Cardiac macrophages and their functions in homeostasis and injury.

Due to their remarkable plasticity, macrophages can adapt to diverse environments and challenges therein, thereby exerting tissue-specific and context-specific functions. Macrophages are the most frequent immune cell population present in the heart and contribute substantially to cardiac homeostasis and function. Moreover, macrophages are key regulators throughout all stages of heart injury, acquiring diverse phenotypes that can either ameliorate or exacerbate cardiac pathology in a context-dependent manner.

Hypoxia inducible factor 1α-driven steroidogenesis impacts systemic hematopoiesis.

Background: Glucocorticoids (GCs) are key regulators of hematopoiesis, but the effects of chronically elevated endogenous GC levels on hematopoietic stem cell (HSC) function and immune cell development remain poorly understood.

Methods: We used a mouse model with adrenocortical cell-specific deletion of hypoxia-inducible factor-1 alpha (HIF1α; P2H1), which results in sustained and systemic elevation of GC. Hematopoietic stem and progenitor cell (HSPC) populations were analyzed phenotypically and functionally.

A DEL-1/αvβ3 integrin axis promotes brown adipocyte progenitor proliferation and cold-induced brown adipose tissue adaptation.

Objectives: Cold-triggered adaptation of the brown adipose tissue (BAT) promotes increased non-shivering thermogenesis and helps maintain body temperature. This study investigated the role of the secreted protein developmental endothelial locus-1 (DEL-1) in regulating BAT adaptation to cold.

Methods: DEL-1 expression in BAT was assessed following cold exposure in mice.

A key role of polyamine metabolism in adipose tissue homeostasis that regulates obesity.

Background And Aims: Adipose tissue function is integral to systemic metabolic homeostasis. Excessive adipose tissue growth is associated with development of chronic low-grade inflammation and whole body dysmetabolism. The cell metabolic pathways regulating adipose tissue growth and homeostasis are little understood.

Central trained immunity in the context of bladder cancer immunotherapy.

Two articles in Immunity and Cancer Cell describe that bladder cancer immunotherapy with Bacillus Calmette-Guerin (BCG) alone or in combination with β-glucan, another agonist of trained immunity (TRIM), involves reprogramming of bone marrow (BM) hematopoiesis. These findings provide additional evidence of the therapeutic potential of BM-mediated TRIM against cancer.

Coagulation Matters: ATIII-Enriched Biomolecular Corona Enhances the Hemocompatibility of PEG Nanoparticles.

Nanoparticles in physiological environments acquire a biomolecular corona that defines their biological identity, mediating immune system recognition and accelerating blood clearance of the nanoparticles. Typically, low-fouling materials are chosen to minimize protein adsorption and thereby immune system responses, contributing to stealth in blood. However, absolute prevention of the biomolecular corona remains tantalizingly out of reach.

Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model.

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic variation remain unclear. Here, we investigated the roots of phenotypic variation by parallel recording of transcriptomic states and morphological history in individual structures modeling embryonic trunk formation.

Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice.

We previously demonstrated that long-term trained immunity (TRIM) involves adaptations that imprint innate immune memory in long-lived myelopoiesis precursors and their progeny, monocytes/macrophages and neutrophils, which thereby acquire enhanced responsiveness to future challenges. Here, we show that a distinct component of myeloid biology, osteoclastogenesis, can also undergo innate immune training. Indeed, β-glucan-induced TRIM was associated with an increased osteoclastogenesis bias in the bone marrow and an expansion of monocytes/osteoclast progenitors in the periphery, resulting in aggravated severity of experimental periodontitis and arthritis.

Adenylate cyclase 10 promotes brown adipose tissue thermogenesis.

Brown adipose tissue (BAT) thermogenesis dissipates energy through heat production and thereby it opposes metabolic disease. It is mediated by mitochondrial membrane uncoupling, yet the mechanisms sustaining the mitochondrial membrane potential (ΔΨm) in brown adipocytes are poorly understood. Here we show that isocitrate dehydrogenase (IDH) activity and the expression of the soluble adenylate cyclase 10 (ADCY10), a CO/bicarbonate sensor residing in mitochondria, are upregulated in BAT of cold-exposed mice.

Perturbations in plasma amino acid and lipoprotein subfraction profiles in anorexia nervosa before and after refeeding: A metabolomic cross-sectional and longitudinal analysis.

