High-mobility group box-1 (HMGB1) is an architectural chromosomal protein with various roles depending on its cellular localization. Extracellular HMGB1 functions as a prototypical damage-associated molecular pattern that triggers inflammation and adaptive immune responses, mediated by specific cell surface receptors, including receptors for advanced glycation end products and toll-like receptors. Post-translational modifications of HMGB1 significantly impact various cellular processes that contribute to the pathogenesis of liver diseases. Recent studies have highlighted the close relationship between HMGB1 and the pathogenesis of acute liver injuries, including acetaminophen-induced liver injury, hepatic ischemia-reperfusion injury, and acute liver failure. In chronic liver diseases, HMGB1 plays a role in nonalcoholic fatty liver disease, alcohol-associated liver disease, liver fibrosis, and hepatocellular carcinoma. Targeting HMGB1 as a therapeutic approach, either by inhibiting its release or blocking its extracellular function, is a promising strategy for treating liver diseases. This review aimed to summarize the available evidence on HMGB1’s role in liver disease, focusing on its multifaceted signaling pathways, impact on disease progression, and the translation of these findings into clinical interventions.

Drug-induced hepatotoxicity is a significant clinical issue worldwide. Given the limited treatment options for these liver injuries, understanding the mechanisms and modes of cell death is crucial for identifying novel therapeutic targets. For the past 60 years, reactive oxygen species and iron-dependent lipid peroxidation (LPO) have been hypothesized to be involved in many models of acute drug-induced liver injury. However, this mechanism of toxicity was largely abandoned when apoptosis became the primary focus of cell death research. More recently, ferroptosis—a novel, non-apoptotic form of cell death—was identified in NRAS-mutant HT-1080 fibrosarcoma cells exposed to erastin and other NRLs. Ferroptosis is characterized by glutathione depletion and the impairment of glutathione peroxidase 4 activity, which hinders the detoxification of lipid hydroperoxides. These hydroperoxides then serve as substrates for iron-dependent LPO propagation. This cell death mechanism is now receiving widespread attention, extending well beyond its original identification in cancer research, including in the field of drug-induced liver injury. However, concerns arise when such mechanisms are applied across different cell types and disease states without sufficient validation. This review critically evaluated the historical evidence for iron-dependent LPO as a mechanism of drug-induced hepatotoxicity and explored how these earlier findings have led to the current concept of ferroptosis. Overall, the published data support the idea that multi-layered endogenous antioxidant defense mechanisms in the liver limit the occurrence of pathophysiologically relevant LPO under normal conditions. Only when these defense mechanisms are severely compromised does ferroptosis become a significant mode of drug-induced cell death.

Obesity is a global health burden and is closely associated with severe chronic co-morbidities, which remain the leading causes of death. Significant progress has been made in the treatment of hypertension, diabetes, and hyperlipidemia over the last half-century. However, advancements in the management of obesity have been slow, with some medications exhibiting inadequate efficacy and dangerous side effects. Improved understanding of the gut-brain axis has inspired the pursuit of novel medications aiming to provide sustainable and safe weight loss. Current evidence-based practices for obesity management involve multi-modal approaches, including lifestyle modification, mechanical gastric restriction, modulation in the secretion of multiple gut hormones, alteration in the composition and secretion of bile acids, and alterations of the gut microbiome. Each physician is responsible for recognizing obesity as a disease and assisting patients in appropriate management based on strong evidence and a good safety profile, aligned with the patient’s goals. Through this review, we aim to inform the readers of recent approaches for managing obesity and comparing their beneficial effects and efficacy on obesity and its long-term co-morbidities.

Chronic liver disease (CLD) represents a significant global health burden, with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease, and hepatitis C virus infection—being major contributors. Recent genome-wide association studies have identified the rs72613567:TA variant in the 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) gene as a protective factor against the development and progression of these conditions. In this review, we summarized the current evidence surrounding the HSD17B13 rs72613567 variant, aiming to elucidate its impact on CLD risk and outcomes, and to explore the potential mechanisms behind its hepatoprotective effects. The rs72613567:TA variant induces a splice donor site mutation, resulting in a truncated, non-functional HSD17B13 protein. Numerous studies have demonstrated that this loss-of-function mutation confers protection against the development of cirrhosis and hepatocellular carcinoma (HCC) in patients with MASH, alcoholic liver disease, and hepatitis C virus infection. Moreover, the rs72613567:TA variant has been associated with reduced liver enzyme levels and improved survival in HCC patients. Integrating this variant into genetic risk scores has shown promise in predicting the progression of fatty liver disease to cirrhosis and HCC. Furthermore, inhibiting HSD17B13 expression through RNA interference and small molecule inhibitors has emerged as a potential therapeutic strategy for MASH. However, the precise molecular mechanisms underlying the hepatoprotective effects of the HSD17B13 rs72613567 variant remain to be fully elucidated. Future research should focus on clarifying the structure-function relationship of HSD17B13 and its role in liver pathophysiology to facilitate the development of targeted therapies for CLD associated with hepatic steatosis.

