Oral squamous cell carcinoma (OSCC) is a predominant type of head and neck cancer in the Indian subcontinent, mostly observed among tobacco and/or alcohol users. Oral leukoplakia (OLK) does not seriously affect patients, so it is often ignored in treatment. Some studies have reported genomic alterations and expression deregulation that drive OLK towards OSCC, conducted in two types of studies based on sample collection from (a) disparate or (b) the same patients. Demographic, tobacco/alcohol habits and biological factors may vary significantly if OLK and OSCC samples are collected from disparate patients, but they remain consistent if both tissue samples are from the same patient. Earlier, both targeted candidate gene-based and large-scale omics-based studies identified somatic mutations in TP53, CDKN2A, and PTEN, as well as broad arm-level copy number alterations and epigenetically dysregulated genes in leukoplakia and tumor tissues from disparate patients. Recent omics-based studies have identified early CASP8 somatic alterations, APOBEC mutagenesis, as well as dysregulated immune cell infiltration (decreased CD8+ T cell abundance, enrichment of pro-inflammatory immune cells) as candidate driver events for oral tumor progression from leukoplakia in the same patient. Recent single-cell transcriptomic-driven studies have also identified immune-transcriptomic features as putative driving molecular events in oral tumor development and progression. Here, we reviewed reported differences in driving gene mutations and expression deregulations in disparate and same patient settings. We also highlighted the challenges in sample collection and the opportunity of genomics and transcriptome studies for their emerging role in early diagnosis and progression.

The brain-gut axis represents a bidirectional communication network that integrates neural, hormonal, and immunological signaling between the central nervous system and the gastrointestinal tract. Adverse childhood experiences (ACEs) have increasingly been recognized for their profound impact on this axis, with implications for both mental and physical health outcomes. This mini-review explores the emerging field of epigenomics—specifically, how epigenetic modifications incurred by ACEs can influence the brain-gut axis and contribute to the pathophysiology of various disorders. We examine the evidence linking epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs to the modulation of gene expression involved in stress responses, neurodevelopment, and immune function—all of which intersect at the brain-gut axis. Additionally, we discuss the emerging potential of the gut microbiome as both a target and mediator of epigenetic changes, further influencing brain-gut communication in the context of ACEs. The methodological and therapeutic challenges posed by these insights are significant. The reversibility of epigenetic marks and the long-term consequences of early life stress require innovative and comprehensive approaches to intervention. This underscores the need for comprehensive strategies encompassing psychosocial, pharmacological, neuromodulation, and lifestyle interventions tailored to address ACEs’ individualized and persistent effects. Future directions call for a multi-disciplinary approach and longitudinal studies to uncover the full extent of ACEs’ impact on epigenetic regulation and the brain-gut axis, with the goal of developing targeted therapies to mitigate the long-lasting effects on health.

Liver cancer is a digestive system malignancy that poses a significant public health challenge globally. This study aimed to analyze and compare the epidemiological trends of liver cancer attributed to hepatitis B (LCHB) and alcohol use (LCAL) over the past 32 years.

Data on mortality and disability-adjusted life years for LCHB and LCAL in China, globally, and across five sociodemographic index regions were obtained from the Global Burden of Disease 2021 database and comprehensively analyzed.

In 2021, the global and Chinese death counts and disability-adjusted life years attributed to LCHB and LCAL showed substantial increases compared to 1990. China had the highest number of deaths from LCHB and LCAL among 204 countries and regions. Gender and age disparities were notable, with males and those aged 40–75 years bearing a higher burden than females and other age groups. Global age-period-cohort analysis revealed an escalating risk of death from LCHB with age, alongside a lower risk in younger cohorts and more recent periods. The mortality risk for LCAL also increased with age but exhibited distinct cohort and period effects compared to LCHB. Decomposition analysis indicated that shifts in the global burden of LCHB and LCAL were influenced by population growth, with population aging playing a crucial role in China.

A significant burden of LCHB and LCAL persists, highlighting the need for tailored prevention, screening, and control strategies to mitigate their incidence, as well as the identification of advanced therapeutics to reduce mortality.

Liver cancer, also identified as hepatic cell carcinoma, is the fifth most prevalent kind of malignancy globally and the fourth foremost cause of cancer-associated mortality. The development and progression of liver cancer are complex processes that involve multiple genetic and environmental factors. As the diagnosis of liver cancer is still worse, with late-stage patients facing a less than 20% 5-year survival rate, there is a critical need for the development of new and effective therapeutic approaches for liver cancer. Mitochondrial alterations and mitochondrial DNA (mtDNA) mutations have long been associated with cancer pathogenesis, including liver cancer. These alterations not only disrupt cellular bioenergetics but also deteriorate the situation by modifying tumor suppressors and oncogenic proteins. Excessive reactive oxygen species generation and flaws in mitochondrial enzymes are among the factors responsible for mitochondrial dysfunction. Additionally, perturbed microRNA levels have also been linked to mtDNA dysfunction and reactive oxygen species generation. Various pharmacological approaches to target mitochondrial dysfunction and mtDNA mutations in cancer have been proposed as potential therapeutic strategies. These approaches include targeting the electron transport chain, which is responsible for the production of adenosine triphosphate in the mitochondria, or transcriptional inhibition of various proteins involved in the mitochondrial biogenesis pathway. Overall, mtDNA is a crucial component of the cell, and alterations in mtDNA make it an attractive target for therapeutic interventions. Hence, we advocate that understanding the role of mtDNA in cancer pathogenesis is important for the development of targeted therapies for these disorders.

