2024-12

Prostaglandins & Other Lipid Mediators

Introduction Aberrant vascular function and cancer growth are closely related, with nitric oxide (NO) being a key factor in vascular tone regulation. This study provides Novel insights into the distinctive mechanisms underlying cancer-associated vascular dysfunction by investigating the involvement of potassium (K+) channels in NO-mediated vasorelaxation within arteries supplying colon cancer. Methods Arterial segments from colon cancer patients were isolated and sectioned into rings, these rings were mounted in an organ bath filled with Krebs' solution and maintained at 37°C. Isometric tension recordings were obtained using a force transducer connected to a PowerLab Data Acquisition System. Arterial segments were pre-incubated with a variety of K+ channel blockers, both individually and in combination, including glibenclamide (GLIB), barium chloride (BaCl2), tetraethylammonium (TEA), and 4-aminopyridine (4-AP). Concentration-response curves were designed to evaluate how K+ channel blocking affected the vasodilation caused by NO. Results Sodium nitroprusside (SNP) induced vasorelaxation in arterial rings from colon cancer, influenced by specific K+ channels. Pre-incubation with TEA significantly reduced Emax to 60.22±8.14%, compared to 124.91±15.07% in controls, while GLIB decreased Emax to 113.10±3.87%. BaCl2 and 4-AP further diminished relaxation, and combined K+ channel blockers showed complex, non-additive effects. Distinct contributions of KCa and KV channels to NO-induced vasodilation were elucidated. Additionally, interaction between NO and L-type calcium (Ca2+) channels suggested a novel vasorelaxation mechanism in cancerous tissues. Conclusion This research offers new perspectives on the intricate relationship between vascular biology and cancer development, emphasizing the promise of targeting potassium channels to address vascular abnormalities in cancer.

2024-03

Expert Review of Endocrinology & Metabolism

Background The effects of pomegranate juice (PJ) and its components on uterine smooth muscle are unknown. Hence, this study unequivocally demonstrates that pomegranate juice (PJ) significantly impacts myometrial function, providing crucial insights into its relaxant properties and their potential therapeutic applications for uterine-related disorders. Research design and methods Rat uterine smooth muscle horn strips were suspended in Krebs solution organ baths. Contractions were measured isometrically using a transducer (AD instrument Australia). The effects of PJ were evaluated on contractile activity elicited by potassium chloride (KCl 60 Mm) depolarization. Inhibitors of nitric oxide (L-NAME 3X10−4), guanylate cyclase (methylene blue 1X10−5), and Prostaglandin I2 (indomethacin 3X10−5), as well as Potassium Channels blockers, were determined. Results The juice at concentrations from 1.5-5 mg/ml significantly decreased the rat uterine horn contraction induced by KCl. The NO, cGMP, and PGI2 inhibitors did not block the relaxation response. Furthermore, the PGI2 inhibitor significantly enhanced the relaxation effects; K+ channel blockers had no inhibitory effects on the relaxation responses. Contrarily, GLIB improved considerably relaxation. Conclusion Research suggests pomegranate juice’s active ingredient may reduce uterine contractions and treat uterotonic disorders, potentially preventing preterm birth and dysmenorrhea. Further research is needed to determine its mechanism of action.

2024-02

Egyptian Heart Journal

Background Unraveling myeloperoxidase’s (MPO) correlation with coronary artery disease (CAD) and genetic variations, this study seeks to enhance diagnostic precision and therapeutic strategies. Results CAD patients were found to be older and more male than controls. Several clinical parameters, including glucose, total bilirubin, alkaline phosphatase, creatinine, and troponin levels, showed significant variations. Moreover, CAD patients had lower red cell distribution width (RDW%) and mean platelet volume (MPV) than controls. Serum MPO levels did not differ significantly between CAD patients and controls, and no correlation was found with other clinical parameters except for glucose, creatinine, and total bilirubin. Conclusions The data suggest that serum MPO levels are not substantially related to CAD patients, as indicated by lower MPO levels in CAD patients compared to controls. While highlighting the potential of MPV and RDW% as predictors of severe atherosclerosis in CAD. Further research is needed to validate the diagnostic and prognostic value of RDW%, MPV, and MPO levels in CAD.

