DHA induced cytotoxicity in NSCLC cells via inhibiting PI3K pathway activation and GLUT2 expression

AIM: To investigate the molecular mechanisms of cytotoxicity induced by dihydroartemisinin (DHA) in non-small cell lung cancer (NSCLC) cells. METHODS: NSCLC cell lines A549 and NCI-H1650 were treated with various concentrations of DHA for indicated time. Subsequently, the effects of DHA on the cell activity, colony formation ability and apoptosis were determined by MTT assay, colony formation assay, Annexin V-FITC/PI staining and flow cytometry, respectively. At the same time, the effects of DHA on glucose, ATP and lactate levels were assessed, and the PI3K pathway activation and glucose transporter 2(GLUT2) expression were detected by Western blot in the A549 cells and NCI-H1650 cells. Overexpression of GLUT2 and Rheb was established in A549 and NCI-H1650 cells by transfection with GST-GLUT2 and GST-Rheb plasmids, respectively, and the effects of DHA on cell activity, apoptosis, glucose level, ATP content and PI3K pathway activation were analyzed in A549 cells and NCI-H1650 cells. The effect of glucose deprivation on the cytotoxicity triggered by DHA in NSCLC cells was also determined. RESULTS: Compared with control group, DHA significantly inhibited cell activity and colony formation ability, and induced remarkable cell apoptosis in the A549 cells and NCI-H1650 cells. At the same time, DHA reduced ATP and lactate contents, and hindered glucose uptake in a time-and dose-dependent manner in A549 cells and NCI-H1650 cells. The activity of PI3K pathway and GLUT2 expression were downregulated, while upregulated GLUT2 expression and activated PI3K pathway reduced the cytotoxicity induced by DHA in NSCLC cells. Glucose deprivation increased DHA-mediated cytotoxicity in NSCLC cells. On the contrary, high levels of glucose inhibited DHA-mediated cytotoxicity in NSCLC cells. CONCLUSION: DHA restrains cell activity and colony formation, and induces apoptosis. DHA induces cytotoxicity via inhibiting PI3K pathway activation and GLUT2 expression, leading to inhibit glycolytic metabolism in NSCLC cells.     

Dimensional stability of wood acetylated with acetic anhydride solution of glucose pentaacetate

Five wood species were acetylated with acetic anhydride (AA) solution of glucose pentaacetate (GPA) at 120°C for 8h, and the effect of GPA on the dimensional stability of the acetylated wood was investigated. Some GPA was introduced into the wood cell wall during acetylation. The GPA remaining in the cell lumen penetrated the cell wall effectively after heating to more than 140°C for 10min. The bulking effects of GPA resulted in a 10%–30% increase in the anti-swelling efficiency of the acetylated wood with 20% GPA/AA solution in place of AA. Hydrophobic GPA did not deliquesce under highly humid conditions and it remained in the cell wall after boiling in water.Part of this paper was presented at the 51st Annual Meeting of the Japan Wood Research Society, Tokyo, April 1988     

Glycemic Status and Predictors of Relapse for Diabetic Cats in Remission

Background

It is unknown if diabetic cats in remission have persistent abnormalities of glucose metabolism and should be considered prediabetic, or have normal glucose tolerance.

Objective

To characterize glycemic status of diabetic cats in remission and to determine predictors of relapse.

Animals

A total of 21 cats in diabetic remission and 28 healthy control cats.

Methods

At a median of 107 days after remission, screening blood glucose concentration was measured on entry to the clinic. After a 24‐hour fast in hospital, fasting blood glucose, fructosamine and feline pancreatic lipase concentrations were measured, and 3 hours later, a simplified IV glucose tolerance test (1 g glucose/kg) performed. Twenty cats were monitored for relapse for at least 9 months.

Results

Of the 21 cats in remission, 19% (4/21) had impaired fasting glucose concentration and 76% (16/21) had impaired glucose tolerance. Of cats followed up for 9 months after testing, 30% (6/20) had relapsed and required insulin treatment. Fasting blood glucose concentration ≥7.5 mmol/L (≥135 mg/dL) (odds ratio [OR] = 12.8) and severely impaired glucose tolerance (≥5 hours to return to <6.5 mmol/L or <117 mg/dL; OR = 15.2) were significantly associated with relapse. Blood glucose concentration >14 mmol/L; 252 mg/dL at 3 hours was significantly associated with relapse (OR = 10.1).

