Association of hypomethylation of LINE-1 repetitive element in blood leukocyte DNA with an increased risk of hepatocellular carcinoma

Global DNA hypomethylation has been associated with increased risk for cancers of the colorectum,bladder,breast,head and neck,and testicular germ cells.The aim of this study was to examine whether global hypomethylation in blood leukocyte DNA is associated with the risk of hepatocellular carcinoma (HCC).A total of 315 HCC cases and 356 age-,sex-and HBsAg status-matched controls were included.Global methylation in blood leukocyte DNA was estimated by analyzing long interspersed element-1 (LINE-1) repeats using bisulfite-polymerase chain reaction (PCR) and pyrosequencing.We observed that the median methylation level in HCC cases (percentage of 5-methylcytosine (5mC)=77.7%) was significantly lower than that in controls (79.5% 5mC) (P=0.004,Wilcoxon rank-sum test).The odds ratios (ORs) of HCC for individuals in the third,second,and first (lowest) quartiles of LINE-1 methylation were 1.1 (95% confidence interval (CI) 0.7-1.8),1.4 (95% CI 0.8-2.2),and 2.6 (95% CI 1.7-4.1) (P for trend <0.001),respectively,compared to individuals in the fourth (highest) quartile.A 1.9-fold (95% CI 1.4-2.6) increased risk of HCC was observed among individuals with LINE-1 methylation below the median compared to individuals with higher (>median) LINE-1 methylation.Our results demonstrate for the first time that individuals with global hypomethylation measured in LINE-1 repeats in blood leukocyte DNA have an increased risk for HCC.Our data provide the evidence that global hypomethylation detected in the easily obtainable DNA source of blood leukocytes may help identify individuals at risk of HCC.

Neuroimaging and neuroendocrine insights into foodcravings and appetite interventions in obesity

This article reviews the previous studies on the distinction between food cravings and appetite,and how they are regulated by hor-mones and reflected in brain activity.Based on existing research,food cravings are defined as individual preferences influenced by hormones and psychological factors,which differ from appetite,as they are not necessarily related to hunger or nutritional needs.The article also evaluates the neuroimaging findings about food cravings,and interventions to reduce food cravings,such as mindfulness training,alternative sweeteners,non-invasive brain stimulation techniques,cognitive-behavioral therapy,and imaginal retraining,and points out their advantages,disadvantages,and limitations.Furthermore,the article delves into the potential future directions in the field,emphasizing the need for a neuroendocrine perspective,considerations for associated psychiatric disorders,innovative clinical interventions,and emerging therapeutic frontiers in obesity management.The article outlines the neuro-endocrine basis of food cravings,including ghrelin,leptin,melanocortin,oxytocin,glucagon-like peptide-1,baclofen,and other hormones and their brain regions of action.The article argues that food cravings are an important target for obesity,and more research is needed to explore their complex characteristics and mechanisms,and how to effectively interact with their neuro-endocrine pathways.The article provides a new perspective and approach to the prevention and treatment of obesity.