Search

Background: Hepatosteatosis is a common condition that can lead to cirrhosis and liver cancer. Galectin-3 (GAL-3) has been implicated in liver fibrosis and inflammation. Objectives: The purpose of this study was to investigate the association between GAL-3 and hepatosteatosis. Design: This study is a retrospective secondary analysis of data from a community health screening program. Methods: A total of 766 participants were included in the final analysis. Hepatosteatosis was diagnosed using ultrasonography, and GAL-3 levels were measured using enzyme-linked immunosorbent assay. Logistic regression analysis was used to examine the association between GAL-3 levels and the presence of hepatosteatosis, adjusting for age, sex, and other potential confounding factors. Results: The prevalence of moderate-to-severe hepatosteatosis in the study population was 31.5%. The participants with hepatosteatosis had a significantly higher mean level of GAL-3 compared to those without hepatosteatosis (16.6 ± 7.3 vs 13.5 ± 7.3 ng/ml; p 1 and GAL-3 >14.4 ng/ml was associated with a significantly increased risk (aOR 3.37, 95% CI: 1.90–5.99, p

IntroductionAtherosclerotic cardiovascular disease is associated with a high mortality rate due to vascular calcification. The role of fetuin-A in aortic arch calcification (AAC) is less well understood.MethodsAn analysis of secondary biomarkers was performed on 800 individuals from the biobank using the community database. AAC was defined by radiologists based on imaging. Multiple variables logical analysis was used for risk analysis.ResultsA total of 736 individual samples were collected based on age and gender. The average age is 65 ± 10 years, and half the population comprises men. In spite of similar body weight, renal function, and hepatic function, the AAC group had higher blood pressure and fetuin-A levels independently: systolic blood pressure (SBP) index ≥130 mmHg [adjusted odds ratio (aOR) 1.85, 95% confidence interval (CI) 1.34–2.57, p = 0.002] and fetuin-A (aOR 0.62, 95% CI 0.50–0.76, p

Abstract Sarcopenia has been associated with conventional chemotherapy-related toxicity, postoperative complications and poor overall survival in patients with genotype-unselected metastatic colorectal cancer (mCRC). This study aimed to evaluate the prognostic implications of sarcopenia and its change after perioperative cetuximab plus doublet chemotherapy and hepatectomy in patients with RAS wild-type colorectal liver metastasis (CRLM). Patients with CRLM from 2007 to 2018 in Chang Gung Research Database were retrospectively analyzed. Baseline characteristics as well as skeletal muscle index (SMI) at baseline and dynamic changes after interventions were collected. A multivariate Cox proportional hazard model was used to evaluate the effect of each parameter on overall survival (OS), and the Kaplan–Meier method was used to establish survival curves. A two-sided p value

Background: Thrombocytopenia is a common extrahepatic manifestation in chronic liver disease. However, there have been rare studies of impacts of risk for hepatitis C virus-associated thrombocytopenia (HCV-TP) and hepatitis B virus-associated thrombocytopenia (HBV-TP). The aim of this study is to evaluate different impacts of risk factors for HCV-TP and HBV-TP. Methods: We retrospectively collected 1803 HCV patients and 1652 HBV patients to examine the risk factors for time to moderate and severe thrombocytopenia (platelet counts

Background Human platelet antigens (HPAs) are alloantigens for antiplatelet alloantibodies and associated with the risk of immune thrombocytopenia (ITP). However, few studies have investigated associations among HPAs, antiplatelet autoantibodies, and cryoglobulins. Methods We enrolled 43 patients with primary ITP, 47 with hepatitis C virus-associated ITP (HCV-ITP), 21 with hepatitis B virus-associated ITP (HBV-ITP), 25 controls with HCV, and 1013 normal controls including HPA data of 998 Taiwanese blood donors. We analyzed HPA allele frequencies including HPA1-6 and 15, antiplatelet antibodies binding to platelet glycoprotein (GP) IIb/IIIa, Ia/IIa, Ib/IX, IV, human leukocyte antigen class I, cryoglobulin IgG/A/M, and their associations with thrombocytopenia. Results In the whole ITP cohort, HPA2ab predicted a low platelet count. HPA2b was associated with the risk of developing ITP, but not with anti-GPIb/IX antibodies. HPA15b was correlated with multiple antiplatelet antibodies. In the primary ITP patients, HPA3b was correlated with cryoglobulin IgG/A/M. In contrast, in the HCV-ITP patients, HPA3b was correlated with anti-GPIIb/IIIa antibodies, HCV-ITP patients with anti-GPIIb/IIIa antibodies had a higher positive rate of cryoglobulin IgG and IgA caomparred with those without anti-GPIIb/IIIa antibodies. Similar to the antiplatelet antibodies, cryoglobulins were associated with clinical thrombocytopenia, especially cryoglobulin IgA. Furthermore, cryoglobulins in the HCV-ITP patients showed characteristics to antiplatelet antibodies. Conclusion HPA alleles were associated with antiplatelet autoantibodies but had different impacts in the patients with primary ITP and HCV-ITP. The pathophysiology and characteristics of antiplatelet antibodies were different between these two groups. HCV-ITP was considered to be a symptom of mixed cryoglobulinemia in the HCV patients.

