Potential antiplatelet agents with grape seed - backbone polyphenols: computational studies.

The study focused on grape seed-derived polyphenols for their antiplatelet, anti-inflammatory, and fibrinolytic properties through molecular docking and dynamics simulations. Compounds were evaluated for their effects on P2Y12, PTP1B, thromboxane A2, and other targets. Compounds 1 and 6 showed strong inhibitory potential on P2Y12. Compounds 2 and 7, plus epigallocatechin gallate, demonstrated effective inhibition on NF-KB and COX1. The compounds exhibited drug-like properties and potential for new thrombotic disease therapies. The research sheds light on the interactions between polyphenols and target proteins, paving the way for novel antiplatelet strategies.

Association of rs5051 and rs699 polymorphisms in angiotensinogen with coronary artery disease in Iranian population: A case-control study.

Coronary artery disease (CAD) is the third most common cause of mortality globally (with 17.8 million deaths annually). Angiotensinogen (AGT) and polymorphisms in this gene can be considered as susceptibility factors for CAD. We performed a retrospective case-control study to determine the correlation of AGT rs5051 and rs699 polymorphisms with CAD in an Iranian population. We genotyped 310 CAD patients and 310 healthy subjects using polymerase chain reaction-based methods. To confirm the accuracy of the screening approach, 10% of genotyped subjects were validated using gold-standard Sanger Sequencing. To evaluate the effect of the candidate polymorphisms, white blood cells were randomly purified from the subjects and AGT expression was measured by quantitative reverse transcriptase-polymerase chain reaction. Sex stratification indicated a significant correlation between CAD and male sex (P = .0101). We found a significant association between the rs5051 A allele (P = .002) and the rs699 C allele, and CAD (P = .0122) in recessive and dominant models. Moreover, our findings showed a significant association of the haplotype, including the rs5051 A/A and rs699 T/C genotypes, with CAD (P = .0405). Finally, AGT mRNA levels were significantly decreased in patients harboring the candidate polymorphisms (P = .03). According to our findings The AGT rs5051 A and AGT rs699 C alleles are predisposing variants of CAD risk and severity in the Iranian population.

Potentilla reptans L. preconditioning regulates H19 and MIAT long noncoding RNAs in H9C2 myoblasts Ischemia/Reperfusion model.

The present study aimed to evaluate the effect of the ethyl acetate fraction of P. reptans root (PEF) preconditioning on expressions of lncRNAs H19 and MIAT in H9C2 myoblasts I/R injury.H9C2 cells were treated with different concentrations ranging from (10-400 µg/ml) of PEF for 24 h, followed by simulation of I/R condition. For I/R experiments, H9C2 cells were subjected with the oxygen and glucose deprivation for 2 h.H9C2 cell viability was significantly enhanced by PEF preconditioning under I/R condition in a concentration-dependent manner up to 200 µg/ml as a EC50. The PEF significantly diminished the expression of lncRNA MIAT and rate of apoptosis against the I/R group. In addition, PEF pretreated before stimulation I/R condition increased H19 expression compared to the normal PEF group with no statistically significant differences between groups. Hence, the results suggest that PEF can protect cardiomyocytes during hypoxia-induced myocardial cell injury by targeting specific involved genes.

Prediction of COVID-19 manipulation by selective ACE inhibitory compounds of Potentilla reptant root: In silico study and ADMET profile.

In the novel SARS-CoV-2 (COVID-19) as a global emergency event, the main reason of the cardiac injury from COVID-19 is angiotensin-converting enzyme 2 (ACE2) targeting in SARS-CoV-2 infection. The inhibition of ACE2 induces an increase in the angiotensin II (Ang II) and the angiotensin II receptor type 1 (AT1R) leading to impaired cardiac function or cardiac inflammatory responses. The ethyl acetate fraction of Potentilla reptans L. root can rescue heart dysfunction, oxidative stress, cardiac arrhythmias and apoptosis. Therefore, isolated components of P. reptans evaluated to identify natural anti-SARS-CoV-2 agents via molecular docking. In silico molecular docking study were carried out using the Auto Dock software on the isolated compounds of Potentilla reptans root. The protein targets of selective ACE and others obtained from Protein Data Bank (PDB). The best binding pose between amino acid residues involved in active site of the targets and compounds was discovered via molecular docking. Furthermore, ADMET properties of the compounds were evaluated. The triterpenoids of P. reptans showed more ACE inhibitory potential than catechin in both domains. They were selective on the nACE domain, especially compound 5. Also, the compound 5 & 6 had the highest binding affinity toward active site of nACE, cACE, AT1R, ACE2, and TNF-α receptors. Meanwhile, compound 3 showed more activity to inhibit TXA2. Drug likeness and ADMET analysis showed that the compounds passed the criteria of drug likeness and Lipinski rules. The current study depicted that P. reptans root showed cardioprotective effect in COVID-19 infection and manipulation of angiotensin II-induced side effects.

