Profiles and transplacental transfer of per- and polyfluoroalkyl substances in maternal and umbilical cord blood: A birth cohort study in Zhoushan, Zhejiang Province, China.

Per- and polyfluoroalkyl substances (PFAS) can pass through the placental barrier and pose health risks to fetuses. However, exposure and transplacental transfer patterns of emerging PFAS remain unclear. Here, 24 PFAS were measured in paired maternal whole blood (n = 228), umbilical cord whole blood (n = 119) and serum (n = 120). Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to differentiate PFAS between different matrices. The transplacental transfer (TPT) of PFAS was calculated using cord to maternal whole blood concentration ratios. PFOS and PFOA were still the dominant PFAS in maternal samples. The emerging PFAS had higher TPT than PFOS and PFOA. Moreover, PFAS with the same chain length but different functional groups and C-F bonds showed different TPT, such as PFOS and PFOSA (C8, median: 0.090 vs. 0.305, p < 0.05) and PFHxS and 4:2 FTS (C6, median: 0.220 vs. 1.190, p < 0.05). A significant sex difference in 4:2 FTS (median: boys 1.250, girls 1.010, p < 0.05) were found. Furthermore, we observed a significant U-shaped trend for the TPT of carboxylates with increasing carbon chain length. PFAS showed a compound-specific transfer through placental barrier and a compound-specific distribution between different matrices in this study.

Should migraine without aura be further divided? A study of 1444 female patients with migraine without aura.

To explore the possibility of further dividing migraine without aura (MWA), 1444 female patients fulfilled the criterion were recruited, and grouped basing on the association of MWA onset with menarche and childbirth (group J1, onset before menarche; group J2, onset between menarche and childbirth; group J3, onset after childbirth). By comparing migraine (side, location, aggravated by routine physical activity, NRS score, frequency, accompanying symptoms, with premonitory symptom (PS) and trigger, sum of PS and trigger) and migraine-related factors [chronic daily headache, medicine overused headache, body mass index (BMI), education level, exercise status, sleep status, consumption of tea/coffee/alcohol, patient health questionnaire-9 (PHQ-9) score and generalized anxiety disorder-7, (GAD-7) score)] among groups, it was found that the J1 group and the J2 group presented more typical migraine features than the J3 group; 2) the J3 group was more prone to emotion and sleep disorders, weight management issues, frequent migraine attacks and medication overuse. This study provided a basis for further dividing MWA. Genetic research should be conducted and treatment should be prescribed accordingly because the underlying pathogenesis may be different.

Optimization and application of a method to determine 24 perfluorinated compounds in umbilical cord serum by using liquid chromatography tandem mass spectrometry.

Perfluorinated compounds (PFCs) are a group of widely used synthetic chemicals. Owing to their unique chemical properties, PFCs can accumulate in the environment and living organisms. In vitro and in vivo studies have demonstrated the adverse effects of exposure to PFCs, resulting in increased concern. Therefore, a fast, reliable analytical method is crucial for human biomonitoring and health risk assessment. This study used two isotope internal standards to identify and quantify 24 PFCs in umbilical cord serum samples, based on classical liquid-liquid extraction (LLE) with liquid chromatography tandem mass spectrometry (LC-MS/MS). According to our review of the literature, this study is the first to determine the TFHSA, S4hPDS, S4hPOS, S4hPHS, SPHeS, SPNoS, and SPPeS by using this developed method. The average spiked recoveries of 24 PFCs were acceptable, ranging from approximately 64.0% to 124%; RSDs ranged from 0.74% to 11.2%; LOD and LOQ ranged from 0.013 to 0.248 µg/L and from 0.030 to 0.747 µg/L, respectively. This method was applied to measure the PFCs in umbilical cord serum samples; 24 PFCs were detected in the investigated samples, which are comparable to those reported in the literature. TFHSA, S4hPDS, S4hPOS, S4hPHS, SPHeS, SPNoS, and SPPeS were also detected in the samples, which should be investigated in further research. The sensitivity, accuracy, and precision of the developed method are sufficient for its application in large-scale biomonitoring studies.