The brain, traditionally regarded as immune-privileged due to the blood-brain barrier, harbors a sophisticated immune system crucial for maintaining neural health and resilience against various challenges. Microglia, the resident immune cells of the central nervous system, actively monitor their environment, participating in immune surveillance, synaptic pruning, and neuroprotection. Astrocytes also play vital roles by regulating neurotransmitter levels, supporting metabolism, and maintaining the blood-brain barrier integrity. Recent research underscores the involvement of T cells and monocytes in modulating neuroinflammation and immune responses within the brain. Neurological disorders such as Alzheimer’s and Parkinson’s disease highlight the brain’s vulnerability to immune dysregulation. This review aimed to elucidate the role of neuroimmune cells in brain health and the progression of neurological diseases. It aimed to identify critical mechanisms to enhance therapeutic strategies and improve outcomes. Understanding these interactions is essential for developing targeted therapies to mitigate neuroinflammation and preserve cognitive functions. This review critically examines neuroinflammation related to aging and disease, with a focus on neuroimmune cells and their underlying mechanisms. It highlights how chronic inflammation, driven by activated microglia and astrocytes, exacerbates neuronal damage, synaptic dysfunction, and cognitive decline. The disruption of immune privilege in these conditions involves complex pathways that trigger inflammatory responses, impairing essential neural functions. Despite its immune-privileged status, the brain’s immune system, primarily involving microglia and astrocytes, is crucial for maintaining homeostasis and managing illness. Our review strongly suggests that neurological diseases, influenced by genetic, environmental, and aging factors, often involve heightened neuroinflammation. Targeted therapies are needed to address infections, chronic inflammation, and environmental impacts. Additionally, research into mental health disorders and advancements in imaging techniques are critical for understanding immune dysfunction and enhancing treatment strategies.

Fuzi, the processed product of daughter roots of Aconitum carmichaelii Debx., is a well-known Chinese medicine for the treatment of heart failure (HF) and related cardiac diseases. This study aimed to investigate the molecular mechanism of the cardioprotective effects of Fuzi water decoction (FWD) and Fuzi water-soluble alkaloids (FWA) on the model of HF.

The HF model of rats was prepared through intravenous injection of propafenone hydrochloride. The normal group, model group, FWD-treated groups (1.25 g/kg, 2.5 g/kg, 5 g/kg) and positive group (Shenfu Injection, 3.3 mL/kg) were set up. Heart rate, LV+dp/dtmax, and LV-dp/dtmax were recorded at 5 m, 10 m, 20 m, 30 m, and 60 m after drug administration, respectively. The contents of atrial natriuretic peptide, brain natriuretic peptide (BNP), angiotensin II, and aldosterone in serum were determined 20 m post-administration. An in vitro cardiomyocyte hypertrophy model with HDAC2 overexpression was constructed and verified by lentivirus transfection. The experiment included a blank group, FWD-treated groups (3 mg/mL, 1.5 mg/mL), and FWA-treated groups (4 mg/mL, 2 mg/mL). For transcriptome analysis, the model group, blank group, and FWD-treated group (2.5 g/kg) at 20 m and 60 m in vivo, and different dose groups in vitro, were selected to analyze the therapeutic mechanisms of FWD and FWA.

All FWD treatment groups showed an increased heart rate, among which the groups with 2.5 g/kg and 5 g/kg FWD showed better effects, significantly increasing LV+dp/dtmax and LV-dp/dtmax after 20 m of administration and significantly reducing BNP and aldosterone serum levels. In the constructed cardiomyocyte hypertrophy model, HDAC2 expression, atrial natriuretic peptide and BNP protein levels, and cell surface area increased. Transcriptome data from both in vivo and in vitro showed that FWD and FWA could exert cardioprotective effects through pathways such as the PI3K-Akt signaling pathway, NF-κB signaling pathway, and ATP-binding cassette (ABC) transporters, involving key genes such as ITGB1, TLR2, and CDKN1A. Fuzi inhibited the hypertrophic gene HDAC2. Additionally, based on weighted gene co-expression network analysis, ABC transporters may be an important molecular pathway for FWA in treating HF.

Both FWD and FWA can ameliorate HF by regulating apoptosis, proliferation, and anti-fibrosis, with ABC transporters potentially being the main pathway for the action of FWA.

