叶酸靶向顺铂聚合物胶束对肺癌细胞SPC-A-1的毒性和辐射增敏作用

以顺铂为对照,使用具有叶酸靶向基团的聚乙二醇枝接聚天冬氨酸聚合物胶束顺铂载体FA-PEG-g-PAsp-CDDP和无叶酸靶向基团的mPEG-g-PAsp-CDDP,通过比较这3种药物对肺癌细胞SPC-A-1体外的细胞毒性以及单独用药和同步放疗对裸鼠移植瘤的生长抑制作用,验证FA-PEG-g-PAsp-CDDP的肿瘤抑制和辐射增敏效果。在体外CCK-8实验中比较顺铂、FA-PEG-g-PAsp-CDDP和mPEG-g-PAsp-CDDP对过表达叶酸受体的肺癌细胞株SPC-A-1的细胞毒性作用,在体内试验中比较顺铂、FA-PEG-g-PAsp-CDDP和mPEG-g-PAsp-CDDP单独用药和同步放疗对裸鼠移植瘤的生长抑制及放射增敏作用,并观察对裸鼠体重的影响。结果显示:含过量叶酸的普通培养基中FA-PEG-g-PAsp-CDDP和mPEG-g-PAsp-CDDP的细胞毒性作用相似,而在不含叶酸培养基中FA-PEG-g-PAsp-CDDP的细胞毒性高于mPEG-g-PAsp-CDDP,IC50约为后者的1/(3p<0.05)。单独用药实验中FA-PEG-g-PAsp-CDDP和CDDP体内抑瘤效果无统计学差异(p>0.05),但均高于mPEG-g-PAsp-CDDP组和空白对照组(p<0.05);同步放化疗实验中FA-PEG-g-PAsp-CDDP的抑瘤效果优于CDDP(p<0.05),并且两者均优于mPEG-g-PAsp-CDDP组和单独放疗组(p<0.05)。裸鼠CDDP给药后体重下降明显,最多下降约10%,而FA-PEG-g-PAsp-CDDP和mPEG-g-PAsp-CDDP组裸鼠体重无明显下降。FA-PEG-g-PAsp-CDDP能有效抑制肿瘤生长,叶酸靶向基团增强了其对过表达叶酸受体肿瘤的抑制作用,并且较CDDP有更强的放射增敏效果和更低的毒副作用。     

Folate‐producing lactic acid bacteria from cow’s milk with probiotic characteristics

The probiotic potential of newly isolated lactic acid bacteria from cow’s milk was analysed and the efficacy of the selected isolates to produce folic acid was determined by microbiological assay. Two isolates, CM 22 and CM 28 were selected for folate production in skim milk medium and the net folate yield was 12.5 ng and 14.2 ng/mL respectively. The two isolates (CM 22 and CM 28) showed more than 98% similarity to Lactococcus subsp. cremoris and Lactococcus lactis subsp. lactis respectively by 16S rRNA sequencing.     

Preparation of ZnFe2O4–chitosan-doxorubicin hydrochloride nanoparticles and investigation of their hyperthermic heat-generating characteristics

In this study, the structural morphology and magnetic effects of magnetic ZnFe₂O₄ nanoparticles loaded with the cancer-fighting drug doxorubicin hydrochloride (DOX-HCl) were investigated. These nanoparticles have been found to have potential biomedical applications in targeted drug-delivery systems. The zinc ferrite nanoparticles were prepared by a chemical coprecipitation method and coated with chitosan. The nanoparticles were loaded with DOX-HCl and their surfaces improved by folic acid, which can be activated to target specific cancer cells. The specific absorption rate (SAR) values of the ZnFe₂O₄–chitosan–DOX-HCl nanoparticles were investigated at a frequency of 200 kHz and 1.5 kA/m amplitude in order to obtain Brownian relaxation time parameters. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), and ultraviolet–visible spectrophotometry (UV–vis) were used to characterize the bulk properties of these nanoparticles. In addition, the impact of the nanoparticles under an alternating current (AC) magnetic field and their heat-generation ability were investigated using an experimental setup. The average nanoparticle size was found to be 8.5 nm. Magnetic hysteresis loops confirmed the superparamagnetism of the nanoparticles. The saturation magnetization was 6 emu/g. UV–vis was used to measure the amount of drug loaded onto the nanoparticles. The amount of drug absorption was significantly higher after 12 h, totaling 75%. The specific absorption rate parameter was 80.66 W/g, and the Brownian relaxation time was 188×10⁻⁹ s.     

