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Urinary tract infections (UTI) are common cause of fever in children. They often manifest with non-specific symptoms. New markers assessed in non-invasively collected urine are needed for quick and reliable diagnosis. This study evaluates the usefulness of calprotectin and YKL-40 in the diagnosis of febrile UTIs among children. 67 children aged between 1 month and 2 years took part in the study. The study group (group UTI) consisted of children with the first episode of febrile UTI (n = 20). Two control groups were created: group F - febrile children with other than UTI cause of the fever (n = 36), group H - healthy children (n = 11). Concentrations of calprotectin and YKL-40 in urine samples were determined with the use of the enzyme-linked immunosorbent assay method (ELISA). In the UTI group, the average calprotectin concentration was 1273.3 ng/ml, which was significantly higher than in group F (35.4 ng/ml) and in group H (8.0 ng/ml) (p < 0.001). The YKL-40 concentration in the UTI group was 15,542.1 pg/ml, which was also significantly higher than in group F (138.1 pg/ml) and in group H (162 pg/ml) (p < 0.01). These findings suggest that urinary YKL-40 and calprotectin could be useful markers in the differential diagnosis of febrile UTI among children., Competing Interests: Declarations Ethics approval and consent to participate The manuscript received ethics approval and consent from the Military Medical Chamber Bioethics Committee in Warsaw by decision number 27/22. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication We obtained informed consent from the parents and legal guardians of the patients to participate in the study, gather samples, and publish the research results. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Adipocytes derived from 3T3-L1 cells are a gold standard for analyses of adipogenesis processes and the metabolism of fat cells. A widely used histological and immunohistochemical staining and mass spectrometry lipidomics are mainly aimed for examining lipid droplets (LDs). Visualizing other cellular compartments contributing to the cellular machinery requires additional cell culturing for multiple labeling. Here, we present the localization of the intracellular structure of the 3T3-L1-derived adipocytes utilizing vibrational spectromicroscopy, which simultaneously illustrates the cellular compartments and provides chemical composition without extensive sample preparation and in the naïve state. Both vibrational spectra (FTIR-Fourier transform infrared and RS-Raman scattering spectroscopy) extended the gathered chemical information. We proved that both IR and RS spectra provide distinct chemical information about lipid content and their structure. Despite the expected presence of triacylglycerols and cholesteryl esters in lipid droplets, we also estimated the length and unsaturation degree of the fatty acid acyl chains that were congruent with known MS lipidomics of these cells. In addition, the clustering of spectral images revealed that the direct surroundings around LDs attributed to lipid-associated proteins and a high abundance of mitochondria. Finally, by using quantified markers of biomolecules, we showed that the fixative agents, paraformaldehyde and glutaraldehyde, affected the cellular compartment differently. We concluded that PFA preserves LDs better, while GA fixation is better for cytochromes and unsaturated lipid analysis. The proposed analysis of the spectral images constitutes a complementary tool for investigations into the structural and molecular features of fat cells.

