Lipid metabolism has been increasingly recognized to play an influencing role in tumor initiation, progression, metastasis, and therapeutic drug resistance. Targeting lipid metabolic reprogramming represents a promising therapeutic strategy. Despite their structural complexity and poor targeting efficacy, lipid-metabolizing drugs, either used alone or in combination with chemotherapeutic agents, have been employed in clinical practice. The advent of nanotechnology offers new approaches to enhancing therapeutic effects, includingthe targeted delivery and integration of lipid metabolic reprogramming with chemotherapy, photodynamic therapy (PDT), and immunotherapy. The integrated nanoformulation, nanomedicine, could significantly advance the field of lipid metabolism therapy. In this review, we will briefly introduce the concept of cancer lipid metabolism reprogramming, then elaborate the latest advances in engineered nanomedicine for targeting lipid metabolism during cancer treatment, and finally provide our insights into future perspectives of nanomedicine for interference with lipid metabolism in the tumor microenvironment.

Skeletal muscle regeneration is a complex process that depends on the interplay between immune responses and muscle stem cell (MuSC) activity. Macrophages play a crucial role in this process, exhibiting distinct polarization states-M1 (pro-inflammatory) and M2 (anti-inflammatory)-that significantly affect tissue repair outcomes. Recent advancements in nanomedicine have positioned gold nanoparticles (Au NPs) as promising tools for modulating macrophage polarization and enhancing muscle regeneration. This review examines the role of Au NPs in influencing macrophage behavior, focusing on their physicochemical properties, biocompatibility, and mechanisms of action. We discuss how Au NPs can promote M2 polarization, facilitating tissue repair through modulation of cytokine production, interaction with cell surface receptors, and activation of intracellular signaling pathways. Additionally, we highlight the benefits of Au NPs on MuSC function, angiogenesis, and extracellular matrix remodeling. Despite the potential of Au NPs in skeletal muscle regeneration, challenges remain in optimizing nanoparticle design, developing targeted delivery systems, and understanding long-term effects. Future directions should focus on personalized medicine approaches and combination therapies to enhance therapeutic efficacy. Ultimately, this review emphasizes the transformative potential of Au NPs in regenerative medicine, offering hope for improved treatments for muscle injuries and diseases.

Tumor-associated macrophages (TAMs) contribute to tumor progression by promoting angiogenesis, remodeling the tumor extracellular matrix, inducing tumor invasion and metastasis, as well as immune evasion. Due to the high plasticity of TAMs, they can polarize into different phenotypes with distinct functions, which are primarily categorized as the pro-inflammatory, anti-tumor M1 type, and the anti-inflammatory, pro-tumor M2 type. Notably, anti-tumor macrophages not only directly phagocytize tumor cells, but also present tumor-specific antigens and activate adaptive immunity. Therefore, targeted regulation of TAMs to unleash their potential anti-tumor capabilities is crucial for improving the efficacy of cancer immunotherapy. Nanomedicine serves as a promising vehicle and can inherently interact with TAMs, hence, emerging as a new paradigm in cancer immunotherapy. Due to their controllable structures and properties, nanomedicines offer a plethora of advantages over conventional drugs, thus enhancing the balance between efficacy and toxicity. In this review, we provide an overview of the hallmarks of TAMs and discuss nanomedicines for targeting TAMs with a focus on inhibiting recruitment, depleting and reprogramming TAMs, enhancing phagocytosis, engineering macrophages, as well as targeting TAMs for tumor imaging. We also discuss the challenges and clinical potentials of nanomedicines for targeting TAMs, aiming to advance the exploitation of nanomedicine for cancer immunotherapy.

The high metastasis rate of lung cancer contributes to its low 5-year survival rate. Bone metastasis is a common complication in advanced lung cancer, adversely affecting postoperative recovery. This study investigates the effects of DHA on macrophage polarization and its underlying mechanisms. In vitro, DHA was found to inhibit M2 polarization while promoting M1 polarization of macrophages, thereby reducing the invasion and migration of lung cancer cells. In vivo, DHA inhibited lung cancer growth and bone metastasis by modulating macrophage M1/M2 polarization in both lung cancer tissues and bone metastatic sites. In addition, through the CCL2/CCR2 pathway, DHA decreased macrophage recruitment and accumulation. These results suggest that DHA is effective in inhibiting lung cancer growth and bone metastasis, offering promising research and application prospects.

Thyroid cancer (TC), which arises from the epithelial cells of the thyroid gland, is experiencing a significant increase in incidence globally. TC encompasses various subtypes, including papillary, follicular, medullary, and anaplastic thyroid cancers, each with distinct pathological and clinical features. Extracellular vesicles (EVs), are naturally occurring and nanosized lipid bilayers, and can be secreted by almost all cell types. EVs, comprising microvesicles and exosomes, are pivotal in mediating intercellular communication within the tumor microenvironment. Notably, EVs possess unique properties such as stability in circulation and the ability to traverse biological barriers, enhancing their role as carriers of molecular information. EVs carry non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, which are crucial regulators of gene expression. Recent studies have highlighted the significant role of EV-derived ncRNAs in influencing thyroid cancer progression, metastasis, and immune modulation by mediating intercellular communication within the tumor microenvironment. The expression of EV-derived ncRNAs varies across different stages of thyroid cancer, reflecting potential as biomarkers for diagnosis and targets for therapy. This review delves into the multifaceted roles of EV-ncRNAs in thyroid cancer, emphasizing their impact on tumor growth, metastatic potential, and immune interactions, while also exploring their promising applications in early diagnosis and targeted treatment strategies. Understanding these dynamics is essential for developing innovative interventions to improve patient outcomes in thyroid cancer.

Cisplatin (DDP) is a key chemotherapeutic agent in the treatment of gastric cancer; however, its efficacy is often limited by chemoresistance, a notable challenge in clinical oncology. The present study aimed to investigate the influence of exosomes derived from M2‑polarized macrophages, which promote this resistance, on the response of gastric cancer cells to DDP, examining both the effects and the underlying mechanisms. M2 macrophages, differentiated from mouse bone marrow cells with interleukin (IL)‑13 and IL‑4, were identified using immunofluorescence staining for CD206 and CD163. Exosomes derived from these macrophages were characterized using transmission electron microscopy and protein markers, including calnexin, tumor susceptibility gene 101 and CD9. The role of exosomal microRNA (miR)‑3681‑3p in DDP resistance was assessed using Cell Counting Kit‑8 and apoptosis assays, while a luciferase reporter assay was used to elucidate the interaction between miR‑3681‑3p and MutL protein homolog 1 (MLH1). Co‑culturing gastric cancer cells with M2 macrophages enhanced DDP resistance, an effect amplified by exosomes from M2 macrophages enriched with miR‑3681‑3p. This microRNA directly targeted and reduced MLH1 protein expression. Overexpression of miR‑3681‑3p through mimic transfection, along with MLH1 silencing by small interfering RNA transfection, significantly increased DDP resistance, as evidenced by elevated IC50 values in AGS cells. By contrast, the overexpression of MLH1 effectively reversed the drug resistance of AGS cells to DDP caused by miR‑3681‑3p mimic transfection, as evidenced by a decrease in the IC50 value. In conclusion, exosomal miR‑3681‑3p from M2 macrophages may have a key role in conferring DDP resistance to gastric cancer by suppressing MLH1, offering a new therapeutic target for overcoming chemoresistance.

