Combined amendment reduces soil Cd availability and rice Cd accumulation in three consecutive rice planting seasons.

The scientific application of stabilized materials has been considered an effective method for the in situ remediation of Cd-contaminated soil. This study aimed to investigate the persistence of the effect of a combined amendment of limestone and sepiolite (LS) on soil Cd availability and accumulation in rice grown in a mildly Cd-contaminated paddy field (0.45 mg/kg of Cd) over three consecutive rice seasons. 1125-4500 kg/ha of LS was applied to the soil before the first rice planting season and 562.5-2250 kg/ha of LS was supplemented before the third rice planting season. The application of LS (1125-4500 kg/ha) increased the soil pH by 0.44-1.09, 0.18-0.53, and 0.42-0.68 in the first, second, and third season, respectively, and decreased the soil acid-extractable Cd content by 18.2-36.4%, 17.7-33.5%, and 9.6-17.6%. LS application significantly decreased the Cd contents in the rice tissues. The application of 4500 kg/ha of LS decreased the Cd content in brown rice to below the National Food Limit Standard of 0.2 mg/kg (GB 2762-2017) in the three consecutive rice seasons. However, the effect of LS on the soil-rice system was significantly weakened in the third season. The supplementary application of 562.5-2250 kg/ha of LS further decreased the Cd content in brown rice by 26.1-56.5% and decreased the health risk index by 23.7-43.8%. Therefore, it was recommended to apply 4500 kg/ha of LS in the first season and to supplement 2250 kg/ha of LS in the third season to effectively guarantee the clean production of rice in three consecutive rice seasons.

Simultaneous mitigation of tissue cadmium and lead accumulation in rice via sulfate-reducing bacterium.

The objectives of this study were to investigate the mechanism responsible for Cd and Pb immobilization by sulfate reduction to sulfide and effectiveness of decreasing Cd2+ and Pb2+ bioavailability in culture solution and paddy soils via sulfate-reducing bacterium (SRB1-1). The SRB1-1 strain, exhibiting high resistances to Cd2+ and Pb2+, was isolated from bulk soils in the metal(loid)-contaminated paddy field. During the culture of the SRB1-1 strain, the removal percentages of Cd2+ and Pb2+ from culture solution reached 99.5% and 76.0% in 72 h, respectively. The surface morphology and composition of metal precipitates formed by SRB1-1 strain were analyzed by transmission electron microscopy (TEM) and further confirmed to be CdS and PbS by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). When living SRB1-1 strain was applied in Cd and Pb-contaminated soils, the SRB1-1 strain could stably colonize using its resistance to rifampicin, and showed significantly impact on the bacterial community composition. Cd and Pb contents in rice grains were decreased by 29.5% and 26.2%, respectively, while Cd and Pb contents in the roots, culms, leaves, and husk were also decreased ranging from 19.1% to 43%, respectively. Due to growth in highly Cd and Pb contaminated soils, Cd content of the rice grains did not meet the standard for limit of Cd and Pb, but safe production of rice plants may be obtained in slightly or moderately metal(loid)-contaminated soils in the presence of the living SRB1-1 strain. These results indicated that the SRB1-1 strain could effectively reduce the Cd and Pb bioavailability in soils and uptake in rice plants. Our results highlighted the possibility to develop a new bacterial-assisted technique for reduced metal accumulation in rice grains, and also showed potential for effective synergistic bioremediation of SRB1-1 strain and rice plants in metal(loid)-contaminated soils.

Space debris detection in optical image sequences.

We present a high-accuracy, low false-alarm rate, and low computational-cost methodology for removing stars and noise and detecting space debris with low signal-to-noise ratio (SNR) in optical image sequences. First, time-index filtering and bright star intensity enhancement are implemented to remove stars and noise effectively. Then, a multistage quasi-hypothesis-testing method is proposed to detect the pieces of space debris with continuous and discontinuous trajectories. For this purpose, a time-index image is defined and generated. Experimental results show that the proposed method can detect space debris effectively without any false alarms. When the SNR is higher than or equal to 1.5, the detection probability can reach 100%, and when the SNR is as low as 1.3, 1.2, and 1, it can still achieve 99%, 97%, and 85% detection probabilities, respectively. Additionally, two large sets of image sequences are tested to show that the proposed method performs stably and effectively.

