Antioxidant, antidiabetic effects and polyphenolic contents of propolis from Siirt, Turkey.

Propolis, a natural product collected by honeybees from various plant sources, has gained significant attention due to its diverse bioactive compounds and potential therapeutic properties. To further explore its contents and biological activities, this study aimed to analyze the phenolic compounds in Siirt propolis extracts obtained using different solvents, namely ethanol, water, and ethanol-water mixtures. The primary objective of this research was to investigate the phenolic profile, as well as the antidiabetic and antioxidant activities of the propolis extracts. Chemical profiling of extracts was performed using LC-MS/MS. The antioxidant potential of the propolis extracts was evaluated through free radical scavenging methods, including DPPH and ABTS assays. As a result of these analyses, propolis extracts showed moderate radical scavenging potential with 13.86%-35.72% for DPPH and 33.62%-62.50% for ABTS at a concentration of 30 µg mL-1, respectively. This radical scavenging potential of the extracts sheds light on its ability to combat oxidative stress, which is implicated in the development of diabetes, and its potential effects on cellular health. Additionally, the study assessed the antidiabetic properties of the propolis extracts by examining their inhibition effects on α-amylase and α-glycosidase enzymes. Extracts with high phenolic content showed a high inhibitory effect against α-glucosidase with an IC50 of 5.72 ± 0.83 µg mL-1. This research provided significant findings regarding the potential use of propolis in the treatment of diabetes and related metabolic disorders.

Explainable artificial intelligence in the design of selective carbonic anhydrase I-II inhibitors via molecular fingerprinting.

Inhibiting the enzymes carbonic anhydrase I (CA I) and carbonic anhydrase II (CA II) presents a potential avenue for addressing nervous system ailments such as glaucoma and Alzheimer's disease. Our study explored harnessing explainable artificial intelligence (XAI) to unveil the molecular traits inherent in CA I and CA II inhibitors. The PubChem molecular fingerprints of these inhibitors, sourced from the ChEMBL database, were subjected to detailed XAI analysis. The study encompassed training 10 regression models using IC50 values, and their efficacy was gauged using metrics including R2, RMSE, and time taken. The Decision Tree Regressor algorithm emerged as the optimal performer (R2: 0.93, RMSE: 0.43, time-taken: 0.07). Furthermore, the PFI method unveiled key molecular features for CA I inhibitors, notably PubChemFP432 (C(O)N) and PubChemFP6978 (C(O)O). The SHAP analysis highlighted the significance of attributes like PubChemFP539 (C(O)NCC), PubChemFP601 (C(O)OCC), and PubChemFP432 (C(O)N) in CA I inhibitiotable n. Likewise, features for CA II inhibitors encompassed PubChemFP528(C(O)OCCN), PubChemFP791 (C(O)OCCC), PubChemFP696 (C(O)OCCCC), PubChemFP335 (C(O)NCCN), PubChemFP580 (C(O)NCCCN), and PubChemFP180 (C(O)NCCC), identified through SHAP analysis. The sulfonamide group (S), aromatic ring (A), and hydrogen bonding group (H) exert a substantial impact on CA I and CA II enzyme activities and IC50 values through the XAI approach. These insights into the CA I and CA II inhibitors are poised to guide future drug discovery efforts, serving as a beacon for innovative therapeutic interventions.

Isolation of phenolic compounds from eco-friendly white bee propolis: Antioxidant, wound-healing, and anti-Alzheimer effects.

This study presents the first findings regarding extraction, isolation, enzyme inhibition, and antioxidant activity. The oral mucosal wound-healing process was investigated using propolis water extract (PWE) incubation with gingival fibroblast cells and concluded that propolis was effective on the oral mucosal wound-healing pattern compared to untreated controls. Additionally, phenolic compounds (fraxetin, apigenin, galangin, pinobanksin, chrysin, etc.) were isolated from propolis, and their chemical structures were elucidated using comprehensive spectroscopic methods. The antioxidant and anti-Alzheimer potential activities of PWE and some isolated compounds were screened and revealing their inhibitory effects on acetylcholinesterase (AChE) with IC50 values ranging from 0.45 ± 0.01 to 1.15 ± 0.03 mM, as well as remarkable free-radical scavenging and metal reduction capacities. The results suggest that these compounds and PWE can be used as therapeutic agents due to their antioxidant properties and inhibitory potential on AChE. It can also be used for therapeutic purposes since its wound-healing effect is promising.

