StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation.

StarD5 is an ER stress protein that binds cholesterol and transfers it to the plasma membrane. It additionally binds and regulates 25-hydroxycholesterol (25-HC) levels. However the full function of the StarD5-25-HC axis is unknown.

Obesity prolongs the pro-inflammatory response and attenuates bone healing on titanium implants.

Obesity is a metabolic disease resulting from excess body fat accumulation associated with chronic systemic inflammation. Obesity has been shown to impact the function and activity of neutrophils, macrophages, and T cells, contributing to higher circulating levels of pro-inflammatory cytokines. Biomaterial surface properties such as roughness and hydrophilicity can influence the behavior of immune cells in the peri-implant microenvironment.

Adoptive transfer of immunomodulatory macrophages reduces the pro-inflammatory microenvironment and increases bone formation on titanium implants.

Macrophages play a central role in orchestrating the inflammatory response to implanted biomaterials and are sensitive to changes in the chemical and physical characteristics of the implant. Macrophages respond to biological, chemical, and physical cues by polarizing into pro-inflammatory (M1) or anti-inflammatory (M2) states. We previously showed that rough-hydrophilic titanium (Ti) implants skew macrophage polarization towards an anti-inflammatory phenotype and increase mesenchymal stem cell (MSC) recruitment and bone formation around the implant.

Adipose tissue-selective ablation of ADAM10 results in divergent metabolic phenotypes following long-term dietary manipulation.

A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10), is involved in several metabolic and inflammatory pathways. We speculated that ADAM10 plays a modulatory role in adipose tissue inflammation and metabolism. To this end, we studied adipose tissue-specific ADAM10 knock-out mice (aKO).

Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells.

There is a clinical need for new treatment options addressing allergic disease. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that have anti-inflammatory properties. We tested the effects of the SSRI fluoxetine on IgE-induced function of mast cells, which are critical effectors of allergic inflammation.

Contribution of αβ T cells to macrophage polarization and MSC recruitment and proliferation on titanium implants.

Physiochemical cues like topography and wettability can impact the inflammatory response and tissue integration after biomaterial implantation. T cells are essential for immunomodulation of innate immune cells and play an important role in the host response to biomaterial implantation. This study aimed to understand how CD4 and CD8 T cell subsets, members of the αβ T cell family, polarize in response to smooth, rough, or rough-hydrophilic titanium (Ti) implants and whether their presence modulates immune cell crosstalk and mesenchymal stem cell (MSC) recruitment following biomaterial implantation.

Inhibiting Isoprenylation Suppresses FcεRI-Mediated Mast Cell Function and Allergic Inflammation.

IgE-mediated mast cell activation is a driving force in allergic disease in need of novel interventions. Statins, long used to lower serum cholesterol, have been shown in multiple large-cohort studies to reduce asthma severity. We previously found that statins inhibit IgE-induced mast cell function, but these effects varied widely among mouse strains and human donors, likely due to the upregulation of the statin target, 3-hydroxy-3-methylgutaryl-CoA reductase.

Reduction of neutrophil extracellular traps accelerates inflammatory resolution and increases bone formation on titanium implants.

Neutrophils are the most abundant immune cells in the blood and the first cells to be recruited to the biomaterial implantation site. Neutrophils are fundamental in recruiting mononuclear leukocytes to mount an immune response at the injury site. Neutrophils exert significant pro-inflammatory effects through the release of cytokines and chemokines, degranulation and release of myeloperoxidase (MPO) and neutrophil elastase (NE), and the production of large DNA-based networks called neutrophil extracellular traps (NETs).

Neutrophil elastase decreases SARS-CoV-2 spike protein binding to human bronchial epithelia by clipping ACE-2 ectodomain from the epithelial surface.

Patients with cystic fibrosis (CF) have decreased severity of severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2) infections, but the underlying cause is unknown. Patients with CF have high levels of neutrophil elastase (NE) in the airway. We examined whether respiratory epithelial angiotensin-converting enzyme 2 (ACE-2), the receptor for the SARS-CoV-2 spike protein, is a proteolytic target of NE.

Immune cell response to orthopedic and craniofacial biomaterials depends on biomaterial composition.

Materials for craniofacial and orthopedic implants are commonly selected based on mechanical properties and corrosion resistance. The biocompatibility of these materials is typically assessed in vitro using cell lines, but little is known about the response of immune cells to these materials. This study aimed to evaluate the inflammatory and immune cell response to four common orthopedic materials [pure titanium (Ti), titanium alloy (TiAlV), 316L stainless steel (SS), polyetheretherketone (PEEK)].

Neutrophilia in severe asthma is reduced in Ormdl3 overexpressing mice.

Genome-wide association studies have linked the ORM (yeast)-like protein isoform 3 (ORMDL3) to asthma severity. Although ORMDL3 is a member of a family that negatively regulates serine palmitoyltransferase (SPT) and thus biosynthesis of sphingolipids, it is still unclear whether ORMDL3 and altered sphingolipid synthesis are causally related to non-Th2 severe asthma associated with a predominant neutrophil inflammation and high interleukin-17 (IL-17) levels. Here, we examined the effects of ORMDL3 overexpression in a preclinical mouse model of allergic lung inflammation that is predominantly neutrophilic and recapitulates many of the clinical features of severe human asthma.

Cellular inhibitor of apoptosis 2 (cIAP2) restricts neuroinflammation during experimental autoimmune encephalomyelitis.

