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Tao Guo

Publications and source records attributed to Tao Guo.

At least 19 recordsLinked to original sources

Genetic Analysis of Genomic and Methylomic Variation and Identification of Multi-Trait Mutants in Rice Carried on Chang'e-5.

Global food security is facing challenges from population growth to diminishing arable land. Space mutation breeding holds promise for overcoming the variation limitations in conventional breeding; however, the mutagenic effects of the deep-space environment on rice and the transgenerational inheritance patterns of induced variations remain unclear. In this study, rice seeds carried by the Chang'e-5 spacecraft were used as materials. Whole-genome sequencing and whole-genome bisulfite sequencing were performed on the first (SP1) and second generations (SP2) of space-mutagenized plants after their return to Earth. The results showed that the number of genomic variants in the SP2 generation increased significantly compared with SP1, and SNPs, homozygous sites, and variants in coding regions were more heritable. The genome-wide methylation level was elevated in the SP2 generation, and among differentially methylated cytosines, those in the CG context exhibited the highest heritability. Furthermore, large-scale screening for nitrogen efficiency, tolerance to PEG-induced stress, and germination-stage cold resistant mutants was conducted in the SP2 generation, and phenotypic validation was performed in the third generation (SP3). By integrating multi-omics analyses of representative mutants to mine candidate genes, a number of heritable elite mutants were obtained, and seven candidate genes for key traits were identified. This study systematically elucidates the transgenerational inheritance patterns of deep-space-induced variation in rice. The multi-trait mutants obtained provide valuable germplasm resources for gene cloning and breeding applications in rice.

DNA methylation↗

A Risk Score for Polycystic Ovary Syndrome Based on Meta-Analysis and Machine Learning of Gut Microbiota Signatures.

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder among reproductive-age women, in which emerging evidence suggests a substantial role played by the gut microbiota. To comprehensively evaluate gut microbiota alterations in PCOS and identify microbial biomarkers through integrated analysis, a systematic search of PubMed, Web of Science, and Embase was conducted for studies employing 16S rRNA gene sequencing of fecal samples from PCOS cohorts. Ten eligible PCOS cohorts, comprising 858 individuals, were included in the study, from which a risk score was derived using a 20-gene gut microbial signature associated with PCOS. Meta-analysis at the genus level identified that Subdoligranulum, NK4A214_group, and Collinsella significantly decreased, and Bacteroides increased in PCOS across multiple cohorts. Machine learning analysis identified a 20-genus microbial signature using the least absolute shrinkage and selection operator (LASSO) method, which was used to construct a risk score with an AUC of 0.835 in diagnosis prediction. Network analysis further identified Negativibacillus and Lachnospiraceae_UCG_010 as potential driver microbes in PCOS. The analysis in this study highlights key alterations in the gut microbiota across PCOS cohorts. The identified gut microbial signature and derived LASSO-based risk model offer novel insights and a potential tool for PCOS diagnosis.

Polycystic Ovary Syndrome↗

PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) remains an incurable haematological malignancy, underscoring the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the clinical and biological significance of peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1) in MM. METHODS: Expression and clinical data were obtained from public databases and an independent local cohort. Kaplan-Meier and Cox regression analyses were performed to evaluate prognostic value. Differential expression analysis, pathway enrichment analysis and single-cell RNA-seq data analysis were used to explore biological functions. PPRC1 was silenced in MM cell lines using siRNA to assess its effects on cell survival and oxidative phosphorylation. RESULTS: PPRC1 was significantly upregulated in MM and was associated with advanced disease stage and poor overall survival. Multivariate Cox analysis identified PPRC1 as an independent prognostic factor. A nomogram incorporating PPRC1 and revised-ISS improved survival prediction. Functional analyses revealed that PPRC1 was positively correlated with oxidative phosphorylation and oncogenic signalling pathways. A potential connection between PPRC1 expression and immune cell infiltration was observed. PPRC1 knockdown inhibited cell proliferation, induced cell cycle arrest and apoptosis and impaired oxidative phosphorylation in MM. CONCLUSIONS: PPRC1 acts as a prognostic biomarker and metabolic regulator in MM by sustaining mitochondrial oxidative phosphorylation. These findings highlight PPRC1 as a potential therapeutic target in MM.

Humans↗

Association of MTHFD1 G1958A (rs2236225) gene polymorphism with the risk of congenital heart disease: a systematic review and meta-analysis.