Effect of fentanyl and remifentanil on neuron damage and oxidative stress during induction neurotoxicity.

Opioids can be used for medical and non-medical purposes. Chronic pain such as cancer, as well as the frequent use of such drugs in places such as operating rooms and intensive care units, and in non-medical areas like drug abuse the effects and side effects of these drugs need to be examined in more detail. For this purpose, the effects of fentanyl and remifentanil drugs on neuroinflammation, oxidative stress and cholinesterase metabolism were investigated. Neuron cells (CRL-10742) were used for the evaluation of the toxicity of fentanyl and remifentanil. MTT, PON1 activity and total thiol levels for its effect on oxidative stress, AChE and BChE activities for its effect on the cholinergic system, and TNF, IL-8 and IL-10 gene levels for its neuroinflammation effect were determined. The highest neurotoxic dose of fentanyl and remifentanil was determined as 10 µg/mL. It was observed that the rate of neuron cells in this dose has decreased by up to 61.80% and 56.89%, respectively. The IL-8 gene expression level in both opioids was down-regulated while IL 10 gene level was up-regulated in a dose-dependent manner compared to the control. In our results, the TNF gene expression level differs between the two opioids. In the fentanyl group, it was seen to be up-regulated in a dose-dependent manner compared to the control. Fentanyl and remifentanil showed an inhibitory effect against PON1, while remifentanil showed an increase in total thiol levels. PON1, BChE and total thiol activities showed similarity with MTT.

Phenolic Content Analysis of Two Species Belonging to the Lamiaceae Family: Antioxidant, Anticholinergic, and Antibacterial Activities.

The Lamiaceae family are utilized as ornamental, medicinal, and food supplements throughout the world. The current study focuses on a comparative analysis of the phenolic compositions and bioactivities (including antioxidant, anticholinergic, and antibacterial activities) of ethanolic extracts derived from the aerial parts of the two species (Lavandula stoechas L. and Thymus sipyleus Boiss). The presence of phenolic compounds and phytochemicals in the plant extracts was identified using the LC-MS/MS technique. The LC-MS/MS analysis revealed that vanillic acid (125,596.66 µg/L) was the most abundant phytochemical in L. stoechas. Kaempferol (8550.52 µg/L) was the most abundant substance in Thymus sipyleus. The assessment of the antioxidant efficacy of the species extracts was conducted using the DPPH (2.2-diphenyl-1-picryl-hydrazyl-hydrate), ABTS (2.2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)), Fe3+-Fe2+ reducing, and CUPRAC (Cu2+-Cu+ reducing) assays. The anticholinergic activity of the samples was determined using the acetylcholinesterase (AChE) inhibition assay. The results of antioxidant activity were higher in the T. sipyleus than in the L. stoechas ethanol extracts. The extracts of L. stoechas exhibited radical scavenging activity ranging from 15 to 18%, while T. sipyleus had activity effects ranging from 34% to 38%. The AChE inhibition potential for L. stoechas and T. sipyleus extracts as IC50 values were 0.221 ± 0.01 mg/mL and 0.067 ± 0.02 mg/mL, respectively. The antibacterial effects of the ethanolic extracts of these species against pathogenic bacteria isolates were determined using the MIC (minimal inhibitory concentration) method. These findings indicated that the extracts from L. stoechas and T. sipyleus possess the potential to be natural antioxidants in the realm of food preservation. Additionally, their antioxidant, anticholinergic, and antimicrobial properties suggest potential therapeutic utility in the management of certain diseases.

Design and Synthesis of Pyrazole Carboxamide Derivatives as Selective Cholinesterase and Carbonic Anhydrase Inhibitors: Molecular Docking and Biological Evaluation.

