Specialized pro-resolving lipid mediators in gut immunophysiology: from dietary precursors to inflammation resolution.

Purpose Of Review: This review aims to examine recent research on the role of specialized pro-resolving mediators (SPMs) in the regulation of gut immunophysiology.

Recent Findings: Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, driven by disruptions in the intestinal barrier and an imbalance between the host immune system and gut microbiota. Dietary polyunsaturated fatty acids (PUFAs), especially ω-3 and ω-6, are key regulators of immune responses and help maintain the integrity of the intestinal barrier.

Patient public perspectives on digital colorectal cancer surgery (DALLAS).

Introduction: The importance of patient perspectives is increasingly appreciated in clinical practice and academia with formal engagement processes developing worldwide. Digital surgery encompasses intraoperative patient data (including surgical video) analysis and so requires public-patient involvement (PPI).

Methods: Engagement events were conducted based on NIHR and GRIPP2 LF guidelines.

Artificial intelligence for optimum tissue excision with indocyanine green fluorescence angiography for flap reconstructions: Proof of concept.

Background: Indocyanine green fluorescence angiography (ICGFA) is gaining popularity as an intraoperative tool to assess flap perfusion. However, it needs interpretation and there is concern regarding a potential for over-debridement with its use. Here we describe an artificial intelligence (AI) method that indicates the extent of flap trimming required.

Development and Validation of Methodologies for the Identification of Specialized Pro-Resolving Lipid Mediators and Classic Eicosanoids in Biological Matrices.

Lipid mediators, which include specialized pro-resolving mediators and classic eicosanoids, are pivotal in both initiating and resolving inflammation. The regulation of these molecules determines whether inflammation resolves naturally or persists. However, our understanding of how these mediators are regulated over time in various inflammatory contexts is limited.

Clinical validation of 3D virtual modelling for laparoscopic complete mesocolic excision with central vascular ligation for proximal colon cancer.

Introduction: Laparoscopic Complete Mesocolic Excision (CME) with Central Vascular Ligation (CVL) in colon cancer surgery has not been broadly adopted in part because of safety concerns. Pre-operative 3-D virtual modelling (3DVM) may help but needs validation.

Methods: 3DVM were routinely constructed from CT mesenteric angiograms (CTMA) using a commercial service (Visible Patient, Strasbourg, France) for consecutive patients during our CMECVL learning curve over three years.

Advancing indocyanine green fluorescence flap perfusion assessment via near infrared signal quantification.

Introduction: Intraoperative indocyanine green fluorescence angiography (ICGFA) perfusion assessment has been demonstrated to reduce complications in reconstructive surgery. This study sought to advance ICGFA flap perfusion assessment via quantification methodologies.

Method: Patients undergoing pedicled and free flap reconstruction were subjected to intraoperative ICGFA flap perfusion assessment using either an open or endoscopic system.

Surgeon assessment of significant rectal polyps using white light endoscopy alone and in comparison to fluorescence-augmented AI lesion classification.

Purpose: Perioperative decision making for large (> 2 cm) rectal polyps with ambiguous features is complex. The most common intraprocedural assessment is clinician judgement alone while radiological and endoscopic biopsy can provide periprocedural detail. Fluorescence-augmented machine learning (FA-ML) methods may optimise local treatment strategy.

The endocannabinoid anandamide activates pro-resolving pathways in human primary macrophages by engaging both CB and GPR18 receptors.

Resolution of inflammation is the cellular and molecular process that protects from widespread and uncontrolled inflammation and restores tissue function in the aftermath of acute immune events. This process is orchestrated by specialized pro-resolving mediators (SPM), a class of bioactive lipids able to reduce immune activation and promote removal of tissue debris and apoptotic cells by macrophages. Although SPMs are the lipid class that has been best studied for its role in facilitating the resolution of self-limited inflammation, a number of other lipid signals, including endocannabinoids, also exert protective immunomodulatory effects on immune cells, including macrophages.

An LGR6 frameshift variant abrogates receptor expression on select leukocyte subsets and is associated with viral infections.

The leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) was recently identified as the cognate receptor for the proresolving mediator maresin 1 (MaR1). To address the biological role of LGR6 in humans, we investigated the functional impact of a genetic variant in the gene encoding for LGR6, which is predicted to lead to a frameshift mutation in one of the receptor isoforms, on both receptor expression and immune cell responses. In neutrophils, monocytes, and natural killer (NK) cells from volunteers homozygous for this variant, we found a significant downregulation in the expression of LGR6 when compared with controls without the variant; whereas the LGR6 expression was essentially similar in monocyte-derived macrophages and CD8+ T cells.

Clinical and computational development of a patient-calibrated ICGFA bowel transection recommender.

Introduction: Intraoperative indocyanine green fluorescence angiography (ICGFA) aims to reduce colorectal anastomotic complications. However, signal interpretation is inconsistent and confounded by patient physiology and system behaviours. Here, we demonstrate a proof of concept of a novel clinical and computational method for patient calibrated quantitative ICGFA (QICGFA) bowel transection recommendation.

