This review aims to advocate for a paradigm shift in herbal safety by proposing a cohesive molecular framework that integrates advanced “omics” technologies with artificial intelligence (AI) to address the clinical challenges of herb-induced liver injury (HILI). Traditional herbal medicine constitutes a substantial, yet often unregulated, component of global healthcare, driving high patient exposure alongside a significant and escalating clinical burden of HILI. Current pharmacovigilance systems are critically undermined by fundamental deficits, including severe underreporting, unknown population denominators, and pervasive product quality failures. Furthermore, the complexity of multi-ingredient formulations and the frequency of herb-drug interactions complicate causality assessment, particularly for high-risk drugs. To bridge the gap between empirical practice and contemporary safety standards, this integrated “omics”-AI paradigm transforms herbal safety from a reactive, population-level assessment into an evidence-based, personalized system. By enabling precise risk mitigation, this approach establishes a scientifically rigorous foundation for the future of integrative liver health. In conclusion, the synergy of molecular profiling and computational intelligence provides the necessary tools to modernize herbal pharmacovigilance, ensuring that traditional wisdom is effectively harmonized with modern technological standards for enhanced patient safety.

Primary biliary cholangitis (PBC) is a chronic cholestatic disorder in which symptoms exert a direct influence on patients’ quality of life. Beyond pruritus and fatigue, patients with PBC are also prone to developing osteoporosis (OP). This skeletal condition not only heightens the likelihood of fractures but is also associated with elevated mortality. With the overall prevalence of PBC rising, a parallel increase in OP incidence among these patients can be anticipated. Early recognition, preventive strategies, and appropriate therapeutic approaches are essential for preserving patients’ quality of life. Nevertheless, current data on the management of OP in PBC remain limited. Most existing recommendations are extrapolated from studies on postmenopausal OP. However, these findings have not been effectively adapted into practical management protocols for PBC-related OP, largely due to distinct pathophysiological mechanisms between the two conditions. The absence of well-established preventive and therapeutic measures continues to represent a major obstacle in addressing OP among patients with PBC. This review offers a detailed synthesis of the epidemiology, underlying mechanisms, and therapeutic considerations of OP linked to PBC.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health concern and encompasses a spectrum ranging from hepatic steatosis and metabolic dysfunction-associated steatohepatitis to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Insulin resistance, the pathogenic cornerstone of MASLD, drives enhanced peripheral lipolysis and increased hepatic de novo lipogenesis, thereby overloading the liver with lipids and inducing steatosis. Subsequent lipotoxicity, inflammation, and gut microbiota dysbiosis further exacerbate disease progression. The gut microbiota and their metabolites communicate with the liver via the gut-liver axis, forming a complex signaling network that directly or indirectly modulates hepatic metabolism, systemic immune responses, oxidative stress, and intestinal barrier integrity. In this review, we synthesize evidence for the beneficial and detrimental effects of the major human gut microbial communities and their metabolites during the course of MASLD. We delineate how these gut-derived factors regulate hepatic function through an integrated tripartite “gut-liver axis–oxidative stress–metabolic reprogramming” mechanism. These insights may inform microbiome-based precision interventions and accelerate the development of therapeutic strategies targeting MASLD.

Cell cycle checkpoint-related genes (CCCRGs) are implicated in the development and progression of hepatocellular carcinoma (HCC). However, their precise roles and underlying mechanisms remain insufficiently characterized and require further investigation. This study aimed to explore the prognostic significance of CCCRGs in HCC, and to investigate the mechanism by which they promote the progression of HCC.

HCC datasets from The Cancer Genome Atlas and International Cancer Genome Consortium were analyzed to identify hub genes. A prognostic model was constructed and validated using Kaplan–Meier analysis, nomogram, calibration curves, decision curve analysis, and receiver operating characteristic analysis. Immune infiltration patterns were assessed using single sample gene set enrichment analysis, while pathway activities were evaluated via gene set variation analysis. Single-cell RNA sequencing data from GSE149614 were analyzed with Seurat and CellChat to investigate cell–cell communication. Patient-derived HCC specimens were examined through immunohistological evaluation, HCC cell lines were used for in vitro functional assays, and in vivo tumor growth was assessed through animal experiments.