The present study focused on the synthesis and characterization of novel pyrazole carboxamide derivatives (SA1-12). The inhibitory effect of the compounds on cholinesterases (ChEs; AChE and BChE) and carbonic anhydrases (hCAs; hCA I and hCA II) isoenzymes were screened as in vitro. These series compounds have been identified as potential inhibitors with a KI values in the range of 10.69±1.27-70.87±8.11 nM for hCA I, 20.01±3.48-56.63±6.41 nM for hCA II, 6.60±0.62-14.15±1.09 nM for acetylcholinesterase (AChE) and 54.87±7.76-137.20 ±9.61 nM for butyrylcholinesterase (BChE). These compounds have a more effective inhibition effect when compared to the reference compounds. In addition, the potential binding positions of the compounds with high affinity for ChE and hCAs were demonstrated by in silico methods. The results of in silico and in vitro studies support each other. As a result of the present study, the compounds with high inhibitory activity for metabolic enzymes, such as ChE and hCA were designed. The compounds may be potential alternative agents used as selective ChE and hCA inhibitors in the treatment of Alzheimer's disease and glaucoma.

Evaluation of the relationship among gene expressions and enzyme activities with antioxidant role and presenilin 1 expression in Alzheimer's disease.

It is known that oxidative stress originating from reactive oxygen species plays a role in the pathogenesis of Alzheimer's disease. In this study, the role of antioxidant status associated with oxidative stress in Alzheimer's disease was investigated. Peripheral blood samples were obtained from 28 healthy individuals (as control) and 28 Alzheimer's patients who met the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria. Catalase, glutathione S-transferase and paraoxonase 1 enzyme activities in blood plasma and glutathione S-transferase enzyme activities in erythrocytes were determined by spectrophotometer. Catalase, glutathione S-transferase and presenilin 1 gene expressions in leukocytes were determined using qRT-PCR. Data were analysed with SPSS one-way anova, a LSD post hoc test at p < 0.05. The activity of each enzyme was significantly reduced in Alzheimer's patients compared to control. The catalase gene expression level did not change compared to the control. Glutathione S-transferase and presenilin 1 gene expression levels were increased compared to the control.

Paramagnetic characterization of fossil mollusc shells at eastern part of the old Konya lake: its importance for EPR dating.

Fossil mollusc shells are used for dating geological materials because they are well preserved throughout geological time. In this study, the radicals in the structure of fossil mollusc shells (Dreissena iconica, Valvata piscinalis, Bithynia tentaculate, Unio pictorum) collected from the Eastern Part of Old Konya Lake in Türkiye were investigated by EPR technique. For all fossil shells, microwave and temperature dependence of the signals were examined, and the signals suitable for dating are discussed. Characteristic features of intrinsic and impurity-related radicals were identified and the importance of paleontological evaluation of molluscs to get a reliable equivalent dose in EPR dating studies was emphasised.

Synthesis and Characterization of Novel 1,3-Diaryltriazene-Substituted Sulfaguanidine Derivatives as Selective Carbonic Anhydrase Inhibitors: Biological Evaluation, in Silico ADME/T and Molecular Docking Study.

Sulfonamide compounds known as human carbonic anhydrase (hCA) inhibitors are used in the treatment of many diseases such as epilepsy, antibacterial, glaucoma, various diseases. 1,3-diaryl-substituted triazenes and sulfaguanidine are used for therapeutic purposes in many drug structures. Based on these two groups, the synthesis of new compounds is important. In the present study, the novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives (SG1-13) were synthesized and fully characterized by spectroscopic and analytic methods. Inhibitory effect of these compounds on the hCA I and hCA II was screened as in vitro. All the series of synthesized compounds have been identified as potential hCA isoenzymes inhibitory with KI values in the range of 6.44±0.74-86.85±7.01 nM for hCA I and with KI values in the range of 8.16±0.40-77.29±9.56 nM for hCA II. Moreover, the new series of compounds showed a more effective inhibition effect than the acetazolamide used as a reference. The possible binding positions of the compounds with a binding affinity to the hCA I and hCA II was demonstrated by in silico studies. In conclusion, compounds with varying degrees of affinity for hCA isoenzymes have been designed and as selective hCA inhibitors. These compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.

