Sepsis-induced changes in pyruvate metabolism: insights and potential therapeutic approaches.

Sepsis is a heterogeneous syndrome resulting from a dysregulated host response to infection. It is considered as a global major health priority. Sepsis is characterized by significant metabolic perturbations, leading to increased circulating metabolites such as lactate.

Microbial metabolome in septic shock: Bridging bench to bedside.

Due to its enormous incidence and mortality, sepsis is a huge health priority. In the latest issue of Cell, an innovative approach is provided that addresses the major sepsis hurdles of today, i.e.

Cell death checkpoints in the TNF pathway.

Tumor necrosis factor (TNF) plays a central role in orchestrating mammalian inflammatory responses. It promotes inflammation either directly by inducing inflammatory gene expression or indirectly by triggering cell death. TNF-mediated cell death-driven inflammation can be beneficial during infection by providing cell-extrinsic signals that help to mount proper immune responses.

Neural network algorithm for detection of erosions and ankylosis on CT of the sacroiliac joints: multicentre development and validation of diagnostic accuracy.

Objectives: To evaluate the feasibility and diagnostic accuracy of a deep learning network for detection of structural lesions of sacroiliitis on multicentre pelvic CT scans.

Methods: Pelvic CT scans of 145 patients (81 female, 121 Ghent University/24 Alberta University, 18-87 years old, mean 40 ± 13 years, 2005-2021) with a clinical suspicion of sacroiliitis were retrospectively included. After manual sacroiliac joint (SIJ) segmentation and structural lesion annotation, a U-Net for SIJ segmentation and two separate convolutional neural networks (CNN) for erosion and ankylosis detection were trained.

Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial.

Background & Aims: Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD.

Methods: A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5.

Association of Cell Death Markers With Tumor Immune Cell Infiltrates After Chemo-Radiation in Cervical Cancer.

Unlabelled: Irradiation induces distinct cellular responses such as apoptosis, necroptosis, iron-dependent cell death (a feature of ferroptosis), senescence, and mitotic catastrophe. Several of these outcomes are immunostimulatory and may represent a potential for immunogenic type of cell death (ICD) induced by radiotherapy triggering abscopal effects. The purpose of this study is to determine whether intra-tumoral ICD markers can serve as biomarkers for the prediction of patient's outcomes defined as the metastasis status and survival over a 5-year period.

Detailed videocapillaroscopic microvascular changes detectable in adult COVID-19 survivors.

Objective: COVID-19 is a multisystem disease that causes endothelial dysfunction and organ damage. Aim of the study was to evaluate the microvascular status in COVID-19 survivors with past different disease severity, in comparison with age and sex-matched primary Raynaud's phenomenon (PRP) patients and control subjects (CNT), including possible effects of concomitant therapies.

Methods: Sixty-one COVID-19 survivors (mean age 58 ± 13 years, mean days from disease onset 126 ± 53 and mean days from recovery 104 ± 53), thirty-one PRP patients (mean age 59 ± 15 years, mean disease duration 11 ± 10 years) and thirty CNT (mean age 58 ± 13 years) underwent nailfold videocapillaroscopy (NVC) examination.

Sepsis: a failing starvation response.

Sepsis is involved in ~ 20% of annual global deaths. Despite decades of research, the current management of sepsis remains supportive rather than curative. Clinical trials in sepsis have mainly been focused on targeting the inflammatory pathway, but without success.

Punching Holes in Cellular Membranes: Biology and Evolution of Gasdermins.

The gasdermin (GSDM) family has evolved as six gene clusters (GSDMA-E and Pejvakin, PJVK), and GSDM proteins are characterized by a unique N-terminal domain (N-GSDM). With the exception of PJVK, the N-GSDM domain is capable of executing plasma membrane permeabilization. Depending on the cell death modality, several protease- and kinase-dependent mechanisms directly regulate the activity of GSDME and GSDMD, the two most widely expressed and best-studied GSDMs.