IL-17 induces MIP-1α expression in primary mouse astrocytes via TRPC channel.

Our previous study demonstrated IL-17-mediated induction of MIP-1α through its binding to the cognate IL-17RA and MIP-1α was involved in astrocyte activation. Transient receptor potential canonical (TRPC) channel was involved in astrocyte activation, however, whether TRPC channel regulates MIP-1α expression in the context of multiple sclerosis (MS) remains largely unknown. In this study we identify the essential role of TRPC channel in IL-17-mediated MIP-1α expression and astrocyte activation. Moreover, treatment of astrocytes with IL-17 activated MAPKs and PI3K/Akt signaling pathways with downstream NF-κB pathways. Interestingly, the TRPC blocker-SKF96365 (10 µM) and Norgestimate (10 µM) significantly inhibited the increased expression of MIP-1α via suppression of IL-17-mediated ERK, p38 and JNK MAPKs and PI3K/Akt pathway activation, thereby underscoring the role of TRPC channel in this process. Together these data underpin the role of TRPC channel as a novel target that regulates MIP-1α expression and cell activation-mediated by IL-17 with implications for therapeutic intervention for reversal of neuroinflammation inflicted by IL-17. Understanding the regulation of MIP-1α expression may provide insights into the development of potential therapeutic targets for neuroinflammation associated with MS.

Decolorization of Alizarin Red and other synthetic dyes by a recombinant laccase from Pichia pastoris.

A cDNA encoding for a laccase was isolated from the white-rot fungus Lenzites gibbosa by RT-PCR and expressed in the Pichia pastoris. The laccase native signal peptide efficiently directed the secretion of the recombinant laccase in an active form. Factors influencing laccase expression, such as pH, cultivation temperature, copper concentration and methanol concentration, were optimized. The recombinant enzyme was purified to electrophoretic homogeneity, and was estimated to have a MW of ~61.5 kDa. The purified enzyme behaved similarly to the native laccase produced by L. gibbosa and efficiently decolorized Alizarin Red, Neutral Red, Congo Red and Crystal Violet, without the addition of redox mediators. The decolorization capacity of this recombinant enzyme suggests that it could be a useful biocatalyst for the treatment of dye-containing effluents. This study is the first report on the synthetic dye decolorization by a recombinant L. gibbosa laccase.

Case Report: Successful retrieval of a migrated left atrial appendage occluder through the synergistic use of a guidewire and a gooseneck snare.

Left atrial appendage occluder (LAAO) dislodgement with embolization is a rare occurrence. If the LAAO migrates into the left atrium or ventricle, it can lead to acute heart failure or even death in a person, necessitating urgent surgical intervention. Currently, most cases of LAAO dislodgement are managed through open-heart surgery, while percutaneous retrieval of the LAAO has been reported only in a few cases with limited associated experience. This article reports a case of a patient in whom a migrated LACbes device was successfully retrieved using a catheter-based approach, demonstrating an innovative and minimally invasive treatment strategy.

Long-term efficacy of left bundle branch pacing and biventricular pacing in patients with heart failure complicated with left bundle branch block.