Iso-suillin-induced DNA damage leading to cell cycle arrest and apoptosis arised from p53 phosphorylation in A549 cells.

Extensive investigations have revealed that iso-suillin, a secondary metabolite isolated from Suillus flavus, could induce cell cycle arrest and apoptosis in human chronic myeloid leukemia K562 cells, human hepatocellular carcinoma SMMC-7721 cell line, and human small cell lung cancer H446 cell line in vitro. In the present study, human lung cancer A549 cells were used to reveal the mechanism of iso-suillin's effects on lung adenocarcinoma, which were detected both in vitro and in vivo. Results showed that iso-suillin potently inhibited A549 cell proliferation through an early G1 arrest. Iso-suillin also induced A549 cell apoptosis in vitro. Phosphorylation of p53 at serines 15 and 20 may be one of the pivotal factors for cell cycle arrest and apoptosis after treatment of iso-suillin in A549 cells. Moreover, in an A549 xenograft model, tumor growth and progression could be inhibited by iso-suillin. Body weight change and some vital organs toxicity was also roughly examined, no significant toxic effects of iso-suillin were shown (at a dose of 5 mg/kg for each administration). The in vitro and in vivo anti-tumor effects implied that iso-suillin may act as a tumor growth inhibitor, and its induction of p53 phosphorylation is pivotal for cell cycle arrest and apoptosis in A549 cells.

Protective effect of coumarin-pi against t-BHP-induced hepatotoxicity by upregulating antioxidant enzymes via enhanced Nrf2 signaling.

Coumarin-pi, a new coumarin derivative isolated from the mushroom Paxillus involutus, has antioxidative activity, but the underlying mechanism against intracellular oxidative stress is still unclear. This study investigated its cytoprotective effects and the antioxidative mechanism in tert-butyl hydroperoxide (t-BHP)-induced HepG2 cells. The results demonstrated that coumarin-pi suppressed t-BHP-stimulated cytotoxicity, cell apoptosis, and generation of reactive oxygen species (ROS). Additionally, coumarin-pi promoted nuclear factor erythroid 2-related factor 2 (Nrf2) expression and upregulated the protein expression of antioxidantenzymes, including heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidase (NQO1), glutamyl cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase regulatory subunit (GCLM). After coumarin-pi treatment, transcriptome sequencing and bioinformatic analysis revealed that 256 genes were differentially expressed; interestingly, only 20 genes were downregulated, and the rest of the genes were upregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation were used to identify changes in metabolic pathways. Collectively, the results presented in this study indicate that coumarin-pi has a protective effect against t-BHP-induced cellular damage and oxidative stress.

Genome survey, high-resolution genetic linkage map construction, growth-related quantitative trait locus (QTL) identification and gene location in Scylla paramamosain.

Scylla paramamosain is one of the most economically important crabs in China. In this study, the first genome survey sequencing of this crab was performed, and the results revealed that the estimated genome size was 1.21 Gb with high heterozygosity (1.3%). Then, RAD technology was used to construct a high-resolution linkage map for this species. A total of 24,444 single nucleotide polymorphism (SNP) makers were grouped into 47 linkage groups. The total length of the linkage groups was 3087.53 cM with a markers interval of 0.92 cM. With the aid of transcriptome and genome scaffold data, 4,271 markers were linked to genes, including several important growth-related genes such as transforming growth factor-beta regulator I, immune related-gene C-type lectin and ecdysone pathway gene broad-complex-like protein. Further, 442 markers, representing 279 QTLs, associated with 24 traits were identified, and of these markers, 78 were linked to genes. Some interesting genes, such as dedicator of cytokinesis protein 3, tenascin-X and DNA helicase MCM8, were believed to have important relationship with specific traits and merit further exploration. The results of this study will accelerate the genetic improvement and genome sequencing analysis of the mud crab.

The role of E2F1-topoIIß signaling in regulation of cell cycle exit and neuronal differentiation of human SH-SY5Y cells.

