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In the intricate landscape of the tumor microenvironment, tumor-associated macrophages (TAMs) emerge as a ubiquitous cellular component that profoundly affects the oncogenic process. The microenvironment of hepatocellular carcinoma (HCC) is characterized by a pronounced infiltration of TAMs, underscoring their pivotal role in modulating the trajectory of the disease. Amidst the evolving therapeutic paradigms for HCC, the strategic reprogramming of metabolic pathways presents a promising avenue for intervention, garnering escalating interest within the scientific community. Previous investigations have predominantly focused on elucidating the mechanisms of metabolic reprogramming in cancer cells without paying sufficient attention to understanding how TAM metabolic reprogramming, particularly lipid metabolism, affects the progression of HCC. In this review article, we intend to elucidate how TAMs exert their regulatory effects via diverse pathways such as E2F1-E2F2-CPT2, LKB1-AMPK, and mTORC1-SREBP, and discuss correlations of TAMs with these processes and the characteristics of relevant pathways in HCC progression by consolidating various studies on TAM lipid uptake, storage, synthesis, and catabolism. It is our hope that our summary could delineate the impact of specific mechanisms underlying TAM lipid metabolic reprogramming on HCC progression and provide useful information for future research on HCC and the development of new treatment strategies.

Ferroptosis, a novel form of cell death discovered in recent years, is typically accompanied by significant iron accumulation and lipid peroxidation during the process. This article systematically elucidates how tumor metabolic reprogramming affects the ferroptosis process in tumor cells. The paper outlines the basic concepts and physiological significance of tumor metabolic reprogramming and ferroptosis, and delves into the specific regulatory mechanisms of glucose metabolism, protein metabolism, and lipid metabolism on ferroptosis. We also explore how complex metabolic changes in the tumor microenvironment further influence the response of tumor cells to ferroptosis. Glucose metabolism modulates ferroptosis sensitivity by influencing intracellular energetic status and redox balance; protein metabolism, involving amino acid metabolism and protein synthesis, plays a crucial role in the initiation and progression of ferroptosis; and the relationship between lipid metabolism and ferroptosis primarily manifests in the generation and elimination of lipid peroxides. This review aims to provide a new perspective on how tumor cells regulate ferroptosis through metabolic reprogramming, with the ultimate goal of offering a theoretical basis for developing novel therapeutic strategies targeting tumor metabolism and ferroptosis.

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming. We demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming.

Glucose metabolic reprogramming describes the alterations in intracellular metabolic pathways in response to variations in the body’s internal environment. This metabolic reprogramming has been the subject of extensive research. The primary function is to enhance glycolysis for rapid ATP production, even with sufficient oxygen, leading to a significant accumulation of lactic acid, which subsequently affects the functions of tumor cells and immune cells within TME. Lactylation represents a newly identified post-translational modification (PTM) that occurs due to lactate accumulation and is observed in various proteins, encompassing both histone and non-histone types. Lactylation alters the spatial configuration of proteins, influences gene transcription, and thereby regulates gene expression. This modification serves as a significant epigenetic regulatory factor in numerous diseases. Glucose metabolic reprogramming and lactylation are intricately linked in the process of tumorigenesis. Glucose reprogramming activates essential enzymes, including hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA), through transcription factors such as HIF-1α and c-Myc, thereby enhancing glycolysis and lactate accumulation. Lactate functions as a metabolite and signaling molecule, acting as a substrate for lactylation facilitated by histone acetyltransferases such as CBP/p300. This epigenetic modification inhibits antitumor immunity through the upregulation of oncogenic signaling pathways, the induction of M2-type macrophage polarization, and the dysfunction of T-cells. Glucose metabolic reprogramming not only influences lactate synthesis but also provides sufficient substrates for lactate modification. The two factors jointly affect gene expression and protein function, acidify the tumor microenvironment, regulate immune evasion, and promote carcinogenesis. This review systematically details the mechanisms of lactylation and glucose metabolic reprogramming, their impacts on immune cells within the tumor microenvironment, and their interrelations in tumor progression, immunity, and inflammation.