Macrophage polarization and energy metabolic reprogramming play pivotal roles in the onset and progression of inflammatory arthritis. Moreover, although previous studies have reported that the proviral integration of Moloney virus 2 (Pim2) kinase is involved in various cancers through the mediation of aerobic glycolysis in cancer cells, its role in inflammatory arthritis remains unclear. In this study, we demonstrated that multiple metabolic enzymes are activated upon Pim2 upregulation during M1 macrophage polarization. Specifically, Pim2 directly phosphorylates PGK1-S203, PDHA1-S300, and PFKFB2-S466, thereby promoting glycolytic reprogramming. Pim2 expression was elevated in macrophages from patients with inflammatory arthritis and collagen-induced arthritis (CIA) model mice. Conditional knockout of Pim2 in macrophages or administration of the Pim2 inhibitor HJ-PI01 attenuated arthritis development by inhibiting M1 macrophage polarization. Through molecular docking and dynamic simulation, bexarotene was identified as an inhibitor of Pim2 that inhibits glycolysis and downstream M1 macrophage polarization, thereby mitigating the progression of inflammatory arthritis. For targeted treatment, neutrophil membrane-coated bexarotene (Bex)-loaded PLGA-based nanoparticles (NM@NP-Bex) were developed to slow the progression of inflammatory arthritis by suppressing the polarization of M1 macrophages, and these nanoparticles (NPs) exhibited superior therapeutic effects with fewer side effects. Taken together, the results of our study demonstrated that targeting Pim2 inhibition could effectively alleviate inflammatory arthritis via glycolysis inhibition and reversal of the M1/M2 macrophage imbalance. NM@NPs loaded with bexarotene could represent a promising targeted strategy for the treatment of inflammatory arthritis.

Acute kidney injury (AKI) is increasingly being recognized as a systemic disorder associated with significant morbidity and mortality. AKI manifests with extensive cellular damage, necrosis, and an intense inflammatory response, often leading to late-stage interstitial fibrosis. Although the mechanisms underlying renal injury and repair remain poorly understood, macrophages (pivotal inflammatory cells) play central roles in AKI. They undergo polarization into pro-inflammatory and anti-inflammatory phenotypes, contributing dynamically to both the injury and repair processes while maintaining homeostasis. Macrophages modulate microenvironmental inflammation by releasing extracellular vesicles (EVs) containing pro- or anti-inflammatory signaling molecules, thereby influencing the regulation of tissue injury. The injured tissue cells release EVs and activate local macrophages to initiate these responses. Our bibliometric analysis indicated that a shift has occurred in AKI macrophage research towards therapeutic strategies and clinical translation, focusing on macrophage-targeted therapies, including exosomes and nanoparticles. This review highlights the roles and mechanisms of macrophage activation, phenotypic polarization, and trans-differentiation in AKI and discusses macrophage-based approaches for AKI prevention and treatment. Understanding the involvement of macrophages in AKI contributes to the comprehension of related immune mechanisms and lays the groundwork for novel diagnostic and therapeutic avenues.

Liver metastasis can occur in a wide range of cancers and have a significant impact on patient survival and prognosis. Once liver metastasis occurs, patients often lose the opportunity for surgery, and although a small percentage of patients can undergo hepatic resection to prolong survival, the benefit is not great. There were also many factors affecting liver metastasis, including reprogramming of the primary tumor metabolism, disturbances in the immune microenvironment and immune cells, alterations in the gut microbiota, and epigenetic changes. Interleukin-10 (IL-10) has a dual role as a cytokine that has been found in recent years to be pro-inflammatory as well as pro-liver metastasis. IL-10 exerts pro-metastatic effects mainly by regulating the polarization of tumor macrophages in the tumor microenvironment, especially by promoting the polarization of M2 macrophages. However, the role of IL-10 in tumorigenesis and progression remains controversial and the molecular mechanism involved in promoting liver metastasis is currently unclear. In view of the increasing role of IL-10 in promoting liver metastasis, this review summarizes the role of IL-10 in liver metastasis of colorectal cancer, breast cancer and other tumors in recent years, and provides ideas for subsequent clinical practice and basic research.

Bone marrow-derived cells in the tumor microenvironment, including macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, eosinophils and basophils, participate in the generation, development, invasion and metastasis of tumors by producing different cytokines and interacting with other cell types, and play a pro-tumor or anti-tumor role in regulating tumor immunity. Due to the complexity of cell types in the tumor microenvironment and the unknown process of tumor development and metastasis, cancer treatment to achieve better survival status remains challenging. In this article, we summarize the effects of myeloid cells in tumor microenvironment on tumor immunity, cancer migration, and crosstalk with metabolism (including glucose metabolism, lipid metabolism, and amino acid metabolism), which will help to further study the tumor microenvironment and seek targeted therapeutic strategies for patients.

