Matthias Hardtke-Wolenski, Sybille Landwehr-Kenzel
Regulatory T cells (Tregs) are a specialized subgroup of T-cell lymphocytes that is crucial for maintaining immune homeostasis and preventing excessive immune responses. Depending on their differentiation route, Tregs can be subdivided into thymically derived Tregs (tTregs) and peripherally induced Tregs (pTregs), which originate from conventional T cells after extrathymic differentiation at peripheral sites. Although the regulatory attributes of tTregs and pTregs partially overlap, their modes of action, protein expression profiles, and functional stability exhibit specific characteristics unique to each subset...
March 20, 2024: Molecular and Cellular Pediatrics
Abigail Schulz, Natalie Huynh, Margaret Heger, Mustafa Bakir
BACKGROUND: Although the severity of coronavirus disease 2019 (COVID-19) tends to be lower in children, it can still lead to severe illness, particularly among those with chronic medical conditions. While remdesivir (RDV) is one of the few approved antiviral treatments for COVID-19 in children in many countries, the available data on the safety of RDV in this population is limited. METHODS: To address this knowledge gap, a multicenter study involving 65 patients retrospectively analyzed the clinical data from individuals aged <18 who were hospitalized due to severe COVID-19 (defined as SpO2 < 94% or requiring supplemental oxygen) and received at least one dose of RDV...
February 21, 2024: Molecular and Cellular Pediatrics
Caroline Vanessa Kliem, Bianca Schaub
BACKGROUND: As the most common chronic disease in childhood, asthma displays a major public health problem worldwide with the incidence of those affected rising. As there is currently no cure for allergic asthma, it is mandatory to get a better understanding of the underlying molecular mechanism. MAIN BODY: By producing IgE antibodies upon allergen contact, B cells play a pivotal role in allergic asthma. Besides that, IL-10-secreting B cell subsets, namely regulatory B cells (Bregs), are reported in mice and humans to play a role in allergic asthma...
January 4, 2024: Molecular and Cellular Pediatrics
G Varga, S Schleifenbaum, U Koenig, J Waldkirch, C Hinze, C Kessel, W Geluk, T Pap, Elke Lainka, Tilmann Kallinich, D Foell, H Wittkowski
BACKGROUND: Familial Mediterranean fever (FMF) is a prototypical autoinflammatory syndrome associated with phagocytic cell activation. Pyrin mutations are the genetic basis of this disease, and its expression has been shown in monocytes, granulocytes, dendritic cells, and synovial fibroblasts. Pyrin functions as a cytosolic pattern recognition receptor and forms a distinct pyrin inflammasome. The phagocyte-specific protein S100A12 is predominantly expressed in granulocytes and belongs to the group of damage associated molecular patterns (DAMP)...
December 13, 2023: Molecular and Cellular Pediatrics
Will W Minuth
BACKGROUND: The kidneys of preterm and low birth weight babies reflect vulnerability, since several noxae can evoke the termination of nephron formation. This again leads to oligonephropathy with severe consequences for health in the later life. While the clinical parameters have been intensely investigated, only little is known about the initial traces left by the noxae. For the fetal human kidney, solely the lack of basophilic S-shaped bodies and the reduction in width of the nephrogenic zone were registered...
November 28, 2023: Molecular and Cellular Pediatrics
Michelle A Farrar, Loudella Calotes-Castillo, Ranil De Silva, Peter Barclay, Lani Attwood, Julie Cini, Monica Ferrie, Didu S Kariyawasam
Onasemnogene abeparvovec has been life-changing for children with spinal muscular atrophy (SMA), signifying the potential and progress occurring in gene- and cell-based therapies for rare genetic diseases. Hence, it is important that clinicians gain knowledge and understanding in gene therapy-based treatment strategies for SMA. In this review, we describe the development and translation of onasemnogene abeparvovec from clinical trials to healthcare practice and share knowledge on the facilitators and barriers to implementation...
November 15, 2023: Molecular and Cellular Pediatrics
Lisa Ruck, Susanna Wiegand, Peter Kühnen
BACKGROUND: Increasing prevalence of morbid obesity accompanied by comorbidities like type 2 diabetes mellitus (T2DM) led to a demand for improving therapeutic strategies and pharmacological intervention options. Apart from genetics, inflammation processes have been hypothesized to be of importance for the development of obesity and related aspects like insulin resistance. MAIN TEXT: Within this review, we provide an overview of the intricate interplay between chronic inflammation of the adipose tissue and the hypothalamus and the development of obesity...
