Extracellular Vesicles in the Pathogenesis, Clinical Characterization, and Management of Dermatomyositis: A Narrative Review.

Extracellular vesicles (EVs) are lipid-bilayer particles secreted from cells that primarily assist in cell-to-cell communication through the content of their cargo, such as proteins and RNA. EVs have been implicated in the pathogenesis of various autoimmune diseases, including dermatomyositis (DM), an inflammatory autoimmune disease characterized by distinct cutaneous manifestations, myopathy, and lung disease. We sought to review the role of EVs in DM and understand how they contribute to the pathogenesis and clinical characterization of the disease. We summarized the research progress on EVs in dermatomyositis based on recent publications. EV cargoes, such as double-stranded DNA, microRNA, and proteins, contribute to DM pathogenesis and mediate the proinflammatory response and cytokine release through signaling pathways such as the stimulator of interferon genes (STING) pathway. These nucleic acids and proteins have been proposed as disease-specific, stable biomarkers to monitor disease activity and responses to therapy. They also correlate with clinical parameters, inflammatory markers, and disease severity scores. Furthermore, some markers show an association with morbidities of DM, such as muscle weakness and interstitial lung disease. The continued study of EVs will help us to further elucidate our understanding of dermatomyositis.

Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling.

Synapses connect discrete neurons into vast networks that send, receive, and encode diverse forms of information. Synaptic function and plasticity, the neuronal process of adapting to diverse and variable inputs, depend on the dynamic nature of synaptic molecular components, which is mediated in part by cell adhesion signaling pathways. Here, we found that the enzyme biliverdin reductase (BVR) physically links together key focal adhesion signaling molecules at the synapse. BVR-null (BVR-/-) mice exhibited substantial deficits in learning and memory on neurocognitive tests, and hippocampal slices in which BVR was postsynaptically depleted showed deficits in electrophysiological responses to stimuli. RNA sequencing, biochemistry, and pathway analyses suggested that these deficits were mediated through the loss of focal adhesion signaling at both the transcriptional and biochemical level in the hippocampus. Independently of its catalytic function, BVR acted as a bridge between the primary focal adhesion signaling kinases FAK and Pyk2 and the effector kinase Src. Without BVR, FAK and Pyk2 did not bind to and stimulate Src, which then did not phosphorylate the N-methyl-d-aspartate (NMDA) receptor, a critical posttranslational modification for synaptic plasticity. Src itself is a molecular hub on which many signaling pathways converge to stimulate NMDAR-mediated neurotransmission, thus positioning BVR at a prominent intersection of synaptic signaling.

Diet and acne: A systematic review.

Background: Acne vulgaris is a common cutaneous disorder. Diet and metabolism, specifically glycemic content and dairy, influence hormones such as insulin, insulin-like growth factor 1, and androgens, which affect acnegenesis. Objective: To systematically review high-quality evidence regarding the association of dietary glycemic and dairy intake with acnegenesis. Methods: A comprehensive literature search, without timeline restriction, of MEDLINE (completed between October and November 2021) for English-language papers that examined the association between diet and acne was conducted. The evidence quality was assessed using the Ottawa quality assessment scale. Results: The literature search yielded 410 articles, of which 34 articles met the inclusion criteria. The literature on whether dairy product intake is associated with acnegenesis is mixed and may be dependent on sex, ethnicity, and cultural dietary habits. High glycemic index and increased daily glycemic load intake were positively associated with acnegenesis and acne severity, an observation supported by randomized controlled trials. Conclusion: High glycemic index, increased glycemic load, and carbohydrate intake have a modest yet significant proacnegenic effect. Increased dairy consumption may have been proacnegenic in select populations, such as those in which a Western diet is prevalent. The impact of diet on acnegenesis is likely dependent on sex and ethnicity. Further randomized trials are necessary to fully characterize the potential associations.

Identification of skin signs in human-trafficking survivors.

Human-trafficking survivors suffer significant physical, mental, and social health consequences, prompting them to seek health care services. Although there is research regarding identification protocols for human-trafficking victims, there is no framework outlining the dermatologic patterns of survivors of human trafficking. We sought to identify the dermatologic signs reported in human-trafficking victims to create a framework for dermatologists and the broader medical community to appropriately screen patients at risk. After screening 577 pertinent records in the PubMed and Google Scholar databases for information about the physical signs of human trafficking in health care, 10 final studies were selected. Significant findings of rashes and brandings, such as tattoos, were more likely in sex-trafficked patients, whereas burns, injuries, and deep cuts were more likely to be found in labor-trafficked patients. This review outlines important identification guidelines that dermatologists and the broader medical community can use to recognize victims and take appropriate action while also raising awareness of human trafficking as an emerging public health issue.

Bilirubin Links Heme Metabolism to Neuroprotection by Scavenging Superoxide.

Bilirubin is one of the most frequently measured metabolites in medicine, yet its physiologic roles remain unclear. Bilirubin can act as an antioxidant in vitro, but whether its redox activity is physiologically relevant is unclear because many other antioxidants are far more abundant in vivo. Here, we report that depleting endogenous bilirubin renders mice hypersensitive to oxidative stress. We find that mice lacking bilirubin are particularly vulnerable to superoxide (O2⋅-) over other tested reactive oxidants and electrophiles. Whereas major antioxidants such as glutathione and cysteine exhibit little to no reactivity toward O2⋅-, bilirubin readily scavenges O2⋅-. We find that bilirubin's redox activity is particularly important in the brain, where it prevents excitotoxicity and neuronal death by scavenging O2⋅- during NMDA neurotransmission. Bilirubin's unique redox activity toward O2⋅- may underlie a prominent physiologic role despite being significantly less abundant than other endogenous and exogenous antioxidants.