Gadolinium is a component of the MRI contrast agent Dotarem. Although Dotarem is the least toxic among MRI contrasts used, gadolinium present in Dotarem accumulates for many years in various organs and tissues exerting toxic effects. We showed previously that gadolinium remains in macrophages for at least 7 days after exposure to Dotarem. However, very little is known about the effect of gadolinium retention on the immune cells such as macrophages. We studied the effect of 1-day and 7-day retention of gadolinium on various functions and molecular pathways of macrophages. Gadolinium retention for 7 days decreased macrophage adhesion and motility and dysregulated the expression of adhesion and fibrotic pathway-related proteins such as Notch1 and its ligand Jagged1, adhesion/migration-related proteins PAK1 and Shp1, immune response-related transcription factors Smad3 and TCF19, and chemokines CXCL10 and CXCL13, and dysregulated the mRNA expression of fibrosis-related genes involved in extracellular matrix (ECM) synthesis, such as Col6a1, Fibronectin, MMP9, and MMP12. It also completely (below a level of detection) shut down the transcription of anti-inflammatory M2 macrophage polarization marker the Arg-1. Such changes, if they occur in MRI patients, can be potentially detrimental to the patient's immune system and immune response-related processes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The full understanding of molecular mechanisms of cell differentiation requires a holistic view. Here we combine label-free FTIR and Raman hyperspectral imaging with data mining to detect the molecular cell composition enabling noninvasive monitoring of cell differentiation and identifying biochemical heterogeneity. Mouse adipose-derived mesenchymal stem cells (AD-MSCs) undergoing adipogenesis were followed by Raman and FT-IR imaging, Oil Red, and immunofluorescence. A workflow of the data analysis (IRRSmetrics4stem) was designed to identify spectral predictors of adipogenesis and test machine-learning (ML) methods (hierarchical clustering, PCA, PLSR) for the control of the AD-MSCs differentiation degree. IRRSmetrics4stem provided insights into the chemism of adipogenesis. With single-cell tracking, we established IRRS metrics for lipids, proteins, and DNA variations during AD-MSCs differentiation. The over 90% predictive efficiency of the selected ML methods proved the high sensitivity of the IRRS metrics. Importantly, the IRRS metrics unequivocally recognize a switch from proliferation to differentiation. This study introduced a new bioassay identifying molecular markers indicating molecular transformations and delivering rapid and machine learning-based monitoring of adipogenesis that can be relevant to other differentiation processes. Thus, we introduce a novel, rapid, machine learning-based bioassay to identify molecular markers of adipogenesis. It can be relevant to identification of differentiation-related molecular processes in other cell types, and beyond the cell differentiation including progression of different cellular pathophysiologies reconstituted in vitro., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

While the vertebrate immune system consists of innate and adaptive branches, invertebrates only have innate immunity. This feature makes them an ideal model system for studying the cellular and molecular mechanisms of innate immunity sensu stricto without reciprocal interferences from adaptive immunity. Although invertebrate immunity is evolutionarily older and a precursor of vertebrate immunity, it is far from simple. Despite lacking lymphocytes and functional immunoglobulin, the invertebrate immune system has many sophisticated mechanisms and features, such as long-term immune memory, which, for decades, have been exclusively attributed to adaptive immunity. In this review, we describe the cellular and molecular aspects of invertebrate immunity, including the epigenetic foundation of innate memory, the transgenerational inheritance of immunity, genetic immunity against invading transposons, the mechanisms of self-recognition, natural transplantation, and germ/somatic cell parasitism.

Testicular macrophages are the principal immune cells in the testis. In addition to their classical immune roles, they regulate male hormone synthesis by Leydig cells, regeneration of Leydig cells, spermatogonia proliferation and differentiation, maintenance of testis-specific environment for sperm formation, and testis development. The juvenile and adult testes contain two distinct macrophage populations with unique tissue localization, genetic markers, morphology, and function. The interstitial macrophages are physically and functionally connected to Leydig cells, while the peritubular macrophages localize around the seminiferous tubules and are crucial for spermatogonia differentiation. Macrophages in the fetal testes regulate testis vasculature formation and clearance of mislocated cells. The origin of testicular macrophages is unclear. Some studies suggest their origin from the yolk sac and others from the bone marrow-derived monocytes. We discuss this issue at the end of this review article., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Macrophages are dynamic and plastic immune cells essential for tissue homeostasis and pathogen defense. Their cell cycle regulation is highly influenced by intrinsic and extrinsic signals facilitating rapid responses to infections and tissue damage. Dysregulation of their cell cycle leads to diseases like cancer and HIV. This chapter highlights aspects of the macrophage cell cycle crucial for the development of targeted therapies., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Timely mitosis is critically important for early embryo development. It is regulated by the activity of the conserved protein kinase CDK1. The dynamics of CDK1 activation must be precisely controlled to assure physiologic and timely entry into mitosis. Recently, a known S-phase regulator CDC6 emerged as a key player in mitotic CDK1 activation cascade in early embryonic divisions, operating together with Xic1 as a CDK1 inhibitor upstream of the Aurora A and PLK1, both CDK1 activators. Herein, we review the molecular mechanisms that underlie the control of mitotic timing, with special emphasis on how CDC6/Xic1 function impacts CDK1 regulatory network in the Xenopus system. We focus on the presence of two independent mechanisms inhibiting the dynamics of CDK1 activation, namely Wee1/Myt1- and CDC6/Xic1-dependent, and how they cooperate with CDK1-activating mechanisms. As a result, we propose a comprehensive model integrating CDC6/Xic1-dependent inhibition into the CDK1-activation cascade. The physiological dynamics of CDK1 activation appear to be controlled by the system of multiple inhibitors and activators, and their integrated modulation ensures concomitantly both the robustness and certain flexibility of the control of this process. Identification of multiple activators and inhibitors of CDK1 upon M-phase entry allows for a better understanding of why cells divide at a specific time and how the pathways involved in the timely regulation of cell division are all integrated to precisely tune the control of mitotic events.