BACKGROUND: We did this study to better clarify the correlations of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-G1958A (rs2236225) gene polymorphism with the risk of congenital heart diseases (CHD) and its subgroups. METHODS: Relevant articles were searched in PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP database and Wanfang DATA until October 2023. We will use odds ratios (ORs) and 95% confidence intervals (CIs) to examine the potential associations of MTHFD1- G1958A gene polymorphism with CHD and its subgroups. RESULTS: We included a total of 9 eligible studies, encompassing 1917 children with CHD, 1863 healthy children, 1717 mothers of the children with CHD and 1666 mothers of healthy children. In our study, the meta-analysis of fetal group revealed no significant association between any of the five genetic models for the MTHFD1-G1958A polymorphism and the risk of CHD. Subgroup analysis showed that associations between the MTHFD1-G1958A polymorphism and Tetralogy of Fallot (TOF) risk in the homozygote model (AA vs. GG, OR = 2.82, 95%CI [1.16, 6.86], P = 0.02) and recessive model (AA vs. GG + GA, OR = 3.09, 95%CI [1.36, 7.03], P = 0.007). In addition, the MTHFD1-G1958A polymorphism was associated with the risk of CHD in racial subgroup, increasing the risk of CHD in Caucasians. In maternal analysis, 2 genetic models of MTHFD1-G1958A polymorphism increased the risk of CHD: the heterozygote model (GA vs. GG, OR = 1.22, 95%CI [1.04, 1.42], P = 0.01), and the dominance model (GA + AA vs. GG, OR = 1.17, 95%CI [1.01, 1.34], P = 0.03). CONCLUSIONS: The fetal MTHFD1-G1958A (rs2236225) gene polymorphism increase their risk of TOF. The maternal MTHFD1-G1958A polymorphism has a strong correlation with the risk of CHD, and there are racial differences in this correlation. Compared with GG genotype, the GA genotype increases the risk of CHD.

Humans↗

The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis.

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 naïve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets. CONCLUSIONS: The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.

Humans↗

[Effects of Helicobacter pylori and Helicobacter pylori-related cytokines on apoptosis of gastric epithelial cells and mechanisms thereof].

OBJECTIVE: To investigate the influence of Helicobacter pylori (H. pylori) and H. pylori-related cytokines on the apoptosis of gastric epithelial cells and mechanisms thereof. METHODS: (1) Human gastric cancer cells of the line AGS and human gastric epithelial cells of the line GES-1 were cultured as control group, or incubated with H. pylori alone or H. pylori in combination with exogenous cytokines: interleukin (IL)-1beta, IL-8, or IL-10 for 24 hours. Then flow cytometry (FCM) was used to determine the rate of apoptosis. (2) The GES-1 and AGS cells were incubated with H. pylori for 24 hours and exogenous cytokines for 2 hours respectively. Then RT-PCR was used to examine the level of Fas mRNA expression. (3) Another GES-1 and AGS cells were cultured as control group, or incubated with FasL alone or FasL + exogenous cytokine for 2 hours (incubated with IL-1beta, IL-8, or IL-10 for 2 hours before being added with FasL). Then FCM was used to detect the apoptosis rate. RESULTS: (1) In comparison to the apoptosis level of control group, H. pylori induced an increase in the apoptosis rate of GES-1 and AGS cells by 113.0% and 47.0% respectively (both P < 0.05). The H. pylori-induced apoptosis rates of GES-1 cells (by 29.6% or 25.8%) and AGS cells (by 19.7% or 21.1%) were reduced by IL-1beta or IL-10 (all P < 0.05). IL-8 increased the H. pylori-induced apoptosis level of GES-1 cells by 19.9% (P < 0.05). (2) In the baseline status, both GES-1 and AGS cells showed Fas mRNA expression. The Fas mRNA expressions of the GES-1 and AGS cells incubated with H. pylori were increased by 89.0% and 36.0% respectively (both P < 0.05) in comparison to that of the control group. IL-1beta and IL-10 had no significant effect on the basal Fas mRNA expressions in both GES-1 and AGS cells (all P > 0.05). IL-8 up-regulated the basal Fas mRNA expression level of the GES-1 cells by 33.0% (P < 0.05). (3) IL-1beta and IL-10 inhibited the FasL-induced apoptosis rate of the GES-1 cells (by 30.3% and 32.5% respectively) and AGS cells (by 44.2% and 51.5% respectively) (all P < 0.05). IL-8 enhanced the FasL-induced apoptosis level of the GES-1 cells by 100% (P < 0.05). CONCLUSION: The gastric epithelium apoptosis induced by H. pylori may be in association with Fas receptor. IL-8 may enhance the H. pylori-induced apoptosis by up-regulating the Fas receptor expression. IL-1beta and IL-10 may modulate the apoptosis through other mechanisms.

