Engineered calprotectin-sensing probiotics for IBD surveillance in humans.

Inflammatory bowel disease (IBD) is a spectrum of autoimmune diseases affecting the gastrointestinal tract characterized by a relapsing and remitting course of gut mucosal inflammation. Disease flares can be difficult to predict, and the current practice of IBD disease activity surveillance through endoscopy is invasive and requires medical expertise. Recent advancements in synthetic biology raise the possibility that symbiotic microbes can be engineered to selectively detect disease biomarkers used in current clinical practice.

Advances in screening and detection of gastric cancer.

With an estimated one million new cases and 769 000 deaths in 2020, gastric cancer is the fifth most frequent cancer and fourth leading cause of cancer death globally. Incidence rates are highest in Asia and Eastern Europe. This manuscript will review the current modalities of diagnosis, staging, and screening of gastric cancer.

Factors Impacting Survival in Those Transplanted for NASH Cirrhosis: Data From the NailNASH Consortium.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is the leading indication for liver transplant (LT) in women and the elderly. Granular details into factors impacting survival in this population are needed to optimize management and improve outcomes.

Methods: Patients receiving LT for NASH cirrhosis from 1997 to 2017 across 7 transplant centers (NailNASH consortium) were analyzed.

Association of body mass index with mortality in cardiovascular disease: New insights into the obesity paradox from multiple perspectives.

Over the past 4 decades, prevalence of obesity has increased rapidly at both the national and global level and presents a major public health challenge. Obesity is associated with increased risk of morbidity from cardiovascular diseases. Data suggesting that the presence of obesity may be protective in individuals with clinically manifest cardiovascular disease have led to discussion of an "obesity paradox", stirring controversy and leading to unclear messaging regarding the true health risks of excess weight.

Acute loss of adipose tissue-derived adiponectin triggers immediate metabolic deterioration in mice.

Aim/hypothesis: Adiponectin (APN), a circulating hormone secreted by mature adipocytes, has been extensively studied because it has beneficial metabolic effects. While many studies have focused on the congenital loss of APN and its effects on systemic body glucose and lipid metabolism, little is known about the effects triggered by acute loss of APN in the adult mouse. We anticipated that genetically induced acute depletion of APN in adult mice would have a more profound effect on systemic metabolic health than congenital deletion of Adipoq, the gene encoding APN, with its associated potential for adaptive responses that may mask the phenotypes.

Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice.

Visceral adiposity confers significant risk for developing metabolic disease in obesity whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective. Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protective thermogenic phenotype characterized by the accumulation of Ucp1 beige/BRITE adipocytes (termed 'browning'). In this study, we investigated the physiological consequences of browning murine visceral WAT by selective genetic ablation of , a transcriptional suppressor of the adipocyte thermogenic program.

Inducible overexpression of adiponectin receptors highlight the roles of adiponectin-induced ceramidase signaling in lipid and glucose homeostasis.

Objective: Adiponectin and the signaling induced by its cognate receptors, AdipoR1 and AdipoR2, have garnered attention for their ability to promote insulin sensitivity and oppose steatosis. Activation of these receptors promotes the deacylation of ceramide, a lipid metabolite that appears to play a causal role in impairing insulin signaling.

Methods: Here, we have developed transgenic mice that overexpress AdipoR1 or AdipoR2 under the inducible control of a tetracycline response element.

Poor outcomes despite aspirin or statin use in high-risk patients with retinal vein occlusion.

Purpose: Since atherosclerosis contributes to the pathophysiology of retinal vein occlusion (RVO), we aimed to assess the effects of aspirin and statins on the visual outcomes of RVO in high-risk patients, whom we define to have hypertension and open-angle glaucoma prior to RVO.

Methods: We conducted a retrospective case-control study of adults diagnosed with RVO between 2006 and 2014. To evaluate for a preventive effect of these medications, we compared the prevalence of aspirin or statin use (either separately or concomitantly) among high-risk patients who developed RVO and among those who did not during at least 2 years of follow-up.

Selective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements.

Dysfunctional adipose tissue represents a hallmark of type 2 diabetes and systemic insulin resistance, characterized by fibrotic deposition of collagens and increased immune cell infiltration within the depots. Here we generate an inducible model of loss of function of the protein phosphatase and tensin homologue (PTEN), a phosphatase critically involved in turning off the insulin signal transduction cascade, to assess the role of enhanced insulin signalling specifically in mature adipocytes. These mice gain more weight on chow diet and short-term as well as long-term high-fat diet exposure.

Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis.

Sphingolipids have garnered attention for their role in insulin resistance and lipotoxic cell death. We have developed transgenic mice inducibly expressing acid ceramidase that display a reduction in ceramides in adult mouse tissues. Hepatic overexpression of acid ceramidase prevents hepatic steatosis and prompts improvements in insulin action in liver and adipose tissue upon exposure to high-fat diet.

Differential transendothelial transport of adiponectin complexes.

Background: Adiponectin's effects on systemic physiology and cell-specific responses are well-defined, but little is known about how this insulin-sensitizing and anti-inflammatory adipokine reaches its target cells. All molecules face active and passive transport limitations, but adiponectin is particularly noteworthy due to the diverse size range and high molecular weights of its oligomers. Additionally, its metabolic target organs possess a range of endothelial permeability.

The adipokine/ceramide axis: key aspects of insulin sensitization.

Until recently, sphingolipid physiology was primarily the domain of oncologists and immunologists. However, mounting evidence implicates ceramides and their derivatives in various aspects of metabolism via directly impacting the insulin receptor as well as modulating cell survival and proliferation. More recent observations suggest a strong link between a number of adipokines and ceramide catabolism.

Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc.

Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase.