Rationale: A genetic locus within the FAM13A gene has been consistently associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies. However, the mechanisms by which FAM13A contributes to COPD susceptibility are unknown.Objectives: To determine the biologic function of FAM13A in human COPD and murine COPD models and discover the molecular mechanism by which FAM13A influences COPD susceptibility. ) were generated and exposed to cigarette smoke. The lung inflammatory response and airspace size were assessed in Fam13a 2/2 and Fam13a 1/1 littermate control mice. Cellular localization of FAM13A protein and mRNA levels of FAM13A in COPD lungs were assessed using immunofluorescence, Western blotting, and reverse transcriptase-polymerase chain reaction, respectively. Immunoprecipitation followed by mass spectrometry identified cellular proteins that interact with FAM13A to reveal insights on FAM13A's function. ) were resistant to chronic cigarette smoke-induced emphysema compared with Fam13a 1/1 mice. In vitro, FAM13A interacts with protein phosphatase 2A and recruits protein phosphatase 2A with glycogen synthase kinase 3b and b-catenin, inducing b-catenin degradation. Fam13a 2/2 mice were also resistant to elastase-induced emphysema, and this resistance was reversed by coadministration of a b-catenin inhibitor, suggesting that FAM13A could increase the susceptibility of mice to emphysema development by inhibiting b-catenin signaling. Moreover, human COPD lungs had decreased protein levels of b-catenin and increased protein levels of FAM13A. Conclusions:We show that FAM13A may influence COPD susceptibility by promoting b-catenin degradation.

Aflatoxins are classified as Group 1 (carcinogenic to humans) by the International Agency for Research on Cancer. In this study, a total of 134 fungal strains were isolated from 65 meju samples, and two fungal isolates were selected as potential aflatoxin B (AFB)-biodetoxification fungi. These fungi were identified as MAO103 and MAO104 by sequencing the beta-tubulin gene. The two strains were able to degrade more than 90% of AFB (initial concentration: 40 μg/l) in a culture broth in 14 days. The mutagenic effects of AFB treated with MAO103 and MAO104 significantly decreased to 5.7% and 6.4%, respectively, in the frame-shift mutation of Ames tests using TA98. The base-substituting mutagenicity of AFB was also decreased by the two fungi. Moreover, AFB production by was significantly decreased by the two strains on soybean-based agar plates. Our data suggest that the two AFB-detoxifying strains have potential application to control AFB in foods and feeds.

BackgroundA keloid is pathological scar caused by aberrant response to skin injuries, characterized by excessive accumulation of histological extracellular matrix, and occurs in genetically susceptible individuals. Plasminogen activator inhibitor-1 (PAI-1) has been implicated in the pathogenesis of keloid. We investigated the association between PAI-1 polymorphisms and plasma PAI-1 level with keloid risk.Material/MethodsA total of 242 Chinese keloid patients and 207 controls were enrolled in this study. Polymerase chain reaction-restriction technique was used to determine PAI-1 promoter polymorphism (-675 4G/5G and -844 A/G) distribution. Plasma PAI-1 levels were detected using enzyme-linked immunosorbent assay (ELISA).ResultsThere was a statistically significant difference in the distribution of PAI-1 -675 4G/5G polymorphism between keloid patients and healthy controls. 4G/4G carriers were more likely to develop keloid. In contrast, the -844 A/G polymorphism distribution did not vary significantly between keloid patients and controls. The keloid patients group had a significantly higher plasma PAI-1 level than the control group. In the -675 4G/4G carrier population, the plasma PAI-1 levels were significant higher in keloid patients compared with controls.ConclusionsOur study provides evidence that PAI-1 promoter polymorphism -675 4G/5G and plasma PAI-1 level are associated with keloid risk. PAI-1 -675 4G/5G polymorphism may be an important hereditary factor responsible for keloid development in the Chinese Han population.

Objective. Adolescent idiopathic scoliosis (AIS) is a relatively common spinal rotation deformity, and the pathogenesis of AIS is accompanied by metabolic dysfunction and changes in biochemical factors. In this study, plasma metabolite changes in AIS patients were analyzed based on nontargeted metabolomics to provide new insights for clarifying functional metabolic abnormalities in AIS patients. Methods. Clinical indexes and blood samples were collected from 12 healthy subjects and 16 AIS patients. Metabolomics was used to analyze the changes in metabolites in plasma samples. The correlation between plasma metabolites and clinical indexes was analyzed by the Spearman rank correlation coefficient. Results. Analysis of clinical data showed that the body weight, body mass index (BMI), and bone mineral density (BMD) index of the AIS group significantly decreased, while the blood phosphorus and Cobb angles increased significantly. Metabolomic analysis showed significant changes in 72 differential metabolites in the plasma of the AIS group, mainly including organooxygen compounds, carboxylic acids and derivatives, fatty acyls, steroids and steroid derivatives, and keto acids and derivatives. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that arginine biosynthesis, D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and citrate cycle (TCA cycle) were significantly enriched in the AIS and healthy groups. Spearman rank correlation coefficient analysis showed that the plasma metabolites C00026 (oxoglutarate), C00062 (L-arginine, arginine), C01042 (N-acetylaspartate), and C00158 (citrate) were significantly correlated with clinical indexes in AIS patients. In the healthy group, the plasma metabolites C00122 (fumarate), C00025 (glutamate and L-glutamic acid) and C00149 (malate, L-malic acid) were significantly correlated with clinical indexes, while C00624 (N-acetylglutamate) was not significantly correlated with the clinical indexes. Conclusion. The occurrence of AIS led to changes in clinical indexes and plasma metabolites. Plasma biomarkers and functional metabolic pathways were correlated with clinical indexes, which might provide new insights for the diagnosis and treatment of AIS.

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