Conclusion and Clinical Importance

Most cats in diabetic remission have impaired glucose tolerance and a minority have impaired fasting glucose concentration and should be considered prediabetic. More severe glucose intolerance and impaired fasting glucose concentration are predictors of relapse. Ongoing glucose monitoring of diabetic cats in remission is recommended.     

Field-scale and laboratory study of factors affecting N2O emissions from a rye stubble field on sandy loam soil

Emission of N₂O from cultivated and fertilised soils may contribute significantly to the total global N₂O emission. This study included laboratory and field investigations of the N₂O production from a dry stubble field as influenced by addition of water, nitrogen and glucose. N₂O fluxes were measured using a closed-chamber technique, and the O₂ content in the soil was measured using soil probes. Results from a laboratory soil core technique were correlated to the relative N₂O emission observed in the field. When the soil water content in the field increased from 14% to 60% water-filled pore space, the N₂O emission increased from non-significant to a constant emission of 30 μg N m^–2 h^–1. At this soil water content the production of N₂O was limited by the availability of nitrogen and carbon. Application of nitrogen at soil temperatures of 13 and 21°C in a pre-wetted soil increased the N₂O emission 3.1- and 3.7-fold, respectively, whereas nitrogen plus carbon application increased the N₂O emission 13.3- and 7.3-fold, respectively. In both treatments the N₂O emission rates were affected by fluctuations in soil temperature and O₂ content. The results indicate that even in a soil producing very little N₂O under dry conditions, the soil microbial community maintains a potential to produce N₂O when favourable conditions occur in terms of availability of water, nitrogen and carbon. Received: 21 October 1996     

Influence of sulphur supply on glucose and ATP concentrations of inoculated broad beans (Vicia faba minor L.)

In the present study, the influence of S supply on S concentrations, N₂ fixation, available amounts of glucose and adenylates of Vicia faba minor L. were weekly investigated, starting 6 weeks after sowing. Glucose was determined photometrically in shoots, roots and nodules and in ATP, ADP and AMP by bioluminescence in roots, mitochondria and bacteroids. Sulphur deficiency resulted in significantly lower S concentrations of shoots, roots and nodules, in a reduced N₂ fixation as well as in significantly lower amounts of glucose in shoots and nodules. In roots and bacteroids, S deficiency resulted in lower ATP concentrations, while the influence of S supply on ADP and AMP was less pronounced. With optimum S supply, the available amounts of glucose and ATP were strongly influenced by flower formation and seed development. Dedicated to Prof. Dr. Dr. h.c. W. Werner on the occasion of his 75th birthday.     

Microbial populations immobilizing NH4-N and NO3-N differ in their sensitivity to sodium chloride salinity in soil

An incubation experiment was conducted to study the response to sodium chloride (NaCl) salinity of microbial population immobilizing NH₄⁺- and NO₃⁻-N using glucose as an easily oxidizable C source. Immobilization of NH₄⁺-N was faster than that of NO₃⁻-N and was complete within 12 h of -incubation. Presence of NaCl retarded the process of N immobilization; that of NO₃⁻-N being more affected. Remineralization of immobilized N started within 48 h in case of both NH₄⁺- and NO₃⁻-N and was faster for the latter. Both remineralization and nitrification were significantly delayed in the presence of NaCl; inhibition being more at 4000 mg NaCl kg⁻¹ soil. The inhibitory effect of NaCl on remineralization of N was relatively more for NH₄⁺-treated soil. The results of the study suggested a higher sensitivity to NaCl of microorganisms assimilating NO₃⁻. However, remineralization of N from NO₃⁻-assimilating microbial population was less affected by NaCl salinity compared to NH₄⁺-assimilating population.     

Interactions in microbial use of soluble plant components in soil

Glucose, glutamic acid, alanine, valine, and albumin were used as model substances to represent readily available soluble plant components. Their mineralisation in soil was monitored by making hourly measurements of total CO₂ evolution and periodic measurements of ¹⁴CO₂ during a 5-day incubation period. When glucose and the amino acids were combined in dual substrates the two components were mineralised simultaneously. In each combination the component with the shortest lag phase or highest specific growth rate () was mineralised preferentially. Glucose accelerated the mineralisation of the amino acids that had longer lag phases than glucose (i.e., alamine and valine). During the first 8 h, glucose mineralisation was reduced in the dual substrates compared with its mineralisation as a single substrate. The smaller the difference between the lag phase of glucose and the amino acid, the greater was the reduction in the glucose mineralisation rate. During the exponential phase, the effects on glucose mineralisation were dependent on the nature and concentration of the amino acid. The interactions observed between glucose and amino acid decomposition indicated that these substances were mineralised, at least partly, by the same microorganisms. In contrast, glucose and the soluble protein albumin were decomposed independently of each other.     

不同产地南果梨果实品质比较

用5个主要南果梨产区的南果梨进行试验,重点测果实糖分组成.结果表明:南果梨果实的糖分组成以果糖为主,占总糖的50%以上;不同产地南果梨果实总糖、可滴定酸、Vc及糖组分含量差异较大,阜新地区南果梨总糖及果糖含量最高,分别为190.27、99.65mg/mL,海城地区南果梨总糖及果糖含量最低,分别为97.74、60.24mg/mL,虽然鞍山地区是南果梨的优势产区,但鞍山地区的南果梨总糖及果糖含量却不是最高的,这个结果与生产中反映的鞍山南果梨果实品质近年来有所下降相符合.     

鸡和兔血糖调节生理差异比较

旨在了解大口黑鲈(Micropterus salmoides )的种质特性，为其种质鉴定提供理论依据。采用传统形态学方法观测样品形态特征，借助肾细胞滴片空气干燥法制备染色体标本并进行核型分析，通过聚丙烯酰胺凝胶电泳法研究大口黑鲈眼晶状体乳酸脱氢酶(LDH)。结果表明：大口黑鲈体呈纺锤形，口裂大，斜裂；背部黑绿色，体侧青绿；吻端至尾鳍基部有排列成带状的黑斑。鳃盖上有3条呈放射状的黑斑；背鳍鳍式 D.VIII~XI-11~14；臀鳍鳍式A.III-9~12；左侧第一鳃弓外侧鳃耙数为6~7，鳔1室，脊椎骨总数30~32。染色体数目2n=46，核型公式为2m+2st+42t，臂数NF=48，未发现带有随体、次缢痕的染色体和异型性染色体，大口黑鲈进化上符合高位类群核型特征；眼晶状体中的LDH酶带5条，观察到LDHA、LDHB和LDHC 3个基因位点。综上所述，在对大口黑鲈进行种质鉴定时，建议采用多种种质鉴定技术手段系统化地考察和评价其种质状况。     

The effect of glucose,lactate and pyruvate on the dynamic adaptation of cardiac mitochondrial oxygen consumption

AIM: To understand the effect of exogenous carbon substrate on the dynamic regulation of cardiac oxidative phosphorylation. METHODS: Method of mean response time measurement of the myocardial mitochondrial O₂ consumption (t_mito) was developed by van Beek. Glucose, lactate, or pyruvate as carbon substrate respectively for myocardial energy supply was perfused in isolated rabbit hearts with Tyrode solution at 37℃. RESULTS: When heart rate was stepped up from 120 to 140 and 220 (beat·min^-1) respectively the t_mito. We have measured was: (6.3±1.0)s and (7.4±0.9) s for glucose; (5.4±1.2) s and (7.0±0.9) s for lactate; (4.0±0.7)s and (6.5±0.6) s for pyruvate (two way ANOVA, P＜0.05, compared with lactate and glucose). CONCLUSION: The transport of reducing equivalent into the mitochondrial matrix might be a limitation factor of dynamic adaptation of cardiac mitochondrial oxidative phosphorylation during fast changes in ATP utilization.