"Combination treatments of imatinib with astaxanthin and crocin efficiently ameliorate antioxidant status, inflammation and cell death progression in imatinib-resistant chronic myeloid leukemia cells".

BACKGROUND: Imatinib resistance remains a major obstacle in the treatment of chronic myelogenous leukemia (CML). Crocin (CRC) and astaxanthin (ATX) are phytochemicals with anti-cancer properties. AIMS: This study aimed to explore the effects of combination treatment of Imatinib with CRC and ATX on Imatinib-resistant K562 (IR-K562) cells. METHODS AND RESULTS: After the establishment of IR-K562 cells, growth inhibitory activity was determined by the MTT assay. To test the regeneration potential, a colony formation assay was performed. Cell cycle analyses were examined by flow cytometry. Cell injury was evaluated by lactate dehydrogenase (LDH) leakage. Real-time PCR was applied to assess the expression of IL6, TNF-α, STAT3, BAD, CASP3, TP53, and Bcl-2 genes. Caspase-3 activity was determined by a colorimetric assay. Antioxidant activity was measured using a diphenylpicrylhydrazyl (DPPH) assay. After 48 h of treatment, ATX (IC50 = 30µM) and CRC (IC50 = 190µM) significantly inhibited cell proliferation and colony formation ability, induced G1 cell cycle arrest and cell injury, upregulated the expression of apoptosis-associated genes, and downregulated the expression of anti-apoptotic and inflammatory genes. The combination of IM with ATX and/or CRC synergistically reduced cell viability (combination index [CI] < 1). CONCLUSION: Our data suggest that IM shows better therapeutic efficacy at lower doses when combined with ATX and/or CRC.

Src homology 2-B adapter protein 3 C784 T and Methylenetetrahydrofolate reductase C677 T Polymorphisms and Inflammation Markers in ST-segment Elevation Myocardial Infarction Patients.

Neutrophil-lymphocyte (NLR), platelet-lymphocyte (PLR), eosinophil-lymphocyte (ELR), and monocyte-lymphocyte (MLR) ratios are systemic inflammatory markers related to myocardial infarction. The aim of this study is to investigate the association of Src homology 2-B adapter protein 3 (SH2B3) C784 T and methylenetetrahydrofolate reductase (MTHFR) C677 T polymorphisms (SNP) with systemic inflammatory markers and the severity of coronary artery disease (CAD) in 150 ST-elevation myocardial infarction (STEMI) patients. Single nucleotide polymorphisms were genotyped using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. The inflammatory markers were calculated. An interventional cardiologist blinded to other data assessed the SYNTAX (SX) Score. Eosinophil and platelet counts were significantly higher in SH2B3 variants than in the wild type. Additionally, SH2B3 variants had significantly higher ELR than the wild type (.12 ± .19 vs .25 ± .34, p = .018). NLR, PLR, ELR, and MLR were considerably higher in MTHFR variants than in the wild type (p < .05). The SX score was significantly higher in both SH2B3 C784 T (21.24 ± 8.90 vs 15.29 ± 9.40, p = .00) and MTHFR C677 T (20.34 ± 10.21 vs 16.08 ± 8.39, p = .00) variants when compared with wild type. In conclusion, these polymorphisms are associated with several markers of systemic inflammation as well as the severity of CAD.

Factor V Leiden, MTHFR, and FXIIIVal34Leu gene polymorphisms and their association with clinical features and risk of diabetic retinopathy in patients with type 2 diabetes.

Background: Diabetic retinopathy (DR) is expanding to epidemic levels globally due to the progressing prevalence of diabetes mellitus (DM). In this study, the association between factor V Leiden (FVL), MTHFRC677T, and FXIIIVal34Leu polymorphisms and diabetic retinopathy was investigated in Eastern Iran. Methods: This case-control study enlisted the participation of 300 people (diabetic patients=100, diabetic retinopathy patients=100, healthy controls=100), and polymorphisms were examined by Tetra primer ARMS-PCR. Results: The frequency of FVL (p=0.294) and FXIIIVal34Leu (P=0.349) polymorphism showed no significant results between the genotype frequency in the mentioned groups. In contrast, MTHFRC677T SNP was significantly different in diabetic patients and controls (P=0.008). The MTHFRC677T polymorphism was found to be connected with increased systolic blood pressure in patients who had the TT genotype (130.96±11.92mm/Hg; P=0.011). Conclusion: Our study recommended that the MTHFRC677T polymorphism may offer to DR development. Studies with larger sample sizes and a wider spectrum of populations are authorized to verify this finding.

A method for estimating the measurement uncertainty of carbon determination in low carbon and low alloy steels by spark atomic emission spectroscopy.

Due to its high analysis speed and acceptable accuracy, the Spark Atomic Emission Spectroscopy method has been used widely in steel production factories. Since the accuracy of the results dramatically impacts the quality of the final product, the measurement uncertainty must be calculated and presented along with the analysis results. The primary purpose of this paper is to present a method for estimating the measurement uncertainty of carbon determination in carbon and low alloy steel by spark atomic emission spectroscopy. After identifying the factors influencing the test results, we presented a method for quantification and calculation of each source contribution to the combined uncertainty using mathematical and statistical methods. Finally, the amount of expanded uncertainty is determined for a 95% of confidence level. It was found that the measurement uncertainty is mainly affected by the calibration curve, while the analyst error has no significant effect on the measurement uncertainty. The extended relative uncertainty of 0.01 was determined at the 95% confidence level with a coverage factor k = 2.