Hepatic Proteomic Changes Associated with Liver Injury Caused by Alcohol Consumption in Mice.

Alcohol-associated liver disease (ALD) is a prevalent medical problem with limited effective treatment strategies. Although many biological processes contributing to ALD have been elucidated, a complete understanding of the underlying mechanisms is still lacking. The current study employed a proteomic approach to identify hepatic changes resulting from ethanol (EtOH) consumption and the genetic ablation of the formyl peptide receptor 2 (FPR2), a G-protein coupled receptor known to regulate multiple signaling pathways and biological processes, in a mouse model of ALD.

A plasma peptidomic signature reveals extracellular matrix remodeling and predicts prognosis in alcohol-related hepatitis.

Unlabelled: Alcohol-related hepatitis (AH) is plagued with high mortality and difficulty in identifying at-risk patients. The extracellular matrix undergoes significant remodeling during inflammatory liver injury that can be detected in biological fluids and potentially used for mortality prediction. EDTA plasma samples were collected from AH patients (n= 62); Model for End-Stage Liver Disease (MELD) score defined AH severity as moderate (12-20; n=28) and severe (>20; n=34).

Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.

Activation and transdifferentiation of hepatic stellate cells (HSC) into migratory myofibroblasts is a key process in liver fibrogenesis. Cell migration requires an active remodeling of the cytoskeleton, which is a tightly regulated process coordinated by Rho-specific guanine nucleotide exchange factors (GEFs) and the Rho family of small GTPases. Rho-associated kinase (ROCK) promotes assembly of focal adhesions and actin stress fibers by regulating cytoskeleton organization.

The plasma degradome reflects later development of NASH fibrosis after liver transplant.

Although liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease and decreased survival. Lack of risk stratification strategies hampers early intervention against development of post-LT NASH fibrosis. The liver undergoes significant remodeling during inflammatory injury.

The plasma degradome reflects later development of NASH fibrosis after liver transplant.

Although liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease, and decreased survival. Lack of risk stratification strategies hamper liver undergoes significant remodeling during inflammatory injury. During such remodeling, degraded peptide fragments (i.

Fibrosis resolution in the mouse liver: Role of Mmp12 and potential role of calpain 1/2.

Although most work has focused on resolution of collagen ECM, fibrosis resolution involves changes to several ECM proteins. The purpose of the current study was twofold: 1) to examine the role of MMP12 and elastin; and 2) to investigate the changes in degraded proteins in plasma (i.e.

Dataset for proteomic analysis of arylamine -acetyltransferase 1 knockout MDA-MB-231 breast cancer cells.

Arylamine -acetyltransferase 1 () is frequently upregulated in breast cancer. An unbiased analysis of proteomes of parental MDA-MB-231 breast cancer cells and two separate knockout (KO) cell lines were performed. Among 4,890 proteins identified, 737 and 651 proteins were found significantly ( < 0.

Quantitative Mass Spectrometry Normalization in Urine Biomarker Analysis in Nephrotic Syndrome.

Chronic kidney disease (CKD) affects 30 million adults, costs ~$79 billion dollars (2016) in Medicare expenditures, and is the ninth leading cause of death in the United States. The disease is silent or undiagnosed in almost half of people with severely reduced kidney function. Urine provides an ideal biofluid that is accessible to high-sensitivity mass spectrometry-based proteomic interrogation and is an indicator of renal homeostasis.

Proteomic analysis of arylamine -acetyltransferase 1 knockout breast cancer cells: Implications in immune evasion and mitochondrial biogenesis.

Previous studies have shown that inhibition or depletion of -acetyltransferase 1 (NAT1) in breast cancer cell lines leads to growth retardation both in vitro and in vivo, suggesting that NAT1 contributes to rapid growth of breast cancer cells. To understand molecular and cellular processes that NAT1 contributes to and generate novel hypotheses in regard to NAT1's role in breast cancer, we performed an unbiased analysis of proteomes of parental MDA-MB-231 breast cancer cells and two separate knockout (KO) cell lines. Among 4890 proteins identified, 737 proteins were found significantly ( < 0.

The Utility of Differential Scanning Calorimetry Curves of Blood Plasma for Diagnosis, Subtype Differentiation and Predicted Survival in Lung Cancer.

Early detection of lung cancer (LC) significantly increases the likelihood of successful treatment and improves LC survival rates. Currently, screening (mainly low-dose CT scans) is recommended for individuals at high risk. However, the recent increase in the number of LC cases unrelated to the well-known risk factors, and the high false-positive rate of low-dose CT, indicate a need to develop new, non-invasive methods for LC detection.

Identification and characterization of a UbK family kinase in Porphyromonas gingivalis that phosphorylates the RprY response regulator.

