy for breast cancer for more than the last thirty years. Moreover, they have been also used for the treatment of ovarian, hormone-refractory prostate, head and neck, and non-small cell lung carcinomas. Even though paclitaxel and docetaxel significantly enhance the overall survival rate of cancer patients, there are some limitations of their use, such as very poor water solubility and the occurrence of severe side effects. However, this is what pushes the research on these microtubule-stabilizing agents further and yields novel taxane derivatives with significantly improved properties. Therefore, this review article brings recent advances reported in taxane research mainly in the last two years. We focused especially on recent methods of taxane isolation, their mechanism of action, development of their novel derivatives, formulations, and improved tumor-targeted drug delivery. Since cancer cell chemoresistance can be an unsurpassable hurdle in taxane administration, a significant part of this review article has been also devoted to combination therapy of taxanes in cancer treatment. Last but not least, we summarize ongoing clinical trials on these compounds and bring a perspective of advancements in this field

Autophagy in cancer resistance to paclitaxel: Development of combination strategies

Paclitaxel, a compound naturally occurring in yew, is a commonly used drug for the treatment of different types of cancer. Unfortunately, frequent cancer cell resistance significantly decreases its anticancer effectivity. The main reason for the resistance development is the paclitaxel-induced phenomenon of cytoprotective autophagy occurring by different mechanisms of action in dependence on a cell type and possibly even leading to metastases. Paclitaxel also induces autophagy in cancer stem cells, which greatly contributes to tumor resistance development. Paclitaxel anticancer effectivity can be predicted by the presence of several autophagy-related molecular markers, such as tumor necrosis factor superfamily member 13 in triple-negative breast cancer or cystine/glutamate transporter encoded by the SLC7A11 gene in ovarian cancer. Nevertheless, the undesired effects of paclitaxel-induced autophagy can be eliminated by paclitaxel co-administration with autophagy inhibitors, such as chloroquine. Interestingly, in certain cases, it is worthy of potentiating autophagy by paclitaxel combination with autophagy inducers, for instance, apatinib. A modern strategy in anticancer research is also to encapsulate chemotherapeutics into nanoparticle carriers or develop their novel derivatives with improved anticancer properties. Hence, in this review article, we summarize not only the current knowledge of paclitaxel-induced autophagy and its role in cancer resistance but mainly the possible drug combinations based on paclitaxel and their administration in nanoparticle-based formulations as well as paclitaxel analogs with autophagy-modulating properties

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly applied in the therapy of non-Hodgkin lymphoma and other malignancies, in which it is combined with drugs of different mechanisms of action, mainly with DNA-interacting compounds (for example cyclophosphamide), or drugs interfering with DNA synthesis (for example methotrexate). Besides, co-administration of vincristine with monoclonal antibodies has also emerged, the typical example of which is the anti-CD20 antibody rituximab. Although in some combination anticancer therapies, vincristine has been replaced with other drugs exhibiting lesser side effects, though, in most cases, it is still irreplaceable. This is strongly evidenced by the number of active clinical trials evaluating vincristine in combination cancer therapy. Therefore, in this article, we have reviewed the most common cancer treatment regimens employing vincristine and bring an overview of current trends in the clinical development of this compound

Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses

Drug repositioning is a successful approach in medicinal research. It significantly simplifies the long-term process of clinical drug evaluation, since the drug being tested has already been approved for another condition. One example of drug repositioning involves cardiac glycosides (CGs), which have, for a long time, been used in heart medicine. Moreover, it has been known for decades that CGs also have great potential in cancer treatment and, thus, many clinical trials now evaluate their anticancer potential. Interestingly, heart failure and cancer are not the only conditions for which CGs could be effectively used. In recent years, the antiviral potential of CGs has been extensively studied, and with the ongoing SARS-CoV-2 pandemic, this interest in CGs has increased even more. Therefore, here, we present CGs as potent and promising antiviral compounds, which can interfere with almost any steps of the viral life cycle, except for the viral attachment to a host cell. In this review article, we summarize the reported data on this hot topic and discuss the mechanisms of antiviral action of CGs, with reference to the particular viral life cycle phase they interfere with

Cardiac Glycosides as Autophagy Modulators

Drug repositioning is one of the leading strategies in modern therapeutic research. Instead of searching for completely novel substances and demanding studies of their biological effects, much attention has been paid to the evaluation of commonly used drugs, which could be utilized for more distinct indications than they have been approved for. Since treatment approaches for cancer, one of the most extensively studied diseases, have still been very limited, great effort has been made to find or repurpose novel anticancer therapeutics. One of these are cardiac glycosides, substances commonly used to treat congestive heart failure or various arrhythmias. Recently, the antitumor properties of cardiac glycosides have been discovered and, therefore, these compounds are being considered for anticancer therapy. Their mechanism of antitumor action seems to be rather complex and not fully uncovered yet, however, autophagy has been confirmed to play a key role in this process. In this review article, we report on the up-to-date knowledge of the anticancer activity of cardiac glycosides with special attention paid to autophagy induction, the molecular mechanisms of this process, and the potential employment of this phenomenon in clinical practice

Human myelin proteolipid protein structure and lipid bilayer stacking

The myelin sheath is an essential, multilayered membrane structure that insulates axons, enabling the rapid transmission of nerve impulses. The tetraspan myelin proteolipid protein (PLP) is the most abundant protein of compact myelin in the central nervous system (CNS). The integral membrane protein PLP adheres myelin membranes together and enhances the compaction of myelin, having a fundamental role in myelin stability and axonal support. PLP is linked to severe CNS neuropathies, including inherited Pelizaeus-Merzbacher disease and spastic paraplegia type 2, as well as multiple sclerosis. Nevertheless, the structure, lipid interaction properties, and membrane organization mechanisms of PLP have remained unidentified. We expressed, purified, and structurally characterized human PLP and its shorter isoform DM20. Synchrotron radiation circular dichroism spectroscopy and small-angle X-ray and neutron scattering revealed a dimeric, α-helical conformation for both PLP and DM20 in detergent complexes, and pinpoint structural variations between the isoforms and their influence on protein function. In phosphatidylcholine membranes, reconstituted PLP and DM20 spontaneously induced formation of multilamellar myelin-like membrane assemblies. Cholesterol and sphingomyelin enhanced the membrane organization but were not crucial for membrane stacking. Electron cryomicroscopy, atomic force microscopy, and X-ray diffraction experiments for membrane-embedded PLP/DM20 illustrated effective membrane stacking and ordered organization of membrane assemblies with a repeat distance in line with CNS myelin. Our results shed light on the 3D structure of myelin PLP and DM20, their structure–function differences, as well as fundamental protein–lipid interplay in CNS compact myelin