Maternal embryonic leucine-zipper kinase (MELK) plays a significant role in cell cycle progression, mitosis, cell migration, cell renewal, gene expression, embryogenesis, proliferation, apoptosis, and spliceosome assembly. In addition, MELK is known to be overexpressed in multiple types of cancer and is associated with cancer proliferation. Tumorigenesis shares many similarities with wound healing, in which the rate of cell proliferation is a critical factor. Therefore, this study aimed to determine the involvement of MELK in the regulation of cell division in two cell types involved in this process, namely fibroblasts and keratinocytes. We examined how temporal overexpression of wild-type and kinase-dead MELK kinase variants affect the rate of proliferation, viability, cell cycle, and phosphorylation state of other kinases involved in these processes, such as ERK1/2, AKT1, MAPK9, p38, and p53. We explored if MELK could be used as a therapeutic stimulator of accelerated wound healing via increased proliferation. We observed that aberrant expression of MELK results in abnormal proliferation, altered cell cycle distribution, and decreased viability of the cells, which challenge the utility of MELK in accelerated wound healing. Our results indicate that, at least in healthy cells, any deviation from precisely controlled MELK expression is harmful to fibroblasts and keratinocytes.

Like all immune cells, macrophages do not act autonomously but in unison with other immune cells, surrounding tissues, and the niche they occupy. Constant exchange of information between cellular and noncellular participants within a tissue allows for preserving homeostasis and defining responses in a pathologic environment. Although molecular mechanisms and pathways involved in reciprocal signaling between macrophages and other immune cells have been known for decades, much less is known about interactions between macrophages and stem/progenitor cells. Based on the time when stem cells form, there are two stem cell types: embryonic stem cells existing only in an early embryo, which are pluripotent and can differentiate into any cell type present in an adult, and somatic (adult) stem cells formed in fetus and persisting for whole adult life. Tissues and organs have their own (tissue-specific and organ-specific) adult stem cells, which serve as a reserve for tissue homeostasis and regeneration after injury. It is still uncertain whether organ- and tissue-specific stem cells are actual stem cells or just progenitor cells. The important question is how stem/progenitor cells can sculpt macrophage phenotype and functions. Even less is known if or how macrophages can shape stem/progenitor cell functions, their divisions, and fate. We describe here examples from recent studies of how stem/progenitor cells can affect macrophages and how macrophages can influence stem/progenitor cell properties, functions, and destiny., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://sci.amegroups.com/article/view/10.21037/sci-2023-009/coif). The authors have no conflicts of interest to declare., (2023 Stem Cell Investigation. All rights reserved.)

Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identified A2780 cells as the most synergistically responding, thus optimal for further analysis. Because hypoxia is the hallmark of the solid tumor microenvironment, we compared the effects of Res alone and in combination with CisPt in hypoxia (pO 2 = 1%) vs. normoxia (pO 2 = 19%). Hypoxia caused an increase (43.2 vs. 5.0%) in apoptosis and necrosis (14.2 vs. 2.5%), reactive oxygen species production, pro-angiogenic HIF-1α (hypoxia-inducible factor-1α) and VEGF (vascular endothelial growth factor), cell migration, and downregulated the expression of ZO1 (zonula occludens-1) protein in comparison to normoxia. Res was not cytotoxic under hypoxia in contrast to normoxia. In normoxia, Res alone or CisPt+Res caused apoptosis via caspase-3 cleavage and BAX, while in hypoxia, it reduced the accumulation of A2780 cells in the G2/M phase. CisPt+Res increased levels of vimentin under normoxia and upregulated SNAI1 expression under hypoxia. Thus, various effects of Res or CisPt+Res on A2780 cells observed in normoxia are eliminated or diminished in hypoxia. These findings indicate the limitations in using Res as an adjuvant with CisPt therapy in OC.

