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Background: The gut mycobiome of patients with lung adenocarcinoma (LUAD) remains unexplored. This study aimed to characterize the gut mycobiome in patients with LUAD and evaluate the potential of gut fungi as non-invasive biomarkers for early diagnosis. Methods: In total, 299 fecal samples from Beijing, Suzhou, and Hainan were collected prospectively. Using internal transcribed spacer 2 sequencing, we profiled the gut mycobiome. Five supervised machine learning algorithms were trained on fungal signatures to build an optimized prediction model for LUAD in a discovery cohort comprising 105 patients with LUAD and 61 healthy controls (HCs) from Beijing. Validation cohorts from Beijing, Suzhou, and Hainan comprising 44, 17, and 15 patients with LUAD and 26, 19, and 12 HCs, respectively, were used to evaluate efficacy. Results: Fungal biodiversity and richness increased in patients with LUAD. At the phylum level, the abundance of Ascomycota decreased, while that of Basidiomycota increased in patients with LUAD. Candida and Saccharomyces were the dominant genera, with a reduction in Candida and an increase in Saccharomyces, Aspergillus, and Apiotrichum in patients with LUAD. Nineteen operational taxonomic unit markers were selected, and excellent performance in predicting LUAD was achieved (area under the curve (AUC) = 0.9350) using a random forest model with outcomes superior to those of four other algorithms. The AUCs of the Beijing, Suzhou, and Hainan validation cohorts were 0.9538, 0.9628, and 0.8833, respectively. Conclusions: For the first time, the gut fungal profiles of patients with LUAD were shown to represent potential non-invasive biomarkers for early-stage diagnosis. [ABSTRACT FROM AUTHOR]

Background: The need for safe and effective treatment of dense virus (DEN), a class A agent that causes dense hemorrhagic fever/dense shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAA)-encoded short interfering RNA's (siRNA) was examined in Vero cells and human dendritic cells (DCs). Methods: A cassette encoding siRNA targeted to a 3' untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAA delivery. Results: Vero cells or DCs infected with AAA-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAA-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. Conclusion: These results demonstrate that AAA-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans. [ABSTRACT FROM AUTHOR]

