Publications

Ten studies showed some concerns of risk of bias (RoB) and four studies had a high RoB for the change in Hb levels during follow-up. The lack of standardized definitions for hypersensitivity reactions and variability in dosing protocols and follow-up durations across studies may affect the generalizability of our safety findings.

Background: Aldosterone synthase inhibitors (ASIs) are a novel class targeting aldosterone biosynthesis, offering a mechanistically distinct approach from mineralocorticoid receptor antagonists. Research Question: Do ASIs significantly reduce blood pressure compared to placebo in patients with hypertension, and what is their associated safety profile? Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating ASIs versus placebo in hypertensive patients. A comprehensive search was performed in Cochrane CENTRAL, PubMed, Scopus, and Web of Science up to April 15, 2025. All available dosages of each agent were pooled into a single treatment node. The primary efficacy outcome was the change in mean seated systolic blood pressure (SBP), while the safety outcome was hyperkalemia. Secondary outcomes included changes in mean seated diastolic blood pressure (DBP), 24-hour ambulatory SBP, serious adverse events (SAEs), and hyponatremia. Data were synthesized using inverse-variance random-effects models. Results: Six RCTs comprising 1,382 participants were included from an initial screening of 855 records. Compared with placebo, ASIs significantly reduced mean seated SBP (mean difference [MD] −6.44 mmHg; 95% CI −8.7 to −4.17; I 2 =0%; p<0.0001). Mean seated DBP was also significantly reduced (MD −2.15 mmHg; 95% CI −3.48 to −0.82; p=0.0015), as was 24-hour ambulatory SBP (MD −6.82 mmHg; 95% CI −8.81 to −4.84; p<0.001). These SBP and DBP reductions were consistent across hypertension subtypes (primary, resistant, and uncontrolled) and among different ASI agents (p for interaction >0.1). The risk of hyperkalemia was significantly elevated (RR 4.48; 95% CI 1.44 to 13.91), primarily driven by lorundrostat (RR 6.96; 95% CI 1.39 to 34.87). However, ASIs were not associated with a significant increase in SAEs (RR: 2.11; 95% CI 0.82 to 5.43; p=0.62) or non-SAEs (RR 1.10; 95% CI 0.76 to 1.57; p=0.62) compared to placebo. No significant increase was observed in hyponatremia risk (RR 1.24; 95% CI 0.34 to 4.46). Conclusions: ASIs significantly and mildly reduced both SBP and DBP in hypertensive patients, with an overall manageable safety profile. The increased risk of hyperkalemia—particularly with lorundrostat—warrants monitoring. These agents may hold promise for enhanced efficacy when combined with other antihypertensive therapies in future trials.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (<i>p</i> > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (<i>p</i> > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (<i>p</i> > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

Abstract This paper presents the results of an experimental research on the assessment of the residual mechanical properties of high strength concretes (HSCs) made with pyrophyllite aggregate (PA) after high temperature. In the study, HSC mixtures with varying PA ratios (0, 25, 50, 75, and 100%) were subjected to elevated temperature (150, 300, 450, 600, and 750°C) and then cooled in two different cooling regimes (air and water‐cooling). The properties examined included compressive strength, weight loss, effects of cooling regime, and microstructure of HSC. The results of the study show that the increase in the PA ratios leads to a decrease in the compressive strength values. The results showed that weight loss of the specimens decreased with increasing PA ratios. It was found that the compressive strength values of HSC with PA cooled in air‐cooling are higher than that cooled in water. When the compressive strength loss and the weight loss values are taken into consideration according to the control samples, the group with the highest resistance to high temperature (750°C) effect was 100% PA group. Also, the internal structures of the samples exposed to high temperature were examined using scanning electron microscope and visual observations.

