The dysfunction of immune cell development often impairs immunological homeostasis, thus causing various human diseases. Accumulating evidence shows that the development of different immune cells from hematopoietic stem cells are highly fine-tuned by different epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodeling and RNA-related regulations. Understanding how epigenetic regulators modulate normal development of immune cells contributes to the identification of new strategies for various diseases. Here, we review recent advances suggesting that epigenetic modulations can orchestrate immune cell development and functions through their impact on critical gene expression. We also discuss the aberrations of epigenetic modulations in immune cells that influence tumor progression, and the fact that underlying mechanisms affect how epigenetic drugs interfere with tumor progression in the clinic.

The occurrence rate of frailty is high among patients with chronic diseases. However, the assessment of frailty among these patients is still far from being a routine part of clinical practice. The aim of this study is to develop a validated predictive model for assessing frailty risk in patients with chronic illnesses. This study recruited 543 patients with chronic diseases, and 237 were included in the development and validation of the predictive model. A total of 57 frailty related indicators were analyzed, encompassing sociodemographic variables, health status, physical measurements, nutritional assessment, physical activity levels, and blood biomarkers. There were 100 cases (42.2%) presenting frailty symptoms. Multivariate logistic regression analysis revealed that gender, age, chronic diseases, Mini Nutritional Assessment score, and Clinical Frailty Scale score were predictive factors for frailty in chronic disease patients. Utilizing these factors, a nomogram model demonstrated good consistency and accuracy. The AUC values for the predictive model and validation set were 0.946 and 0.945, respectively. Calibration curves, ROC, and DCA indicated the nomogram had favorable predictive performance. Altogether, the comprehensive nomogram developed here is a promising and convenient tool for assessing frailty risk in patients with chronic diseases, aiding clinical practitioners in screening high-risk populations.

Frailty is a common medical syndrome which largely increases the risk of disability, depression, falls, hospitalization and mortality. An increasing number of research suggests that frailty is reversible by medical interventions at its early stage. Therefore, efficient detection is utterly important for frail population. Since numerous biological processes have been indicated in frail population, the critical regulators in these biological processes could provide biomarkers for early detection or treatment for frailty. The brain-derived neurotrophic factor (BDNF) has been associated with several biological process ranging from cognitive function to inflammation, therefore it could be an important regulator for frailty. In this review, we would discuss the mechanism association between different indicators of frailty and BDNF. Furthermore, we summarize the approaches to interfere with BDNF in healthy and pathologic condition, which could lead to identification of potential interventional strategies for frailty.

Although leucine zipper tumour suppressor 1 (LZTS1) has been considered a potential tumour suppressor, accumulating evidence suggests that LZTS1 is highly expressed in many cancer types. To unravel the exact role of LZTS1 in colorectal carcinogenesis, we performed the bioinformatic analysis of LZTS1, including expression differences, correlations between expression levels and survival, methylation status of LZTS1 promoter and related cellular pathways based on TCGA dataset, GEO databases and our own CRC patient cohort. Furthermore, we confirmed the oncogenic function of LZTS1 in human mammalian cells by employing a series of assays including tissue microarray, immunoblotting, cell proliferation and migration assay. We found that the expression of LZTS1 is higher in tumour samples compared to paired normal tissue in CRC cancer and its different clinical subtypes, which is, at least in part, due to the low methylation status of LZTS1 promoter in CRC tumour samples. Functional analysis identified the close relationship between high expression of LZTS1 and PI3K‐AKT pathway and the epithelial–mesenchymal transition (EMT) process. Consistently, we found that the expression of LZTS1 positively correlated with the expression PIK3CD, N‐cadherin in CRC tumour samples, while the expression of LZTS1 negatively correlated with the expression of E‐cadherin and PTEN in CRC tumour samples. Experimental data further confirmed that overexpression of LZTS1 upregulated activity of AKT and promoted EMT process. Furthermore, depletion of LZTS1 repressed the proliferation and migration rate of CRC cells. Thus, this study indicates that LZTS1 plays an oncogenic role in colorectal carcinogenesis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The vascular endothelial cells (VECs) play a pivotal role in the progression of sepsis-induced vascular leakage. While therapeutic strategies targeting pathogen elimination and inflammation exist, direct interventions on the endothelial barrier are limited. The mechanisms of endothelial damage related to mitochondrial dysfunction during sepsis require further elucidation. The study utilized a cecal ligation and puncture (CLP) rat model of sepsis and lipopolysaccharide (LPS)-stimulated VECs to investigate vascular leakage mechanisms. These models were utilized to investigate the changes in vascular permeability, mitochondrial function and protein crotonylation in VECs, aiming to identify potential therapeutic targets for sepsis. In septic rats, significant lung injury and increased vascular leakage were observed, linked to mitochondrial dysfunction and decreased survival rates. A marked downregulation of Platelet Activating Factor Acetylhydrolase 2 (PAFAH2) in VECs was identified post-sepsis, causing an upregulation of Enoyl-CoA Hydratase, Short Chain 1 (ECHS1), which inhibited crotonylation and compromised mitochondrial function, leading to increased apoptosis of VECs. Restoration experiments showed that modulating PAFAH2 and ECHS1 levels could mitigate these adverse effects. PAFAH2 overexpression alleviated sepsis-induced vascular leakage by downregulating ECHS1 and enhancing crotonylation. The study identifies the PAFAH2-ECHS1 pathway as a critical axis in sepsis-induced vascular leakage, influencing mitochondrial function and crotonylation, which leads to endothelial apoptosis. These insights could guide the development of new therapies targeting the endothelial barrier for treating sepsis.