COVID-19 vaccination in pregnant and lactating women

Introduction: The COVID-19 pandemic significantly changed the lifestyle of pregnant women. Pregnant women with COVID-19 are more likely to suffer from severe disease, as well as unfavorable pregnancy and childbirth. Currently, there is no causal treatment for this disease available, so attention should be paid to preventing infection with vaccines. Aim of the study: A review of the literature on the influence of COVID-19 vaccines on the course of pregnancy and summary of recommendations regarding the use of COVID-19 vaccines during pregnancy and breastfeeding.  State of knwoledge: Three types of COVID-19 vaccines are most commonly used: mRNA vaccines, vector vaccines as well as subunit vaccines. In preclinical developmental and reproductive toxicity studies in animal models, there were no alarming safety signals, and observations of vaccinated pregnant women did not reveal any complications with respect to the course of pregnancy and development of the fetus. No cases of neonatal death have been reported in the first 28 days after birth. Most of the side effects following vaccination, such as injection site pain or tenderness, fatigue, fever or muscle pain, were moderate and resolved within 24 hours. The current research results confirm a positive immune response in pregnant women. Moreover, it is important that the presence of antibodies in the umbilical cord blood makes it possible to protect and reduce the risk of SARS-CoV-2 infection of the newborn. Summary: All pregnant women, irrespective of trimester, and breastfeeding mothers are advised to administer a booster dose of the COVID-19 vaccine within an appropriate period of time after the primary vaccination schedule

A critical look at the new possibilities of therapeutic use of statins – a summary of the current state of knowledge

Hypercholesterolemia is a condition characterized by total cholesterol levels exceeding 200 mg/dl. A breakthrough in its treatment was the introduction of the first representative of the status - lovastatin. The mechanism of their action relies on inhibition of the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme responsible for converting HMG-CoA to mevalonic acid, the main substrate in the synthesis of endogenous cholesterol. The progress of experimental and clinical studies on action statins indicates a number of other biological properties of this group of compounds, and thus their pharmacological potential. The possibility of their use in the pharmacotherapy of cardiovascular diseases, hyperandrogenism in women with polycystic ovary syndrome (PCOS), osteoporosis, type 2 diabetes, neurodegenerative diseases, or cancer has been so far highlighted. The aim of this paper was to systematize the knowledge of statin drugs in terms of the progress of studies on their biological activity indicating the possibility of their potential use in the treatment of diseases other than those related to the cardiovascular system, along with verification of their safety profile and demonstrated adverse effects (DN) as a result of their intake. The literature review was conducted by a screening of the following scientific databases - PubMed and Google Scholar (the analysis lasted from March 2022 to February 2023). The keywords used for searching were disease-related and DN-related. Statins have shown potential to alleviate symptoms of androgen excess in women suffering from polycystic ovary syndrome (PCOS). Studies relating to their effect on the treatment of Alzheimer's disease and dementia indicate a reduction in progressive neurodegenerative changes, and thus suggest their potential use in the prevention and treatment of comorbid cardiovascular disease. Moreover, statins tend to reduce morbidity, increase survival, and alleviate the progression of cancer. The results of studies of the effects of these drugs on the possibility or development of Parkinson's disease, osteoporosis and the etiology of muscle symptoms appear to be inconsistent in the relationship of their benefits to DN. Unfortunately, it seems that they have also led to disturbances in carbohydrate metabolism and increased the risk of type II diabetes mellitus (NODM). Studies on the effect of the nocebo effect during statin therapy on the frequency with which patients experience DN have confirmed the presence of this effect. Analysis of the collected studies shows considerable potential for expanding the current therapeutic indications of the drugs in question. However, further randomized controlled trials are required to determine the precise effective dose, duration of therapy for a specific statin

Studies in Law. Research Papers

Słowo wstępne: "Drodzy Czytelnicy, Prezentujemy Państwu kolejny numer naszego periodyku. W tym bogatym zbiorze wypowiedzi przedstawicieli doktryny prawa i praktyki prawniczej znalazło się miejsce dla prac autorów z różnych dziedzin prawa. Analizowane zagadnienia odnoszą się w szczególności do problematyki prawa konstytucyjnego, prawa cywilnego, prawa pracy, prawa karnego. Zgromadziliśmy cenne spostrzeżenia autorów z różnych ośrodków akademickich – tak z Polski, jak i z zagranicy. Obok interesujących artykułów naukowych oraz glos przedstawiamy też niemałą liczbę innych tekstów, przede wszystkim recenzji publikacji naukowych i sprawozdań pokonferencyjnych. Mamy nadzieję, że ten, jak i przyszłe numery czasopisma stanowić będą dla Państwa interesującą lekturę, skłaniającą do refleksji nad poruszanymi tematami i prowokującą do tworzenia kolejnych prac naukowych. Liczymy, że zechcą Państwo publikować je – jak do tej pory – na łamach czasopisma „Studia Prawnicze. Rozprawy i Materiały”. Życzę inspirującej lektury!"(...

