Immune system-related plasma extracellular vesicles in healthy aging.

Objectives: To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults.

Methods: EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers.

Liver-derived plasminogen mediates muscle stem cell expansion during caloric restriction through the plasminogen receptor Plg-R.

An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRS (MetRS) transgenic mouse to identify liver-secreted plasminogen as a candidate for regulating satellite cell expansion during short-term CR. Knockdown of circulating plasminogen prevents satellite cell expansion during short-term CR.

Anti-CMV IgG Seropositivity is Associated with Plasma Biomarker Evidence of Amyloid-β Accumulation.

Background: Some human studies have identified infection with cytomegalovirus (CMV), a member of the alpha herpesvirus family, as a risk factor for Alzheimer's disease and related dementias (ADRD). To our knowledge, no studies have evaluated associations of CMV seropositivity with plasma biomarkers of ADRD risk in middle-aged adults.

Objective: In participants recruited for an exercise study, we evaluated cross-sectional associations of CMV seropositivity with: Aβ42/Aβ40 ratio, a low ratio suggestive of central nervous system Aβ accumulation; glial fibrillary acidic protein (GFAP), a measure of neuroinflammation; and neurofilament light (NfL), a measure of neurodegeneration.

Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores.

The glycosaminoglycan hyaluronan (HA) plays important roles in diverse physiological functions where the distribution of its molecular weight (MW) can influence its behavior and is known to change in response to disease conditions. During inflammation, HA undergoes a covalent modification in which heavy chain subunits of the inter-alpha-inhibitor family of proteins are transferred to its structure, forming heavy chain-HA (HC•HA) complexes. While limited assessments of HC•HA have been performed previously, determining the size distribution of its HA component remains a challenge.

Metabolomic profiling during ex situ normothermic perfusion before heart transplantation defines patterns of substrate utilization and correlates with markers of allograft injury.

Background: Cardiac metabolism is altered in heart failure and ischemia-reperfusion injury states. We hypothesized that metabolomic profiling during ex situ normothermic perfusion before heart transplantation (HT) would lend insight into myocardial substrate utilization and report on subclinical and clinical allograft dysfunction risk.

Methods: Metabolomic profiling was performed on serial samples of ex situ normothermic perfusate assaying biomarkers of myocardial injury in lactate and cardiac troponin I (TnI) as well as metabolites (66 acylcarnitines, 15 amino acids, nonesterified fatty acids [NEFA], ketones, and 3-hydroxybutyrate).

Links between three chronic and age-related diseases, osteoarthritis, periodontitis, and osteoporosis, in a wild mammal (moose) population.

Objective: Osteoarthritis, periodontitis and osteoporosis are chronic, age-related diseases which adversely impact millions of people worldwide. Because these diseases pose a major global public health challenge, there is an urgent need to better understand how these diseases are interrelated. Our objective was to document the age and sex-specific prevalence of each disease and assess interrelationships among the three diseases in a wild mammal (moose, Alces alces) population.

Increased Effusion Synovitis for Those With a Dysregulated Inflammatory Response After an Anterior Cruciate Ligament Injury.

Introduction The progression to posttraumatic osteoarthritis (PTOA) after an anterior cruciate ligament (ACL) injury is likely multifactorial, involving biological, mechanical, and psychosocial factors. Following acute joint trauma, there appears to be a subset of patients that demonstrate a dysregulated inflammatory response. This pro-inflammatory phenotype, or "Inflamma-type," is characterized by an amplified pro-inflammatory response combined with a lack of attendant anti-inflammatory response and has been observed following both an ACL injury and an intra-articular fracture.

RELATIONSHIP BETWEEN REPRODUCTIVE AND BONE BIOMARKERS AND OSTEOARTHRITIS IN ZOO ASIAN () AND AFRICAN () ELEPHANTS.

Osteoarthritis (OA) is common in zoo Asian () and African () elephants. This study investigated the relationship between confirmed or suspected OA with ovarian cyclicity, gonadotropins, progestagens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and collagen type I (CTX-I) in zoo elephants. In Asian elephants, odds of having confirmed or suspected OA decreased with cycling (OR = 0.

Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.

Background: The kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer's disease and related dementias (ADRD).

Objective: The objective of this study was to determine the associations of plasma KP metabolites (kynurenine [KYN], kynurenic acid [KA], and tryptophan [TRP]) with a panel of plasma ADRD biomarkers (Aβ42/ β40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and cognitive performance in a subset of older adults drawn from the Duke Physical Performance Across the LifeSpan (PALS) study.

Methods: The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance.

The association of accelerated epigenetic age with all-cause mortality in cardiac catheterization patients as mediated by vascular and cardiometabolic outcomes.

Background: Epigenetic age is a DNA methylation-based biomarker of aging that is accurate across the lifespan and a range of cell types. The difference between epigenetic age and chronological age, termed age acceleration (AA), is a strong predictor of lifespan and healthspan. The predictive capabilities of AA for all-cause mortality have been evaluated in the general population; however, its utility is less well evaluated in those with chronic conditions.

Tibiofemoral knee osteoarthritis progresses symmetrically by knee compartment in the GOGO cohort.

Objective: To evaluate the degree of symmetry of knee osteoarthritis (OA) structural severity and progression of participants with a mean follow-up time of 3.8 years.