Apoptosis↗

Repetition rates of specific interval patterns in single spike train reflect excitation level of specific receptor types, shown by high-speed favored-pattern detection method.

UNLABELLED: Interval patterns in single spike train, e.g. "favored patterns (FPs, the FP is a sequence of successive intervals of action potentials that occur more often than what is reasonably expected at random.)", may represent neural codes containing information. The present study developed a "high-speed FP-detection method" which could qualitatively and quantitatively analyze FPs. By using this method, single spike trains of nucleus paraventricularis (NPV) and rostral ventrolateral medulla (RVL) having different firing patterns, being involved in regulation of arterial pressure, and controlled by different transmitters, were chosen for analysis. RESULTS: (1) Corticotropin releasing factor, substance P and agonists of alpha-, beta- and M-receptor microinjected into these brain areas, respectively, induced dominant change of specific FP. Repetition rates of specific FPs reflect excitation level of specific receptor types. It shows that chemical codes (different transmitters with their receptor types or subtypes) are transformed into electrical codes (different FPs). (2) When alpha-, beta- and M-receptors of RVL neurons were activated simultaneously by intrinsic excitatory transmitters released due to activation of input pathway, only repetition rate of the specific FP that represented the predominant activity of the receptor type (alpha-adrenergic receptor) markedly increased. The activities of other receptor types (beta- and M-receptors) were masked. (3) Intrinsic inhibitory transmitters (GABA, beta-endorphin) in the RVL all decreased specific FP repetition rate of dominant receptor type. These results may provide a new way to further explore how information in the CNS is conveyed and processed.

Action Potentials↗

Predictors of in-hospital mortality difference between male and female patients with acute myocardial infarction.

Many studies have demonstrated that, compared with men, women have increased long- and short-term mortality after acute myocardial infarction (AMI). The reasons for this mortality difference remain in dispute. We analyzed baseline characteristics, in-hospital management, and short-term outcomes of 1,246 men and 537 women with AMI to identify clinical variables that can predict the in-hospital mortality difference between genders. A higher in-hospital mortality was found in women with AMI than in men (11.9% vs 6.9%, p <0.001). Women were generally older, had a higher incidence of hypertension, diabetes mellitus, and hyperlipidemia, and had a higher Killip class of cardiac function compared with men. Reperfusion therapy and beta-receptor blockers were underused in women. Using a multivariate logistic regression model, we identified age, history of hypertension and diabetes mellitus, Killip class of cardiac function, and administration of reperfusion therapy and beta-receptor blockers as significant predictors of in-hospital mortality in patients with AMI, with odds ratios of 1.05 (95% confidence interval [CI] approximately 1.03 to 1.07), 1.65 (95% CI 1.12 to 2.41), 1.92 (95% CI 1.27 to 2.90), 3.62 (95% CI 2.88 to 4.56), 0.39 (95% CI 0.24 to 0.66), and 0.63 (95% CI 0.43 to 0.93), respectively. In conclusion, women with AMI had a higher in-hospital mortality rate than did men, probably due to older age, higher incidence of hypertension, diabetes mellitus, and hyperlipidemia, a higher Killip class of cardiac function, and less utilization of reperfusion therapy and beta-receptor blockers.

Adult↗

Differential effects of haloperidol, clozapine and olanzapine on learning and memory functions in mice.

Many schizophrenic patients exhibit impairments in neurocognitive functions. Typical antipsychotic drugs such as haloperidol, have limited or even detrimental influence on cognitive functions. In contrast, atypical antipsychotic drugs, such as clozapine and olanzapine, may improve memory function in schizophrenics. However, only a few studies have been conducted to directly compare the effects of olanzapine, clozapine and haloperidol on memory functions in animal models. Thus, their effects on this issue were investigated in the present studies by using one-way step-through passive avoidance task and Morris water maze as models of learning and memory. The results showed that olanzapine did not affect acquisition, consolidation or retrieval process in step-through test. Moreover, it improved spatial learning function in mice in Morris water maze task. Clozapine and haloperidol appeared to impair acquisition process and consolidation process, respectively, in step-through test. Both drugs impaired spatial learning function in mice in Morris water maze task. The results suggested a positive implication for the clinical medication of olanzapine in schizophrenic treatment.

Animals↗

Ca2+/Calmodulin-dependent protein kinase II phosphorylation of ryanodine receptor does affect calcium sparks in mouse ventricular myocytes.