November 14, 2023: Molecular and Cellular Pediatrics
Adam Klocperk, Marketa Bloomfield, Zuzana Parackova, Ludovic Aillot, Jiri Fremuth, Lumir Sasek, Jan David, Filip Fencl, Aneta Skotnicova, Katerina Rejlova, Martin Magner, Ondrej Hrusak, Anna Sediva
BACKGROUND: Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after the original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia, and activation of T cells with elevated IFN-γ. Observing the production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II, and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19...
October 28, 2023: Molecular and Cellular Pediatrics
Dirk Foell, Melanie Saers, Carolin Park, Ninna Brix, Mia Glerup, Christoph Kessel, Helmut Wittkowski, Claas Hinze, Lillemor Berntson, Anders Fasth, Charlotte Myrup, Ellen Nordal, Marite Rygg, Henrik Hasle, Birgitte Klug Albertsen, Troels Herlin, Dirk Holzinger, Christian Niederberger, Bernhard Schlüter
BACKGROUND: Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings...
October 25, 2023: Molecular and Cellular Pediatrics
Ana Renata Pinto de Toledo, Higor Arruda Caetano, Jovito Adiel Skupien, Carina Rodrigues Boeck, Humberto Fiori, Rosane Souza da Silva
OBJECTIVE: Scientific scrutiny has proved the safety and benefits of caffeine to treat apnoea of prematurity (AOP). However, there is no consensus on the effects of this treatment on sleep, especially considering the key role of adenosine and early brain development for sleep maturation. We systematically reviewed studies with sleep as a primary and/or secondary outcome or any mention of sleep parameters in the context of caffeine treatment for AOP. METHODS: We performed a systematic search of PubMed, Web of Science and the Virtual Health Library from inception to 7 September 2022 to identify studies investigating the short- and long-term effects of caffeine to treat AOP on sleep parameters...
September 18, 2023: Molecular and Cellular Pediatrics
Jonathan Woods, Susmito Biswas
INTRODUCTION: Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the premature retina with the potential to progress to extraretinal neovascularisation. This review serves as an introduction to retinopathy of prematurity (ROP), outlining key parts of ROP pathophysiology, diagnosis and treatment. ROP is traditionally diagnosed by indirect ophthalmoscopy and classified using anatomical zones, stages of disease, and the presence or absence of "plus disease" (dilation and tortuosity of the major retinal arterioles and venules)...
September 15, 2023: Molecular and Cellular Pediatrics
Vasil Toskov, Stephan Ehl
Many inborn errors of immunity (IEI) manifest with hallmarks of both immunodeficiency and immune dysregulation due to uncontrolled immune responses and impaired immune homeostasis. A subgroup of these disorders frequently presents with autoimmunity and lymphoproliferation (ALPID phenotype). After the initial description of the genetic basis of autoimmune lymphoproliferative syndrome (ALPS) more than 20 years ago, progress in genetics has helped to identify many more genetic conditions underlying this ALPID phenotype...
September 13, 2023: Molecular and Cellular Pediatrics
Sebastian Felix Nepomuk Bode, Anja Schwender, Monika Toth, Christine Kaeppler-Schorn, Ute Siebeneich, Joachim Freihorst, Ales Janda, Dorit Fabricius
BACKGROUND: The SARS-CoV-2 pandemic has caused significant pulmonary morbidity and mortality in the adult population. Children and adolescents typically show milder symptoms; however, a relevant proportion of them report persistent pulmonary symptoms even after mild SARS-CoV-2 infection. Functional respiratory disorders may be relevant differential diagnoses of persistent dyspnea. This study aims at characterizing functional respiratory disorders that may arise after SARS-CoV-2 infection regarding their clinical presentation and pulmonary function tests as well as gaining insights into the clinical course after initiation of appropriate therapy...
September 12, 2023: Molecular and Cellular Pediatrics
Francesco Foppiano, Bianca Schaub
BACKGROUND: Asthma is an inflammatory lung disease that constitutes the most common noncommunicable chronic disease in childhood. Childhood asthma shows large heterogeneity regarding onset of disease, symptoms, severity, prognosis, and response to therapy. MAIN BODY: Evidence suggests that this variability is due to distinct pathophysiological mechanisms, which has led to an exhaustive research effort to understand and characterize these distinct entities currently designated as "endotypes...
