This study investigates the antitumor efficacy of cantharidin against cholangiocarcinoma (CCA) using patient-derived organoids (PDOs) that faithfully replicate the histological and genomic features of original tumors. Results demonstrate that cantharidin effectively inhibits CCA PDO growth, showing comparable or superior efficacy to conventional chemotherapeutics such as cisplatin, though slightly less potent than gemcitabine or Adriamycin. Critically, drug sensitivity in PDOs correlated perfectly with clinical responses in five patients, validating the model's predictive relevance. Mechanistic studies revealed that cantharidin suppresses proliferation and induces apoptosis primarily through downregulation of the p-ERK1/2-c-Fos signaling pathway, both in vitro and in patient-derived organoids-based xenografts. These effects were reversible upon treatment with a p-ERK agonist, confirming pathway specificity. The study highlights cantharidin's potential as a targeted therapeutic agent in CCA and underscores the utility of PDOs in personalized drug screening and mechanistic investigation.

INTRODUCTION: Cholangiocarcinoma (CCA) is a highly aggressive biliary malignancy with a very poor prognosis. How to screen the optimal chemotherapy regimen is crucial for enhancing the prognosis of CCA patients. The study aims to develop patient-derived tumor organoid (PDO) models and patient-derived tumor xenograft (PDX) models of CCA to simulate clinical responses to chemotherapy. METHODS: Tumor tissues were collected from patients undergoing surgical resection and subsequently utilized to establish PDO and PDX models. Hematoxylin-eosin (H&E), immunohistology (IHC), and immunofluorescence (IF) were conducted to analyze the biological characteristics of these PDXs and PDOs. Whole exome sequencing (WES) was performed to identify the mutation types of primary tumor, PDO, and PDX. Drug sensitivity assays were conducted utilizing PDO and PDX models to compare clinical treatment responses. RESULTS: In this study, we successfully established 18 PDO (success rate, 56.3%) models and 21 PDX models (success rate, 65.6%) from 32 patients diagnosed with CCA. PDO and PDX preserved the mutational profiles characteristic of the primary tumor samples. The drug screening results from PDOs demonstrated a correlation with the actual clinical response to chemotherapy regimens, and these findings were further validated in PDX models. CONCLUSIONS: Our findings indicate that the integration of PDO and PDX models can successfully guide clinical treatment strategies, facilitating effective personalized therapy for CCA patients.

Primary liver cancer (PLC) is one of the most commonly diagnosed cancers worldwide and a leading cause of cancer-related deaths. However, traditional liver cancer models fail to replicate tumor heterogeneity and the tumor microenvironment, limiting the study and personalized treatment of liver cancer. To overcome these limitations, scientists have introduced three-dimensional (3D) culture models as an emerging research tool. These 3D models, utilizing biofabrication technologies such as 3D bioprinting and microfluidics, enable more accurate simulation of the in vivo tumor microenvironment, replicating cell morphology, tissue stiffness, and cell-cell interactions. Compared to traditional two-dimensional (2D) models, 3D culture models better mimic tumor heterogeneity, revealing differential sensitivity of tumor cell subpopulations to targeted therapies or immunotherapies. Additionally, these models can be used to assess the efficacy of potential treatments, providing guidance for personalized therapy. 3D liver cancer models hold significant value in tumor biology, understanding the mechanisms of disease progression, and drug screening. Researchers can gain deeper insights into the impact of the tumor microenvironment on tumor cells and their interactions with the surrounding milieu. Furthermore, these models allow for the evaluation of treatment responses, offering more accurate guidance for clinical interventions. In summary, 3D models provide a realistic and reliable tool for advancing PLC research. By simulating tumor heterogeneity and the microenvironment, these models contribute to a better understanding of the disease mechanisms and offer new strategies for personalized treatment. Therefore, 3D models hold promising prospects for future PLC research.