Previous studies in transgenic mice and with isolated ryanodine receptors (RyR) have indicated that Ca2+-calmodulin-dependent protein kinase II (CaMKII) can phosphorylate RyR and activate local diastolic sarcoplasmic reticulum (SR) Ca2+ release events (Ca2+ sparks) and RyR channel opening. Here we use relatively controlled physiological conditions in saponin-permeabilized wild type (WT) and phospholamban knockout (PLB-KO) mouse ventricular myocytes to test whether exogenous preactivated CaMKII or endogenous CaMKII can enhance resting Ca2+ sparks. PLB-KO mice were used to preclude ancillary effects of CaMKII mediated by phospholamban phosphorylation. In both WT and PLB-KO myocytes, Ca2+ spark frequency was increased by both preactivated exogenous CaMKII and endogenous CaMKII. This effect was abolished by CaMKII inhibitor peptides. In contrast, protein kinase A catalytic subunit also enhanced Ca2+ spark frequency in WT, but had no effect in PLB-KO. Both endogenous and exogenous CaMKII increased SR Ca2+ content in WT (presumably via PLB phosphorylation), but not in PLB-KO. Exogenous calmodulin decreased Ca2+ spark frequency in both WT and PLB-KO (K0.5 approximately 100 nmol/L). Endogenous CaMKII (at 500 nmol/L [Ca2+]) phosphorylated RyR as completely in <4 minutes as the maximum achieved by preactivated exogenous CaMKII. After CaMKII activation Ca2+ sparks were longer in duration, and more frequent propagating SR Ca2+ release events were observed. We conclude that CaMKII-dependent phosphorylation of RyR by endogenous associated CaMKII (but not PKA-dependent phosphorylation) increases resting SR Ca2+ release or leak. Moreover, this may explain the enhanced SR diastolic Ca2+ leak and certain triggered arrhythmias seen in heart failure.

Animals↗

Effects of clozapine, olanzapine and haloperidol on nitric oxide production by lipopolysaccharide-activated N9 cells.

Schizophrenia is a devastating illness of unknown etiology and the basis for its treatment rests in the symptomatic response to antipsychotics. It was found that some of the patients with schizophrenia elicited microglia activation. The present study used lipopolysaccharide (LPS)-activated mouse microglial cell line N9 as an in vitro model to mimic microglia activation seen in the patients with schizophrenia. The effects of clozapine, olanzapine and haloperidol on the release of nitric oxide (NO) by LPS-stimulated N9 cells were investigated. The results showed that olanzapine significantly inhibited NO release by LPS-stimulated N9 cells. Clozapine and haloperidol did not show significant effects on this model. The present study suggested that the inhibiting effect of olanzapine on the NO release by LPS-stimulated microglial cells might be a new mechanism through which olanzapine exhibits its therapeutic effect in the treatment of schizophrenia.

Animals↗

Allogeneic peripheral blood hematopoietic stem cell transplantation for patients with hematologic malignancies.

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT). 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2. The acute graft-versus host disease (aGVHD) was prevented by cyclosporin A and short-term MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox (CD25 MAb) at dosage of 1 mg/kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil (MMF). Transfusion of the donor cells: The median of the transfused nucleated cells was 5.38 x 10(8)/kg and that of the CD34+ cells was 7.8 x 10(6)/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got II degrees-IV degrees aGVHI) and the incidence was 17.5%. Fourteen patients got cGVHD and the incidence was 53.8% in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality (TRM) was 17.5% and 2 patients relapsed (5.0%). It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.

Adolescent↗

Brain-derived neurotrophic factor promotes growth and migration of multiple myeloma cells.

The evolution of multiple myeloma (MM) depends on complex signals from the bone marrow microenvironment, which support proliferation and survival of malignant plasma cells. Previous study defined a brain-derived neurotrophic factor-tyrosine kinase receptor B (BDNF/TrkB) axis in myeloma and autocrine growth stimulation by BDNF in various tumor cells. We examined the biological effects of BDNF on MM cells. Using a reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry, we observed that both BDNF and its high-affinity receptor TrkB are expressed by MM cell lines (RPMI 8226, U266, and KM3) and primary MM cells. Functional studies revealed that BDNF was a potent growth factor for MM. BDNF (5-500 ng/mL) had strong proliferative effects on both MM cell lines and primary MM cells, shown by [(3)H]thymidine incorporation assay. BDNF (12.5-200 ng/mL) also induced migration of MM cells, as indicated by the Transwell migration assay. Together, our data indicate that BDNF is a potent myeloma growth and chemotactic factor and suggest that the BDNF/TrkB pathway is a potential therapeutic target in MM.

Base Sequence↗

Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity.