Monoamine oxidase inhibitors (MAOIs) have been crucial in the search for anti-neurodegenerative medications and continued to be a vital source of molecular and mechanistic diversity. Therefore, the search for selective MAOIs is one of the main areas of current drug development. To increase the effectiveness and safety of treating Parkinson’s disease, new scaffolds for reversible MAO-B inhibitors are being developed. A total of 24 pyridazinobenzylpiperidine derivatives were synthesized and evaluated for MAO. Most of the compounds showed a higher inhibition of MAO-B than of MAO-A. Compound S5 most potently inhibited MAO-B with an IC50 value of 0.203 μM, followed by S16 (IC50 = 0.979 μM). In contrast, all compounds showed weak MAO-A inhibition. Among them, S15 most potently inhibited MAO-A with an IC50 value of 3.691 μM, followed by S5 (IC50 = 3.857 μM). Compound S5 had the highest selectivity index (SI) value of 19.04 for MAO-B compared with MAO-A. Compound S5 (3-Cl) showed greater MAO-B inhibition than the other derivatives with substituents of -Cl &gt; -OCH3 &gt; -F &gt; -CN &gt; -CH3 &gt; -Br at the 3-position. However, the 2- and 4-position showed low MAO-B inhibition, except S16 (2-CN). In addition, compounds containing two or more substituents exhibited low MAO-B inhibition. In the kinetic study, the Ki values of S5 and S16 for MAO-B were 0.155 ± 0.050 and 0.721 ± 0.074 μM, respectively, with competitive reversible-type inhibition. Additionally, in the PAMPA, both lead compounds demonstrated blood–brain barrier penetration. Furthermore, stability was demonstrated by the 2V5Z-S5 complex by pi–pi stacking with Tyr398 and Tyr326. These results suggest that S5 and S16 are potent, reversible, selective MAO-B inhibitors that can be used as potential agents for the treatment of neurological disorders.

Introduction: Vorapaxar is an inhibitor of protease-activated receptor-1 (PAR1) and primarily blocks thrombin mediated platelet activation. There are discrepancies in the literature regarding whether vorapaxar alleviates ischemic outcomes and increases bleeding in patients with peripheral arterial disease (PAD). Purpose: The aim of this study is to evaluate the efficacy and safety of Vorapaxar in patients with PAD. Methods: A comprehensive literature search of Cochrane CENTRAL, PubMed, Ovid Medline, and Web of Science databases was conducted. Randomized controlled trials (RCTs) comparing Vorapaxar in patients with PAD were included. Primary efficacy outcome was defined as hospitalization for acute limb ischemia, while primary safety outcome was assessed for severe bleeding events according to GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) trial. Summary effect measures of the primary outcomes were obtained by pooling the data with an inverse variance–weighted random-effects model. Statistical analyses were performed with “meta” package in R (version 4.3.2). Results: Three unique RCTs involving 4825 patients were included in the analysis. Vorapaxar was associated with a significantly less rate of hospitalization for acute limb ischemia (Risk Ratio [RR] 0.57, 95% Confidence Interval (CI) 0.39 to 0.83, I 2 : 0%) and significantly less requirement of peripheral revascularization (RR 0.85, 95% CI 0.76 to 0.97, I 2 : 0%) compared to placebo. Furthermore, no significant differences were observed between Vorapaxar and placebo groups in fatal bleeding (RR 1.00, 95% CI 0.38 to 2.66, I 2 : 0), severe bleeding according to GUSTO trial (RR 1.38, 95% CI 0.84 to 2.27, I 2 : 0%), and lower extremity amputation (RR 0.53, 95% CI 0.17 to 1.67, I 2 : 0%). Conclusion: In patients with PAD, Vorapaxar significantly reduces hospitalizations due to acute limb ischemia and the need for peripheral revascularizations compared to placebo. However, it does not have a significant effect on the need for lower extremity amputations. In terms of safety, Vorapaxar does not lead to fatal or severe bleedings compared to placebo. Therefore, Vorapaxar should remain one of the treatment options for patients with PAD.

Abstract The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin‐angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II‐induced hypertension in rats. Sprague Dawley rats were subject to 4‐week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 μg/kg), AVE0991 (576 μg/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail‐cuff plethysmography at 1, 15, and 29 days post‐treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin‐A (CYP‐A), monocyte chemoattractant protein‐1 (MCP‐1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase‐2 and ‐9, NADPH oxidase‐4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP‐1 and CYP‐A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin‐converting enzyme‐2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II‐induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.

