Shenghe Deng

Chronic liver diseases impose a considerable global public health burden, yet available treatment options remain largely inadequate. The gut microbiota exerts a key modulatory effect on liver disease pathogenesis via the gut-liver axis. Among them, Lachnospiraceae, a dominant bacterial family in the healthy adult gut, has drawn growing interest in recent years. Lachnospiraceae exert protective functions by producing short-chain fatty acids, participating in secondary bile acid conversion, and synthesizing active metabolites such as N-acetyl-glutamic acid, thereby maintaining intestinal barrier integrity and regulating host metabolic and immune homeostasis. Extensive evidence indicates that in cirrhosis, alcohol-associated liver disease, and metabolic dysfunction-associated steatotic liver disease, Lachnospiraceae abundance is consistently and significantly reduced, and this decrease is closely correlated with disease severity and adverse prognosis. In hepatocellular carcinoma, however, different members of Lachnospiraceae exhibit functional divergence, with some butyrate-producing genera decreasing while other subgroups may become enriched and influence the tumor immune microenvironment. Live biotherapeutic products based on Lachnospiraceae have achieved clinical breakthroughs in recurrent Clostridioides difficile infection and metabolic syndrome, providing important references for their translational application in liver diseases. This review systematically synthesizes the abundance changes and mechanisms of Lachnospiraceae across major liver diseases, evaluates their biomarker and therapeutic target potential, and seeks to provide fresh perspectives for precision microbiome-modulating strategies in chronic liver disease management.

Patients with obstructive colorectal cancer (OCRC) have poor prognosis, and conventional prognostic tools such as TNM staging alone are insufficient for accurate assessment; thus, this study aimed to develop and validate nomograms for predicting overall survival (OS) and disease-free survival (DFS) in OCRC patients. A total of 1,650 eligible colorectal cancer patients were enrolled, including 1,520 from Center A (randomly split 6:4 into training and internal validation cohorts) and 130 from Center B as the external validation cohort; clinicopathological and lipid profile data were collected retrospectively, independent prognostic factors were identified via univariate and multivariate Cox regression, and OS/DFS nomograms were constructed and evaluated using ROC curves, C-index, calibration curves, and DCA. The OS nomogram included 8 factors with 1-, 3-, 5-year AUCs of 0.761–0.793 (training), 0.759–0.788 (internal validation), and 0.723–0.856 (external validation), while the DFS nomogram included 6 factors with corresponding AUCs of 0.777–0.822, 0.750–0.841, and 0.775–0.820, and all evaluations confirmed excellent model performance. In conclusion, two nomograms incorporating lipid and clinicopathological factors were developed and validated, which effectively predict OS and DFS in OCRC patients with good discrimination, calibration, and clinical utility, providing new tools for individualized risk prediction.

Cuproptosis is a newly identified type of copper (Cu)-dependent programmed cell death (PCD), triggered when Cu directly interacts with the lipoylated components of the tricarboxylic acid (TCA) cycle, and it has shown significant antitumor potential. However, challenges such as insufficient Cu accumulation in tumor cells, systemic toxicity, and the lack of specific carriers for effectively inducing cuproptosis hinder its practical application. Inorganic nanoparticles (INPs) present a promising solution due to their unique ability to target specific areas, potential for multifunctional modification, and controlled release capabilities. Their distinctive physicochemical properties also enable the integration of synergistic multimodal cancer therapies. Therefore, utilizing INPs to induce cuproptosis represents a promising strategy for cancer treatment. This review systematically elucidates the regulatory mechanisms of Cu homeostasis and the molecular pathways underlying cuproptosis, thoroughly discusses current INP-based strategies designed to trigger cuproptosis, and comprehensively examines the multi-modal synergistic antitumor mechanisms based on cuproptosis. Finally, we also address the current challenges and future perspectives in developing clinically applicable nanoplatforms aimed at harnessing cuproptosis for effective cancer therapy.

Objective: This study aims to determine how intestinal obstruction influences the tumor immune microenvironment (TIME) and its impact on prognosis in colorectal cancer (CRC). Methods: Immune cell densities (CD4⁺, CD8⁺, CD20⁺, CD68⁺) within central tumor (CT) and invasive margin (IM) compartments were quantitatively analyzed using immunohistochemistry (IHC) and QuPath digital pathology in surgical resection samples from 328 patients (164 obstructed colon cancer [OCRC] vs. 164 non-obstructed [NOCRC], cohorts matched by propensity scoring). Findings on tumor-infiltrating immune cell spatial distribution were integrated with peripheral blood immune cell counts and clinicopathological characteristics to characterize the obstructed colon cancer immune microenvironment. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated. Results: OCRC exhibited higher lymphocytic infiltration, particularly in the CT compartment, compared to NOCRC, with significantly elevated CT-CD8⁺ T cell density in T4-stage OCRC (p < 0.005). Obstruction enhanced immune cell correlations across compartments, especially in T4 tumors, and the CD68⁺/CD8⁺ ratio effectively discriminated obstruction status (CT area under the curve (AUC): T4 = 0.879). Peripheral lymphocytopenia was pronounced in obstructive cases (p = 0.003). Critically, T4 OCRC showed a complete loss of all correlations between tumor-infiltrating immune cells and peripheral parameters. Despite increased infiltration, high CD8⁺ density in OCRC correlated with worse prognosis, indicating a paradoxical role influenced by obstruction context. CD68⁺ macrophages in the invasive margin consistently predicted improved survival (Disease-free survival [DFS]: Hazard ratio [HR] = 0.59, p = 0.008). Conclusions: Intestinal obstruction in CRC, particularly in T4-stage tumors, may represent an immunologically active state that alters local immune infiltration and systemic–local immune crosstalk. These findings suggest that obstruction status could refine prognostic stratification and inform therapeutic strategies, although validation in larger cohorts is warranted.

