Uncovering protein prenylation in Th1 cells: novel prenylation sites and insights into statin and farnesyltransferase inhibition.

Background: T helper 1 (Th1) cell activation is an essential process for immune responses and is tightly regulated, including the prenylation of proteins critical for T cell function. Prenylation facilitates membrane association and protein function and, according to current consensus, is confined to C-terminal prenylation motifs. However, the full extent of the prenylated proteome, a broader understanding of prenylation sites, and the effects of inhibiting prenylation or blocking isoprenoid synthesis using statins remain incompletely understood.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

Background: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined.

Methods: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors.

Dupilumab-associated ocular surface disease is characterized by a shift from Th2/Th17 toward Th1/Th17 inflammation.

Background: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab-associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy.

Granzymes, IL-16, and poly(ADP-ribose) polymerase 1 increase during wildfire smoke exposure.

Background: Given the increasing prevalence of wildfires worldwide, understanding the effects of wildfire air pollutants on human health-particularly in specific immunologic pathways-is crucial. Exposure to air pollutants is associated with cardiorespiratory disease; however, immune and epithelial barrier alterations require further investigation.

Objective: We sought to determine the impact of wildfire smoke exposure on the immune system and epithelial barriers by using proteomics and immune cell phenotyping.

Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80.

Background: The rising prevalence of many chronic diseases related to gut barrier dysfunction coincides with the increased global usage of dietary emulsifiers in recent decades. We therefore investigated the effect of the frequently used food emulsifiers on cytotoxicity, barrier function, transcriptome alterations, and protein expression in gastrointestinal epithelial cells.

Methods: Human intestinal organoids originating from induced pluripotent stem cells, colon organoid organ-on-a-chip, and liquid-liquid interface cells were cultured in the presence of two common emulsifiers: polysorbate 20 (P20) and polysorbate 80 (P80).

Disrupted epithelial permeability as a predictor of severe COVID-19 development.

Background: An impaired epithelial barrier integrity in the gastrointestinal tract is important to the pathogenesis of many inflammatory diseases. Accordingly, we assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID-19.

Methods: Levels of bacterial DNA and zonulin family peptides (ZFP) as markers of bacterial translocation and intestinal permeability and a total of 180 immune and inflammatory proteins were analyzed from the sera of 328 COVID-19 patients and 49 healthy controls.

Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.

Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium.

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs.

Multidimensional endotyping using nasal proteomics predicts molecular phenotypes in the asthmatic airways.

Background: Unsupervised clustering of biomarkers derived from noninvasive samples such as nasal fluid is less evaluated as a tool for describing asthma endotypes.

Objective: We sought to evaluate whether protein expression in nasal fluid would identify distinct clusters of patients with asthma with specific lower airway molecular phenotypes.

Methods: Unsupervised clustering of 168 nasal inflammatory and immune proteins and Shapley values was used to stratify 43 patients with severe asthma (endotype of noneosinophilic asthma) using a 2 "modeling blocks" machine learning approach.

Butyrate Inhibits Osteoclast Activity and Regulates Systemic Inflammation and Bone Healing in a Murine Osteotomy Model Compared to Antibiotic-Treated Mice.

Short-chain fatty acids (SCFAs) produced by the gut microbiota have previously been demonstrated to play a role in numerous chronic inflammatory diseases and to be key mediators in the gut-bone signaling axis. However, the role of SCFAs in bone fracture healing and its impact on systemic inflammation during the regeneration process has not been extensively investigated yet. The aim of this study was to first determine the effects of the SCFA butyrate on key cells involved in fracture healing , namely, osteoclasts and mesenchymal stromal cells (MSCs), and second, to assess if butyrate supplementation or antibiotic therapy impacts bone healing, systemic immune status, and inflammation levels in a murine osteotomy model.

In Vitro 3D Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells.

is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic infections, it remains unknown whether SACs directly trigger MDSC expansion. To investigate this, a previously developed 3D in vitro SAC model was co-cultured with murine and human bone marrow cells.

Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System.

Importance: As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)-authorized mRNA COVID-19 vaccines have been reported.

Objective: To characterize the immunologic mechanisms underlying allergic reactions to these vaccines.

Fentanyl Plasma Concentrations after Application of a Transdermal Patch in Three Different Locations to Refine Postoperative Pain Management in Rabbits.

Transdermal patches allow a noninvasive and "stress free" analgesia in rabbits. As fentanyl uptake is dependent on exogenous and endogenous factors of the area where the patch is applied, this study investigated three different locations (neck, inner and outer surfaces of the ear) for fentanyl patch application to provide adequate and reliable fentanyl plasma concentrations above those previously shown to be analgesic. Fentanyl plasma concentration was measured at different time points (3, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120 h) and rabbits were assessed for their general conditions and treatment-related side effects.

Transdermal Fentanyl Uptake at Two Different Patch Locations in Swiss White Alpine Sheep.

When using animals in biomedical research, investigators have the responsibility to ensure adequate analgesia. Currently, transdermal fentanyl patches (TFP) are often used to provide postoperative analgesia in large laboratory animals. The aim of this study was to compare the fentanyl uptake resulting from TFP applied at two different locations, namely the foreleg and the thorax, in healthy adult sheep.

A wide diversity of bacteria from the human gut produces and degrades biogenic amines.

: Biogenic amines (BAs) are metabolites produced by the decarboxylation of amino acids with significant physiological functions in eukaryotic and prokaryotic cells. BAs can be produced by bacteria in fermented foods, but little is known concerning the potential for microbes within the human gut microbiota to produce or degrade BAs. : To isolate and identify BA-producing and BA-degrading microbes from the human gastrointestinal tract.