Phosphorylation of proteins is a key component of bacterial signaling systems that can control important functions such as community development and virulence. We report here the identification of a Ubiquitous bacterial Kinase (UbK) family member, designated UbK1, in the anaerobic periodontal pathogen, Porphyromonas gingivalis. UbK1 contains conserved SPT/S, Hanks-type HxDxYR, EW, and Walker A motifs, and a mutation analysis established the Walker A domain and the Hanks-type domain as required for both autophosphorylation and transphosphorylation.

Exosome-Like Nanoparticles From GG Protect Against Alcohol-Associated Liver Disease Through Intestinal Aryl Hydrocarbon Receptor in Mice.

Alcohol-associated liver disease (ALD) is a major cause of mortality. Gut barrier dysfunction-induced bacterial translocation and endotoxin release contribute to the pathogenesis of ALD. Probiotic GG (LGG) is known to be beneficial on experimental ALD by reinforcing the intestinal barrier function.

Effect of Epidermal Growth Factor Treatment and Polychlorinated Biphenyl Exposure in a Dietary-Exposure Mouse Model of Steatohepatitis.

Background: Polychlorinated biphenyls (PCBs) are signaling disrupting chemicals that exacerbate nonalcoholic steatohepatitis (NASH) in mice. They are epidermal growth factor receptor (EGFR) inhibitors that enhance hepatic inflammation and fibrosis in mice.

Objectives: This study tested the hypothesis that epidermal growth factor (EGF) administration can attenuate PCB-related NASH by increasing hepatic EGFR signaling in a mouse model.

The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling.

Alphaviruses are arthropod-borne RNA viruses which can cause either mild to severe febrile arthritis which may persist for months, or encephalitis which can lead to death or lifelong cognitive impairments. The non-assembly molecular role(s), functions, and protein-protein interactions of the alphavirus capsid proteins have been largely overlooked. Here we detail the use of a BioID2 biotin ligase system to identify the protein-protein interactions of the Sindbis virus capsid protein.

Patients with Proliferative Lupus Nephritis Have Autoantibodies That React to Moesin and Demonstrate Increased Glomerular Moesin Expression.

Kidney involvement in systemic lupus erythematosus (SLE)-termed lupus nephritis (LN)-is a severe manifestation of SLE that can lead to end-stage kidney disease (ESKD). LN is characterized by immune complex deposition and inflammation in the glomerulus. We tested the hypothesis that autoantibodies targeting podocyte and glomerular cell proteins contribute to the development of immune complex formation in LN.

Differentiating Staphylococcus infection-associated glomerulonephritis and primary IgA nephropathy: a mass spectrometry-based exploratory study.

Staphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC-MS/MS) (n = 27) and immunohistochemistry (IHC) (n = 64), on four main diagnostic groups-SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies).

Proteomic Analysis Identifies Distinct Glomerular Extracellular Matrix in Collapsing Focal Segmental Glomerulosclerosis.

Background: The mechanisms leading to extracellular matrix (ECM) replacement of areas of glomerular capillaries in histologic variants of FSGS are unknown. This study used proteomics to test the hypothesis that glomerular ECM composition in collapsing FSGS (cFSGS) differs from that of other variants.

Methods: ECM proteins in glomeruli from biopsy specimens of patients with FSGS not otherwise specified (FSGS-NOS) or cFSGS and from normal controls were distinguished and quantified using mass spectrometry, verified and localized using immunohistochemistry (IHC) and confocal microscopy, and assessed for gene expression.

Arsenite Exposure Displaces Zinc from ZRANB2 Leading to Altered Splicing.

Exposure to arsenic, a class I carcinogen, affects 200 million people globally. Skin is the major target organ, but the molecular etiology of arsenic-induced skin carcinogenesis remains unclear. Arsenite (As)-induced disruption of alternative splicing could be involved, but the mechanism is unknown.

Predicting and Defining Steroid Resistance in Pediatric Nephrotic Syndrome Using Plasma Proteomics.

Introduction: Nephrotic syndrome (NS) is a characterized by massive proteinuria, edema, hypoalbuminemia, and dyslipidemia. Glucocorticoids (GCs), the primary therapy for >60 years, are ineffective in approximately 50% of adults and approximately 20% of children. Unfortunately, there are no validated biomarkers able to predict steroid-resistant NS (SRNS) or to define the pathways regulating SRNS.

Evaluating the Effects of Fibrinogen αC Mutations on the Ability of Factor XIII to Crosslink the Reactive αC Glutamines (Q237, Q328, Q366).

Fibrinogen (Fbg) levels and extent of fibrin polymerization have been associated with various pathological conditions such as cardiovascular disease, arteriosclerosis, and coagulation disorders. Activated factor XIII (FXIIIa) introduces γ-glutamyl-ε-lysinyl isopeptide bonds between reactive glutamines and lysines in the fibrin network to form a blood clot resistant to fibrinolysis. FXIIIa crosslinks the γ-chains and at multiple sites in the αC region of Fbg.