Modification of Flavobacterium johnsoniae genome to investigate the functions of alternative complex III ActD and ActE subunits

Alternatywny kompleks III (ACIII) występujący w błonie niektórych bakterii stanowi kluczowy element łańcucha oddechowego. Pełni taką samą rolę jak kompleks III w błonie mitochondrialnej, którego zadaniem jest utlenienie chinolu. W mitochondriach reakcji tej towarzyszy translokacja protonów przez błonę. W ten sposób powstaje gradient protonów, który jest jednym ze składowych siły protonomotorycznej, potrzebnej do produkcji uniwersalnego nośnika energii - ATP, wykorzystywanego do wielu procesów zachodzących w komórce. Mimo tej samej funkcji, ACIII posiada całkowicie odmienną strukturę niż mitochondrialny kompleks III. Dwie podjednostki kompleksu, ActA oraz ActE, zawierają hemy typu c, które umożliwiają transfer elektronu poprzez procesy utlenienia oraz redukcji (reakcje redoks). Podjednostka ActA przenosi elektron na cytochrom aa3, pełniący funkcję terminalnej oksydazy, która redukuje cząsteczkę tlenu. Z kolei podjednostka ActE nie jest kluczowa dla tego transferu i prawdopodobnie jest częścią alternatywnego szlaku elektronowego, który wpływa na bardziej wydajny wzrost bakterii. Pierwszym celem tej pracy była izolacja kompleksu ACIII z dodaną metką białkową i znalezienie potencjalnych partnerów oddziałujących z podjednostką ActE. Z użyciem tradycyjnego klonowania molekularnego, skonstruowano plazmid z którego zachodzi ekspresja genu kodującego białko ActD z genetycznie dodaną metką Strep-tag. Następnie przeniesiono plazmid do szczepu F. johnsoniae, aby oczyścić kompleks ACIII z użyciem chromatografii powinowactwa. Kolejnym podejściem do zrealizowania tego celu była konstrukcja mutanta z delecją podjednostki ActD z użyciem metody rekombinacji homologicznej. Następnie szczep skomplementowano tym samym plazmidem i podjęto próbę izolacji kompleksu. Drugim celem pracy było określenie, czy podjednostka ActD jest kluczowa dla złożenia się kompleksu i wbudowania go w błonę. Wykonano to poprzez izolację błon ze szczepów z delecją oraz komplementacją genu actD i sprawdzenie obecności poszczególnych podjednostek kompleksu. Porównano także szybkość wzrostu mutantów z delecją i komplementacją ze szczepem dzikim. Wyniki pracy nie pozwoliły na identyfikację białek oddziałujących z ACIII z powodu uzyskania niewielkiej ilości kompleksu, ale są wskazaniem do innego rozwiązania, aby wyizolować kompleks zastosowaną metodą. Ponadto udowodniono, że podjednostka ActD nie jest kluczowa dla wbudowania się kompleksu w błonę, ale jej brak obniża szybkość wzrostu bakterii. Wyniki przeprowadzonych badań mogą przyczynić się do lepszego zrozumienia działania alternatywnego kompleksu III u F. johnsoniae.Alternative complex III (ACIII) localized in the membrane of some bacterial species is the key element of respiratory chain. It performs the same function as typical complex III in mitochondrial membranes, which is the electron transfer from the quinol pool to the complex IV (terminal oxidase). In mitochondria this reaction is coupled with the proton translocation through the membrane. This way the proton gradient is formed, which is the component of protonmotive force needed for the ATP synthesis. ATP is the universal energy carrier utilized to drive many processes in the cell. Despite the same function, ACIII is structurally different from mitochondrial complex III. Two ACIII subunits – ActA and ActE contain type c hemes, which allow the transfer of electron through the oxidation and reduction of the cofactors (redox reactions). ActA transfers the electron to the cytochrome aa3, which performs the role of terminal oxidase and reduce the oxygen molecule. In turn, ActE subunit is not essential for this transfer and most probably is the part of the alternative electron pathway for quinol pool oxidation, which is beneficial for bacterial growth. First aim of this work was to isolate ACIII with genetically-added protein tag and identification of potential redox partners interacting with ActE. By using traditional cloning techniques the plasmid was constructed, from which the expression of actD gene with the genetically added protein tag occurs. The plasmid was transferred to the F. johnsoniae strain to purify the complex using affinity chromatography. Another approach to achieve this aim was to construct a deletion mutant lacking ActD subunit using the homologous recombination. The obtained strain was complemented with the same plasmid and the trial to isolate the complex was made. The second aim was to assess if ActD subunit is necessary for the complex assembly in the membrane. It was done by isolation of the membranes from deletion and complementation strains, and verification of the individual complex subunits presence. Also, the comparison of growth rates of the obtained strains was performed. Results of this work did not allow to identify proteins interacting with ACIII because of the low amount of the obtained complex, however they are an indication for another solution to the complex isolation with this method. Moreover, it was proven that ActD subunit is not essential for the complex assembly in the membrane, however its absence slows down the bacterial growth. Results of this work may contribute to the better understanding of ACIII activity in F. johnsoniae

