The role of Box A of HMGB1 in producing γH2AX associated DNA breaks in lung cancer.

An ideal chemotherapeutic agent damages DNA, specifically in cancer cells, without harming normal cells. Recently, we used Box A of HMGB1 plasmid as molecular scissors to produce DNA gaps in normal cells. The DNA gap relieves DNA tension and increases DNA strength, preventing DNA double-strand breaks (DSBs).

Altered Methylation Levels in LINE-1 in Dental Pulp Stem Cell-Derived Osteoblasts.

Objectives: Long interspersed nuclear element-1 (LINE-1) and Alu elements are major targets of methylation, an epigenetic mechanism that is associated with several biological processes. Alterations of methylation of LINE-1 and Alu have been reported in cancers, diseases, and ageing. However, these alterations have not been studied in osteogenic differentiation of dental pulp stem cells (DPSCs), which are a promising source of tissue regeneration.

Alu methylation level, morphological, and senescence changes during in vitro aging of human dental pulp stem cells.

Introduction: Human dental pulp stem cells (DPSCs) are pivotal in tissue engineering and cell-based therapies due to their significant differentiation potential and accessibility. A major challenge in in vitro cell expansion is their replicative senescence, which impacts their regeneration and differentiation capabilities. While genetic factors influence these processes, epigenetic regulations such as Alu methylation also play crucial roles.

Box A of HMGB1 Maintains the DNA Gap and Prevents DDR-induced Kidney Injury in D-galactose Induction Rats.

Background/aim: Disability and mortality rates for renal failure are still increasing. DNA damage and oxidative stress intoxication from body metabolism, high blood glucose, or the environment cause significant kidney damage. Recently, we reported that Box A of HMGB1 (Box A) acts as molecular scissors, producing DNA gaps that prevent DNA damage in kidney cell lines and ultimately reverse aging phenotypes in aging rat models.

The high FKBP1A expression in WBCs as a potential screening biomarker for pancreatic cancer.

Given the limitation of current routine approaches for pancreatic cancer screening and detection, the mortality rate of pancreatic cancer cases is still critical. The development of blood-based molecular biomarkers for pancreatic cancer screening and early detection which provide less-invasive, high-sensitivity, and cost-effective, is urgently needed. The goal of this study is to identify and validate the potential molecular biomarkers in white blood cells (WBCs) of pancreatic cancer patients.

Changes in immune cell subtypes during ageing.

Background: The immune system comprises many different types of cells, each with different functions and properties during immune defence. The numbers and types of immune cells in the circulation is highly dynamic and regulated by infections, ageing and certain types of cancers. It is recognised that immune function decreases during ageing, but the biological age at which these functional changes occur is variable, and how ageing affects the different sub-types of lymphocytes, monocytes and NK cells in the circulation is not fully defined.

CpG methylation changes in Alu repetitive sequences in normal aging due to diastolic hypertension in human dermal fibroblasts from the facial area.

Aging fibroblasts, an important factor contributing to skin aging, are affected by numerous mechanisms, including alterations in DNA methylation and age-related diseases. The current study aimed to investigate the role of Alu methylation in aging fibroblasts and hypertension. The Alu methylation levels in dermal fibroblasts obtained from patients of different ages and blood pressure status were analyzed using the combined bisulfite restriction analysis technique.

The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus.

Naturally occurring DNA gaps have been observed in eukaryotic DNA, including DNA in nondividing cells. These DNA gaps are found less frequently in chronologically aging yeast, chemically induced senescence cells, naturally aged rats, D-galactose-induced aging model rats, and older people. These gaps function to protect DNA from damage, so we named them youth-associated genomic stabilization DNA gaps (youth-DNA-gaps).

Decreased Alu methylation in type 2 diabetes mellitus patients increases HbA1c levels.

Introduction: Alu hypomethylation is a common epigenetic process that promotes genomic instability with aging phenotypes, which leads to type 2 diabetes mellitus (type 2 DM). Previously, our results showed significantly decreased Alu methylation levels in type 2 DM patients. In this study, we aimed to investigate the longitudinal changes in Alu methylation levels in these patients.

The Role of Box A of in Enhancing Stem Cell Properties of Human Mesenchymal Cells: A Novel Approach for the Pursuit of Anti-aging Therapy.

Background/aim: Box A is a highly conserved DNA-binding domain of high-mobility group box 1 (HMGB1) and has been shown to reverse senescence and aging features in many cell models. We investigated whether the activation of box A can influence stem cell properties.

Materials And Methods: Human dermal papilla (DP) cells and primary human white pre-adipocytes (HWPc) were employed as mesenchymal cell models.

High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma.

Objective:  4-1BB is a costimulatory immune-activating molecule. Increased amounts of this protein have previously been found in the plasma of patients with oropharyngeal and oral cancer. Here, we focused on this molecule that functions as part of the immune system.

Identification and validation of a novel ferroptosis-related gene signature for prognosis and potential therapeutic target prediction in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a highly heterogeneous and aggressive malignancy of the bile ducts with a poor prognosis and high mortality rate. Effective targeted therapy and accurate prognostic biomarkers are still lacking. Ferroptosis is a form of regulated cell death implicated in cancer progression and has emerged as a potential therapeutic target in various cancers.

Associations between maternal plasma zinc concentrations in late pregnancy and LINE-1 and Alu methylation loci in the young adult offspring.

