Increased co-expression of ICOS and PD-1 predicts poor overall survival in patients with acute myeloid leukemia.

BACKGROUND: Inducible co-stimulatory factor (ICOS) has a dual role: activating cytotoxic T cells against tumors or exacerbating immunosuppression of regulatory T cells (Tregs) to participate in immune evasion. However, the correlation between ICOS and its co-expression with inhibitory immune checkpoints (IICs) and prognosis in acute myeloid leukemia (AML) is little known. METHODS: The prognostic importance of ICOS and IICs in 62 bone marrow (BM) samples of de novo AML patients from our clinical center (GZFPH) was explored and then the RNA sequencing data of 155 AML patients from the Cancer Genome Atlas (TCGA) database was used for validation. RESULTS: In both GZFPH and TCGA cohorts, high expression of ICOS was significantly associated with poor overall survival (OS) in patients with AML (P < 0.05). Importantly, co-expression of ICOS and PD-1, PD-L1, PD-L2, CTLA-4, and LAG-3 predicted poor OS in AML; among them, ICOS/PD-1 was the optimal combination of immune checkpoints (ICs). The co-expression of ICOS and PD-1 was correlated with poor OS in non-acute promyelocytic leukemia (non-APL) patients following chemotherapy. Additionally, ICOS/PD-1 was an independent OS-predicting factor (P < 0.05). Notably, a nomogram model was constructed by combining ICOS/PD-1, age, European Leukemia Net (ELN) risk stratification, and therapy to visually and personalized predict the 1-, 3-, and 5-year OS of patients with non-APL. CONCLUSION: Increased expression of ICOS predicted poor outcomes, and ICOS/PD-1 was the optimal combination of ICs to predict outcomes in patients with AML, which might be a potential immune biomarker for designing novel AML therapy.

Immune effector dysfunction signatures predict outcomes in patients with colorectal cancer.

BACKGROUND: Immune effector dysfunction (IED) is mainly manifested as immune exhaustion and senescence, which are the primary obstacles to the success of cancer immunotherapy. In the current study, we characterized the prognostic relevance of IED signatures in patients with colorectal cancer (CRC). METHODS: Immunohistochemistry (IHC) data of CRC tissue samples from 41 newly diagnosed patients in our clinical center (HDPH cohort) were used to investigate the prognostic importance of IED signatures. The results were validated by the RNA sequencing data of 372 CRC patients from the Cancer Genome Atlas (TCGA) database. RESULTS: In the HDPH cohorts, high Natural Killer (NK) and CD8+ tumor-infiltrating lymphocytes (TILs) were associated with poor overall survival (OS) and relapse-free survival (RFS) in CRC patients. Optimal IED signatures, including high expression of CCR9, ISG20, and low expression of ICOS, and CACNA2D2, predicted poor OS and RFS. Moreover, high-risk scores estimated by a weighted combination of these four IED genes were associated with poor OS and RFS. Notably, risk stratification was constructed by combining risk score and tumor node metastasis (TNM) stage better than TNM stage alone in predicting OS and RFS for CRC patients. The above results were confirmed in the TCGA cohort. CONCLUSION: CCR9, ISG20, ICOS, and CACNA2D2 were optimal IED signatures for predicting the outcomes of CRC patients, which might be a potential biomarker for prognostic stratification and designing novel CRC therapy.

Two previously undescribed cholestanol saponins from the rhizomes of Paris fargesii var. petiolata.

Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.

Erratum: CircRNA_100395 inhibits cell proliferation and metastasis in ovarian cancer via regulating miR-1228/p53/epithelial-mesenchymal transition (EMT) axis: Erratum.

[This corrects the article DOI: 10.7150/jca.35041.].

Structure Guided Discovery of Novel Pan Metallo-ß-Lactamase Inhibitors with Improved Gram-Negative Bacterial Cell Penetration.