Background: Left bundle branch pacing (LBBP) can physiologically correct complete left bundle branch block (CLBBB), and has become the best alternative to biventricular pacing (BiVP). Objective: To compare the efficacy of LBBP and BiVP in patients with heart failure (HF) complicated with CLBBB. Methods: This was a single-center retrospective study. Patients with HF complicated with CLBBB who underwent successful cardiac resynchronization therapy (CRT) in Wuhan Asian Heart Hospital from June 2018 to June 2023 were enrolled and divided into LBBP group and BiVP group according to the pacing method. The primary endpoints were the absolute increase of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and echocardiographic response rate. Secondary endpoints were all-cause mortality, heart failure hospitalization (HFH), NT-proBNP, paced QRS duration, pacing threshold, and procedural duration. Results: A total of 120 patients were enrolled in this study, including 60 patients in LBBP group and 60 patients in BiVP group. The median follow-up time was 37 ± 19 months. Compared with BiVP group, LBBP group had a more significant increase in absolute LVEF (ΔLVEF) (14.8 ± 9.9% vs. 10.7 ± 9.0%, P = 0.02), a more significant reduction in LVEDD (56.9 ± 10.9 mm vs. 61.1 ± 10.8 mm, P = 0.03), and a higher echocardiographic super response rate (65% vs. 45%, P = 0.02). There were no significant differences in all-cause mortality (1.7% vs. 10.0%, P = 0.11) and HFH (6.7% vs. 13.3%, P = 0.22). In terms of paced QRS duration (128.7 ± 14.1 ms vs. 137.5 ± 16.5 ms, P = 0.002), pacing threshold (0.72 ± 0.21 V/0.4 ms vs. 1.39 ± 0.51 V/0.4 ms, P < 0.001), procedural duration (134.1 ± 32.2 min vs. 147.7 ± 39.4 min, P = 0.04), the LBBP group was superior to the BiVP group. Conclusion: In nonischemic cardiomyopathy (NICM) patients with HF combined with CLBBB and LVEF ≤ 35%, LBBP is better than BiVP.

T-bet Regulates Ion Channels and Transporters and Induces Apoptosis in Intestinal Epithelial Cells.

T-bet, encoded by TBX21, is extensively expressed across various immune cell types, and orchestrates critical functions in their development, survival, and physiological activities. However, the role of T-bet in non-immune compartments, notably the epithelial cells, remains obscure. Herein, a Tet-O-T-bet transgenic mouse strain is generated for doxycycline-inducible T-bet expression in adult animals. Unexpectedly, ubiquitous T-bet overexpression causes acute diarrhea, intestinal damage, and rapid mortality. Cell-type-specific analyses reveal that T-bet-driven pathology is not attributable to its overexpression in CD4+ T cells or myeloid lineages. Instead, inducible T-bet overexpression in the intestinal epithelial cells is the critical determinant of the observed lethal phenotype. Mechanistically, T-bet overexpression modulates ion channel and transporter profiles in gut epithelial cells, triggering profound fluid secretion and subsequent lethal dehydration. Furthermore, ectopic T-bet expression enhances gut epithelial cell apoptosis and markedly suppresses colon cancer development in xenograft models. Collectively, the findings unveil a previously unrecognized role of T-bet in intestinal epithelial cells for inducing apoptosis, diarrhea, and local inflammation, thus implicating its potential as a therapeutic target for the treatment of cancer and inflammatory diseases.

Treatment of osteoporotic vertebral compression fractures with percutaneous kyphoplasty: a report of 196 cases.

The incidence of osteoporotic vertebral compression fracture (OVCF) is increased recently. Percutaneous kyphoplasty (PKP) has recently been shown to have a curative effect on OVCF. Unfortunately, related complications arising from PKP cannot be ignored, such as cement leaks, fever, and intercostal neuralgia. This study aimed to investigate the common complications of PKP in the treatment of OVCF patients and analyze the causes and assess prevention and control measures. A total of 196 patients (204 vertebrae) underwent PKP procedures at the Department of Spine Surgery, Shenzhen Sixth People's Hospital, Guangdong, China, from June 2004 to August 2010. The data on incidence rates of the various complications were compiled. All patients were successfully operated without death, paraplegia, or pulmonary embolism. Incidence of various complications resulting from different types of bone cement leakage was 27.45 %, including 0.51 % for postoperative elevated fever, 4.08 % for intercostal neuralgia, 2.55 % for trailing of bone cement, 0.51 % for refracture at adjacent vertebrae, and 0.51 % for cerebrospinal fluid leakage. These results suggest that PKP is an effective surgical technique for the treatment of OVCF, resulting in limited trauma with satisfactory curative effects. Skillful mastery of this technology will help reduce the incidence rate of complications.

Selenium-enriched Bifidobacterium longum protected alcohol and high fat diet induced hepatic injury in mice.

