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The present work examines the relationship between aerial spraying and its health impacts on the population living in the banana production areas of Ecuador (the rural sectors of the cantons Milagro and Naranjito, Guayas Province). Objectives: the objectives of this study are to obtain information on sanitation, basic services, and environmental rationality and to interpret the low levels of cholinesterase and prevalent diseases among the population. Methods: the methodology involved a face-to-face questionnaire, the formal authorization of an informed consent document, and venipuncture for cholinesterase tests. The information was processed in the EPI–INFO system 7.2 (statistical software for professionals and researchers dedicated to public health), with the certification of protocols issued by the Bioethics Committee of the Kennedy Hospital Clinic of Ecuador. Results: the results showed that 89.5% of inhabitants do not have access to drinking water, 92.5% do not have a sewage disposal service, 97.50% experience aerial spraying at their homes or workplaces, and 57% have low cholinesterase levels. Additionally, several gastrointestinal, respiratory, neurological, dermatological, and reproductive disorders were detected among the inhabitants. Conclusions: we found that companies in the banana sector have not implemented corporate social responsibility measures. For example, no blood tests are conducted to monitor cholinesterase levels or to track hereditary disorders. Moreover, entities such as the Ministry of Public Health have not taken action to serve this at-risk population. [ABSTRACT FROM AUTHOR]

Six novel brominated bis-pyridinium oximes were designed and synthesized to increase their nucleophilicity and reactivation ability of phosphorylated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Their pKa was valuably found lower to parent non-halogenated oximes. Stability tests showed that novel brominated oximes were stable in water, but the stability of di-brominated oximes was decreased in buffer solution and their degradation products were prepared and characterized. The reactivation screening of brominated oximes was tested on AChE and BChE inhibited by organophosphorus surrogates. Two mono-brominated oximes reactivated AChE comparably to non-halogenated analogues, which was further confirmed by reactivation kinetics. The acute toxicity of two selected brominated oximes was similar to commercially available oxime reactivators and the most promising brominated oxime was tested in vivo on sarin- and VX-poisoned rats. This brominated oxime showed interesting CNS distribution and significant reactivation effectiveness in blood. The same oxime resulted with the best protective index for VX-poisoned rats. [ABSTRACT FROM AUTHOR]

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Background Adolescents living in agricultural communities may be at risk for the adverse effects of pesticide exposure because they are involved in agriculture either as a career or to support their families. Objective The purpose of this study was to investigate the association of farm activities related to pesticide exposure on blood cholinesterase (ChE) levels among adolescents from farming families in the north of Thailand. Material and Methods This cross-sectional study included 336 adolescents aged 12-19 years from farming families in Chiang Dao District, Chiang Mai Province. Data on pesticide exposure was collected using a questionnaire, and blood ChE activity was assessed using a ChE reactive paper test kit via fingerstick blood sampling. Results Overall, 51.2% of participants had abnormal blood ChE levels. Univariable logistic regression analysis revealed that pesticide-related activities on farms associated with abnormal ChE levels were mixing/spraying (OR=10.54; 95%CI=4.63-23.99), assisting or working in areas with pesticide application (OR=5.54; 95%CI=3.45-8.89), and harvesting (OR=3.70; 95%CI=2.35-5.82). In a multivariable model (Nagelkerke R2=0.374), mixing/spraying (OR=4.90; 95%CI=2.03-11.83) and assisting or working in areas with pesticide application (OR=2.61; 95%CI=1.49-4.57) were significantly associated with abnormal ChE levels, but harvesting (OR=1.48; 95%CI=0.84-2.61) was not significant after adjusting for sex, age in years, and entering or walking through a farm. Conclusions The findings indicated that Thai adolescents living in farming families are at risk of pesticide exposure, particularly those involved in agricultural activities such as pesticide applicators. An intervention and measure to raise awareness and reduce the risk of pesticide exposure in adolescents is required.

