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Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass. As the genetic biomarkers for sarcopenia are not yet well characterised, this study aimed to investigate the genetic variations related to sarcopenia in a relatively aged cohort, using genome-wide association study (GWAS) meta-analyses of lean body mass (LBM) in 6961 subjects. Two Korean cohorts were analysed, and subgroup GWAS was conducted for appendicular skeletal muscle mass (ASM) and skeletal muscle index. The effects of significant single nucleotide polymorphisms (SNPs) on gene expression were also investigated using multiple expression quantitative trait loci datasets, differentially expressed gene analysis, and gene ontology analyses. Novel genetic biomarkers were identified for LBM (rs1187118; rs3768582) and ASM (rs6772958). Their related genes, including RPS10, NUDT3, NCF2, SMG7, and ARPC5, were differently expressed in skeletal muscle tissue, while GPD1L was not. Furthermore, the 'mRNA destabilisation' biological process was enriched for sarcopenia. Our study identified RPS10, NUDT3, and GPD1L as significant genetic biomarkers for sarcopenia. These genetic loci were related to lipid and energy metabolism, suggesting that genes involved in metabolic dysregulation may lead to the pathogenesis of age-related sarcopenia. [ABSTRACT FROM AUTHOR]

Food allergy (FA) is a widespread issue, affecting as many as 10% of the population. Over the past two to three decades, the prevalence of FA has been on the rise, particularly in industrialized and westernized countries. FA is a complex, multifactorial disease mediated by type 2 immune responses and involving environmental and genetic factors. However, the precise mechanisms remain inadequately understood. Metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. A metabolome approach would facilitate the identification of surrogate metabolite markers reflecting the disease activity and prognosis. Here, we present a literature overview of recent metabolomic studies conducted on children with FA. [ABSTRACT FROM AUTHOR]

Background: Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA. Methods: We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry‐based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA. Results: In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid. Conclusion: Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies. [ABSTRACT FROM AUTHOR]

Background: Obesity is a common comorbid condition in adult asthmatics and known as a feature of asthma severity. However, the molecular mechanism under obesity‐induced inflammation has not yet been fully understood. Objective: Considering the essential role of hydrophobic surfactant protein B (SP‐B) in lung function, SP‐B was targeted to examine its involvement in the development of obesity‐induced airway inflammation in asthmatics. Methods: The aim was to examine an alteration in circulating SP‐B according to obesity in adult asthmatics, 129 asthmatics were enrolled and classified into 3 groups (obese, overweight and normal‐weight groups) according to body mass index (BMI). Circulating SP‐B levels were determined by enzyme‐linked immunosorbent assay. Four single nucleotide polymorphisms of SFTPB gene were genotyped. Serum ceramide levels were measured by liquid chromatography‐tandem mass spectrometry. Results: Significantly lower serum SP‐B levels were noted in the obese group than in the overweight or normal‐weight group (p =.002). The serum SP‐B level was significantly correlated with serum levels of C18:0 ceramide and transforming growth factor beta 1 as well as BMI (r = −0.200; r = −0.215; r = −0.332, p <.050 for all). An inverse correlation was noted between serum SP‐B and fractional exhaled nitric oxide levels in female asthmatics (r = −0.287, p =.009). Genetic predisposition of the SFTPB gene at 9306 A>G to the obese and overweight groups was noted. Conclusion: Obesity altered ceramide metabolism leading to pulmonary surfactant dysfunction and impaired resolution of airway inflammation, finally contributing to the phenotypes of obese asthmatics. [ABSTRACT FROM AUTHOR]

In vitro and animal experiments demonstrated that lumican exerts anabolic effects on bone and muscle by stimulating osteoblastogenesis, suppressing osteoclastogenesis and increasing myogenesis. However, the relationship between circulating lumican and musculoskeletal phenotypes in humans remains unclear. We aimed to analyze the relationship between serum lumican levels and osteosarcopenia in older adults. Blood samples were collected from 134 participants (age: 65 years and older) who underwent comprehensive assessment of bone and muscle phenotypes. Osteoporosis and sarcopenia were diagnosed based on World Health Organization and Asian consensus guidelines, respectively. Osteosarcopenia was defined as the simultaneous presence of osteoporosis and sarcopenia. After adjusting for sex, age, and body mass index, older adults with osteosarcopenia had 20.2 % lower serum lumican levels than those without (P = 0.010). The odds ratio (OR) for osteosarcopenia per standard deviation decrease in serum lumican level was 4.17 (P = 0.003). Consistently, higher serum lumican levels were correlated with higher bone mass at all measured sites (P = 0.004 to 0.045) and higher grip strength (P = 0.023). Furthermore, participants in the lowest tertile (T1) had 7.56-fold higher OR for osteosarcopenia (P = 0.024) than those in the highest lumican tertile (T3). In conclusion, these findings clinically validate previous experimental data showing the musculoskeletal protective effects of lumican and suggest that blood lumican levels could be used as a potential biomarker to assess the risk of not only osteosarcopenia but also osteoporosis or sarcopenia in older adults. • Older adults with osteosarcopenia had 20.2 % lower serum lumican levels than controls. • Lower serum lumican was associated with higher risk for osteosarcopenia. • Serum lumican had positive associations with bone mass and grip strength. [ABSTRACT FROM AUTHOR]