Determination of folate in some cereals and commercial cereal-grain products consumed in Poland using trienzyme extraction and high-performance liquid chromatography methods

A trienzyme treatment (rat plasma conjugase, -amylase, protease) followed by affinity chromatography (with folate-binding protein from bovine milk) and reversed-phase high-performance liquid chromatography with UV and fluorescence detections was performed for quantification of different folate derivatives in some commercial cereal-grain products and cereals cultivated in Poland. The method described allowed good separation of the main folate vitamins. Of the commercial cereal-grain products analyzed, buckwheat groats (30 g/100 g) had the highest content of total folate, followed by rye flour (29 g/100 g), barley groats (21 g/100 g) and wheat flours (19–20 g/100 g). Two of the ready-to eat breakfast products were found to be fortified with folic acid with the level slightly exceeding the label declaration. The total folate content of whole-grain wheat flours was more than half as much as in white flours (33–40 g/100 g), and the highest folate content was found in rye whole grains (123–135 g/100 g). 5-Formyltetrahydrofolate was the predominating folate form in the cereal products analyzed, above all in rye flour.     

High-pressure treatments induce folate polyglutamate profile changes in intact broccoli (Brassica oleraceae L. cv. Italica) tissue

In plant matrices, folates exist largely as folylpoly-γ-glutamates requiring deglutamylation to monoglutamates prior to absorption, which might impair dietary folate bioavailability. This study investigated folylpoly-γ-glutamate stability and conversions in broccoli tissue during thermal (25–90 °C, 30 min) and high-pressure treatments (0.1–600 MPa, 25–45 °C, 30 min) after vacuum packaging. Folates were analyzed based on poly-γ-glutamate side chain length by RP-HPLC. During thermal treatments, folates were stable up to 90 °C, whereas differences in folylpoly-γ-glutamate profiles towards higher conjugated folylpoly-γ-glutamates were observed at elevated temperatures (70–90 °C). High-pressure treatments resulted in significant folate losses (48–78%). Depending on the pressure–temperature combinations studied, folylpoly-γ-glutamates were converted to folylmono- and folyldi-γ-glutamates, which was shown to occur mainly during the initial stages of the high-pressure treatments, i.e. during pressure build-up and subsequent equilibration. Targeted application of high-pressure treatments can hence be applied to obtain broccoli with higher monoglutamate folate content. Implications towards folate bioavailability in relation to the observed folate degradation, however, requires further investigation.     

Folate content in frozen vegetarian ready meals and folate retention after different reheating methods

Folate content and retention were evaluated in 10 different precooked vegetarian ready meals before and after reheating. Folate was quantified using a validated high-performance liquid chromatography method. The only form of folate found was 5-methyltetrahydrofolate. Folate content in thawed ready meals varied from 23 to 81 μg/portion (400 g) on fresh weight basis. Products served with couscous and potatoes contained more folate than products served with rice. Folate retention during reheating was investigated in the microwave oven (900 W/5.5 min), in a saucepan on stove until the food reached 85 °C, and in oven (225 °C/40 min). The true vitamin retention varied for the three investigated portions as follows: on stove (63-93%), microwaving (55-89%) and in oven (50-92%). Our results indicate that folate content in the ready meals prior to reheating, contributed to 6-27% of the recommended intake (300 or 400 μg folate per day). After reheating folate content was significantly (P<0.05) reduced in some meals but were kept constant in others and folate content was reduced to 3-25% of the recommended value. No clear pattern in folate retention between different heating methods was seen. However, the meals with ingredients suggesting high concentrations of antioxidants were less prone to loose folate when heated since the antioxidants probably protected the folates.     