To the Editor: There are no data regarding expressed and functional characterisation of cytoskeleton-related non-coding RNA has been reported in prostate cancer (PCa). Here, we report a cytoskeleton regulator RNA (CYTOR)-regulated process that mediates castration-resistant PCa (CRPC)-specific androgen receptor splice variant 7 (AR-V7) generation, and further explore the vulnerability of CRPC growth through CYTOR-targeted locked nucleic acid (LNA). We retrieved public castration-sensitive PCa (CSPC) datasets (n = 65), neuroendocrine PCa (NEPC) datasets (n = 49) and CRPC datasets (including two studies, n = 171 and n = 118).1 Across the above RNA-seq data, CYTOR was found to be upregulated in CRPC with low expression in CSPC and NEPC (Figure 1A). RNA in situ hybridisation (RISH) assays2 of our centre samples confirmed the public domain data (Figure 1B and Figure S1A). Consistent with tissue detection, androgen-influenced CYTOR revealed significant increase in our two continuous established castration-resistant cell lines: LNCaP-AI,3 C4-2 Enz-R (Figure 1C and Figure S1B–G). Additionally, progression was more common in CSPC with higher CYTOR expression (Figure 1D). Expression analysis of CYTOR in flash-frozen surgical specimens was conducted in 11 CRPC patients (Figure 1E). Patients with high expression of CYTOR received worse PSA response to subsequential enzalutamide than those with CYTOR low expression (Figure 1F). Then, gene functional assays suggested knockdown of CYTOR suppressed the cancer cells growth (Figure 1G–J). The above results hint the association of CYTOR with CRPC development and inferior clinical outcomes. As it is, the primary therapeutic intervention for advanced PCa is androgen-deprivation therapy (ADT) with the goal of castration to suppress androgen receptor (AR) signalling. Although most patients respond to ADT, some inevitably develop resistance and progress to CRPC because of AR-V7 expression.4 Extensively investigated AR-V7 is a typically truncated AR without the ligand-binding domain but retaining transcriptional-regulated activity to mediate ligand-independent AR signalling.5 RNA-seq analysis revealed many AR-V7 downstream genes were differentially regulated as CYTOR knockdown (Figure 2A, Table S2). Most of them were enriched in metabolic pathways (Figure 2B). We validated the downregulation of AR-V7 canonic-activated genes (Figure 2C) after silencing CYTOR. Interestingly, knockdown of CYTOR resulted in specific decrease of AR-V7 without concurrent decrease of full-length AR (AR-FL) (Figure 2D), suggesting the critical role of CYTOR in AR-V7 mRNA splicing process. Multiplexed RISH assays of CRPC specimens revealed colocalisation and positive correlation of CYTOR and AR-V7 (pre-mRNA accumulated in nuclei) (Figure 2E). Their positive correlation was also confirmed by RT-PCR in four flash-frozen specimens (Figure 2F). Because key RNA-binding protein families involved in alternative splicing may include serine/arginine-rich proteins (SR proteins) and heterogeneous nuclear ribonucleoproteins (hnRNPs), we conducted differential expression analysis of SR proteins and hnRNPs between LNCaP-AI and LNCaP cells by our published RNA-arrays (GSE124291), and screened six upregulated splicing factors in LNCaP-AI cells (>1.5-fold) (Figure 2G). We further confirmed the upregulation of three genes (Figure 2H and Figure S2A). By Human Splicing Finder,6 the similar consensus splice site value for splice junctions of intron 3/cryptic exon 3 (CE3) (80.38) (as in AR-V7) and intron 3/exon 4 (80.1) (as in AR-FL) (Figure S2B) suggested the existence of a mechanism for CRPC-specific CE3 splice site utilisation. Given the established role of SR proteins in binding to pre-mRNA that prevents exon skipping, and the classical role of hnRNPs as splicing repressors, we postulated that nuclear-localised SRSF4 and SRSF7 (Figure 2I) may repress CE3 skipping, thus ensuring the correct 5′ to 3′ linear order of exons (exon1-3/CE3) in AR-V7 mRNA. Indeed, knockdown of SRSF4 or SRSF7 resulted in decreased expression of AR-FL and AR-V7, while withoutimpact on CYTOR (Figure 2J). The catRAPID strength algorithm computed output suggested the high specificity of CYTOR–SRSF4 interaction and CYTOR–SRSF7 interaction, respectively (Figure 2K,L).7 RNA immunoprecipitation results revealed both SRSF4 and SRSF7 proteins interacted with CYTOR, AR-V7 pre-mRNA and AR-V7 mRNA (Figure 2K,L), indicating nuclear binding of SRSF4 and SRSF7 to AR-V7 pre-mRNA and CYTOR was responsible for AR-V7 generation, even though there was weak interaction of SRSF4 and SRSF7 (Figure 2M). According to the functional interaction of CYTOR and SRSF4/7 proteins, we hypothesised that CYTOR may recognise AR-V7 pre-mRNA to induce this splicing process. Toward this end, maximum entropy modeling was used to collect motifs in the intron3/CE3 flanking sequence and identified the 3′ motif (3′ site of intron 3) and the 5′ motif (first 20 bp of CE3) (Figure 3A–C).6 The complementary sequence of the 5′ motif in the sequence of CYTOR (5′-UUCCAACCGC-3′) suggested that CYTOR may recognise the 5′ motif of CE3 (5′-GGGUUGGCAA-3′) to initiate the splicing process (Figure 3C). Next, we designed an 18 bp antisense oligonucleotides (ASO) to the 5′ motif of CE3 (ASOCE3) to prevent the recognition. The ASOCE3 suppressed, in a concentration- and time-dependent manner, the expression of AR-V7 mRNA (Figure 3D). We then designed an 18 bp ASOCYTOR to the complementary sequence of CE3 5′ motif in CYTOR. ASOCYTOR inhibited expression of AR-V7 mRNA without interfering CYTOR expression (Figure 3E and Figure S2C). Also as shown in C4-2 Enz-R cells, the ASOCE3 and ASOCYTOR prevented the generation of AR-V7 mRNA (Figure 3F,G). To validate this splicing model, truncated mutant assays confirmed the pivotal role of 5′-UUCCAACCGC-3′ in CYTOR on AR-V7 expression (Figure S2D,E). Together, CYTOR/SRSF4/SRSF7 complex interacts with AR-V7 pre-mRNA to regulate its splicing by recognising a specific signal element in CE3 (Figure 3H). Then LNAs GapmeRCYTOR were designed to silence CYTOR (Figure 4A). In C4-2 Enz-R cells, AR-V7 expression was largely suppressed in parallel with the silenced pattern of CYTOR in a concentration- and time-dependent manner (Figure 4B–E). GapmeRCYTOR could attenuate the resistance of enzalutamide significantly in vitro (Figure 4F). We then established in vivo mouse models and found that enzalutamide significantly suppressed C4-2 tumours, shCYTOR- and GapmeRCYTOR-treated C4-2 Enz-R tumours (Figure 4G,H). The expressions of CYTOR and AR-V7 were validated in each group (Figure S2F,G). As such, our data suggested that on-target effect of CYTOR knockdown with GapmeRCYTOR can be used as an option in castration resistance to provide therapeutic efficacy. In conclusion, we propose the importance of a novel complex composed of CYTOR/SRSF4/SRSF7 that mediates AR-V7 generation, and a critical role in suppressing PCa progression by targeting CYTOR/AR-V7 axis with shRNA or preclinical LNA GapmerCYTOR. Some of the biospecimens used in the present study were provided by the Chungbuk National University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health, Welfare, and Family Affairs. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board-approved protocols. The authors wish to thank Ms. Eun-Ju Shim from the National Biobank of Korea at Chungbuk National University Hospital for the sample preparations and her excellent technical assistance. The authors declare they have no conflicts of interest. National Natural Science Foundation of China, Grant Numbers: 91959114, 81872106, 82072851, 81872100, 81972654, 82273262; National Natural Science Foundation of China, International (Regional) Cooperation and Exchange Program, Grant Number: 82061160493; Natural Science Foundation of Tianjin, Grant Numbers: 18PTLCSY00030, 21JCQNJC01700; Tianjin Key Medical Discipline (Specialty) Construction Project, Grant Numbers: TJYXZDXK-023A, TJYXZDXK-065B; The Second Hospital of Tianjin Medical University, Grant Number: 2020ydey01; Scientific Research Project of Tianjin Education Commission, Grant Number: 2021KJ225 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract Background: N7-methylguanosine (m7G) is an essential epigenetic modification and there is increasing evidence that it is closely associated with tumorigenesis progression. However, the expression pattern of m7G-related genes in hepatocellular carcinoma (HCC) remains systematically analyzed.Methods: We downloaded HCC genetic and transcriptomic data from TCGA and GEO datasets. Unsupervised clustering methods identified different m7G-related gene subtypes, and then an m7G_score for predicting overall survival and characterizing the tumor microenvironment (TME) was constructed. Eventually, a highly accurate nomogram was constructed based on the score.Results: In this study, two m7G-related gene subtypes were obtained by unsupervised clustering analysis of 18 m7G-related genes, and the relationship between different subtypes and clinicopathological features and TME was systematically evaluated.Conclusion: N7-methylguanosine-related patterns are closely related to the clinical characteristics and tumor microenvironment of HCC patients, providing a new perspective on the treatment of HCC patients. Meanwhile, m7G_score can improve the clinical applicability with HCC patients.

