Deep learning-based clustering for endotyping and post-arthroplasty response classification using knee osteoarthritis multiomic data.

Objectives: Primary knee osteoarthritis (KOA) is a heterogeneous disease with clinical and molecular contributors. Biofluids contain microRNAs and metabolites that can be measured by omic technologies. Multimodal deep learning is adept at uncovering complex relationships within multidomain data.

Cell and transcriptomic diversity of infrapatellar fat pad during knee osteoarthritis.

Objectives: In this study, we employ a multiomic approach to identify major cell types and subsets, and their transcriptomic profiles within the infrapatellar fat pad (IFP), and to determine differences in the IFP based on knee osteoarthritis (KOA), sex and obesity status.

Methods: Single-nucleus RNA sequencing of 82 924 nuclei from 21 IFPs (n=6 healthy control and n=15 KOA donors), spatial transcriptomics and bioinformatic analyses were used to identify contributions of the IFP to KOA. We mapped cell subclusters from other white adipose tissues using publicly available literature.

Characterisation of myeloid cells in circulation and synovial fluid of patients with psoriatic arthritis.

Objective: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. Adding to studies focused on the role of T cells and macrophages, we sought to investigate the systemic activation of leukocytes in PsA.

Methods: We assessed the activation state of leukocyte populations, including polymorphonuclear neutrophils (PMNs) and monocyte/macrophages, in blood and synovial fluid (SF) by multicolour flow cytometry.

The chemorepellent, SLIT2, bolsters innate immunity against .

Neutrophils are essential for host defense against (). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might, therefore, be expected to impair antibacterial responses. We report here that, unexpectedly, neutrophils exposed to the N-terminal SLIT2 (N-SLIT2) fragment kill extracellular more efficiently.

Analysis of Human and Mouse Neutrophil Phagocytosis by Flow Cytometry.

Neutrophils are primary phagocytes that recognize their targets through surface chemistry, either through pattern recognition receptor (PPR) interaction with pathogen-associated molecular patterns (PAMPs) or through immunoglobulin (Ig) or complement mediated recognition. Opsonization can be important for target recognition and phagocytosis by neutrophils. Therefore, phagocytosis assays performed using neutrophils in whole blood, compared to isolated cells, will differ due to the presence of opsonizing blood serum components, as well as other blood components like platelets.

Discovery of phosphorylated lantibiotics with proimmune activity that regulate the oral microbiome.

Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome-derived commensals produce lantibiotics to impair pathogens' colonization and promote healthy microbiomes.

A Primed Neutrophil Subset Predicts the Risk of Bloodstream Infections in Allogeneic Hematopoietic Stem-Cell Transplant Patients: A Prospective Study.

Background: Bloodstream infections (BSIs) are the most common infectious complication in patients who receive allogeneic hematopoietic stem-cell transplants (allo-HSCTs). Polymorphonuclear neutrophils (PMNs) are quantified to monitor the susceptibility to BSIs; however, their degree of activation is not. We previously identified a population of primed PMNs (pPMNs) with distinct markers of activation representing approximately 10% of PMNs in circulation.

Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum.

Intervertebral disc degeneration (IDD) and osteoarthritis (OA) affecting the facet joint of the spine are biomechanically interdependent, typically occur in tandem, and have considerable epidemiological and pathophysiological overlap. Historically, the distinctions between these degenerative diseases have been emphasized. Therefore, research in the two fields often occurs independently without adequate consideration of the co-dependence of the two sites, which reside within the same functional spinal unit.

Metronidazole enhances killing of by human PMNs.

Background And Objectives: Periodontitis affects the supporting structures of the teeth as a result of the interactions between the subgingival biofilm and the host immune system. Periodontal therapy in severe forms of periodontitis often utilizes antimicrobial agents with some potential to improve host defense responses. In the present study, we investigated the effect of metronidazole (MTZ) at concentrations achievable in the periodontal pocket on PMN activation and PMN mediated killing of .

The Effect of Intensity-Modulated Radiotherapy to the Head and Neck Region on the Oral Innate Immune Response and Oral Microbiome: A Prospective Cohort Study of Head and Neck Tumour Patients.

Neutrophils, also known as polymorphonuclear leukocytes (PMNs), form a significant component of the innate host response, and the consequence of the interaction between the oral microbiota and PMNs is a crucial determinant of oral health status. The impact of radiation therapy (RT) for head and neck tumour (HNT) treatment on the oral innate immune system, neutrophils in particular, and the oral microbiome has not been thoroughly investigated. Therefore, the objective of this study was to characterize RT-mediated changes in oral neutrophils (oPMNs) and the oral microbiome in patients undergoing RT to treat HNTs.

The Crossroads of Periodontitis and Oral Squamous Cell Carcinoma: Immune Implications and Tumor Promoting Capacities.

Periodontitis (PD) is increasingly considered to interact with and promote a number of inflammatory diseases, including cancer. In the case of oral squamous cell carcinoma (OSCC) the local inflammatory response associated with PD is capable of triggering altered cellular events that can promote cancer cell invasion and proliferation of existing primary oral carcinomas as well as supporting the seeding of metastatic tumor cells into the gingival tissue giving rise to secondary tumors. Both the immune and stromal components of the periodontium exhibit phenotypic alterations and functional differences during PD that result in a microenvironment that favors cancer progression.