The use of ß-lactam (BL) and ß-lactamase inhibitor combination to overcome BL antibiotic resistance has been validated through clinically approved drug products. However, unmet medical needs still exist for the treatment of infections caused by Gram-negative (GN) bacteria expressing metallo-ß-lactamases. Previously, we reported our effort to discover pan inhibitors of three main families in this class: IMP, VIM, and NDM. Herein, we describe our work to improve the GN coverage spectrum in combination with imipenem and relebactam. This was achieved through structure- and property-based optimization to tackle the GN cell penetration and efflux challenges. A significant discovery was made that inhibition of both VIM alleles, VIM-1 and VIM-2, is essential for broad GN coverage, especially against VIM-producing P. aeruginosa. In addition, pharmacokinetics and nonclinical safety profiles were investigated for select compounds. Key findings from this drug discovery campaign laid the foundation for further lead optimization toward identification of preclinical candidates.

Sn Whiskers from Ti2 SnC Max Phase: Bridging Dual-Functionality in Electromagnetic Attenuation.

In the ever-evolving landscape of complex electromagnetic (EM) environments, the demand for EM-attenuating materials with multiple functionalities has grown. 1D metals, known for their high conductivity and ability to form networks that facilitate electron migration, stand out as promising candidates for EM attenuation. Presently, they find primary use in electromagnetic interference (EMI) shielding, but achieving a dual-purpose application for EMI shielding and microwave absorption (MA) remains a challenge. In this context, Sn whiskers derived from the Ti2 SnC MAX phase exhibit exceptional EMI shielding and MA properties. A minimum reflection loss of -44.82 dB is achievable at lower loading ratios, while higher loading ratios yield efficient EMI shielding effectiveness of 42.78 dB. These qualities result from a delicate balance between impedance matching and EM energy attenuation via adjustable conductive networks; and the enhanced interfacial polarization effect at the cylindrical heterogeneous interface between Sn and SnO2 , visually characterized through off-axis electron holography, also contributes to the impressive performance. Considering the compositional diversity of MAX phases and the scalable fabrication approach with environmental friendliness, this study provides a valuable pathway to multifunctional EM attenuating materials based on 1D metals.

Polymeric biomaterials: Advanced drug delivery systems in osteoarthritis treatment.

Polymeric biomaterials have emerged as a highly promising candidate for drug delivery systems (DDS), exhibiting significant potential to enhance the therapeutic landscape of osteoarthritis (OA) therapy. Their remarkable capacity to manifest desirable physicochemical attributes, coupled with their excellent biocompatibility and biodegradability, has greatly expanded their utility in pharmacotherapeutic applications. Nevertheless, an urgent necessity exists for a comprehensive synthesis of the most recent advances in polymeric DDS, providing valuable guidance for their implementation in the context of OA therapy. This review is dedicated to summarizing and examining recent developments in the utilization of polymeric DDS for OA therapy. Initially, we present an overview of the intricate pathophysiology characterizing OA and underscore the prevailing limitations inherent to current treatment modalities. Subsequently, we introduce diverse categories of polymeric DDS, including hydrogels, nanofibers, and microspheres, elucidating their inherent advantages and limitations. Moreover, we discuss and summarize the delivery of bioactive agents through polymeric biomaterials for OA therapy, emphasizing key findings and emerging trends. Finally, we highlight prospective directions for advancing polymeric DDS, offering a promising approach to enhance their translational potential for OA therapy.

Styrax (Liquidambar orientalis Mill.) promotes mitochondrial function and reduces cardiac damage following myocardial ischemic injury: the role of the AMPK-PGC1α signaling pathway.