Resolvin D2 prevents vascular remodeling, hypercontractility and endothelial dysfunction in obese hypertensive mice through modulation of vascular and proinflammatory factors.

During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there might be a dysregulation of SPMs pathways in pathological vascular remodeling and that resolvin D2 (RvD2) might prevent vascular remodeling and contractile and endothelial dysfunction in a model of obesity and hypertension. In aortic samples of patients with or without abdominal aortic aneurysms (AAA), we evaluated gene expression of enzymes involved in SPMs synthesis (ALOXs), SPMs receptors and pro-inflammatory genes.

A feasibility study assessing quantitative indocyanine green angiographic predictors of reconstructive complications following nipple-sparing mastectomy.

Introduction: Immediate post-mastectomy breast reconstruction offers benefits; however, complications can compromise outcomes. Intraoperative indocyanine green fluorescence angiography (ICGFA) may mitigate perfusion-related complications (PRC); however, its interpretation remains subjective. Here, we examine and develop methods for ICGFA quantification, including machine learning (ML) algorithms for predicting complications.

Corrigendum: Arachidonate 15-lipoxygenase-mediated production of Resolvin D5 abrogates pancreatic stellate cell-induced cancer cell invasion.

[This corrects the article DOI: 10.3389/fimmu.2023.

Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease.

While cardiovascular disease (CVD) is one of the major co-morbidities in patients with rheumatoid arthritis (RA), the mechanism(s) that contribute to CVD in patients with RA remain to be fully elucidated. Herein, we observe that plasma concentrations of 13-series resolvin (RvT)4 negatively correlate with vascular lipid load in mouse inflammatory arthritis. Administration of RvT4 to male arthritic mice fed an atherogenic diet significantly reduces atherosclerosis.

Impact of standardising indocyanine green fluorescence angiography technique for visual and quantitative interpretation on interuser variability in colorectal surgery.

Aim/background: Intra-operative colonic perfusion assessment via indocyanine green fluorescence angiography (ICGFA) aims to address malperfusion-related anastomotic complications; however, its interpretation suffers interuser variability (IUV), especially early in ICGFA experience. This work assesses the impact of a protocol developed for both operator-based judgement and computational development on interpretation consistency, focusing on senior surgeons yet to start using ICGFA.

Methods: Experienced and junior gastrointestinal surgeons were invited to complete an ICGFA-experience questionnaire.

Efferocyte-Derived MCTRs Metabolically Prime Macrophages for Continual Efferocytosis via Rac1-Mediated Activation of Glycolysis.

Clearance of multiple rounds of apoptotic cells (ACs) through continual efferocytosis is critical in the maintenance of organ function, the resolution of acute inflammation, and tissue repair. To date, little is known about the nature of mechanisms and factors that govern this fundamental process. Herein, the authors reported that breakdown of ACs leads to upregulation of 12-lipoxygenase in macrophages.

Arachidonate 15-lipoxygenase-mediated production of Resolvin D5 abrogates pancreatic stellate cell-induced cancer cell invasion.

Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a key driver of pancreatic ductal adenocarcinoma (PDAC) chemoresistance leading to poor prognosis. Specialized pro-resolving mediators (SPMs) are prime modulators of inflammation and its resolution, traditionally thought to be produced by immune cells. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipid mediator profiling PSCs as well as primary human CAFs express enzymes and receptors to produce and respond to SPMs.

The Annexin-A1 mimetic RTP-026 promotes acute cardioprotection through modulation of immune cell activation.

Aims: The cardio-protective and immuno-regulatory properties of RTP-026, a synthetic peptide that spans the Annexin-A1 (AnxA1) N-terminal region, were tested in rat acute myocardial infarction.

Methods And Results: In vitro, selective activation of formyl-peptide receptor type 2 (FPR2) by RTP-026 occurred with apparent EC in the 10-30 nM range. With human primary cells, RTP-026 counteracted extension of neutrophil life-span and augmented phagocytosis of fluorescent E.

CLASSICA: Validating artificial intelligence in classifying cancer in real time during surgery.

Aim: Treatment pathways for significant rectal polyps differ depending on the underlying pathology, but pre-excision profiling is imperfect. It has been demonstrated that differences in fluorescence perfusion signals following injection of indocyanine green (ICG) can be analysed mathematically and, with the assistance of artificial intelligence (AI), used to classify tumours endoscopically as benign or malignant. This study aims to validate this method of characterization across multiple clinical sites regarding its generalizability, usability and accuracy while developing clinical-grade software to enable it to become a useful method.

Stereoselective Synthesis, Pro-resolution, and Anti-inflammatory Actions of RvD5.

The methyl ester of resolvin D5, a lipid mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid, was stereoselectively prepared in 8% yield over 12 steps (longest linear sequence). The key steps for the introduction of the two stereogenic secondary alcohols were an organocatalyzed oxyamination and the Midland Alpine borane reduction. For the assembly of the carbon chain, the Sonogashira cross-coupling reaction and the Takai olefination were utilized.