Clinical unmet need in managing nonalcoholic fatty liver disease (NAFLD), a common liver disorder affecting 25–30% of American adults is to develop noninvasive and robust biomarkers.

We re-measured liver AC by placing a region of interest (ROI, 3 cm tall and 3 cm wide) at 4.5 cm, 6 cm, and 7.5 cm from the skin and a large ROI (6.0 cm tall and 7.3 cm wide) on pre-recorded ATI images from 117 participants screened for NAFLD. The difference in AC value at variable ROI depths was tested using one-way ANOVA (analysis of variance). Diagnostic performances of AC at variable depths in determining hepatic steatosis were examined by area under receiver operating characteristic curve (AUC) using MRI-proton density fat fraction (MRI-PDFF) as reference and were compared using paired-sample Z-test.

Based on MRI-PDFF, 117 livers were divided to 27 normal livers (MRI-PDFF < 5%) or 90 steatotic livers (MRI-PDFF ≥ 5%). Differences in AUC and AC value at variable depths and size were statistically significant (p < 0.01). The best performance for determining hepatic steatosis was the AC measured at 6 cm from the skin (AUC = 0.92). Sources of errors in performing ATI included reverberation, blank color region, and acoustic shadowing within the measurement ROI.

ROI depth significantly influences liver AC estimation. The best ROI depth to measure liver AC in patients with BMI ≥ 30 may be at a depth of 6 cm from the skin. Technical considerations should be taken in performing liver ATI.

With the highest incidence rate and death rate among malignant tumors, lung cancer is the most prevalent malignant tumor worldwide. Tumor-node-metastasis (TNM) staging provides a basis for clinical therapy and prognosis while the fundamental principle of traditional Chinese medicine (TCM) is the syndrome differentiation and treatment. This study offers an objective foundation for the distinction and classification of TCM syndromes by methodically assessing the relationship between TNM staging indicators and the various types of the syndrome in lung cancer.

To find pertinent material, we searched a number of databases, including CNKI, PubMed, VIP, and Wanfang. Literature on the relationship between TCM syndrome categories and TNM staging indexes of lung cancer published from the database’s inception until May 2023 was gathered. The meta-analysis was carried out using Rev Man 5.4.

In the end, seven pieces of literature totaling 264 patients were included. Lung cancer is mainly characterized by phlegm dampness syndrome, Qi Yin deficiency syndrome, Yin deficiency internal heat syndrome, and Qi stagnation and blood stasis syndrome. In stage I and II, phlegm dampness syndrome > Yin deficiency internal heat syndrome (p < 0.5), phlegm dampness syndrome > Qi Yin deficiency syndrome (p < 0.5), phlegm dampness syndrome > Qi stagnation and blood stasis syndrome (p < 0.5). In stages III and IV, Qi Yin deficiency syndrome > Qi stagnation and blood stasis syndrome > Yin deficiency internal heat syndrome > phlegm dampness syndrome (p < 0.5).

Phlegm dampness syndrome is the main syndrome in stages I and II of lung cancer, while Qi and Yin deficiency syndromes are the main syndromes in stages III and IV of lung cancer.

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.

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.

Circulating tumor cells (CTCs), originating from primary neoplastic tissues, infiltrate blood vessels, migrate through the bloodstream, and establish secondary tumor foci. The detection of CTCs holds significant promise for early-stage identification, diagnostic precision, therapeutic monitoring, and prognostic evaluation. It offers a non-invasive approach and has broad clinical relevance in cancer management. This comprehensive review primarily focused on CTCs as biomarkers in the diagnostic, therapeutic, and prognostic surveillance of hepatocellular carcinoma, compared their correlation with key clinical parameters and the identification of gene characteristics. It also highlighted current methodologies in CTC detection. Despite approval by the U.S. Food and Drug Administration for select malignancies, the comprehensive integration of CTCs into routine clinical practice requires procedural standardization and a deeper understanding of the underlying molecular intricacies. The challenges in CTC detection, including limited quantity, technical impediments, and cellular heterogeneity, call for concerted and further investigational efforts to advance precision in cancer diagnostics and prognostication, thus realizing the objectives of precise and personalized medicine.

Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the GI tract. The etiology is unclear, and most clinical symptoms are nonspecific, making the diagnosis and prognosis of IBD challenging as there is no gold-standard diagnostic test. Both endoscopy and imaging are essential diagnostic tools for determining disease state, location, and severity. However, the high cost and invasive nature of these tests make them unrealistic for frequent assessment. Given these limitations, laboratory testing of blood and feces has proven to be a viable alternative for routine disease monitoring. To integrate more efficient and personalized treatment strategies, new studies are consistently emerging to develop minimally invasive testing that can predict disease severity and response to available treatments. The goal is to develop better predictors of disease course, response to therapy, and therapy-related adverse events, thereby establishing a more efficient and personalized treatment strategy. This review aimed to delve into existing literature to assemble a collection of currently used biomarkers that aid in monitoring treatment response, as well as highlight select novel and combined biomarkers that hold promise for future management of IBD.