Human decellularized dermal matrix seeded with adipose-derived stem cells enhances wound healing in a murine model: Experimental study.

Objective: Full-thickness cutaneous wounds treated with split-thickness skin grafts often result in unaesthetic and hypertrophic scars. Dermal substitutes are currently used together with skin grafts in a single treatment to reconstruct the dermal layer of the skin, resulting in improved quality of scars. Adipose-derived stem cells (ASCs) have been described to enhance wound healing through structural and humoral mechanisms.

Xenogen-free isolation and culture of human adipose mesenchymal stem cells.

Background: Adipose-derived Stem Cells (ASCs) present great potential for reconstructive procedures. Currently, isolation by enzyme digestion and culturing using xenogenic substances remain the gold standard, impairing clinical use.

Methods: Abdominal lipo-aspirate and blood samples were obtained from healthy patients.

ZEBs: Novel Players in Immune Cell Development and Function.

ZEB1 and ZEB2 are zinc-finger E homeobox-binding transcription factors best known for their role in driving epithelial to mesenchymal transition. However, in recent years our understanding of these two transcription factors has broadened, and it is now clear that they are expressed by a variety of immune cells of both myeloid and lymphoid lineages, including dendritic cells, macrophages, monocytes, B, T, and NK cells. In these cells, ZEBs function to regulate important transcriptional networks necessary for cell differentiation, maintenance, and function.

Microglia in Central Nervous System Inflammation and Multiple Sclerosis Pathology.

Microglia are the resident macrophages of the central nervous system (CNS). They have important physiological functions in maintaining tissue homeostasis but also contribute to CNS pathology. Microglia respond to changes in the microenvironment, and the resulting reactive phenotype can be very diverse, with both neuroinflammatory and neuroprotective properties, illustrating the plasticity of these cells.

Easy Access to and Applications of the Sequences of All Protein-Coding Genes of All Sequenced Mouse Strains.

An easily accessible and searchable overview of all protein sequences in the 36 genome-sequenced mouse strains, compared to those in the reference strain C57BL/6J, is now available, as well as an overview of the aberrant proteins in this reference strain. We provide an insight into the advantages of using these databases.

The Role of the Microbiome in Gut and Joint Inflammation in Psoriatic Arthritis and Spondyloarthritis.

Spondyloarthritis (SpA) encompasses a group of diseases characterized by an inflammatory arthritis involving both joints and entheses. However, extraarticular symptoms constitute a large element of the pathology and should not be underestimated. Microscopic gut inflammation is observed in 50% of patients with SpA and has been linked to disease activity, underscoring the effect of gut inflammation in SpA.

Therapeutic Mechanisms of Glucocorticoids.

Glucocorticoids (GCs) have been used clinically for decades as potent anti-inflammatory and immunosuppressive agents. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of glucocorticoid resistance (GCR). Therefore, efforts to understand the complex mechanisms underlying GC function and GCR are ongoing.

Cellular Functions of Optineurin in Health and Disease.

Optineurin (OPTN) was initially identified as a regulator of NF-κB and interferon signaling, but attracted most attention because of its association with various human disorders such as glaucoma, Paget disease of bone, and amyotrophic lateral sclerosis. Importantly, OPTN has recently been identified as an autophagy receptor important for the autophagic removal of pathogens, damaged mitochondria, and protein aggregates. This activity is most likely compromised in patients carrying OPTN mutations, and contributes to the observed phenotypes.

The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2.

Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development.

Targeting MALT1 Proteolytic Activity in Immunity, Inflammation and Disease: Good or Bad?

MALT1 is a signaling protein that plays a key role in immunity, inflammation, and lymphoid malignancies. For a long time MALT1 was believed to function as a scaffold protein, providing an assembly platform for other signaling proteins. This view changed dramatically when MALT1 was also found to have proteolytic activity and a capacity to fine-tune immune responses.