Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production

Pattern recognition receptors (PRRs) such as Toll-like receptors are aberrantly expressed of peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients, for playing immunopathological roles. basal productions of cytokines (IL-6, IL-8 and IL-10) were significantly increased in immunosuppressant naïve patients and patients with active disease despite immunosuppressants compared with HCs. Upon MDP stimulaiton, relative induction (%) of cytokines (IL-1β) from PBMC was significantly increased in immunosuppressant naïve patients with inactive disease, and patients with active disease despite immunosuppressant treatment compared with HCs. Immunosuppressant usage was associated with a decreased basal production and MDP induced relative induction (%) of IL-10 in patients with inactive disease compared with immunosuppressant naïve patients and HCs.Bacterial exposure may increase the NOD2 expression in monocytes in immunosuppressant naïve SLE patients which can subsequently lead to aberrant activation of PBMCs to produce proinflammatory cytokines, implicating the innate immune response for extracellular pathogens in the immunopathological mechanisms in SLE. Immunosuppressant therapy may downregulate NOD2 expression in CD8+ T lymphocytes, monocytes, and DCs in SLE patients which subsequently IL-10 reduction, contributing towards the regulation of immunopathological mechanisms of SLE, at the expense of increasing risk of bacterial infection

A homozygous MED11 C-terminal variant causes a lethal neurodegenerative disease

Purpose: The mediator (MED) multisubunit-complex modulates the activity of the transcriptional machinery, and genetic defects in different MED subunits (17, 20, 27) have been implicated in neurologic diseases. In this study, we identified a recurrent homozygous variant in MED11 (c.325C>T; p.Arg109Ter) in 7 affected individuals from 5 unrelated families. Methods: To investigate the genetic cause of the disease, exome or genome sequencing were performed in 5 unrelated families identified via different research networks and Matchmaker Exchange. Deep clinical and brain imaging evaluations were performed by clinical pediatric neurologists and neuroradiologists. The functional effect of the candidate variant on both MED11 RNA and protein was assessed using reverse transcriptase polymerase chain reaction and western blotting using fibroblast cell lines derived from 1 affected individual and controls and through computational approaches. Knockouts in zebrafish were generated using clustered regularly interspaced short palindromic repeats/Cas9. Results: The disease was characterized by microcephaly, profound neurodevelopmental impairment, exaggerated startle response, myoclonic seizures, progressive widespread neurodegeneration, and premature death. Functional studies on patient-derived fibroblasts did not show a loss of protein function but rather disruption of the C-terminal of MED11, likely impairing binding to other MED subunits. A zebrafish knockout model recapitulates key clinical phenotypes. Conclusion: Loss of the C-terminal of MED subunit 11 may affect its binding efficiency to other MED subunits, thus implicating the MED-complex stability in brain development and neurodegeneration

Laser and Light-Based Therapies in the Treatment of Hair Loss

Laser and light-based therapies including low-level laser and light therapy, fractional, excimer, and other lasers are increasingly well-regarded treatment options for patients with hair loss. Lasers emit wavelengths of light specific to a chromophore in the tissue, causing a targeted thermal response with minimal damage to surrounding tissue. The cascade of events downstream of the initial injury is responsible for the clinical effects seen. Low-level laser or light therapy (LLLT) was accidentally discovered in the 1960s when Hungarian scientist Endre Mester attempted to repeat an experiment performed by American Paul McGuff, who had cured malignant tumors in rats using a ruby laser. Mester’s laser was much less powerful than McGuff’s, and while he did not successfully cure any tumors, he observed for the first time that a low-level laser induced hair growth and improved wound healing. The mechanism by which this occurs is described as photobiomodulation or the stimulation of biological processes in the target tissue. This accidental discovery is the basis for the huge variety of LLLT products available on the market today. In the last 2 years alone, the number of approved items classified as laser, comb, or hair products intended for the purpose of the growth of scalp hairs on the FDA’s 510(k) premarket notification list, meaning the device is demonstrated to be at least safe and effective, has nearly doubled to a total of 50. This chapter will summarize current knowledge regarding all laser and light devices for patients with various forms of alopecia and will outline treatment strategy, device parameters, and appropriate limitations of use to guide providers toward optimal patient management