Regulation of Adipose-Derived Stem Cell Activity by Melatonin Receptors in Terms of Viability and Osteogenic Differentiation

Melatonin is a hormone secreted mainly by the pineal gland and acts through the Mel1A and Mel1B receptors. Among other actions, melatonin significantly increases osteogenesis during bone regeneration. Human adipose-derived mesenchymal stem cells (ADSCs) are also known to have the potential to differentiate into osteoblast-like cells; however, inefficient culturing due to the loss of properties over time or low cell survival rates on scaffolds is a limitation. Improving the process of ADSC expansion in vitro is crucial for its further successful use in bone regeneration. This study aimed to assess the effect of melatonin on ADSC characteristics, including osteogenicity. We assessed ADSC viability at different melatonin concentrations as well as the effect on its receptor inhibitors (luzindole or 4-P-PDOT). Moreover, we analyzed the ADSC phenotype, apoptosis, cell cycle, and expression of MTNR1A and MTNR1B receptors, and its potential for osteogenic differentiation. We found that ADSCs treated with melatonin at a concentration of 100 µM had a higher viability compared to those treated at higher melatonin concentrations. Melatonin did not change the phenotype of ADSCs or induce apoptosis and it promoted the activity of some osteogenesis-related genes. We concluded that melatonin is safe, non-toxic to normal ADSCs in vitro, and can be used in regenerative medicine at low doses (100 μM) to improve cell viability without negatively affecting the osteogenic potential of these cells

Impact of Natural Genetic Variation on Gene Expression Dynamics

<div><p>DNA sequence variation causes changes in gene expression, which in turn has profound effects on cellular states. These variations affect tissue development and may ultimately lead to pathological phenotypes. A genetic locus containing a sequence variation that affects gene expression is called an “expression quantitative trait locus” (eQTL). Whereas the impact of cellular context on expression levels in general is well established, a lot less is known about the cell-state specificity of eQTL. Previous studies differed with respect to how “dynamic eQTL” were defined. Here, we propose a unified framework distinguishing static, conditional and dynamic eQTL and suggest strategies for mapping these eQTL classes. Further, we introduce a new approach to simultaneously infer eQTL from different cell types. By using murine mRNA expression data from four stages of hematopoiesis and 14 related cellular traits, we demonstrate that static, conditional and dynamic eQTL, although derived from the same expression data, represent functionally distinct types of eQTL. While static eQTL affect generic cellular processes, non-static eQTL are more often involved in hematopoiesis and immune response. Our analysis revealed substantial effects of individual genetic variation on cell type-specific expression regulation. Among a total number of 3,941 eQTL we detected 2,729 static eQTL, 1,187 eQTL were conditionally active in one or several cell types, and 70 eQTL affected expression changes during cell type transitions. We also found evidence for feedback control mechanisms reverting the effect of an eQTL specifically in certain cell types. Loci correlated with hematological traits were enriched for conditional eQTL, thus, demonstrating the importance of conditional eQTL for understanding molecular mechanisms underlying physiological trait variation. The classification proposed here has the potential to streamline and unify future analysis of conditional and dynamic eQTL as well as many other kinds of QTL data.</p></div

eQTL tissue specificity.

<p>Proportion of tissue-specific eQTL reported in different studies in mouse and human. We report the tissues/cell types that were analyzed, whether only local (i.e. <i>cis</i>) eQTL or both local and distant eQTL were inferred. The last column describes whether eQTL mapping was conducted separately in each cell type or by including a tissue factor into the analysis.</p

Number of <i>cis</i>- and <i>trans</i>-eQTL in different eQTL classes.

<p>Numbers of significant eQTL with shown separately for cis-eQTL (left) and trans-eQTL (right). Static, conditional and dynamic eQTL are distinguished (see labels at the bottom). Further, the figure discriminates simultaneous and separate eQTL mappings, which represent alternative ways for distinguishing static and conditional eQTL. Simultaneous mapping increases the statistical power leading to substantially more eQTL significant at the same level (). Even though both, <i>cis</i>- and <i>trans</i>-eQTL are increased when performing simultaneous mapping, <i>trans</i>-eQTL benefit more from the increase in power. See main text for exact definitions of the various eQTL types.</p

Number of cell types in which eQTL are active.

<p>The bars show the number of eQTL conditional in one, two, three or four cell types. Results are obtained from post-hoc Wald tests in the linear model comprising the eQTL marker, the cell type and their interaction. Only models with a significant marker - cell type interaction are considered. eQTL that are conditionally active in exactly one cell type are further classified by cell type (S - stem, P - progenitor, E - erythroid and M - myeloid cells).</p