Enhanced antitumor activity of bovine lactoferrin through immobilization onto functionalized nano graphene oxide: an in vitro/in vivo study.

This study aims to improve the anticancer activity of bovine lactoferrin through enhancing its stability by immobilization onto graphene oxide. Bovine lactoferrin was conjugated onto graphene oxide and the conjugation process was confirmed by FT-IR, SDS-PAGE, and UV spectrophotometry. Physical characterization was performed by DLS analysis and atomic force microscopy. The cytotoxicity and cellular uptake of the final construct (CGO-PEG-bLF) was inspected on lung cancer TC-1 cells by MTT assay and flow cytometry/confocal microscopy. The anticancer mechanism of the CGO-PEG-bLF was studied by cell cycle analysis, apoptosis assay, and western blot technique. Finally, the anticancer activity of CGO-PEG-bLF was assessed in an animal model of lung cancer. Size and zeta potential of CGO-PEG-bLF was obtained in the optimum range. Compared with free bLF, more cytotoxic activity, cellular uptake and more survival time was obtained for CGO-PEG-bLF. CGO-PEG-bLF significantly inhibited tumor growth in the animal model. Cell cycle arrest and apoptosis were more induced by CGO-PEG-bLF. Moreover, exposure to CGO-PEG-bLF decreased the phospho-AKT and pro-Caspase 3 levels and increased the amount of cleaved caspase 3 in the treated cells. This study revealed the potential of CGO-PEG as a promising nanocarrier for enhancing the therapeutic efficacy of anticancer agents.

Possible resting metabolic rate modification by the circulating RBP4 in obese subjects.

AIM: Adipose tissue derived retinol-binding protein 4 (RBP-4), known as one of the most important adipokins, has a link with insulin resistance and metabolic syndrome in obesity. The purpose of this study was to investigate the possible correlation between fasting serum RBP4 and resting metabolic rate (RMR) as a predictor of weight gain, body composition and insulin resistance in obese and non-obese subjects. MATERIALS AND METHODS: In this case-control study, 73 obese and 90 non-obese participants were assessed following an overnight fasting for RMR by means of indirect calorimetry. Body composition was measured using body composition analyzer. Serum RBP4 levels were quantified by ELISA method. RESULTS: Circulating RBP4 level correlated positively with log insulin (r=0.278, p=0.04) in obese subjects. There were no significant correlation between RBP4 and body composition in obese subjects except fat free mass (r=0.42, p=0.001). We found reduced RMR/kg in higher RBP4 concentration, moreover, a negative correlation was found between RBP4 and RMR/kg (r=-0.35, p=0.01) in obese group. Based on ROC analysis and RMR/kg cut-off value (=20 kcal/24 h/kg) for predicting the risk of obesity, 83.3% of participants with RMR/kg<20 kcal/24 h/kg had high RBP4 concentration, however in subjects with RMR/kg≥20 kcal/24 h/kg this percentage was 16.7 (p=0.01). CONCLUSION: Our findings demonstrated that RBP4 concentration had relation with RMR which was different among obese and non-obese groups. These results may suggest the possible role of RBP4 in alteration of metabolic rate through insulin or other metabolic effects.

Inflammatory profile, age of onset, and the MTHFR polymorphism in patients with multiple sclerosis.

Both genetic and inflammatory factors are suspected in the etiology of multiple sclerosis (MS). Of genetic factors, the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with increased levels of plasma homocysteine, a neuronal excitotoxic amino acid. Sclerotic patients also have elevated levels of plasma and CSF homocysteine. In this study, the association between C677T polymorphism and MS was tested by recruiting 230 healthy and 194 multiple sclerotic age- and gender-matched patients. The MTHFR C677T polymorphism and the serum levels of inflammatory mediators IL-1ß, TNFα, and CRP were measured. TNFα, CRP, and IL-1ß levels were significantly higher in sclerotic patients. T allele was 1.7 times more present in this group. In patient's group, the levels of all inflammatory mediators were higher in T/T compared to two other genotypes. Evaluation of the age of onset of disease revealed that subjects with T allele developed the MS disease, almost 4 years sooner than other genotype. We concluded that having T allele of C677T in MS might be accompanied with higher levels of serum inflammatory mediators and a vulnerability to earlier age of onset of disease. Further studies are needed to elucidate the underlying mechanisms.

The influence of folic acid supplementation on maternal and fetal bone turnover.

The aim of our study was to investigate the relationship between maternal and fetal bone turnover markers and folic acid supplementation during pregnancy. In an observational study performed in Tehran University of Medical Sciences related hospitals, 113 healthy pregnant women with gestational age between 8 and 12 weeks and aged between 15 and 42 years were recruited and followed until delivery time. The participants were divided into two groups; women who took 1 mg of folic acid daily supplement from the beginning of the pregnancy until the end of the second trimester entered into group I and women who choose to continue their daily intake of folic acid until the delivery time entered into group II. The two groups were matched based on the maternal anthropometric data, energy, calcium and vitamin D intake. Following the delivery, venous blood samples were collected from mothers and umbilical cords of the neonates. Maternal and fetal serum concentrations of 25-hydroxy vitamin D3, PTH, osteocalcin (OC), crosslaps and maternal serum level of homocysteine, folate, soluble receptor activator of NF-kappaB ligand (sRANKL), osteoprotegerin (OPG), calcium, and phosphate were measured. Measured birth outcome parameters included weight, length, head circumference, appearance, and respiration. With regard to maternal assessment, the serum levels of OC and OPG and folate were significantly higher in group II compared to group I, while the serum levels of RANKL and homocysteine were significantly higher in group I. We did not find significant differences in serum levels of 25-OH vitamin D, PTH, crosslaps, calcium, or phosphate between the two groups. The neonates from mothers recruited in group II had higher (but not significantly) serum level of OC. We observed that the neonates born from mothers in group II had overall better birth outcome parameters and apgar scores compare to the neonates born from mothers in group I. Our results show that daily supplementation of folic acid during pregnancy could have a positive impact on the bone turnover markers in mothers and their newborns. This may suggest that both pregnant mothers and their fetuses could benefit from positive effects of folic acid taken during the whole period of pregnancy.