The objective of this study was to verify the protective effect of Bifidobacterium longum (BL) and the synergistical effect of Selenium and BL on alcohol plus high fat diet (HFD) induced hepatic injury in mice. We also want to explore the mechanism of Selenium-enriched Bifidobacterium longum (SeBL). C57BL/6 mice were treated with alcohol plus HFD with or without different dosage of BL or SeBL for 4 weeks. Serum levels of ALT, AST, TC, TG, LDL-C, HDL-C, FFAs, TNF-α, IL-6 and IL-1ß, hepatic MDA level, SOD activity, the mRNA levels of AMPK, PPAR-α and SREBP1 were invested. SeBL inhibited lipid accumulation in hepatocytes; reduced serum AST and ALT levels; improved dyslipidemia; decreased serum FFAs, TC, TG and LDL-C levels. SeBL also inhibited alcohol plus HFD-induced hepatocyte oxidative stress through decrease in hepatic MDA levels and increase in SOD activity. SeBL also regulated lipid metabolism related genes such as AMPK, PPAR-α and SREBP1. Although BL had similar effect as SeBL, SeBL is more effective than BL. SeBL protected mice from alcohol plus HFD-induced hepatic injury in mice because of its inhibitory effect on hepatocellular oxidative stress, lipogenesis and inflammation. Selenium enhanced the protective effect of BL.

Corrigendum: DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia.

[This corrects the article DOI: 10.3389/fgene.2018.00646.].

Fatty liver diseases, mechanisms, and potential therapeutic plant medicines.

The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins (SIRTs), Forkhead box O (FoxO), Sterol-regulatory element-binding proteins (SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.

Effect of three Napier grass varieties on phytoextraction of Cd- and Zn-contaminated cultivated soil under mowing and their safe utilization.

The use of Napier grass to remediate heavy metal-contaminated soil is a new phytoremediation technique. The objective of this study was to evaluate the ability of Napier grass (Pennisetum purpureum Schumach.) to remediate Cd- and Zn-contaminated cultivated soil under nonmowing and mowing and the possibility of safe utilization of the stem and leaf after detoxification by liquid extraction. Three Napier grass varieties, P. purpureum cv. Mott (PM), P. purpureum cv. Red (PR), and P. purpureum cv. Guiminyin (PG), were planted in a field with 3.74 mg kg-1 Cd and 321.26 mg kg-1 Zn for 180 days. The maximum amounts of Cd and Zn removed by PG were 197.5 and 5023.9 g ha-1, respectively, almost equaling those of hyperaccumulators. Compared with nonmowing, mowing did not decrease the Cd and Zn contents in various tissues but increased the biomasses of PM, PR, and PG by 86.6%, 18.9%, and 26.1%, respectively. Compared with nonmowing, the amounts of Cd removed by PM, PR, and PG under mowing increased by 110.5%, 40.0%, and 107.9%, respectively, and that of Zn increased by 63.0%, 53.1%, and 71.6%. The dominant Cd and Zn chemical fractions in Napier grass were the pectate- and protein-integrated fractions. After liquid extraction, although the nutrient element (Ca, K, Mg, and Mn) contents in the stem and leaf were reduced significantly, the Cd and Zn contents decreased below the limit of the Chinese Hygienic Standard for Feeds, and the crude protein content was largely retained. Such detoxified stems and leaves can be safely used as feeds or as raw materials for energy production.

Isosteviol Protects Free Fatty Acid- and High Fat Diet-Induced Hepatic Injury via Modulating PKC-ß/p66Shc/ROS and Endoplasmic Reticulum Stress Pathways.

