Prediction of HCV load using genotype, liver biomarkers, and clinical symptoms by a mathematical model in patients with HCV infection.

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross-sectional study, blood samples were taken from 249 recently diagnosed HCV-infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV-RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut-off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV-RNA load. Regression model: log viral load = 7.69 - 1.01 × G3 - 0.7 × G1 + 0.002 × ALT - 0.86 × fatigue.

Reduced Serum Levels of Zinc and Superoxide Dismutase in Obese Individuals.

The oxidant-stress (OS) has an essential role to play in the pathogenesis and progression of many diseases. OS is the outcome when the level of free-radical-formation is increased or protective-antioxidant-mechanisms are compromised. Its value is expected to increase, although its emerging roles have not been conclusive in different studies. The objective of this study was to explore the level of zinc, copper, and antioxidant in response to obesity-related-stress by measuring superoxide-dismutase (SOD) levels as a key antioxidant-enzyme in 706 individuals with/without obesity. Anthropometric/biochemical parameters including total-cholesterol (TC), fasting-blood-glucose, high-density-lipoprotein (HDL), low-density-lipoprotein, and triglycerides were determined. The activity of SOD was measured followed by the measurement of Cu and Zn levels. Obese subjects had a significantly higher level of body mass index (BMI) and TC, while the level of HDL was lower in the obese group, as compared to the related values in control subjects. The level of Zn was significantly decreased in the obese group, while the level of Cu and Cu/Zn ratio increased. Additionally, we observed that the SOD level was less in obese subjects when compared to that in the non-obese subjects. In addition to the complications of high BMI, low level of Zn and SOD in obesity can be considered a risk factor, resulting in a reduced antioxidant response, supporting the need for identifying a suitable treatment option for this group.

Biologically relevant doses of mixed aflatoxins B and G up-regulate MyD88, TLR2, TLR4 and CD14 transcripts in human PBMCs.

CONTEXT: Aflatoxins (AFs) are highly hazardous carcinogenic mycotoxins originated from very common fungi present in the environment. Their effect on key immune-surveillance molecules is unclear. OBJECTIVE: We aimed to examine the effect of mixed AFs on immunologically relevant molecules and on viability in human peripheral blood mononuclear cells (PBMCs), in conditions similar to those occurring naturally, i.e. using a mixture of environmentally relevant levels of AFB1, AFB2, AFG1 and AFG2. MATERIALS AND METHODS: We evaluated the mRNA expression of MyD88, toll-like receptor (TLR)-2, TLR4 and CD14, in human PBMCs treated with a mixture of AFB1, AFB2, AFG1 and AFG2 at different doses for 2, 12 and 24 h. We used qRT-PCR to assess changes in transcripts of MyD88, TLR2, TLR4 and CD14 in PBMCs. We also evaluated the viability of PBMCs exposed to AFs. RESULTS: Biologically relevant levels of mixed AFs elicited early immune modulation in human PBMCs. qRT-PCR results showed several folds increase of MyD88, TLR2, TLR4 and CD14 transcripts in PBMCs as early as 2 h post-exposure to mixed AFs. Kinetics and dose-response of the up-regulation differed for mentioned gene transcripts. Further, prolonged exposure to mixed AFs decreased PBMCs viability. CONCLUSION: Immunotoxicity of AFs on PBMCs may be mediated by up-regulation of key immune-surveillance molecule transcripts. The description of these effects induced by AFs on PBMCs are novel and should be taken into account when considering AF-related infectious and noninfectious diseases in areas highly exposed to AFs.