Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.

Lysosomal acid lipase (LAL) is the only known enzyme that degrades cholesteryl esters and triglycerides at an acidic pH. In LAL deficiency (LAL-D), dysregulated expression of matrix metalloproteinase 12 (MMP-12) has been described. The overexpression of MMP-12 in myeloid lineage cells causes an immune cell dysfunction resembling that of knockout ( KO) mice.

Regional Differences in the Small Intestinal Proteome of Control Mice and of Mice Lacking Lysosomal Acid Lipase.

The metabolic contribution of the small intestine (SI) is still unclear despite recent studies investigating the involvement of single cells in regional differences. Using untargeted proteomics, we identified regional characteristics of the three intestinal tracts of C57BL/6J mice and found that proteins abundant in the mouse ileum correlated with the high ileal expression of the corresponding genes in humans. In the SI of C57BL/6J mice, we also detected an increasing abundance of lysosomal acid lipase (LAL), which is responsible for degrading triacylglycerols and cholesteryl esters within the lysosome.

Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice.

Background: Matrix metalloproteinase 12 (MMP12) is a macrophage-secreted protein that is massively upregulated as a pro-inflammatory factor in metabolic and vascular tissues of mice and humans suffering from cardiometabolic diseases (CMDs). However, the molecular mechanisms explaining the contributions of MMP12 to CMDs are still unclear.

Methods: We investigated the impact of MMP12 deficiency on CMDs in a mouse model that mimics human disease by simultaneously developing adipose tissue inflammation, insulin resistance, and atherosclerosis.

Impact of (intestinal) LAL deficiency on lipid metabolism and macrophage infiltration.

Objective: To date, the only enzyme known to be responsible for the hydrolysis of cholesteryl esters and triacylglycerols in the lysosome at acidic pH is lysosomal acid lipase (LAL). Lipid malabsorption in the small intestine (SI), accompanied by macrophage infiltration, is one of the most common pathological features of LAL deficiency. However, the exact role of LAL in intestinal lipid metabolism is still unknown.

Detection rates for adenomas, serrated polyps and clinically relevant serrated polyps can be easily estimated by individually calculated detection rate ratios.

Adenoma detection rate (ADR) is a key quality indicator for colonoscopy; however, it is cumbersome to obtain. We investigated if detection rates (DRs) for adenomas, serrated polyps (SPs) and clinically relevant SP (crSPDR) can be accurately estimated by individualized DR ratios (DRRs) in a multicenter primary colonoscopy screening cohort of average-risk individuals. DRRs were calculated by dividing DRs for a certain polyp entity by polyp detection rate (PDR) for each endoscopist individually on the basis of his/her first 50 (DRR) and 100 (DRR) consecutive colonoscopies.

Ileal intubation is not associated with higher detection rate of right-sided conventional adenomas and serrated polyps compared to cecal intubation after adjustment for overall adenoma detection rate.

Background: High cecal intubation rate (CIR) is associated with significant improved adenoma detection rate (ADR), however, self-reported CIR may be overestimated and inadequate documentation of cecal intubation is associated with a lower polyp detection rate compared to clear documentation. We aimed to investigate if ileal intubation may be associated with higher detection rates (DR) for right-sided conventional adenomas (cAD) and serrated polyps (SP) compared to cecal intubation in a large screening colonoscopy cohort.

Material And Methods: Retrospective analysis of individuals ≥50 years with average risk for colorectal cancer (CRC) who underwent screening colonoscopy between 01/01/2012 and 14/12/2016 at a tertiary academic hospital and six community-based private practices.

Assessing guideline adherence in patients with non-variceal upper gastrointestinal bleeding receiving antiplatelet and anticoagulant therapy.

Non-variceal upper gastrointestinal bleeding (NVUGIB) occurs frequently and is associated with a significant morbidity and mortality, especially in patients receiving antiplatelet or anticoagulant therapy (APT and ACT, respectively). We aimed to evaluate adherence to guideline recommendations published by European Society of Gastrointestinal Endoscopy (ESGE). Retrospective analysis of patients with NVUGIB und prior exposition to APT or ACT at a single university hospital between 01 January 2016 and 31 December 2017.

Effects of Antibiotics on Gut Microbiota.

The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease.