Non-Targeted Metabolic Profiling of Cerebellum in Spina Bifida Fetal Rats.

Spina bifida, known more commonly as myelomeningocele, is a neural tube defect that results in herniation of the cerebellum through the foramen magnum into the central canal as part of the Chiari II malformation. Effects stemming from the herniated cerebellum and its metabolic profile have not been extensively studied. The objective of this study is to examine the metabolic effects of this disease on the cerebellum in utero through the utilization of a retinoid acid-induced Spina bifida rat model.

Drug resistance mechanisms create targetable proteostatic vulnerabilities in Her2+ breast cancers.

Oncogenic kinase inhibitors show short-lived responses in the clinic due to high rate of acquired resistance. We previously showed that pharmacologically exploiting oncogene-induced proteotoxic stress can be a viable alternative to oncogene-targeted therapy. Here, we performed extensive analyses of the transcriptomic, metabolomic and proteostatic perturbations during the course of treatment of Her2+ breast cancer cells with a Her2 inhibitor covering the drug response, resistance, relapse and drug withdrawal phases.

Choline supplementation attenuates experimental sepsis-associated acute kidney injury.

Acute kidney injury (AKI) is common in critically ill patients, and sepsis is its leading cause. Sepsis-associated AKI (SA-AKI) causes greater morbidity and mortality than other AKI etiologies, yet the underlying mechanisms are incompletely understood. Metabolomic technologies can characterize cellular energy derangements, but few discovery analyses have evaluated the metabolomic profile of SA-AKI.

Head and Neck Cancer Susceptibility and Metabolism in Fanconi Anemia.

Fanconi anemia (FA) is a rare inherited, generally autosomal recessive syndrome, but it displays X-linked or dominant negative inheritance for certain genes. FA is characterized by a deficiency in DNA damage repair that results in bone marrow failure, and in an increased risk for various epithelial tumors, most commonly squamous cell carcinomas of the head and neck (HNSCC) and of the esophagus, anogenital tract and skin. Individuals with FA exhibit increased human papilloma virus (HPV) prevalence.

Role of GM-CSF in regulating metabolism and mitochondrial functions critical to macrophage proliferation.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) exerts pleiotropic effects on macrophages and is required for self-renewal but the mechanisms responsible are unknown. Using mouse models with disrupted GM-CSF signaling, we show GM-CSF is critical for mitochondrial turnover, functions, and integrity. GM-CSF signaling is essential for fatty acid β-oxidation and markedly increased tricarboxylic acid cycle activity, oxidative phosphorylation, and ATP production.

Fibrinogen activates focal adhesion kinase (FAK) promoting colorectal adenocarcinoma growth.

Background: We previously showed that fibrinogen is a major determinant of the growth of a murine model of colorectal cancer (CRC).

Objective: Our aim was to define the mechanisms coupling fibrin(ogen) to CRC growth.

Results: CRC tumors transplanted into the dorsal subcutis of Fib mice were less proliferative and demonstrated increased senescence relative to those grown in Fib mice.

PKM2-dependent metabolic skewing of hepatic Th17 cells regulates pathogenesis of non-alcoholic fatty liver disease.

Emerging evidence suggests a key contribution to non-alcoholic fatty liver disease (NAFLD) pathogenesis by Th17 cells. The pathogenic characteristics and mechanisms of hepatic Th17 cells, however, remain unknown. Here, we uncover and characterize a distinct population of inflammatory hepatic CXCR3Th17 (ihTh17) cells sufficient to exacerbate NAFLD pathogenesis.

Erratum: Romero-Lopez et al. Lung Metabolomics Profiling of Congenital Diaphragmatic Hernia in Fetal Rats. 2021, , 177.

The authors wish to make the following corrections to this paper [...

Lung Metabolomics Profiling of Congenital Diaphragmatic Hernia in Fetal Rats.

Congenital diaphragmatic hernia (CDH) is characterized by the herniation of abdominal contents into the thoracic cavity during the fetal period. This competition for fetal thoracic space results in lung hypoplasia and vascular maldevelopment that can generate severe pulmonary hypertension (PH). The detailed mechanisms of CDH pathogenesis are yet to be understood.

Human Papillomavirus Oral- and Sero- Positivity in Fanconi Anemia.

High-risk human papillomavirus (HPV) is prevalent and known to cause 5% of all cancers worldwide. The rare, cancer prone Fanconi anemia (FA) population is characterized by a predisposition to both head and neck squamous cell carcinomas and gynecological cancers, but the role of HPV in these cancers remains unclear. Prompted by a patient-family advocacy organization, oral HPV and HPV serological studies were simultaneously undertaken.

Tryptophan metabolism is dysregulated in individuals with Fanconi anemia.