Background The metabolic benefits of bariatric surgery that contribute to the alleviation of metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. However, the processes and mechanisms underlying the contribution of lipid metabolic reprogramming after bariatric surgery to attenuating MASLD remain elusive. Methods A case–control study was designed to evaluate the impact of three of the most common adipokines (Nrg4, leptin, and adiponectin) on hepatic steatosis in the early recovery phase following sleeve gastrectomy (SG). A series of rodent and cell line experiments were subsequently used to determine the role and mechanism of secreted adipokines following SG in the alleviation of MASLD. Results In morbidly obese patients, an increase in circulating Nrg4 levels is associated with the alleviation of hepatic steatosis in the early recovery phase following SG before remarkable weight loss. The temporal parameters of the mice confirmed that an increase in circulating Nrg4 levels was initially stimulated by SG and contributed to the beneficial effect of SG on hepatic lipid deposition. Moreover, this occurred early following bariatric surgery. Mechanistically, gain- and loss-of-function studies in mice or cell lines revealed that circulating Nrg4 activates ErbB4, which could positively regulate fatty acid oxidation in hepatocytes to reduce intracellular lipid deposition. Conclusions This study demonstrated that the rapid effect of SG on hepatic lipid metabolic reprogramming mediated by circulating Nrg4 alleviates MASLD.

Background Current evidence underlines the active role of neural infiltration and axonogenesis within the tumor microenvironment (TME), with implications for tumor progression. Infiltrating nerves stimulate tumor growth and dissemination by secreting neurotransmitters, whereas tumor cells influence nerve growth and differentiation through complex interactions, promoting tumor progression. However, the role of neural infiltration in the progression of non-small cell lung cancer (NSCLC) remains unclear. Methods This study employs the techniques of immunohistochemistry, immunofluorescence, RNA sequencing, molecular biology experiments, and a murine orthotopic lung cancer model to deeply analyze the specific mechanisms behind the differential efficacy of NSCLC immunotherapy from the perspectives of neuro-tumor signal transduction, tumor metabolism, and tumor immunity. Results This study demonstrates that nerve growth factor (NGF) drives neural infiltration in NSCLC, and 5-hydroxytryptamine (5-HT), which is secreted by nerves, is significantly elevated in tumors with extensive neural infiltration. Transcriptome sequencing revealed that 5-HT enhanced glycolysis in NSCLC cells. Pathway analysis indicated that 5-HT activated the PI3K/Akt/mTOR pathway, promoting tumor metabolic reprogramming. This reprogramming exacerbated immunosuppression in the TME. Neutralizing 5-HT-mediated metabolic reprogramming in tumor immunity enhanced the efficacy of PD-1 monoclonal antibody treatment in mice. Conclusions The findings of this study provide a novel perspective on the crosstalk between nerves and lung cancer cells and provide insights into further investigations into the role of nerve infiltration in NSCLC progression.

Diabetic kidney disease (DKD) is one of the major complications of diabetes, and its pathological progression is closely associated with lipid metabolic reprogramming. Under diabetic conditions, renal cells undergo significant lipid metabolic abnormalities, including increased lipid uptake, impaired fatty acid oxidation, disrupted cholesterol efflux, and enhanced lipid catabolism, as adaptive responses to metabolic stress. These changes result in the accumulation of lipids such as free fatty acids, diacylglycerol, and ceramides, leading to lipotoxicity that triggers inflammation and fibrosis. Hypoxia in the DKD microenvironment suppresses fatty acid oxidation and promotes lipid synthesis through the HIF-1α pathway, while chronic inflammation exacerbates lipid metabolic disturbances via inflammatory cytokines, inflammasomes, and macrophage polarization. Targeting lipid metabolism represents a promising therapeutic strategy for alleviating DKD; however, further clinical translational studies are warranted to validate the efficacy and safety of these approaches.