Abstract Objective This study is to evaluate the association between preoperative cholinesterase levels and all-cause mortality in geriatric hip fractures. Methods Elderly patients with hip fractures were screened between Jan 2015 and Sep 2019. Demographic and clinical characteristics of patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between preoperative cholinesterase levels and mortality in these patients. Analyses were performed using EmpowerStats and the R software. Results Two thousand three hundred eighty-seven patients were included in this study. The mean follow-up period was 37.64 months. Seven hundred eighty-seven (33.0%) patients died due to all-cause mortality. Preoperative cholinesterase levels were 5910 ± 1700 U/L. Linear multivariate Cox regression models showed that preoperative cholinesterase level was associated with mortality (HR = 0.83, 95% CI: 0.78–0.88), P 5940 U/L, the mortality was no longer decreased with the rise of cholinesterase (HR = 1.01, 95%CI: 0.91–1.11, P = 0.9157). We found the nonlinear association was very stable in the propensity score-matching sensitive analysis. Conclusions Preoperative cholinesterase levels were nonlinearly associated with mortality in elderly hip fractures, and cholinesterase was a risk indicator of all-cause mortality. Trial registration This study is registered on the website of the Chinese Clinical Trial Registry (ChiCTR: ChiCTR2200057323) (08/03/2022).

Abstract Aim Serum cholinesterase (ChE) levels are considered to reflect nutritional status. Although ChE has been well documented as a prognostic factor for some cancers, no clear consensus on its use for colorectal cancer (CRC) has been reached. The aim of this study was to investigate the relationship between preoperative serum ChE and postoperative long‐term prognosis in CRC patients. Methods A total of 1053 CRC patients who underwent curative surgery were included in this study. The correlations between the preoperative ChE value and overall survival (OS) or cancer‐specific survival (CSS) were assessed. By dividing patients into two groups according to their ChE value, OS and CSS were compared between the groups. Results Multivariate analysis revealed that the continuous ChE value was a significant predictor of OS (hazard ratio, 0.996; 95% CI, 0.993–0.998; p = 0.002) and CSS (hazard ratio, 0.994; 95% CI, 0.991–0.998; p = 0.001), independent of other variables. The low‐ChE (≤234 U/L) group had a significantly poorer prognosis than the high‐ChE (>234 U/L) group for both OS (5‐year OS for low ChE and high ChE: 79.8% and 93.3%, respectively; p

A novel series of ligustrazine derivatives was designed, synthesized, and evaluated as acetylcholinesterase (AChE) and butylcholinesterase (BuChE) inhibitors for the treatment of Alzheimer's disease (AD). In vitro studies displayed that some of the synthesized compounds revealed promising AChE and BuChE inhibitory effects. Particularly, compounds E12 and E27, indicated highly AChE inhibitory activity with IC50 values of 1.85 μM and 0.98 μM, respectively and showed noteworthy protective effects against on glutamate-induced SH-SY5Y cells damage at 1 μM and 10 μM concentrations. Furthermore, molecular simulation docking elucidates compounds E12 and E27 interacting with residues in the binding site of AChE (PDB code: 4EY7) and BuChE (PDB code: 1P0I), emphasizing the protein residues that participate in the main interactions with the two targets. Taken together, these results revealed that compounds E12 and E27 might be potential lead compounds for further structure optimization in the drug-discovery process against AD. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between serum cholinesterase (ChE) levels and islet α-cell dysfunction in patients with type 2 diabetes mellitus (T2DM).Methods This was a cross-sectional study. T2DM patients were recruited for this study at the Department of Endocrinology of Nantong First People′s Hospital between July 2022 and December 2023. Anthropological parameters, including age, sex, blood pressure and body mass index (BMI) were collected. Duration of diabetes and the use of medications, including hypoglycemic agents and statins, were documented. Serum ChE, liver function indices, blood lipids, serum creatinine (SCr), uric acid (UA), cystatin C (CysC) and glycated hemoglobin A 1c (HbA 1c) were measured in all patients. 75 g oral glucose tolerance test was also performed to simultaneously detect glucose, insulin and glucagon (GLA) at fasting (0 min), 30, 60, 120 and 180 min. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Overall glucose levels after glucose load were evaluated by the area under the curve (AUC glu). The indices of islet α-cell function included GLA 0, GLA 30, GLA 60, GLA 120 and overall glucagon levels after glucose load (area under the curve of glucagon, AUC gla). All patients were divided into three subgroups according to the tertiles of serum ChE levels: group T 1 (range of ChE, 3.71-7.84 kU/L, 167 patients), group T 2 (range of ChE, 7.85-9.44 kU/L, 168 patients) and group T 3 (range of ChE, 9.45-17.94 kU/L, 167 patients). One-way analysis of variance (ANOVA) with linear polynomial contrasts, the Jonckheere-Terpstra test, or the χ ² test with linear-by-linear association was used to analyze the trend of clinical data between subgroups. Pearson ′s correlation analysis was used to analyze the relationship between ChE and islet α-cell function, and multivariate linear regression analysis was used to analyze whether ChE was an independent factor for islet α-cell function. Results A total of 502 eligible T2DM patients were recruited. From T 1 to T 2 to T 3 of ChE, BMI, HOMA-IR, GLA 0, GLA 30, GLA 60, GLA 120 and AUC gla gradually increased ( P for trend<0.001), but HbA 1c did not. Pearson ′s correlation analysis revealed that the serum ChE levels were significantly correlated with GLA 0, GLA 30, GLA 60, GLA 120 and AUC gla ( r=0.264, 0.230, 0.217, 0.229 and 0.245, respectively; P<0.001). After adjusting for age, sex, BMI, blood pressure, diabetes duration, hypoglycemic agents, statins, liver function indices, blood lipids, UA, SCr, CysC, HbA 1c, AUC glu, HOMA-IR and other clinical variables via multivariate linear regression, serum ChE levels were independently associated with GLA 0 (β=0.196, t=4.333, P<0.001), GLA 30 (β=0.188, t=4.309, P<0.001), GLA 60 (β=0.175, t=3.936, P<0.001), GLA 120 (β=0.186, t=4.195, P<0.001) and AUC gla (β=0.199, t=4.525, P<0.001). Conclusion ncreased serum ChE levels were associated with increased fasting glucagon and postprandial glucagon levels in patients with T2DM and could be considered an independent risk factor for islet α-cell dysfunction. [ABSTRACT FROM AUTHOR]