Skin wounds remain a significant problem for the healthcare system, affecting the clinical outcome, patients' quality of life, and financial costs. Reduced wound healing times would improve clinical, economic, and social aspects for both patients and the healthcare system. Skin wound healing has been studied for years, but effective therapy that leads to accelerated wound healing remains to be discovered. This study aimed to evaluate the potential of MELK silencing to accelerate wound healing. A vectorless, transient knockdown of the MELK gene using siRNA was performed in a murine skin wound model. The wound size, total collagen, type 3 collagen, vessel size, vessel number, cell proliferation, cell apoptosis, number of mast cells, and immune infiltration by CD45, CD11b, CD45, and CD8a cells were evaluated. We observed that treatment with MELK siRNA leads to significantly faster wound closing associated with increased collagen deposition.

Immunological memory is a crucial part of the immune defense that allows organisms to respond against previously encountered pathogens or other harmful factors. Immunological memory is based on the establishment of epigenetic modifications of the genome. The ability to memorize encounters with pathogens and other harmful factors and mount enhanced defense upon subsequent encounters is an evolutionarily ancient mechanism operating in all animals and plants. However, the term immunological memory is usually restricted to the organisms (invertebrates and vertebrates) possessing the immune system. The mammalian immune system, with innate and adaptive branches, is the most sophisticated among vertebrates. The concept of innate memory and memory macrophages is relatively new and thus understudied. We introduce the concept of immunological memory and describe types of memory in different species and their evolutionary status. We discuss why the traditional view of innate immune cells as the first-line defenders is too restrictive and how the innate immune cells can accumulate and retain immunologic memory. We describe how the initial priming leads to chromatin remodeling and epigenetic changes, which allow memory macrophage formation. We also summarize what is currently known about the mechanisms underlying development of memory macrophages; their molecular and metabolic signature and surface markers; and how they may contribute to immune defense, diseases, and organ transplantation., Competing Interests: The authors declare no conflict of interest.

Atherosclerosis is an inflammatory disease depending on the buildup, called plaque, of lipoproteins, cholesterol, extracellular matrix elements, and various types of immune and non-immune cells on the artery walls. Plaque development and growth lead to the narrowing of the blood vessel lumen, blocking blood flow, and eventually may lead to plaque burst and a blood clot. The prominent cellular components of atherosclerotic plaque are the foam cells, which, by trying to remove lipoprotein and cholesterol surplus, also participate in plaque development and rupture. Although the common knowledge is that the foam cells derive from macrophages, studies of the last decade clearly showed that macrophages are not the only cells able to form foam cells in atherosclerotic plaque. These findings give a new perspective on atherosclerotic plaque formation and composition and define new targets for anti-foam cell therapies for atherosclerosis prevention. This review gives a concise description of foam cells of different pedigrees and describes the main mechanisms participating in their formation and function.

This review introduces the subject of senescence, aging, and the formation of senescent multinucleated giant cells. We define senescence and aging and describe how molecular and cellular senescence leads to organismal senescence. We review the latest information on senescent cells' cellular and molecular phenotypes. We describe molecular and cellular features of aging and senescence and the role of multinucleated giant cells in aging-related conditions and cancer. We explain how multinucleated giant cells form and their role in aging arteries and gonads. We also describe how multinucleated giant cells and the reversibility of senescence initiate cancer and lead to cancer progression and metastasis. We also describe molecules and pathways regulating aging and senescence in model systems and their applicability to clinical therapies in age-related diseases.

Cell fusion (fusogenesis) occurs in natural and pathological conditions in prokaryotes and eukaryotes. Cells of monocyte-macrophage lineage are highly fusogenic. They create syncytial multinucleated giant cells (MGCs) such as osteoclasts (OCs), MGCs associated with the areas of infection/inflammation, and foreign body-induced giant cells (FBGCs). The fusion of monocytes/macrophages with tumor cells may promote cancer metastasis. We describe types and examples of monocyte-macrophage lineage cell fusion and the role of actin-based structures in cell fusion.