Background: Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes. Results: In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites. Additionally, dual near-infrared (NIR) irradiation at the tumor site facilitated photosynthesis in CP, enabling the breakdown of excessive intratumoral interstitial fluid by generating oxygen from water decomposition. This process effectively reduced the interstitial pressure, thereby promoting enhanced perfusion of blood into the tumor, significantly improving deep-seated penetration of chemotherapeutic agents, and alleviating tumor hypoxia. Conclusions: CP@ICG demonstrated a combined effect of photothermal/photodynamic/starvation therapy, exhibiting excellent in vitro/in vivo anti-tumor efficacy and favorable biocompatibility. This work provides a scientific foundation for the application of microbial-enhanced intratumoral drug delivery and tumor therapy. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis affects the mandible resulting in bone loss. Though impairments are not life threatening, they affect a person's quality-of-life particularly vulnerable elderly. MicroRNAs (miRNAs) are novel regulatory factors that play an important role in regulating bone metabolism. Autophagy is evolutionarily conserved intracellular self-degradation process and is vital in the maintenance of both miRNA and bone homeostasis. However, the role of autophagy in the pathogenesis of miRNA regulating osteoporosis remains unclear. Methods: In the study, we established a rat osteoporosis model induced by ovariectomy (OVX) and isolated mesenchymal stem cells from mandible (MMSCs-M). Several miRNAs were identified to regulate osteoporosis in some studies. qRT-PCR was applied to examine the expression of miRNA, autophagy and osteogenic differentiation-related genes. Western blotting assays were performed to detect the expression of autophagy and osteogenic differentiation proteins. Immunofluorescence and transmission electron microscope were used to verify the autophagy activity. Transfecting technology was used to enhance or suppress the expression of miR-152-5p which enable us to observe the relationship between miR-152-5p, autophagy and osteogenic differentiation. Additionally, the measurement of reactive oxygen species was used to investigate the mechanism of autophagy affecting osteogenic differentiation. Results: We found an upregulated expression of miR-152-5p in MMSCs-M in OVX group. Downregulated autophagy-related gene, proteins and autophagosome were detected in vitro of OVX group compared with sham group. Moreover, downregulation of miR-152-5p promoted osteogenic differentiation of MMSCs-M as well as enhanced autophagy-related proteins in OVX group. Conversely, overexpression of miR-152-5p showed opposite effect in sham group. Meanwhile, we found Atg14 (autophagy-related protein homolog 14) was identified to be a direct target of miR-152-5p theoretically and functionally. In other words, we confirmed inhibition of miR-152-5p promoted the osteogenic differentiation via promoting ATG14-mediated autophagy. Furthermore, miR-152-5p/ATG14-mediated autophagy regulated osteogenic differentiation by reducing the endogenous ROS accumulation and maintaining cellular redox homeostasis. Conclusion: Our data suggest that miR-152-5p is the first identified to regulate osteogenic differentiation by directly targeting autophagy-related protein ATG14 and regulating oxidative stress and therapeutic inhibition of miR-152-5p may be an efficient anabolic strategy for osteoporosis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative disease. It is common in middle-aged and elderly people and is one of the main causes of disability. Currently, the etiology of OA is unclear, and no specific biomarkers for the diagnosis of OA have been identified. Therefore, finding a highly sensitive biomarker is essential for a proper diagnosis. TRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are newly discovered classes of noncoding RNAs. tRF has been proven in several studies to have significant associations with tumor diagnosis, making it a promising biomarker in cancer research. However, the diagnostic utility of tRF in OA patients and the correlation between OA progression and trf differential expression have yet to be elaborated. The purpose of this research was to identify tRFs with differential expression in OA to assess their potential as OA biomarkers. To determine the tRF-5022B expression level in this research, real-time fluorescence quantitative PCR has been employed. Agarose gel electrophoresis, Sanger sequencing, and other investigations have been employed for evaluating tRF-5022B's molecular properties. Receiver operating characteristic curve analysis has been utilized for assessing the diagnostic effectiveness of the tRF-5022B. The findings demonstrated that tRF-5022B expression was considerably lower in OA serum. The Kellgren–Lawrence grading scale was shown to correspond with serum expression levels. The ROC curve confirmed that tRF-5022B serum expression levels might differentiate OA cases from healthy individuals and RA patients. According to the aforementioned findings, tRF-5022B may be employed as a novel biomarker for OA diagnosis due to its excellent diagnostic value. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative disease. It is common in middle-aged and elderly people and is one of the main causes of disability. Currently, the etiology of OA is unclear, and no specific biomarkers for the diagnosis of OA have been identified. Therefore, finding a highly sensitive biomarker is essential for a proper diagnosis. TRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are newly discovered classes of noncoding RNAs. tRF has been proven in several studies to have significant associations with tumor diagnosis, making it a promising biomarker in cancer research. However, the diagnostic utility of tRF in OA patients and the correlation between OA progression and trf differential expression have yet to be elaborated. The purpose of this research was to identify tRFs with differential expression in OA to assess their potential as OA biomarkers. To determine the tRF-5022B expression level in this research, real-time fluorescence quantitative PCR has been employed. Agarose gel electrophoresis, Sanger sequencing, and other investigations have been employed for evaluating tRF-5022B's molecular properties. Receiver operating characteristic curve analysis has been utilized for assessing the diagnostic effectiveness of the tRF-5022B. The findings demonstrated that tRF-5022B expression was considerably lower in OA serum. The Kellgren–Lawrence grading scale was shown to correspond with serum expression levels. The ROC curve confirmed that tRF-5022B serum expression levels might differentiate OA cases from healthy individuals and RA patients. According to the aforementioned findings, tRF-5022B may be employed as a novel biomarker for OA diagnosis due to its excellent diagnostic value. [ABSTRACT FROM AUTHOR]

Background: Male factors-caused decline in total fertility has raised significant concern worldwide. LncRNAs have been identified to play various roles in biological systems, including spermatogenesis. This study aimed to explore the role of lncRNA5251 in mouse spermatogenesis. Methods: The expression of lncRNA5251 was modulated in mouse testes in vivo or spermatogonial stem cells (C18-4 cells) in vitro by shRNA. Results: The sperm motility in two generations mice after modulation of lncRNA5251 (muF0 and muF1) was decreased significantly after overexpression of lncRNA5251. GO enrichment analysis found that knockdown lncRNA5251 increased the expression of genes related to cell junctions, and genes important for spermatogenesis in mouse testes. Meanwhile, overexpressing lncRNA5251 decreased the gene and/or protein expression of important genes for spermatogenesis and immune pathways in mouse testes. In vitro, knockdown lncRNA5251 increased the expression of genes for cell junction, and the protein levels of some cell junction proteins such as CX37, OCLN, JAM1, VCAM1 and CADM2 in C18-4 cells. LncRNA5251 is involved in spermatogenesis by modulation of cell junctions. Conclusion: This will provide a theoretical basis for improving male reproductive ability via lncRNA. [ABSTRACT FROM AUTHOR]