Alzheimer’s disease (AD), an enduring neurodegenerative malady, contributes significantly to dementia cases, with late-onset AD being more common than early-onset AD. Despite extensive research to diagnose and treat AD, the intricate protein network impedes the development of efficacious drugs or targets. This study endeavored to identify previously undiscovered genetic reservoirs associated with AD progression, which could be targeted as therapeutic markers.

Employing the robust tools of R-language, we dissected vast RNA sequence datasets comprising numerous samples and thousands of genes, pinpointing potential candidates implicated in AD’s trajectory. Thus, we selected the GSE203206 dataset, which includes AD patients and non-dementia controls, based on our criteria. After normalization, RNA-Seq data was compared, and log2fold change was calculated to determine the highly dysregulated genes. Further network analysis of genes and their associated miRNA was performed to determine a characteristic change in control and patient groups.

Differential expression analysis revealed 13 dysregulated genes in AD, wherein 12 were upregulated, and one was down-regulated. Furthermore, we identified hsa-miR-30-5p as a significant miRNA associated with AD, aligning with previous studies and highlighting its high involvement.

This investigation has unveiled four novel genes and a paramount miRNA implicated in AD, thus furnishing potential targets for therapeutic interventions. These discoveries pave the way for further exploration into the intricate functions and implications of these genetic entities in AD.

Glutathione peroxidase 4 (GPX4) is a key factor in ferroptosis, which is involved in ischemia-reperfusion injury. However, little is known about its role in hepatic ischemia-reperfusion injury (HIRI). This study aimed to investigate the role of GPX4 methylation in ferroptosis during HIRI.

For the in vitro experiments, an oxygen and glucose deprivation cell model was established. For the in vivo experiments, an ischemia-reperfusion model was created by subjecting mice to simulated HIRI. Ferroptosis occurrence, GPX4 promoter methylation, and global methylation levels were then assessed.

Ferroptosis was observed in oxygen and glucose deprivation, characterized by a significant decrease in cellular viability (P < 0.05), an increase in lipid peroxidation (P < 0.01), iron overload (P < 0.05), and down-regulation of GPX4 (P < 0.05). This ferroptosis was exacerbated by GPX4 knockdown (P < 0.01) and mitigated by exogenous glutathione (P < 0.01). Similarly, ferroptosis was evident in mice subjected to HIRI, with a down-regulation of GPX4 mRNA and protein expression (all P < 0.01), and an upregulation of acyl-CoA synthetase long-chain family member 4 mRNA and protein (all P < 0.01), as well as prostaglandin-endoperoxide synthase 2 mRNA and protein expression (all P < 0.05). Methylation levels increased, evidenced by upregulation of DNA methylation transferase expression (P < 0.05) and down-regulation of Ten-eleven translocation family demethylases (P < 0.01), along with an upregulation of GPX4 promoter methylation.

Ferroptosis may be the primary mode of cell death in hepatocytes following ischemia-reperfusion injury. The methylation of the GPX4 promoter and elevated levels of global hepatic methylation are involved in the regulation of ferroptosis.

T-cell receptor (TCR) sequencing provides a novel platform for insight into and characterization of intricate T-cell profiles, advancing the understanding of tumor immune heterogeneity. Recently, transarterial chemoembolization (TACE) combined with systemic therapy has become the recommended regimen for advanced hepatocellular carcinoma. The regulation of the immune microenvironment after TACE and its impact on tumor progression and recurrence has been a focus of research. By examining and tracking fluctuations in the TCR repertoire following combination treatment, novel perspectives on the modulation of the tumor microenvironment post-TACE and the underlying mechanisms governing tumor progression and recurrence can be gained. Clarifying the distinctive metrics and dynamic alterations of the TCR repertoire within the context of combination therapy is imperative for understanding the mechanisms of anti-tumor immunity, assessing efficacy, exploiting novel treatments, and further advancing precision oncology in the treatment of hepatocellular carcinoma. In this review, we initially summarized the fundamental characteristics of TCR repertoire and depicted immune microenvironment remodeling after TACE. Ultimately, we illustrated the prospective applications of TCR repertoires in TACE combined with systemic therapy.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin (AAT) within hepatocytes, which limits its access to the circulation and exposes the lungs to protease-mediated tissue damage. This results in progressive liver disease secondary to AAT polymerization and accumulation, and chronic obstructive pulmonary disease (COPD) due to deficient levels of AAT within the lungs. Our goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene expression.

A subcohort of AATD individuals with COPD (n = 33) and AATD individuals without COPD (n = 14) were evaluated in this study from our previously reported cross-sectional cohort. We used immunohistochemistry to assess the AATD liver phenotype, and RNA sequencing to explore liver transcriptomics. We observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those without.

A total of 339 genes were differentially expressed. Canonical pathways related to fibrosis, extracellular matrix remodeling, collagen deposition, hepatocellular damage, and inflammation were significantly upregulated in the livers of AATD individuals with COPD. Histopathological analysis also revealed higher levels of fibrosis and hepatocellular damage in these individuals.

Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is present. We believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.