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.

The incidence of cardia gastric cancer (CGC) is rising worldwide, particularly in East Asia. There has been a debate over whether Helicobacter pylori (H. pylori) constitutes a risk factor for CGC. This study aimed to evaluate the relative risk of H. pylori infection and CGC in Asian countries.

Relevant studies examining H. pylori and CGC were searched in PubMed, Embase, and Web of Science from their inception to June 30, 2024. Either a random-effect model or a fixed-effect model was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analyses and assessments of publication bias were performed. The stability of results was evaluated in cases where publication bias was detected.

A total of 24 studies were included in the meta-analysis. A significant association between H. pylori and CGC was observed (OR = 2.20, 95% CI 1.73–2.80). In a subgroup analysis of different countries, a significant association was observed in East Asian countries, including China (OR = 2.12, 95% CI 1.63–2.77), Japan (OR = 2.21, 95% CI 1.16–4.20), and Korea (OR = 2.36, 95% CI 1.58–3.54), but not in Iran (OR = 1.48, 95% CI 0.77–2.84). The pooled OR from five prospective cohort studies revealed a strong association between H. pylori and CGC (OR = 2.32, 95% CI 1.47–3.66).

East Asia bears a significant burden of H. pylori-related CGC. A clear association between H. pylori infection and CGC was observed in this region.

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.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with difficulties in early diagnosis, poor prognosis, and limited effective therapies. Early detection and effective treatment offer the optimal chance to improve survival rates. Various studies have shown that gut microbiota dysbiosis is closely related to PDAC, with potential mechanism involving immune regulation, metabolic process impact, and reshaping the tumor microenvironment. A comprehensive understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy such as fecal microbiota transplantation, creating new opportunities and fostering hope for desperate PDAC patients.

Despite the large number of cancer chemotherapeutics, cancer treatment is still not very satisfactory. Immune checkpoint inhibition has emerged as a new ray of hope in the immunotherapy approach for cancer treatment. Immune checkpoint inhibitors are molecules located on the surface of immune cells that regulate unnecessary immune responses and keep autoimmune reactions in check. Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 and anti-programmed cell death ligand-1, have been employed to activate receptors on immune cells like T-cells, which can deactivate the immune checkpoint and thus reactivate them against cancer cells. However, ICI therapy has limitations, including resistance development in patients, its suitability for all patients, multiple organ disorders, and hyper-progression. Therefore, understanding the chemical structures of small molecule ICIs may aid in designing and developing novel ICIs with improved efficacy and efficiency for cancer chemotherapy. This review’s novelty lies in its summary of the U.S. Food and Drug Administration-approved drugs, repurposed drugs, candidate drugs used alone or in combination with monoclonal antibodies, and novel potential lead molecules under preclinical investigation, which may be useful for designing new chemical entities as ICIs. The review describes 10 different drugs approved by the U.S. Food and Drug Administration that have demonstrated immune checkpoint inhibition targeting the programmed cell death ligand-1/programmed cell death protein-1 signaling, CTLA-4/CD28, TIGIT/PVR, and CD47/SIRPα pathways, as well as three repurposed drugs, 11 candidate drugs, and nine drugs in combination with monoclonal antibodies that are in various phases of clinical trials.

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.

Thrombocytopenia in cirrhosis presents significant challenges in clinical practice. To help clinicians rapidly understand and standardize the diagnosis and treatment of this condition, the Liver Fibrosis, Cirrhosis, and Portal Hypertension Group under the Chinese Society of Hepatology, Chinese Medical Association, convened experts across relevant fields to formulate the Expert Consensus for the Management of Thrombocytopenia in Cirrhosis. This consensus aimed to provide evidence-based guidance for clinical diagnosis and treatment.

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.

The diagnostic value of primary biliary cholangitis (PBC)-specific antibodies in patients with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, and other identifiable causes, was unclear. Our study aimed to determine whether etiological treatments in PBC-specific antibody-positive patients could improve liver biochemical tests, thereby distinguishing them from individuals with PBC.

We enrolled patients who were positive for PBC-specific antibodies and elevated ALP and/or GGT levels but with other identifiable etiologies. Changes in liver biochemistry following non-ursodeoxycholic acid etiological treatments were monitored.

A total of 155 patients with positive PBC-specific antibodies and elevated ALP and/or GGT levels due to non-PBC diseases were enrolled. Among them, 100 patients were diagnosed with non-PBC liver diseases, mainly metabolic-associated fatty liver disease, drug-induced liver injury, and autoimmune hepatitis. Additionally, 55 patients had non-liver diseases, predominantly connective tissue diseases. The median follow-up duration was 15.9 (4.7–25.6) months. Among 141 patients who completed follow-up after receiving etiological treatments, 85.1% (120/141) showed improvement in ALP and/or GGT levels, with 51.8% (73/141) achieving normalization of both ALP and GGT. However, 68 patients continued to exhibit elevated ALP and/or GGT, with 55 patients displaying isolated GGT elevation and 11 patients showing liver histological changes not consistent with PBC.

PBC-specific antibodies, along with elevated ALP and GGT levels, may occur in various non-PBC diseases. Etiological treatments may improve or even resolve cholestatic biochemistry. For these patients, initiating etiological treatment rather than immediately starting ursodeoxycholic acid therapy would be justified.