Glioblastoma remains one of the most lethal malignancies, largely due to its resistance to standard chemotherapy such as temozolomide. This study investigates a novel resistance mechanism involving glioblastoma stem cells (GSCs) and the polarization of M2-type macrophages, mediated by the extracellular vesicle (EV)-based transfer of Clusterin. Using 6-week-old male CD34+ humanized huHSC-(M-NSG) mice (NM-NSG-017) and glioblastoma cell lines (T98G and U251), we demonstrated that GSC-derived EVs enriched with Clusterin induce M2 macrophage polarization, thereby enhancing temozolomide resistance in glioblastoma cells. Single-cell and transcriptome sequencing revealed close interactions between GSCs and M2 macrophages, highlighting Clusterin as a key mediator. Our findings indicate that Clusterin-rich EVs from GSCs drive glioblastoma cell proliferation and resistance to temozolomide by modulating macrophage phenotypes. Targeting this pathway could potentially reverse resistance mechanisms, offering a promising therapeutic approach for glioblastoma. This study not only sheds light on a critical pathway underpinning glioblastoma resistance but also lays the groundwork for developing therapies targeting the tumor microenvironment. Our results suggest a paradigm shift in understanding glioblastoma resistance, emphasizing the therapeutic potential of disrupting EV-mediated communication in the tumor microenvironment.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a curative therapeutic option for patients with high-risk hematologic malignancies. When a fully matched donor is unavailable, haploidentical hematopoietic stem cell transplantation (haplo-HCT) provides a viable alternative. Over time, haplo-HCT procedures have significantly evolved, improving outcomes in treatment related mortality (TRM), especially in graft-versus-host disease (GvHD). However, challenges such as delayed immune reconstitution and disease relapse persist. Advances in in vivo graft manipulation techniques, such as post-transplant cyclophosphamide (PTCy) and ex vivo approaches, including TCRα/β and CD19 depletion, have shown promise in reducing the risk of severe GvHD without increasing the relapse rates. Innovative strategies, such as haploidentical donor lymphocyte infusions, "suicide-switch" mechanisms, ORCA-Q product infusions, and CAR based therapies offer potential to further optimize outcomes. This review examines the graft manipulation modalities in the haplo-HCT setting, highlighting their role in advancing cellular therapies and providing new hope in the fight against life-threatening diseases.

Injury and inflammatory activate and polarize macrophages in intervertebral disc degeneration (IVDD). Further research needs to be carried to explore the mechanisms that regulate macrophage polarization, providing new insights and targets for IVDD treatment. The aim of our study was to evaluate the influence of LT-α on aerobic glycolysis (AG) and polarization in macrophages.

M0 macrophages were achieved by stimulating THP-1 cells with PMA. M1 macrophages were obtained by IFN-γ and LPS stimulation in M0 macrophages. Energy metabolomics, AG and apoptosis related protein expression, migration and invasion measurement, proliferation was analyzed. Polarization of macrophages, AG associated genes expression, macrophage recruitment was evaluated. NF-κB signaling was ascertained by laser confocal and Western blotting.

The propanoate metabolism pathway was enriched in LT-α overexpressing M0 macrophages, and various energy metabolites were detected. Glucose absorption, lactic acid production, and levels of AG proteins were strikingly increased in LT-α overexpression macrophages and remarkably repressed in LT-α knockdown macrophages, accompanied by activated and inactivated NF-κB signaling, respectively. Suppressed migration and invasion ability, restrained proliferation, activated AG, and enhanced apoptosis were observed in nucleus pulposus (NP) cells treated by LT-α overexpressed macrophages, accompanied by reduced macrophage recruitment, with opposite results when treated by LT-α knockdown macrophages. The enhanced M1 polarization and activated AG in LT-α overexpression macrophages were abolished by co-culturing with NF-κB inhibitor.

LT-α facilitates the AG and M1 polarization of macrophages via activating the NF-κB signaling pathway.

In the progression of gastric cancer (GC), various cell types in the tumor microenvironment (TME) exhibit upregulated expression of programmed death ligand 1 (PD-L1), leading to impaired T-cell function and evasion of immune surveillance. Infection with H. pylori and EBV leads to increased PD-L1 expression in various cell types within TME, resulting in immune suppression and facilitating immune escape of GC cells. In the TME, mesenchymal stem cells (MSCs), M1-like tumor-associated macrophages (MI-like TAM), and myeloid-derived suppressor cells (MDSCs) contribute to the upregulation of PD-L1 expression in GC cells. Conversely, mast cells, M2-like tumor-associated macrophages (M2-like TAM), and tumor-associated neutrophils (TANs) exhibit elevated levels of PD-L1 expression in response to the influence of GC cells. Together, these factors collectively contribute to the upregulation of PD-L1 expression in GC. This review aims to provide a comprehensive summary of the cellular expression patterns of PD-L1 in GC and the underlying molecular mechanisms. Understanding the complex regulatory pathways governing PD-L1 expression may offer novel insights for the development of effective immunotherapeutic interventions.

Huachansu (HCS), a traditional Chinese medicine (TCM), has been used as an adjuvant therapy for colorectal cancer (CRC). However, its underlying mechanisms for combating CRC require further investigation.

To comprehensively evaluate the anti-CRC effects of HCS and elucidate its underlying mechanisms, with a focus on elucidating the key pathways and targets involved.

A series of cell experiments and xenograft tumor models were used to evaluate the inhibitory effects of HCS. The key components and potential targets of HCS against CRC were identified through network pharmacology and molecular docking. To further investigate the mechanisms, transcriptomics and proteomics were integrated, and the findings were supported by systematic pharmacological validation. Finally, the efficacy of HCS was further confirmed in CRC Patients-derived organoid and orthotopic models.

HCS could inhibit proliferation, disrupt the cell cycle, induce apoptosis of CRC cells, and suppress the growth of CRC xenograft tumors. Then eight components and six proteins (PIK3CA, CTNNB1, TP53, AKT1, CCND1, and CDH1) were identified as critical for HCS's anti-CRC activity. Notably, HCS inhibited the PI3K/AKT signaling pathway and glycolysis in CRC cells, with these findings validated in both in vitro and in vivo models. Additionally, HCS reduced growth in CRC patient-derived organoids and orthotopic models.

This study elucidates the mechanisms of HCS to combat CRC, offering a valuable reference for future clinical applications. It also presents a distinctive strategy for exploring TCM formulations' active components and effective mechanisms.

Tumor-associated macrophages play a critical role in regulating the progression of lung adenocarcinoma (LUAD). Platelet-derived protein thrombospondin-2 (THBS2) has been identified as a tumor marker and is known to be overexpressed in LUAD. However, the specific role of THBS2 in M2 macrophage polarization within LUAD remains unclear. We conducted bioinformatics analyses to assess the clinical significance of THBS2 expression in LUAD, which was subsequently validated using quantitative PCR. We examined the relationship between THBS2 expression and M2 macrophage infiltration. A coculture system of LUAD cells and M0 macrophages was established to investigate the influence of THBS2 on macrophage infiltration and polarization through immunofluorescence and ELISA. We explored the impact of THBS2 on fatty acid metabolism (FAM) using oil red O staining and relevant kits and elucidated the role of THBS2 in regulating M2 macrophage polarization and LUAD proliferation through cell counting kit-8 (CCK-8) and colony formation assays. Western blot was employed to assess expression changes of Bax and Bcl-2. THBS2 was highly expressed in LUAD and was associated with poor prognosis in patients. In-vitro experiments demonstrated that silencing THBS2 significantly inhibited macrophage infiltration and polarization. THBS2 primarily activated FAM pathways, inducing M2 macrophage polarization and promoting LUAD cell proliferation. THBS2 enhanced LUAD proliferation by regulating FAM to induce M2 macrophage polarization. These findings provide a theoretical basis for targeting THBS2 as a novel therapeutic strategy in LUAD.