Background: To explore the biological and clinical effects of titin-antisense RNA1 (TTN-AS1) in bladder cancer (BC) and the association between TTN-AS1 and activating transcription factor 2 (ATF2) in BC. Methods: The Kaplan–Meier method was performed to analyze the association between the expression of TTN-AS1 and prognosis of BC patients from TCGA data set and our institution. Quantitative real-time PCR (RT-PCR) was conducted to explore the expression of TTN-AS1 between the patients who underwent TURBT and Re-TURBT. MTT, colony formation, and tumor formation assays were conducted to evaluate the effect of TTN-AS1 on the ability of proliferation in BC cell lines. Transwell assay was performed to evaluate the effect of TTN-AS1 on the ability of invasion in BC cell lines. Bioinfomatics and immunohistochemical staining was used to identify the relationship between TTN-AS1 and ATF2. Results: The higher expression of TTN-AS1 was related to poorer disease-free survival (DFS) in patients with BC. The expression of TTN-AS1 was higher in BC patients who underwent Re-TURBT compared with BC patients who underwent TURBT. Knocking down TTN-AS1 resulted in inhibiting the ability of proliferation and invasion of BC cells. ATF2 may serve as a downstream target of TTN-AS1 in BC, and the high expression of ATF2 is also related to adverse DFS. Conclusion: Our study reveals that TTN-AS1 serves as an oncogene by activating ATF2 in BC. The findings suggest that TTN-AS1 may act as a novel therapeutic target for patients with BC.

