Peanut seeds are enriched with protein and fatty acids, making them susceptible to infection by Aspergillus flavus (A. flavus). The infected seeds are harmful to human health due to the aflatoxin contamination. Despite ongoing research, a comprehensive understanding of the metabolite variations in peanut seeds during A. flavus infection remains elusive. In this study, we established a detailed endogenous chemical profile consisting of 1462 metabolites in shelled peanut seeds, identified 895 and 671 differentially expressed metabolites (DEMs) on the 3rd and 6th days post-infection by A. flavus, respectively. Among these, 425 DEMs were common to both profiles, with the majority of co-expressed DEMs displaying an up-regulated expression pattern in response to A. flavus infection. Further metabolites interaction analysis indicated that phenolic acids significantly correlated with A. flavus infection. Specifically, five metabolites classified as phenolic acids demonstrated the ability to repress A. flavus growth in vitro. The anti-infection properties of peanut phenolic acids were confirmed by their higher content in resistant peanut varieties. Overall, our study elucidates the chemical profile of endogenous metabolite variations in A. flavus infected peanut seeds, demonstrating that elevated phenolic acid content can be employed as a biomarker for identifying peanut varieties resistant to A. flavus infection.

β-sitosterol is a natural plant steroidal compound with anti-cancer properties against various tumors. This work explored the inhibitory effect of β-sitosterol on the progression of lung adenocarcinoma (LUAD) and further analyzed its targets. We applied network pharmacology to obtain the components and targets of Ganoderma spore powder. The biological functions of β-sitosterol and CHRM2 were studied using the homograft mouse model and a series of in vitro experiments involving quantitative reverse transcription polymerase chain reaction, western blot, CCK-8, flow cytometry, immunohistochemistry and immunofluorescence. The regulatory influence of β-sitosterol on the glycolysis pathway was validated by measuring glucose consumption and lactate production, as well as the extracellular acidification rate and oxygen consumption rate. We found that CHRM2 binds directly to β-sitosterol. In vitro, CHRM2 overexpression repressed the apoptosis rate and expression of apoptosis-related proteins in LUAD cells, and promoted glycolysis, while the addition of lonidamine attenuated the apoptosis-inhibiting effect conferred by CHRM2 overexpression. Furthermore, β-sitosterol hindered glycolysis as well as the growth of tumors in vitro and in vivo. CHRM2 overexpression reversed the effect of β-sitosterol on the biological behavior of LUAD cells. Our results emphasize that CHRM2 is a direct target of β-sitosterol in LUAD cells. β-sitosterol can repress the glycolysis pathway, exerting an anti-tumor effect. These findings provide new support for the use of β-sitosterol as a therapeutic agent for LUAD.

β‑sitosterol (SIT) has anti‑inflammatory, anti‑tumor and anti‑fibrotic effects. However, the precise mechanisms underlying its efficacy in keloid treatment remain elusive. The present study aimed to elucidate the therapeutic effect of SIT on keloids. The active components of Fructus arctii, target molecules of these components and disease‑associated target molecules were identified and retrieved from various databases. Molecular docking was employed to evaluate the binding affinity of the active compounds for key targets. Cell viability and proliferation were evaluated via CCK‑8 and EdU assays, while cell migration capacity was assessed via wound healing assays and cell migration and invasion abilities were determined via Transwell assays. A rescue study involving YS‑49 was conducted. Western blot analysis was performed to assess the expression levels of proteins associated with EMT and proteins involved in the PI3K/AKT signaling pathway. A subcutaneous keloid fibroproliferative model was established in nude mice and immunohistochemical staining was performed on tissue sections. By intersecting the keloid targets, 29 targets were identified, with 10 core targets revealed by protein-protein interaction analysis. Molecular docking revealed a robust binding affinity between SIT and PTEN. In addition to inhibiting cell viability, invasion and migration, SIT significantly decreased the levels of phosphorylated (p‑)PI3K and p‑AKT, downregulated the protein expression of Vimentin and Snail proteins and increased the protein expression of Zonula Occludens‑1 and E‑cadherin. YS‑49 reversed the inhibitory effect of SIT on keloid in SIT‑treated cells. In vivo experiments demonstrated that SIT suppressed the growth of a keloid model in nude mice and increased PTEN expression. The present study provided the first evidence that SIT inhibits keloid proliferation, migration and invasion by modulating the PTEN/PI3K/AKT signaling pathway, suggesting its potential as a novel therapeutic approach for keloid treatment.