Typically, all cells of a given organism have the same set of chromosomes. However, there are exceptions to this rule, and in many organisms, the somatic cells and germ cells, various types of somatic cells or organs, or females and males, have different genomes. One of the sources of such differences is chromosome/DNA elimination/chromatin diminution that is a naturally programmed phenomenon. We describe chromosome/DNA elimination in various organisms and present the current hypotheses on its origin, mechanisms, significance, and consequences., Competing Interests: Declaration of competing interest None of the authors has any conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Patients with hemato-oncologic diseases are particularly vulnerable to severe infections. Adult patients with blood cancers infected with SARS-CoV-2 had poorer treatment outcomes and higher mortality than patients with COVID-19 without burden. However, in pediatric patients with hemato-oncologic diseases the course of COVID-19 is milder than in adults in the same group of patients. In this report, we describe the case of our patient with acute lymphoblastic leukemia infected with SARS-CoV-2 and treated with remdesivir. We also review the existing literature of pediatric patients who have been diagnosed with both hemato-oncologic diseases and COVID-19., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The actin cytoskeleton and actin-dependent molecular and cellular events are responsible for the organization of eukaryotic cells and their functions. Viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), depend on host cell organelles and molecular components for cell entry and propagation. Thus, it is not surprising that they also interact at many levels with the actin cytoskeleton of the host. There have been many studies on how different viruses reconfigure and manipulate the actin cytoskeleton of the host during successive steps of their life cycle. However, we know relatively little about the interactions of SARS-CoV-2 with the actin cytoskeleton. Here, we describe how the actin cytoskeleton is involved in the strategies used by different viruses for entry, assembly, and egress from the host cell. We emphasize what is known and unknown about SARS-CoV-2 in this regard. This review should encourage further investigation of the interactions of SARS-CoV-2 with cellular components, which will eventually be helpful for developing novel antiviral therapies for mitigating the severity of COVID-19., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cell to cell interactions are crucial for morphogenesis and tissue formation. Desmoplakin (encoded by the Dsp gene) is a component of desmosomes and anchors the transmembrane adhesion proteins to the cytoskeleton. Its role in gonad development remains vague. To study the role of desmoplakin in gonad development, we used a tissue-specific knockout of the Dsp gene in the NR5A1+ somatic cells of the gonads. We show here that desmoplakin is necessary for the survival of germ cells in fetal testes and ovaries. The Dspknockout in NR5A1+ somatic cells in testes decreased the number of germ cells, and thus the size of the testes, but did not affect the Sertoli cells or the structure of testis cords and interstitium. The Dspknockout in NR5A1+ somatic cells in ovaries decreased the number of female germ cells and drastically reduced the formation of ovarian follicles. Dsp knockout in NR5A1+ somatic cells did not affect the sex determination and sexual differentiation of the gonads, as judged from an unchanged expression of genes essential for these processes. We conclude that mediation by desmoplakin cell adhesion between the gonadal cells is necessary for germ cell survival.

Vitamin D is a hormone regulating the immune system and playing a pivotal role in responses to microbial infections. It regulates inflammatory processes by influencing the transcription of immune-response genes in macrophages, T cells, and dendritic cells. The proven role of vitamin D in many infectious diseases of the respiratory tract indicated that vitamin D should also play a role in SARS-CoV-2 infection. Vitamin D inhibits cytokine storm by switching the pro-inflammatory Th1 and Th17 to the anti-inflammatory Th2 and Treg response. Vitamin D is therefore expected to play a role in preventing, relieving symptoms, or treating SARS-CoV-2 infection symptoms, including severe pneumonia. There are several possible mechanisms by which vitamin D may reduce the risk of COVID-19 infection, such as induction of the transcription of cathelicidin and defensin. Also a nongenomic antiviral action of vitamin D and lumisterol, the molecule closely related to vitamin D, was reported. Despite this enormous progress, currently, there is still insufficient scientific evidence to support the claim that vitamin D supplementation may help treat COVID-19 infection. The pandemic restrictions were also shown to impact vitamin D uptake by limiting exposure to sunlight., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tomaszewska, Rustecka, Lipińska-Opałka, Piprek, Kloc, Kalicki and Kubiak.)