Pancreatic adenocarcinoma (PAAD) is a fatal malignant tumor of the digestive system, and immunotherapy has currently emerged as a key therapeutic approach for treating PAAD, with its efficacy closely linked to T-cell subsets and the tumor immune microenvironment. However, reliable predictive markers to guide clinical immunotherapy for PAAD are not available. We analyzed the single-cell RNA sequencing (scRNA-seq) data focused on PAAD from the GeneExpressionOmnibus (GEO) database. Then, the information from the Cancer Genome Atlas (TCGA) database was integrated to develop and validate a prognostic risk model derived from T-cell marker genes. Subsequently, the correlation between these risk models and the effectiveness of immunotherapy was explored. Analysis of scRNA-seq data uncovered six T-cell subtypes and 1837 T-cell differentially expressed genes (DEGs). Combining these data with the TCGA dataset, we constructed a T-cell prognostic risk model containing 16 DEGs, which can effectively predict patient survival and immunotherapy outcomes. We have found that patients in the low-risk group had better prognostic outcomes, increased immune cell infiltration, and signs of immune activation compared to those in the high-risk group. Additionally, analysis of tumor mutation burden showed higher mutation rates in patients with PAAD in the high-risk group. Risk scores with immune checkpoint gene expression and drug sensitivity analysis provide patients with multiple therapeutic targets and drug options. Our study constructed a prognostic risk model for PAAD patients based on T-cell marker genes, providing valuable insights into predicting patient prognosis and the effectiveness of immunotherapy.

Macrophages are key tumor microenvironment (TME) regulators, exhibiting remarkable plasticity that enables them to either suppress or promote cancer progression. Emerging evidence highlights the critical role of macrophage-derived long non-coding RNAs (lncRNAs) in shaping tumor immunity, influencing macrophage polarization, immune evasion, angiogenesis, metastasis, and therapy resistance. This review comprehensively elucidates the functional roles of M1- and M2-associated lncRNAs, detailing their molecular mechanisms and impact on cancer pathogenesis. In summary, elucidating the roles of lncRNAs derived from macrophages in cancer progression offers new avenues for therapeutic strategies, significantly improving patient outcomes in the fight against the disease. Further research into the functional significance of these lncRNAs and the development of targeted therapies is essential to harness their potential fully in clinical applications. We further explore their potential as biomarkers for cancer prognosis and therapeutic targets for modulating macrophage activity to enhance anti-cancer immunity. Targeting macrophage-derived lncRNAs represents a promising avenue for precision oncology, offering novel strategies to reshape the TME and improve cancer treatment outcomes.

Reportedly, there is an association between body metabolites and the risk of Hepatocellular Carcinoma (HCC) & Cholangiocarcinoma (CCA), possibly due to disrupted metabolic pathways leading to oxidative stress and an imbalance in cell proliferation and apoptosis, thereby increasing the risk of cancer. However, whether metabolites play a role in the onset of HCC or CCA remains inconclusive.

The aim of our study is to explore the potential causal relationship between metabolites and the risk of HCC&CCA.

Our study investigated the causal relationship between 1400 metabolites and HCC&CCA using publicly available genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with both metabolites and HCC&CCA were chosen as instrumental variables (IVs). The main approaches employed include inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), with odds ratios (OR) used as the assessment criterion. Heterogeneity testing and sensitivity analyses were conducted to validate the results. We also conducted a reverse MR analysis to further validate the relationship between exposure and disease outcomes.

This Mendelian Randomization (MR) study indicates a significant causal relationship between 19 metabolites and the risk of HCC&CCA. Among them, the risk factors include "Bilirubin (E, Z or Z, E) levels," "Bilirubin (Z, Z) to taurocholate ratio," "Dimethylarginine (sdma + adma) levels," "N-methyltaurine levels," "4-vinylguaiacol sulfate levels," "Cholate to adenosine 3',5'-cyclic monophosphate (cAMP) ratio," "Glycohyocholate levels," "Cholesterol levels," and "4-methylguaiacol sulfate levels." The incidence risk of HCC and CCA increases with the elevation of these metabolites. Protective factors include "Ursodeoxycholate levels," "3-hydroxybutyroylglycine levels," "Linoleoylcholine levels," "Nonanoylcarnitine (C9) levels," "Pristanate levels," "Heptenedioate (C7:1-DC) levels," "Mannonate levels," "N-acetyl-L-glutamine levels," "Sphinganine levels," and "N-lactoyl isoleucine levels." The incidence risk of HCC and CCA potentially decreases as the levels of these metabolites increase. Heterogeneity tests show that most instrumental variables do not exhibit inter-gene heterogeneity, and the possibility of pleiotropy in the analysis is very low according to the sensitivity analysis. The reverse MR analysis did not yield positive results.

Our study has unveiled the intricate causal relationships between metabolites and the risk of HCC&CCA. Through our analysis, we identified nine metabolites, including "Bilirubin (E, Z or Z, E) levels," "Dimethylarginine (sdma + adma) levels," "Cholesterol levels,"ect, as risk factors for HCC&CCA. The incidence risk of HCC and CCA increases with their elevation. On the other hand, ten metabolites, such as "Ursodeoxycholate levels," "Linoleoylcholine levels," "Pristanate levels," ect, were identified as protective factors for HCC&CCA. The risk of developing HCC and CCA decreases with an increase in these metabolites. In conclusion, these findings further explore the physiological metabolic pathways underlying the pathogenesis of HCC and CCA, emphasizing future research directions. They pave the way for researchers to delve into the biological mechanisms of these diseases, facilitating early intervention and treatment strategies for these conditions.

