Sarcopenia assessed using bioimpedance analysis is associated independently with significant liver fibrosis in patients with chronic liver diseases.

AIM: Sarcopenia is common in patients with advanced fibrosis or cirrhosis. We investigated the correlation between sarcopenia and other clinical variables, in particular, significant liver fibrosis in patients with chronic liver diseases (CLDs). PATIENTS AND METHODS: Patients with CLDs who underwent transient elastography (TE) and bioelectrical impedance analysis between 2015 and 2017 were retrospectively recruited. The sarcopenia index (SI) was calculated as follows: SI = total appendicular skeletal muscle mass (kg)/ body mass index (BMI) (kg/m). Sarcopenia was defined as SI less than 0.789 for men and less than 0.521 for women. Significant liver fibrosis and fatty liver were defined using TE liver stiffness value more than 7 kPa and controlled attenuation parameter more than 250 dB/m, respectively. RESULTS: Of 2168 patients recruited, 218 (10.1%) had sarcopenia. Age, BMI, diabetes, hypertension, fasting glucose, aspartate aminotransferase, and liver stiffness value were correlated positively with sarcopenia (all P < 0.05), whereas male sex, viral etiology, obesity (BMI > 25 kg/m), total bilirubin, and serum albumin were correlated negatively with sarcopenia (all P < 0.05). On multivariate analysis, TE-defined significant liver fibrosis was associated independently with sarcopenia (odds ratio = 1.597; 95% confidence interval: 1.174-2.172; P = 0.003), together with age, male sex, viral etiology, and TE-defined fatty liver (all P < 0.05). Among the subgroups with ultrasonography-defined nonalcoholic fatty liver disease (n = 957), sarcopenia was also associated independently with TE-defined significant liver fibrosis (odds ratio = 1.887; 95% confidence interval: 1.261-2.823; P < 0.001). CONCLUSION: Sarcopenia is associated independently with significant liver fibrosis in patients with CLDs. Further studies are required to determine whether interventions to improve muscle mass can improve liver fibrosis.

Evolutionary, computational, and biochemical studies of the salicylaldehyde dehydrogenases in the naphthalene degradation pathway.

Salicylaldehyde (SAL) dehydrogenase (SALD) is responsible for the oxidation of SAL to salicylate using nicotinamide adenine dinucleotide (NAD+) as a cofactor in the naphthalene degradation pathway. We report the use of a protein sequence similarity network to make functional inferences about SALDs. Network and phylogenetic analyses indicated that SALDs and the homologues are present in bacteria and fungi. The key residues in SALDs were analyzed by evolutionary methods and a molecular simulation analysis. The results showed that the catalytic residue is most highly conserved, followed by the residues binding NAD+ and then the residues binding SAL. A molecular simulation analysis demonstrated the binding energies of the amino acids to NAD+ and/or SAL and showed that a conformational change is induced by binding. A SALD from Alteromonas naphthalenivorans (SALDan) that undergoes trimeric oligomerization was characterized enzymatically. The results showed that SALDan could catalyze the oxidation of a variety of aromatic aldehydes. Site-directed mutagenesis of selected residues binding NAD+ and/or SAL affected the enzyme's catalytic efficiency, but did not eliminate catalysis. Finally, the relationships among the evolution, catalytic mechanism, and functions of SALD are discussed. Taken together, this study provides an expanded understanding of the evolution, functions, and catalytic mechanism of SALD.

Alteromonas naphthalenivorans sp. nov., a polycyclic aromatic hydrocarbon-degrading bacterium isolated from tidal-flat sediment.

A Gram-staining-negative and halotolerant bacterium, designated SN2T, capable of biodegrading polycyclic aromatic hydrocarbons, was isolated from a tidal flat contaminated with crude oil in Korea. Cells were strictly aerobic, catalase- and oxidase-positive, motile rods, with a single polar flagellum. Growth was observed at 4-37 °C (optimum, 25-30 °C) at pH 6.0-9.0 (optimum, pH 7.0-7.5) and in the presence of 0.5-9.0% (w/v) NaCl (optimum, 2.0%). Only ubiquinone 8 was detected as the isoprenoid quinone, and summed feature 3 (comprising C16:1ω7c and/or iso-C15:0 2-OH), C16:0, C18:1ω7c and C12:0 were observed as the major cellular fatty acids. The major polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, a glycolipid, an aminolipid and three unidentified lipids. The DNA G+C content was 43.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SN2T formed a phylogenetic lineage with Alteromonas stellipolaris and Alteromonas addita within the genus Alteromonas, which was consistent with multilocus phylogenetic and MALDI-TOF MS analyses. Strain SN2T was most closely related to the type strains of A. stellipolaris, A. addita and Alteromonas macleodii, with 16S rRNA gene sequence similarities of 99.5, 99.3 and 98.4% and DNA-DNA relatedness of 48.7 ± 6.6, 24.9 ± 7.5 and 27.9 ± 8.4%, respectively. In conclusion, strain SN2T represents a novel species of the genus Alteromonas, for which the name Alteromonas naphthalenivorans sp. nov. is proposed. The type strain is SN2T ( = KCTC 11700BPT = JCM 17741T =KACC 18427T).

The structural biology of growth factor receptor activation.

Stimulation of cells by growth factors triggers cascades of signalling that result in cellular responses such as growth, differentiation, migration and survival. Many growth factors signal through receptor tyrosine kinases, leading to dimerization, trans-phosphorylation and activation of tyrosine kinases that phosphorylate components further downstream of the signal transduction cascade. Using insulin-like growth factor, nerve growth factor, hepatocyte growth factor and fibroblast growth factor as examples, we show that the globular architecture of the growth factors is essential for receptor binding. We describe how nerve growth factor (NGF) is a symmetrical dimer that binds four storage proteins (two alpha-NGF and two gamma-NGF) to give a symmetrical hetero-hexameric 7SNGF organised around the beta-NGF dimer. It binds the extracellular domains of two receptor molecules in a similar way, so dimerising the receptor. Hepatocyte growth factor/scatter factor (HGF/SF) probably binds its receptor as a dimer stabilised by interactions with heparan sulfate, and fibroblast growth factor (FGF) binds its receptor as a dimer cross-linked by heparan sulfate. Surprisingly, insulin and insulin-like growth factor (IGF) bind in the monomeric form to receptors that are already covalent dimers. We propose that, in general, weak binary interactions between growth factor and individual domains of receptors are enhanced by cooperative interactions with further receptor domains, and sometimes other components like heparan, to give rise to specific multi-protein/domain complexes.