The STAT3/SETDB2 axis dictates NF-κB-mediated inflammation in macrophages during wound repair.

Macrophage transition from an inflammatory to reparative phenotype after tissue injury is controlled by epigenetic enzymes that regulate inflammatory gene expression. We have previously identified that the histone methyltransferase SETDB2 in macrophages drives tissue repair by repressing NF-κB-mediated inflammation. Complementary ATAC-Seq and RNA-Seq of wound macrophages isolated from mice deficient in SETDB2 in myeloid cells revealed that SETDB2 suppresses the inflammatory gene program by inhibiting chromatin accessibility at NF-κB-dependent gene promoters.

The histone methyltransferase Mixed-lineage-leukemia-1 drives T cell phenotype via Notch signaling in diabetic tissue repair.

Immune cell-mediated inflammation is important in normal tissue regeneration but can be pathologic in diabetic wounds. Limited literature exists on the role of CD4+ T cells in normal or diabetic wound repair; however, the imbalance of CD4+ Th17/Tregs has been found to promote inflammation in other diabetic tissues. Here, using human tissue and murine transgenic models, we identified that the histone methyltransferase Mixed-lineage-leukemia-1 (MLL1) directly regulates the Th17 transcription factor RORγ via an H3K4me3 mechanism and increases expression of Notch receptors and downstream Notch signaling.

Histone demethylase JARID1C/KDM5C regulates Th17 cells by increasing IL-6 expression in diabetic plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are first responders to tissue injury, where they prime naive T cells. The role of pDCs in physiologic wound repair has been examined, but little is known about pDCs in diabetic wound tissue and their interactions with naive CD4+ T cells. Diabetic wounds are characterized by increased levels of inflammatory IL-17A cytokine, partly due to increased Th17 CD4+ cells.

Diabetic Wound Keratinocytes Induce Macrophage JMJD3-Mediated Nlrp3 Expression via IL-1R Signaling.

Macrophage (Mφ) plasticity is critical for normal wound repair; however, in type 2 diabetic wounds, Mφs persist in a low-grade inflammatory state that prevents the resolution of wound inflammation. Increased NLRP3 inflammasome activity has been shown in diabetic wound Mφs; however, the molecular mechanisms regulating NLRP3 expression and activity are unclear. Here, we identified that diabetic wound keratinocytes induce Nlrp3 gene expression in wound Mφs through IL-1 receptor-mediated signaling, resulting in enhanced inflammasome activation in the presence of pathogen-associated molecular patterns and damage-associated molecular patterns.

Populational Variations of Cheiloscopy Patterns: A cross-sectional observation pilot study.

Lip prints are unique and have potential for use as a human identifier. The purpose of this study was to observe possible cheiloscopy differences of individuals with and without parafunctional oral habits such as smoking, vaping, playing a wind instrument or using an asthma inhaler. This IRB approved blinded cross-sectional observation pilot study collected lip prints from sixty-six individuals, three of which were excluded.

Cheiloscopy patterns in individuals with and without parafunctional oral habits: A cross-sectional observation pilot study.

Purpose: Lip prints are unique and have potential for use as a human identifier. The purpose of this study was to observe possible cheiloscopy differences of individuals with and without parafunctional oral habits such as smoking, vaping, playing a wind instrument or using an asthma inhaler.

Methods: This IRB approved blinded cross-sectional observation pilot study collected lip prints from 66 individuals, three of which were excluded.

The Histone Methyltransferase SETDB2 Modulates Tissue Inhibitors of Metalloproteinase-Matrix Metalloproteinase Activity During Abdominal Aortic Aneurysm Development.

Objective: To determine macrophage-specific alterations in epigenetic enzyme function contributing to the development of abdominal aortic aneurysms (AAAs).

Background: AAA is a life-threatening disease, characterized by pathologic vascular remodeling driven by an imbalance of matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). Identifying mechanisms regulating macrophage-mediated extracellular matrix degradation is of critical importance to developing novel therapies.

The histone methyltransferase MLL1/KMT2A in monocytes drives coronavirus-associated coagulopathy and inflammation.

Coronavirus-associated coagulopathy (CAC) is a morbid and lethal sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CAC results from a perturbed balance between coagulation and fibrinolysis and occurs in conjunction with exaggerated activation of monocytes/macrophages (MO/Mφs), and the mechanisms that collectively govern this phenotype seen in CAC remain unclear. Here, using experimental models that use the murine betacoronavirus MHVA59, a well-established model of SARS-CoV-2 infection, we identify that the histone methyltransferase mixed lineage leukemia 1 (MLL1/KMT2A) is an important regulator of MO/Mφ expression of procoagulant and profibrinolytic factors such as tissue factor (F3; TF), urokinase (PLAU), and urokinase receptor (PLAUR) (herein, "coagulopathy-related factors") in noninfected and infected cells.

Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair.

Macrophage plasticity is critical for normal tissue repair following injury. In pathologic states such as diabetes, macrophage plasticity is impaired, and macrophages remain in a persistent proinflammatory state; however, the reasons for this are unknown. Here, using single-cell RNA sequencing of human diabetic wounds, we identified increased JMJD3 in diabetic wound macrophages, resulting in increased inflammatory gene expression.

IFN-κ is critical for normal wound repair and is decreased in diabetic wounds.

Wound repair following acute injury requires a coordinated inflammatory response. Type I IFN signaling is important for regulating the inflammatory response after skin injury. IFN-κ, a type I IFN, has recently been found to drive skin inflammation in lupus and psoriasis; however, the role of IFN-κ in the context of normal or dysregulated wound healing is unclear.