AIM: To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. METHODS: The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-x(L), XIAP and Bax protein were detected using Western blotting analysis. RESULTS: Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-x(L) and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC50 values of 64+/-8 micromol/L, 93+/-11 micromol/L, and 153+/-11 micromol/L, respectively. Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity. CONCLUSION: Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9.

Antineoplastic Agents, Phytogenic↗

The course of uncarinic acid E-induced apoptosis of HepG2 cells from damage to DNA and p53 activation to mitochondrial release of cytochrome c.

Uncarinic acid E, an active component isolated from Gelsemium elegans BENTH, has been reported to exhibit antitumor effects, but little is known about its molecular mechanisms of action. In this study, the growth-inhibitory activity of uncarinic acid E for HepG2 cells is in time- and dose-dependent manner. HepG2 cells treated with uncarinic acid E exhibited several typical characteristics of apoptosis through photomicroscopical observation, DNA agarose gel electrophoresis. The inhibitory effect of uncarinic acid E on HepG2 cells was partially reversed by the inhibitors of pan-caspase, caspase-3 and caspase-6. The protein expression ratio of Bcl-xL/Bax and Bcl-2/Bax was down-regulated and uncarinic acid E-induced apoptosis involves the initial phase mediated by the balance among Bcl-xL, Bcl-2 and Bax proteins, resulting in cytochrome c release from the mitochondria. Uncarinic acid E significantly increased the expression of p53 proteins indicates that p53 plays a pivotal role in the initiation phase of uncarinic acid E-induced HepG2 cell apoptosis. The phoshatidylinositol 3-kinase (PI3-K) family inhibitor wortmanin and the MEK inhibitor (PD98059) rescued the viability loss induced by uncarinic acid E through the expression of p53. Taken together, uncarinic acid E induces apoptosis in HepG2 cells via accumulation of p53, alters the Bax/Bcl-2 ratio, and activates caspases, resulting in cytochrome c release from the mitochondria.

Apoptosis↗

Effect of shikonin on human breast cancer cells proliferation and apoptosis in vitro.

Shikonin, isolated from the plant Lithospermum erythrorhizon Sieb. Et Zucc, has been reported to induce apoptosis in several tumor cells. However, such effect of shikonin on human breast cancer cells has not been reported. Thus, in the present study, whether shikonin could induce MCF-7 human breast cancer cell apoptosis was investigated. The results showed that shikonin (2.5-80 microM) induced MCF-7 cell death in a time- and dose-dependent manner, as measured by MTT assay. The IC(50) of a 24 h, 48 h and 72 h time course for MCF-7 cells was 7.4+/-0.4, 6.3+/-0.6 and 3.9+/-0.5 microM, respectively. Cellular morphology observation showed that MCF-7 cells underwent marked apoptotic morphological changes upon treatment with 10 microM shikonin compared with the untreated control. Flow cytometric analysis of shikonin-treated MCF-7 cells showed that the ratio of the apoptotic DNA fragmentation increased in a dose-dependent manner. The present study demonstrated for the first time that the cytotoxic effect of shikonin on MCF-7 cells underwent apoptosis process.

Anti-Inflammatory Agents, Non-Steroidal↗

Determination of the concentration of diallyl trisulfide in rat whole blood using gas chromatography with electron-capture detection and identification of its major metabolite with gas chromatography mass spectrometry.

A simple, rapid, and sensitive procedure has been developed using gas chromatography with electron-capture detection to measure diallyl trisulfide levels in rat blood. Blood samples were acidified, and the analyte was extracted with hexane, and then degradation was stopped with acetonitrile before gas chromatographic separation. Two calibration curves were linear over the range of 10-500 ng/ml and 0.2-20 microg/ml, with typical r values of 0.9986 and 0.9993, respectively. The structure of its major metabolite was confirmed using combined gas chromatography-mass spectrometry. The limit of detection was less than 10 ng/ml, and the assay was highly reproducible, giving peaks with excellent chromatographic properties. The method is suitable for pharmacokinetic and therapeutic purposes.

Allyl Compounds↗

Ethanol inducing ascorbic acid release in the prefrontal cortex and striatum of freely moving mice.

Previous studies have shown that acute systemic administration of ethanol induced striatal ascorbic acid (AA) release in mice and rats. Undercutting the prefrontal cortex completely eliminated ethanol-induced AA release in rat striatum. In the present study, in vivo brain dialysis coupled with high performance liquid chromatography (HPLC)-electrochemical detection was used to evaluate the effect of ethanol on the release of AA in the prefrontal cortex, compared to that in the striatum of freely moving mice. The results showed that ethanol (4.0 g/kg i.p.) similarly induced AA release in the prefrontal cortex and striatum of freely moving mice.

Animals↗