The infiltration and excessive polarization of M1 macrophages contribute to the induction and persistence of low-grade inflammation in joint-related degenerative diseases such as osteoarthritis (OA). The lipid metabolism dysregulation promotes M1 macrophage polarization by coordinating the compensatory pathways of the inflammatory and oxidative stress responses. Here, a self-assembling, licofelone-loaded nanoparticle (termed LCF-CSBN), comprising chondroitin sulfate and bilirubin joined by an ethylenediamine linker, is developed to selectively reprogram lipid metabolism in macrophage activation. LCF-CSBN is internalized by M1 macrophages via CD44-mediated endocytosis and targets the Golgi apparatus accompanied with the reactive oxygen species-responsive release of licofelone (LCF, dual inhibitor of arachidonic acid metabolism). LCF-CSBN effectively promotes M1 to M2 macrophage transition by reprogramming the Golgi apparatus-related sphingolipid metabolism and arachidonic acid metabolism. Intra-articularly injected LCF-CSBN retains in the joint for up to 28 days and accumulates into M1 macrophages. Moreover, LCF-CSBN can effectively attenuate joint inflammation, oxidative stress, and cartilage degeneration in OA model rats. These findings indicate the promising potential of lipid-metabolism-reprogramming LCF-CSBN in the targeted therapy of OA.

In vitro cell models are an effective way to evaluate the biological activities of functional compounds. Hesperetin (HST) is a flavanone with various potential health-related benefits, and encapsulation improved its stability and bioavailability. This study aimed to investigate the anti-inflammatory effects of encapsulated HST using different delivery systems, including β-cyclodextrin (CD), nanoliposomes (NL), and NL coated with chitosan (CH) and carrageenan (CGN). A Caco-2 and THP-1 co-culture model characterized by direct cell-to-cell contact was developed, and these delivery systems were digested in vitro and subsequently tested on this model. The addition of lipopolysaccharide (LPS) in the model resulted in high secretion of the pro-inflammatory cytokines (IL-8, TNF-α, and IL-1β), the upregulation of the phenotype genes (CD68 and CD80) and the inflammation-related genes (MYD88, NFκB, and COX-2), marking the differentiation of M0 macrophages into M1 macrophages. Among the delivery systems, HST encapsulated in CH and CGN coated NL (CGN-CH-NL-HST) was the most effective in suppressing the production of IL-8 and expression of MYD88 and COX-2 in the inflammatory co-culture model. Metabolomic data showed that the M1 macrophage metabolic profile was changed by applying free HST and encapsulated HST, mostly in glycolysis and amino acid metabolism. Encapsulated HST in the CGN-CH-NL delivery system showed anti-inflammatory activity in the Caco-2 and THP-1 direct co-culture model, suggesting a potential of encapsulated bioactive compounds in treating inflammatory bowel disease.

Immunometabolic variations in macrophages critically influence their differentiation into pro-inflammatory or anti-inflammatory phenotypes, thereby contributing to immune homeostasis, defense against infection, and tissue repair. Dysregulation of macrophage immunometabolism has been closely implicated in several metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), hypertension, atherosclerosis, and gout, which positions macrophages as potential therapeutic targets. Recently, several natural products that target macrophage metabolic pathways have shown significant efficacy in managing metabolic diseases; however, a systematic review of these findings has yet to be conducted. This study consolidates natural products with immunoregulatory properties, including flavonoids, phenols, terpenoids, and naphthoquinones, which can alleviate chronic inflammation associated with metabolic disorders by modulating macrophage metabolic pathways, such as aerobic glycolysis, oxidative phosphorylation (OXPHOS), and fatty acid oxidation (FAO). This review aims to elucidate the metabolic regulation of the immune system, analyze metabolic alterations in macrophage associated with metabolic diseases, and summarize the beneficial roles of natural products in immunometabolism, providing novel insights for the prevention and therapeutic management of metabolic diseases.

Harnessing cross-species regenerative cues to direct human regenerative potential is increasingly recognized as an excellent strategy in regenerative medicine, particularly for addressing the challenges of impaired wound healing in aging populations. The skin mucus of Andrias davidianus plays a critical role in self-protection and tissue repair, yet the fundamental regenerative factors and mechanisms involved remain elusive. Here, this work presents evidence that glycosaminoglycans (GAGs) derived from the skin secretion of Andrias davidianus (SAGs) serve as potent mediators of angiogenesis and inflammatory remodeling, facilitating efficient healing of diabetic wounds. Mechanistic studies reveal that SAGs promote macrophage polarization toward an anti-inflammatory and pro-regenerative phenotype (CD206+/Arg1+) via glucolipid metabolic reprogramming. This process suppresses excessive inflammation and enhances the expression of VEGF and IL-10 to create a facilitative microenvironment for tissue regeneration. Additionally, this work develops SAGs-GelMA composite microspheres that address multiple stages of wound healing, including rapid hemostasis, exudate control, and activation of endogenous regenerative processes. This engineered approach significantly improves the scarless healing of diabetic wounds by facilitating the recruitment and activation of reparative macrophages. The findings offer new insights into the regenerative mechanisms of Andrias davidianus and highlight the potential therapeutic application of SAGs in tissue repair.

Equol, a naturally occurring phytoestrogen derived from the fermentation of soy and soy-based products by gut bacteria, is recognized for its diverse health benefits. While there is speculation about its association with cancer prevention, the scientific community has yet to reach a consensus due to the variability in research findings. Our study aims to shed light on this topic by examining the correlation between urine equol concentrations and the cancer risk among the American population. The National Health and Nutrition Examination Survey (NHANES) is a national survey of U.S. civilians in which cancer participants are enrolled in a database by a sample questionnaire. This study included 2797 Americans aged 40 years and older in the NHANES database (2005-2010). The relationship between urine equol concentration and cancer was analysed using weighted logistic regression models, stratified analysis, smoothed curve fitting and threshold effect analysis were also performed. Among the 2797 participants in our study, 390 individuals received a cancer diagnosis. Our findings indicate a positive correlation between urine equol levels and the risk of cancer. Notably, individuals in the highest quartile of equol excretion exhibited a significantly elevated risk of cancer, with a 25.4% increase compared to those in the lowest quartile (POR = 1.254, 95% CI: 1.252, 1.256), after fully adjusting for confounders. Similar results were observed in other adjusted models. A non-linear relationship in the shape of an inverted U-shape can be observed by smoothed curve fitting, and the inflection point is 25.5. Urinary equol concentrations below 25.5 ng/ml were positively associated with cancer risk, while equol concentrations above 25.5 ng/ml showed a slight negative trend in cancer risk. However, further prospective studies are needed to provide more robust evidence and confirmed in large clinical trials.