CCCRGs showed significant associations with prognosis, malignant biological behavior, and immune responses in HCC. Centromere protein (CENP) I was identified as a critical hub gene that markedly promoted HCC proliferation, metastasis, and epithelial–mesenchymal transition, while inhibiting apoptosis. Mechanistically, CENPI suppressed YAP phosphorylation, enhancing its nuclear translocation and thereby driving malignant progression. Additionally, CENPI impaired immune effector cell infiltration, likely by disrupting tumor antigen presentation and chemokine-mediated CD8+ T cell chemotaxis, thereby promoting immune escape.

This study underscores the prognostic significance of CCCRGs in HCC and identifies CENPI as a key driver of tumor progression through the Hippo pathway. Furthermore, it reveals CENPI’s role in promoting immune escape, suggesting novel therapeutic targets for HCC treatment.

Empirical and theoretical studies can be distinguished among the areas of investigation of the renin-angiotensin-aldosterone system (RAAS) and its relationship with the development of cardiovascular diseases. Theoretical work is based mainly on the bioinformatic analysis of key elements of RAAS (genes, proteins, metabolites), on calculations and predictions of protein interactions, and on mechanisms of RAAS gene expression regulation. An associative gene network based on big data analysis allows us to reveal relationships among the proteins, regulatory pathways, and biological processes acting in RAAS, as well as to identify new diagnostic markers, therapeutic targets, putative molecular mechanisms of the development of RAAS-associated diseases, drug interactions, and drug toxicity.

The reconstruction and analysis of associative gene networks were performed using ANDSystem. The regulation of RAAS-associated gene expression was analyzed by transcription factor (TF) binding sites (TFBSs) prediction in the proximal promoters of these genes and by studying interactions between TFs themselves using the Ensembl Biomart web service and AnimalTFDB 4.0. The recognition of potential TFBSs in RAAS gene promoters was performed using MoLoTool.

According to the centrality criteria of the RAAS associative gene network, the following proteins were identified as exerting a significant influence on information interplay between network components: IL6, EDN1, TNFA, MK01, LEP, and JUN. Analysis of the ten identified TFs and their TFBSs among the genes in the RAAS network under study revealed clusters of three to 26 genes regulated by them.

Components with the highest values of centrality and vertex degrees were identified in the reconstructed associative gene network of the RAAS, and ten TFs supposed to regulate 26 RAAS genes were determined.

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family regulates fundamental processes in both innate and adaptive immunity. Aberrant NF-κB activation, whether through canonical or non-canonical signaling pathways, contributes to chronic inflammation, autoimmunity, allergy, and primary immunodeficiency/autoinflammatory syndromes, while also influencing host defense and tissue repair mechanisms. The present review aims to synthesize molecular architecture, upstream triggers, ubiquitin-centered relay systems, and the dynamic regulation of NF-κB activity. The major findings on the NF-κB signaling pathway encompass its dual molecular mechanisms (canonical and non-canonical), its central roles in immune and inflammatory responses, cell survival, and development, as well as its complex regulatory networks. We interpret NF-κB as a master integrator of diverse signals, essential for both acute and long-term physiological processes. Dysregulation of NF-κB underlies many diseases, and while it is a promising therapeutic target, its ubiquitous functions demand precise modulation to avoid adverse effects. In conclusion, the proper function of the NF-κB signaling pathway is essential for maintaining cellular homeostasis and immune defense; its dysregulation is linked to chronic inflammatory diseases, autoimmune disorders, and cancer, which underscores the pathway’s significance as a therapeutic target. Although it elucidates molecular processes and treatment options, experimental validation of emerging therapeutic concepts such as ubiquitin code editing and spatial immunology remains limited.

Hepatic metastasis (HM) and lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC) are associated with worse overall survival, largely due to the immunosuppressive microenvironment. However, the key immunosuppressive cells within this microenvironment remain inadequately defined. This study aimed to identify the cells contributing to HM and lymph node metastasis in PDAC and to investigate their regulatory mechanisms.

