COVID-19, Vaccination,and Female Fertility in the Czech Republic

The fast-track process to approve vaccines against COVID-19 has raised questions about their safety, especially in relation to fertility. Over the last 2 years, studies have appeared monitoring female fertility, especially from assisted reproduction centers or in animal experiments. However, studies monitoring healthy populations are still limited. The aim of our study was to monitor the relevant parameters of female fertility (sex and other steroids, LH, FSH, SHBG, Antimüllerian hormone and antral follicle count) before and then 2–4 months after the third dose of vaccination against COVID-19 in a group of 25 healthy fertile woman. In addition, anti-SARS-CoV-2 and anti-SARS-CoV-2S antibodies were determined. We did not observe significant changes in the measured parameters before and after the third dose of vaccination. By comparing levels of the analytes with antibodies indicating a prior COVID-19 infection, we found that women who had experienced the disease had statistically lower levels of estrone, estradiol, SHBG and 5α-dihydroprogesterone, and conversely, higher levels of androgen active dehydroepiandrosterone and dihydrotestosterone. Our results confirm that vaccination does not affect female fertility, and that what fertile women should be worried about is not vaccination, but rather COVID-19 infection itself.     

ERAP/HLA-C and KIR Genetic Profile in Couples with Recurrent Implantation Failure

Proper embryo implantation depends on the tolerance of the maternal immune system to the fetus and its foreign paternal antigens. During implantation and early pregnancy, the dominant leukocytes in the uterus are uterine NK cells, expressing killer immunoglobulin-like receptors (KIR). KIRs recognize human leukocyte antigens (HLA-C) on the human trophoblast inherited from the father and mother. The antigenic peptides presented by the HLA are formed via their cleavage by endoplasmic reticulum aminopeptidases ERAP1 and ERAP2. The aim of this study was to assess the association of combined KIR genes and their HLA-C ligands, as well as ERAP1 and ERAP2 polymorphisms with recurrent implantation failure after in vitro fertilization (RIF). We tested 491 couples who underwent in vitro fertilization (IVF) and 322 fertile couples. Genotype CC rs27044 ERAP1 in female with a male’s HLA-C1C1 or HLA-C1C2 protected from RIF (p/p_corr. = 0.005/0.044, OR = 0.343; p/p_corr. = 0.003/0.027, OR = 0.442, respectively). Genotype TT rs30187 ERAP1 in female with a male’s HLA-C1C2 genotype increased the risk of RIF. Summarizing, in the combination of female ERAP1 and an HLA-C partner, the rs30187 C>T and rs27044 C>G polymorphisms play an important role in implantation failure.     

Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents

Schizophrenia is a chronic mental illness, which remains difficult to treat. A high resistance to the available therapies, their insufficient efficacy, and numerous side effects are the reasons why there is an urgent need to develop new antipsychotics. This study aimed to assess the antipsychotic-like effects of JJGW08, a novel arylpiperazine alkyl derivative of salicylamide, in rodents. First, considering the JJGW08 receptor profile, we investigated the compound’s intrinsic activity towards dopamine D₂ and serotonin 5-HT_1A, 5-HT_2A, and 5-HT₇ receptors using functional assays. Next, we assessed the effect of JJGW08 on MK-801- and amphetamine-induced hyperlocomotion, its risk of inducing catalepsy and impairing motor coordination, as well as the anxiolytic-like effects in the four-plate and marble burying tests in mice. Finally, we investigated the antipsychotic-like properties of JJGW08 in rats using MK-801-induced hyperlocomotion and prepulse inhibition tests. We found that JJGW08 showed antagonistic properties at dopamine D₂ and serotonin 5-HT_1A, 5-HT_2A, and 5-HT₇ receptors. However, the effect on the 5-HT_2A and 5-HT₇ receptors was very weak. Moreover, the tested compound showed an antipsychotic-like effect in MK-801- and amphetamine-induced hyperlocomotion but not in a prepulse inhibition test in rats. Notably, JJGW08 demonstrated anxiolytic-like properties in both behavioral tests. Importantly, the compound did not induce catalepsy or motor coordination impairment in mice at antipsychotic-like doses. Our study suggests it is worth searching for new potential antipsychotics among arylpiperazine alkyl derivatives of salicylamide.     

