Ultrasound-Guided Injections of HYADD4 for Knee Osteoarthritis Improves Pain and Functional Outcomes at 3, 6, and 12 Months without Changes in Measured Synovial Fluid, Serum Collagen Biomarkers, or Most Synovial Fluid Biomarker Proteins at 3 Months.

Background: Prior studies have demonstrated improved efficacy when intra-articular (IA) therapeutics are injected using ultrasound (US) guidance. The aim of this study was to determine if clinical improvement in pain and function after IA hyaluronic acid injections using US is associated with changes in SF volumes and biomarker proteins at 3 months.

Methods: 49 subjects with symptomatic knee OA, BMI < 40, and KL radiographic grade II or III participated.

Cytokine signatures of end organ injury in COVID-19.

Increasing evidence has shown that Coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunologic response. We aimed to assess the differences in inflammatory cytokines in COVID-19 patients compared to contemporaneously hospitalized controls and then analyze the relationship between these cytokines and the development of Acute Respiratory Distress Syndrome (ARDS), Acute Kidney Injury (AKI) and mortality. In this cohort study of hospitalized patients, done between March third, 2020 and April first, 2020 at a quaternary referral center in New York City we included adult hospitalized patients with COVID-19 and negative controls.

Complement C6 deficiency exacerbates pathophysiology after spinal cord injury.

Historically, the membrane attack complex, composed of complement components C5b-9, has been connected to lytic cell death and implicated in secondary injury after a CNS insult. However, studies to date have utilized either non-littermate control rat models, or mouse models that lack significant C5b-9 activity. To investigate what role C5b-9 plays in spinal cord injury and recovery, we generated littermate PVG C6 wildtype and deficient rats and tested functional and histological recovery after moderate contusion injury using the Infinite Horizon Impactor.

Histone Deacetylase 7 Inhibition in a Murine Model of Gram-Negative Pneumonia-Induced Acute Lung Injury.

Background: Pulmonary infections remain the most common cause of Acute Respiratory Distress Syndrome (ARDS), a pulmonary inflammatory disease with high mortality, for which no targeted therapy currently exists. We have previously demonstrated an ameliorated syndrome with early, broad spectrum Histone Deacetylase (HDAC) inhibition in a murine model of gram-negative pneumonia-induced Acute Lung Injury (ALI), the underlying pulmonary pathologic phenotype leading to ARDS. With the current project we aim to determine if selective inhibition of a specific HDAC leads to a similar pro-survival phenotype, potentially pointing to a future therapeutic target.

Timing of valproic acid in acute lung injury: prevention is the best therapy?

Background: Acute lung injury and respiratory distress syndrome is characterized by uncontrolled inflammation of the lungs after a severe inflammatory stimulus. We have previously demonstrated an ameliorated syndrome and improved survival in mice with early administration of valproic acid (VPA), a broad-spectrum histone deacetylase inhibitor, while studies in humans have shown no benefit when anti-inflammatories are administered late. The current study tested the hypothesis that early treatment would improve outcomes in our gram-negative pneumonia-induced acute lung injury.

Characterization of recovery, repair, and inflammatory processes following contusion spinal cord injury in old female rats: is age a limitation?

Background: Although the incidence of spinal cord injury (SCI) is steadily rising in the elderly human population, few studies have investigated the effect of age in rodent models. Here, we investigated the effect of age in female rats on spontaneous recovery and repair after SCI. Young (3 months) and aged (18 months) female rats received a moderate contusion SCI at T9.

Complement protein C1q and adiponectin stimulate Mer tyrosine kinase-dependent engulfment of apoptotic cells through a shared pathway.

The failure to clear apoptotic cells is linked to defects in development and autoimmunity. Complement component C1q is required for efficient engulfment of apoptotic cells (efferocytosis), and C1q deficiency leads to the development of lupus. We recently identified a novel molecular mechanism for C1q-dependent efferocytosis in murine macrophages.

C1q and phagocytosis: the perfect complement to a good meal.

Complement component C1q is a member of a family of soluble proteins called defense collagens, which are important in host defense and apoptotic cell clearance. Failure to efficiently clear apoptotic cells in the absence of C1q is associated with autoimmunity. Here, we review the literature describing a central role for C1q in the enhancement of phagocyte function and focus specifically on C1q in apoptotic cell clearance.

Complement component C1q regulates macrophage expression of Mer tyrosine kinase to promote clearance of apoptotic cells.

Failure to efficiently clear apoptotic cells is linked to defects in development and the onset of autoimmunity. Complement component C1q is required for efficient engulfment of apoptotic cells in mice and humans; however, the molecular mechanisms leading to C1q-dependent engulfment are not fully understood. In this study, we used primary mouse macrophages to identify and characterize a novel molecular mechanism for macrophage-mediated C1q-dependent engulfment of apoptotic cells.

CD93: recent advances and implications in disease.

While it has been known for some time that CD93 regulates several processes involved in innate immunity and inflammation including phagocytosis and adhesion, the function of CD93 in disease progression is only now being elucidated. Recent in vivo studies in mice, and genome wide studies in mice and humans, have provided clues about its molecular function. Following a comprehensive review of CD93 expression patterns, this review will focus on recent findings over the last three years that address the putative function of CD93 in inflammation and innate immunity.

Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment.

Traumatic injury to the central nervous system results in the disruption of the blood brain/spinal barrier, followed by the invasion of cells and other components of the immune system that can aggravate injury and affect subsequent repair and regeneration. Although studies of chronic neuroinflammation in the injured spinal cord of animals are clinically relevant to most patients living with traumatic injury to the brain or spinal cord, very little is known about chronic neuroinflammation, though several studies have tested the role of neuroinflammation in the acute period after injury. The present study characterizes a novel cell preparation method that assesses, quickly and effectively, the changes in the principal immune cell types by flow cytometry in the injured spinal cord, daily for the first 10 days and periodically up to 180 days after spinal cord injury.

Comparison of immunopathology and locomotor recovery in C57BL/6, BUB/BnJ, and NOD-SCID mice after contusion spinal cord injury.

Studies of cell transplantation therapeutics in animal models of traumatic spinal cord injury (SCI) are often hampered by partial or complete rejection of the graft by the host. Pharmacological immunosuppression is rarely sufficient to prevent rejection. Further, the immunological niche created by both the host immune response and immunosuppressant drugs could hypothetically influence the proliferation, differentiation, and fate of transplanted progenitor/stem cells.

Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury.

Although studies have suggested a role for the complement system in the pathophysiology of spinal cord injury (SCI), that role remains poorly defined. Additionally, the relative contribution of individual complement pathways in SCI is unknown. Our initial studies revealed that systemic complement activation was strongly influenced by genetic background and gender.

Characterization of early and terminal complement proteins associated with polymorphonuclear leukocytes in vitro and in vivo after spinal cord injury.

Background: The complement system has been suggested to affect injury or disease of the central nervous system (CNS) by regulating numerous physiological events and pathways. The activation of complement following traumatic CNS injury can also result in the formation and deposition of C5b-9 membrane attack complex (C5b-9/MAC), causing cell lysis or sublytic effects on vital CNS cells. Although complement proteins derived from serum/blood-brain barrier breakdown can contribute to injury or disease, infiltrating immune cells may represent an important local source of complement after injury.