Fanconi anemia (FA) is a complex genetic disorder associated with progressive marrow failure and a strong predisposition to malignancy. FA is associated with metabolic disturbances such as short stature, insulin resistance, thyroid dysfunction, abnormal body mass index (BMI), and dyslipidemia. We studied tryptophan metabolism in FA by examining tryptophan and its metabolites before and during the stress of hematopoietic stem cell transplant (HSCT).

Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats.

The gut microbiota, via the production of metabolites entering the circulation, plays a role in blood pressure regulation. Blood pressure is also affected by the characteristics of sleep. To date, no studies have examined relationships among the gut microbiota/metabolites, blood pressure, and sleep.

Reduced Gut Microbiome Diversity and Metabolome Differences in Rhinoceros Species at Risk for Iron Overload Disorder.

Iron overload disorder (IOD) affects many wildlife species cared for . Two of the four rhinoceros species in human care, Sumatran rhinoceros () and black rhinoceros (), are susceptible, whereas the other two, white rhinoceros () and greater one-horned (GOH) rhinoceros (), are relatively resistant to IOD. Complex interrelationships exist between mammalian hosts, their indigenous gut microbiota, metabolome, physical condition, and iron availability.

A Pilot Study of Human Milk to Reduce Intestinal Inflammation After Bone Marrow Transplant.

Objective: Human milk administration in the early peritransplant period would lower intestinal inflammation after bone marrow transplant (BMT).

Materials And Methods: Children 0-5 years undergoing BMT received either a ready-to-feed human milk preparation designed for these children (Prolacta Bioscience, Duarte, CA) or standard formula. Babies breastfeeding at the time of BMT were also enrolled on the human milk arm.

Using urine metabolomics to understand the pathogenesis of infant respiratory syncytial virus (RSV) infection and its role in childhood wheezing.

Background: Respiratory syncytial virus (RSV) infection in infants causes significant morbidity and is the strongest risk factor associated with asthma. Metabolites, which reflect the interactions between host cell and virus, provide an opportunity to identify the pathways that underlie severe infections and asthma development.

Objective: To study metabolic profile differences between infants with RSV infection, and human rhinovirus (HRV) infection, and healthy infants.

Therapeutic reduction of lysophospholipids in the digestive tract recapitulates the metabolic benefits of bariatric surgery and promotes diabetes remission.

Objective: Obesity and obesity-related metabolic disorders are major health problems worldwide. The most effective obesity intervention is bariatric surgery. This study tested the hypothesis that bariatric surgery alters phospholipid metabolism in the gastrointestinal tract to favor a metabolically healthy gut microbiota profile and therapeutic intervention of phospholipid metabolism in the gastrointestinal may have similar metabolic benefits.

Chronic Dysregulation of Cortical and Subcortical Metabolism After Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. Although chronic disability is common after TBI, effective treatments remain elusive and chronic TBI pathophysiology is not well understood. Early after TBI, brain metabolism is disrupted due to unregulated ion release, mitochondrial damage, and interruption of molecular trafficking.

Antibiotic Exposure and Reduced Short Chain Fatty Acid Production after Hematopoietic Stem Cell Transplant.

Human studies have shown loss of diversity of the gut microbiome following hematopoietic stem cell transplantation (HSCT) in association with significant gut injury caused by the preparative regimen. Prolonged antibiotic use worsens loss of microbiome diversity and increases risk of complications such as graft-versus-host disease (GVHD). Our data support the hypothesis that loss of intestinal commensals that produce short-chain fatty acids (SCFAs) may increase dysbiosis.

Dehydration prompts increased activity and blood feeding by mosquitoes.

Current insights into the mosquito dehydration response rely on studies that examine specific responses but ultimately fail to provide an encompassing view of mosquito biology. Here, we examined underlying changes in the biology of mosquitoes associated with dehydration. Specifically, we show that dehydration increases blood feeding in the northern house mosquito, Culex pipiens, which was the result of both higher activity and a greater tendency to land on a host.

Lipidomic Profiling Links the Fanconi Anemia Pathway to Glycosphingolipid Metabolism in Head and Neck Cancer Cells.

Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC), and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway-dependent lipid metabolism and to extract lipid-based signatures and effectors of invasion in FA-deficient cells. We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells.

Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis.

The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood.

A review of metabolomics approaches and their application in identifying causal pathways of childhood asthma.

Because asthma is a disease that results from host-environment interactions, an approach that allows assessment of the effect of the environment on the host is needed to understand the disease. Metabolomics has appealing potential as an application to study pathways to childhood asthma development. The objective of this review is to provide an overview of metabolomics methods and their application to understanding host-environment pathways in asthma development.