In this study, we investigated the effects of paraoxonase 1 (PON1) activities and the variant PON1-Q192R on the ferric reducing ability of plasma (FRAP) and total thiol. In addition, we examined the distribution of genotypes of this variant and the relationship of the genotypes with age in patients with type 2 diabetes (T2D). A total of 115 patients with T2D were enrolled in this study. Paraoxonase activity (PON-para) and arylesterase activity (PON-aryl) were determined using spectrophotometric assays. The distribution of the Q192R genotypes was determined by the double substrate method. The antioxidant status was evaluated by determining FRAP and total thiol. The frequencies of Q and R allozyme were 0.78 and 0.22, respectively. The multivariate analysis identified a significant association between the variables PON1-Q192R (Wilks' λ = 0.85, P = 0.002) and PON-aryl (Wilks' λ = 0.896, P = 0.017), with FRAP and total thiol. The significant difference observed for PON1-Q192R and PON-aryl is primarily due to the changes in FRAP levels (η(2 )= 0.127, P = 0.002 for PON1-Q192R; η(2 )= 0.083, P = 0.011 for PON-aryl). The interaction PON1-Q192R-PON-aryl increased the effect sizes from 8 to 19% for FRAP. Only in R-carrying genotypes, there were significant correlations between both PON-para/HDL (r = -0.574, P < 0.001) and PON-aryl/HDL (r = -0.577, P < 0.001) with age. Our data suggest that the variant PON1-Q192R and PON1 activity, particularly PON-aryl, influenced the antioxidant status in T2D. The interaction of this variant and PON1 activity increased the effect size on the antioxidant capacity. Moreover, the presence of the R allozyme may potentiate the effects of age on susceptibility to cardiovascular diseases in T2D.
In the field of pavement engineering, the determination of the mechanical characteristics is one of the essential processes for reliable material design and highway sustainability. Early determination of the mechanical characteristics of pavement is essential for road and highway construction and maintenance. Tensile strength (TS), compressive strength (CS), and flexural strength (FS) of roller-compacted concrete pavement (RCCP) are crucial characteristics. In this research, the classification-based regression models random forest (RF), M5rule model tree (M5rule), M5prime model tree (M5p), and chi-square automatic interaction detection (CHAID) are used for simulation of the mechanical characteristics of RCCP. A comprehensive and reliable dataset comprising 621, 326, and 290 data records for CS, TS, and FS experimental cases was extracted from several open sources in the literature. The mechanical properties are determined based on influential input combinations that are processed using principle component analysis (PCA). The PCA method specifies that volumetric/weighted content forms of experimental variables (e.g., coarse aggregate, fine aggregate, supplementary cementitious materials, water, and binder) and specimens’ age are the most effective inputs to generate better performance. Several statistical metrics were used to evaluate the proposed classification-based regression models. The RF model revealed an optimistic classification capacity of the CS, TS, and FS prediction of the RCCP in comparison with the CHAID, M5rule, and M5p models. Monte-Carlo simulation was used to verify the results in terms of the uncertainty and sensitivity of variables. Overall, the proposed methodology formed a reliable soft computing model that can be implemented for material engineering, construction, and design.
Background
Paraoxonase 1 (PON1) and lipid abnormalities contribute to the development of cardiovascular disease, which is the principal cause of mortality in patients with type 2 diabetes (T2D). Data are not available on the potential association between salt-stimulated activity of PON1 (PON1-salt) and the atherogenic indices in T2D, therefore, we focused on these associations and evaluated whether the functional variants PON1-Q192R and PON1-L55M influence the associations.
Methods
Paraoxonase activity (PON1-para), arylesterase activity (PON1-aryl) and salt-stimulated activity (PON1-salt) were measured by spectrophotometric assays. The atherogenic index of plasma (AIP) was calculated from the log (TG/HDL-C). The genetic analyses were made by the restricted fragment length polymorphism after PCR amplification.
Results
We observed that PON1-salt was negatively correlated with total cholesterol (TC)/HDL-C (
r
= −0.441,
p
= 0.006), LDL-C/HDL-C (
r
= −0.415,
p
= 0.011), and AIP (
r
= −0.422,
p
= 0.009). Correlations between PON1-salt and all three atherogenic indices were significantly affected by PON1-L55M and PON1-Q192R. Linear regression showed that AIP (
p
= 0.002), LDL-C/HDL-C (
p
= 0.005), and TC/HDL-C (p = 0.002) were independently associated with PON1-salt. Based on Ridge regression, the standardized coefficients −0.358, −0.297, and − 0.044 were obtained for AIP, LDL-C/HDL-C, and TC/HDL-C, respectively, and this shows that AIP could have more negative effect on PON1-salt than the others.
Conclusions
The decreased PON1-salt may be considered as a risk factor for atherosclerosis in T2D, therefore, understanding the associations between PON1-salt as an important although neglected property and atherogenic indices may be valuable in T2D. Accordingly, detection of PON1-salt status (phenotype and genotype) together with the atherogenic indices particularly AIP could be beneficial in identifying the increased atherogenicity in T2D.
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