2023-12

Expert Review of Endocrinology & Metabolism

Background This study aimed to identify the prevalence and factors associated with abnormal liver enzyme profiles in individuals with type 2 diabetes (T2D) in Zakho, to assess the association between demographic characteristics, clinical parameters, kidney function tests, lipid profiles, glucose levels, and T2D, and to identify resident risk factors. Research design and methods A cross-sectional analysis of T2D patients admitted to Zakho General Hospital was conducted utilizing hospital records. The primary endpoint of interest was attaining HbA1C levels ≥ 6.5%. Analytical methodologies encompassed linear and multivariate logistic regression analyses, with due consideration of the association between diverse parameters and glycemic alterations. Further, the predictive value of biomarkers was evaluated through Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) analyses, complemented by Spearman correlation analysis to explore relationships among laboratory parameters. Results The study found that 89.4% of participants had HbA1C levels above 6.5%, with a preference for T2D among older individuals (mean age: 52.93–49.89 respectively) and females. Age, glucose levels, and liver enzymes positively correlated with HbA1C. Conclusions The study emphasizes the diagnostic importance of liver enzymes in individuals with type 2 diabetes, suggesting that these biomarkers could be valuable indicators of disease severity and progression.

2023-10

Molecular Biology Reports

Objective Coronary artery disease (CAD) is a complex disorder influenced by genetic and environmental factors. This case-control study investigated the association between Sirtuin SIRT3 gene polymorphisms, serum malondialdehyde (MDA) levels, and CAD susceptibility. Methods Blood samples were collected from 70 CAD cases and 30 controls at the Cardiac Center, Azadi Teaching Hospital, Duhok, Iraq. Genomic DNA was extracted, and PCR-based allele genotyping determined SIRT3 rs11246029 T/C polymorphisms. Serum MDA levels were measured using ELISA. Statistical analysis included t-tests, Mann-Whitney tests, and Spearman correlations. Odds ratios (OR) with 95% confidence intervals (CI) assessed genotypes/alleles and CAD associations. The accuracy of serum MDA in predicting the severity of CAD was evaluated using receiver operating characteristic (ROC) curve analysis. Results There were no significant variations in serum MDA levels between controls and CAD patients in the study. The diagnostic accuracy of serum MDA for CAD severity prediction was modest (Area Under Curve (AUC) = 0.56). Correlations revealed associations between MDA and total bilirubin (negative) and Troponin (positive). CRP correlated positively with LDH, glucose, cholesterol, LDL, CKmB, and Troponin. CKmB and Troponin are positively associated with clinical characteristics. Genotype analysis identified a significantly higher CAD risk with the CC genotype compared to controls. Conclusion These findings shed light on the potential role of SIRT3 gene polymorphisms and serum MDA levels in CAD susceptibility. Further research is needed to understand underlying mechanisms and therapeutic implications based on these markers.

2023-02

Prostaglandins & Other Lipid Mediators (Volume : 165)

Purpose The study aimed to examine if the polymorphism of the endothelial nitric oxide synthase (eNOS) gene variable number of tandem repeats (VNTR) and the serum NO levels are associated with CAD. Materials/methods Case-control study, 70 CAD and 30 control subjects were enrolled. The eNOS gene polymorphism was measured by polymerase chain reaction–agarose gel electrophoresis and the serum NO was assessed by using an ELISA plate and reader covering 540 nm. Results Uncovering the area under curve (AUC) for serum NO, which was (0.6821), indicating that NO seemed to be a critical prognostic biomarker of CAD; also, glucose, serum creatinine and total bilirubin proved to be significant predictors of CAD with AUC (0.6793, 0.6717 and 0.6662) respectively. Furthermore, higher serum NO levels were associated with the eNOS (ab) genotype. Revealing the intron (a) allele was protective against CAD. Moreover, diminished levels of serum NO in CAD groups compared to controls (P < 0.05). Additionally, Multiple logistic regression analysis shows a significantly high Odds ratio associated with CAD in the Duhok population. Conclusions The eNOS (ab) variant seems to be a protective CAD factor for patients. Low serum NO levels are another risk factor for the advancement of CAD, suggesting their involvement in atherosclerosis. The (a) allele's protective effect is mediated through changes in eNOS promoter activity and higher NO levels.

2018-04

academic journal international university of Erbil (Issue : 25196928) (Volume : 1)

