Defining a Unique Gene Expression Profile in Mature and Developing Keloids.

Keloids are benign, fibroproliferative dermal tumors that typically form owing to abnormal wound healing. The current standard of care is generally ineffective and does not prevent recurrence. To characterize keloid scars and better understand the mechanism of their formation, we performed transcriptomic profiling of keloid biopsies from a total of 25 subjects of diverse racial and ethnic origins, 15 of whom provided a paired nonlesional sample, a longitudinal sample, or both.

Association of complement pathways with COVID-19 severity and outcomes.

Objectives: Complement activation has been implicated in COVID-19 pathogenesis. This study aimed to assess the levels of complement activation products and full-length proteins in hospitalized patients with COVID-19, and evaluated whether complement pathway markers are associated with outcomes.

Methods: Longitudinal measurements of complement biomarkers from 89 hospitalized adult patients, grouped by baseline disease severity, enrolled in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial and treated with intravenous sarilumab (200 mg or 400 mg) or placebo (NCT04315298), were performed.

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy.

Background: C3 glomerulopathy (C3G) is characterized by the alternative-pathway (AP) hyperactivation induced by nephritic factors or complement gene mutations. Mice deficient in complement factor H (CFH) are a classic C3G model, with kidney disease that requires several months to progress to renal failure. Novel C3G models can further contribute to understanding the mechanism behind this disease and developing therapeutic approaches.

Defining the Activated Fibroblast Population in Lung Fibrosis Using Single-Cell Sequencing.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disorder driven by unrelenting extracellular matrix deposition. Fibroblasts are recognized as the central mediators of extracellular matrix production in IPF; however, the characteristics of the underlying fibroblast cell populations in IPF remain poorly understood. Here, we use an unbiased single-cell RNA sequencing analysis of a bleomycin-induced pulmonary fibrosis model to characterize molecular responses to fibrotic injury.

Computational stress analysis of atherosclerotic plaques in ApoE knockout mice.

The aortic sinus lesions of apolipoprotein E knockout (ApoE KO) mice seldom show any signs of fibrous cap disruption, whereas cap ruptures have been recently reported in the proximal part of their brachiocephalic arteries (BCA). We use histology based finite element analysis to evaluate peak circumferential stresses in aortic and BCA lesions from six 42-56 week-old fat-fed ApoE KO mice. This analysis is able to both explain the greater stability of aortic lesions in mice and provide new insight into the BCA lesion as a model for the stability of human lesions with and without microcalcifications in their fibrous caps.

Optimization of methods to study pulmonary dendritic cell migration reveals distinct capacities of DC subsets to acquire soluble versus particulate antigen.

Dendritic cell migration from the airway to lymph nodes is a key event in the development of airway immunity during infection, allergy, and vaccination. To identify the best approaches to investigate DC migration to lung-draining lymph nodes, we directly compared three methods previously used to track DC migration: airway administration of fluorescent OVA, latex beads, or carboxyfluorescein succinimidyl ester (CFSE). We show that two of the methods employed in optimal conditions-administration of fluorescent OVA or latex particles-have broadly relevant utility in studies of pulmonary DC migration, both in the presence and absence of inflammatory mediators.

Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques.

Monocytes participate critically in atherosclerosis. There are 2 major subsets expressing different chemokine receptor patterns: CCR2(+)CX3CR1(+)Ly-6C(hi) and CCR2(-)CX3CR1(++)Ly-6C(lo) monocytes. Both C-C motif chemokine receptor 2 (CCR2) and C-X(3)-C motif chemokine receptor 1 (CX3CR1) are linked to progression of atherosclerotic plaques.

Ultrastructural evidence for mu-opioid modulation of cholinergic pathways in rat dentate gyrus.

Within the rat hippocampal formation, cholinergic afferents and mu-opioid receptors (MORs) are involved in many crucial learning processes, including those associated with drug reward. Pharmacological data, and the overlapping distributions of cholinergic and mu-opioid systems, particularly in the dentate gyrus, suggest that MOR activation is a potential mechanism for endogenous opioid modulation of cholinergic activity. To date, anatomical evidence supporting this has not been reported.