Modeling the diagnosis of coronary artery disease by discriminant analysis and logistic regression: a cross-sectional study.

PURPOSE: Coronary artery disease (CAD) is one of the most significant cardiovascular diseases that requires accurate angiography to diagnose. Angiography is an invasive approach involving risks like death, heart attack, and stroke. An appropriate alternative for diagnosis of the disease is to use statistical or data mining methods. The purpose of the study was to predict CAD by using discriminant analysis and compared with the logistic regression. MATERIALS AND METHODS: This cross-sectional study included 758 cases admitted to Fatemeh Zahra Teaching Hospital (Sari, Iran) for examination and coronary angiography for evaluation of CAD in 2019. A logistics discriminant, Quadratic Discriminant Analysis (QDA) and Linear Discriminant Analysis (LDA) model and K-Nearest Neighbor (KNN) were fitted for prognosis of CAD with the help of clinical and laboratory information of patients. RESULTS: Out of the 758 examined cases, 250 (32.98%) cases were non-CAD and 508 (67.22%) were diagnosed with CAD disease. The results indicated that the indices of accuracy, sensitivity, specificity and area under the ROC curve (AUC) in the linear discriminant analysis (LDA) were 78.6, 81.3, 71.3, and 81.9%, respectively. The results obtained by the quadratic discriminant analysis were respectively 64.6, 88.2, 47.9, and 81%. The values of the metrics in K-nearest neighbor method were 74, 77.5, 63.7, and 82%, respectively. Finally, the logistic regression reached 77, 87.6, 55.6, and 82%, respectively for the evaluation metrics. CONCLUSIONS: The LDA method is superior to the Quadratic Discriminant Analysis (QDA), K-Nearest Neighbor (KNN) and Logistic Regression (LR) methods in differentiating CAD patients. Therefore, in addition to common non-invasive diagnostic methods, LDA technique is recommended as a predictive model with acceptable accuracy, sensitivity, and specificity for the diagnosis of CAD. However, given that the differences between the models are small, it is recommended to use each model to predict CAD disease.

Six new triterpenoids from the root of Potentilla reptans and their cardioprotective effects in silico.

Tormentic acid ester glucosides derivatives (1, 2 and 4), 3-oxoursane ester glycoside (3) and 11-methoxy-ursane ester glycosides (5, 6) as six new triterpenoids, along with catechin were isolated from the ethyl acetate fraction of Potentilla reptans root (Et) methanolic extract. The structures of the compounds were elucidated by 1D, 2D NMR, IR and MS spectroscopy. Additionally, isolated triterpenoid compounds (1-6) and catechin were evaluated for their cardioprotective effects via glycogen synthase kinase 3ß (GSK-3ß) and glucocorticoid regulated kinase-1 (SGK1) protein kinase inhibition by Molecular Docking. Compound 1 and catechin (compound 7) exhibited significant inhibitory effects against GSK-3ß and SGK1 protein kinases with a binding energy value -9.1 and -8.8 kcal/mol, respectively. Hence, Et can be a suitable natural candidate to protect cardiomyocytes injury.

Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heart.