This study aims to test the role of E2F1-topoIIß signaling in neuronal differentiation of SH-SY5Y cells. With retinoic acid (RA) induction, a high percentage of cells were found to be arrested at the G0/G1 phase, with decreased levels of cyclinD1, CDK4, phosphorylation status of pRb and E2F1, in addition to an elevated level of p27. The cells were shown to differentiate into neuronal phenotypes characterized by highly expressed neuronal markers, MAP2 and enriched topoIIß, and remarkable neurite outgrowth. Exogenously forced E2F1 expression with a specific E2F1 plasmid led to suppression of topoIIß expression and disruption of the neuronal differentiation of SH-SY5Y cells. On further examination using the ChIP assay, we found that E2F1 bound directly to the promoter region of topoIIß, and its binding ability was inversely correlated with topoIIß expression in response to RA induction. Thus, our findings suggest that E2F1-topoIIß signaling may play a role in regulation of cell cycle exit and neuronal differentiation.

Non-linear ICA Analysis of Resting-State fMRI in Mild Cognitive Impairment.

Compared to linear independent component analysis (ICA), non-linear ICA is more suitable for the decomposition of mixed components. Existing studies of functional magnetic resonance imaging (fMRI) data by using linear ICA assume that the brain's mixed signals, which are caused by the activity of brain, are formed through the linear combination of source signals. But the application of the non-linear combination of source signals is more suitable for the mixed signals of brain. For this reason, we investigated statistical differences in resting state networks (RSNs) on 32 healthy controls (HC) and 38 mild cognitive impairment (MCI) patients using post-nonlinear ICA. Post-nonlinear ICA is one of the non-linear ICA methods. Firstly, the fMRI data of all subjects was preprocessed. The second step was to extract independent components (ICs) of fMRI data of all subjects. In the third step, we calculated the correlation coefficient between ICs and RSN templates, and selected ICs of the largest spatial correlation coefficient. The ICs represent the corresponding RSNs. After finding out the eight RSNs of MCI group and HC group, one sample t-tests were performed. Finally, in order to compare the differences of RSNs between MCI and HC groups, the two-sample t-tests were carried out. We found that the functional connectivity (FC) of RSNs in MCI patients was abnormal. Compared with HC, MCI patients showed the increased and decreased FC in default mode network (DMN), central executive network (CEN), dorsal attention network (DAN), somato-motor network (SMN), visual network(VN), MCI patients displayed the specifically decreased FC in auditory network (AN), self-referential network (SRN). The FC of core network (CN) did not reveal significant group difference. The results indicate that the abnormal FC in RSNs is selective in MCI patients.

Abnormal Functional Connectivity of Resting State Network Detection Based on Linear ICA Analysis in Autism Spectrum Disorder.

Some functional magnetic resonance imaging (fMRI) researches in autism spectrum disorder (ASD) patients have shown that ASD patients have significant impairment in brain response. However, few researchers have studied the functional structure changes of the eight resting state networks (RSNs) in ASD patients. Therefore, research on statistical differences of RSNs between 42 healthy controls (HC) and 50 ASD patients has been studied using linear independent component analysis (ICA) in this paper. Our researches showed that there was abnormal functional connectivity (FC) of RSNs in ASD patients. The RSNs with the decreased FC and increased FC in ASD patients included default mode network (DMN), central executive network (CEN), core network (CN), visual network (VN), self-referential network (SRN) compared to HC. The RSNs with the increased FC in ASD patients included auditory network (AN), somato-motor network (SMN). The dorsal attention network (DAN) in ASD patients showed the decreased FC. Our findings indicate that the abnormal FC in RSNs extensively exists in ASD patients. Our results have important contribution for the study of neuro-pathophysiological mechanisms in ASD patients.

Novel rhodamine Schiff base type naked-eye fluorescent probe for sensing Fe3+ and the application in cell.

Three rhodamine schiff-base type fluorescent sensors R1-R3 for detecting iron ion (Fe3+), 2-furanacrolein rhodamine hydrazone (R1), furfural rhodamine hydrazone (R2) and 2-furanacrolein rhodamine ethylenediamine (R3) have been synthesized by using rhodamine B derivatives and furan derivatives as staring materials. And their recognition abilities for Fe3+ were studied by fluorescence spectroscopy. The result showed that R1 is a best selective probe for Fe3+ over other metal ions in EtOH/H2O (1:1, v/v) due to having 2-furanacrolein for unique space coordination structural. The recognition of Fe3+ and mechanism of the sensor were characterized and determined by fluorescence spectra and Fukui function. And the fluorescence intensity of the probe R1 for Fe3+ was proportional to its concentration with the linear correlation coefficient of 0.9965 and the binding constant of 7.66×104M-1. And the cell imaging experiment indicated a successful application of the probe R1 for Fe3+ in living cell.