This study aimed to provide scientific data on the anti-Alzheimer's disease (AD) effects of phenolic compounds from Drynariae Rhizoma (DR) extract using a multi-component approach. Screening of DR extracts, fractions, and the ten phenolic compounds isolated from DR against the key AD-related enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and monoamine oxidase-B (MAO-B) confirmed their significant inhibitory activities. The DR extract was confirmed to have BACE1-inhibitory activity, and the ethyl acetate and butanol fractions were found to inhibit all AD-related enzymes, including BACE1, AChE, BChE, and MAO-B. Among the isolated phenolic compounds, compounds (2) caffeic acid 4-O-β-D-glucopyranoside, (6) kaempferol 3-O-rhamnoside 7-O-glucoside, (7) kaempferol 3-o-b-d-glucopyranoside-7-o-a-L-arabinofuranoside, (8) neoeriocitrin, (9) naringin, and (10) hesperidin significantly suppressed AD-related enzymes. Notably, compounds 2 and 8 reduced soluble Amyloid Precursor Protein β (sAPPβ) and β-secretase expression by over 45% at a concentration of 1.0 μM. In the thioflavin T assay, compounds 6 and 7 decreased Aβ aggregation by approximately 40% and 80%, respectively, and degraded preformed Aβ aggregates. This study provides robust evidence regarding the potential of DR as a natural therapeutic agent for AD, highlighting specific compounds that may contribute to its efficacy. [ABSTRACT FROM AUTHOR]

In an effort to develop new and effective therapeutic agents for Alzheimer's disease, a series of hydrazone derivatives bearing piperidine rings have been designed and synthesized. The chemical structures of the compounds were characterized by various spectroscopic techniques. In vitro antioxidant and cholinesterase activities of the compounds were evaluated. Among the compounds, N12 exhibited the most antioxidant activity in all methods (CUPRAC, FRAP, DPPH, ABTS). In vitro acetylcholinesterase (AChE) activity results of the compounds showed good IC50 values between 14.124 ± 0.084 and 49.680 ± 0.110 µM were obtained (IC50 = 38.842 ± 0.053 µM for Donepezil). Among the compounds, N7 and N6 are much more effective derivatives than the standard compound donepezil with IC50 values of 14.124 ± 0.084 and 17.968 ± 0.072 µM, respectively. In vitro, butyrylcholinesterase (BChE) inhibition values of the compounds were between 13.505 ± 0.025 and 52.230 ± 0.027 μm. Among the compounds, N6 has the highest BChE inhibition with an IC50 value of 13.505 μm in the series. The cytotoxicity and AChE inhibitory activity of the compounds on SH‐SY5Y cell lines were also evaluated. Kinetic studies were also performed to determine the behavior of the compounds as competitive or noncompetitive inhibitors. The binding modes of N6, which was determined to be highly effective according to in vitro analyses, with AChE and BChE were investigated using molecular docking studies, and the stability of the complexes was determined by molecular dynamics simulations. These findings indicated that AChE and BChE enzymes maintained their overall structural stability and compactness during interactions with compound N6. [ABSTRACT FROM AUTHOR]