Aims: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases. However, there are no approved pharmacotherapies for the treatment of NAFLD other than managing life style and controlling diets. Extensive studies have demonstrated that multiple mechanisms are involved in free fatty acid (FFA)- and high fat diet (HFD)-induced hepatic injury, including mitochondrial dysfunction, activation of oxidative stress and endoplasmic reticulum (ER) stress, and lysosome dysfunction. A previous study reported that Isosteviol (ISV), a derivative of stevioside, prevents HFD-induced hepatic injury. However, the underlying mechanisms remain unclear. Results: In this study, we examined the potential cellular/molecular mechanisms underlying ISV-mediated protective effect against FFA-/HFD-induced hepatic lipotoxicity by using both in vitro primary rat hepatocytes and the in vivo rat NAFLD model. The results indicated that ISV inhibits FFA-/HFD-induced hepatic injury via reducing oxidative and ER stress. Specifically, ISV inhibited the expression, activation, and mitochondrial translocation of Src-homology-2-domain-containing transforming protein 1 (p66Shc), an adapter protein that mediates oxidative stress-induced injury and is a substrate of protein kinase C-ß (PKC-ß), via inhibition of PKC-ß activity. However, ISV had no effect on the expression and activity of peptidyl-prolyl cis-trans isomerase and serine/threonine protein phosphatase 2A, isomerase and phosphorylase of p66Shc. In addition, ISV also inhibited FFA-induced ER stress and decreased ER-mitochondrial interaction. Innovation and Conclusion: We first identified that ISV prevents FFA-/HFD-induced hepatic injury through modulating PKC-ß/p66Shc/oxidative and ER stress pathways. ISV represents a promising therapeutic agent for NAFLD in the future. Antioxid. Redox Signal. 30, 1949-1968.

Astilbin inhibits the adhesion of T lymphocytes via decreasing TNF-alpha and its associated MMP-9 activity and CD44 expression.

Our previous study has revealed that astilbin, a flavonoid isolated from the rhizome of Smilax glabra, improves an immunological liver injury and its mechanism includes an inhibition of the lymphocyte adhesion. The present study further examined the anti-adhesive activity in various assays by using human leukemia T cell line Jurkat cells. We found that astilbin inhibited the adhesion of Con A or PMA-activated Jurkat cells to fibronectin, type IV collagen, hyaluronic acid, and [corrected] ECV-304 cells. Astilbin inhibited the adhesion of Jurkat cells to PMA-activated but not non-activated ECV-304 cells without any influence on the survival of the ECV-304 cells and Jurkat cells. Astilbin also inhibited the CD44 expression and TNF-alpha production in Jurkat cells. In the co-culture assay between Jurkat cells and ECV-304 cells, the MMP-9 secretion from Jurkat cells was inhibited after astilbin-treatment, while the exogenous TNF-alpha increased the MMP-9 secretion in a dose-dependent manner. These findings suggest that the inhibition of T lymphocyte adhesion by astilbin may be related to the reduction of the CD44 expression and TNF-alpha production in the cells, which may further cause a decreased MMP-9 secretion.

Inflammatory factors that contribute to upregulation of ERG and cardiac arrhythmias are suppressed by CPU86017, a class III antiarrhythmic agent.

The aim of this study was to verify whether exaggerated arrhythmogenesis is attributed to inflammatory factors actively involving an excess of reactive oxygen species (ROS), transforming growth factor (TGF)-beta and endothelin (ET). We hypothesized that CPU86017, derived from berberine, which possesses multi-channel blocking activity, could suppress inflammatory factors, resulting in inhibition of over-expression of ether-a-go-go (ERG) and an augmented incidence of ventricular fibrillation (VF) in ischaemia/reperfusion (I/R). Rats with cardiomyopathy (CMP) induced by thyroxine (0.2 mg(-1)kg(-1) s.c. daily for 10 days) were treated with propranolol (10 mgkg(-1) p.o.) or CPU86017 (80 mgkg(-1) p.o.) on days 6-10. On the 11th day, arrhythmogenesis of the CMP was evaluated by I/R. In the CMP control group, an increase in VF incidence was found with the I/R episode, accompanied by increased ROS, which manifested as an increased level of malondialdehyde and decreased activities of SOD, glutathione peroxidase and catalase in the myocardium. Levels of inducible nitric oxide synthase and TGF-beta mRNA were increased in association with upregulation of preproET-1 and ET-converting enzyme. We found increased levels of ERG, which correlated well with arrhythmogenesis. Treatment with CPU86017 or propranolol reversed these changes. These experiments verified our hypothesis that the inflammatory factors ROS, iNOS, TGF-beta and ET-1 are actively involved in upregulation of ERG and arrhythmogenesis. CPU86017 and propranolol reduced VF by suppressing these inflammatory factors in the myocardium.

DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia.

