ABSTRACT
Background/Aims@#Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. @*Methods@#We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. @*Results@#Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. @*Conclusions@#The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.
ABSTRACT
Background/Aims@#Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression. @*Methods@#A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited. @*Results@#Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis. @*Conclusions@#LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.
ABSTRACT
Background/Aims@#Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression. @*Methods@#A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited. @*Results@#Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis. @*Conclusions@#LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.
ABSTRACT
Objective To study the effect of bone mineral density (BMD) change on response of human spine to landing impact by numerical simulation. Methods The three-dimensional material point model of human head skull, cervical vertebrae, thoracic, lumbar vertebra, pelvis, ligament and disc was constructed from the computed tomography (CT) scanned images, and they were attached together as a human spine model and placed on the backrest of the chair, which was constructed by the MPM3D program. The acceleration loading was applied on the back rest of the chair to simulate the landing impact loading when the human spine model was laid on the back of the chair. The different responses of human spine to landing impact were simulated by changing the BMD and the corresponding elastic modulus. Results The general risk of injury γ value of normal BMD was 1.589 3, and when the BMD was reduced by 2%, 4%, 6%, 8%, 10%, respectively, γ values were 1.608 6, 1.634 7, 1.641 0, 1.662 5, 1.680 5, correspondingly. Conclusions Under the same landing impact loading, the smaller the bone mineral density, the larger the response of human spine to landing impact loading, and human body is more vulnerable to injuries.
ABSTRACT
Objective To investigate the effects of muscles and boundary conditions on head impact response. Methods Three different 3D material point impact models of human head were constructed from the CT scanned images. The first model was the simple head model (SHFr) including skull, membrane and brain, in which the head was free. The second model was the simple head model with muscle (MHFr) including skull, membrane, brain and muscle of the head, in which the head was free. The third model was the MHFr model with shoulder, in which the bottom edge of the shoulder was fixed (MHSFi). The three models were under the impact of a cylindrical lead hammer projected at a speed of 6.4 m/s to simulate the dynamic response of the three models using 3D explicit material point method code. Results The peak values of acceleration of the head centroid for the SHFr, MHFr and MHSFi model were 6.018×103, 4.69×103 and 4.76×103 m/s2, respectively. Conclusions The muscle of the head can disperse distributions of the contact force, enlarge the damage area and relieve the damage of the head. In case of short-time impact, whether the boundary of the head is free or the shoulder is fixed does not affect the dynamic response of the head impact.