Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite.

Dietary Linoleic Acid and Its Oxidized Metabolites Exacerbate Liver Injury Caused by Ethanol via Induction of Hepatic Proinflammatory Response in Mice.

Alcoholic liver disease is a major human health problem leading to significant morbidity and mortality in the United States and worldwide. Dietary fat plays an important role in alcoholic liver disease pathogenesis. Herein, we tested the hypothesis that a combination of ethanol and a diet rich in linoleic acid (LA) leads to the increased production of oxidized LA metabolites (OXLAMs), specifically 9- and 13-hydroxyoctadecadienoic acids (HODEs), which contribute to a hepatic proinflammatory response exacerbating liver injury.

Activation of autophagy attenuates EtOH-LPS-induced hepatic steatosis and injury through MD2 associated TLR4 signaling.

Autophagy serves as a protective mechanism to degrade damaged organelles and proteins. Acute alcohol exposure is known to activate the hepatic autophagy response, whereas chronic alcohol exposure slows autophagosome formation along with an elevation of gut-derived endotoxin. In the current study, we examined whether lipopolysaccharide (LPS) administration decreased autophagic response in the liver of mice treated by short-term alcohol and whether activation of autophagy by rapamycin attenuates EtOH-LPS-induced liver steatosis and injury.

Phosphodiesterase 4b expression plays a major role in alcohol-induced neuro-inflammation.

It is increasingly evident that alcohol-induced, gut-mediated peripheral endotoxemia plays a significant role in glial cell activation and neuro-inflammation. Using a mouse model of chronic alcohol feeding, we examined the causal role of endotoxin- and cytokine-responsive Pde4 subfamily b (Pde4b) expression in alcohol-induced neuro-inflammation. Both pharmacologic and genetic approaches were used to determine the regulatory role of Pde4b.

Rate of hepatitis C viral clearance by human livers in human patients: Liver transplantation modeling primary infection and implications for studying entry inhibition.

Unlabelled: To better understand the dynamics of early hepatitis C virus (HCV) infection, we determined how rapidly non-cirrhotic HCV-uninfected liver allografts clear HCV from the circulation of cirrhotic HCV-infected patients at the time of transplantation but before administration of immunosuppression. Specifically, we characterized serum HCV kinetics during the first 90 min of reperfusion for 19 chronically HCV-infected patients transplanted with an HCV-uninfected liver by measuring serum viral load immediately prior to reperfusion (t = 0) and then every 15 min for a total of 90 min (t = 90). Immunosuppression was withheld until all samples were taken to better model primary infection.

The Evolution of Energetic Scaling across the Vertebrate Tree of Life.

Metabolism is the link between ecology and physiology-it dictates the flow of energy through individuals and across trophic levels. Much of the predictive power of metabolic theories of ecology derives from the scaling relationship between organismal size and metabolic rate. There is growing evidence that this scaling relationship is not universal, but we have little knowledge of how it has evolved over macroevolutionary time.

Analysis of Stable Isotope Assisted Metabolomics Data Acquired by High Resolution Mass Spectrometry.

Stable isotope assisted metabolomics (SIAM) uses stable isotope tracers to support studies of biochemical mechanisms. We report a suite of data analysis algorithms for automatic analysis of SIAM data acquired on a high resolution mass spectrometer. To increase the accuracy of isotopologue assignment, metabolites detected in the unlabeled samples were used as reference metabolites to generate possible isotopologue candidates for analysis of peaks detected in the labeled samples.

Practices and promises of Facebook for science outreach: Becoming a "Nerd of Trust".

Arguably, the dissemination of science communication has recently entered a new age in which science must compete for public attention with fake news, alternate facts, and pseudoscience. This clash is particularly evident on social media. Facebook has taken a prime role in disseminating fake news, alternate facts, and pseudoscience, but is often ignored in the context of science outreach, especially among individual scientists.

Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

Objective: Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children.

Analysis of stable isotope assisted metabolomics data acquired by GC-MS.

Stable isotope assisted metabolomics (SIAM) measures the abundance levels of metabolites in a particular pathway using stable isotope tracers (e.g., C, O and/or N).

Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis.

Aims: Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD). Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis.

Role of Zinc in the Development/Progression of Alcoholic Liver Disease.

Many variables, aside from the amount and duration of alcohol consumption, play a role in the development and progression of alcoholic liver disease (ALD). One critical factor that can be modified is diet/nutrition. We have made major recent advances in our understanding of the interactions of nutrition and ALD.

Summary Points and Consensus Recommendations From the International Protein Summit.

The International Protein Summit in 2016 brought experts in clinical nutrition and protein metabolism together from around the globe to determine the impact of high-dose protein administration on clinical outcomes and address barriers to its delivery in the critically ill patient. It has been suggested that high doses of protein in the range of 1.2-2.