A Primary Study of the Antioxidant, Hypoglycemic, Hypolipidemic, and Antitumor Activities of Ethanol Extract of Brown Slimecap Mushroom, Chroogomphus rutilus (Agaricomycetes).

In vivo and in vitro treatments were carried out to investigate the effects of a 95% ethanol extract of Chroogomphus rutilus (CRE) on antioxidant, hypoglycemic, hypolipidemic, and antitumor properties. CRE showed potent radical scavenging activity against DPPH in vitro. It could increase antioxidant enzymatic activities (superoxide dismutase and glutathione peroxidase) and could reduce malondialdehyde content in vivo in mice in which aging was induced by D-galactose. CRE had hypoglycemic activity and could significantly inhibit α-glucosidase activity in vitro and decrease blood glucose concentration in vivo. CRE could decrease the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and increase the high-density lipoprotein cholesterol level in diabetic mice. The MTT assay showed that CRE also had a certain inhibitory effect on the tumor cells. These results suggest that CRE may be beneficial for human health and could be useful for applications in medicine, the food industry, and agriculture.

Hierarchical trie packet classification algorithm based on expectation-maximization clustering.

With the development of computer network bandwidth, packet classification algorithms which are able to deal with large-scale rule sets are in urgent need. Among the existing algorithms, researches on packet classification algorithms based on hierarchical trie have become an important packet classification research branch because of their widely practical use. Although hierarchical trie is beneficial to save large storage space, it has several shortcomings such as the existence of backtracking and empty nodes. This paper proposes a new packet classification algorithm, Hierarchical Trie Algorithm Based on Expectation-Maximization Clustering (HTEMC). Firstly, this paper uses the formalization method to deal with the packet classification problem by means of mapping the rules and data packets into a two-dimensional space. Secondly, this paper uses expectation-maximization algorithm to cluster the rules based on their aggregate characteristics, and thereby diversified clusters are formed. Thirdly, this paper proposes a hierarchical trie based on the results of expectation-maximization clustering. Finally, this paper respectively conducts simulation experiments and real-environment experiments to compare the performances of our algorithm with other typical algorithms, and analyzes the results of the experiments. The hierarchical trie structure in our algorithm not only adopts trie path compression to eliminate backtracking, but also solves the problem of low efficiency of trie updates, which greatly improves the performance of the algorithm.

Immunohistochemical investigation of topoIIß, H3K27me3 and JMJD3 expressions in medulloblastoma.

Topoisomerase IIß (topoIIß) is a nuclear enzyme specifically expressed in neurons, and plays an important role in the development of the cerebellum. To date, the expression of topoIIß protein in medulloblastoma (MB) has not been investigated. In this study, 16 MB specimens including 10 classical subtypes of MB and 6 desmoplastic subtypes of MB (DMB), along with 5 normal cerebellum samples, were obtained from clinics. With immunohistochemical staining, prominently expressed topoIIß was seen in normal cerebellar tissues, while there was no or less pronounced staining in classical MB cells. Interestingly, on comparing topoIIß expression in different regions of DMB samples, relatively high levels of topoIIß were revealed within nodules composed of differentiated neurocytic cells, which are known to predict a favorable clinical outcome for MB. We also examined the expression of two epigenetic factors, H3K27me3 and JMJD3 in the different tissues. Very high levels of H3K27me3 were found in all MB samples, except the intranodules of DMB, where JMJD3 expression was more prominent. Furthermore, a negative correlation between topoIIß and H3K27me3 in MB was revealed in this study. Thus, our data primarily indicate that topoIIß can be used to estimate neuronal differentiation in MB, and may serve as a target for improving the survival rates for this condition. We speculate that H3K27me3 repression of topoIIß at the transcriptional level may occur, although this needs to be verified using larger numbers of MB samples in future experiments.