Gliomas, a heterogeneous group of tumors affecting the brain and spinal cord, present a significant clinical challenge. Ephrin B1 (EFNB1) has been implicated in various malignancies. However, its role in gliomas remained poorly understood. Hence, this study aimed to elucidate the connection between EFNB1 and the progression of glioma. A retrospective RNA-seq analysis was conducted by utilizing the data from glioma patients in the TCGA and CGGA databases. Kaplan-Meier survival analysis and multivariate regression models were employed to evaluate the prognostic significance of EFNB1. RT-PCR was used to quantify EFNB1 expression in glioma tissues and cell lines. Meanwhile, in vitro assays were carried out to assess its functional roles in glioma cells. Our findings demonstrated that EFNB1 expression was significantly elevated in gliomas and other cancers. Moreover, high EFNB1 expression was closely correlated with advanced clinical stages and poor prognosis. Notably, multivariate analysis identified EFNB1 as an independent prognostic factor for overall survival. KEGG pathway analysis suggested that EFNB1 was involved in critical biological processes, including the cell cycle, protein processing in the endoplasmic reticulum, Epstein-Barr virus infection, and Salmonella infection. Furthermore, EFNB1 expression was associated with immune cell infiltration, particularly Th2 cells, macrophages, and plasmacytoid dendritic cells. In glioma cells, EFNB1 expression was markedly increased. Consequently, functional experiments demonstrated that EFNB1 knockdown inhibited glioma cell proliferation, invasion, and migration. These results highlighted EFNB1 as a novel independent prognostic biomarker and suggest its potential role in shaping the immunological microenvironment of gliomas.

N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, plays a critical role in the development and progression of various diseases, including cancer, through its regulation of RNA degradation, stabilization, splicing, and cap-independent translation. Emerging evidence underscores the significant role of m6A modifications in both pro-tumorigenic and anti-tumorigenic immune responses. In this review, we provide a comprehensive overview of m6A modifications and examine the relationship between m6A regulators and cancer immune responses. Additionally, we summarize recent advances in understanding how m6A modifications influence tumor immune responses by directly modulating immune cells (e.g., dendritic cells, tumor-associated macrophages, and T cells) and indirectly affecting cancer cells via mechanisms such as cytokine and chemokine regulation, modulation of cell surface molecules, and metabolic reprogramming. Furthermore, we explore the potential synergistic effects of targeting m6A regulators in combination with immune checkpoint inhibitor (ICI) therapies. Together, this review consolidates current knowledge on the role of m6A-mediated regulation in tumor immunity, offering insights into how a deeper understanding of these modifications may identify patients who are most likely to benefit from immunotherapies.

Tumour-associated macrophages (TAMs) are critical components of the tumour microenvironment (TME), significantly influencing cancer progression and treatment resistance. This review aims to explore the innovative use of engineered bacteria to reprogram TAMs, enhancing their anti-tumour functions and improving therapeutic outcomes.

We conducted a systematic review following a predefined protocol. Multiple databases were searched to identify relevant studies on TAMs, their phenotypic plasticity, and the use of engineered bacteria for reprogramming. Inclusion and exclusion criteria were applied to select studies, and data were extracted using standardised forms. Data synthesis was performed to summarise the findings, focusing on the mechanisms and therapeutic benefits of using non-pathogenic bacteria to modify TAMs.

The review summarises the findings that engineered bacteria can selectively target TAMs, promoting a shift from the tumour-promoting M2 phenotype to the tumour-fighting M1 phenotype. This reprogramming enhances pro-inflammatory responses and anti-tumour activity within the TME. Evidence from various studies indicates significant tumour regression and improved immune responses following bacterial therapy.

Reprogramming TAMs using engineered bacteria presents a promising strategy for cancer therapy. This approach leverages the natural targeting abilities of bacteria to modify TAMs directly within the tumour, potentially improving patient outcomes and offering new insights into immune-based cancer treatments. Further research is needed to optimise these methods and assess their clinical applicability.

Glycolytic reprogramming of macrophages is a decisive factor in atherosclerosis (AS) plaque formation. Eukaryotic elongation factor 1A1 (eEF1A1) plays an important role in protein synthesis, ubiquitination degradation, and nuclear translocation. However, the potential function of eEF1A1 in AS has not yet been fully understood. Here, the natural small molecule neferine (Nef), which targets eEF1A1 to suppress macrophage glycolytic reprogramming is discovered. In this work, chemical genetics and non-modified target confirmation assays are used to confirm that eEF1A1 is a direct target of Nef. Mechanically, Nef disrupted the formation of the eEF1A1/ARID3A/PKC-δ complex, inhibits phosphorylation of ARID3A at Thr491, and consequently prevents its nuclear translocation. Meanwhile, it is verified that ARID3A is a transcriptional regulator of enolase 2 (ENO2), an important enzyme in the glycolytic process. Nef suppresses ENO2 transcription activation by affecting ARID3A binding to the promoter region of ENO2, which results in macrophage glycolytic reprogramming inhibition and transformation of macrophages from M1 to M2. Collectively, these findings provide an attractive future direction for AS therapy by inhibiting ARID3A/ENO2-mediated macrophage glycolytic reprogramming by targeting eEF1A1.

Metastasis is a hallmark of advanced cancer, and the liver is a common site for secondary metastasis of many tumor cells, including colorectal, pancreatic, gastric, and prostate cancers. Macrophages in the tumor microenvironment (TME) promote tumor cell metastasis through various mechanisms, including angiogenesis and immunosuppression, and play a unique role in the development of liver metastasis. Macrophages are affected by a variety of factors. Under conditions of hypoxia and increased acidity in the TME, more factors are now found to promote the polarization of macrophages to the M2 type, including exosomes and amino acids. M2-type macrophages promote tumor cell angiogenesis through a variety of mechanisms, including the secretion of factors such as VEGF, IL-1β, and TGF-β1. M2-type macrophages are subjected to multiple regulatory mechanisms. They also interact with various cells within the tumor microenvironment to co-regulate certain conditions, including the creation of an immunosuppressive microenvironment. This interaction promotes tumor cell metastasis, drug resistance, and immune escape. Based on the advent of single-cell sequencing technology, further insights into macrophage subpopulations in the tumor microenvironment may help in exploring new therapeutic targets in the future. In this paper, we will focus on how macrophages affect the TME, how tumor cells and macrophages as well as other immune cells interact with each other, and further investigate the mechanisms involved in liver metastasis of tumor cells and their potential as therapeutic targets.

Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance in gastrointestinal cancers (GI), particularly through the pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth and reshape the TME, creating conditions such as nutrient depletion, hypoxia, and acidity that impair antitumor immune responses. Immune cells within the TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes that promote tumor progression and reduce the efficacy of therapies. The competition for essential nutrients, particularly glucose, between cancer and immune cells compromises the antitumor functions of effector immune cells, such as T cells. Additionally, metabolic by-products like lactate and kynurenine further suppress immune activity and promote immunosuppressive populations, including regulatory T cells and M2 macrophages. Targeting metabolic pathways such as fatty acid oxidation and glycolysis presents new opportunities to overcome drug resistance and improve therapeutic outcomes in GI cancers. Modulating these key pathways has the potential to reinvigorate exhausted immune cells, shift immunosuppressive cells toward antitumor phenotypes, and enhance the effectiveness of immunotherapies and other treatments. Future strategies will require continued research into TME metabolism, the development of novel metabolic inhibitors, and clinical trials evaluating combination therapies. Identifying and validating metabolic biomarkers will also be crucial for patient stratification and treatment monitoring. Insights into metabolic reprogramming in GI cancers may have broader implications across multiple cancer types, offering new avenues for improving cancer treatment.

With the development of public health, female diseases have become the focus of current concern. The unique reproductive anatomy of women leads to the development of gynecological diseases gradually become an important part of the socio-economic burden. Epigenetics plays an irreplaceable role in gynecologic diseases. As an important mRNA modification, m6A is involved in the maturation of ovum cells and maternal-fetal microenvironment. At present, researchers have found that m6A is involved in the regulation of gestational diabetes and other reproductive system diseases, but the specific mechanism is not clear. In this manuscript, we summarize the components of m6A, the biological function of m6A, the progression of m6A in the maternal-fetal microenvironment and a variety of gynecological diseases as well as the progression of targeted m6A treatment-related diseases, providing a new perspective for clinical treatment-related diseases.

Osteosarcoma, a highly malignant bone tumor, poses significant treatment challenges due to its propensity for stemness and drug resistance, particularly against doxorubicin (DOX). This study aims to investigate the mechanism by which β-elemene reduces the stemness of osteosarcoma stem cells and ultimately decreases DOX resistance by inhibiting the Akt/FoxO1 signaling pathway and activating a macrophage-mediated inflammatory microenvironment.

Osteosarcoma stem cells were isolated and induced for DOX resistance. In vitro and in vivo models were employed to assess β-elemene's impact on cell viability, stemness, and drug resistance. Bioinformatics analysis, flow cytometry, and immunofluorescence staining were used to evaluate signaling pathway activity and macrophage polarization. Additionally, an osteosarcoma xenograft mouse model was established to confirm the therapeutic effects of β-elemene.

In vivo animal experiments demonstrated that β-elemene reduces osteosarcoma resistance. Bioinformatics analysis revealed that AKT1 is a key core gene in osteosarcoma progression, acting through the FOXO signaling pathway. Additionally, AKT inhibits immune cell infiltration in osteosarcoma and suppresses immune responses during osteosarcoma progression. β-elemene may influence osteosarcoma progression by mediating TP53 to regulate PTEN and subsequently AKT1. In vitro experiments showed that β-elemene promotes M1 macrophage activation by inhibiting the Akt/FoxO1 signaling axis, thereby reducing the stemness of osteosarcoma stem cells. Finally, in vivo animal experiments confirmed that β-elemene reduces osteosarcoma resistance by promoting M1 macrophage activation through inhibition of the Akt/FoxO1 signaling axis.

β-Elemene demonstrates promising potential in reducing osteosarcoma stemness and drug resistance via dual mechanisms: targeting the AKT/FOXO1 pathway and modulating the tumor immune microenvironment. These findings suggest β-elemene as a potential adjunct therapy for osteosarcoma, providing novel therapeutic strategies to overcome chemotherapy resistance and improve patient outcomes.

PARP (poly (ADP-ribose) polymerase) inhibitors (PARPi) have demonstrated significant potential in cancer treatment, particularly in tumors with breast cancer susceptibility gene (BRCA) mutations and other DNA repair deficiencies. However, the development of resistance to PARPi has become a major challenge in their clinical application. The emergence of drug resistance leads to reduced efficacy of the PARPi over time, impacting long-term treatment outcomes and survival rates. PARPi resistance in tumors often arises as cells activate alternative DNA repair pathways or evade the effect of PARPi, diminishing therapeutic effectiveness. Consequently, overcoming resistance is crucial for maintaining treatment efficacy and improving patient prognosis. This paper reviews the strategies to overcome PARPi resistance through combination treatment and nanotechnology therapy. We first review the current combination therapies with PARPi, including anti-angiogenic therapies, radiotherapies, immunotherapies, and chemotherapies, and elucidate their mechanisms for overcoming PARPi resistance. Additionally, this paper focuses on the application of nanotechnology in improving the effectiveness of PARPi and overcoming drug resistance. Subsequently, this paper presents several promising strategies to tackle PARPi resistance, including but not limited to: structural modifications of PARPi, deployment of gene editing systems, implementation of "membrane lipid therapy," and modulation of cellular metabolism in tumors. By integrating these strategies, this research will provide comprehensive approaches to overcome the resistance of PARPi in cancer treatment and offer guidance for future research and clinical practice.

Non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), is influenced by tumor-immune interactions. M2 macrophages play a significant role in the tumor microenvironment. This study explores the role of MRO, an M2 macrophage-associated gene, in NSCLC, focusing on immune infiltration, prognostic significance, and therapeutic potential.

NSCLC samples from The Cancer Genome Atlas (TCGA) were analyzed using the CIBERSORT algorithm to quantify immune cell compositions. Differential gene expression and correlation studies examined MRO's association with M2 macrophages. Univariate Cox regression and Kaplan-Meier analyses assessed prognostic significance. Single-cell RNA sequencing data from TISCH2 evaluated MRO expression in different cell types. The ESTIMATE algorithm analyzed correlations between MRO expression and immune scores, while TIDE and Submap analyses predicted immunotherapy responses.

MRO was highly expressed in NSCLC, particularly in LUAD and LUSC, and associated with M2 macrophages. MRO correlated with key immune pathways, including TNFα signaling via NFκB, inflammatory response, and IL6 JAK STAT3 signaling. High MRO expression correlated with poorer overall survival (OS) and disease-specific survival (DSS). Single-cell analysis confirmed MRO expression in macrophages. The ESTIMATE algorithm showed positive correlations between MRO expression and immune scores. TIDE and Submap analyses suggested low MRO expression in LUSC patients might predict better immunotherapy responses.

MRO is a critical M2 macrophage-associated gene in NSCLC, influencing immune infiltration and prognosis. It may serve as a biomarker for prognostication and a target for therapeutic intervention in NSCLC.