BACKGROUND: Our previous study indicated that Potentilla reptans root has a preconditioning effect by its antioxidant and anti-apoptotic effects in an isolated rat heart ischemia/reperfusion (IR) model. In the present study, we investigated the post-conditioning cardio-protective effects of Potentilla reptans and its active substances. METHODS: The ethyl acetate fraction of P. reptans root (Et) was subjected to an IR model under 30 min of ischemia and 100 min of reperfusion. To investigate the postconditioning effect, Et was perfused for 15 min at the early phase of reperfusion. RISK/SAFE pathway inhibitors, 5HD and L-NAME, were applied individually 10 min before the ischemia, either alone or in combination with Et during the early reperfusion phase. The hemodynamic factors and ventricular arrhythmia were calculated during the reperfusion. Oxidative stress, apoptosis markers, GSK-3ß and SGK1 proteins were assessed at the end of experiments. RESULTS: Et postconditioning (Etpost) significantly reduced the infarct size, arrhythmia score, ventricular fibrillation incidence, and enhanced the hemodynamic parameters by decreasing the MDA level and increasing expression of Nrf2, SOD and CAT activities. Meanwhile, Etpost increased the BCl-2/BAX ratio and decreased Caspase-3 expression. The cardioprotective effect of Etpost was abrogated by L-NAME, Wortmannin (a PI3K/Akt inhibitor), and AG490 (a JAK/STAT3 inhibitor). Finally, Etpost reduced the expression of GSK-3ß and SGK1 proteins pertaining to the IR group. CONCLUSION: P. reptans reveals the post-conditioning effects via the Nrf2 pathway, NO release, and the RISK/SAFE pathway. Also, Etpost decreased apoptotic indexes by inhibiting GSK-3ß and SGK1 expressions. Hence, our data suggest that Etpost can be a suitable natural candidate to protect cardiomyocytes during reperfusion injury.

The comparison of waist circumference, waist-to-hip ratio, and waist-to-height ratio among rural women adults in the North of Iran, between the years 2004 and 2013.

BACKGROUND: Central obesity is a common health disorder, and the main objective of this study was to compare its changings among rural women in the north of Iran, between the years 2004 and 2013. METHODS: Two cross-sectional studies were established on the 2839 and 2478 subjects in 2004 (first stage) and 2013 (second stage), respectively. Among 118 villages, 20 were selected using random sampling; they were the same in two studies. Central obesity was defined as waist circumference (WC) > 88 cm, waist-to-hip ratio (WHR) > 0.8, and waist-to-height ratio (WHtR) > 0.5. RESULTS: The prevalence of central obesity in 2013 based on WC, WHR, and WHtR were 37.4%, 73.5%, and 67.8%, respectively. Compared with 2004, the prevalence of central obesity based on WHR increased as 5.4% (68.1% vs. 73.5%) (P = 0.001), whereas morbid obesity (WHtR > 0.6) based on WHtR decreased as 3.7% in 2013 (28.8% vs. 25.1%) (P = 0.004). Central obesity based on WHR significantly decreased in less or equal 24-year-old group (76.6% vs. 70.1%) (P = 0.003), while it increased in 25-34- (65.1% vs. 74.0%) and in equal or more than 35-year-old group (54.1% vs. 78.9%) (P = 0.001 for all). Moreover, morbid obesity decreased in all age, economic, and education groups (except uneducated one) (P < 0.050 for all). CONCLUSION: Despite the decrease in central obesity based on WC and WHR indices in 2004-2013 duration, we found the evidence of a decline in sever obesity based on WHtR in that period. These trends have an alarm for health policy makers, not only in this area but also in same communities. Comprehensive studies are recommended to determine the best obesity indicator related to health in future.

Association between NOS3 G894T, T-786C and 4a/4b Variants and Coronary Artery Diseases in Iranian Population.

BACKGROUND: Endothelial nitric oxide synthase, encoded by NOS3, produces an atheroprotective metabolite. The G894T, T-786C and 4a/4b variants of this gene associated with increased risk for coronary artery diseases (CAD) have been evaluated in different populations worldwide, and inconsistent results have been obtained. We investigated the association between these three polymorphisms and presence of CAD in Iranian individuals. METHODS: Overall, 234 people including angiography-positive patients from Amir-Almomenin Hospital (Heart Center), Kordkoy City, Golestan Province, northern Iran in 2016, angiography-negative subjects and healthy individuals from north of Iran were genotyped for the G894T and T-786C variations by PCR-RFLP, and 4a/4b VNTR only by PCR. RESULTS: The genotype distribution and allelic frequencies for the three variants tested were not dramatically different between CAD and control subjects and also between CAD patients and people with pains and symptoms very similar to CAD but no stenosis (P>0.05). Moreover, the odds ratio for CAD related to the G894T (OR=1.09, 95% CI=(0.60-2.00), T-786C (OR=1.04, 95% CI=(0.57-1.89) and 4a/4b (OR=1.75, 95% CI=(0.92-3.32) variants did not show statistical significance. Similarly, the odds ratio for stenosis confirmed by angiography related to the 894T (OR=1.03, 95% CI= (0.61-1.74), -786C (OR=0.90, 95% CI=(0.54-1.50) and 4b (OR=1.64, 95% CI=(0.92 -2.93) alleles were not significant. CONCLUSION: G894T, T-786C and 4a/4b variants were not associated with risk for CAD and occurrence of angiography-assessed stenosis in Northern Iranian population (P>0.05). These alleles might be population-specific and not to be associated with their corresponding gene pool. However, further analysis is required to clarify other CAD-correlated markers in our community.