Background In diabetic retinopathy (DR), neutrophil extracellular traps (NET) and kallikrein-kinin system are considered as contributing factors. However, the detail activation mechanisms has not been fully understood. Since the NET could provide negative-charged surface for factor XII activation and the activated factor XII (XIIa) can initiate kallikrein-kinin system, this study investigated whether patients with DR show activation of NET, factor XII and kallikrein-kinin system. Methods The markers related to NET (DNA-histone complex) and kallikrein-kinin system (high-molecular-weight kininogen, prekallikrein, bradykinin) and factor XIIa were measured in 253 patients with diabetes. To access ex vivo effect of glucose, DNA-histone complex and factor XIIa were measured in whole blood stimulated by glucose. Results The circulating level of DNA-histone complex and factor XIIa were significantly higher in patients with DR than those without DR. In logistic regression analysis, DNA-histone complex, factor XIIa, and high-molecular-weight kininogen were the risk factors of DR. In recursive partitioning analysis, among patients with diabetes duration less than 10 years, patients with high level of DNA-histone complex (>426 AU) showed high risk of DR. In ex vivo experiment, glucose significantly elevated both DNA-histone complex and factor XIIa. Conclusion Our findings suggest that activation of factor XII and kallikrein-kinin system combined with NET formation actively occur in patients with DR and circulating levels of DNA-histone complex, factor XIIa and HMWK can be potential biomarkers to estimate the risk of DR. Strategies against factor XII activation may be beneficial to inhibit DR. [ABSTRACT FROM AUTHOR]

Heavy metals are commonly released into the environment through industrial processes such as mining and refining. The rapid industrialization that occurred in South Korea during the 1960s and 1970s contributed significantly to the economy of the country; however, the associated mining and refining led to considerable environmental pollution, and although mining is now in decline in South Korea, the detrimental effects on residents inhabiting the surrounding areas remain. The bioaccumulation of toxic heavy metals leads to metabolic alterations in human homeostasis, with disruptions in this balance leading to various health issues. This study used metabolomics to explore metabolomic alterations in the plasma samples of residents living in mining and refining areas. The results showed significant increases in metabolites involved in glycolysis and the surrounding metabolic pathways, such as glucose-6-phosphate, phosphoenolpyruvate, lactate, and inosine monophosphate, in those inhabiting polluted areas. An investigation of the associations between metabolites and blood clinical parameters through meet-in-the-middle analysis indicated that female residents were more affected by heavy metal exposure, resulting in more metabolomic alterations. For women, inhabiting the abandoned mine area, metabolites in the glycolysis and pentose phosphate pathways, such as ribose-5-phosphate and 3-phosphoglycerate, have shown a negative correlation with albumin and calcium. Finally, Mendelian randomization(MR) was used to determine the causal effects of these heavy metal exposure-related metabolites on heavy metal exposure-related clinical parameters. Metabolite biomarkers could provide insights into altered metabolic pathways related to exposure to toxic heavy metals and improve our understanding of the molecular mechanisms underlying the health effects of toxic heavy metal exposure. [ABSTRACT FROM AUTHOR]

Myonectin is a muscle-secreted factor that helps maintain homeostasis in the body by regulating several functions, including lipid metabolism. Previous studies suggested that myonectin may play a role in muscle health in an autocrine manner, but its impact on human skeletal muscle is still unclear. We aimed to investigate the relationship of serum myonectin levels with sarcopenia and related muscle parameters. We conducted a cross-sectional study of 142 older adults whose muscle mass, grip strength, gait speed, chair stands, and short physical performance battery (SPPB) were evaluated in the geriatric clinic of a tertiary medical center. Sarcopenia was defined based on Asian-specific cutoff values, and circulating myonectin levels were measured using an enzyme immunoassay. Before and after adjusting for age, sex, and body mass index, the serum myonectin level was not significantly different when the patients were stratified by status of sarcopenia, muscle mass, muscle strength, and physical performance. Furthermore, whether given as a continuous variable or divided into quartile groups, the serum myonectin level had no association with the skeletal muscle mass, grip strength, gait speed, chair stand test, or SPPB score. Our findings did not confirm the potential role of myonectin in muscle metabolism observed in experimental research. Thus, serum myonectin levels cannot predict the risk of sarcopenia in older Asian adults. • Serum myonectin was not different according to sarcopenia or related parameters. • The null association was consistent in age, sex, and BMI adjusted models. • Serum myonectin cannot predict the risk of sarcopenia in older Asian adults. [ABSTRACT FROM AUTHOR]