The core clock gene period 1 (PER1) has been reported to possess tumor-suppressive functions; however, its role in regulating tumor vascular abnormalities in hepatocellular carcinoma (HCC) remains incompletely understood. Here, we integrated bioinformatics analysis with validation using clinical HCC specimens, cell-line experiments, and mouse models to investigate the role of PER1 in vascular structure-related phenotypes, angiogenesis-related factor expression, and hypoxia-inducible factor-1α (HIF-1α) signaling. PER1 was significantly downregulated in HCC tissues, and low PER1 expression was associated with poor patient prognosis. Restoration of PER1 expression inhibited HCC cell growth. Mechanistically, PER1 interacted with HIF-1α at the protein level and reduced its nuclear accumulation without markedly altering HIF-1α mRNA or total protein abundance. This change was accompanied by an angiogenesis-related factor profile characterized by increased TSP-1 and TIMP-2 expression and decreased VEGFA, TGF-β, SDF-1, and FGF-2 expression. Histological analyses further showed that PER1 overexpression was associated with increased CD31-positive vascular structures, enhanced α-SMA-positive perivascular/pericyte-like components, and more continuous collagen IV deposition, whereas PER1 knockdown produced the opposite effects. These findings indicate that PER1 participates in vascular structural remodeling in HCC. Collectively, our study suggests that PER1 modulates HIF-1α-associated angiogenic signaling and vascular structural remodeling, providing new insight into the interaction between circadian rhythm regulation and the HCC vascular microenvironment.

Ethnopharmacological relevance Patients with intermediate and advanced hepatocellular carcinoma (HCC) often derive limited benefit from systemic therapy and experience a substantial symptom burden with deterioration in quality of life. These challenges underscore the need for safe, effective adjunctive or alternative therapies. The traditional Chinese medicine concept of Central Qi shows conceptual contemporary with contemporary understanding of the gut-liver axis and microbiome biology. Chinese herbal medicines centered on tonifying the central and replenishing qi (Buzhong Yiqi) are considered adjunctive or alternative therapeutic options for alleviating symptoms, improving quality of life, and enhancing tolerance and adherence to standard treatments. Aim of this review To delineate links among the interrelations among Central Qi, the gut microbiota, and HCC, to synthesize evidence on how Buzhong Yiqi medicines modulate the gut microbiota, and to elucidate the proposed mechanistic bases for their potential adjunctive effects in HCC. This review aims to provide a biologically plausible framework to inform microbiome-based mechanistic research and clinical translation. Methods Databases including PubMed, Web of Science, Elsevier ScienceDirect, CNKI, and Google Scholar were searched using predefined terms related to hepatocellular carcinoma, gut microbiota, and the gut-liver axis, nutrient absorption, metabolic regulation, immune modulation, and Buzhong Yiqi medicines, as well as their representative herbs. In vivo, in vitro, and clinical studies published from 2000 to October 2025 were included. Results Dysbiosis disrupts the metabolic pathways of bile acid, short-chain fatty acid, and tryptophan metabolic pathways, while compromising the intestinal barrier. This disruption can worsen appetite regulation and energy imbalance, as well as weaken antitumor immunity. Buzhong Yiqi medicines have been reported to enrich beneficial taxa, reduce pathogens and pathobionts, and improve microbial metabolite profiles, restoration of barrier integrity, improvements in nutrient intake and energy homeostasis. These findings are heterogeneous and largely derived from non-HCC models, but collectively suggest potential support of metabolic and immune homeostasis, with possible influence on the tumor immune microenvironment. Early exploratory data also indicate a potential interaction with immune checkpoint inhibitors, although its clinical significance remains uncertain. Conclusion Central Qi deficiency provides a biologically plausible conceptual framework linking impaired digestion, disrupted energy metabolism, microbial dysbiosis, and reduced immune responsiveness in HCC. Modulation of the GM through Buzhong Yiqi medicines may offer supportive metabolic and immunological benefits, but current evidence is preliminary, based mainly on associative findings, and requires cautious interpretation. Key uncertainties remain regarding causal relationships, HCC-specific mechanisms, and the consistency of clinical effects. Future research should prioritize standardized preparations, mechanistic validation, biomarker-guided stratification, and rigorously designed clinical trials to clarify the clinical relevance of these proposed pathways and to advance global acceptance of integrative therapy.