The comparison of acute myocardial infarction serum anticardiolipin antibody with healthy subjects, in Gorgan (Northern Iran).

Arthrosclerosis considered one of the most important causes of morbidity and mortality in industrial and developing countries. The rate of myocardial infarction in some countries is about 2 million annually with 1/4 of them is leading to death. This study was a case-control research, which was carried out as cross-sectional project in two groups, healthy and case subjects. The mean age and standard deviation of patients and control groups were nearly equal (55 +/- 10). The ELISA technique was applied to measure the serum antibody level. The sample populations in each group were exactly the same (120 person in each group). The gender distribution in case and control group was 44 female, 76 male and 45 female and 75 male, respectively. The Mean +/- SD of IgM in case group and control groups were 3.10 +/- 2.54 and 1.54 +/- 1.00, respectively. The Mean +/- SD for IgG in case and control groups were 5.90 +/- 3.84 and 3.08 +/- 1.95, respectively. The differences, between the mean of IgM and IgG in two groups of cases and control statistically were significant (p = 0.0001). In case group the Mean +/- SD for IgM for men and woman were 2.98 +/- 1.97 and 3.17 +/- 2.83, respectively, which this differences statistically, were not significant. In case group the Mean +/- SD for IgG were 5.14 +/- 3.45 and 6.35. The above findings indicated that the average of both IgG and IgM are higher among men compared to women. Due to high prevalence of acute coronary syndrome in Iran, the determination of anticardiolipin antibody (IgG) are applied for suspected acute coronary syndrome patients and further prevention measure should be taken for patient with higher serum anticardiolipin antibody.

The effect of Computerized Physician Order Entry and decision support system on medication errors in the neonatal ward: experiences from an Iranian teaching hospital.

Medication dosing errors are frequent in neonatal wards. In an Iranian neonatal ward, a 7.5 months study was designed in three periods to compare the effect of Computerized Physician Order Entry (CPOE) without and with decision support functionalities in reducing non-intercepted medication dosing errors in antibiotics and anticonvulsants. Before intervention (Period 1), error rate was 53%, which did not significantly change after the implementation of CPOE without decision support (Period 2). However, errors were significantly reduced to 34% after that the decision support was added to the CPOE (Period 3; P < 0.001). Dose errors were more often intercepted than frequency errors. Over-dose was the most frequent type of medication errors and curtailed-interval was the least. Transcription errors did not reduce after the CPOE implementation. Physicians ignored alerts when they could not understand why they appeared. A suggestion is to add explanations about these reasons to increase physicians' compliance with the system's recommendations.

Altered levels of nodal excitability by rate-dependent inhibitory effects of essential oil of Citrus aurantium on the electrophysiological properties of isolated perfused rabbit AV-Node: protective role in the prevention of ouabain toxicity / Alteración de los niveles de excitabilidad nodal por efectos inhibitorios velocidad-dependiente del aceite esencial de Citrus aurantium sobre las propiedades electrofisiológicas del nodo AV Aislado y perfundido de conejo: papel protector en la prevención de toxicidad por ouabaína