Background: Exposure to particulate matter (PM) may contribute to lung inflammation and injury. The therapeutic effect of N-acetylcysteine (NAC), a well-known antioxidant, with regards to the prevention and treatment of fine PM (PM2.5)-induced lung injury is poorly understood. This study aimed to determine the effect of PM2.5 on the recruitment of neutrophils and Ly6Chigh monocytes into lung alveoli and the production of proinflammatory proteins by stimulating the generation of reactive oxygen species (ROS), and to investigate the therapeutic effect of NAC on PM2.5-induced lung injury. Methods: C57BL/6 mice were exposed to a single administration of PM2.5 (200 μg/100 μl/mouse) or phosphate-buffered saline (control) via intratracheal instillation. The mice were injected intratracheally via a microsprayer aerosolizer with NAC (20 or 40 mg/kg) 1 h before PM2.5 instillation and 24 h after PM2.5 instillation. Total protein, VEGF, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF) were measured. Oxidative stress was evaluated by determining levels of malondialdehyde (MDA) and nitrite in BALF. Flow cytometric analysis was used to identify and quantify neutrophils and Ly6Chigh and Ly6Clow monocyte subsets. Results: Neutrophil count, total protein, and VEGF content in BALF significantly increased after PM2.5 exposure and reached the highest level on day 2. Increased levels of TNF-alpha, IL-6, nitrite, and MDA in BALF were also noted. Flow cytometric analysis showed increased recruitment of neutrophils and Ly6Chigh, but not Ly6Clow monocytes, into lung alveoli. Treatment with NAC via the intratracheal spray significantly attenuated the recruitment of neutrophils and Ly6Chigh monocytes into lung alveoli in PM2.5-treated mice in a dose-dependent manner. Furthermore, NAC significantly attenuated the production of total protein, VEGF, nitrite, and MDA in the mice with PM2.5-induced lung injury in a dose-dependent manner. Conclusion: PM2.5-induced lung injury caused by the generation of oxidative stress led to the recruitment of neutrophils and Ly6Chigh monocytes, and production of inflammatory proteins. NAC treatment alleviated PM2.5-induced lung injury by attenuating the ROS-mediated recruitment of neutrophils and Ly6Chigh monocytes and lung inflammation.

Neddylation, or the covalent addition of NEDD8 to specific lysine residue of proteins, is a reversible posttranslational modification, which regulates numerous biological functions; however, its involvement and therapeutic significance in osteoporosis remains unknown. Our results revealed that during the soluble receptor activator of nuclear factor-κB ligand (sRANKL)-stimulated osteoclast differentiation, the neddylation and expression of UBA3, the NEDD8-activating enzyme (NAE) catalytic subunit, were dose- and time-dependently upregulated in RAW 264.7 macrophages. UBA3 knockdown for diminishing NAE activity or administering low doses of the NAE inhibitor MLN4924 significantly suppressed sRANKL-stimulated osteoclast differentiation and bone-resorbing activity in the macrophages by inhibiting sRANKL-stimulated neddylation and tumor necrosis factor receptor-associated factor 6 (TRAF6)-activated transforming growth factor-β-activated kinase 1 (TAK1) downstream signaling for diminishing nuclear factor-activated T cells c1 (NFATc1) expression. sRANKL enhanced the interaction of TRAF6 with the neddylated proteins and the polyubiquitination of TRAF6’s lysine 63, which activated TAK1 downstream signaling; however, this process was inhibited by MLN4924. MLN4924 significantly reduced osteoporosis in an ovariectomy- and sRANKL-induced osteoporosis mouse model in vivo. Our novel finding was that NAE-mediated neddylation participates in RANKL-activated TRAF6–TAK1–NFATc1 signaling during osteoclast differentiation and osteoporosis, suggesting that neddylation may be a new target for treating osteoporosis.