Antilipotoxicity Activity of Osmanthus fragrans

The excess influx of free fatty acids (FFAs) into nonadipose tissues, such as those of liver and kidney, induces lipotoxicity leading to hepatic steatosis and renal dysfunction. The aim of this study was to investigate the protective effects of methanolic flower extracts of Osmanthus fragrans (OF) and Chrysanthemum morifolium (CM) against FFA-induced lipotoxicity in hepatocytes (human HepG2 cells) and renal glomerular mesangial cells (mouse SV40-Mes13 cells). The results showed that OF and CM significantly suppressed FFA-induced intracellular triacylglycerol accumulation via partially inhibiting the gene expression of sterol regulatory element-binding protein-1c (SREBP-1c) and glycerol-3-phosphate acyltransferase (GPAT) in HepG2 cells. Both extracts inhibited reactive oxygen species (ROS) generation by FFA-stimulated HepG2 cells. OF and CM also suppressed the mRNA expression of interleukin- (IL-) 1β, IL-6, IL-8, tumor necrosis factor- (TNF-) α, and transforming growth factor- (TGF-) β by HepG2 cells treated with conditioned medium derived from lipopolysaccharide-treated THP-1 monocytes. Furthermore, OF and CM effectively inhibited oleate-induced cellular lipid accumulation, TGF-β secretion, and overexpression of fibronectin in mesangial cells. In conclusion, OF and CM possess hepatoprotective activity by inhibiting hepatic fat load and inflammation and renal protection by preventing FFA-induced mesangial extracellular matrix formation

Effects of size and surface of zinc oxide and aluminum-doped zinc oxide nanoparticles on cell viability inferred by proteomic analyses

Although the health effects of zinc oxide nanoparticles (ZnONPs) on the respiratory system have been reported, the fate, potential toxicity, and mechanisms in biological cells of these particles, as related to particle size and surface characteristics, have not been well elucidated. To determine the physicochemical properties of ZnONPs that govern cytotoxicity, we investigated the effects of size, electronic properties, zinc concentration, and pH on cell viability using human alveolar-basal epithelial A549 cells as a model. We observed that a 2-hour or longer exposure to ZnONPs induced changes in cell viability. The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs. Proteomic profiling of A549 exposed to ZnONPs for 2 and 4 hours was used to determine the biological mechanisms of ZnONP toxicity. p53-pathway activation was the core mechanism regulating cell viability in response to particle size. Activation of the Wnt and TGFβ signaling pathways was also important in the cellular response to ZnONPs of different sizes. The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences. These results suggested that the size and surface characteristics of ZnONPs might play an important role in their observed cytotoxicity. This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles

Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma

Abstract Background Vascular abnormalities are the predominant histologic changes associated with radiation in nasopharyngeal carcinoma (NPC). This study examined if the duration after radiotherapy correlates with the progression of carotid intima-media thickness (IMT) and investigated its relationship with inflammatory markers. Methods One hundred and five NPC patients post-radiotherapy for more than one year and 25 healthy control subjects were examined by B-mode ultrasound for IMT measurement at the far wall of the common carotid artery (CCA). Surrogate markers including lipid profile, HbA1c, and high sensitive C-reactive protein (hs-CRP) were assessed. Results The IMT of CCA was significantly increased in NPC patients and carotid plaque was detected in 38 NPC patients (38/105, 36.2%). Significant risk factors for carotid plaques included age, duration after radiotherapy, and HbA1c levels. Age, duration after radiotherapy, hs-CRP, HbA1c, and platelet count positively correlated with IMT. The cut-off value of age and duration after radiotherapy for the presence of plaque was 52.5 years and 42.5 months, respectively. In NPC subjects, multiple linear regression analysis revealed that age, gender, duration after radiotherapy and platelet counts were independently associated with CCA IMT. After adjustments for age, gender and platelet counts, IMT increased in a linear manner with duration after radiotherapy. Conclusions Radiation-induced vasculopathy is a dynamic and progressive process due to late radiation effects. Extra-cranial color-coded duplex sonography can be part of routine follow-up in NPC patients aged ≥50 years at 40 months post-radiotherapy. </jats:sec

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Genome-Wide Association Study and Functional Characterization Identifies Candidate Genes for Insulin-Stimulated Glucose Uptake

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in \u3e55,000 participants from three ancestry groups. We identified ten new loci (P \u3c 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits

Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC

Management of Crohn’s disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023

Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049