Background: Anorexia nervosa (AN) is a life-threatening eating disorder, which is increasingly being considered a metabo-psychiatric condition. We aimed to assess how the lipoprotein subfraction and plasma metabolome are altered in acutely underweight patients with AN (AcAN), if they change with short-term weight-restoration, and whether these changes point towards altered cardiometabolic risk.

Methods: Using nuclear magnetic resonance spectroscopy, we measured and compared the plasma concentrations of 132 metabolites, aminoacids and lipoprotein subfractions in young female patients with AcAN before (n = 72) versus after (n = 46) a short-term inpatient refeeding program resulting in weight-restoration (longitudinal analysis), as well as versus female healthy control (HC) participants of similar age (n = 74) (cross-sectional analysis).

Trained immunity in chronic inflammatory diseases and cancer.

A decade after the term 'trained immunity' (TRIM) was coined to reflect the long-lasting hyper-responsiveness of innate immune cells with an epigenetically imprinted 'memory' of earlier stimuli, our understanding has broadened to include the potential implications of TRIM in health and disease. Here, after summarizing the well-documented beneficial effects of TRIM against infections, we discuss emerging evidence that TRIM is also a major underlying mechanism in chronic inflammation-related disorders such as periodontitis, rheumatoid arthritis and cardiovascular disease. Furthermore, mounting evidence indicates that the induction of TRIM by certain agonists confers protective antitumour responses.

Validating Centralized Biobanking Workflows for NMR Metabolomics Using the PRIMA Panel.

The quality of biological samples used in metabolomics research is significantly influenced by preanalytical factors, such as the timing of centrifugation and freezing. This study aimed to evaluate how preanalytical factors, like delays in centrifugation and freezing, affect metabolomics research. Blood samples, collected in various tube types, were subjected to controlled pre- and postcentrifugation delays.

Arginine metabolism in myeloid cells in health and disease.

Metabolic flexibility is key for the function of myeloid cells. Arginine metabolism is integral to the regulation of myeloid cell responses. Nitric oxide (NO) production from arginine is vital for the antimicrobial and pro-inflammatory responses.

Proteomic and Metabolomic Signatures in Prediabetes Progressing to Diabetes or Reversing to Normoglycemia Within 1 Year.

Objective: Progression of prediabetes to type 2 diabetes has been associated with β-cell dysfunction, whereas its remission to normoglycemia has been related to improvement of insulin sensitivity. To understand the mechanisms and identify potential biomarkers related to prediabetes trajectories, we compared the proteomics and metabolomics profile of people with prediabetes progressing to diabetes or reversing to normoglycemia within 1 year.

Research Design And Methods: The fasting plasma concentrations of 1,389 proteins and the fasting, 30-min, and 120-min post-oral glucose tolerance test (OGTT) plasma concentrations of 152 metabolites were measured in up to 134 individuals with new-onset diabetes, prediabetes, or normal glucose tolerance.

Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality.

Enhancing thermogenic brown adipose tissue (BAT) function is a promising therapeutic strategy for metabolic disease. However, predominantly thermoneutral modern human living conditions deactivate BAT. We demonstrate that selective adipocyte deficiency of the oxygen-sensor HIF-prolyl hydroxylase (PHD2) gene overcomes BAT dormancy at thermoneutrality.

Formyl peptide receptor 2 regulates dendritic cell metabolism and Th17 cell differentiation during neuroinflammation.

Formyl peptide receptor 2 (FPR2) is a receptor for formylated peptides and specific pro-resolving mediators, and is involved in various inflammatory processes. Here, we aimed to elucidate the role of FPR2 in dendritic cell (DC) function and autoimmunity-related central nervous system (CNS) inflammation by using the experimental autoimmune encephalomyelitis (EAE) model. EAE induction was accompanied by increased mRNA expression in the spinal cord.

Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss.

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H.

Accurate redox state indication by in situ derivatization with N-ethylmaleimide - Profiling of transsulfuration and glutathione pathway metabolites by UPLC-MS/MS.

Background: Reduced and oxidized glutathione play an important role for the intracellular detoxification of reactive oxygen species. The iron-dependent formation of such reactive oxygen species in conjunction with the inhibition of the redox-balancing enzyme glutathione peroxidase 4 underlie an imbalance in the cellular redox state, thereby resulting in a non-apoptotic form of cell death, defined as ferroptosis, which is relevant in several pathologies.

Methods: Here we present a rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based method providing the accurate quantification of 12 glutathione pathway metabolites after in situ derivatization with N-Ethylmaleimide (NEM).