OBJECTIVES: To explore the effect of extract of Styrax (ES) on myocardial ischemic injury and its molecular mechanism, indirectly providing a theoretical basis for the development of ES. METHODS: In order to assess the impact of ES treatment on ischemic heart disease, both a left anterior descending ligation-induced myocardial infarction (MI) model and an ischemia/hypoxia (I/H)-induced H9c2 cell injury model have been constructed. Specifically, Sprague-Dawley rats were randomly assigned to the following groups (n = 8) and administered intragastrically once a day for seven consecutive days: Sham group, MI group, ES-L (0.2 g/kg) group, ES-M (0.4 g/kg) group, ES-H (0.8 g/kg) group, and trimetazidine (TMZ, 0.02 g/kg) group. The cardiac functions and biochemical assessment of rats were detected. Then, we validated experimentally the targets and mechanism of ES on these pathological processes in I/H-induced H9c2 cell injury model. KEY FINDINGS: These results showed that different doses of ES (0.2 g/kg, 0.4 g/kg, 0.8 g/kg, intragastric) significantly improved myocardial structure and function when compared to the MI group. The results of 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin, and masson staining indicated that ES could significantly reduce infarct size, inhibit myocardium apoptosis, and decrease myocardial fibrosis. Moreover, ES distinctly suppressed the serum levels of lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and creatine kinase-MB (CK-MB), alleviated myocardial mitochondrial morphology, and stimulated adenosine triphosphate (ATP) production, increased the level of succinate dehydrogenase (SDH), complex I and complex V activity. Different doses of ES (5 µg/ml, 10 µg/ml, 20 µg/ml) also improved cardiomyocyte morphology and decreased the apoptosis rate in H9c2 cells that had been exposed to I/H. Furthermore, the results of western blotting and qRT-PCR indicated that ES promoted the expression of proteins and mRNA related to energy metabolism, including phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), peroxisome proliferator activated receptor gamma coactivator 1 alpha (PCG-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM). Mechanically, after the administration of Compound C (dorsomorphin), an AMPK inhibitor, these effects of myocardial protection produced by ES were reversed. CONCLUSIONS: Collectively, these results demonstrated that ES could improve myocardial mitochondrial function and reduce ischemic injury by activating AMPK/PCG-1α signaling pathway, while indicating its potential advantages as a dietary supplement.

Steroid and triterpenoid saponins from the rhizomes of Paris polyphylla var. stenophylla.

Five new saponins, including three steroid saponins, paristenoids A-C (1-3), and two triterpenoid saponins, paristenoids D-E (4-5), along with four known ones (6-9) were isolated from the rhizomes of Paris polyphylla var. stenophylla. The structures of the isolated compounds were identified mainly by detailed spectroscopic analysis, including extensive 1D and 2D NMR, MS, as well as chemical methods. Compound 3 is a new cyclocholestanol-type steroidal saponin with a rare 6/6/6/5/5 fused-rings cholestanol skeleton, and this skeleton has been first found from the genus Paris. The cytotoxicities of the isolated compounds against three human three glioma cell lines (U87MG, U251MG and SHG44) were evaluated, and compound 7 displayed certain inhibitory effect with IC50 values of 15.22 ± 1.73, 18.87 ± 1.81 and 17.64 ± 1.69 µmol·L-1, respectively.

Investigation and analysis of training injury and its psychological effects on firefighters in Beijing A cross-sectional study.

Firefighters' high-intensity training often leads to injuries in the musculoskeletal system. Studies have found that these injuries in the musculoskeletal system may contribute to poor psychological issues. At the same time, low psychological well-being increases the risk of injuries, illness, and mortality. According to research reports, firefighters generally have a good psychological state. So this study aims to survey and analyze the training-related injuries and psychological states of firefighting and rescue personnel in Beijing. This cross-sectional study employed a questionnaire survey to gather data from a total of 214 firefighters in a certain city. The participants were required to complete a questionnaire about musculoskeletal injuries and psychological status, and then these data were statistically analyzed. The incidence of training-related injuries is relatively high among firefighting and rescue teams, with the highest proportions observed in the lower back, knees, and ankles. Overweight and obese firefighters are more prone to ankle injuries. In the group with injuries, the subjective well-being index is lower compared to the group without injuries. Firefighters experiencing moderate to severe pain due to injuries exhibit lower subjective well-being indices compared to those with mild pain. Psychological resilience and the impact of pain on training and sleep can predict the subjective well-being index of firefighters. It is recommended that firefighting and rescue teams enhance preventive measures for musculoskeletal injuries during training to elevate the subjective well-being of firefighters.