Objective. Acute kidney injury (AKI) is a common and severe complication in critically ill patients, often caused by renal ischemia-reperfusion (RIR). Previous studies have confirmed that lung injury, rather than renal injury, is one of the leading causes of AKI-induced death. The pathophysiological mechanisms of acute lung injury (ALI) resulting from AKI are very complex and remain unclear. In the present study, we aimed to explore the protective effects and potential mechanism of sodium hydrosulfide (NaHS) on lung injury in RIR mice. Methods. The RIR model was established in wild-type and Nrf2(-/-) mice. Different groups of mice were treated with NaHS and MCC950. Lung tissues were harvested to detect lung injury, mitochondrial function, cell apoptosis, the NLRP3 inflammasome, and Nrf2 pathway-related molecules. Results. RIR led to a deterioration in lung histology, the wet/dry weight ratio, PaO2/FiO(2), and mitochondrial function, in addition to stimulating the activation of the NLRP3 and Nrf2 pathways. MCC950 alleviated mitochondrial dysfunction, lung apoptosis, and histology injury in the lungs after RIR. NaHS treatment markedly improved the lung histological scores, the wet/dry weight ratio, bronchoalveolar lavage fluid (BALF) cell counts, BALF neutrophil counts, BALF neutrophil elastase activity, BALF protein concentration, PaO2/FiO(2), mitochondrial morphology, the red/green fluorescence intensity that indicates changes in mitochondrial membrane potential, respiratory control rate (RCR), ATP, reactive oxygen species (ROS) release, and cell apoptosis via Nrf2-mediated NLRP3 pathway inhibition. Conclusion. NaHS protected against RIR-induced lung injury, mitochondrial dysfunction, and inflammation, which is associated with Nrf2 activation-mediated NLRP3 pathway inhibition.

Objective. To investigate the expression of kinesin family member 20A (KIF20A) in bladder cancer, the effect of KIF20A on the proliferation and metastasis of bladder cancer cells, and the effect of KIF20A expression on the prognosis of bladder cancer patients.Methods. Bladder cancer tissue and its adjacent tissues were collected from tumour patients. The mRNA and protein expression levels of KIF20A in the tissue samples were detected by qRT-PCR and western blot. Immunohistochemical (IHC) staining was used to identify the expression and distribution of KIF20A proteins in the tissue samples. The relationship between the KIF20A expression and the clinical pathology of bladder cancer was analysed. The effect of the differential expression of KIF20A on the prognosis of patients with bladder cancer was analysed by the TCGA database. The plasmid was transfected into the bladder cell lines T24 and 5637 to construct two stable cell lines with knocked down KIF20A. The effect of KIF20A expression on the proliferation and invasion of T24 and 5637 bladder cells was explored in vitro using the abovementioned stable cell lines. The effect of the KIF20A expression on the proliferation of bladder cancer cells was evaluated by a mouse xenograft model.Results. The expression of KIF20A was significantly higher in the bladder cancer tissues than in the adjacent control tissues. The expression of KIF20A was significantly associated with the degree of pathological differentiation of bladder cancer. Patients with a higher expression of KIF20A had a higher tumour grade and a more advanced stage. The mean survival of patients with a high KIF20A expression was significantly lower than the mean survival of patients with a low KIF20A expression. The in vitro experiments demonstrated that the knockdown of KIF20A significantly inhibited T24 and 5637 cell proliferation and invasion. The in vivo experiments showed that the knockdown of KIF20A significantly inhibited the proliferation of the bladder tumours.Conclusion. KIF20A promotes the proliferation and metastasis of bladder cancer cells. Bladder cancer patients with a high KIF20A expression have a worse tumour differentiation and a poor prognosis. KIF20A may become an independent factor that affects the prognosis of bladder cancer patients and a therapeutic target for bladder cancer.