August 30, 2023: Molecular and Cellular Pediatrics
Carlos Menendez-Castro, Nada Cordasic, Fabian B Fahlbusch, Joachim Woelfle, Karl F Hilgers, Andrea Hartner
BACKGROUND: Clinical studies suggest that female sex plays a protective role in the development and progression of kidney disease. Recent experimental studies indicate that in male rats early nephron loss under ongoing nephrogenesis is accompanied by severe long-term sequelae. In humans, nephron formation occurs mainly in the third trimester, ceasing with 36 weeks of gestation. Due to perinatal complications, preterm infants delivered during this vulnerable period may undergo acute nephron loss...
August 25, 2023: Molecular and Cellular Pediatrics
Frank Jochum, Martina Meyer-Krott, Tina Hübler, Maja Lorenz, Raffi Bedikian, Joseph Zakarian, Anja Litzka, Guido Judex, Holger Hertzberg, Daniela Klee, Lothar Maurer, Martin Schacht, Adnan Al-Radhi, Jan Maier, Alexander Kröckel, Christian Faustmann, Luca Lavalle, Samir Dahbane
INTRODUCTION: Human milk oligosaccharides (HMOs) are important components of human milk having diverse functions in the development of infants. Randomized controlled trials (RCTs) have demonstrated that infant formulas with the HMOs 2'-fucosyllactose (2'FL) and lacto-N-neotetraose (LNnT) are safe, well-tolerated, and support normal growth. This study aimed to generate real-world evidence (RWE) on growth and gastrointestinal (GI) tolerance in infants consuming a formula with 1 g/L 2'FL and 0...
August 19, 2023: Molecular and Cellular Pediatrics
Markos K Tomidis Chatzimanouil, Ines Goppelt, Yvonne Zeissig, Ulrich J Sachs, Martin W Laass
Metamizole is an analgesic, antipyretic, and spasmolytic drug in Germany only approved for the treatment of severe pain or high fever that does not respond to other measures. In recent years, an increased use has been described among both adults and children, often against the approved indication. The most important side effect of metamizole is the development of agranulocytosis (neutrophil count < 500/µL). Incidence of metamizole-induced agranulocytosis (MIA) ranges depending on the study from 0...
August 17, 2023: Molecular and Cellular Pediatrics
Valentina Natoli, Amandine Charras, Gabriele Hahn, Christian M Hedrich
Systemic lupus erythematosus (SLE) is a rare autoimmune/inflammatory disease with significant morbidity and mortality. Approximately 15-20% of SLE patients develop the disease during childhood or adolescence (juvenile-onset SLE/jSLE). Patients with jSLE exhibit more variable and severe disease when compared to patients with disease-onset during adulthood. Neuropsychiatric (NP) involvement is a clinically heterogenous and potentially severe complication. Published reports on the incidence and prevalence of NP-jSLE are scarce, and the exact pathophysiology is poorly understood...
August 9, 2023: Molecular and Cellular Pediatrics
I Mižíková, B Thébaud
Bronchopulmonary dysplasia (BPD) is a multifactorial disease occurring as a consequence of premature birth, as well as antenatal and postnatal injury to the developing lung. BPD morbidity and severity depend on a complex interplay between prenatal and postnatal inflammation, mechanical ventilation, and oxygen therapy as well as associated prematurity-related complications. These initial hits result in ill-explored aberrant immune and reparative response, activation of pro-fibrotic and anti-angiogenic factors, which further perpetuate the injury...
April 18, 2023: Molecular and Cellular Pediatrics
Valentina Bruno, Anne Katrin Mühlig, Jun Oh, Christoph Licht
Podocytes are differentiated epithelial cells which play an essential role to ensure a normal function of the glomerular filtration barrier (GFB). In addition to their adhesive properties in maintaining the integrity of the filtration barrier, they have other functions, such as synthesis of components of the glomerular basement membrane (GBM), production of vascular endothelial growth factor (VEGF), release of inflammatory proteins, and expression of complement components. They also participate in the glomerular crosstalk through multiple signalling pathways, including endothelin-1, VEGF, transforming growth factor β (TGFβ), bone morphogenetic protein 7 (BMP-7), latent transforming growth factor β-binding protein 1 (LTBP1), and extracellular vesicles...
April 15, 2023: Molecular and Cellular Pediatrics
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