Development of a simple and sensitive HPLC-DAD method for quantification of vitamin B12 fortified in infant food.

To prevent infants from vitamin B12 deficiency, infant food is designed based on cow's milk or cereal with the fortification of vitamin B12. A method for quantitative determination of vitamin B12 in infant food was developed with hydrophilic high performance liquid chromatography (HPLC) coupled with a diode array detector (DAD). The sensitivity of the detector was enhanced by implementing a 60 mm high-sensitivity LightPipe flow cell, and the limit of detection (LOD) and limit of quantification (LOQ) were improved as low as 0.006 µg 100 g-1 and 0.02 µg 100 g-1 respectively. The effect of sample extraction and enrichment, chromatography separation parameters on the analyte, were studied in detail and optimized. Under these conditions, the method performed a good linear analytical range of 0.3-50 µg L-1, and a good repeatability with % RSD below 2.8% and recovery of 90.2-96.5% (n = 6). To the best of our knowledge, for the first time, 60 mm high-sensitivity LightPipe flow cell was included in the HPLC-DAD method for determination of the trace amount of vitamin B12 in infant food. The proposed method was further validated by analysis of FAPAS QC samples (T21120 and T21118), and it was specific and precise for the intended use.

Interaction between glutathione S-transferase M1-null/present polymorphism and adjuvant chemotherapy influences the survival of breast cancer.

Glutathione S-transferase M (GSTM) family is concerned with oxidative stress, which is associated with breast carcinogenesis and chemotherapy response. The null polymorphism of GSTM1 gene results in a thorough absence of the enzyme function. Our study was to evaluate the association between GSTM1 null/present polymorphism and chemotherapy treatment outcome in breast cancer patients. A total of unrelated 714 patients with a histologically confirmed breast cancer were randomly selected from two independent cancer centers. Polymerase chain reaction was performed to analyze null/present genotypes of GSTM1 in our study. Our study found that the present genotype of GSTM1 was associated with a better relapse-free survival (RFS) (P = .03) with adjusted hazard ratio (HR) [95% confidence interval (CI)] of 0.63 (95% CI: 0.42-0.93). The present genotype of GSTM1 was significantly correlated with a better RFS compared with the null genotype in the nonchemotherapy group (HR = 0.17, 95% CI: 0.06-0.50; P = 0.001), but no effect was observed in the chemotherapy group (HR = 0.81, 95% CI: 0.52-1.26; P = 0.35). Moreover, the interaction between the GSTM1-null/present genotype and adjuvant chemotherapy was significant (P = 0.04) in further analysis. Our study suggests that the GSTM1 polymorphism plays a complex role in influencing the chemotherapy response and breast cancer survival. It is suggested that the GSTM1-present genotype might prevent progression in breast cancer patients. In the meanwhile, it could damage the benefit of adjuvant chemotherapy as well in certain ways.

Mfsd2a-based pharmacological strategies for drug delivery across the blood-brain barrier.

The blood-brain barrier (BBB) keeps the central nervous system (CNS) safe from various brain diseases, while the BBB makes it difficult for effective drugs to enter the CNS. Mfsd2a is specifically expressed on the cell membrane of brain-microvascular endothelial cell (BMEC) and is implicated in the delivery of some substances across the BBB. Mfsd2a is the first inhibitor of the transcytosis and the first transporter for lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA) in BMECs. The crucial dual function of Mfsd2a puts forward two kinds of Mfsd2a-based strategies for carrying drugs from blood to the CNS. First, the reversible inhibition of Mfsd2a may temporarily induce a general disinhibition of the transcytosis in BMECs to transport macromolecular drugs across the BBB (Strategy One). Second, Mfsd2a could be used for the transport of some small-molecule drugs chemically coupled to LPC across the BBB (Strategy Two), which is quite similar to the carrier-mediated transport (CMT) via the glucose transporter (GluT1) and the L-type amino acid transporter 1 (LAT1). We here analyze and discuss the clinical significance of the two Mfsd2a-based strategies, including therapeutic potential, available pharmaceuticals, side effects, administration procedures, and disease types. In summary, the regulatory role of Mfsd2a deepens our knowledge of the function of the BBB, potentially contributing to the effective drug delivery in the treatments for neurodegenerative diseases, brain tumors, and life-threatening infections in the CNS.