Epigenetic marks, such as DNA methylation and posttranslational modifications of core histones, are the key regulators of gene expression. In the mouse, many of these marks are erased during gamete formation and must be introduced de novo after fertilization. Some of them appear synchronously, but the others are deposited asynchronously and/or remain differently distributed on maternal and paternal chromatin. Although the mechanisms regulating these processes are not entirely understandable, it is commonly accepted that epigenetic reprogramming occurring during the first cell cycle of a mouse embryo is crucial for its further development. This chapter focuses on selected epigenetic modifications, such as DNA methylation, the introduction of histone variants, histones acetylation, phosphorylation, and methylation. Properly depositing these marks on maternal and paternal chromatin is crucial for normal embryonic development., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: The main source of vitamin D is skin synthesis, which depends on sunlight exposure. During the pandemic, COVID-19 children were obliged to home confinement, which potentially limiting sunlight exposure. The aim of this study was to evaluate whether home confinement led to decreased vitamin D serum levels in children in Warsaw, Poland., Methods: The study included 1472 children who were divided into two groups, based on the date of 25(OH)D level blood sampling: before and during the pandemic. Children under 1 year of age (infants) were analysed separately., Results: A statistically significant decrease in the average level of vitamin D was observed between groups of children over 1 year of age (35 ng/mL ± 18 vs. 31 ng/mL ± 14). In infants from both groups, the mean vitamin D levels were within the normal range (Group 1 inf 54 ng/mL ± 21 vs. Group 2 inf 47 ng/mL ± 15). The characteristic seasonal variability was observed before the pandemic, with maximal vitamin D levels in summer (40 ng/mL ± 17) and minimal levels in winter (30 ng/mL ± 14). During the pandemic, no seasonal variability was observed (summer 30 ng/mL ± 11 vs. winter 30 ng/mL ± 19)., Conclusions: The COVID-19 pandemic restrictions led to a significant decrease in vitamin D serum levels in children.

Macrophages were discovered in the 19th century by Ukrainian biologist Élie Metchnikoff who worked in Ukraine, Russia, and France [...].

Actin is one of the most abundant proteins in eukaryotic cells. There are different pools of nuclear actin often undetectable by conventional staining and commercial antibodies used to identify cytoplasmic actin. With the development of more sophisticated imaging and analytical techniques, it became clear that nuclear actin plays a crucial role in shaping the chromatin, genomic, and epigenetic landscape, transcriptional regulation, and DNA repair. This multifaceted role of nuclear actin is not only important for the function of the individual cell but also for the establishment of cell fate, and tissue and organ differentiation during development. Moreover, the changes in the nuclear, chromatin, and genomic architecture are preamble to various diseases. Here, we discuss some of the newly described functions of nuclear actin.

Human placenta formation relies on the interaction between fused trophoblast cells of the embryo with uterine endometrium. The fusion between trophoblast cells, first into cytotrophoblast and then into syncytiotrophoblast, is facilitated by the fusogenic protein syncytin. Syncytin derives from an envelope glycoprotein (ENV) of retroviral origin. In exogenous retroviruses, the envelope glycoproteins coded by env genes allow fusion of the viral envelope with the host cell membrane and entry of the virus into a host cell. During mammalian evolution, the env genes have been repeatedly, and independently, captured by various mammalian species to facilitate the formation of the placenta. Such a shift in the function of a gene, or a trait, for a different purpose during evolution is called an exaptation (co-option). We discuss the structure and origin of the placenta, the fusogenic and non-fusogenic functions of syncytin, and the mechanism of cell fusion. We also comment on an alleged danger of the COVID-19 vaccine based on the presupposed similarity between syncytin and the SARS-CoV-2 spike protein.

