Preparation of S-iron-enriched yeast using siderophores and its effect on iron deficiency anemia in rats.

Efforts to obtain organic trace elements have been made, including yeast enrichment and transformation, but the application of yeast for this purpose is restricted by poor tolerance and low enrichment. Siderophores play an important role in iron transport. Thus, the role of siderophores in iron transport under high-iron conditions and the application of siderophores in the enrichment of elements was explored. The results showed that some siderophores from iron-tolerant strains promoted yeast growth and increased its intracellular iron content. Among them, siderophore TZT-12 (from LK1110) was the best for promoting yeast growth and iron conversion. The siderophore-iron-enriched yeast (S-iron-enriched yeast) effectively restored the iron concentration, and an iron concentration of 59.40 mg/g was obtained by adding TZT-12. Iron deficiency anemia in rats was significantly mitigated with S-iron-enriched yeast compared with ferrous sulfate. These findings provide a new perspective on the preparation of organic trace elements for supplementation or food fortification.

Expression and Purification of Delta Sleep-Inducing Peptide Fused with Protein Transduction Domain and Human Serum Albumin in Pichia pastoris.

BACKGROUND: Sleep is a natural part of every individual's life. Delta sleep-inducing peptide (DSIP) is a nonapeptide that could promote sleep through the induction of slow wave sleep. However, little is known about the pharmacological effect of DSIP on insomnia. OBJECTIVES: The main objective of this study was to analyze the pharmacological effect of DSIP on insomnia. METHODS: We designed a fusion protein containing N-terminal TAT-based transduction domain followed by human serum albumin and DSIP and designated this protein as PHD fusion protein. The PHD fusion protein were expressed in Pichia pastoris and purified. Mice were administered single subcutaneous injections three concentrations of PHD fusion protein (0.5, 1, 2 mg/kg), and the pharmacological activity of PHD fusion protein was studied using classic pentobarbitalinduced sleep test. RESULTS: We expressed the PHD fusion protein in P. pastoris; furthermore, the PHD fused protein was purified to near homogeneity by DEAE Sepharose FF, Phenyl Sepharose HP and Blue Sepharose 6 FF. Our result showed that the increase of pentobarbital-induced hypnotic effect characterized by reducing sleep latency and prolonged sleep duration was observed for increasing concentrations of PHD fusion protein (P<0.05); moreover, different dose of PHD fusion protein could induce the mice to re-sleep in a dose-dependent manner, whereas higher doses of PHD fusion protein (1.0, 2.0 mg/kg) significantly increased the rate of sleep re-onset compared with the vehicle group of mice (P<0.05). CONCLUSION: PHD fusion protein increased the hypnotic effects of pentobarbital by reducing sleep latency and prolonged sleep duration. The present study suggested PHD fusion protein could be a new drug candidate for insomnia.

Effects of Fe-YM1504 on iron deficiency anemia in rats.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. It is possible that some strains present in the natural environment possess a higher tolerance to inorganic iron and a higher ability to convert and accumulate iron compared with Saccharomyces cerevisiae wild-type strain. In the present study, the strain no. YM1504, able to grow in an iron-rich environment, was used as a potential organic iron supplement, and its efficacy in alleviating IDA in rats was investigated. Sixty female weanling Sprague-Dawley rats were randomly divided into a normal control group fed with a standard diet and a model group fed with an iron-deficient diet to create the IDA model. After the model was established, IDA rats were further randomly divided into five subgroups: the IDA group, the ferrous sulfate (FeSO4) group and Fe-YM1504 low-, medium- or high-dose groups receiving different concentrations of Fe-YM1504 supplements. Our results showed that Fe-YM1504 has an effective restorative function by returning the hemoglobin (Hb), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), serum iron (SI), total iron binding capacity (TIBC), serum ferritin (SF), etc. in IDA animals to the normal level. Moreover, malondialdehyde and the enzyme activities of superoxide dismutase and glutathione peroxidase in both plasma and liver homogenate were improved. Finally, compared with the FeSO4 group, the Fe-YM1504 middle-dose was more effective in alleviating IDA and fewer side effects were observed. The present study indicated that iron-enriched strain no. YM1504 might play a significant role in ameliorating IDA rats and might be exploited as a new iron supplement.

Higher Bioavailability of Organic Bound Zinc from High Zinc-Enriched Fungi.

The organic forms of trace elements are considered more bioavailable than the inorganic forms. Although yeast can enrich metal elements and convert inorganic zinc to organic species, its tolerability and transforming capacity are limited. It would therefore be very interesting to look for higher conversion and accumulation in zinc fungi to obtain organic bound zinc from the natural environment. In this paper, potato dextrose agar (PDA) medium containing 800 µg/mL zinc was used for initial screening, with twenty-two fungal strains that tolerated high zinc isolated from the natural environment, and one strain (No.LZ-1108) growing well at a zinc (II) concentration of 10,000 µg/mL. According to morphological analysis, 18S rDNA sequence analysis, and biophysical and biochemical characteristics, No.LZ-1108 was tentatively identified as Fusarium oxysporum. Using atomic absorption spectrometry, the zinc content in the No.LZ-1108 cells was found to be 6.7 mg/g dry cell. After oral administration to rats at a dose of 10 mg Zn (II)/kg body weight, the area under the plasma concentration-time curve (AUC) and the maximum zinc blood concentration (Cmax) of No.LZ-1108 and zinc gluconate were 8.10 g/L.min and 4.28 g/L.min, 23.72 µg/mL and 6.23 µg/mL, respectively. The AUC of No.LZ-1108 was significantly higher than those of zinc gluconate (P<0.05), and the mean relative bioavailability of AUC(test)/AUC(zinc gluconate) was 190 %, which showed that the bound zinc in No.LZ-1108 was more bioavailable than zinc gluconate. The present study reports an interesting alternative to developing zinc-based supplements from a natural source of zinc.