Background: In animal models, prenatal zinc deficiency induced epigenetic changes in the fetus, but data in humans are lacking. We aimed to examine associations between maternal zinc levels during pregnancy and DNA methylation in LINE-1 and Alu repetitive sequences in young adult offspring, as well as anthropometry and cardiometabolic parameters.

Methods: Participants were 74 pregnant women from the Chiang Mai Low Birth Weight cohort, and their offspring followed up at 20 years of age.

Upregulation of p16INK4A in Peripheral White Blood Cells as a Novel Screening Marker for Colorectal Carcinoma.

Objective: Screening of colorectal cancer (CRC) is important for the early detection. CRC is relating to aging and immuno-senescence. One such senescent marker is p16INK4A expression in immune cells.

Breast Cancer Sera Changes in Alu Element Methylation Predict Metastatic Disease Progression.

Background/aim: During metastatic disease development, the cancer-immune system crosstalk induces epigenetic modifications to immune cells, impairing their functions. Recently, Alu elements methylation changes were widely studied in terms of early cancer detection. This study aimed to demonstrate in vitro Alu element methylation changes in peripheral immune cells in a metastatic setting and examine their prognostic values in metastatic breast cancer.

Differential expression of immune-regulatory proteins C5AR1, CLEC4A and NLRP3 on peripheral blood mononuclear cells in early-stage non-small cell lung cancer patients.

Changes in gene expression profiling of peripheral blood mononuclear cells (PBMC) appear to represent the host's response to the cancer cells via paracrine signaling. We speculated that protein expression on circulating T-lymphocytes represent T-lymphocyte trafficking before infiltration into the tumor microenvironment. The possibility of using protein expression on circulating T-lymphocytes as a biomarker to discriminate early-stage non-small cell lung cancer (NSCLC) was explored.

Identification of Shared Neoantigens in -Related Breast Cancer.

Personalized neoantigen-based cancer vaccines have been shown to be safe and immunogenic in cancer patients; however, the manufacturing process can be costly and bring about delays in treatment. Using off-the-shelf cancer vaccines targeting shared neoantigens may circumvent these problems. Unique mutational signatures and similar phenotypes found among -mutated breast cancer make it an ideal candidate for discovering shared neoantigens within the group.

Immune-associated plasma proteins in oral and oropharyngeal cancer patients.

Background: Plasma protein patterns differ between cancer patients and healthy donors. This study aimed to examine the plasma levels of several cytokines and immunological checkpoint proteins between patients with oral and oropharyngeal cancer and healthy donors.

Materials And Methods: Plasma samples from healthy donors, oral cancer patients, and oropharyngeal cancer patients were analyzed using the Human Th Cytokine Panel 13-plex (IL-2, 4, 5, 6, 9, 10, 13, 17A, 17F, 21, 22, IFN-γ, and TNF-α) and Human Immune Checkpoint Panel1 12-plex [sCD25 (IL-2Ra), 4-1BB, sCD27, B7.

Alu hypomethylation in naturally and surgically postmenopausal women; a cross-sectional study.

Menopause, which may accelerate the hallmarks of the natural aging process, represents a point in time characterized by the permanent cessation of menstruation following the loss of ovarian estrogen production. Unlike natural menopause, which is characterized by a gradual decrease in estrogen production, when both ovaries are removed before the natural age of menopause, the onset of estrogen deprivation is abrupt. Further, a decrease in genome methylation frequently occurs in aging cells, and the major interspersed repetitive DNA elements in humans are Alu elements.

Magnetic bioassembly platforms for establishing craniofacial exocrine gland organoids as aging in vitro models.

A multitude of aging-related factors and systemic conditions can cause lacrimal gland (LG) or salivary gland (SG) hypofunction leading to degenerative dry eye disease (DED) or dry mouth syndrome, respectively. Currently, there are no effective regenerative therapies that can fully reverse such gland hypofunction due to the lack of reproducible in vitro aging models or organoids required to develop novel treatments for multi-omic profiling. Previously, our research group successful developed three-dimensional (3D) bioassembly nanotechnologies towards the generation of functional exocrine gland organoids via magnetic 3D bioprinting platforms (M3DB).

Mononucleotide A-repeats may Play a Regulatory Role in Endothermic Housekeeping Genes.

Background: Coding and non-coding short tandem repeats (STRs) facilitate a great diversity of phenotypic traits. The imbalance of mononucleotide A-repeats around transcription start sites (TSSs) was found in 3 mammals: , and .

Principal Findings: We found that the imbalance pattern originated in some vertebrates.

The association between Alu hypomethylation and the severity of hypertension.

Introduction: Epigenetic changes that cause genomic instability may be the basis of pathogenic processes of age-associated noncommunicable diseases (NCDs). Essential hypertension is one of the most common NCDs. Alu hypomethylation is an epigenetic event that is commonly found in elderly individuals.

Human RNA-directed DNA methylation methylates high-mobility group box 1 protein-produced DNA gaps.

DNA sequences around HMGB1-produced DNA gaps are hypermethylates. DNA methylation of interspersed repetitive sequences (IRS) such as elements can be established through AGO4-mediating, RNA-directed DNA methylation (RdDM). HMGB1 depletion, DNA gap reduction and global hypomethylation promote genomic instability.