Cold tumors often show poor effector immune cell entry or impaired effector function and therefore respond poorly to immunotherapy. Growing evidence suggests that neutrophil extracellular traps (NETs) are not simply by-products of tumor-associated inflammation. In some tumor settings, they can persist within lesions and act as retained local mediators. Among the upstream factors that may sustain this process, microbial signals warrant particular attention. In selected cancers, persistent lesion-related microbial signals may convert an initially transient NET response into persistent NET states. These states are linked to restricted effector immunity, stromal remodeling, vascular abnormalities, and other tumor-promoting consequences. This review reorganizes current evidence around the axis of lesion-related microbial signals, persistent NET states, and the cold tumor-related local restrictive environment. On this basis, a context-dependent working model is proposed in which lesion-related microbial signals contribute to the formation and maintenance of this environment through persistent NET states. Support for this sequence is not uniform across tumor types. Colorectal cancer currently provides the clearest line of support. Hepatocellular carcinoma is better understood as a setting in which the same framework is expressed more through organ conditioning and local amplification. Evidence from other tumors remains more limited and is often partial rather than fully resolved. Most available studies are still preclinical. Even so, current findings suggest that reducing sustained microbial stimulation or directly intervening in persistent NET states may help relieve this restrictive environment and inform future translational strategies.

To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5

Introduction:Polygonatum cyrtonema Hua (PC) is an essential herbal medicine in China, known for improving muscle quality and enhancing physical function; its active ingredients are polysaccharides (PCPs). A previous study revealed the anti-atrophy effects of PCPs in cachectic mice. However, whether the effects of PCPs on anti-atrophy are associated with gut microenvironment remain elusive. This research endeavored to assess the medicinal efficacy of PCPs in alleviating muscle atrophy and fat lipolysis and explore the potential mechanisms.Methods: A cancer cachexia model was induced by male C57BL/6 mice bearing Lewis lung tumor cells and chemotherapy. The pharmacodynamics of PCPs (32 and 64 mg/kg/day) was investigated through measurements of tumor-free body weight, gastrocnemius muscle weight, soleus muscle weight, epididymal fat weight, tissue histology analysis, and pro-inflammatory cytokines. Immunohistochemistry and Western blotting assays were further used to confirm the effects of PCPs. 16S rRNA sequencing, LC-MS and GC-MS-based metabolomics were used to analyze the gut microbiota composition and metabolite alterations. Additionally, the agonist of free fatty acid receptor 2 (FFAR2)—a crucial short-chain fatty acid (SCFA) signaling molecule—was used to investigate the role of gut microbiota metabolites, specifically SCFAs, in the treatment of cancer cachexia, with comparisons to PCPs.Results: This study demonstrated that PCPs significantly mitigated body weight loss, restored muscle fiber atrophy and mitochondrial disorder, alleviated adipose tissue wasting, strengthened the intestinal barrier integrity, and decreased the intestinal inflammation in chemotherapy-induced cachexia. Furthermore, the reversal of specific bacterial taxa including Klebsiella, Akkermansia, norank_f__Desulfovibrionaceae, Enterococcus, NK4A214_group, Eubacterium_fissicatena_group, Eubacterium_nodatum_group, Erysipelatoclostridium, Lactobacillus, Monoglobus, Ruminococcus, Odoribacter, and Enterorhabdus, along with alterations in metabolites such as amino acids (AAs), eicosanoids, lactic acid and (SCFAs), contributed to the therapeutic effects of PCPs.Conclusion: Our findings suggest that PCPs can be used as prebiotic drugs targeting the microbiome–metabolomics axis in cancer patients undergoing chemotherapy.