CVD22: Explainable artificial intelligence determination of the relationship of troponin to D-Dimer, mortality, and CK-MB in COVID-19 patients.

BACKGROUND AND PURPOSE: COVID-19, which emerged in Wuhan (China), is one of the deadliest and fastest-spreading pandemics as of the end of 2019. According to the World Health Organization (WHO), there are more than 100 million infectious cases worldwide. Therefore, research models are crucial for managing the pandemic scenario. However, because the behavior of this epidemic is so complex and difficult to understand, an effective model must not only produce accurate predictive results but must also have a clear explanation that enables human experts to act proactively. For this reason, an innovative study has been planned to diagnose Troponin levels in the COVID-19 process with explainable white box algorithms to reach a clear explanation. METHODS: Using the pandemic data provided by Erzurum Training and Research Hospital (decision number: 2022/13-145), an interpretable explanation of Troponin data was provided in the COVID-19 process with SHApley Additive exPlanations (SHAP) algorithms. Five machine learning (ML) algorithms were developed. Model performances were determined based on training, test accuracies, precision, F1-score, recall, and AUC (Area Under the Curve) values. Feature importance was estimated according to Shapley values by applying the SHApley Additive exPlanations (SHAP) method to the model with high accuracy. The model created with Streamlit v.3.9 was integrated into the interface with the name CVD22. RESULTS: Among the five-machine learning (ML) models created with pandemic data, the best model was selected with the values of 1.0, 0.83, 0.86, 0.83, 0.80, and 0.91 in train and test accuracy, precision, F1-score, recall, and AUC values, respectively. As a result of feature selection and SHApley Additive exPlanations (SHAP) algorithms applied to the XGBoost model, it was determined that DDimer mean, mortality, CKMB (creatine kinase myocardial band), and Glucose were the features with the highest importance over the model estimation. CONCLUSIONS: Recent advances in new explainable artificial intelligence (XAI) models have successfully made it possible to predict the future using large historical datasets. Therefore, throughout the ongoing pandemic, CVD22 (https://cvd22covid.streamlitapp.com/) can be used as a guide to help authorities or medical professionals make the best decisions quickly.

Novel bis-ureido-substituted sulfaguanidines and sulfisoxazoles as carbonic anhydrase and acetylcholinesterase inhibitors.

To discover alternative substances to compounds used to treat many diseases, especially treating Alzheimer's disease (AD) and Parkinson's disease targeting carbonic anhydrase (hCA) and acetylcholinesterase (AChE) enzymes, is important. For this purpose, a series of novel bis-ureido-substituted sulfaguanidine (SG1-4) and sulfisoxazole (SO1-4) derivatives were synthesized, and their inhibitory capacities were screened against hCA isoenzymes (hCA I and II) and AChE. Possible binding mechanisms of inhibitors to the active site were elucidated by in silico studies, and the results were supported by in vitro results. Moreover, the percent radical scavenging capacities of the derivatives were also evaluated. The derivatives (SG1-4 and SO1-4) were more effective against hCAs compared to standard drug acetazolamide (KI values of 98.28-439.17 nM for hCA I and II, respectively) and exhibited the highest inhibition with the KIs in the ranges of 2.54 ± 0.50-41.02 ± 7.52 nM for hCA I, 11.20 ± 2.97-67.14 ± 13.58 nM for hCA II, and 257.60 ± 27.84-442.60 ± 52.13 nM for AChE. Also, compounds SG1 and SO1 also showed ABTS radical scavenging activity at the rate of 70% and 78%, respectively. These results will contribute to the literature for the rational design and synthesis of new potent and selective inhibitors targeting hCAs and AChE with multifunctional effects such as radical scavenging as well as inhibition. This study focused on the synthesis and inhibitory effects of bis-ureido-substituted sulfaguanidine (SG1-4) and sulfisoxazole (SO1-4) derivatives against human hCA I and II isoforms and AChE. In order to test synthesized derivatives' free radical scavenging potentials were the DPPH and ABTS assays. In silico studies elucidated possible binding mechanisms of inhibitors to the active site.