Background: Immune activation, neuroinflammation, and cell death are the hallmarks of multiple sclerosis (MS), which is an autoimmune demyelinating disease of the central nervous system (CNS). It is well-documented that the cellular inhibitor of apoptosis 2 (cIAP2) is induced by inflammatory stimuli and regulates adaptive and innate immune responses, cell death, and the production of inflammatory mediators. However, the impact of cIAP2 on neuroinflammation associated with MS and disease severity remains unknown.

Isolation of the Stromal Vascular Fraction from Adipose Tissue and Subsequent Differentiation into White or Beige Adipocytes.

Non-alcoholic steatohepatitis (NASH) is linked to adipose tissue dysfunction, with weight loss being the only treatment shown to reverse it. Due to this correlation with obesity, the study of adipose tissue and adipocytes is an important step in understanding the pathogenesis of this disease. Here, we describe the isolation process of the stromal vascular fraction (SVF) of adipose tissue.

Dissecting the Balance Between Metabolic and Oncogenic Functions of Astrocyte-Elevated Gene-1/Metadherin.

Obesity is an enormous global health problem, and obesity-induced nonalcoholic steatohepatitis (NASH) is contributing to a rising incidence and mortality for hepatocellular carcinoma (HCC). Increase in de novo lipogenesis and decrease in fatty acid β-oxidation (FAO) underlie hepatic lipid accumulation in NASH. Astrocyte-elevated gene-1/metadherin (AEG-1) overexpression contributes to both NASH and HCC.

Fast SARS-CoV-2 Variant Detection Using Snapback Primer High-Resolution Melting.

SARS-CoV-2, the virus responsible for COVID-19, emerged in late 2019 and has since spread throughout the world, infecting over 200 million people. The fast spread of SARS-CoV-2 showcased the need for rapid and sensitive testing methodologies to help track the disease. Over the past 18 months, numerous SARS-CoV-2 variants have emerged.

Extraction-Free Rapid Cycle Quantitative RT-PCR and Extreme RT-PCR for SARS-CoV-2 Virus Detection.

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, molecular diagnostic testing for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has faced substantial supply chain shortages and noteworthy delays in result reporting after sample collection. Supply chain shortages have been most evident in reagents for RNA extraction and rapid diagnostic testing. This study explored the kinetic limitations of extraction-free rapid cycle quantitative real-time RT-PCR for SARS-CoV-2 virus detection using the commercially available capillary-based LightCycler.

Stat5B is required for IgE-Mediated mast cell function in vitro and in vivo.

Mast cells are found primarily at interfaces with the external environment, where they provide protection from pathogens but also elicit allergic inflammation. Mast cell activation by antigen-induced aggregation of IgE bound to the high affinity receptor, FcεRI, is a critical factor leading to inflammation and bronchoconstriction. We previously found that Stat5 is activated by FcεRI and that Stat5B suppression decreased IgE-induced cytokine production in vitro, but in vivo responses have not been assessed.

Identification of the transgene insertion site for an adipocyte-specific adiponectin-cre model and characterization of the functional consequences.

The transgenic mouse is widely used in the development of adipocyte-specific genetic manipulations for the study of obesity and type 2 diabetes. In the process of developing a new mouse model utilizing the adipocyte selective transgenic mouse, strong genetic linkage between a gene of interest, , and the transgene was discovered. Whole-genome sequencing of the transgenic mouse model identified the genomic insertion site within the gene locus on chromosome 9 and this insertion causes a significant decrease in gene expression in adipose tissue.

Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma.

Background: Nothing is known about the mechanisms by which increased ceramide levels in the lung contribute to allergic responses and asthma severity.

Objective: We sought to investigate the functional role of ceramide in mouse models of allergic airway disease that recapitulate the cardinal clinical features of human allergic asthma.

Methods: Allergic airway disease was induced in mice by repeated intranasal administration of house dust mite or the fungal allergen Alternaria alternata.

T cell receptor signaling defines the fate and pathway of ICOS internalization.

The role of the inducible costimulatory of T cells (ICOS) has been shown to be important for many different T cell outcomes and is indispensable for follicular helper T cell (T) responses. Since its discovery, there have been several studies on the regulation of ICOS at a transcriptional level. However, the post-translational regulation of ICOS has not been well characterized.

Adipocyte ADAM17 plays a limited role in metabolic inflammation.

The role of ADAM17, its substrates, and its natural inhibitor has been well studied in the context of inflammation, including metabolic inflammation, with mixed results. Previous studies examining global knockdown models and ADAM17 inhibition using overexpression of endogenous ADAM17 inhibitors have shown improved metabolic health and decreased metabolic inflammation. However, there have been no studies examining the role of adipocyte ADAM17 using models.

Immunization against Anaplasma phagocytophilum Adhesin Binding Domains Confers Protection against Infection in the Mouse Model.

causes granulocytic anaplasmosis, a debilitating infection that can be fatal in the immunocompromised. It also afflicts animals, including dogs, horses, and sheep. No granulocytic anaplasmosis vaccine exists.

Fluvastatin Induces Apoptosis in Primary and Transformed Mast Cells.

Statin drugs are widely employed in the clinic to reduce serum cholesterol. Because of their hydroxymethylglutaryl coenzyme A reductase antagonism, statins also reduce isoprenyl lipids necessary for the membrane anchorage and signaling of small G-proteins in the Ras superfamily. We previously found that statins suppress immunoglobulin E (IgE)-mediated mast cell activation, suggesting these drugs might be useful in treating allergic disease.