Single-cell RNA sequencing was used to profile the tumor microenvironment in HM, lymph node-negative, and lymph node-positive (LNP) PDAC tissues. Bioinformatic analyses revealed subtypes of immunosuppressive myeloid-derived suppressor cells (MDSCs). Immunofluorescence and flow cytometry were performed to detect the distribution and proportion of interleukin-1 receptor antagonist (IL1RA+) MDSCs. The immunosuppressive and pro-tumorigenic functions of IL1RA+ MDSCs were analyzed using enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and Transwell assays. Patient-derived xenograft mouse models were employed to validate the role of IL1RA+ MDSCs in vivo.

Polymorphonuclear-MDSCs were found to be recruited to metastatic PDAC tissues. Among these, IL1RA+ MDSCs were enriched in HM/LNP tissues and correlated with poorer prognosis. IL1RA+ MDSCs promoted M2 macrophage polarization and suppressed the activity of natural killer cells and cytotoxic T cells. Furthermore, IL1RA+ MDSCs accelerated PDAC migration and progression by upregulating epithelial–mesenchymal transition-related proteins in both in vitro and in vivo models.

IL1RA+ MDSCs represent a key immunosuppressive and pro-tumorigenic subtype in HM/LNP PDAC, providing a solid theoretical basis for prognostic prediction and the development of immunotherapeutic strategies targeting these cells in HM/LNP PDAC.

The incidence and mortality of stroke are gradually increasing. In this context, post-stroke neuronal loss and the related long-term complications, along with costly treatment strategies, are significant concerns for healthcare professionals, and effective, convenient, and inexpensive therapeutic modalities are required. Natural and easily accessible herbal remedies may be the optimal option in post-stroke recovery. This narrative review aims to summarize the neuroprotective properties of Withania somnifera (Ashwagandha) and its therapeutic efficacy in neuronal plasticity and recovery after stroke. Original research articles, reviews, and case studies were sourced from databases such as PubMed, Web of Science, Scopus, Google Scholar, Medline, and Embase. Only full articles published in English up to July 2025 were considered. Keywords including W. somnifera, Ashwagandha, stroke, cerebral ischemia, neurodegeneration, neuronal loss, and post-stroke recovery were utilized for the literature search. It has been found that various plant parts of W. somnifera are abundant in bioactive compounds. The neuroprotective effects of W. somnifera are documented in numerous diseases. Nevertheless, W. somnifera is reported to be involved in modulating various biological pathways to mitigate neuroinflammation, apoptosis, and oxidative stress in stroke. W. somnifera promotes cell proliferation and enhances neurogenesis. Preclinical experiments on murine models show the effectiveness of W. somnifera in post-stroke recovery by enhancing neural plasticity and reducing neuronal loss in the infarct area. Furthermore, W. somnifera boosts neurotransmitter levels, improves motor functions, and enhances memory. It also decreases neutrophil infiltration in the infarct region and lessens neuronal loss. Therefore, the application of W. somnifera may prove advantageous in facilitating post-stroke recovery by enhancing neural function. However, well-designed clinical trials are needed to confirm the efficacy of W. somnifera in post-stroke recovery in humans.

Early and accurate prognostic assessment is crucial to avoid serious disease progression in patients with liver failure. Thyroid hormone is an important metabolic regulator involved in hepatic function. This review examines the pathophysiological regulation in detail of the hypothalamic-pituitary-thyroid axis in patients with liver failure and emphasizes the importance of thyroid profiling (thyroid-stimulating hormone, T3, and T4) in prognostic assessment and risk stratification. T3 can enhance liver regeneration. The clinical application of thyroid hormone replacement therapy in patients with acute-on-chronic liver failure complicated by non-thyroidal illness syndrome is controversial. This review aims to inform clinical practice regarding the relevance of thyroid hormone level assessment in liver failure and to provide novel insights into the prognostic evaluation and comprehensive care of liver failure complicated by thyroid dysfunction.