Design: Participants from the Genetics of Generalized Osteoarthritis (GOGO) study (n = 705) were selected on the basis of radiographic evidence of OA in at least 1 knee, availability of radiographs at baseline and follow-up, and no history of prior knee injury or surgery.

Association of Biomarkers with Individual and Multiple Body Sites of Pain: The Johnston County Osteoarthritis Project.

Introduction: Biochemical biomarkers may provide insight into musculoskeletal pain reported at individual or multiple body sites. The purpose of this study was to determine if biomarkers or pressure-pain threshold (PPT) were associated with individual or multiple sites of pain.

Methods: This cross-sectional analysis included 689 community-based participants.

Biomarker clusters differentiate phenotypes of lumbar spine degeneration and low back pain: The Johnston County Osteoarthritis Project.

Objective: Describe the association between biomarkers and lumbar spine degeneration (vertebral osteophytes [OST], facet joint osteoarthritis [FOA], and disc space narrowing [DSN]), for persons with and without low back pain (LBP) and determine whether clusters based on biomarkers differentiate lumbar spine structure with and without LBP.

Methods: Using data from the Johnston County Osteoarthritis Project (2006-2010), we measured serum N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, HA, IL-6, BDNF, OPG, and NPY, and urinary CTX-II. Biomarkers were used to group participants using k-means cluster analysis.

Evaluating immune response and metabolic related biomarkers pre-allogenic hematopoietic stem cell transplant in acute myeloid leukemia.

Although hematopoietic stem cell transplantation (HCT) is the only curative treatment for acute myeloid leukemia (AML), it is associated with significant treatment related morbidity and mortality. There is great need for predictive biomarkers associated with overall survival (OS) and clinical outcomes. We hypothesized that circulating metabolic, inflammatory, and immune molecules have potential as predictive biomarkers for AML patients who receive HCT treatment.

Field-Based Assessments of Behavioral Patterns During Shiftwork in Police Academy Trainees Using Wearable Technology.

Circadian misalignment, as occurs in shiftwork, is associated with numerous negative health outcomes. Here, we sought to improve data labeling accuracy from wearable technology using a novel data pre-processing algorithm in 27 police trainees during shiftwork. Secondarily, we explored changes in four metabolic salivary biomarkers of circadian rhythm during shiftwork.

TNF-α Carried by Plasma Extracellular Vesicles Predicts Knee Osteoarthritis Progression.

Objectives: To identify plasma extracellular vesicles (EVs) associated with radiographic knee osteoarthritis (OA) progression.

Methods: EVs of small (SEV), medium (MEV) and large (LEV) sizes from plasma of OA participants (n=30) and healthy controls (HCs, n=22) were profiled for surface markers and cytokine cargo by high-resolution flow cytometry. The concentrations of cytokines within (endo-) and outside (exo-) EVs were quantified by multiplex ELISA.

A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis.

Objective: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis.

Methods: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure.

Extracellular Vesicles as Biological Indicators and Potential Sources of Autologous Therapeutics in Osteoarthritis.

Along with cytokines, extracellular vesicles (EVs) released by immune cells in the joint contribute to osteoarthritis (OA) pathogenesis. By high-resolution flow cytometry, we characterized 18 surface markers and 4 proinflammatory cytokines carried by EVs of various sizes in plasma and synovial fluid (SF) from individuals with knee OA, with a primary focus on immune cells that play a major role in OA pathogenesis. By multiplex immunoassay, we also measured concentrations of cytokines within (endo) and outside (exo) EVs.

A phase 2 trial of the somatostatin analog pasireotide to prevent GI toxicity and acute GVHD in allogeneic hematopoietic stem cell transplant.

Background: Allogeneic hematopoietic stem cell transplantation (HCT) is an often curative intent treatment, however it is associated with significant gastrointestinal (GI) toxicity and treatment related mortality. Graft-versus-host disease is a significant contributor to transplant-related mortality. We performed a phase 2 trial of the somatostatin analog pasireotide to prevent gastrointestinal toxicity and GVHD after myeloablative allogeneic HCT.

Exercise protects against cardiac and skeletal muscle dysfunction in a mouse model of inflammatory arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory arthritis impacting primarily joints and cardiac and skeletal muscle. RA's distinct impact on cardiac and skeletal muscle tissue is suggested by studies showing that new RA pharmacologic agents strongly improve joint inflammation, but have little impact on RA-associated mortality, cardiovascular disease, and sarcopenia. Thus, the objective is to understand the distinct effects of RA on cardiac and skeletal muscle, and to therapeutically target these tissues through endurance-based exercise as a way to improve RA mortality and morbidity.

Initial displacement of the intra-articular surface after articular fracture correlates with PTA in C57BL/6 mice but not "superhealer" MRL/MpJ mice.

Posttraumatic arthritis (PTA) occurs commonly after articular fracture and may arise, in part, from joint surface incongruity after injury. MRL/MpJ (MRL) "super-healer" mice are protected from PTA compared to C57BL/6 (B6) mice following articular fracture. However, the relationship between the initial displacement of the articular surface, biologic response, and susceptibility to PTA after fracture remains unclear.

Degenerative joint changes following intra-articular fracture are more severe in mice with T cell deficiency.

The inflammatory response to joint injury, specifically intra-articular fracture, has been implicated in posttraumatic arthritis development. However, the role of T cells in regulating the development of posttraumatic arthritis is unclear. We hypothesized that the absence of T cells would lead to less severe posttraumatic arthritis following intra-articular fracture.