Cholinesterases are well‐known and widely studied enzymes crucial to human health and involved in neurology, Alzheimer's, and lipid metabolism. The protonation pattern of active sites of cholinesterases influences all the chemical processes within, including reaction, covalent inhibition by nerve agents, and reactivation. Despite its significance, our comprehension of the fine structure of cholinesterases remains limited. In this study, we employed enhanced‐sampling quantum‐mechanical/molecular‐mechanical calculations to show that cholinesterases predominantly operate as dynamic mixtures of two protonation states. The proton transfer between two non‐catalytic glutamate residues follows the Grotthuss mechanism facilitated by a mediator water molecule. We show that this uncovered complexity of active sites presents a challenge for classical molecular dynamics simulations and calls for special treatment. The calculated proton transfer barrier of 1.65 kcal/mol initiates a discussion on the potential existence of two coupled low‐barrier hydrogen bonds in the inhibited form of butyrylcholinesterase. These findings expand our understanding of structural features expressed by highly evolved enzymes and guide future advances in cholinesterase‐related protein and drug design studies. [ABSTRACT FROM AUTHOR]

The relationship between amyloid beta (Aβ) and oxidative stress (OS), both prominent factors in Alzheimer's disease-related neural degeneration, is deeply interconnected. The cleavage of the extracellular domain of Amyloid precursor protein (APP) and phosphorylating different substrates, respectively, the β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) and Glycogen synthase kinase-3-beta (GSK-3β) enzymes initiate the synthesis of Aβ, which causes cognitive deficits in AD. This study aimed to explore the protective potential of Coenzyme Q10 (CoQ10). It also sought to uncover any synergistic effects when combined with donepezil, an acetylcholinesterase inhibitor, in treating Alzheimer's disease in male albino rats, focusing on the modulation of the BACE-1/GSK-3β pathway. The experiment involved 70 rats categorized into different groups: control, donepezil alone, CoQ10 alone, AD-model, donepezil co-treatment, CoQ10 co-treatment, and CoQ10 + donepezil combination. Various assessments, such as cholinesterase activity, oxidative stress, serum iron profile, Brain Derived Neurotrophic Factor (BDNF), Tau protein, β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), phosphatase and tensin homolog (Pten), and Glycogen synthase kinase-3-beta (GSK-3β), were conducted on behavioral and biochemical aspects. CoQ10 treatment demonstrated memory improvement, enhanced locomotion, and increased neuronal differentiation, mainly through the inhibition of the dual BACE-1/GSK-3β. These findings were substantiated by histological and immunohistological examinations of the hippocampus. Highlights Alzheimer's disease (AD) led to the alteration of BACE-1/GSK-3β. Coenzyme Q10 (CoQ10) alleviated D-Gal and AlCl3-induced passive avoidance memory deficits in rats. CoQ10 counteracts Alzheimer's disease by inhibiting acetylcholine esterase. CoQ10 significantly increases levels of BDNF and diminishes Tau burden. CoQ10 acts as a dual BACE1/GSK3β inhibitor. The combination of CoQ10 treatment and donepezil demonstrated potential as a therapeutic approach. [ABSTRACT FROM AUTHOR]

Objective: This study is to evaluate the association between preoperative cholinesterase levels and all-cause mortality in geriatric hip fractures. Methods: Elderly patients with hip fractures were screened between Jan 2015 and Sep 2019. Demographic and clinical characteristics of patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between preoperative cholinesterase levels and mortality in these patients. Analyses were performed using EmpowerStats and the R software. Results: Two thousand three hundred eighty-seven patients were included in this study. The mean follow-up period was 37.64 months. Seven hundred eighty-seven (33.0%) patients died due to all-cause mortality. Preoperative cholinesterase levels were 5910 ± 1700 U/L. Linear multivariate Cox regression models showed that preoperative cholinesterase level was associated with mortality (HR = 0.83, 95% CI: 0.78–0.88), P < 0.0001) for every 1000 U/L. However, the linear association was unstable, and nonlinearity was identified. A cholinesterase concentration of 5940 U/L was an inflection point. When preoperative cholinesterase level < 5940 U/L, the mortality decreased by 28% for every 1000 U/L increase in cholinesterase (HR = 0.72, 95%CI: 0.66–0.79, P < 0.0001). When cholinesterase was > 5940 U/L, the mortality was no longer decreased with the rise of cholinesterase (HR = 1.01, 95%CI: 0.91–1.11, P = 0.9157). We found the nonlinear association was very stable in the propensity score-matching sensitive analysis. Conclusions: Preoperative cholinesterase levels were nonlinearly associated with mortality in elderly hip fractures, and cholinesterase was a risk indicator of all-cause mortality. Trial registration: This study is registered on the website of the Chinese Clinical Trial Registry (ChiCTR: ChiCTR2200057323) (08/03/2022). [ABSTRACT FROM AUTHOR]