The biological pathology of deficit schizophrenia (DS) remains unclear. Matrix metalloproteinase 9 (MMP9) might be associated with neural plasticity and glutamate regulation, involved in schizophrenia pathogenesis. This study explores gene expression and DNA methylation of MMP9 in peripheral blood mononuclear cells (PBMCs) and their relationship with clinical symptoms in DS and non-deficit schizophrenia (NDS). Pyrosequencing was used to determine DNA methylation at CpG sites in exon 4 and exon 5 of MMP9 in 51 DS patients, 53 NDS patients and 50 healthy subjects (HC). RT-qPCR was used to detect MMP9 expression. Clinical symptoms were assessed by BPRS, SANS and SAPS scales. MMP9 expression in PBMCs was significantly higher in DS than NDS and HC subjects. Compared to NDS patients, DS patients had significantly lower DNA methylation at individual CpG sites in exon 4 and exon 5 of MMP9. Correlation analysis showed that DNA methylation in exon 4 was negatively correlated with gene expression in DS group. Positive correlation was found between MMP9 expression and negative symptoms in total schizophrenic patients. The social amotivation factor of SANS and negative syndrome of BPRS was negatively correlated with DNA methylation of CpG5-1 in DS patients but not in NDS patients. DS patients showed a specific abnormality of peripheral MMP9 expression and DNA methylation, indicating a pathological mechanism underlying DS as a specific subgroup of schizophrenia.

DNA methylation and gene expression of the chemokine (C-X-C motif) ligand 1 in patients with deficit and non-deficit schizophrenia.

This study detected the differences in gene expression and DNA methylation of CpG sites in CXCL1 gene and further investigated their associations with clinical symptoms in deficit schizophrenia (DS) and non-deficit schizophrenia (NDS). Pyrosequencing and RT-qPCR were separately used to determine DNA methylation and mRNA expression of CXCL1 gene. Both DNA methylation and expression were significantly different among DS, NDS and healthy control (HC) groups. Correlation analysis revealed that CXCL1 gene expression was associated with the negative syndrome in NDS patients, while no association in DS patients was observed. All together, these results suggest that DS may be a specific subgroup of schizophrenia with the characteristic abnormality of peripheral CXCL1 DNA methylation and gene expression.

Simultaneous quantification of five major bioactive flavonoids in Rhizoma smilacis glabrae by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of five flavonoids, taxifolin, neoastilbin, astilbin, neoisoastilbin and isoastilbin, contained in rhizoma smilacis glabrae. The optimal conditions of separation and detection were achieved on a Lichrospher C18 column (250 mm x 4.6 mm, 5 microm), with a gradient elution program, detected at 291 nm. The correlation coefficients of all the calibration curves showed good linearity (r>0.999) within test ranges. The relative deviation of this method was less than 3% for intra- and inter-day assays, and the average recoveries (n=3) were between 96.2 and 103.1%. The extraction process was also optimized as 2 h immersion and 30 min sonication in 60% ethanol. Eight samples of rhizoma smilacis glabrae from different locations in China were analyzed. The results indicate that the assay is reproducible and precise and could be readily utilized for the quality control of rhizoma smilacis glabrae.

A novel synthetic oleanolic acid derivative with amino acid conjugate suppresses tumour growth by inducing cell cycle arrest.

Oleanolic acid (3beta-hydroxy-olean-12-en-28-oic acid; OA) has a wide variety of bioactivities and is used for medicinal purposes in many Asian countries. Various derivatives of OA have been synthesized in attempts to improve the potency. Here we describe the anti-tumour activity of a novel OA derivative, N-[(3beta)-3-(acetyloxy)-28-oxoolean-12-en-28-yl]-glycine methyl ester (AOA-GMe). AOAGMe was a more potent inhibitor of the growth of B16 melanoma cells than its parent compound OA, both in-vitro and in-vivo. AOA-GMe also exhibited dose-dependent inhibition of human K562 leukaemia cells, but had almost no toxicity in normal human peripheral blood mononuclear cells. AOA-GMe induced cell cycle arrest in G0/G1 and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D, cyclin-dependent kinase CDK4 and phosphorylated retinoblastoma protein, and increases in the cyclin-dependent kinase inhibitor p15. OA did not show such activities. These results suggest that AOA-GMe may induce growth arrest in tumour cells through regulation of proteins involved in the cell cycle.