Nanotechnology-Boosted Biomaterials for Osteoarthritis Treatment: Current Status and Future Perspectives.

Osteoarthritis (OA) is a prevalent global health concern, posing a significant and increasing public health challenge worldwide. Recently, nanotechnology-boosted biomaterials have emerged as a highly promising strategy for OA therapy due to their exceptional physicochemical properties and capacity to regulate pathological processes. However, there is an urgent need for a deeper understanding of the potential therapeutic applications of these biomaterials in the clinical management of diseases, particularly in the treatment of OA. In this comprehensive review, we present an extensive discussion of the current status and future prospects concerning nanotechnology-boosted biomaterials for OA therapy. Initially, we discuss the pathophysiology of OA and the constraints associated with existing treatment modalities. Subsequently, various types of nanomaterials utilized for OA therapy, including nanoparticles, nanofibers, and nanocomposites, are thoroughly discussed and summarized, elucidating their respective advantages and challenges. Furthermore, we analyze recent preclinical and clinical studies that highlight the potential of nanotechnology-boosted biomaterials in OA therapy. Additionally, future research directions in this evolving field are highlighted. By establishing a link between the structural properties of nanotechnology-boosted biomaterials and their therapeutic functions in OA treatment, we aim to foster advances in designing sophisticated nanomaterials for OA, ultimately resulting in improved therapeutic efficacy of OA therapy through translation into clinical setting in the near future.

Protective effect and mechanism of styrax on ischemic stroke rats: metabonomic insights by UPLC-Q/TOF-MS analysis.

CONTEXT: Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear. OBJECTIVE: To elucidate styrax's anti-ischemic stroke protective effects and underlying mechanisms. MATERIALS AND METHODS: An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax's cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify. RESULTS: The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1ß, and increase SOD and GSH-Px in ischemic-stroke rats (p < 0.05; MDA, p < 0.05 only at 0.4 g/kg dose). Biochemical indicators and metabolic-profile analyses (PCA, PLS-DA, and OPLS-DA) also supported styrax's protective effects. Endogenous metabolites (22) were identified in ischemic-stroke rats, and these perturbations were reversible via styrax intervention, which is predominantly involved in energy metabolism, glutathione and glutamine metabolism, and other metabolic processes. Additionally, styrax significantly upregulated phosphorylated AMP-activated protein kinase and glutaminase brain-tissue expression. CONCLUSION: Styrax treatment could ameliorate ischemic-stroke rats by intervening with energy metabolism and glutamine metabolism. This can help us understand the mechanism of styrax, inspiring more clinical application and promotion.

A high-efficiency gene silencing in plants using two-hit asymmetrical artificial MicroRNAs.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. They are produced through an enzyme-guided process called dicing and have an asymmetrical structure with two nucleotide overhangs at the 3' ends. Artificial microRNAs (amiRNAs or amiRs) are designed to mimic the structure of miRNAs and can be used to silence specific genes of interest. Traditionally, amiRNAs are designed based on an endogenous miRNA precursor with certain mismatches at specific positions to increase their efficiency. In this study, the authors modified the highly expressed miR168a in Arabidopsis thaliana by replacing the single miR168 stem-loop/duplex with tandem asymmetrical amiRNA duplexes that follow the statistical rules of miRNA secondary structures. These tandem amiRNA duplexes, called "two-hit" amiRNAs, were shown to have a higher efficiency in silencing GFP and endogenous PDS reporter genes compared to traditional "one-hit" amiRNAs. The authors also demonstrated the effectiveness of "two-hit" amiRNAs in silencing genes involved in miRNA, tasiRNA, and hormone signalling pathways, individually or in families. Importantly, "two-hit" amiRNAs were also able to over-express endogenous miRNAs for their functions. The authors compare "two-hit" amiRNA technology with CRISPR/Cas9 and provide a web-based amiRNA designer for easy design and wide application in plants and even animals.

Loganin alleviates myocardial ischemia-reperfusion injury through GLP-1R/NLRP3-mediated pyroptosis pathway.