INTRODUCTION:In recent years, the effect of "intestinal-hepatic axis" in tumorigenesis of hepatocellular carcinoma (HCC) has been paid more and more attention, and the imbalance of gut microbiota is closely related to the pathogenesis of HCC. The Xiayuxue decoction (XYXD) has inhibitory effect on hepatic fibrosis, but the effect of XYXD on HCC is not clear. METHODS:We induced HCC mouse model by diethylnitrosamine and CCL4. HCC mice were treated with XYXD gavage. Hematoxylin-eosin staining was used to detect the pathological changes of liver tissue in mice. Immunohistochemistry was used to detect the level of Ki-67 in liver tumor and ZO-1 in colon tissue. The level of inflammatory factors in plasma, liver, and colon tissue of mice was detected by ELISA. The changes of macrophages and neutrophils in colorectal tissues of mice were counted by immunofluorescence. 16S sequencing was used to analyze the effect of XYXD treatment on gut microbiota of HCC mice. RESULTS:Our study found that XYXD could inhibit the progress of HCC. XYXD upregulated the expression levels of ZO-1, occludin, and claudin in colon tissue to repair intestinal mucosal barrier. XYXD could alleviate the infiltration of intestinal immune cells in HCC mice by inhibiting the data of macrophages and neutrophils in colon tissue and downregulating SIgA level. XYXD also regulated the composition of intestinal microorganisms and improved the diversity of gut microbiota, thus affecting the progress of HCC. CONCLUSION:XYXD inhibits the progress of HCC by influencing gut microbiota to regulate intestinal and liver inflammation and intestinal immune response.

Rheumatoid arthritis (RA) is driven by immune dysregulation, with macrophage polarization playing a central role in disease progression. A critical bottleneck in current rheumatoid arthritis (RA) management is that a subset of patients display inadequate responses to existing anti-inflammatory therapies (e.g., TNF-α inhibitors), leading to persistent inflammation that remains refractory to complete control. To identify new therapeutic targets and interventions, we analyzed single-cell RNA sequencing (scRNA-seq) data from 20 RA patients and identified a distinct M1-like pro-inflammatory macrophage population. Among 50 differentially expressed genes, CCL4 emerged as a novel pro-inflammatory target associated with M1 polarization. To counter this phenotype, we evaluated Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA), an engineered bacterium, in in vitro, ex vivo, and in vivo models. PA-MSHA promoted M2 polarization, enhanced anti-inflammatory markers, and suppressed M1-associated cytokines. In an adjuvant-induced arthritis (AIA) rat model, PA-MSHA significantly reduced paw swelling, improved joint integrity, and decreased macrophage and T cell infiltration. Mechanistically, PA-MSHA inhibited NF-κB and STAT1 signaling and downregulated CCL4 expressions. In vivo overexpression of CCL4 aggravated RA symptoms and sustained M1 polarization, confirming its pathogenic role. These findings highlighted CCL4 as a novel therapeutic target and demonstrated PA-MSHA's potential to reprogram macrophage phenotypes and ameliorate RA pathology.

Cancer immunotherapy faces significant limitations due to therapeutic resistance. Emerging evidences have identified the gut microbiota (GM) as a crucial regulator of antitumor immunity through its effects on the tumor immune microenvironment (TIME). Guided by the principle of "fu zheng qu xie" (fortifying healthy qi to reinforce immune homeostasis and eliminating pathogenic factors to promote immune clearance), traditional Chinese medicine (TCM) exerts multi-target systemic regulation. Specifically, TCM modulates gut microecology, which in turn regulates the production of microbial metabolites (e.g., short-chain fatty acids, bile acids), ultimately reprogramming TIME by enhancing immune cell infiltration into the tumor parenchyma, optimizing T-cell cytotoxicity and differentiation, improving antigen presentation, and alleviating immunosuppression. This review systematically summarizes the causal chain of "TCMGMmetabolitesimmune cellsTIME" across different immune phenotypes, emphasizing how bioactive TCM components and classical formulas reshape microbial communities, enrich beneficial bacteria, and regulate metabolic pathways to potentiate cancer immunotherapy. Despite promising preclinical data, challenges persist due to mechanistic complexity, the lack of standardization, and limited clinical translation. Potential solutions include multi-omics integration, intelligent screening of herbal compounds, and targeted delivery systems. With advancing pharmacological insights, TCM-derived microbiome modulators (TMMs), defined as phytochemicals and formulations that systematically modulate gut microecology, may overcome immunotherapy resistance, representing a novel strategy for enhancing cancer immunotherapy.