Increasing the folate content in Egyptian baladi bread using germinated wheat flour

The main objective of this study was to increase the folate content in Egyptian baladi bread using germinated wheat flour (GWF). The effect of germination temperature and drying conditions on the folate content of wheat grains was studied. Wheat flour was substituted with unsieved and sieved GWF at different levels and the effects on folate content and the rheological properties of dough were determined. Germination of wheat grains resulted in a 3- to 4-fold higher folate content depending on the germination temperature. Maximum folate content (61 μg/100 g dry matter (DM)) occurred at 30 °C. Drying did not affect folate content in germinated grains. After replacement with GWF, folate content in both flour and bread increased 1.5- to 4-fold depending on the level of replacement. Rheological properties of dough were adversely affected by increasing replacement level (as determined by farinograph). While the folate content in bread was as high as 66 μg/100 g DM at complete replacement of flour with sieved GWF, the bread was dark and layers were not separated. After replacement of half of the flour with sieved GWF (50 g/100 g), the baladi bread was acceptable with respect to colour and layer separation. The folate content in this bread was 50 μg/100 g DM, compared with 30 μg/100 g DM in bread without GWF (0 g/100 g).     

Maternal folate supply and sex influence gene‐specific DNA methylation in the fetal gut

Scope : Epidemiological evidence supports the developmental origins of health and disease hypothesis that developmental under/over‐nutrition increases adulthood disease risk. Epigenetic markings are one potential mechanism mediating these effects. Altered folate supply may influence methyl group availability for DNA methylation. We reported low folate supply in utero was associated with reduced global DNA methylation in the murine small intestine of adult offspring. We hypothesised that aberrant methylation would be observed during early development. Methods and results : Female C57BL/6J mice were fed diets containing 2 mg folic acid/kg or 0.4 mg folic acid/kg 4 wk before mating and during pregnancy. At 17.5 day gestation, gene methylation in fetal gut was analysed by Pyrosequencing^®. Low folate reduced overall methylation of Slc394a by 3.4% (p=0.038) but did not affect Esr1 or Igf2 differentially methylated region (DMR) 1. There were sex‐specific differences in Slc394a and Esr1 methylation (2.4% higher in females (p=0.002); 4% higher in males (p=0.0014), respectively). Conclusion : This is the first study reporting causal effects of maternal folate depletion on gene‐specific methylation in fetal gut. These observations support reports that altered methyl donor intake during development affects DNA methylation in the offspring. The consequences of epigenetic changes for health throughout the life course remain to be investigated.     

Folate and colorectal cancer: an evidence-based critical review

Currently available evidence from epidemiologic, animal, and intervention studies does not unequivocally support the role of folate, a water-soluble B vitamin and important cofactor in one-carbon transfer, in the development and progression of colorectal cancer (CRC). However, when the portfolio of evidence from these studies is analyzed critically, the overall conclusion supports the inverse association between folate status and CRC risk. It is becoming increasingly evident that folate possesses dual modulatory effects on colorectal carcinogenesis depending on the timing and dose of folate intervention. Folate deficiency has an inhibitory effect whereas folate supplementation has a promoting effect on the progression of established colorectal neoplasms. In contrast, folate deficiency in normal colorectal mucosa appears to predispose it to neoplastic transformation, and modest levels of folic acid supplementation suppress, whereas supraphysiologic supplemental doses enhance, the development of cancer in normal colorectal mucosa. Several potential mechanisms relating to the disruption of one-carbon transfer reactions exist to support the dual modulatory role of folate in colorectal carcinogenesis. Based on the lack of compelling supportive evidence and on the potential tumor-promoting effect, routine folic acid supplementation should not be recommended as a chemopreventive measure against CRC at present.