Myocardial ischemia-reperfusion (I/R) injury is one of main pathological manifestations of cardiovascular outcomes related to NLRP3 inflammasome-mediated pyroptosis pathway. Loganin is an iridoid glycoside extracted from traditional Chinese medicines, which has multiple activities. However, the roles and mechanism of loganin in myocardial I/R injury remain largely unknown. The models of myocardial I/R injury were established using I/R-treated rats or OGD/R-treated H9C2 cardiomyocytes. Myocardial damage was assessed by TTC and hematoxylin-eosin staining. Pyroptosis-related marker levels were detected by immunohistochemistry, immunofluorescence and western blotting assays. Cell proliferation was examined via EdU assay. Cell apoptosis was investigated by LDH release and flow cytometry. The integrity of cell membrane was analyzed via Dil staining. GLP-1R and NLRP3 levels were detected by immunofluorescence and western blotting assays. Our results showed that loganin suppressed I/R-induced myocardial damage in rats by reducing myocardial infarct, injury and pyroptosis. In addition, loganin attenuated OGD/R-induced cardiomyocyte apoptosis through increasing cell proliferation and reducing LDH release and apoptotic rate. Loganin also mitigated OGD/R-induced cardiomyocyte pyroptosis by reducing cell membrane damage and levels of cleaved caspase-1, IL-1ß and IL-18. Furthermore, loganin repressed GLP-1R/NLRP3 pathway activation in OGD/R-treated H9C2 cardiomyocytes by enhancing GLP-1R expression and decreasing NLRP3 level. GLP-1R/NLRP3 activation by GLP-1R inhibition or NLRP3 overexpression reversed the suppressive effects of loganin on OGD/R-induced cardiomyocyte pyroptosis. These data indicated that loganin prevented OGD/R-induced proliferation inhibition, apoptosis and pyroptosis in OGD/R-treated cardiomyocytes by inhibiting GLP-1R/NLRP3 activity, indicating the therapeutic potential of loganin in myocardial I/R injury.

Temporal trends in the disease burden of osteoarthritis from 1990 to 2019, and projections until 2030.

This study aimed to report trends in the global burden of osteoarthritis (OA) from 1990 to 2019 and predict the trends in the following years based on Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The study included reporting on the prevalence and incidence rates, as well as disability-adjusted life years (DALYs). Additionally, the age-standardized incidence rate (ASR) and Estimated Annual Percent Change (EAPC) were analyzed along with related factors, finally, Bayesian age-period-cohort (BAPC) analysis were utilized to predict the trends in the upcoming years. In 2019, globally, there were about 414.7 million (95%UI: 368.8 to 464.4 million) OA incident cases, with an age-standardized incidence rate (ASR) about 492.21 (95% UI:438.66 to 551.5) per 100000. And there were about 527.8 million (95% UI: 478.7 to 584.8 million) OA prevalent cases in 2019. The DALYs for OA increased to about 189.49 million (95%UI: 95.71 to 376.60 million) from 1990 to 2019 (EAPC:0.14%; 95%CI: 0.12% to 0.16%). There was a positive association between ASR and Socio-demographic index (SDI) both at the regional and national level. BAPC results showed that ASR in females would decrease but increase in males in the following years. In conclusion, the global burden of OA has risen steadily between 1990 and 2019, placing a significant strain on society. This trend is expected to continue in the coming years. To alleviate this burden, it is necessary to implement measures that target risk factors such as high body mass index.

Novel 2D/2D 1T-MoS2/Ti3C2Tz heterostructures for high-voltage symmetric supercapacitors.

