Glycated LDL-C and glycated HDL-C in association with adiposity, blood and atherogenicity indices in metabolic syndrome patients with and without prediabetes

Background: The aim of the study was to compare and correlate glycated high-density lipoprotein (GHDL-C) and glycated low-density lipoprotein (GLDL-C) plasma levels with adiposity indices [weight/hip ratio (WHR) and body adiposity index (BAI)], lipid ratios and hematological indices [platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR)]. Methods: This was a cross-sectional study of 30 nondiabetic metabolic syndrome (MetS) patients, 30 prediabetic or type 2 diabetes mellitus (T2DM) patients and 30 normoglycemic controls. Results: Remarkably both GHDL-C and GLDL-C levels lacked any intergroup statistically significant discrepancy in either MetS or MetS-pre/T2DM versus control ( p > 0.05). Unlike GLDL-C/LDL-C ratios for either MetS groups; there were highly significant intergroup differences in the means of GHDL-C/HDL-C ratios when comparing both nondiabetic MetS and MetS-pre/T2DM groups versus controls ( p = 0.001). In MetS patients; GHDL-C and GLDL-C proportionally correlated with WHR ( p < 0.05). Also, MetS GHDL-C correlated inversely with MLR and monocytes ( p < 0.05). In MetS-pre/T2DM; GLDL-C directly correlated with BAI, platelet count and PLR ( p < 0.05). Conclusion: GLDL-C and GHDL-C are dysfunctional glucolipotoxicity lipoproteins and may present putatively surrogate biomarkers for prediction/prevention of metabolic disturbances

Cross-sectional correlates of paraoxonase 1 and soluble intercellular adhesion molecule-1 in metabolic syndrome patients with and without diabetes

Background: Paraoxonase 1 (PON1) and soluble intercellular adhesion molecule-1(sICAM-1) are intricately involved in metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) pathophysiology. This study aimed to investigate PON1 and sICAM-1 plasma levels in addition to correlating them with adiposity, atherogenicity and hematological indices in T2DM and MetS. Methods: This cross-sectional study composed of 28 healthy lean subjects (control), 29 normoglycemic MetS subjects and 30 MetS-Pre/T2DM. Results: The sICAM-1 levels (ng/ml) were markedly higher in the pre/diabetic MetS group (828 ± 250.37 versus controls’ 608.62 ± 184; p < 0.05). Conversely, PON1 levels (mlU/ml) were markedly lower in the pre/diabetic MetS group [252,700 (163,950, 362,800) versus controls’ 394,900 (212,550, 469,350); p < 0.05]. sICAM-1 correlated directly with all adiposity indices [conicity index (CI), waist circumference (WC), waist–hip ratio (WHR) waist-to-height (WHtR) ratio, hip circumference (HC) and body adiposity index (BAI)] in addition to the atherogenicity index of plasma (AIP). PON1 correlated negatively and significantly with CI, WC, WHR, WHtR and HC but directly with lymphocyte. Significantly, a reciprocal sICAM-1–PON1 relationship was observed in the total population ( r = −0.262, p = 0.015). Conclusion: Utility of sICAM-1 and PON1 as surrogate prognostic biomarkers and putative therapeutic targets in the management of diabetes and MetS is strongly suggested

Cross-sectional correlates of increased IL-18 but reduced fetuin-A and oxytocin with adiposity and blood indices in metabolic syndrome patients with and without prediabetes

Background: Oxytocin (OXT), fetuin-A and interleukin-18 (IL-18) are involved in the development and progression of metabolic syndrome (MetS) and prediabetes (pre/T2DM). Aims, participants and methods: This study aimed to compare and correlate the plasma levels of OXT, fetuin-A and IL-18 with clinical parameters, haematological indices and adiposity indices in Jordanian MetS subjects. In a cross-sectional study, 30 normoglycaemic lean study participants (control), 30 MetS study participants, and 29 MetS pre/T2DM study participants were recruited. Results: Median circulating levels of both OXT and fetuin-A were lower in MetS and MetS pre/T2DM versus control group. OXT (pg/ml; median interquartile range): MetS 1975.4 and MetS pre/T2DM 1403 versus control 4176.6 ( p = 0.009 and p = 0.001, respectively). For fetuin-A (ng/ml), MetS (5784) and MetS pre/T2DM (2154) were lower versus control (6756.3) ( p = 0.040 and p = 0.007, respectively). Neither biomarker was described as substantially different in MetS versus MetS pre/T2DM ( p = 0.071 and p = 0.155, respectively). Conversely, a non-significant increase in IL-18 was observed in the MetS and MetS pre/T2DM groups compared to normoglycaemic lean controls (232 and 287.5, p > 0.05 versus 108 for both). In addition, conicity index (C-index), atherogenicity index (TG-HDL-C), waist to hip ratio, mean platelet volume (MPV; fl) and red cell distribution width (RDW-CV%) in both MetS and MetS pre/T2DM were significantly higher ( p < 0.001) versus controls. However all above MetS-related indices were not ascribed any statistically marked variation in the MetS group when compared to the MetS pre/T2DM group. Both total study pool of recruits’ fetuin-A (Spearman r = – 2.66, p = 0.049) as well as MetS pre/T2DM group IL-18 (Spearman r = 0.380, p = 0.046) were inversely correlated with RDW-CV%. OXT in MetS inversely correlated with waist circumference/hip circumference ratio (Spearman r = −0.387, p = 0.038). No other pronounced associations between biomarkers could be detected in any study arm. Conclusion: These findings substantiate the clinical relevance and significance of OXT, fetuin-A and IL-18 as surrogate screening/prognostic tools and therapeutic targets to predict/prevent metabolic dysregularities and anomalies