Anticholinergic, Antioxidant, and Antibacterial Properties of Vitex Agnus-Castus L. Seed Extract: Assessment of Its Phenolic Content by LC/MS/MS.

In this current study, Vitex agnus-castus seed ethanol extracts were analyzed for their phytochemical component content, anticholinergic and antioxidant activities, and antibacterial properties. The phenolic compound composition of these seeds was determined by using LC/MS/MS. Antioxidant activity of the seeds was examined by the DPPH, ABTS, Fe3+ -Fe2+ reducing, and CUPRAC. Also, the anticholinergic activity was measured by the inhibition of acetylcholinesterase (AChE). The antibacterial activity was performed by disc diffusion and minimum inhibitory concentration methods. The main phenolic compound was vanillic acid (22812.05 µg/L) and followed by luteolin, fumaric acid, quercetin, caffeic acid, 4-hydroxybenzoic acid, salicylic acid, kaempferol, butein, ellagic acid, resveratrol, catechin hydrate, phloridzin dehydrate, naringenin, respectively. The DPPH free radical scavenging value of ethanol extract of plant seeds was 9.41 %, while the ABTS radical scavenging activity was determined as 12.66 %. The ethanol extract of the seeds exhibited antibacterial activity on Escherichia coli, Staphylococcus aureus, and Salmonella Typhimurium, differently. S. aureus was found to be more susceptible to the extract than other bacteria. Also, the inhibition effect of seed ethanolic extract on the AChE with IC50 values were 36.34±5.6 µg/mL. From the results, V. agnus-castus seed can be suggested as a promising natural antioxidant and antibacterial candidate for the preservation of foods.

Oxidative Stress and Changes of Important Metabolic Gene Expressions as a Potential Biomarker in the Diagnosis of Atherosclerosis in Leukocytes.

INTRODUCTION: Presenilin 1 (PSEN1), catalase (CAT), glutathione-S-transferase (GST) and paraoxonase 1 (PON1) play a vital role in prediction, diagnosis and therapy of metabolic disorders. METHODS: Metabolic enzyme activities and lipid peroxidation in serum of cerebrovascular diseases (CVD) and coronary artery diseases were measured by spectrophotometric methods. mRNA was isolated from leukocytes of the patient group and healthy adult patients. Quantitative gene expression of PSEN1, CAT and GST mRNA was identified by quantitative real-time polymerase chain reaction (qPCR). RESULTS: The PSEN1, CAT and GST expression in patients showed significant differences compared to the control group. PSEN1 expression in leukocytes was significantly about twice as high as that of the control group in patients with CVD. The GST, CAT and PON1 activity showed significant differences in patient groups compared to the control group. CONCLUSION: The mRNA expression levels can be used as a potential biomarker in the diagnosis of atherosclerosis that occurs as a result of the metabolic disorder. In atherosclerotic patients, antioxidant status is independently related to an increased risk of cardiovascular events. Antioxidant activities and mRNA expressions may have predictive value, as well as available risk factors.

Phenolic Profile and Antioxidant, Anticholinergic, and Antibacterial Properties of Corn Tassel.

Corn tassel (CT) is a waste part of the corn plant. It is a good co-product and rich in terms of bioactive compounds and phytochemicals. This research tried to show the phenolic profile, antioxidants, anticholinergic activities, and antibacterial properties of CT ethanol extract. The phenolic content analysis of the CT was determined quantitatively by LC-MS/MS, and the antioxidant capacity was measured using ABTS, DPPH, Cu2+-Cu+, and Fe3+-Fe2+ reducing methods. The anticholinergic measurements of CT were detected by inhibition of acetylcholinesterase (AChE). The antibacterial activity was determined by MIC and disc diffusion methods. Many phenolic compounds such as vanillic acid, caffeic acid, fumaric acid, acetohydroxamic acid, butein, myricetin, resveratrol, catechin hydrate, and 4-hydroxybenzoic acid were detected in ethanol extract of CT. The obtained plant ethanol extract had a 7.04% DPPH value, while it showed ABTS activity at 9.45%. Moreover, it had a 0.10 mg/mL inhibition effect on the AChE in terms of IC50 values. The ethanol extract of the CT had an antibacterial property on the investigated bacteria at different ratios. In conclusion, this research aims to consider CT as a source of phenolic compounds and to reveal its bioactive properties and its effects on the treatment of some diseases.