Electrode materials play a crucial role in the electrochemical performance of supercapacitors (SCs). In recent years, 1T-MoS2 and MXene have been extensively studied as potential electrode materials. However, 1T-MoS2 suffers from the metastable property, rigorous synthesis process, and nanosheet restacking issue, while the specific capacitance of MXene is restricted, limiting their supercapacitor performance. To fully exploit the advantages of both materials and address their respective problems, 1T-MoS2/Ti3C2Tz 2D/2D heterostructures are synthesized through a simple hydrothermal method. The existence of heterojunctions is confirmed by XPS and TEM. The different ratios between MoS2 and Ti3C2Tz are investigated, and the electrochemical test is carried out in a "water-in-salt" electrolyte (20 mol kg-1 LiCl). The results demonstrate that the heterostructures exhibit enhanced electrochemical performance. The optimized ratio of 1T-MoS2/Ti3C2Tz is 2 : 1, and the specific capacitance reaches 250 F g-1 at 1 A g-1 with a wide potential window of -0.9 to 0.5 V vs. Ag/AgCl. The capacitance retention is 82.3% (at 10 A g-1) after 5000 cycles, and the average coulombic efficiency (ACE) was 99.96%. Assembled into symmetric SCs (SSCs), the energy density of 12.0 W h kg-1 at a power density of 139.9 W kg-1 is achieved with a high voltage of 1.4 V. It also has 82.6% capacitance retention and 99.95% ACE after 5000 cycles at 5 A g-1. This work is expected to stimulate novel research towards the wide application of 2D/2D heterostructures in SCs.

Cytotoxic Steroidal Saponins Containing a Rare Fructosyl from the Rhizomes of Paris polyphylla var. latifolia.

A phytochemical investigation of the steroidal saponins from the rhizomes of Paris polyohylla var. latifolia led to the discovery and characterization of three new spirostanol saponins, papolatiosides A-C (1-3), and nine known compounds (4-12). Their structures were established via extensive spectroscopic data analysis and chemical methods. Interestingly, compounds 1 and 2 possessed a fructosyl in their oligosaccharide moiety, which is rare in natural product and was firstly reported in family Melanthiaceae. The cytotoxicity of these saponins against several human cancer cell lines was evaluated by a CCK-8 experiment. As a result, compound 1 exhibited a significant cytotoxic effect on LN229, U251, Capan-2, HeLa, and HepG2 cancer cells with IC50 values of 4.18 ± 0.31, 3.85 ± 0.44, 3.26 ± 0.34, 3.30 ± 0.38 and 4.32 ± 0.51 µM, respectively. In addition, the result of flow cytometry analysis indicated that compound 1 could induce apoptosis of glioma cells LN229. The underlying mechanism was explored by network pharmacology and western bolt experiments, which indicated that compound 1 could induce glioma cells LN229 apoptosis by regulating the EGFR/PI3K/Akt/mTOR pathway.

Will ChatGPT/GPT-4 be a Lighthouse to Guide Spinal Surgeons?

The advent of artificial intelligence (AI), particularly ChatGPT/GPT-4, has led to advancements in various fields, including healthcare. This study explores the prospective role of ChatGPT/GPT-4 in various facets of spinal surgical practice, especially in supporting spinal surgeons during the perioperative management of endoscopic spinal surgery for patients with lumbar disc herniation. The AI-driven chatbot can facilitate communication between spinal surgeons, patients, and their relatives, streamline the collection and analysis of patient data, and contribute to the surgical planning process. Furthermore, ChatGPT/GPT-4 may enhance intraoperative support by providing real-time surgical navigation information and physiological parameter monitoring, as well as aiding in postoperative rehabilitation guidance. However, the appropriate and supervised use of ChatGPT/GPT-4 is essential, considering the potential risks associated with data security and privacy. The study concludes that ChatGPT/GPT-4 can serve as a valuable lighthouse for spinal surgeons if used correctly and responsibly.

New steroidal saponins from the roots of Paris verticillata.

Four new polyhydroxylated steroidal saponins, parisverticillatosides A-D (1-4), together with four known spirostanol saponins (5-8) were isolated from the roots of Paris verticillata. Their structures were elucidated on the basis of extensive spectroscopic analysis and chemical evidences. The discovery of the new compounds 1-4 extended the diversity and complexity of this spirostanol saponin family. The saponins 5 and 6 exhibited cytotoxicities against two human glioma cell lines.