TWIST1 is aberrantly expressed in ovarian cancer (OC). MFAP2 is a downstream target of TWIST1, and we previously found MFAP2 facilitated OC development by activating FOXM1/β-catenin. We planned to investigate the mechanisms of TWIST1 in OC. GEPIA (a database for gene expression analysis) and UALCAN (a database containing comprehensive cancer transcriptome and clinical patient data) investigated TWIST1's connection to MFAP2 and patient survival in ovarian serous cystadenocarcinoma (OV). Human OC cells (A2780 and CAOV3) were transfected with si-TWIST1, oe-TWIST1, oe-MFAP2, or si-TWIST1 + oe-MFAP2. Cellular apoptosis, viability, migration, and invasion were detected. TWIST1, MFAP2, FOXM1, and β-catenin protein expressions were tested. Dual-luciferase and ChIP-qPCR validated the correlation between MFAP2 and TWIST1. Moreover, OC mice were established by injecting OC cells subcutaneously. The pathology, apoptosis, as well as Ki67, TWIST1, MFAP2, FOXM1, and β-catenin protein levels of tumors were assessed. TWIST1 expression positively correlated with MFAP2 expression, but negatively related to patients' survival in OV. TWIST1 overexpression promoted malignant behaviors, and increased MFAP2, FOXM1, and β-catenin protein levels for OC cells. TWIST1 knockdown exhibited the opposite trend. In vivo, TWIST1 knockdown disrupted tissue structure, induced apoptosis, decreased Ki67, TWIST1, MFAP2, FOXM1, and β-catenin protein levels in tumor. Interestingly, MFAP2 overexpression reversed the effects of TWIST1 knockdown in vitro and in vivo. Additionally, dual-luciferase and ChIP-qPCR confirmed MFAP2 was a downstream target for TWIST1 in OC. TWIST1 regulated FOXM1/β-catenin to promote the growth, migration, and invasion of OC cells by activating MFAP2, indicating that targeting TWIST1 may be effective for treating OC.

Chronic pain strongly affects the quality of life of patients with liver cancer pain. Safe and effective management of cancer-related pain is a worldwide challenge. Traditional Chinese medicine (TCM) has rich clinical experience in the treatment of cancer pain. The Fuzhengxiaoliu patch (FZXLP) is a compound TCM with the effects of detoxification and pain relief and has shown great efficacy in the treatment of patients with liver cancer, but high-quality clinical research that provides research-based evidence is lacking. We designed a randomized, double-blind, placebo-controlled trial to explore and evaluate the efficacy of FZXLP for the treatment of liver cancer pain.

This is a prospective, randomized, double-blind, placebo-controlled trial. The trial will enrol 72 participants with primary liver cancer with cancer pain (damp-heat stagnation and toxin and blood stasis syndrome). The primary objective is to measure the reduction in pain using FZXLP in combination with tegafur, gimeracil and oteracil potassium capsule (S-1) compared to the placebo group with S-1. Pain will be measured by the number of opioids used, Chinese versions of the numerical rating scale (NRS), pain relief rate and number of breakthrough cases of cancer pain (BTcP). The secondary objectives include response evaluation criteria in solid tumors (RECIST), tumor markers, TCM syndrome scores, weight, functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire scores, and self-rating anxiety scale scores. Adverse events (AEs) will be recorded throughout the study.

This study integrated TCM with clinical research to assess the efficacy and safety of the addition of FZXLP in the treatment of primary liver cancer pain.

Chinese clinical trial registry, ChiCTR2300076951, Registered on October 25, 2023. https://www.chictr.org.cn/showproj.html?proj=209608.

Yiqi Liangxue Jiedu prescription (YLJP), a Chinese medicine that is commonly used to prevent liver cancer and is authorized by a national patent (patent No. ZL202110889980.5) has a therapeutic effect on precancerous lesions; however, the underlying mechanism remains unclear. This study is aimed at determining the clinical therapeutic efficacy of YLJP in patients with precancerous liver lesions and to explore and validate its possible effector mechanism.

The 1-year incidence of hepatocellular carcinoma (HCC) was retrospectively analyzed in 241 patients with cirrhosis complicated by abnormal alpha-fetoprotein precancer. Network pharmacological analysis, molecular docking, and molecular dynamics simulation were used to explore the key targets and compounds of YLJP in treating HCC. Immunohistochemical methods were used to detect the expression of key proteins in tumor and cirrhotic tissues. Finally, the mechanism underlying the effects of YLJP was verified in rats with precancerous lesions.