An innovative approach to lifelong delayed ejaculation: does attachment style play a role?

PURPOSE: To examine whether there is a correlation between attachment styles, which is a developmental psychology theory, and lifelong DE. METHODS: The research was planned as prospective, multi-centric and cross-sectional study. Thirty patients who were consecutively admitted to the urology outpatient clinic and diagnosed with lifelong DE and 30 age-matched healthy controls were included in the study. All participants gave a detailed medical history and underwent a complete physical examination, and their laboratory and endocrine (prolactin and testosterone) results were evaluated. Additionally, all patients had to fill out socio-demographic information form, the Experiences in Close Relationships-Revised (ECR-R) Questionnaire, Arizona Sexual Experiences Scale (ASEX), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI). RESULTS: The mean age of the DE patients was 33.5 ± 7.5 years. In the DE group, insecure attachment (both anxious and avoidant attachment), anxiety and depression scores were found to be significantly higher (p < 0.001, effect size medium or large) than the control group. Ejaculation times (both for vaginal intercourse and masturbation) were correlated with both insecure (anxious and avoidant) attachment types, as well as their anxiety and depression scores (p < 0.001). The ASEX satisfaction, ejaculation and total scores were found to be higher in DE patients (higher scores indicating greater sexual dysfunction) than in the control group. CONCLUSION: The large and significant relationships found between lifelong DE and attachment insecurities point to childhood developmental processes. The findings may help us better understand lifelong DE. There is a need for further extensive research on this subject.

The Evaluation of Thiol/Disulfide Homeostasis and Oxidative DNA Damage in Patients with Obsessive Compulsive Disorder.

Objective: In this study, we aimed to examine thiol/disulfide homeostasis and oxidative DNA damage in patients with OCD and compare them with healthy controls. Methods: Thirty-five patients previously diagnosed with OCD in Van Yuzuncu Yil University Department of Psychiatry and thirty-three healthy volunteers were included in the study. The severity of the symptoms was measured using the Yale-Brown Obsessive-Compulsive Scale. Five ml of blood samples were taken from the patient and control groups. The samples were stored at appropriate conditions until use. Leukocyte DNA was isolated and the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and deoxyguanosine were detected to assess the oxidative DNA damage. The level of oxidative DNA damage was expressed as 8-OHdG/106dG. Total thiol/native thiol levels were measured for thiol/disulfide homeostasis. The level of disulfide was determined by subtracting the native thiol value from the total thiol value and the result was divided by two. Results: were given as percentages. Results: The total and native thiol levels in patients with OCD were significantly lower, and the disulfide levels were significantly higher in patients with OCD than healthy control subjects. In addition, 8-OHdG, an indicator of DNA damage, was significantly lower in the control group compared to the patient group. Conclusion: Increased levels of disulfide/native thiol and disulfide/total thiol in patients with OCD show that levels of oxidative stress were elevated and therefore, higher 8-OHdG levels in patients with OCD is a marker of oxidative DNA damage.

The mediating effect of attachment insecurity on circadian consequences of childhood trauma.