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with drugs is challenging because KRAS is considered undruggable due to the lack of classic drug binding sites. Over the past 40 years, great efforts have been made to explore routes for indirect targeting of KRAS mutant cancers, including KRAS expression, processing, upstream regulators, or downstream effectors. With the advent of KRAS (G12C) inhibitors, KRAS mutations are now druggable. Despite such inhibitors showing remarkable clinical responses, resistance to monotherapy of KRAS inhibitors is eventually developed. Significant progress has been made in understanding the mechanisms of drug resistance to KRAS-mutant inhibitors. Here we review the most recent advances in therapeutic approaches and resistance mechanisms targeting KRAS mutations and discuss opportunities for combination therapy. [ABSTRACT FROM AUTHOR]

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with drugs is challenging because KRAS is considered undruggable due to the lack of classic drug binding sites. Over the past 40 years, great efforts have been made to explore routes for indirect targeting of KRAS mutant cancers, including KRAS expression, processing, upstream regulators, or downstream effectors. With the advent of KRAS (G12C) inhibitors, KRAS mutations are now druggable. Despite such inhibitors showing remarkable clinical responses, resistance to monotherapy of KRAS inhibitors is eventually developed. Significant progress has been made in understanding the mechanisms of drug resistance to KRAS-mutant inhibitors. Here we review the most recent advances in therapeutic approaches and resistance mechanisms targeting KRAS mutations and discuss opportunities for combination therapy. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet. Methods: Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR. Results: UbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models. Conclusions: These results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent. [ABSTRACT FROM AUTHOR]

Background: Mechanical thrombectomy has been widely performed for large vessel occlusion stroke. The present study aimed to determine whether cumulative experience could improve thrombectomy outcomes.Methods: In this retrospective single-center analysis, patients who underwent mechanical thrombectomy with the Solitaire stent in 3 years from 25 April 2015 were enrolled in the current study. Patients' characteristics, durations of admission and treatment, recanalization rates, clinical outcomes, and hemorrhage transformation rates were compared among the 3 years. Logistic analysis was used to analyze the independent correlation of the years and procedural outcomes.Results: A total of 222 patients underwent mechanical thrombectomy in the 3 years: 50 in the first year, 68 in the second year, and 104 in the third year. Door-to-puncture time (P < 0.001) and puncture-to-recanalization time (P = 0.033) decreased significantly among the 3 years, while successful recanalization rates increased (P = 0.001). Logistic regression analysis showed an independent increase in the successful recanalization rates in the second year and third year (P = 0.020, P = 0.001) as compared to that in the first year.Conclusions: Cumulative experience might improve the procedures of mechanical thrombectomy. The current findings suggested a potential benefit for centralization in the treatment of large vessel occlusion stroke. [ABSTRACT FROM AUTHOR]