Intratumoral bacteria play a critical role in prostate cancer (PCa) progression by altering the tumor microenvironment. Modulating these bacterial populations can significantly enhance the effectiveness of cancer therapies, including chemotherapy and immunotherapy. However, the use of antibiotics often yields inconsistent results due to poor targeting and the potential for bacterial resistance. In this study, we propose a novel therapeutic approach combining 3-acetyl-11-keto-β-boswellic acid (AKBA) with chitosan-coated silver nanoparticles (Chi-Ag NPs) to enhance PCa treatment efficacy by eliminating tumor-resident bacteria and inhibiting tumor invasion and metastasis. To address the challenge of drug targeting in vivo, we designed nanocomposites (SZTI01@Chi-Ag@PLGA@AKBA) that specifically target prostate-specific membrane antigen (PSMA) receptors on PCa cells. Compared to free drugs, SZTI01@APA NPs showed a 1.67-fold increase in accumulation at the tumor site. Once localized, the AKBA and Chi-Ag NP combination effectively inhibited tumor proliferation, induced apoptosis, and eliminated tumor-resident bacteria. Additionally, the nanocomposites suppressed Th17 cell infiltration and reduced IL-17 secretion, thereby inhibiting primary tumor growth and metastasis. In summary, this bacteria-targeting strategy enhances chemotherapy efficacy and immune responses, presenting a promising therapeutic approach for improving PCa treatment outcomes and advancing the development of more effective therapies.

The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as Anaerotruncus colihominis and Dysosmobacter welbionis, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.

To investigate the role of Fuzi polysaccharide(FPS) in combination with lenvatinib(LEN) in regulating tumor-associated macrophage(TAM) polarization to enhance the anti-hepatocellular carcinoma(HCC) efficacy, the non-toxic concentrations of FPS and LEN on RAW264.7 cells were screened by cell counting kit-8(CCK-8). The co-culture system of RAW264.7 and Hepa1-6 cells was established, and flow cytometry was used to detect changes in M1 and M2 macrophage phenotypes. Quantitative real-time polymerase chain reaction(qRT-PCR) was performed to assess the mRNA expression levels of M1-associated factors, inducible nitric oxide synthase(iNos) and interleukin 12b(IL-12b), as well as M2-associated factors arginase 1(Arg-1) and IL-10. The effects of macrophages treated with FPS and LEN on HCC cell proliferation, migration, invasion, and apoptosis were evaluated by 5-ethynyl-2'-deoxyuridine(EdU) staining, wound healing assay, Transwell invasion assay, and Annexin V/PI double-staining flow cytometry. A C57BL/6 subcutaneous HCC xenograft mouse model was established to observe the tumor growth, body weight, spleen index, and tumor-infiltrating macrophage polarization. CCK-8 assay showed that 50-200 mg·L~(-1) FPS and 1-5 μmol·L~(-1) LEN had no inhibitory effects on RAW264.7 macrophages. Flow cytometry and qRT-PCR results demonstrated that 200 mg·L~(-1) FPS + LEN significantly increased the proportion of M1 macrophages(P<0.01) and the M1/M2 ratio(P<0.01), upregulated the expressions of M1-associated genes iNos and IL-12b(P<0.01), reduced the proportion of M2 macrophages(P<0.01), and inhibited the expressions of M2-associated genes Arg-1 and IL-10(P<0.01). Functional assays revealed that macrophages of the FPS + LEN group inhibited Hepa1-6 proliferation(P<0.01), promoted apoptosis(P<0.01), and reduced migration and invasion(P<0.01). In vivo experiments showed that compared to those of the LEN group, the tumor volume was significantly reduced(P<0.05), and the spleen index was significantly increased(P<0.05) in the FPS + LEN group. The body weight was not decreased, and the proportion of M1 macrophages and the M1/M2 ratio in the tumors were significantly increased in the FPS + LEN group(P<0.01). In conclusion, FPS combined with LEN enhances the anti-HCC effect by promoting the M1 polarization of TAMs.

