The assessment of metabolite alteration induced by -OH functionalized multi-walled carbon nanotubes in mice using NMR-based metabonomics.

Introduction: There is a fundamental need to characterize multiwalled carbon nanotubes (MWCNTs) toxicity to guarantee their safe application. Functionalized MWCNTs have recently attracted special interest in order to enhance biocompatibility. The aim of the current work was to study the underlying toxicity mechanism of the -OH-functionalized MWCNTs (MWCNTs-OH), using the powerful NMR-based metabonomics technique. Methods: Following intraperitoneal single-injection of mice with 3 doses of MWCNTs-OH and one control, samples were collected at four time points during 22-days for NMR, biochemistry, and histopathology analysis. Metabolome profiling and pathway analysis were implemented by chemometrics tools and metabolome databases. Results: Based on the 1H-NMR data, metabolic perturbation induced by MWCNTs-OH were characterized by altered levels of steroid hormones, including elevated androgens, estrogens, corticosterone, and aldosterone. Moreover, increased L-lysine, aminoadipate, taurine and taurocholic acid and decreased biotin were observed in the high-dose group (1 mg.kg-1 B.W.) compared to the control. The findings also indicated that steroid hormone biosynthesis, lysine biosynthesis, and biotin metabolism are the most affected pathways by MWCNTs-OH. Conclusion: These pathways can reflect perturbation of energy, amino acids, and fat metabolism, as well as oxidative stress. The data obtained by biochemistry, metabonomics, and histopathology were in good agreement, proving that MWCNTs-OH was excreted within 24 h, through the biliary pathway.

Are Serum Levels of F2-Isoprostane and Oxidized-LDL Related to Vitamin D Status in Type 2 Diabetic Patients? A Case-Control Study.

BACKGROUND: Considerable evidence suggests that oxidative stress affects diabetes mellitus (DM) and contributes to its complications. Vitamin D has been shown to possess antioxidant properties. The aim of this study was to determine the association between serum levels of calcifediol (25-OH-D), an indicator of vitamin D status, and lipid profiles with oxidative stress in patients with type 2 diabetes mellitus (T2DM). METHODS: In this case-control study, 57 T2DM patients with low vitamin D status (< 30 ng/mL) and 48 T2DM patients with normal vitamin D status (> 30 ng/mL) were enrolled. Fasting concentrations of 25-OH-D, calcium, phosphorus, parathyroid hormone (PTH), lipid profiles, fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), F2-isoprostane, and oxidized-low-density lipoprotein (ox-LDL) were measured. RESULTS: The mean fasting serum concentrations of 25-OH-D, calcium, and phosphorus in patients with low vitamin D status were significantly lower than in controls (p < 0.001). The mean concentrations of ox-LDL, F2-isoprostane, total cholesterol, and LDL were significantly higher in patients with low vitamin D status than in controls. There was a negative correlation between vitamin D levels and F2-isoprostane (r = 0.647and P = 0.0001), LDL (r = -0.218 and P = 0.030), and ox-LDL (r = -0.637 and P = 0.0001). CONCLUSION: The results of present study indicated that serum concentrations of 25-OH-D were inversely correlated with F2-isoprostane, LDL, and ox-LDL. Therefore, vitamin D may have a beneficial effect on the control of lipid profiles and oxidative stress in T2DM patients.

Evaluation of hypoxia inducible factor-1 alpha gene expression in colorectal cancer stages of Iranian patients.

AIM OF STUDY: Colorectal cancer (CRC) is the fourth most prevalent cancer globally. Several factors have roles in cancer establishment. One of the most important factors is hypoxia that induces hypoxia inducible factor-1 (HIF-1). The HIF-1 alpha overexpressed in hypoxia conditions and plays a pivotal role in carcinogenesis features. In this study, we aimed to examine the efficiency of HIF-1 alpha gene expression at mRNA and protein's level for CRC diagnosing and staging. MATERIALS AND METHODS: In this study, the cases included into 75 cancer specimens in different stages (Group 2 = Stage 1, Group 3 = Stage 2, and Group 4 = Stage 3, 4) and ten normal specimens as control (Group 1). Real-time reverse transcription-polymerase chain reaction and immunohistochemistry (IHC) were performed for measuring gene expression at RNA and protein's level, respectively. The raw data were analyzed in the SPSS20 software. RESULTS: HIF-1 alpha gene expression rate (2-ΔΔCT) and ΔCT values were significantly higher increased in Group 4 in compare to control (P < 0.001). Other cancer groups (2 and 3) had greater ΔCT values than control, but it was not statistically significant. Moreover, the rate of HIF-1 alpha gene expression (2-ΔΔCT) was increased with cancer stages. According to the IHC results, there was a positive relationship between CRC stages and HIF-1 alpha protein expression (P < 0.05). CONCLUSIONS: HIF-1 alpha gene expression increased in earlier up to metastasis stages of CRC, but the assessment of HIF-1 alpha gene expression has not important role in the diagnosis of cancer in early stages and classification of carcinoma because the increasing of HIF-1 alpha gene expression is not significant in early cancer stages.