Background: Lipid expression is increased in the atrial myocytes of mitral regurgitation (MR) patients. This study aimed to investigate key regulatory genes and mechanisms of atrial lipotoxic myopathy in MR. Methods: The HL-1 atrial myocytes were subjected to uniaxial cyclic stretching for eight hours. Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism were analyzed by PCR assay (168 genes). Results: The stretched myocytes had significantly larger cell size and higher lipid expression than non-stretched myocytes (all p < 0.001). Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism in the myocytes were analyzed by PCR assay (168 genes). In comparison with their counterparts in non-stretched myocytes, seven genes in stretched monocytes (Idi1, Olr1, Nr1h4, Fabp2, Prkag3, Slc27a5, Fabp6) revealed differential upregulation with an altered fold change >1.5. Nine genes in stretched monocytes (Apoa4, Hmgcs2, Apol8, Srebf1, Acsm4, Fabp1, Acox2, Acsl6, Gk) revealed differential downregulation with an altered fold change <0.67. Canonical pathway analysis, using Ingenuity Pathway Analysis software, revealed that the only genes in the “superpathway of cholesterol biosynthesis” were Idi1 (upregulated) and Hmgcs2 (downregulated). The fraction of stretched myocytes expressing Nile red was significantly decreased by RNA interference of Idi1 (p < 0.05) and was significantly decreased by plasmid transfection of Hmgcs2 (p = 0.004). Conclusions: The Idi1 and Hmgcs2 genes have regulatory roles in atrial lipotoxic myopathy associated with atrial enlargement.

The prognostic value of easily accessible hematologic biomarkers, such as the neutrophil-to-HDL ratio, as well as the monocyte-to-HDL, lymphocyte-to-HDL, and platelet-to-HDL ratios, remains underexplored in patients with established ischemic heart disease (IHD). Community-dwelling adults aged ≥ 20 with established IHD from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were eligible. Mortality was tracked through linkage to the National Death Index (NDI) until the end of 2019. Cox regressions examined the associations between these hematologic ratios and all-cause mortality. Receiver operating characteristic (ROC) curve analysis assessed the predictive accuracy of these ratios for mortality. A total of 2265 patients were analyzed, with a median follow-up period of 80 months. After adjusting for demographic factors, lifestyle variables, and comorbidities, patients in the highest quartile of the neutrophil/HDL had a significantly increased all-cause mortality risk (aHR = 1.41, 95% CI: 1.13–1.77) compared to those in the lowest quartile. No significant associations were found between the other ratios and mortality. In conclusion, this study found that among the hematologic ratios analyzed, an elevated neutrophil-to-HDL ratio has the strongest potential for mortality risk stratification in community-dwelling patients with ischemic heart disease in the US, offering important guidance for both patients and clinicians.

4118 Background: Gastric cancer (GC) is one of the most common malignancies and the second leading cause of cancer death worldwide. The REGATE international disease registry was designed to describe the geographic pattern of GC treatment in order to improve patient (pt) care. Methods: From August 2004 to July 2008, 10,124 pts with newly diagnosed primary GC were enrolled; data were collected at an initial visit and <10 months later. Sample size was dependent on GC prevalence in participating countries. Treatments are reported globally and by region. Other characteristics, including staging of disease, are described elsewhere. Results: Analyses were performed for 9,965 pts (98%) who had documentation on treatment received in Europe (E), Asia-Pacific (AP), Latin America (LA), North Africa (NA) and on the Indian subcontinent (IS). In all regions, neoadjuvant (Neoadj) therapy was planned and received in fewer pts than adjuvant (Adj) and palliative (Pal) therapies. Radiotherapy was used for more pts in LA (26%) than elsewhere (5–16%). Fluoropyrimidines (Fp) (mostly 5-fluorouracil) remained the worldwide chemotherapy (CT) backbone in Adj (96%, 92–99%) and Pal (92%, 87–>99%) settings. Platinum agents (mostly cisplatin) were widely used for Pal CT (70%, 50% [NA] to 87% [IS]) and for Adj CT (35%). Anthracyclines were received by 23% pts for Pal CT (7% in AP to 31% in E), and by 11% pts for Adj CT. Globally, taxanes (docetaxel: 79%) were given to 22% of pts receiving Pal CT, including 34% of pts in AP. Conclusions: Analyses of the REGATE registry showed regional variations in the Adj and Pal treatment of GC, particularly in the use of mono- or polytherapy. Globally, 5-fluorouracil remained the most common CT backbone.

Dimethomorph (DIM) is a commonly applied morpholine fungicide, yet its potential toxicity to non-target organisms raises significant environmental concerns. This study aims to elucidate the toxicological effects of DIM on zebrafish, with a particular focus on its cardiovascular impacts. Zebrafish embryos were exposed to a range of DIM concentrations for 48 h, and their cardiac and vascular performance was meticulously assessed to determine the extent of cardiovascular toxicity. The findings revealed notable cardiac hypertrophy, evidenced by a substantial enlargement in heart size, alongside a dose-dependent reduction in heart rate. These observations suggest direct impairment of cardiac function following DIM exposure. To further investigate the molecular underpinnings of these effects, gene expression analysis was conducted using quantitative real-time PCR (qRT-PCR). The results demonstrated significant alterations in the expression of key genes associated with cardiovascular development and function, providing mechanistic insights into DIM’s toxic effects. In addition to cardiac abnormalities, DIM exposure led to a significant increase in the metabolic rate of the zebrafish embryos, indicating a potential disruption in energy homeostasis. To explore possible protective measures, a rescue experiment was performed using Astaxanthin, a potent antioxidant. Notably, Astaxanthin treatment partially mitigated the observed cardiac and metabolic phenotypes, suggesting its potential as a therapeutic agent to counteract DIM-induced toxicity. In summary, this study provides compelling evidence of the cardiovascular toxicity of DIM in zebrafish, highlighting its potential to disrupt cardiac function and metabolic regulation. The observed effects underscore the importance of re-evaluating the environmental impact of DIM and emphasize the need for further research to fully understand its mechanisms of toxicity. The findings also suggest that Astaxanthin (AST) could serve as a protective agent against DIM-induced toxicity, opening avenues for future studies aimed at mitigating the adverse effects of this widely used fungicide. This research study contributes to the growing body of knowledge on the environmental and health risks associated with pesticide use, advocating for more stringent regulations and safer alternatives.