BACKGROUND:3-acetyl-11-keto-beta-boswellic acid (AKBA) is a monomer extracted from the traditional Chinese herbs of Boswellia that has antitumor effects. However, the therapeutic effects and mechanisms of AKBA in prostate cancer (PCa) are unclear. OBJECTIVE:To predict the target of AKBA treatment of PCa using network pharmacology methods and validate the predicted targets through CCK-8, flow cytometry, cell scratch test, Transwell chamber assay, and proteomics. METHODS:The protein-protein interaction (PPI) network was established. Further analysis was performed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes for biological functionality and pathway enrichment. CCK-8 assay, flow cytometry, wound healing assay, and Transwell chamber assay were used to detect cell proliferation, apoptosis, invasion, and metastasis, respectively. Transcriptomics was used to detect the effects of AKBA on protein levels in PCa cells. RESULTS:120 potential targets for the AKBA treatment of PCa were obtained. GO enrichment analysis revealed that the biological processes of AKBA treatment of PCa include the steroid metabolic process, drug response, and fatty acid metabolic process. The results of KEGG enrichment revealed that the IL-17 signaling pathway is the key pathway for the AKBA treatment of PCa. In addition, experimental results demonstrate that AKBA inhibits the proliferation of PCa cells, induces cell apoptosis, and suppresses cell invasion and metastasis. Proteomics identified 119 differentially expressed proteins, which were primarily enriched in pathways closely related to the phogosome, pathways in cancer, IL-17 signaling pathway, spliceosome, PPAR signaling pathway, and HIF-1 signaling pathway. CONCLUSION:Through the methodologies of network pharmacology and transcriptomics, AKBA may exert its therapeutic effects on PCa by modulating the expression of the IL-17 signaling pathway.

Background:Rising cancer incidence in reproductive-aged individuals, coupled with improved long-term survival, indicates an increasing need for fertility preservation (FP) in this population. However, limited evidence exists on the decision-making of FP from the perspectives of cancer patients in a Chinese context. This qualitative study aimed to examine the patient perceptions of the FP decision and to identify barriers and unmet needs, addressing a significant gap within evolving precision oncology and fertility care contexts. Methods:Face-to-face, semi-structured interviews were conducted with 12 cancer patients from a tertiary hospital in Hunan Province, China, from March 2024 to June 2024. The interviews were audio-recorded, transcribed verbatim, and analyzed thematically using Colaizzi's seven-step analysis. Results:Three themes and nine subthemes were identified: insufficient information support (lack of information sources, inappropriate timing of information disclosure, and poor doctor-patient communication); personal and family concerns (impact on cancer treatment, impact on offspring health, marital and reproductive status, financial constraints); ethical dilemmas (conflicts with survival needs, and emotional challenges). Conclusion:Young cancer patients predominantly aspire to preserve fertility but face multiple decision-making challenges. To address these challenges, healthcare professionals should fully understand the patients' needs, provide accurate and timely information tailored to their needs, and enhance communication skills to facilitate informed decision-making regarding FP, with important implications for clinical practice and public health.

[This corrects the article DOI: 10.1016/j.heliyon.2024.e32914.].