Aim: The aim of this study is to provide a qualitative and quantitative explanation of the structure activity relationships with pharmacophore analysis and Quantitative Structure Activity Relationship (QSAR) studies of the compounds synthesized as acetylcholinesterase enzyme inhibitor by our research group. Material and Methods: Maestro 11.9 (Schrodinger, New York) was used for pharmacophore model studies. Pharmacophore analysis was performed for all compounds showing acetylcholine esterase inhibitory effect. For QSAR studies, various physicochemical parameters of these compounds were calculated using GaussView 5.0 and ChemDraw 15.0 programs. Regression analysis was performed by using these parameters and QSAR equation was obtained. Results: All compounds overlapped and hypotheses generated. The most appropriate pharmacophore model was created by comparing the hypothesis and activity results of the compounds. The analyses were performed using 8 different parameters for all compounds. R2 value of equation was found 1. Conclusion: The pharmacophore analysis and the QSAR equation are applicable for all compounds synthesized as acetylcholinasterase inhibitory and containing pyridazinon-2-ylacetohydrazide structure. Also, the estimated IC50 values can be calculated before the compounds are synthesized using the QSAR equation.

The successful application of extrusion-based 3D-printed geopolymer mortars largely depends on precursor chemistry, activator composition, mixture proportions, and fresh-state behavior, which is highly sensitive to time-dependent structural build-up. This review examines the relationships among mix design, geopolymerization chemistry, rheological properties, and printability requirements for 3D-printed geopolymer mortars. Particular emphasis is placed on the effects of precursor type, alkaline activator characteristics, liquid-to-solid ratio, additives, and fibers on flowability, yield stress, viscosity, extrudability, buildability, shape retention, and interlayer bonding. The review further discusses how geopolymerization kinetics influence the evolution of fresh-state properties, the printable time window, and the transition from extrusion to structural stability. In addition, early-age performance is evaluated in terms of setting behavior, green strength development, and layer-interface integrity. Current challenges, including the lack of standardized test methods, limited comparability among published studies, and the complex coupling between material design and process parameters, are also highlighted. Finally, the review identifies key research gaps and proposes future directions for developing robust, printable, and sustainable geopolymer mortar systems for additive manufacturing in construction.

ABSTRACT Alamandine (ALA) is a heptapeptide discovered in 2013 within the renin‐angiotensin system (RAS). Given the high prevalence of diabetes mellitus (DM) in society and its comorbidities, especially renal failure, which significantly impairs the quality of life, this study aimed to investigate the protective effects of ALA against renal ischemia‐reperfusion (I/R) injury in diabetic rats. Our aim was to develop preventive therapies for DM and diabetic renal failure. Forty‐eight 3‐month‐old male Sprague‐Dawley rats were induced by administering a single intraperitoneal dose of 50 mg/kg of streptozotocin (STZ). Rats were divided into four groups. Right nephrectomy was performed through dorsolateral incisions in all rats, followed by occlusion of the left renal vessels for 1 h to induce ischemia. Reperfusion of the left kidney was initiated by removing the clamp and allowing 24 h of reperfusion. Histopathological examination of the kidney tissues revealed necrotic changes and tubular dilatation in the I/R group, which were significantly reduced in the ALA + I/R group. Immunohistochemical analysis showed increased immunoreactivity for interleukin‐6 (IL‐6) and caspase‐3 in the I/R group, whereas the ALA + I/R group demonstrated significantly lower immunoreactivity for these markers. Liver histology showed irregular hepatocyte cords and sinusoidal dilatation in the I/R group, whereas the ALA + I/R group exhibited a preserved classical lobular structure with reduced histopathological changes. Blood parameters, serum biochemistry, and tissue findings were also analyzed. Our study demonstrated the protective effects of ALA on renal and liver tissues against damage induced by renal I/R injury in a diabetic background. Moreover, ALA exhibited protective effects against liver damage resulting from renal I/R injury.