Clinical data suggest that during the current COVID-19 pandemic, children are less prone than adults to SARS-CoV-2 infection. Our purpose was to determine the frequency of SARS-CoV-2 in children vs. adults during the 2020 pandemic in Warsaw, Poland, and to investigate whether RSV and/or influenza A/B infections were associated with SARS-CoV-2 infections. We present results of RT-PCR tests for SARS-CoV-2 performed in Warsaw, Poland. Some of the pediatric subjects were also PCR-tested for RSV, and A and B influenza. We compared the test results from the four groups of symptomatic and asymptomatic subjects: 459 symptomatic pediatric patients (children 0-18 years old), 1774 symptomatic adults, 445 asymptomatic children, and 239 asymptomatic adults. 3.26% (15/459) of symptomatic pediatric patients were positive for SARS-CoV-2 in contrast to 5.58% (99/1774) of symptomatic adults (p = 0.0448). There were no SARS-CoV-2 positive cases in the group of asymptomatic children (0/445) and two positive cases in the group of asymptomatic adults (2/239), i.e., 0.83%. In the group of symptomatic pediatric patients, 17.14% (6/35) (p = 0.0002) were positive for RSV, 8.16% (4/49) were positive for influenza A, and 2.04% (1/49), thus 10.20% (5/49) (p = 0.0176) for influenza A/B. Children were less prone to SARS-CoV-2 infection than the adults during the COVID-19 pandemic in Warsaw. Higher percentage of symptomatic children was infected with RSV or influenza A/B than with SARS-CoV-2. This suggests a necessity for the testing for all these viruses for an early identification and isolation of SARS-CoV-2-positive patients for an ensuing 2020 autumn return of COVID-19.

Vitamin D regulates homeostasis, anti-microbial response, and inflammation. The vitamin D receptors are expressed in the macrophages and other immune cells, regulating the transcription of many different genes, including those coding the anti-microbial peptides. One of the most severe complications of the SARS-CoV-2 infection is the acute respiratory distress syndrome (ARDS) caused by the hyperinflammatory response (commonly called cytokine storm) of the lung macrophages. Studies showed that Vitamin D deficiency increases the severity of the ARDS in COVID-19 infection. We discuss here how the vitamin D supplementation may influence macrophage and myeloid-derived suppressor cells (MDSCs) inflammatory response, subdue the hyperinflammatory response, and lessen the ARDS in COVID-19 patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1and and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other's studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.

Vitamin D, in addition to its superior role as a factor regulating calcium-phosphate metabolism, shows wide effects in other processes in the human body, including key functions of the immune system. This is due to the presence of vitamin D receptors in most cells of the human body. In our study, we aimed to assess whether there is a correlation between vitamin D content and the clinical course of allergic diseases as well as establish their immunological parameters in children. We found that vitamin D deficiency was significantly more frequent in the group of children with an allergic disease than in the control group ( p = 0.007). Statistically significant higher vitamin D concentrations in blood were observed in the group of children with a mild course of the disease compared to children with a severe clinical course ( p = 0.03). In the group of children with vitamin D deficiency, statistically significant lower percentages of NKT lymphocytes and T-regulatory lymphocytes were detected compared to the group of children without deficiency (respectively, p = 0.02 and p = 0.05), which highlights a potential weakness of the immune system in these patients. Furthermore, statistically higher levels of interleukin-22 were observed in the group of children with vitamin D deficiency ( p = 0.01), suggesting a proinflammatory alert state. In conclusion, these results confirm the positive relationship between the optimal content of vitamin D and the lesser severity of allergic diseases in children, establishing weak points in the immune system caused by vitamin D deficiency in children.

The timing of the M-phase is precisely controlled by a CDC6-dependent mechanism inhibiting the mitotic histone H1 kinase. Here, we describe the differential regulation of the dynamics of this mitotic kinase activity by exogenous cyclin A or cyclin B in the Xenopus laevis cycling extracts. We show that the experimental increase in cyclin A modifies only the level of histone H1 kinase activity, while the cyclin B increase modifies two parameters: histone H1 kinase activity and the timing of its full activation, which is accelerated. On the other hand, the cyclin A depletion significantly delays full activation of histone H1 kinase. However, when CDC6 is added to such an extract, it inhibits cyclin B-associated histone H1 kinase, but does not modify the mitotic timing in the absence of cyclin A. Further, we show via p9 co-precipitation with Cyclin-Dependent Kinases (CDKs), that both CDC6 and the bona fide CDK1 inhibitor Xic1 associate with the mitotic CDKs. Finally, we show that the Xic1 temporarily separates from the mitotic CDKs complexes during the peak of histone H1 kinase activity. These data show the differential coordination of the M-phase progression by cyclin A- and cyclin B-dependent CDKs, confirm the critical role of the CDC6-dependent histone H1 kinase inhibition in this process, and show that CDC6 acts differentially through the cyclin B- and cyclin A-associated CDKs. This CDC6- and cyclins-dependent mechanism likely depends on the precisely regulated association of Xic1 with the mitotic CDKs complexes. We postulate that: i. the dissociation of Xic1 from the CDKs complexes allows the maximal activation of CDK1 during the M-phase, ii. the switch between cyclin A- and cyclin B-CDK inhibition upon M-phase initiation may be responsible for the diauxic growth of mitotic histone H1 kinase activity.