Synthesis, and Antitumor Activity of Some N1-(Coumarin-7-yl) Amidrazones and Related Congeners

A series of new N1-(coumarin-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-amino-4-methylcoumarin with the appropriate piperazines. The chemical structures of the newly prepared compounds were supported by elemental analyses, 1H-NMR, 13C-NMR, and ESI-HRMS spectral data. The antitumor activity of the newly synthesized compounds was evaluated. Among all the compounds tested, 7-{2-[1-(4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)piperazin-1-yl)-2-oxopropylidene]hydrazinyl}-4-methyl-2H-chromen-2-one (3n) was the most potent against MCF-7 and K562 cells, with IC50 values of 20.2 and 9.3 μM, respectively

An intronic single-nucleotide polymorphism (rs13217795) in FOXO3 is associated with asthma and allergic rhinitis: a case–case–control study

Abstract Background Asthma and allergic rhinitis are respiratory diseases with a significant global burden. Forkhead box O3 (FOXO3) is a gene involved in the etiology of a number of respiratory diseases. The objective of this study is to assess the association of rs13217795, an intronic FOXO3 single-nucleotide polymorphism, with asthma and allergic rhinitis. Methods In this case–case–control genetic association study, genotyping was conducted using the PCR–RFLP method. Genotype-based associations were investigated under the general, recessive, and dominant models of disease penetrance using binomial logistic regression; and, allele-based associations were tested using Pearson’s chi-squared test. Results The final study population consisted of 94 controls, 124 asthmatics, and 110 allergic rhinitis patients. The general and recessive models of disease penetrance were statistically significant for both case–control comparisons. Under the general model, the odds of the asthma phenotype were 1.46 (0.64 to 3.34) and 3.42 (1.37 to 8.57) times higher in heterozygotes and derived allele homozygotes, respectively, compared to ancestral allele homozygotes. The corresponding odds ratios for the allergic rhinitis phenotype were 1.05 (0.46 to 2.40) and 2.35 (0.96 to 5.73), respectively. The dominant model of disease penetrance was not statistically significant. The minor allele in all study groups was the ancestral allele, with a frequency of 0.49 in controls. There was no deviation from Hardy–Weinberg equilibrium in controls. Both case–control allele-based associations were statistically significant. Conclusions Herein we present the first report of the association between rs13217795 and allergic rhinitis, and the first independent verification of the association between rs13217795 and asthma. Marker selection in future genetic association studies of asthma and allergic rhinitis should include functional polymorphisms in linkage disequilibrium with rs13217795

The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

We demonstrated that the plasma membrane Ca2+ ATPase PMCA4b inhibits migration and metastatic activity of BRAF mutant melanoma cells. Actin dynamics are essential for cells to move, invade and metastasize, therefore, we hypothesized that PMCA4b affected cell migration through remodeling of the actin cytoskeleton. We found that expression of PMCA4b in A375 BRAF mutant melanoma cells induced a profound change in cell shape, cell culture morphology, and displayed a polarized migratory character. Along with these changes the cells became more rounded with increased cell–cell connections, lamellipodia and stress fiber formation. Silencing PMCA4b in MCF-7 breast cancer cells had a similar effect, resulting in a dramatic loss of stress fibers. In addition, the PMCA4b expressing A375 cells maintained front-to-rear Ca2+ concentration gradient with the actin severing protein cofilin localizing to the lamellipodia, and preserved the integrity of the actin cytoskeleton from a destructive Ca2+ overload. We showed that both PMCA4b activity and trafficking were essential for the observed morphology and motility changes. In conclusion, our data suggest that PMCA4b plays a critical role in adopting front-to-rear polarity in a normally spindle-shaped cell type through F-actin rearrangement resulting in a less aggressive melanoma cell phenotype

Correction to: The antiangiogenic activities of ethanolic crude extracts of four Salvia species

Correction After the publication [1] it came to the attention of the authors that one of the co-authors was incorrectly included as Hamza Somrain. The correct spelling is as follows: Hamzeh Sumrein

Additional file 1: of An intronic single-nucleotide polymorphism (rs13217795) in FOXO3 is associated with asthma and allergic rhinitis: a case–case–control study

Raw data. Demographic and genotype data for all participants. (XLS 56 kb