Abstarct: Background: Cytosine-phosphate-guanine (CpG) dinucleotides has been used as adjuvants for cancer immunotherapy. However, unmodified CpG are not very efficient in clinical trials. Glucose, ligand of C-type lectin receptors (CLRs), can promote DC maturation and antigen presentation, which is the first step of induction of adaptive immune responses. Therefore, conjugation of type B CpG DNA to glucose-containing glycopolymers may enhance the therapeutic effects against tumor by CpG-based vaccine. Methods: gCpG was developed by chemical conjugation of type B CpG DNA to glucose-containing glycopolymers. The therapeutic effects of gCpG-based vaccine were tested in both murine primary melanoma model and its metastasis model. Results: gCpG based tumor vaccine inhibited both primary and metastasis of melanoma in mice which was dependent on CD8 + T cells and IFNγ. In tumor microenvironment, gCpG treatment increased Th1 and CTL infiltration, increased M1 macrophages, decreased Tregs and MDSCs populations, and promoted inflammatory milieu with enhanced secretion of IFNγ and TNFα. The anti-tumor efficacy of gCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. Conclusions: We confirmed that gCpG was a promising adjuvant for vaccine formulation by activating both tumor-specific Th1 and Tc1 responses, and regulating tumor microenvironments. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese Medicine (TCM) is distinguished by Syndrome differentiation, which prescribes various formulae for different Syndromes of same disease. This study aims to investigate the underlying mechanism. Methods: Using a strategy which integrated proteomics, metabolomics study for clinic samples and network pharmacology for six classic TCM formulae, we systemically explored the biological basis of TCM Syndrome differentiation for two typical Syndromes of CHD: Cold Congealing and Qi Stagnation (CCQS), and Qi Stagnation and Blood Stasis (QSBS). Results: Our study revealed that CHD patients with CCQS Syndrome were characterized with alteration in pantothenate and CoA biosynthesis, while more extensively altered pathways including D-glutamine and D-glutamate metabolism; alanine, aspartate and glutamate metabolism, and glyoxylate and dicarboxylate metabolism, were present in QSBS patients. Furthermore, our results suggested that the down-expressed PON1 and ADIPOQ might be potential biomarkers for CCQS Syndrome, while the down-expressed APOE and APOA1 for QSBS Syndrome in CHD patients. In addition, network pharmacology and integrated analysis indicated possible comorbidity differences between the two Syndromes, that is, CCQS or QSBS Syndrome was strongly linked to diabetes or ischemic stroke, respectively, which is consistent with the complication disparity between the enrolled patients with two different Syndromes. These results confirmed our assumption that the molecules and biological processes regulated by the Syndrome-specific formulae could be associated with dysfunctional objects caused by the Syndrome of the disease. Conclusion: This study provided evidence-based strategy for exploring the biological basis of Syndrome differentiation in TCM, which sheds light on the translation of TCM theory in the practice of precision medicine. Highlights: 1. Our work was based on clinical samples rather than pure data analysis or animal models. 2. We conducted multiple omics studies. Especially, as for metabolomics study, we performed both untargeted and targeted metabolomics experiments. 3. We performed network pharmacological study to cross-validated the results of multi-omics study. Although the data sources of network pharmacology were completely unrelated with our omics data, they came to the same conclusion about the difference of the two Syndromes. 4. In the network pharmacological study, we made efforts to collect and screen high-quality data. We collected data from multiple TCM databases and conducted drug likeness screening. Especially, we added quality markers of each herb, whose pharmacological relevance had been validated. To enhance the reliability of targets, for each Syndrome, we only studied common targets of 3 different TCM formulae prescribed for this Syndrome. [ABSTRACT FROM AUTHOR]

Background: RelB, a member of the NF-κB family, plays a critical role in the development of T cells. However, the role of RelB in Foxp3+ regulatory T cells (Tregs) remains controversial. Results: Using a bone marrow chimeric mouse model, we demonstrated that the expansion of Foxp3+ Tregs in vivo could be mediated by extrinsic mechanisms. RelB plays an important role in inhibiting the homeostatic proliferation of Tregs, but not their survival. Even with the heightened expansion, RelB−/− Treg cells displayed normal suppressive function in vitro. Among the expanded populations of Treg cells, most were nTreg cells; however, the population of iTregs did not increase. Mechanistically, RelB seems to regulate Treg proliferation independently of the signal transducer and activator of transcription 5 (STAT5) pathway. Conclusions: These data suggest that RelB regulates Treg proliferation independently of the STAT5 pathway, but does not alter the function of Tregs. Further studies are warranted to uncover such mechanisms. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. Methods: Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. Results: Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. Conclusions: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings. [ABSTRACT FROM AUTHOR]

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1471-2407-14-689. [ABSTRACT FROM AUTHOR]

Background: Injection drug use (IDU) is one of the major modes of HIV transmission in China. Drug use is illegal in China, all identified drug users are registered by Public Security Bureau, and most were sent to detention; most detainees engaged in high risk behaviours. In order to well understand the HIV/AIDS knowledge among detainees, a survey was conducted in different detention settings in Hunan province in 2008 to assess knowledge and attitudes about HIV among detainees and to provide useful information for HIV prevention and intervention strategies in detention centers.Methods: A cross-sectional survey was conducted in 10 detentions in Hunan province, China, and demographic information along with knowledge and attitude of HIV/AIDS was collected through standardized interviews. Descriptive statistics were used to describe HIV knowledge, attitudes, and education services among detainees.Results: There were 956 detainees interviewed from 10 detention centers. The male to female ratio was 2.24:1. The majority detainees received nine years of compulsory education, accounting for 51.5%. There were nine questions to assess HIV/AIDS knowledge of detainees, and 35.7% of those surveyed answered all nine questions correctly. There were 92.3% (882/956) who consented to be informed about the HIV antibody test results when tested, and 81% (774/956) elected that their family members were also informed. All detention centers had an organized HIV/AIDS education program.Conclusion: This study gives us an overview about HIV/AIDS knowledge in detention in Hunan province, and all detention sites in the study provided HIV/AIDS intervention services among detainees that focused on HIV/AIDS knowledge, attitude, and health behaviors. [ABSTRACT FROM AUTHOR]