The development, progression, or stabilization of the atherosclerotic plaque depends on the pro-inflammatory and anti-inflammatory macrophages. The influx of the macrophages and the regulation of macrophage phenotype, inflammatory or anti-inflammatory, are controlled by the small GTPase RhoA and its downstream effectors. Therefore, macrophages and the components of the RhoA pathway are attractive targets for anti-atherosclerotic therapies, which would inhibit macrophage influx and inflammatory phenotype, maintain an anti-inflammatory environment, and promote tissue remodeling and repair. Here, we discuss the recent findings on the role of macrophages and RhoA pathway in the atherosclerotic plaque formation and resolution and the novel therapeutic approaches.

Tissue-resident macrophages and those conscripted from the blood/bone marrow are professional phagocytes. They play a role in tissue homeostasis, replacement, and healing, and are the first-line responders to microbial (viral, bacterial, and fungi) infections. Intrinsic ameboid-type motility allows non-resident macrophages to move to the site of inflammation or injury, where, in response to the inflammatory milieu they perform the anti-microbial and/or tissue repair functions. Depending on the need and the signaling from the surrounding tissue and other immune cells, macrophages acquire morphologically and functionally different phenotypes, which allow them to play either pro-inflammatory or anti-inflammatory functions. As such, the macrophages are also the major players in the rejection of the transplanted organs making an excellent target for the novel anti-rejection therapies in clinical transplantation. In this review, we describe some of the less covered aspects of macrophage response to microbial infection and organ transplantation.

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but they also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes and facilitate the capacitation of sperm in the female reproductive tract and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins; however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and we suggest topics for future research.

Diabetes mellitus (DM) augments the risk of hospitalization and mortality resulting from viral, bacterial, or fungal pathogen infection. This has been also true for the past SARS and MERS, and current SARS-CoV-2 coronavirus epidemics. Clinical data indicate that SARS-CoV-2 infection triggers a severe course of COVID-19 more frequently in diabetic than non-diabetic patients. Here we overview the cellular and molecular mechanisms associated with this phenomenon. We focus on alterations in the immune cells, especially monocytes and macrophages, involved in innate immune response and inflammatory processes, which differ in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). We also describe the DM-related changes in the monocyte/macrophages functions, how they could lead to the severe outcome of SARS-CoV-2 infection, and importantly, if and how they could initiate DM in DM-susceptible patients., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Springer Nature Switzerland AG 2020.)

Children, because of having an immature immune system, are usually more prone than the adults to the microbial infections and have more severe symptoms, which is especially true for the newborns, and very young children. However, the review of clinical data from the current COVID-19 pandemic indicates otherwise. We discuss here what are the main features and components of children's immune system, the role of maternal transmission of immunity, and what are the possible explanations for the seemingly lower infection rate and severity of COVI-19 in children., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Cytokines are important immune modulator factors controlling homeostasis of the body and are involved in tissue regeneration after wound healing. The encapsulation of cytokines in liposomes has many advantages potentially useful for their transfer to the cells. Liposomes protect cytokines from neutralization, improving their pharmacokinetics or biologic activity in vivo . They are targeted to specific cell types and may delay the release of cytokines, allowing their sustained paracrine delivery. Their physicochemical characteristics such as size, shape, charge, and stability are important parameters improving bio-distribution and prolonged pharmacokinetics of encapsulated cytokines., Material and Methods: We developed an efficient protocol for the encapsulation of two types of cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), in liposomes that can be stored long term in the active state., Results: This method allows for the encapsulation of 12-13% of the total amount of cytokines and 50% of encapsulated cytokines are entrapped in liposomes of more than ≤ 600 nm in diameter. We show that in the studied cell lines the liposome-encapsulated cytokines do not affect cell morphology, proliferation or mortality., Conclusions: The G-CSF or GM-CSF can be delivered to the cells in working concentrations through the encapsulation in the liposomes. Before the clinical application, the efficiency of these liposomes should be confirmed by an in vivo study., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)