The effect of coal grain size on the sorption of hydrocarbons from gas mixtures

The flow of gas mixtures through coal, accompanied by sorption, is one of the natural processes occurring in the spontaneous heating of coal in underground mines. So far, studies on the sorption of mine gases have been mostly performed with regard to single components. In turn, sorption measurements with the use of gaseous mixtures were performed only on coals with grain size at the narrow range of 0.5 to 0.7 mm. In this paper, a dynamic sorption of a mixture of propylene, ethylene, propane, and ethane in a fixed‐bed column was investigated. Coal samples of various grain classes, ie, 0.25 to 0.50, 0.7 to 1.00, and 1.00 to 2.00 mm, were used as an adsorbent. The sorption tests were conducted at a constant gas flow rate of 2.17·10^?7 m³/s and the pressure of approximately 1 atm. Next, the results of the sorption tests were compared with parameters characterizing the porous structure of the materials used. The total amount of sorbed gases decreases as the grain size becomes larger. The samples characterized by a lower carbon content (<70% w/w), a slightly higher oxygen content, and a larger surface area dominated by micropores at the range of 0.6 to 2.0 nm and mesopores with diameter of 2.0 to 10.0 nm had a higher sorption capacity than samples with the structure determined mainly by mesopores. It has been noticed that a high sorption ability of ethane results from its highest concentration in the mixture at the inlet of the sorption column. In most cases, propylene was sorbed in larger amount than ethylene, independently of grain size of coal and pore size distribution.     

Phytochemical Composition and Biological Activities of Scorzonera Species

The genus Scorzonera comprises nearly 200 species, naturally occurring in Europe, Asia, and northern parts of Africa. Plants belonging to the Scorzonera genus have been a significant part of folk medicine in Asia, especially China, Mongolia, and Turkey for centuries. Therefore, they have become the subject of research regarding their phytochemical composition and biological activity. The aim of this review is to present and assess the phytochemical composition, and bioactive potential of species within the genus Scorzonera. Studies have shown the presence of many bioactive compounds like triterpenoids, sesquiterpenoids, flavonoids, or caffeic acid and quinic acid derivatives in extracts obtained from aerial and subaerial parts of the plants. The antioxidant and cytotoxic properties have been evaluated, together with the mechanism of anti-inflammatory, analgesic, and hepatoprotective activity. Scorzonera species have also been investigated for their activity against several bacteria and fungi strains. Despite mild cytotoxicity against cancer cell lines in vitro, the bioactive properties in wound healing therapy and the treatment of microbial infections might, in perspective, be the starting point for the research on Scorzonera species as active agents in medical products designed for miscellaneous skin conditions.     

The Role of CXCL16 in the Pathogenesis of Cancer and Other Diseases

CXCL16 is a chemotactic cytokine belonging to the α-chemokine subfamily. It plays a significant role in the progression of cancer, as well as the course of atherosclerosis, renal fibrosis, and non-alcoholic fatty liver disease (NAFLD). Since there has been no review paper discussing the importance of this chemokine in various diseases, we have collected all available knowledge about CXCL16 in this review. In the first part of the paper, we discuss background information about CXCL16 and its receptor, CXCR6. Next, we focus on the importance of CXCL16 in a variety of diseases, with an emphasis on cancer. We discuss the role of CXCL16 in tumor cell proliferation, migration, invasion, and metastasis. Next, we describe the role of CXCL16 in the tumor microenvironment, including involvement in angiogenesis, and its significance in tumor-associated cells (cancer associated fibroblasts (CAF), microglia, tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), mesenchymal stem cells (MSC), myeloid suppressor cells (MDSC), and regulatory T cells (T_reg)). Finally, we focus on the antitumor properties of CXCL16, which are mainly caused by natural killer T (NKT) cells. At the end of the article, we summarize the importance of CXCL16 in cancer therapy.     