Background. Gecko has been widely documented in Chinese scientific literature as an anti-tumor agent for various illnesses for thousands of years, and more recently, it has been examined for its anti-tumor effects on several cancers. The effect of Gecko microRNAs (miRNAs) on hepatocellular carcinoma (HCC) has not yet been reported. Objectives. This study was designed to identify miRNAs in Gecko through small RNA sequencing and utilize bioinformatics techniques to construct a potential regulatory network and explore the possible mechanisms of exogenous miRNAs involved in HCC. Materials and methods. RNA was extracted from Gecko tablets, and we screened the Gecko miRNA expression dataset after high-throughput sequencing. Bioinformatics analysis was used to identify novel Gecko and HCC survival-related miRNA-mRNA cross -species regulation networks. Results. miR-100-5p, miR-99a-5p and miR-101-3p were identified as critical for the role of Geckos in HCC. Nine downstream mRNAs ( EZH2 , KPNA2 , LMNB1 , LRRC1 , MRGBP , SMARCD1 , STMN1 , SUB1 , and UBE2A ) were identified as target genes for critical miRNAs. A miRNA-mRNA regulatory network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed these key mRNAs might be associated with both the suppression and progression of HCC. The novel network significantly correlated with the abundance of multiple immune cells, as determined with immune infiltration analysis. Conclusions. These findings suggest that Gecko may inhibit progression and exert a therapeutic effect on HCC by targeting critical miRNA-mRNA networks for cross -species regulation. It also provides a reference for future research and development of traditional Chinese medicine (TCM).

Based on the focal adhesion kinase (FAK)/steroid receptor coactivator (Src)/extracellular regulated protein kinase (ERK) pathway,this study explored the effects of Xihuang Pills on angiogenesis,invasion,and metastasis in prostate cancer.Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze and identify the active ingredients of Xihuang Pills.Bioinformatics techniques,including R language and Perl programs,were employed to analyze the interactions between prostate cancer-related targets and the potential targets of Xihuang Pills.A subcutaneous transplantation tumor model of prostate cancer was established in nude mice using PC3 cells to verify the efficacy and molecular mechanisms of Xihuang Pills.In vitro cellular experiments,including cell proliferation assays (CCK-8),Transwell assays,scratch assays,real-time quantitative reverse transcription PCR,and Western blot,were used to detect the effects of Xihuang Pills on the proliferation,invasion,and migration of prostate cancer cells,as well as on FAK/Src/ERK pathway-related targets.LC-MS/MS identified 99 active ingredients in Xihuang Pills,including gallic acid,gentisic acid,artemisinin,corilagin,phenylbutazone-glucoside,thujic acid,and arecoic acid B.Network pharmacological analysis of the active ingredients in Xihuang Pills revealed that the FAK/Src/ERK signaling pathway was a key pathway in its anti-prostate cancer effects.In vivo and in vitro experiments confirmed that Xihuang Pills significantly inhibited the proliferation,invasion,and migration of PC3 and LNCaP cells,suppressed the growth of PC3 subcutaneous tumors,and reduced the protein expression levels related to the FAK/Src/ERK signaling pathway.In conclusion,the inhibition of angiogenesis,invasion,and metastasis by regulating the FAK/Src/ERK pathway is one of the mechanisms by which Xihuang Pills exert anti-prostate cancer effects.

Plant-derived exosome-like nanoparticles (PELNs) are natural nanocarriers and effective delivery systems for plant microRNAs (miRNAs). These PELN-carrying plant miRNAs can regulate mammalian genes across species, thereby increasing the diversity of miRNAs in mammals and exerting multi-target effects that play a crucial role in diseases, particularly cancer. PELNs demonstrate exceptional stability, biocompatibility, and targeting capabilities that protect and facilitate the up-take and cross-kingdom communication of plant miRNAs in mammals. Primarily ingested and absorbed within the gastrointestinal tract of mammals, PELNs preferentially act on the intestine to regulate intestinal homeostasis through functional miRNA activity. The oncogenesis and progression of cancer are closely associated with disruptions in intestinal barriers, ecological imbalances, as well as secondary changes, such as abnormal inflammatory reactions caused by them. Therefore, it is imperative to investigate whether PELNs exert their anticancer effects by regulating mammalian intestinal homeostasis and inflammation. This review aims to elucidate the intrinsic crosstalk relationships and mechanisms of PELNs-mediated miRNAs in maintaining intestinal homeostasis, regulating inflammation and cancer treatment. Furthermore, serving as exceptional drug delivery systems for miRNAs molecules, PELNs offer broad prospects for future applications, including new drug research and development along with drug carrier selection within targeted drug delivery approaches for cancer therapy.