The present study focused on the mechanisms of smooth muscle relaxation induced by Punica granatum juice (PJ) in the rat thoracic aorta. The thoracic aorta was removed from female adult albino rat and placed in an organ bath containing Kreb’s solution and the contractions were recorded isometrically. The results demonstrated that the P. granatum juice (1.5 to 5 mg/ml) significantly reduces the contractions induced by phenylephrine (PE) (0.01 mM), with IC50 ± SEM of 2.859 ± 0.101 mg/ml, and percentage of relaxation for PE-induced contraction was 81.8 ± 0.358. Also, the vasodilatory activity of PJ was not modified by endothelial denuded aorta with IC50 ± SEM 3.389 ± 0.084 mg/ml and the percentage of relaxation was 79.77 ±0.824 %. Pomegranate juice induced relaxation in the PE-induced contraction in intact aorta was unaffected by nitric oxide synthase inhibitor (L-NAME) (3*10-4), gaunyl cyclase inhibitor (methylene blue) (1*10-5) and PGI2 inhibitor (Indomethacin) (3*10-5) with IC50 ± SEM 3.424 ± 0.065, 3.286 ± 0.168 and 3.490 ± 0.054, respectively. The percentage of relaxation was 75.23 ± 0.661, 119.61 ± 4.128 and 83.87 ± 0.715%, respectively. In addition, Pre-incubation of aortic rings with TEA (1mM), GLIB (10-5), BaCl2 (1mM) and 4-AP (1mM) with IC50 ± SEM 3.099 ± 0.049mg/ml, 2.759 ± 0.087mg/ml, 2.889 ± 0.054mg/ml and 2.436±0.049 mg/ml, and the percentages of relaxation were 101.38 ± 0.151%, 88.55±0.58%, 90.25±0.168%, and 104.72±0.939%, respectively. Finally, PJ significantly increased dose-response relaxation after incubation of thoracic aortic rings with Nifedipine (10-6 M) with IC50 ± SEM, 3.495 ± 0.1012 and the percentage of relaxation was 100.276 ± 3.378%.

2017-06

Science Journal of University of Zakho (Issue : 24146943) (Volume : 5)

The monoterpene, α-terpinyle acetate (TA) is a constituent of essential oils present in aromatic plants. Since the role of ion channels and endothelial hyperpolarizing factors in TA induced relaxation in rat’s aorta is unknown, the current study aimed to study the mechanism underlying the vasodilatory effect of TA in isolated aortic rings. Terpinyle acetate induced a potent vasodilation in rat aortic rings with a percentage of relaxation of 63.79 %. The results of the role of K+ channel subtypes in vasorelaxation revealed that both Kv and KATP played a major role since GLIB produced a maximum percent of inhibition in the relaxation produced by TA to 8.91 %; this was followed by 4-AP in which the percent of inhibition reduced to 14.95. On the other hand, Kir played no role in the TA induced vasorelaxation since BaCl2 did not produce any inhibition in aortic relaxation. Furthermore, also L-type Ca2+ channel played no role in TA induced relaxation since the L-type Ca2+ channel inhibitor Nifedipine did not reduce the percent of relaxation. Endothelium also played a considerable role in the induced vasorelaxation since, in denuded aorta, the percent of relaxation was reduced to 36%. Preincubation of the aortic ring with methylene blue, a soluble cGMP inhibitor also significantly reduced the TA induced relaxation to 16.39%. In contrast, preincubation with cyclooxygenase inhibitor Indomethacin did not produce any inhibitory effect on AT induced vasorelaxation. It can be concluded from these novel results that AT induced vasorelaxation involve the activation of KV, KATP channels and at least partly dependent on endothelium via the activation NO-cGMP signal transduction pathway.

2017-03

Science Journal of University of Zakho (Issue : 24146943) (Volume : 5)

The aim of the present study was to evaluate the physiological effect of the Punica granatum hydromethanol seeds extract on the contractility of isolated rat aortic rings. The isolated rat’s thoracic aorta was placed in an organ bath containing Krebs solution and the contraction was recorded isometrically. The results demonstrated that P. granatum hydro- methanol extract (1.5 to 5 mg/ml) caused a significant relaxant effect on the contractions induced by phenylephrine (0.01 mM) with IC50 ± SEM of 2.682 ± 0.197 mg/ml and the percentage of relaxation for PE-induced contraction was 52.88 ± 0.831. In endothelium intact and denuded aortic rings, the extract induced more or less the same response, except at high concentrations used (4.5 – 5.0 mg/ml) in which the endothelium denuded rings produced a significant reduction in the percent of relaxation from 49.91 to 25.42. Relaxant effect of hydromethanol seed extracts on intact aorta was not affected by nitric oxide synthase sinhsibitor ( L-NAME, 3*10-4), gaunyl cyclase inhibitor ( methylene blue 1*10-5) and PGI2 inhibitor (Indomethacin, 3*10-5), and thus, the percentages of relaxation were 59.85 ± 0.084, 58.59 ± 0.566 and 56.76 ± 0.693 respectively. In addition, incubation of aortic rings with the K+ channels blockers TEA, GLIB,, 4AP and BaCl2, that Kca, KATP and Kv channels played no role on vasorelaxation induced by hydromethanol extract, while Kir enhanced the relaxation induced by the extract to76.40%. Finally, hydro methanol extract significantly enhanced dose-response relaxation after incubation of thoracic aortic rings with Nifedipine (10-6 M) to 91.91 % with IC50 ± SEM 1.774 ± 0.096. It can be concluded from the results of the current work that the fraction of Punica granatum hydromethanol seed extract has vasorelaxant effects on rat aortic which was partially dependent on endothelium, Kir and Ca channels.