The 1-year incidence of HCC was lower in the YLJP group than in the Western medicine group. The Wnt pathway protein, CTNNB1, is a key target of YLJP in preventing and treating HCC, and the canonical Wnt pathway is the key signaling pathway and is overexpressed in human liver tumors. In vivo experiments showed that YLJP significantly inhibited the canonical Wnt pathway and reduced the abnormal differentiation of hepatic oval cells. The binding of CTNNB1 to oleanolic acid, stigmasterol, and beta-sitosterol was found to be stable, indicating the action of these compounds in treating HCC.

YLJP reduces the 1-year incidence of HCC, with its mechanism likely due to oleanolic acid, beta-sitosterol, and stigmasterol inhibition of the CTNNB1 activation of the β-catenin protein, which in turn regulates the Wnt signaling pathway and prevents the abnormal differentiation of hepatic oval cells into cancer cells, thus delaying the occurrence and progression of the disease.

Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies, liver cancer remains the fourth leading cause of cancer-related mortality worldwide. Tumor relapse, resistance to current anti-cancer drugs, metastasis, and organ toxicity are the major challenges that prevent considerable improvements in patient survival and quality of life. Calculus bovis (CB), an ancient Chinese medicinal drug, has been used to treat various pathologies, including stroke, convulsion, epilepsy, pain, and cancer. In this editorial, we discuss the research findings recently published by Huang et al on the therapeutic effects of CB in inhibiting the development of liver cancer. Utilizing the comprehensive transcriptomic analyses, in vitro experiments, and in vivo studies, the authors demonstrated that CB treatment inhibits the tumor-promoting M2 phenotype of tumor-associated macrophages via downregulating Wnt pathway. While multiple studies have been performed to explore the molecular mechanisms regulated by CB, this study uniquely shows its role in modulating the M2 phenotype of macrophages present within the tumor microenvironment. This study opens new avenues of future investigations aimed at investigating this drug's efficacy in various mouse models including the effects of combination therapy, and against drug-resistant tumors.

β-Sitosterol is a natural compound with demonstrated anti-cancer properties against various cancers. However, its effects on hepatocellular carcinoma (HCC) and the underlying mechanisms are not well understood. This study aims to investigate the impact of β-sitosterol on HCC. In this study, we investigated the effects of β-sitosterol on HCC tumour growth and metastasis using a xenograft mouse model and a range of molecular analyses, including bioinformatics, real-time PCR, western blotting, lentivirus transfection, CCK8, scratch and transwell assays. The results found that β-sitosterol significantly inhibits HepG2 cell proliferation, migration and invasion both in vitro and in vivo. Bioinformatics analysis identifies forkhead box M1 (FOXM1) as a potential target for β-sitosterol in HCC treatment. FOXM1 is upregulated in HCC tissues and cell lines, correlating with poor prognosis in patients. β-Sitosterol downregulates FOXM1 expression in vitro and in vivo. FOXM1 overexpression mitigates β-sitosterol's inhibitory effects on HepG2 cells. Additionally, β-sitosterol suppresses epithelial-mesenchymal transition (EMT) in HepG2 cells, while FOXM1 overexpression promotes EMT. Mechanistically, β-sitosterol inhibits Wnt/β-catenin signalling by downregulating FOXM1, regulating target gene transcription related to HepG2 cell proliferation and metastasis. β-Sitosterol shows promising potential as a therapeutic candidate for inhibiting HCC growth and metastasis through FOXM1 downregulation and Wnt/β-catenin signalling inhibition.

Gastrointestinal (GI) cancer stands as one of the most prevalent forms of cancer globally, presenting a substantial medical and economic burden on cancer treatment. Despite advancements in therapies, it continues to exhibit the second highest mortality rate, primarily attributed to drug resistance and post-treatment side effects. There is an urgent need for novel therapeutic approaches to tackle this persistent challenge. Scutellaria baicalensis, widely used in Traditional Chinese Medicine (TCM), holds a profound pharmaceutical legacy. Modern pharmacological studies have unveiled its anticancer, antioxidant, and immune-enhancing properties. S. baicalensis contains hundreds of active ingredients, with flavonoids, polysaccharides, phenylethanoid glycosides, terpenoids, and sterols being the principal components. These constituents contribute to the treatment of GI cancer by inducing apoptosis in tumor cells, arresting the cell cycle, inhibiting tumor proliferation and metastasis, regulating the tumor microenvironment, modulating epigenetics, and reversing drug resistance. Furthermore, the utilization of modern drug delivery technologies can enhance the bioavailability and therapeutic efficacy of TCM. The treatment of GI cancer with S. baicalensis is characterized by its multi-component, multi-target, and multi-pathway advantages, and S. baicalensis has a broad prospect of becoming a clinical adjuvant or even the main therapy for GI cancer.