Mining of organophosphorous (OPs)-degrading bacterial enzymes in collections of known bacterial strains and in natural biotopes are important research fields that lead to the isolation of novel OP-degrading enzymes. Then, implementation of strategies and methods of protein engineering and nanobiotechnology allow large-scale production of enzymes, displaying improved catalytic properties for medical uses and protection of the environment. For medical applications, the enzyme formulations must be stable in the bloodstream and upon storage and not susceptible to induce iatrogenic effects. This, in particular, includes the nanoencapsulation of bioscavengers of bacterial origin. In the application field of bioremediation, these enzymes play a crucial role in environmental cleanup by initiating the degradation of OPs, such as pesticides, in contaminated environments. In microbial cell configuration, these enzymes can break down chemical bonds of OPs and usually convert them into less toxic metabolites through a biotransformation process or contribute to their complete mineralization. In their purified state, they exhibit higher pollutant degradation efficiencies and the ability to operate under different environmental conditions. Thus, this review provides a clear overview of the current knowledge about applications of OP-reacting enzymes. It presents research works focusing on the use of these enzymes in various bioremediation strategies to mitigate environmental pollution and in medicine as alternative therapeutic means against OP poisoning. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract that affects millions of people worldwide. Since acetylcholine is one of the effective factors in reducing inflammation and considering the benefits of using saliva, in this study, the amount of cholinesterase activity in saliva and serum in patients with IBD and healthy people was investigated. Materials and Methods: Thirty patients with IBD who were referred to Imam Reza Hospital, as well as 30 healthy individuals, participated in this study. Saliva and serum samples were collected in the morning. Cholinesterase activity was evaluated using the photometric method, and data were analyzed using an unpaired Student’s t-test or Mann-Whitney test. Results: The mean activity of cholinesterase and saliva flow rate in saliva and serum were not significantly different between the two groups. Xerostomia inventory score was significantly higher in the IBD group (P<0.05). Conclusion: It seems that cholinesterase activity does not change in patients with IBD, but patients feel more dry mouth than healthy people. [ABSTRACT FROM AUTHOR]

This research aimed to determine the antioxidant capacity of Tribulus terrestris extracts made using various solvents and their effects on some metabolic enzymes. Five different antioxidant methods were used to assess the antioxidant capacities of the water, ethanol, acetone, chloroform, and hexane extracts of T. terrestris. The inhibitory effects of the extracts on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glycosidase enzymes and human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were investigated. The study showed that acetone extract had the strongest inhibition effects in DPPH (IC 50 :25.86 ± 0.010 µg/mL) and ABTS (IC 50 :10.13 ± 0.023 µg/mL) radical scavenging activities. In CUPRAC/Fe3+-Fe2+/FRAP reduction tests, ethanol extract showed the highest reducing power. The ethanol extract exhibited the highest level of inhibition for the AChE/BChE and α -glycosidase enzymes (IC 50 :12.13 ± 0.37 µg/mL, IC 50 :22.33 ± 0.27 µg/mL and IC 50 :25.98 ± 0.75 µg/mL), respectively. Chloroform extract showed the strongest inhibition effect on hCA-I/hCA-II isoenzymes (IC 50 :21.82 ± 0.55 µg/mL, IC 50 :20.97 ± 0.63 µg/mL), respectively. [Display omitted] • The antioxidant capacity of different solvent extracts of T. terrestris was determined by five different methods. The extracts demonstrated significant antioxidant properties. • All the extracts inhibited acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase isoenzymes (hCA-I/hCA-II), and α-glycosidase enzymes. • For these reasons, natural inhibitors and antioxidants in T. terrestris extracts may help improve the treatment of Diabetes Mellitus, Alzheimer's disease and Glaucoma. [ABSTRACT FROM AUTHOR]

