Phospholipase A2 group IVD mediates the transacylation of glycerophospholipids and acylglycerols.

In mammalian cells, glycerolipids are mainly synthesized using acyl-CoA-dependent mechanisms. The acyl-CoA-independent transfer of fatty acids between lipids, designated as transacylation reaction, represents an additional mechanism for lipid remodeling and synthesis pathways. Here, we demonstrate that human and mouse phospholipase A2 group IVD (PLA2G4D) catalyzes transacylase reactions using both phospholipids and acylglycerols as substrates.

The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity.

Dendritic cell (DC) progenitors adapt their transcriptional program during development, generating different subsets. How chromatin modifications modulate these processes is unclear. Here, we investigate the impact of histone deacetylation on DCs by genetically deleting histone deacetylase 1 (HDAC1) or HDAC2 in hematopoietic progenitors and CD11c-expressing cells.

Effect of astaxanthin in type-2 diabetes -induced APPxhQC transgenic and NTG mice.

Objectives: Aggregation and misfolding of amyloid beta (Aβ) and tau proteins, suggested to arise from post-translational modification processes, are thought to be the main cause of Alzheimer's disease (AD). Additionally, a plethora of evidence exists that links metabolic dysfunctions such as obesity, type 2 diabetes (T2D), and dyslipidemia to the pathogenesis of AD. We thus investigated the combinatory effect of T2D and human glutaminyl cyclase activity (pyroglutamylation), on the pathology of AD and whether astaxanthin (ASX) treatment ameliorates accompanying pathophysiological manifestations.

Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes-secondary analysis of a randomized placebo-controlled parallel intervention trial.

Background: Aronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints.

Liver X receptor activation mitigates oxysterol-induced dysfunction in fetoplacental endothelial cells.

Maintaining the homeostasis of the placental vasculature is of paramount importance for ensuring normal fetal growth and development. Any disruption in this balance can lead to perinatal morbidity. Several studies have uncovered an association between high levels of oxidized cholesterol (oxysterols), and complications during pregnancy, including gestational diabetes mellitus (GDM) and preeclampsia (PE).

Adoptive transfer of allergen-expressing B cells prevents IgE-mediated allergy.

Introduction: Prophylactic strategies to prevent the development of allergies by establishing tolerance remain an unmet medical need. We previously reported that the transfer of autologous hematopoietic stem cells (HSC) expressing the major timothy grass pollen allergen, Phl p 5, on their cell surface induced allergen-specific tolerance in mice. In this study, we investigated the ability of allergen-expressing immune cells (dendritic cells, CD4 T cells, CD8 T cells, and CD19 B cells) to induce allergen-specific tolerance in naive mice and identified CD19 B cells as promising candidates for allergen-specific cell therapy.

A Person-Centered Perspective on Physical Activity-Related Barriers Perceived by Male Fluctuators 50 Plus: A Cross-Sectional Study.

Men aged 50 or older (50 plus) represent a hard-to-reach target group for health-enhancing physical activity (PA) interventions. However, a considerable percentage of men 50 plus do not entirely fail to achieve the PA milestones set by the World Health Organization (WHO) guidelines. They show fluctuating PA behavior, influenced by various barriers hindering or preventing regular PA participation.

Exploring Species-Specificity in TLR4/MD-2 Inhibition with Amphiphilic Lipid A Mimicking Glycolipids.

The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex is a key receptor of the innate immune system and a major driver of inflammation that is responsible for the multifaceted defense response to Gram-negative infections. However, dysfunction in the tightly regulated mechanisms of TLR4-mediated signaling leads to the uncontrolled upregulation of local and systemic inflammation, often resulting in acute or chronic disease. Therefore, the TLR4/MD-2 receptor complex is an attractive target for the design and development of anti-inflammatory therapies which aim to control the unrestrained activation of TLR4-mediated signaling.

Microenvironmental and cell intrinsic factors governing human cDC2 differentiation and monocyte reprogramming.

cDC2s occur abundantly in peripheral tissues and arise from circulating blood cDC2s. However, the factors governing cDC2 differentiation in tissues, especially under inflammatory conditions, remained poorly defined. We here found that psoriatic cDC2s express the efferocytosis receptor Axl and exhibit a bone morphogenetic protein (BMP) and p38MAPK signaling signature.

Liver X Receptor Activation Attenuates Oxysterol-Induced Inflammatory Responses in Fetoplacental Endothelial Cells.

Oxysterols are oxidized cholesterol derivatives whose systemic levels are found elevated in pregnancy disorders such as gestational diabetes mellitus (GDM). Oxysterols act through various cellular receptors and serve as a key metabolic signal, coordinating inflammation. GDM is a condition of low-grade chronic inflammation accompanied by altered inflammatory profiles in the mother, placenta and fetus.

Individual Treatment Trials-Do Experts Know and Use This Option to Improve the Treatability of Mucopolysaccharidosis?

Mucopolysaccharidoses (MPS) are a group of rare, heterogeneous, lysosomal storage disorders. Patients show a broad spectrum of clinical features with a substantial unmet medical need. Individual treatment trials (ITTs) might be a valid, time- and cost-efficient way to facilitate personalized medicine in the sense of drug repurposing in MPS.

A novel 3D cell culture model to study the human small intestinal immune landscape.

Several subsets of mononuclear phagocytes and DCs (MDC) populate the small intestine (SI), and these cells reportedly exert specialized functions in anti-microbial immunity and tolerance. Given the specialized phenotype of these cells, differing from other MDC family members, including their putative circulating blood precursors, local intestinal factors play key instructive roles in their differentiation. We designed an SI cell culture model composed of three intestinal epithelial cell (IEC) types, including absorptive enterocytes (E cells), antigen delivering microfold (M) cells, and mucus-producing goblet (G) cells plus T lymphocytes and soluble B cell-derived factors.