Liver injury is a serious clinical syndrome that characterized by inflammatory response. Engeletin is known to have anti-inflammatory activity. However, the effects of engeletin on liver injury remain unclear. We aimed to assess the protective effect of engeletin on Lipopolysaccharide (LPS)/d-galactosamine (D-gal)-induced liver injury in mice. Engeletin was administered intraperitoneally 1 h before and 12 h after LPS/D-gal treatment. The results showed that engeletin treatment on LPS/D-gal-induced liver injury in mice have a significant protective effect, as confirmed by the attenuation of liver histopathologic changes, MPO activity, and serum AST and ALT levels. At the meanwhile, it also showed that engeletin inhibited the levels of IL-β and TNF-α in serum and liver tissues. Besides, engeletin blocked the activation of NF-κB induced by LPS/D-gal and induced the expression of PPAR-γ in a dose-dependently manner. These findings suggested that engeletin may have a protective effect against liver injury.

Purpose To compare the expression level of apelin in muscle-invasive bladder cancer and matched paracarcinoma tissues and investigate the relationship between apelin and clinical prognosis in the patients. Methods To assess apelin expression by using immunohistochemical method compared with bladder tumors and matched paracarcinoma tissues. Subsequently, the correlation of apelin expression with the clinicopathological features of bladder cancer patients was analyzed. Kaplan-Meier survival curves method was used to analyze apelin prognostic significance for muscle-invasive bladder cancer patients (including 404 muscle-invasive bladder cancer patients and 28 normal bladder tissues, in TCGA dataset). Results Apelin protein level was overexpressed in bladder tumor tissues compared with paracarcinoma tissues. Furthermore, high apelin expression was associated with high tumor stage (P < 0.05), distant metastasis (P < 0.05), and vascular invasion (P < 0.05). Kaplan-Meier curve analyses showed that the overexpression of apelin was a potential predictor of overall survival and disease-free survival. Conclusion Apelin was upregulated in bladder tumor tissues compared with matched adjacent noncancer tissues, especially in the high tumor stage, distant metastasis, and vascular invasion. What is more, high expression of apelin in muscle-invasive bladder cancer indicates the poor prognosis. These data suggested that apelin might be a therapeutic potential biomarker in muscle-invasive bladder cancer patients.

Rationale:Thyroid follicular carcinoma-like renal tumor (TFCLRT) is a rare primary renal epithelial tumor that was first reported in 2006. We report a case diagnosed of TFCLRT by us to observe the pathological feature and analyze comparatively the clinical and pathologic characteristics with all cases of reviewed literatures.Patient concerns:A 54-year-old female patient had the urinary frequency with the symptom of right flank pain with a history of more than half a year of hypertension and received uterine fibroid resection 12 years ago. B-mode ultrasound examination and renal magnetic resonance showed a right renal sinus nodule.Diagnoses:Histopathology revealed thyroid follicle-like structures of different sizes, containing a colloid-like substance, while the periodic acid-Schiff (PAS) and diastase-resistant PAS staining confirmed that it was mucus protein. Immunohistochemical staining showed that it expresses the transcription factor PAX-8 but does not express the thyroid-specific antibodies TG and TTF-1.Interventions:The patient underwent a tumor enucleation of right kidney. No other treatment was conducted after surgery.Outcomes:No metastases to lymph nodes and other organs were found, and 9-months of follow-up did not reveal any tumor progression.Lessons:We should differentially diagnose the renal metastasis of thyroid follicular carcinoma or papillary carcinoma. Some related literatures reported that the tumour cells had significant heteromorphism, several of which metastasized to lymph nodes or distal organs. Its biological behavior need to be studied intensively by further expanding the number of cases.