Background Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, marked by progressive renal damage. Recent evidence indicates that metabolic reprogramming is crucial to DN pathogenesis, yet its underlying mechanisms are not well understood. This study aimed to examine how metabolic reprogramming-related genes (MRRGs) are differentially expressed and to explore their potential mechanisms in the development of DN. Methods We analyzed the datasets GSE30528 and GSE96804 from the Gene Expression Omnibus (GEO), comprising 50 DN samples and 33 controls. MRRGs were sourced from GeneCards and PubMed. Data preprocessing included batch effect correction using the R package sva, followed by normalization and differential expression analysis with limma (|logFC|> 0.5, adj.p < 0.05). Functional enrichment analyses (GO, KEGG, GSEA) were performed using clusterProfiler. Protein–protein interaction (PPI) networks were constructed via STRING, identifying hub genes through CytoHubba. Regulatory networks (mRNA-TF, mRNA-miRNA) were derived from ChIPBase and StarBase. Validation of hub genes and ROC analysis assessed diagnostic performance. ssGSEA quantified immune cell infiltration. Results Our analysis identified 708 differentially expressed genes (DEGs), including 119 metabolic reprogramming-related DEGs (MRRDEGs). Enrichment analyses revealed significant roles for MRRDEGs in processes such as wound healing and pathways like MAPK signaling. The PPI network identified nine hub genes: FN1, CD44, KDR, EGF, HSPG2, HGF, FGF9, IGF1, and ALB , which exhibited high diagnostic accuracy (AUC 0.7 to 0.9). Notably, FN1 and CD44 showed significant association with renal fibrosis and could serve as potential biomarkers for early diagnosis and therapeutic targets in DN. Immune infiltration analysis showed notable differences in immune cell composition between DN and control samples. Conclusion This study identifies hub genes such as FN1 and CD44, with potential diagnostic value in DN. It also reveals immune cell infiltration differences between DN patients and controls, offering insights into disease progression and potential therapeutic targets.

MYC plays a pivotal role in the biology of various sarcoma subtypes, acting as a key regulator of tumor growth, proliferation, and metabolic reprogramming. This oncogene is frequently dysregulated across different sarcomas, where its expression is closely intertwined with the molecular features unique to each subtype. MYC interacts with critical pathways such as cell cycle regulation, apoptosis, and angiogenesis, amplifying tumor aggressiveness and resistance to standard therapies. Furthermore, MYC influences the tumor microenvironment by modulating cell–extracellular matrix interactions and immune evasion mechanisms, further complicating therapeutic management. Despite its well-established centrality in sarcoma pathogenesis, targeting MYC directly remains challenging due to its “undruggable” protein structure. However, emerging therapeutic strategies, including indirect MYC inhibition via epigenetic modulators, transcriptional machinery disruptors, and metabolic pathway inhibitors, offer new hope for sarcoma treatment. This review underscores the importance of understanding the intricate roles of MYC across sarcoma subtypes to guide the development of effective targeted therapies. Given MYC’s central role in tumorigenesis and progression, innovative approaches aiming at MYC inhibition could transform the therapeutic landscape for sarcoma patients, providing a much-needed avenue to overcome therapeutic resistance and improve clinical outcomes.

Colon cancer ranked third among the most frequently diagnosed cancers worldwide. Amino acid metabolic reprogramming was related to the occurrence and development of colon cancer. We looked for the amino acid metabolism genes (AMGs) associated with amino acid metabolism from molecular signatures database as prognostic markers and constructed amino acid metabolism scoring model (AMS). According to AMS, the patients were divided into high AMS and low AMS groups, and the prognostic characteristics, molecular phenotypes, somatic cell mutation characteristics, immune cell infiltration characteristics, and immunotherapy effect of the two groups were systematically analyzed. Finally, the compounds targeting AMGs were also screened. We screen out 6 prognostic AMGs ( P  < 0.05) and construct an AMS model based on them. K-M curve indicated that OS in low AMS group was significantly higher than that in high group ( P  < 0.05), which were validated in multiple datasets. And different AMS groups had different molecular phenotypes, somatic cell mutation characteristics and immune cell infiltration characteristics. Low AMS group had a better effect for immunotherapy. In addition, we predicted potential therapeutic compounds that could bind to AMGs target proteins. AMS model can be used as a hierarchical tool to evaluate the prognosis, immune infiltration characteristics and immunotherapy response ability of colon cancer. And the compounds screened based on AMGs may become new anti-tumor drugs.