Immunomodulatory Effects of Aronia Juice Polyphenols-Results of a Randomized Placebo-Controlled Human Intervention Study and Cell Culture Experiments.

Dietary polyphenols, which are present in have been associated with various beneficial effects on human health including antioxidant, antiviral, and anti-inflammatory activities. We aimed to investigate the immunomodulatory effects of aronia juice polyphenols in a randomized placebo-controlled human intervention study and cell culture experiments. A total of 40 females were asked to consume either 200 mL of aronia juice or a placebo drink for six weeks and were investigated again after a washout period of another six weeks.

BMPR1a Is Required for the Optimal TGFβ1-Dependent CD207 Langerhans Cell Differentiation and Limits Skin Inflammation through CD11c Cells.

The cytokine TGFβ1 induces epidermal Langerhans cell (LC) differentiation from human precursors, an effect mediated through BMPR1a/ALK3 signaling, as revealed from ectopic expression and receptor inhibition studies. Whether TGFβ1‒BMPR1a signaling is required for LC differentiation in vivo remained incompletely understood. We found that TGFβ1-deficient mice show defective perinatal expansion and differentiation of LCs.

Factors influencing the effectiveness of a Cooperative Planning approach in the school setting.

The purpose of the Health.edu project was to develop, implement and evaluate effective and feasible measures addressing students' health-related knowledge and understanding (HKU) in physical education (PE) with a specific focus on a co-creation approach (Cooperative Planning). The general procedure was identical in the four intervention schools involved; however, effectiveness (i.

Evaluation of community readiness for change prior to a participatory physical activity intervention in Germany.

A lack of communities' readiness for change is reported as a major barrier toward an effective implementation of health promoting interventions in community settings. Adding an alternative readiness assessment approach to existing research practice, this study aimed to investigate how a selected community could be evaluated in-depth regarding its readiness for change based on multiple key informant perspectives, with the intention of using this knowledge for the preparation of improved local physical activity (PA) interventions for men above 50 years of age. We conducted semi-structured face-to-face key informant interviews with stakeholders and relevant persons from a local German community (N = 15).

[Changes in Children's Physical Fitness during Corona-Related Restrictions in Spring/Summer 2020].

Aim Of The Study: Due to the increasing spread of the coronavirus (SARS-CoV-2) and the accompanying containment measures, physical activity opportunities for children in the context of school and sport clubs were severely restricted in the spring/summer of 2020. The present study focuses on changes in children's physical fitness during this period.

Methods: We conducted an almost full census of 131 primary school children in the 2nd grade in Bad Dürkheim, assessing their physical fitness immediately before the school closures on 16 March 2020 and after the end of the summer holidays (end of August) in Rhine-land-Palatinate, Germany.

The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling.

Transforming growth factor β (TGF-β) family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β family signaling for their differentiation, and canonical TGF-β1 signaling secures a non-activated LC state. LCs reportedly control skin inflammation and are replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs).

Induction of the sphingosine-1-phosphate signaling pathway by TGF-β1 during Langerhans-type dendritic cell differentiation.

Gene profiling revealed that the S1P signaling pathway is induced by TGF-β1 during LC commitment of monocytopoietic cells. Constitutive-active TGF-β1-S1P signaling seems to elevate the activation threshold of LCs and thereby prevent inappropriate and overshooting immune responses to microbial and physicochemical environmental signals. In turn, signals that lead to LC migration may disrupt this pathway via inhibiting S1P bioavailability.

Psoriatic skin inflammation is promoted by c-Jun/AP-1-dependent CCL2 and IL-23 expression in dendritic cells.

Toll-like receptor (TLR) stimulation induces innate immune responses involved in many inflammatory disorders including psoriasis. Although activation of the AP-1 transcription factor complex is common in TLR signaling, the specific involvement and induced targets remain poorly understood. Here, we investigated the role of c-Jun/AP-1 protein in skin inflammation following TLR7 activation using human psoriatic skin, dendritic cells (DC), and genetically engineered mouse models.

[The Person Who Plays Handball Needs the Ball, the Contact and the Community - Changes in Sport Club Activities Due to the COVID-19 Pandemic and its Significance for Sports Clubs].

Aim: Sports clubs play an important role in the promotion of physical activity and health in Germany. Against the background of restrictions due to the COVID-19 pandemic, the present study explores the changes in sport activities and their significance for sports clubs.

Methods: We conducted 15 expert interviews with representatives of Bavarian sports clubs.

Micro-RNA-125a mediates the effects of hypomethylating agents in chronic myelomonocytic leukemia.

Background: Chronic myelomonocytic leukemia (CMML) is an aggressive hematopoietic malignancy that arises from hematopoietic stem and progenitor cells (HSPCs). Patients with CMML are frequently treated with epigenetic therapeutic approaches, in particular the hypomethylating agents (HMAs), azacitidine (Aza) and decitabine (Dec). Although HMAs are believed to mediate their efficacy via re-expression of hypermethylated tumor suppressors, knowledge about relevant HMA targets is scarce.

Bone morphogenetic protein signaling regulates skin inflammation via modulating dendritic cell function.

Background: Bone morphogenetic proteins (BMPs) are members of the TGF-β family that signal via the BMP receptor (BMPR) signaling cascade, distinct from canonical TGF-β signaling. BMP downstream signaling is strongly induced within epidermal keratinocytes in cutaneous psoriatic lesions, and BMP7 instructs monocytic cells to acquire characteristics of psoriasis-associated Langerhans dendritic cells (DCs). Regulatory T (Treg)-cell numbers strongly increase during psoriatic skin inflammation and were recently shown to limit psoriatic skin inflammation.