Circadian preferences have been associated with mental health as well as social and physical health in recent years. However, factors associated with circadian preferences have not been fully elucidated. The main aim of this study is to investigate the associations of childhood trauma and attachment styles with circadian preferences. A total of 673 participants were evaluated using the Morningness-Eveningness Questionnaire (MEQ), the Childhood Trauma Questionnaire 28 (CTQ-28), and the Experiences in Close Relationships-Revised (ECR-R) questionnaire. The results indicated that 14.9% (n = 100) of the participants were morning type, 20.6% (n = 139) were evening type, and 64.5% (n = 434) were intermediate type. Both childhood trauma and attachment-related anxiety/avoidance scores were associated with being evening type (p < .01). Moreover, attachment-related anxiety and avoidance fully mediated the association between childhood trauma and circadian preferences. The present study showed that attachment styles might be associated with circadian preferences. Further studies are needed to replicate these results and to infer explanatory mechanisms for these cross-sectional associations.

Vortioxetine-Induced Amenorrhea: A Case Report.

BACKGROUND: Vortioxetine is a novel multimodal antidepressant for the treatment of major depressive disorders and is widely used in clinical practice. Vortioxetine has a safe profile. However, there are case reports of other adverse effects in the literature. In this article, a case of amenorrhea due to vortioxetine is presented. CASE: The patient is 36 years old, married, female, and is an anesthesiologist. She applied to the psychiatric outpatient clinic with symptoms of major depression. Vortioxetine was initiated at 10 mg/d and then gradually increased to 20 mg/d. She had regular menstruation until now. However, she did not menstruate after taking vortioxetine. The patient used vortioxetine for 3 months and never had a period. Pregnancy test and other tests to investigate organic etiology were normal. Two weeks after discontinuation of vortioxetine, the patient had a menstrual period. CONCLUSIONS: Further research is needed on the relationship and possible mechanisms between vortioxetine and amenorrhea.

AChE mRNA expression as a possible novel biomarker for the diagnosis of coronary artery disease and Alzheimer's disease, and its association with oxidative stress.

Oxidative metabolic reactions and their by products have played a role in coronary artery disease (CAD) and Alzheimer's disease (AD) pathogenesis. This study was carried out on 28 patients with AD, 21 patients with CAD, and 28 healthy as control. Oxidative stress biomarkers and acetylcholinesterase (AChE) activity were assayed in plasma. mRNA expression of AChE was investigated in leukocytes of patients with CAD and AD. Thus, Alzheimer's and coronary artery patients were observed that the protein carbonyl levels and mRNA expression of AChE were increased (p<.05, p<.01, respectively). The plasma total thiol levels were decreased compared to the control group (p<.05). There was a significant relationship between amyloid ß (Aß) accumulation and oxidative stress, cholinergic gene expression. AChE gene expression and protein oxidation were increased in patients with AD and CAD. These results suggest that increased release of AChE from cells produces neurotoxic ß-amyloid plaques and may cause neurodegenerative diseases.

Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors.

The underlying cause of many metabolic diseases is abnormal changes in enzyme activity in metabolism. Inhibition of metabolic enzymes such as cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) and α-glucosidase (α-GLY) is one of the accepted approaches in the treatment of Alzheimer's disease (AD) and diabetes mellitus (DM). Here we reported an investigation of a new series of novel ureido-substituted derivatives with sulfamethazine backbone (2a-f) for the inhibition of AChE, BChE, and α-GLY. All the derivatives demonstrated activity in nanomolar levels as AChE, BChE, and α-GLY inhibitors with KI values in the range of 56.07-204.95 nM, 38.05-147.04 nM, and 12.80-79.22 nM, respectively. Among the many strong N-(4,6-dimethylpyrimidin-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamide derivatives (2a-f) detected against ChEs, compound 2c, the 4-fluorophenylureido derivative, demonstrated the most potent inhibition profile towards AChE and BChE. A comprehensive ligand/receptor interaction prediction was performed in silico for the three metabolic enzymes providing molecular docking investigation using Glide XP, MM-GBSA, and ADME-Tox modules. The present research reinforces the rationale behind utilizing inhibitors with sulfamethazine backbone as innovative anticholinergic and antidiabetic agents with a new mechanism of action, submitting propositions for the rational design and synthesis of novel strong inhibitors targeting ChEs and α-GLY.Communicated by Ramaswamy H. Sarma.