Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ∼70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle. Hepatokines are proteins that are secreted by hepatocytes, and many hepatokines have been linked to the induction of metabolic dysfunction, including fetuin A, fetuin B, retinol-binding protein 4 (RBP4) and selenoprotein P. In this Review, we describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication.

Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance

Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies

Graphene was utilized for the first time as a matrix for the analysis of low molecular weight compounds using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Polar compounds including amino acids, polyamines, anticancer drugs, and nucleosides could be successfully analyzed. Additionally, nonpolar compounds including steroids could be detected with high resolution and sensitivity. Compared with a conventional matrix, graphene exhibited a high desorption/ionization efficiency for nonpolar compounds. The graphene matrix functions as a substrate to trap analytes, and it transfers energy to the analytes upon laser irradiation, which allows for the analytes to be readily desorbed/ionized and interference of intrinsic matrix ions to be eliminated. The use of graphene as a matrix avoided the fragmentation of analytes and provided good reproducibility and a high salt tolerance, underscoring the potential application of graphene as a matrix for MALDI MS analysis of pract...

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Graphene as a Novel Matrix for the Analysis of Small Molecules by MALDI-TOF MS

Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise

Methods for samples preparation in proteomic research

Secretome profiling of primary human skeletal muscle cells

In two-dimensional gel electrophoresis-based proteomic experiments matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) peptide mass fingerprinting is often the technique of choice in identifying proteins. Here, we present a novel surface coating technique for MALDI-MS targets that improves manual and automatic sample analysis. A mixture of silicone and graphite is spread in the form of a thin layer over the target. Due to the hydrophobicity of the coating, aqueous solutions can be applied to relatively small spots very precisely using a robotic system. At least four times more liquid can be concentrated on the same area compared to uncoated steel targets. alpha-cyano-4-hydrocinnamic acid crystallizes in form of very small crystals evenly distributed over the surface. The search for "hot spots" during the analysis is not necessary, which supports the automatic acquisition of data. The homogeneous crystal layer can be very effectively washed on-target without encountering major sample losses. This efficient washing and the focused application of aqueous samples replace expensive and time-consuming reversed phase micro column based sample clean-ups. When analyzing peptide mixtures, the signal intensities are up to five times higher than with preparations of the same un-desalted samples on steel targets, since four times more sample can be loaded. The mass resolution remains unaffected by the surface coating. After usage the coating can be removed, followed by a new coating avoiding any carry-over of sample to the next analysis. All these properties make the precoating of MALDI-MS targets with a silicone/graphite layer an ideal technique for routine analysis in large-scale proteomic experiments.

Silicone/graphite coating for on‐target desalting and improved peptide mapping performance of matrix‐assisted laser desorption/ionization‐mass spectrometry targets in proteomic experiments

Threshold values for detergents in protein and peptide samples for mass spectrometry

Respiratory diseases are highly prevalent and affect humankind worldwide, causing extensive morbidity and mortality with the environment playing an important role. Given the complex structure of the airways, sophisticated tools are required for early diagnosis; initial symptoms are nonspecific, and the clinical diagnosis is made frequently late. Over the past few years, proteomics has made high technological progress in mass-spectrometry-based protein identification and has allowed us to gain new insights into disease mechanisms and identify potential novel therapeutic targets. This review will highlight the contributions of proteomics toward the understanding of the respiratory proteome listing potential biomarkers and its potential application to the clinic. We also outline the contributions of proteomics to creating a personalized approach in respiratory medicine.

Respiratory proteomics: from descriptive studies to personalized medicine

During analysis of the proteome in the cerebrospinal fluid (CSF) of the Caucasian form of moyamoya disease (MMD), a novel post-translational modification of human transthyretin was observed. Two-dimensional electrophoresis and subsequent peptide sequencing with ESI-MS/MS were performed to discover the gamma-carboxylation of the Glu-42 (Gla-42).

Xinping Li

Papers

Secretome profiling of primary human skeletal muscle cells

Silicone/graphite coating for on‐target desalting and improved peptide mapping performance of matrix‐assisted laser desorption/ionization‐mass spectrometry targets in proteomic experiments

Threshold values for detergents in protein and peptide samples for mass spectrometry

Respiratory proteomics: from descriptive studies to personalized medicine

Detection of a gamma-carboxy-glutamate as novel post-translational modification of human transthyretin.