Protein and Calorie Requirements Associated With the Presence of Obesity.

Obesity compounds the metabolic response to critical illness and increases the risk for overfeeding complications due to its comorbidities. Hypocaloric, high-protein nutrition therapy affords the hospitalized patient with obesity the opportunity to achieve net protein anabolism with a reduced risk of overfeeding complications. The intent of this review is to provide the theoretical framework for development of a hypocaloric high-protein regimen, scientific evidence to support this mode of therapy, and unique considerations for its use in specialized subpopulations.

Building Workforce Capacity Abroad While Strengthening Global Health Programs at Home: Participation of Seven Harvard-Affiliated Institutions in a Health Professional Training Initiative in Rwanda.

A consortium of 22 U.S. academic institutions is currently participating in the Rwanda Human Resources for Health Program (HRH Program).

Protein Requirements for Critically Ill Patients With Renal and Liver Failure.

Diseases leading to critical illness induce proteolysis resulting in muscle wasting and negative nitrogen balance. Muscle wasting has been associated with poor intensive care unit (ICU)-related outcomes, including an increased risk for mortality. Acute kidney injury (AKI) represents a common organ dysfunction associated with ICU-related disorders, such as sepsis, trauma, and respiratory failure.

Nutrition Support for Persistent Inflammation, Immunosuppression, and Catabolism Syndrome.

Despite tremendous advances in critical care, multiple-organ failure continues to be a significant problem. However, in recent years, far fewer patients with multiple-organ failure die early, but many experience ongoing immune dysregulation and are developing persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Most PICS patients are discharged to nonhome destinations, fail to rehabilitate, and succumb to indolent death.

Liver Injury and Endotoxemia in Male and Female Alcohol-Dependent Individuals Admitted to an Alcohol Treatment Program.

Background: Interactions between the liver, the gut, and the immune system are critical components of alcoholic liver disease (ALD). The aim of this study was to explore the associations between alcohol-induced liver injury, endotoxemia, and inflammation at admission and over time during abstinence, as well as to examine the sex-related differences in these parameters in alcohol-dependent individuals admitted to an alcohol treatment program.

Methods: A cohort of 48 otherwise healthy participants with alcohol use disorder, but no clinical signs of alcoholic liver injury (34 males [M]/14 females [F]) admitted to an alcohol detoxification program, was stratified into 2 groups based on baseline plasma alanine aminotransferase (ALT) levels (as a marker of liver injury).

A Review on the Sex Differences in Organ and System Pathology with Alcohol Drinking.

Hazardous consequences of alcohol consumption adversely influence overall health, specifically physical and mental health. Differences in alcohol consumption and manifestations in pathology have been observed between males and females, however research on understanding these differences is limited. Negative consequences of alcohol consumption have now been studied including sex as a significant factor.

Acrolein Is a Pathogenic Mediator of Alcoholic Liver Disease and the Scavenger Hydralazine Is Protective in Mice.

Background & Aims: Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality, with no Food and Drug Administration-approved therapy. Chronic alcohol consumption causes a pro-oxidant environment and increases hepatic lipid peroxidation, with acrolein being the most reactive/toxic by-product. This study investigated the pathogenic role of acrolein in hepatic endoplasmic reticulum (ER) stress, steatosis, and injury in experimental ALD, and tested acrolein elimination/scavenging (using hydralazine) as a potential therapy in ALD.

PI3K Inhibition Reduces Mammary Tumor Growth and Facilitates Antitumor Immunity and Anti-PD1 Responses.

Metastatic breast cancers continue to elude current therapeutic strategies, including those utilizing PI3K inhibitors. Given the prominent role of PI3Kα,β in tumor growth and PI3Kγ,δ in immune cell function, we sought to determine whether PI3K inhibition altered antitumor immunity. The effect of PI3K inhibition on tumor growth, metastasis, and antitumor immune response was characterized in mouse models utilizing orthotopic implants of 4T1 or PyMT mammary tumors into syngeneic or -null mice, and patient-derived breast cancer xenografts in humanized mice.

Medical Management of Severe Alcoholic Hepatitis: Expert Review from the Clinical Practice Updates Committee of the AGA Institute.

The purpose of this clinical practice update is to review diagnostic criteria for severe acute alcoholic hepatitis and to determine the current best practices for this life-threatening condition. The best practices in this review are based on clinical trials, systematic reviews including meta-analysis and expert opinion to develop an approach to diagnosis and management. Best Practice Advice 1: Abstinence from drinking alcohol is the cornerstone of treatment for alcohol hepatitis (AH).