The oligopeptide transporter PEPT2 is a key transporter mediating the reabsorption of drugs and peptide substances. Unfortunately, there are currently no biomarkers to evaluate the function of the PEPT2 transporter. The aim of this study was to screen and validate endogenous biomarkers of renal tubular PEPT2. Through metabolomics and literature searches, we initially identified two endogenous substrates of PEPT2: carnosine and 5-ALA. By evaluating the uptake of a PEPT2-overexpressing cell line, protein binding rates, and substrate specificity, carnosine was screened as a potential endogenous biomarker for PEPT2. In rats subjected to inhibitor intervention, the level of carnosine significantly increased. In a gentamicin-induced renal injury model, carnosine and creatinine levels changed almost simultaneously. Carnosine is primarily filtered by the glomeruli (with an albumin binding rate of 33%), and subsequently reabsorbed by the PEPT2 transporter, exhibiting appropriate affinity (Km of 59.04μM) and a half-life of 5.5±2.2 hours. These results indicate that carnosine is a suitable endogenous biomarker that can predict renal injury through the detection of its levels.
Purpose: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for nearly 90% of cases and causing over 700,000 deaths annually. Increasing evidence indicates that dysregulated lipid metabolism plays a critical role in hepatocarcinogenesis by promoting tumor initiation, progression, metastasis, and drug resistance. This review provides a comprehensive overview of the molecular mechanisms underlying lipid metabolic reprogramming in HCC, highlights key therapeutic targets, and discusses emerging inhibitors with potential for future drug development. Methods: A comprehensive literature search was conducted by critically reviewing published research articles, review papers, and clinical studies on lipid metabolism in liver cancer. Current advances were systematically evaluated, focusing on lipid metabolic pathways, associated molecular targets and signaling mechanisms, as well as small-molecule inhibitors, natural products, and clinically relevant therapeutic agents. Results: Dysregulated lipid metabolism is a hallmark of HCC, contributing to cancer cell proliferation, survival, angiogenesis, metastasis, immune evasion, and resistance to conventional therapies. Alterations in de novo lipogenesis, fatty acid uptake, fatty acid oxidation, cholesterol biosynthesis, and phospholipid metabolism are frequently observed in HCC. Key enzymes and regulatory proteins, including fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase-1 (SCD1), ATP citrate lyase (ACLY), sterol regulatory element-binding proteins (SREBPs), and peroxisome proliferator-activated receptors (PPARs), have emerged as promising therapeutic targets. Numerous synthetic compounds, natural products, and investigational inhibitors targeting these regulators have demonstrated encouraging preclinical and clinical potential for suppressing HCC progression. Conclusion: Targeting aberrant lipid metabolism represents a promising therapeutic strategy for HCC. Improved understanding of lipid metabolic reprogramming and its regulatory networks has enabled the identification of novel molecular targets and therapeutic inhibitors. Future studies integrating lipid metabolism with precision medicine may accelerate the development of effective targeted therapies, facilitate early intervention, and improve clinical outcomes in patients with liver cancer.
The immunosuppressive stroma in colorectal cancer (CRC) plays a central role in therapeutic resistance. Modulating key targets within this stromal compartment has been proposed as a promising strategy for restoring antitumor immunity and overcoming resistance mechanisms. Several immunomodulatory agents, including next-generation immunotherapies, small-molecule inhibitors targeting specific receptors or signaling pathways, and natural compounds, have shown potential for remodeling the tumor immune microenvironment (TIME). In addition, nanoparticle-based delivery systems may further enhance the therapeutic efficacy of these agents. Evidence from both preclinical and clinical studies suggests that targeting stromal and immunosuppressive cells can effectively remodel the antitumor immune response in CRC. Furthermore, specific inhibitors, natural products, and their nanoformulations may enhance antitumor immunity by suppressing the recruitment and activity of immunosuppressive stromal and immune cells. This review summarizes the current knowledge of emerging pharmacological agents, including immunomodulators, therapeutic drugs, and their nanoformulations, for restoring antitumor immunity in CRC. It first discusses the fundamental immunosuppressive interactions within the TME and subsequently examines how these agents enhance immune responses by reprogramming stromal and immune cells, as well as their secreted mediators within the TIME.
Background and purpose: Colorectal cancer (CRC) continues to be a major contributor to cancer-related mortality despite advances in diagnosis and management, highlighting the need for targeted, cost-effective therapies. Phytochemicals like curcumin (Cur) and silibinin (Sil) show promising anticancer effects, supported by preclinical and clinical evidence. Nanocarriers, such as niosomes (Nio), enhance the delivery and bioavailability of these bioactive molecules. The present study evaluates the anticancer potency of Cur and Sil, alone and in combination, in free and niosome-encapsulated forms against HCT116 cells, advancing plant-based nanotherapeutics for CRC. Methods: Niosomes were prepared by thin-film hydration; physicochemical characterization was carried out using DLS, FE-SEM, and FTIR. Cytotoxicity of free, encapsulated, and combined drugs on HCT116 cells was measured using the MTT assay. Cell cycle and apoptosis were analyzed via flow cytometry. Gene expressions of hTERT, BAX, BCL-2, Casp3, Casp7, CCND1, and MMP9 were assessed by qRT-PCR. Cell migration was evaluated with a scratch assay. Results: The synthesized niosomes exhibited suitable physicochemical characteristics for effective drug delivery. MTT assays demonstrated that both curcumin (Cur) and silibinin (Sil) inhibited HCT116 cell proliferation individually. Their combination – whether free, niosome-encapsulated, or niosome-encapsulated with hyaluronic acid – produced a significant decrease in IC₅₀ values. The nano-formulated combination also showed superior induction of apoptosis and cell cycle arrest compared to free drugs. These effects were supported by significant changes in gene expression (p < 0.05). Conclusion: These findings show that co-loaded formulation reduced viability in the tested colorectal cancer cell line, with greater in vitro activity observed for the hyaluronic acid decorated formulation.
Abstract Purpose: Despite advances in food and disease databases, a lack of integrated resources remains that systematically elucidate molecular-level food-disease associations. This study aims to introduce a comprehensive framework for mapping associations between foods, their metabolites, molecular targets, and diseases, using breast cancer as a case study. Methods: We integrated data from FooDB, HMDB, and DisGeNET to extract information on foods, food-derived metabolites, protein/gene targets, and disease associations. Data cleaning and mapping were performed in Excel 2019. Networks illustrating food-metabolite-protein/gene-disease interactions were constructed and visualized using Cytoscape 3.7.2. Functional enrichment and topological analyses (degree and betweenness centrality) identified key nodes. Additionally, a systematic literature review was conducted in PubMed to synthesize evidence from systematic reviews and meta-analyses on dietary factors and breast cancer risk. Results: The integrated network included nearly 1,000 foods, 61,500 ingredients, 250,000 metabolites, and 15,000 disease variants. The breast cancer network comprised 15,966 nodes and 321,144 edges. APOE emerged as the central gene, connected to 13,628 metabolites, while major food groups also featured as key nodes. Literature synthesis confirmed that high intake of fruits and vegetables is protective against breast cancer, while alcohol, fats, and processed meats increase risk, aligning with network findings. Conclusion: This study proposes a molecular framework that links foods to diseases through metabolites and pathways, enabling testable hypotheses and informing precision nutrition. It urges improved data integration, control of confounders, and experimental validation to support personalized dietary recommendations. Keywords food-disease associations, molecular nutrition, relation extraction, precision nutrition, network analysis