Treatment of supraventricular arrhythmia includes a wide range of medical interventions. Herbal remedies are suitable alternatives to synthetic drugs due to their availability, minimal side effects and lower price. Pharmacological studies and traditional medical literature point to the cardiovascular effects of Citrus aurantium L. (Rutaceae) in many instances. In the present study we used isolated perfused AV-node of rabbit as an experimental model to determine the effect of various concentrations of essential oil of C. aurantium (0.1-0.3 v/v) on the nodal conduction time and refractoriness of an isolated rabbit AV-nodal preparations. Selective stimulation protocols were used to independently quantify AV nodal recovery, facilitation and fatigue in 18 rabbits. Our results showed concentration-dependent and rate-independent suppressive effects of essence of C. aurantium on the Wenchebach cycle length (WBCL), AV Conduction Time (AVCT) and effective and functional refractory periods (ERP & FRP). Functional properties such as facilitation and fatigue were significantly increased by this plant. Citrus aurantium plays a protective role against the toxic effects of ouabaine by increasing AV nodal conduction time and refractoriness. The above results indicated differential effects of C. aurantium on slow and fast pathways, with a dominant role on fast pathways. This research has explained the protective role of C. aurantium on ouabaine toxicity. All results indicated the potential anti-arrhythmic effects of C. aurantium in treating supraventricular tachyarrhythmia.

El tratamiento de la arritmia supraventricular incluye una amplia gama de intervenciones médicas. Los remedios herbarios son alternativas adecuadas a las drogas sintéticas debido a su disponibilidad, con escasos efectos secundarios y bajo precio. Estudios farmacológicos y la literatura médica tradicional señalan los efectos cardiovasculares de Citrus aurantium L. (Rutaceae) en muchos casos. En el presente estudio se usaron aislados perfundidos del nodo AV de conejo como modelo experimental para determinar el efecto de diferentes concentraciones de aceite esencial de C. aurantium (0,1-0,3 v/v) sobre en el tiempo de conducción nodal y refractariedad. Un protocolo de estimulación selectiva se utilizó para cuantificar de forma independiente la recuperación, la facilitación y la fatiga del nodo AV en 18 conejos. Nuestros resultados muestran efectos supresores dependientes de la concentración e independiente de la velocidad de la esencia de C. aurantium sobre la duración del ciclo Wenchebach (WBCL), tiempo de conducción AV (AVTC) y períodos refractarios eficaz y funcional (PRE y PRF). Propiedades funcionales tales como la facilitación y la fatiga se incrementaron de manera significativa por esta planta. La Citrus aurantium juega un papel protector contra los efectos tóxicos de ouabaína al incrementar el tiempo de conducción AV nodal y la refractariedad. Los resultados indican efectos diferenciales de C. aurantium sobre las vías lentas y rápidas, con un papel dominante en las vías rápidas. Esta investigación ha explicado el papel protector de C. aurantium sobre la toxicidad ouabaine. Todos los resultados indican los posibles efectos anti-arrítmicos de C. aurantium en el tratamiento de taquiarritmias supraventriculares.

CPOE in Iran--a viable prospect? Physicians' opinions on using CPOE in an Iranian teaching hospital.

BACKGROUND: In recent years, the theory that on-line clinical decision support systems can improve patients' safety among hospitalised individuals has gained greater acceptance. However, the feasibility of implementing such a system in a middle or low-income country has rarely been studied. Understanding the current prescription process and a proper needs assessment of prescribers can act as the key to successful implementation. OBJECTIVES: The aim of this study was to explore physicians' opinions on the current prescription process, and the expected benefits and perceived obstacles to employ Computerised Physician Order Entry in an Iranian teaching hospital. METHODS: Initially, the interview guideline was developed through focus group discussions with eight experts. Then semi-structured interviews were held with 19 prescribers. After verbatim transcription, inductive thematic analysis was performed on empirical data. Forty hours of on-looker observations were performed in different wards to explore the current prescription process. RESULTS: The current prescription process was identified as a physician-centred, top-down, model, where prescribers were found to mostly rely on their memories as well as being overconfident. Some errors may occur during different paper-based registrations, transcriptions and transfers. Physician opinions on Computerised Physician Order Entry were categorised into expected benefits and perceived obstacles. Confidentiality issues, reduction of medication errors and educational benefits were identified as three themes in the expected benefits category. High cost, social and cultural barriers, data entry time and problems with technical support emerged as four themes in the perceived obstacles category. CONCLUSIONS: The current prescription process has a high possibility of medication errors. Although there are different barriers confronting the implementation and continuation of Computerised Physician Order Entry in Iranian hospitals, physicians have a willingness to use them if these systems provide significant benefits. A pilot study in a limited setting and a comprehensive analysis of health outcomes and economic indicators should be performed, to assess the merits of introducing Computerised Physician Order Entry with decision support capabilities in Iran.