The global burden of liver diseases continues to rise, encompassing diverse pathologies such as viral hepatitis, alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatocellular carcinoma (HCC). In recent years, TNFR1-associated death domain protein (TRADD), a pivotal adaptor molecule in the TNF signaling pathway, has been found to play a dual regulatory role in the pathogenesis of liver diseases. Through its death domain, TRADD binds to TNFR1 and dynamically recruits downstream factors (e.g., TRAF2, RIPK1, FADD) to form Complex I or IIa, thereby activating pro-survival or pro-apoptotic signals that dictate hepatocyte fate and modulate the inflammatory microenvironment. This review systematically summarizes the molecular structure and functional networks of TRADD, along with its mechanistic roles in liver diseases: in HCC, TRADD expression correlates with tumor differentiation and is regulated by miRNA targeting; in ALD and MASLD, TRADD-mediated apoptosis is closely linked to fibrotic progression; and in acute liver injury, TRADD signaling is modulated by factors such as HO-1 to mitigate damage. Furthermore, TRADD inhibitors and antisense oligonucleotides demonstrate therapeutic potential. This review highlights the clinical translational value of TRADD as a diagnostic, therapeutic, and prognostic biomarker for liver diseases, providing a theoretical foundation for future precision medicine strategies.

The intratumoral microbiota, as an important component of the tumor microenvironment, is increasingly recognized as a key factor in regulating responses to cancer immunotherapy. Recent studies have revealed that the intratumoral microbiota is not uniformly distributed but instead exhibits significant spatial heterogeneity, with its distribution patterns influenced by factors such as tumor anatomy, local immune status, and therapeutic interventions. This spatial heterogeneity not only alters the interactions between microbes and the host immune system but may also reshape the immunogenic and immunosuppressive landscapes of tumors. The enrichment or depletion of microbiota in different tumor regions can influence immune cell infiltration patterns, metabolic pathway activities, and immune checkpoint molecule expression, thereby driving the development of resistance to immunotherapy. Moreover, certain bacterial metabolites form concentration gradients between the tumor core and margins, thereby regulating immune cell function. Therefore, understanding and manipulating the spatial distribution of intratumoral microbiota, particularly in resistant patients, holds promise for developing new strategies to overcome immunotherapy resistance. In the future, precise modulation strategies targeting microbial spatial heterogeneity, such as engineered bacterial vectors, probiotic combinations, and phage therapy, may open new avenues for immunotherapy.

Colorectal cancer poses a significant threat to human health due to its high aggressiveness and poor prognosis. Key factors impacting patient outcomes include post-surgical recurrence, chemotherapeutic drug resistance, and insensitivity to immunotherapy. Consequently, early diagnosis and the development of effective targeted therapies are essential for improving prevention and treatment strategies. Inorganic nanomaterials have gained prominence in the diagnosis and treatment of colorectal cancer owing to their unique size, advantageous properties, and high modifiability. Various types of inorganic nanomaterials—such as metal-based, metal oxide, quantum dots, magnetic nanoparticles, carbon-based, and rare-earth nanomaterials—have demonstrated significant potential in enhancing multimodal imaging, drug delivery, and synergistic therapies. These advancements underscore their critical role in improving therapeutic outcomes. This review highlights the properties and development of inorganic nanomaterials, summarizes their recent applications and progress in colorectal cancer diagnosis and treatment, and discusses the challenges in translating these materials into clinical use. It aims to provide valuable insights for future research and the clinical application of inorganic nanomaterials in colorectal cancer management.

Liver health is integral to overall human well-being and the pathogenesis of various diseases. In recent years, kynurenine and its derivatives have gradually been recognized for their involvement in various pathophysiological processes, especially in the regulation of liver diseases, such as acute liver injury, non-alcoholic fatty liver disease, cirrhosis, and liver cancer. Kynurenine and its derivatives are derived from tryptophan, which is broken down by the enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO), converting the essential amino acid tryptophan into kynurenine (KYN) and other downstream metabolites, such as kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and quinolinic acid (QA). In liver diseases, kynurenine and its derivatives can promote the activity of the transcription factor aryl hydrocarbon receptor (AhR), suppress T cell activity for immune modulation, inhibit the activation of inflammatory signaling pathways, such as NF-κB for anti-inflammatory effects, and inhibit the activation of hepatic stellate cells to slow down fibrosis progression. Additionally, kynurenine and other downstream metabolites can influence the progression of liver diseases by modulating the gut microbiota. Therefore, in this review, we summarize and explore the mechanisms by which kynurenine and its derivatives regulate liver diseases to help develop new diagnostic or prognostic biomarkers and effective therapies targeting the kynurenine pathway for liver disease treatment.