DNA Demethylation in Response to Heat Stress in Arabidopsis thaliana

Environmental stress is one of the most important factors affecting plant growth and development. Recent studies have shown that epigenetic mechanisms, such as DNA methylation, play a key role in adapting plants to stress conditions. Here, we analyzed the dynamics of changes in the level of DNA methylation in Arabidopsis thaliana (L.) Heynh. (Brassicaceae) under the influence of heat stress. For this purpose, whole-genome sequencing of sodium bisulfite-treated DNA was performed. The analysis was performed at seven time points, taking into account the control conditions, heat stress, and recovery to control conditions after the stress treatment was discontinued. In our study we observed decrease in the level of DNA methylation under the influence of heat stress, especially after returning to control conditions. Analysis of the gene ontology enrichment and regulatory pathways showed that genes characterized by differential DNA methylation are mainly associated with stress response, including heat stress. These are the genes encoding heat shock proteins and genes associated with translation regulation. A decrease in the level of DNA methylation in such specific sites suggests that under the influence of heat stress we observe active demethylation phenomenon rather than passive demethylation, which is not locus specific.     

New Succinimides with Potent Anticancer Activity: Synthesis,Activation of Stress Signaling Pathways and Characterization of Apoptosis in Leukemia and Cervical Cancer Cells

Based on previously identified dicarboximides with significant anticancer and immunomodulatory activities, a series of 26 new derivatives were designed and synthesized by the Diels–Alder reaction between appropriate diene and maleimide or hydroxymaleimide moieties. The resulting imides were functionalized with alkanolamine or alkylamine side chains and subsequently converted to their hydrochlorides. The structures of the obtained compounds were confirmed by 1H and 13C NMR and by ESI MS spectral analysis. Their cytotoxicity was evaluated in human leukemia (K562, MOLT4), cervical cancer (HeLa), and normal endothelial cells (HUVEC). The majority of derivatives exhibited high to moderate cytotoxicity and induced apoptosis in K562 cells. Microarray gene profiling demonstrated upregulation of proapoptotic genes involved in receptor-mediated and mitochondrial cell death pathways as well as antiapoptotic genes involved in NF-kB signaling. Selected dicarboximides activated JNK and p38 kinases in leukemia cells, suggesting that MAPKs may be involved in the regulation of apoptosis. The tested dicarboximides bind to DNA as assessed by a plasmid DNA cleavage protection assay. The selected dicarboximides offer new scaffolds for further development as anticancer drugs.     

Pathomechanisms in the Kidneys in Selected Protozoan Parasitic Infections

Leishmaniasis, malaria, toxoplasmosis, and acanthamoebiasis are protozoan parasitic infections. They remain important contributors to the development of kidney disease, which is associated with increased patients’ morbidity and mortality. Kidney injury mechanisms are not fully understood in protozoan parasitic diseases, bringing major difficulties to specific therapeutic interventions. The aim of this review is to present the biochemical and molecular mechanisms in kidneys infected with Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. We present available mechanisms of an immune response, oxidative stress, apoptosis process, hypoxia, biomarkers of renal injury in the serum or urine, and the histopathological changes of kidneys infected with the selected parasites. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys are not well known yet. Deeper knowledge of kidney involvement in leishmaniasis and malaria by presenting their mechanisms provides insight into how to create novel and effective treatments. Additionally, the presented work shows gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis, which need further research.     

Searching for New Beneficial Bacterial Isolates of Wild Raspberries for Biocontrol of Phytopathogens-Antagonistic Properties and Functional Characterization

The threat caused by plants fungal and fungal-like pathogens is a serious problem in the organic farming of soft fruits. The European Commission regulations prohibit some commercially available chemical plant protection products, and instead recommend the use of natural methods for improving the microbial soil status and thus increasing resistance to biotic stresses caused by phytopathogens. The solution to this problem may be biopreparations based on, e.g., bacteria, especially those isolated from native local environments. To select proper bacterial candidates for biopreparation, research was provided to preliminarily ensure that those isolates are able not only to inhibit the growth of pathogens, but also to be metabolically effective. In the presented research sixty-five isolates were acquired and identified. Potentially pathogenic isolates were excluded from further research, and beneficial bacterial isolates were tested against the following plant pathogens: Botrytis spp., Colletotrichum spp., Phytophthora spp., and Verticillium spp. The eight most effective antagonists belonging to Arthrobacter, Bacillus, Pseudomonas, and Rhodococcus genera were subjected to metabolic and enzymatic analyses and a resistance to chemical stress survey, indicating to their potential as components of biopreparations for agroecology.