Iso-suillin from Suillus flavus Induces Apoptosis in Human Small Cell Lung Cancer H446 Cell Line.

BACKGROUND: The suillin isoform iso-suillin is a natural substance isolated from a petroleum ether extract of the fruiting bodies of the mushroom Suillus flavus. Previous studies have found its inhibition effect on some cancer cells, and we aimed to study its effects on human small cell lung cancer H446 cell line. METHODS: Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cellular morphological changes (apoptosis and necrosis) were evaluated using an electron microscope and Hoechst 33258 staining detected by the inverted microscope. Flow cytometry was used to detect cell apoptosis, cell cycle distribution, and mitochondrial membrane potential. Protein expression was determined by Western blotting analysis. RESULTS: Here, we describe the ability of iso-suillin to inhibit the growth of H446 cells in time- and dose-dependent way. Iso-suillin had no obvious impact on normal human lymphocyte proliferation at low concentrations (9.09, 18.17, or 36.35 µmol/L) but promoted lymphocyte proliferation at a high concentration (72.70 µmol/L). After treatment of different concentrations of iso-suillin (6.82, 13.63, or 20.45 µmol/L), the apoptosis rate of H446 cells increased with increasing concentrations of iso-suillin (16.70%, 35.54%, and 49.20%, respectively, all P < 0.05 compared with the control), and the expression of related apoptotic proteins in the mitochondrial pathway including cytochrome c and caspase-9 were up-regulated compared with the control (all P < 0.05). On the contrary, Bcl-2/Bax ratio was down-regulated compared with the control. Besides, the expression of pro-apoptotic proteins in the death receptor apoptosis pathway, including Fas-associating protein with a novel death domain and caspase-8, and the expression of caspase-3, a downstream regulatory protein of apoptosis, were also increased compared with the control (all P < 0.05). Inhibitors of caspase-9 and caspase-8 reversed the apoptosis process in H446 cells to varying degrees. CONCLUSIONS: These results suggest that iso-suillin could induce H446 cell apoptosis through the mitochondrial pathway and the death-receptor pathway. Therefore, iso-suillin might have a potential application as a novel drug for lung cancer treatment.

Tetramethylpyrazine induces SH-SY5Y cell differentiation toward the neuronal phenotype through activation of the PI3K/Akt/Sp1/TopoIIß pathway.

Tetramethylpyrazine (TMP) is an active compound extracted from the traditional Chinese medicinal herb Chuanxiong. Previously, we have shown that TMP induces human SH-SY5Y neuroblastoma cell differentiation toward the neuronal phenotype by targeting topoisomeraseIIß (TopoIIß), a protein implicated in neural development. In the present study, we aimed to elucidate whether the transcriptional factors specificity protein 1 (Sp1) and nuclear factor Y (NF-Y), in addition to the upstream signaling pathways ERK1/2 and PI3K/Akt, are involved in modulating TopoIIß expression in the neuronal differentiation process. We demonstrated that SH-SY5Y cells treated with TMP (80µM) terminally differentiated into neurons, characterized by increased neuronal markers, tubulin ßIII and microtubule associated protein 2 (MAP2), and increased neurite outgrowth, with no negative effect on cell survival. TMP also increased the expression of TopoIIß, which was accompanied by increased expression of Sp1 in the differentiated neuron-like cells, whereas NF-Y protein levels remained unchanged following the differentiation progression. We also found that the phosphorylation level of Akt, but not ERK1/2, was significantly increased as a result of TMP stimulation. Furthermore, as established by chromatin immunoprecipitation (ChIP) assay, activation of the PI3K/Akt pathway increased Sp1 binding to the promoter of the TopoIIß gene. Blockage of PI3K/Akt was shown to lead to subsequent inhibition of TopoIIß expression and neuronal differentiation. Collectively, the results indicate that the PI3K/Akt/Sp1/TopoIIß signaling pathway is necessary for TMP-induced neuronal differentiation. Our findings offer mechanistic insights into understanding the upstream regulation of TopoIIß in neuronal differentiation, and suggest potential applications of TMP both in neuroscience research and clinical practice to treat relevant diseases of the nervous system.

Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms.

Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs). In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL). CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET) and 5.3% of cases with primary myelofibrosis (PMF). Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR). Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP) expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.

[Identification of a novel aberrant spliceosome of MPL gene (MPLL391-V392ins12)in patients with myeloproliferative neoplasms].

OBJECTIVE: To identify the MPL L391-V392ins12 spliceosome and analyze its frequencies in patients with myeloproliferative neoplasms (MPN). METHODS: MPL aberrant spliceosome was identified through reverse transcription polymerase chain reaction (RT-PCR)combined with cloning sequencing. The mutation of this spliceosome in 248 MPN patients and 200 normal people was determined by allele-specific polymerase chain reaction (AS-PCR). RESULTS: A novel aberrant spliceosome of MPL gene (MPL L391-V392ins12)was identified, i.e. 36 bp intron was retained between exon7 and exon8, and there were 12 amino acids (EGLKLLPADIPV)inserted. MPL L391-V392ins12 mutation was detected in 19 (7.66%)of the 248 patients with MPN, including 1 (1.92%) of 52 patients with PV, 14 (9.66%) of 145 with ET, and 4 (7.84%) of 51 with PMF. And the mutation was not detected in the group of 200 normal people. CONCLUSION: MPL L391-V392ins12 spliceosome is an aberrant spliceosome present in the MPN. It can be detected in PV, ET and PMF, and more frequently in ET and PMF. This mutation may play an important role in the process of MPN.

Specificity protein 1 regulates topoisomerase IIß expression in SH-SY5Y cells during neuronal differentiation.

Topoisomerase IIß (top IIß) is a nuclear enzyme with an essential role in neural development. The regulation of top IIß gene expression during neural differentiation is poorly understood. Functional analysis of top IIß gene structure displayed a GC box sequence in its transcription promoter, which binds the nuclear transcription factor specificity protein 1 (Sp1). Sp1 regulates gene expression via multiple mechanisms and is essential for early embryonic development. This study seeks to determine whether Sp1 regulates top IIß gene expression during neuronal differentiation. For this purpose, human neuroblastoma SH-SY5Y cells were induced to neuronal differentiation in the presence of all-trans retinoic acid (RA) for 5 days. After incubation with 10 µM RA for 3-5 days, a majority of the cells exited the cell cycle to become postmitotic neurons, characterized by the presence of longer neurite outgrowths and expression of the neuronal marker microtubule-associated protein-2 (MAP2). Elevated Sp1 and top IIß mRNA and protein levels were detected and found to be positively correlated with the differentiation stage. Chromatin immunoprecipitation assay demonstrated an increased recruitment of Sp1 to the top IIß promoter after RA treatment. Mithramycin A, a compound that interferes with Sp1 binding to GC-rich DNA sequences, downregulated the expression of top IIß, resulting in reduced expression of MAP2 and decreased neurite length compared with the control group. Our results indicate that Sp1 regulates top IIß expression by binding to the GC box of the gene promoter during neuronal differentiation in SH-SY5Y cells.

Iso-suillin isolated from Suillus luteus, induces G1 phase arrest and apoptosis in human hepatoma SMMC-7721 cells.

Iso-suillin, a natural product isolated from Suillus luteus, has been shown to inhibit the growth of some cancer cell lines. However, the molecular mechanisms of action of this compound are poorly understood. The purpose of this study was to investigate how iso-suillin inhibits proliferation and induces apoptosis in a human hepatoma cell line (SMMC-7721). We demonstrated the effects of iso-suillin on cell proliferation and apoptosis in SMMC-7721 cells, with no apparent toxicity in normal human lymphocytes, using colony formation assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Western blotting was used to examine the expression of G1 phase-regulated and apoptosis-associated protein levels in iso-suillin treated SMMC-7721 cells. The results indicated that iso-suillin significantly decreased viability, induced G1 phase arrest and triggered apoptosis in SMMC-7721cells. Taken together, these results suggest the potential of iso-suillin as a candidate for liver cancer treatment.