Background/Aims: miR-146a has recently been shown to promote cell proliferation, migration, and invasion in many cancers, but the role of miR-146a in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: Reverse transcription quantitative PCR (RT-qPCR) was performed to investigate the mRNA expression of miR-146a and CADM2 in ccRCC tissues. The luciferase reporter assay, Western blotting, and ChIP assay were carried out to explore the promoter and the transcription factor of miR-146a. Moreover, the effect of miR-146a and CADM2 on ccRCC cells was explored using methyl thiazolyl tetrazolium, colony formation, and migration and invasion assays. The luciferase reporter assay, RT-qPCR, western blotting, and immunofluorescence assay were carried out to investigate whether CADM2 is directly regulated by miR-146a. A tumor xenograft model and immunohistochemical staining were used to examine the carcinogenic effect of miR-146a and CADM2 in vivo. Results: miR-146a has been shown to promote cell proliferation, migration, and invasion. Here, we found that miR-146a is highly expressed in ccRCC tissues, whereas CADM2 is down-regulated. Hypoxia can induce the expression of miR-146a by stimulating its promoter. In addition, we demonstrated that miR-146a promoted and CADM2 inhibited proliferation, migration, and invasion of ccRCC cells. The 3’ untranslated region (UTR) luciferase reporter assay identified that miR-146a targeted the 3’ UTR of CADM2 and negatively regulated its expression. Ectopic expression of CADM2 counteracted the promoting effect of miR-146a on cell proliferation, migration, invasion, and the epithelial–mesenchymal transition process. Conclusion: Together, the finding of down-regulation of CADM2 by miR-146a can provide new insights into ccRCC pathogenesis and might contribute to the development of novel therapeutic strategies.

Rationale: Thyroid follicular carcinoma-like renal tumor (TFCLRT) is a rare primary renal epithelial tumor that was first reported in 2006. We report a case diagnosed of TFCLRT by us to observe the pathological feature and analyze comparatively the clinical and pathologic characteristics with all cases of reviewed literatures. Patient concerns: A 54-year-old female patient had the urinary frequency with the symptom of right flank pain with a history of more than half a year of hypertension and received uterine fibroid resection 12 years ago. B-mode ultrasound examination and renal magnetic resonance showed a right renal sinus nodule. Diagnoses: Histopathology revealed thyroid follicle-like structures of different sizes, containing a colloid-like substance, while the periodic acid-Schiff (PAS) and diastase-resistant PAS staining confirmed that it was mucus protein. Immunohistochemical staining showed that it expresses the transcription factor PAX-8 but does not express the thyroid-specific antibodies TG and TTF-1. Interventions: The patient underwent a tumor enucleation of right kidney. No other treatment was conducted after surgery. Outcomes: No metastases to lymph nodes and other organs were found, and 9-months of follow-up did not reveal any tumor progression. Lessons: We should differentially diagnose the renal metastasis of thyroid follicular carcinoma or papillary carcinoma. Some related literatures reported that the tumour cells had significant heteromorphism, several of which metastasized to lymph nodes or distal organs. Its biological behavior need to be studied intensively by further expanding the number of cases.

Urinary metabolites of liquiritigenin were investigated in rats after intravenous administration. Four major urinary metabolites, isoliquiritigenin ( 2 ), liquiritigenin-4′-O- β -D-glucuronide ( 3 ), liquiritigenin-7-O- β -Dglucuronide ( 4 ), and davidigenin-2′-O- β -D-glucuronide ( 5 ), were isolated from the urine of rats. Their structures were elucidated on the basis of extensive spectroscopic methods, among which 5 was a new compound. Compound 2 showed significant inhibition of platelet aggregation induced by ADP, whose 50% inhibitory concentration (IC 50 ) value was 20.38 ± 1.68 μM.

从覆盆子中分离得到13个化合物,通过波谱数据和理化性质分别鉴定为:β-谷甾醇(1)、7α-羟基-3β-谷甾醇(2)、胡萝卜苷(3)、熊果酸(4)、对羟基苯乙酸(5)、水杨酸(6)、腺苷(7)、1-氧-1,2-二氢异喹啉-4-羧酸(8)、香橙素(9)、金丝桃苷(10)、ligballinol(11)、阿魏酸二十六醇酯(12)、香豆酸二十四醇酯(13).化合物10为首次从该植物中分离得到,化合物2、5、7、9、12、13为首次从悬钩子属植物中分离得到.