Dextran-Mimetic Quantum Dots for Multimodal Macrophage Imaging , and .

Macrophages are white blood cells with diverse functions contributing to a healthy immune response as well as the pathogenesis of cancer, osteoarthritis, atherosclerosis, and obesity. Due to their pleiotropic and dynamic nature, tools for imaging and tracking these cells at scales spanning the whole body down to microns could help to understand their role in disease states. Here we report fluorescent and radioisotopic quantum dots (QDs) for multimodal imaging of macrophage cells , , and .

The Utility of Hepatobiliary Scintigraphy Scans in the Tokyo Guidelines Era for Acute Cholecystitis.

Background: Hepatobiliary Scintigraphy (HIDA) aids the diagnosis of acute cholecystitis (AC) but has limitations. We sought to design a model based on the Tokyo Guidelines 2018 (TG18) to predict HIDA results.

Methods: A retrospective review of patients who underwent a HIDA scan during the evaluation of AC was performed.

Coronavirus induces diabetic macrophage-mediated inflammation via SETDB2.

COVID-19 induces a robust, extended inflammatory "cytokine storm" that contributes to an increased morbidity and mortality, particularly in patients with type 2 diabetes (T2D). Macrophages are a key innate immune cell population responsible for the cytokine storm that has been shown, in T2D, to promote excess inflammation in response to infection. Using peripheral monocytes and sera from human patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a murine hepatitis coronavirus (MHV-A59) (an established murine model of SARS), we identified that coronavirus induces an increased Mφ-mediated inflammatory response due to a coronavirus-induced decrease in the histone methyltransferase, SETDB2.

Macrophage-mediated inflammation in diabetic wound repair.

Non-healing wounds in Type 2 Diabetes (T2D) patients represent the most common cause of amputation in the US, with an associated 5-year mortality of nearly 50%. Our lab has examined tissue from both T2D murine models and human wounds in order to explore mechanisms contributing to impaired wound healing. Current published data in the field point to macrophage function serving a pivotal role in orchestrating appropriate wound healing.

Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype.

International Delphi Expert Consensus on Safe Return to Surgical and Endoscopic Practice: From the Coronavirus Global Surgical Collaborative.

Objective: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities.

Background: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled.

Epigenetic regulation of the PGE2 pathway modulates macrophage phenotype in normal and pathologic wound repair.

Macrophages are a primary immune cell involved in inflammation, and their cell plasticity allows for transition from an inflammatory to a reparative phenotype and is critical for normal tissue repair following injury. Evidence suggests that epigenetic alterations play a critical role in establishing macrophage phenotype and function during normal and pathologic wound repair. Here, we find in human and murine wound macrophages that cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) is elevated in diabetes and regulates downstream macrophage-mediated inflammation and host defense.

Palmitate-TLR4 signaling regulates the histone demethylase, JMJD3, in macrophages and impairs diabetic wound healing.

Chronic macrophage inflammation is a hallmark of type 2 diabetes (T2D) and linked to the development of secondary diabetic complications. T2D is characterized by excess concentrations of saturated fatty acids (SFA) that activate innate immune inflammatory responses, however, mechanism(s) by which SFAs control inflammation is unknown. Using monocyte-macrophages isolated from human blood and murine models, we demonstrate that palmitate (C16:0), the most abundant circulating SFA in T2D, increases expression of the histone demethylase, Jmjd3.

Epigenetic Regulation of TLR4 in Diabetic Macrophages Modulates Immunometabolism and Wound Repair.

Macrophages are critical for the initiation and resolution of the inflammatory phase of wound healing. In diabetes, macrophages display a prolonged inflammatory phenotype preventing tissue repair. TLRs, particularly TLR4, have been shown to regulate myeloid-mediated inflammation in wounds.

Feasibility and efficacy of gamification in general surgery residency: Preliminary outcomes of residency teams.

Background: Comprehensive studies evaluating the efficacy of team-based competition ("Gamification") in surgery have not been performed. Board pass rates and resident satisfaction may improve if surgical residents are involved in competition.

Methods: Residents at Montefiore Medical Center (Bronx, New York) were surveyed and separated into teams during a draft.

Sepsis Induces Prolonged Epigenetic Modifications in Bone Marrow and Peripheral Macrophages Impairing Inflammation and Wound Healing.

Objective: Sepsis represents an acute life-threatening disorder resulting from a dysregulated host response. For patients who survive sepsis, there remains long-term consequences, including impaired inflammation, as a result of profound immunosuppression. The mechanisms involved in this long-lasting deficient immune response are poorly defined.

Long-term reported outcomes of transoral incisionless fundoplication: an 8-year cohort study.

Background: Transoral incisionless fundoplication (TIF) offers an endoscopic approach to the treatment of gastroesophageal reflux disease (GERD). Controlled trials have demonstrated the short-term efficacy of this procedure, but long-term follow-up studies are lacking. The objective of this study was to evaluate the long-term impact of TIF on disease-specific quality of life and antisecretory medication use.

Protracted Hypocalcemia following 3.5 Parathyroidectomy in a Kidney Pancreas Recipient with a History of Robotic-Assisted Roux-en-Y Gastric Bypass.

Background: Hypocalcemia is a frequent complication of parathyroidectomy for secondary/tertiary hyperparathyroidism. In patients with a history of prior Roux-en-Y gastric bypass (RYGBP), changes in nutritional absorption make management of hypocalcemia after parathyroidectomy difficult.

Case Report: A 41-old-year morbidly obese female with c-peptide negative diabetes mellitus and renal failure had RYGBP.