Development and optimization of an in vivo electrocardiogram recording method and analysis program for adult zebrafish.

Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiological abnormalities and disease. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources of phenotypic variation that could obscure data interpretation. Thus, we developed a novel platform to ensure high-quality recording of in vivo subdermal adult zebrafish ECGs and zebrafish ECG reading GUI (zERG), a program to acquire measurements from traces that commercial software cannot examine owing to erroneous peak calling.

Metabolites of the oral microbiome: important mediators of multikingdom interactions.

The oral cavity hosts over 700 different microbial species that produce a rich reservoir of bioactive metabolites critical to oral health maintenance. Over the last two decades, new insights into the oral microbiome and its importance in health and disease have emerged mainly due to the discovery of new oral microbial species using next-generation sequencing. This advancement has revolutionized the documentation of unique microbial profiles associated with different niches and health/disease states within the oral cavity and the relation of the oral bacteria to systemic diseases.

The role of CRISPR-Cas in advancing precision periodontics.

The significant advancement of molecular biology has revolutionized medicine and provided important technologies to further clinical research development. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are DNA sequences derived from bacteriophages which have previously infected the bacterial species. The CRISPR-Cas system plays a key role in bacterial defense by detecting and destroying DNA fragments during subsequent bacteriophage invasions.

Inhibition of BRD4 Reduces Neutrophil Activation and Adhesion to the Vascular Endothelium Following Ischemia Reperfusion Injury.

Renal ischemia reperfusion injury (IRI) is associated with inflammation, including neutrophil infiltration that exacerbates the initial ischemic insult. The molecular pathways involved are poorly characterized and there is currently no treatment. We performed an in silico analysis demonstrating changes in NFκB-mediated gene expression in early renal IRI.

GEF-H1 Is Required for Colchicine Inhibition of Neutrophil Rolling and Recruitment in Mouse Models of Gout.

Gout is a painful arthritic inflammatory disease caused by buildup of monosodium urate (MSU) crystals in the joints. Colchicine, a microtubule-depolymerizing agent that is used in prophylaxis and treatment of acute gout flare, alleviates the painful inflammatory response to MSU crystals. Using i.

Tissue-specific murine neutrophil activation states in health and inflammation.

Neutrophils are quickly recruited to tissues in response to proinflammatory cues; however, little is known about tissue neutrophil phenotypes in health. We employ a multicolor flow cytometric approach to assess surface markers of activation on neutrophils from the bone marrow, blood, peritoneum, spleen, liver, fat, colon, and oral cavity of healthy mice. Cell preparations were promptly fixed to preserve native surface marker expression levels.

The Neutrophil: Constant Defender and First Responder.

The role of polymorphonuclear neutrophils (PMNs) in biology is often recognized during pathogenesis associated with PMN hyper- or hypo-functionality in various disease states. However, in the vast majority of cases, PMNs contribute to resilience and tissue homeostasis, with continuous PMN-mediated actions required for the maintenance of health, particularly in mucosal tissues. PMNs are extraordinarily well-adapted to respond to and diminish the damaging effects of a vast repertoire of infectious agents and injurious processes that are encountered throughout life.

Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way.

Periodontitis is a highly prevalent disease. As it progresses, it causes serious morbidity in the form of periodontal abscesses and tooth loss and, in the latter stages, pain. It is also now known that periodontitis is strongly associated with several nonoral diseases.

Stressed-Out Oral Immunity: A Gateway From Socioeconomic Adversity to Periodontal Disease.

Objective: It has been suggested that adverse socioeconomic conditions "get under the skin" by eliciting a stress response that can trigger periodontal inflammation. We aimed to a) estimate the extent to which socioeconomic position (SEP) is associated with periodontal disease (PD) and proinflammatory oral immunity, and b) determine the contribution of psychosocial stress and stress hormones to these relationships.

Methods: In this cross-sectional study (n = 102), participants (20-59 years old) completed financial and perceived stress questionnaires and underwent full-mouth periodontal examinations.

In Vitro Assay for Sensitive Determination of Human Blood PMN Responses.

Polymorphonuclear neutrophils (PMNs) are the most common leukocytes in the circulation and exhibit a wide range of distinct cellular phenomena as part of their microbicidal killing activities, including degranulation, phagocytosis, reactive oxygen species (ROS) production, adhesion, chemotaxis and production of PMN Extracellular Traps (NETs). As a simple in vitro test of PMN functional responses in human blood we have developed a multicolor flow cytometry-based assay of PMN cluster of differentiation (CD) surface marker expression. Short incubations of whole human blood can be performed in the presence of a wide range of agonists or inhibitors, followed by sensitive detection of changes in CD marker expression.

Primed PMNs in healthy mouse and human circulation are first responders during acute inflammation.

Polymorphonuclear neutrophils (PMNs) are the most abundant circulating leukocytes, and the first cells recruited to sites of tissue inflammation. Using a fixation method to preserve native CD marker expression prior to immunophenotyping, we identified a distinct population of "primed for recruitment" PMNs in healthy mouse and human blood that has high expression of adhesion and activation markers compared with the bulk resting-state PMNs. In response to acute tissue inflammation, primed PMNs (pPMNs) were rapidly depleted from the circulation and recruited to the tissue.