KRAS is one of the most mutated genes, driving alternations in metabolic pathways that include enhanced nutrient uptaking, increased glycolysis, elevated glutaminolysis, and heightened synthesis of fatty acids and nucleotides. However, the beyond mechanisms of KRAS-modulated cancer metabolisms remain incompletely understood. In this review, we aim to summarize current knowledge on KRAS-related metabolic alterations in cancer cells and explore the prevalence and significance of KRAS mutation in shaping the tumor microenvironment and influencing epigenetic modification via various molecular activities. Given that cancer cells rely on these metabolic changes to sustain cell growth and survival, targeting these processes may represent a promising therapeutic strategy for KRAS-driven cancers.

Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, and recognizing lactyl groups on proteins. Macrophages, as cells of the immune system, maintain homeostasis, responding dynamically to diverse internal and external stimuli. Emerging researches unveil that lactylation, through inducing macrophage activation and polarization, affects their functionality in pathological conditions such as inflammation, tumor microenvironment, and fibrosis. Evidence progressively indicates that lactate-driven alterations in lactylation levels within macrophages can influence the pathogenesis of numerous diseases. This review aims to systematically summarize the research progress of lactylation in macrophages, explore its functions and mechanisms by which lactylation contributes to the pathology of different disease phenotypes, and propose future research directions along with potential diagnostic and therapeutic strategies.

Immune checkpoint therapies have spearheaded drug innovation over the last decade, propelling cancer treatments toward a new era of precision therapies. Nonetheless, the challenges of low response rates and prevalent drug resistance underscore the imperative for a deeper understanding of the tumor microenvironment (TME) and the pursuit of novel targets. Recent findings have revealed the profound impacts of biomechanical forces within the tumor microenvironment on immune surveillance and tumor progression in both murine models and clinical settings. Furthermore, the pharmacological or genetic manipulation of mechanical checkpoints, such as PIEZO1, DDR1, YAP/TAZ, and TRPV4, has shown remarkable potential in immune activation and eradication of tumors. In this review, we delved into the underlying biomechanical mechanisms and the resulting intricate biological meaning in the TME, focusing mainly on the extracellular matrix, the stiffness of cancer cells, and immune synapses. We also summarized the methodologies employed for biomechanical research and the potential clinical translation derived from current evidence. This comprehensive review of biomechanics will enhance the understanding of the functional role of biomechanical forces and provide basic knowledge for the discovery of novel therapeutic targets.

Golgi Protein 73 (GP73) is a Golgi-resident protein that is highly expressed in primary tumor tissues. Initially identified as an oncoprotein, GP73 has been shown to promote tumor development, particularly by mediating the transport of proteins related to epithelial-mesenchymal transition (EMT), thus facilitating tumor cell EMT. Though our previous review has summarized the functional roles of GP73 in intracellular signal transduction and its various mechanisms in promoting EMT, recent studies have revealed that GP73 plays a crucial role in regulating the tumor and immune microenvironment. GP73 can modulate intracellular signaling pathways to influence cytokine and chemokine networks, resulting in inflammation caused by viral and bacterial infection or immune diseases, and leading tumor microenvironment deteriorated. Additionally, extracellular GP73 can also regulate signaling pathways of target cells by binding to their cell-surface receptors or entering the acceptor cells, thereby facilitating inflammation or promoting tumor development. In this review, we aim to summarize the findings, providing insights for future investigations on GP73 and its potential as a therapeutic target in ameliorating chronic inflammation in the immune and tumor microenvironment.

Background: The progression and metastasis of colorectal cancer (CRC) remain major clinical challenges due to a lack of effective therapeutic targets. Our preliminary study identified the upregulation of the propionyl-CoA carboxylase alpha chain (PCCA) gene in CRC, prompting further investigation into its functional roles. Methods: Bioinformatics analysis, colorectal tumor tissues, and CRC cell lines were used to determine PCCA expression. Wound healing, Transwell, and cell counting kit-8 (CCK-8) assays were conducted to evaluate the impacts of PCCA expression on CRC cell migration, invasion, and proliferation. Western blotting was used to assess epithelial-mesenchymal transition (EMT) markers and associated signaling pathways. Mouse models, flow cytometry, and quantitative polymerase chain reaction (PCR) were performed to investigate the influences of PCCA on CRC tumor growth, lung metastasis, and macrophage polarization. Results: PCCA is highly expressed in CRC tumor tissues compared to normal tissues and is associated with a poor prognosis. Knocking down PCCA reduced CRC cell migration, invasion, and proliferation, which were associated with the upregulation of E-cadherin, the downregulation of N-cadherin, Vimentin, and Fibronectin, as well as the inactivation of the extracellular signal-regulated kinase (ERK)/glycogen synthase kinase 3 beta (GSK3β) signaling pathway. Moreover, PCCA knockdown suppressed CRC tumor growth and lung metastasis, accompanied by an increase in M1-macrophage polarization. Conclusion: Knockdown PCCA inhibits the progression and metastasis of CRC, which is associated with EMT reversion, ERK/GSK3β signaling inactivation, and M1-macrophage polarization. These findings suggest that PCCA is a potential target for controlling CRC.

To evaluate the efficacy of re-resection in recurrent hepatocellular carcinoma (rHCC), identify prognostic factors, and provide clinical guidance.

A retrospective analysis was conducted on 130 rHCC patients undergoing re-resection and 60 primary HCC patients undergoing initial hepatectomy at Peking University People's Hospital (2014-2022). Disease-free survival (DFS) and overall survival (OS) were compared. Prognostic factors were identified using univariate and multivariate COX regression analyses.

Baseline characteristics were comparable between groups (P > 0.05). DFS was similar between groups (30.8 vs. 32.2 months, P = 0.612). The 1-year, 2-year, and 3-year DFS rates for the re-resection group were 88.5 %, 64.9 %, and 56.7 %, respectively, versus 88.3 %, 65.0 %, and 53.3 % for the primary resection group. OS was lower in the re-resection group (36.1 vs. 47.2 months, P = 0.041) with 1-year, 2-year, and 3-year OS rates of 90.8 %, 73.1 %, and 60.0 %, compared to 95.0 %, 80.0 %, and 68.3 % for the primary resection group. Significant factors affecting DFS were Child-Pugh classification (P = 0.044), time to recurrence (P = 0.002), tumor differentiation (P = 0.044), and satellite nodules (P = 0.019). Factors influencing OS included Child-Pugh classification (P = 0.040), time to recurrence (P = 0.002), and tumor differentiation (P = 0.032).

Re-resection is an effective treatment option for rHCC, with favorable outcomes as measured by DFS and OS, though OS is lower compared to initial hepatectomy. Key prognostic factors include Child-Pugh classification, time to recurrence, tumor differentiation, and satellite nodules.