BackgroundThe long history of clinical experience in China have confirmed the effectiveness of traditional Chinese medicine (TCM) in treating prostate cancer (PCa). Until now, several bioactive compounds with anti-PCa potential, such as curcumin, gallic acid, and quercetin, have been extracted from TCM. Recent studies have shown that encapsulating these TCM bioactive compounds into nano-delivery system enhanced their bioavailability and improved their ability to target PCa tumors. Purpose: This review aims to summarize the anti-PCa effects and molecular mechanisms of TCM bioactive compounds and discuss the clinical application prospects and future research trends of nano-delivery system based on these compounds.MethodsLiteratures focusing on the treatment of PCa using traditional Chinese medicine compounds via nano-drug delivery system were searched from Electronic databases, including PubMed, Web of Science, and Scopus until December 2023.ResultsPolyphenols, alkaloids, terpenes, and quinones exhibit anti-PCa effects through various pathways. Notably, compounds like curcumin, gallic acid, quercetin, and tanshinone have been extensively studied in nano-delivery systems for anti-PCa purpose. Nano-delivery systems enhance the biological activity of free compounds and reduce toxic side effects, as well. Commonly used nanomaterials for delivering TCM compounds include polymer nanomaterials, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and niosomes.ConclusionResearch on nano-delivery systems for TCM bioactive compounds holds promising prospects for anti-PCa therapy. However, extensive clinical trials are necessary to evaluate the effectiveness and safety of these nanodrugs.

BACKGROUND Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation. METHODS This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway, contributing to the suppression of liver cancer growth.

ObjectiveProstate cancer, marked by a high incidence and mortality rate, presents a significant challenge, especially in the context of castration-resistant prostate cancer (CRPC) with limited treatment options due to drug resistance. This study aims to explore the anti-tumor effects of Xihuang Pills (XHP) on CRPC, focusing on metabolic reprogramming and the Wnt/β-catenin pathway.MethodsIn vitro and in vivo biofunctional assays were employed to assess the efficacy and mechanisms of XHP. Subcutaneous xenografts of PC3 in mice served as an in vivo model to evaluate XHP's anti-tumor activity. Tumor volume, weight, proliferation, and apoptosis were monitored. Various assays, including CCK8, TUNEL assay, QRT-PCR, and Western Blotting, were conducted to measure metabolic reprogramming, proliferation, apoptosis, and cell cycle in prostate cancer cells. RNA-seq analysis predicted XHP's impact on prostate cancer, validating the expression of Wnt/β-catenin-related proteins and mRNA. Additionally, 58 compounds in XHP were identified via LC-MS/MS, and molecular docking analysis connected these compounds to key genes.ResultsIn vitro and in vivo experiments demonstrated that XHP significantly inhibited CRPC cell viability, induced apoptosis, and suppressed invasion and migration. mRNA sequencing revealed differentially expressed genes, with functional enrichment analysis indicating modulation of key biological processes. XHP treatment downregulated Wnt signaling pathway-related genes, including CCND2, PRKCG, and CCN4. Moreover, XHP effectively inhibited glucose uptake and lactate production, leading to reduced HIF-1α and glycolytic enzymes (GLUT1, HK2, PKM2), suggesting its potential in attenuating the Warburg effect. Molecular docking analysis suggested a plausible interaction between XHP's active compounds and Wnt1 protein, indicating a mechanism through which XHP modulates the Wnt/β-catenin pathway.ConclusionXHP demonstrated remarkable efficacy in suppressing the growth, proliferation, apoptosis, migration, and invasiveness of prostate tumors. The interaction between XHP's active constituents and Wnt1 was evident, leading to the inhibition of Wnt1 and downstream anti-carcinogenic factors, thereby influencing the β-catenin/HIF-1α-mediated glycolysis.