Background: Cardamonin, a chalcone isolated from Alpiniae katsumadai, has anti-inflammatory and anti-tumor activities. However, the molecular mechanism by which cardamonin inhibits breast cancer progression largely remains to be determined. Methods: CCK-8 and Hoechst 33258 staining were used to detect cell growth and apoptosis, respectively. HIF-1α driven transcription was measured by luciferase reporter assay. Glucose uptake and lactate content were detected with 2-NBDG and L-Lactate Assay Kit. Cell metabolism assays were performed on Agilent's Seahorse Bioscience XF96 Extracellular Flux Analyzer. Mitochondrial membrane potential was measured with JC-1 probe. DCFH-DA was used to measure ROS level. Protein expression was detected by western blotting assay. Immunohistochemistry was performed to measure the expression of HIF-1α, LDHA and CD31 in tumor tissues. Results: Cardamonin inhibited growth of the triple negative breast cancer cell line MDA-MB-231 in vitro and in vivo by suppressing HIF-1α mediated cell metabolism. Cardamonin inhibited the expression of HIF-1α at mRNA and protein levels by repressing the mTOR/p70S6K pathway, and subsequently enhanced mitochondrial oxidative phosphorylation and induced reactive oxygen species (ROS) accumulation. We also found that cardamonin inhibited the Nrf2-dependent ROS scavenging system which further increased intracellular ROS levels. Eventually, accumulation of the intracellular ROS induced apoptosis in breast cancer cells. In addition, cardamonin treatment reduced glucose uptake as well as lactic acid production and efflux, suggesting its function in repressing the glycolysis process. Conclusions: These results reveal novel function of cardamonin in modulating cancer cell metabolism and suppressing breast cancer progression, and suggest its potential for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Hypericum japonicum Thunb. ex Murray is widely used as an herbal medicine for the treatment of hepatitis and tumours in China. However, the molecular mechanisms of its effects are unclear. Our previous research showed that extracts of H. japonicum can induce apoptosis in leukaemia cells. We also previously systematically analysed and isolated the chemical composition of H. japonicum.Methods: The fluorescence polarisation experiment was used to screen for inhibitors of Bcl-2 proteins which are proved as key proteins in apoptosis. The binding mode was modelled by molecular docking. We investigated the proliferation attenuating and apoptosis inducing effects of active compound on cancer cells by MTT assay and flow cytometry analysis. Activation of caspases were tested by Western blot. A broad-spectrum caspase inhibitor Z-VAD-FMK was used to investigate the caspases-dependence. In addition, co-immunoprecipitation was performed to analyse the inhibition of heterodimerization between anti-apoptotic Bcl-2 proteins with pro-apoptotic proteins. Moreover, in vivo activity was tested in a mouse xenograph tumour model.Result: Jacarelhyperol A (Jac-A), a characteristic constituent of H. japonicum, was identified as a potential Bcl-2 inhibitor. Jac-A showed binding affinities to Bcl-xL, Bcl-2, and Mcl-1 with Ki values of 0.46 μM, 0.43 μM, and 1.69 μM, respectively. This is consistent with computational modelling results, which show that Jac-A presents a favorable binding mode with Bcl-xL in the BH3-binding pocket. In addition, Jac-A showed potential growth inhibitory activity in leukaemia cells with IC50 values from 1.52 to 6.92 μM and significantly induced apoptosis of K562 cells by promoting release of cytochrome c and activating the caspases. Jac-A also been proved that its effect is partly caspases-dependent and can disrupt the heterodimerization between anti-apoptotic Bcl-2 proteins with pro-apoptotic proteins. Moreover, Jac-A dose-dependently inhibited human K562 cell growth in a mouse xenograph tumour model with low toxicity.Conclusion: In this study, a characteristic constituent of H. japonicum, Jac-A, was shown to induce apoptosis in leukaemia cells by mediating the Bcl-2 proteins. Therefore, we propose a new lead compound for cancer therapy with a low toxicity, and have provided evidence for using H. japonicum as an anti-cancer herb. [ABSTRACT FROM AUTHOR]