Aim: Serum cholinesterase (ChE) levels are considered to reflect nutritional status. Although ChE has been well documented as a prognostic factor for some cancers, no clear consensus on its use for colorectal cancer (CRC) has been reached. The aim of this study was to investigate the relationship between preoperative serum ChE and postoperative long‐term prognosis in CRC patients. Methods: A total of 1053 CRC patients who underwent curative surgery were included in this study. The correlations between the preoperative ChE value and overall survival (OS) or cancer‐specific survival (CSS) were assessed. By dividing patients into two groups according to their ChE value, OS and CSS were compared between the groups. Results: Multivariate analysis revealed that the continuous ChE value was a significant predictor of OS (hazard ratio, 0.996; 95% CI, 0.993–0.998; p = 0.002) and CSS (hazard ratio, 0.994; 95% CI, 0.991–0.998; p = 0.001), independent of other variables. The low‐ChE (≤234 U/L) group had a significantly poorer prognosis than the high‐ChE (>234 U/L) group for both OS (5‐year OS for low ChE and high ChE: 79.8% and 93.3%, respectively; p < 0.001) and CSS (5‐year CSS for low ChE and high ChE: 84.8% and 95.6%, respectively; p < 0.001). Conclusions: Lower preoperative serum ChE levels are a predictive factor of poor prognosis for CRC patients. As serum ChE levels can be measured quickly and evaluated easily, ChE could become a useful marker for predicting the postoperative long‐term outcomes of CRC patients. [ABSTRACT FROM AUTHOR]

The fruit juice industry generates a significant amount of waste, with a strong impact on the environment and the economy. Therefore, researchers have been focusing on the characterization of resources considered as food waste. This work provides information about the lipophilic and polar metabolites of pear pomace flours (PPFs) as a tool that can shed more light on the bioactive potential of this residue. Using UPLC-PDA, UPLC-FLR, and GC-MS, the study identified and quantified PPF's polar and non-polar metabolites. Essential, conditional, and non-essential amino acids were found, with asparagine being the most abundant. Isoprenoids, including lutein, zeaxanthin, and carotene isomers, ranged from 10.8 to 22.9 mg/100 g dw. Total flavonoids and phenolic compounds were 520.5–636.4 mg/100 g dw and 536.9–660.1 mg/100 g dw, respectively. Tocotrienols and tocopherols were identified, with concentrations of 173.1–347.0 mg/100 g dw and 468.7–913.4 mg/100 g dw. Fatty acids were the major non-polar compounds. All fractions significantly reduced matrix metalloproteinase-9 (MMP-9) activity. Although PPF had lower antioxidant potential (3–6 mmol Trolox/100 g dw), it inhibited AChE and BuChE by 23–30% compared to physostigmine salicylate. These findings suggest that pear pomace waste can be repurposed into functional products with valuable bioactive properties by re-introducing it in the food chain. [ABSTRACT FROM AUTHOR]

Triazoles are compounds with various biological activities, including fungicidal action. They became popular through cholinesterase studies after the successful synthesis of the dual binding femtomolar triazole inhibitor of acetylcholinesterase (AChE, EC 3.1.1.7) by Sharpless et al. via in situ click chemistry. Here, we evaluate the anticholinesterase effect of the first isopropanol triazole fungicide mefentrifluconazole (Ravystar®), developed to overcome fungus resistance in plant disease management. Mefentrifluconazole is commercially available individually or in a binary fungicidal mixture, i.e., with pyraclostrobin (Ravycare®). Pyraclostrobin is a carbamate that contains a pyrazole ring. Carbamates are known inhibitors of cholinesterases and the carbamate rivastigmine is already in use for the treatment of Alzheimer's disease. We tested the type and potency of anticholinesterase activity of mefentrifluconazole and pyraclostrobin. Mefentrifluconazole reversibly inhibited human AChE and BChE with a seven-fold higher potency toward AChE (Ki = 101 ± 19 μM). Pyraclostrobin (50 μM) inhibited AChE and BChE progressively with rate constants of (t1/2 = 2.1 min; ki = 6.6 × 103 M−1 min−1) and (t1/2 = 1.5 min; ki = 9.2 × 103 M−1 min−1), respectively. A molecular docking study indicated key interactions between the tested fungicides and residues of the lipophilic active site of AChE and BChE. Additionally, the physicochemical properties of the tested fungicides were compared to values for CNS-active drugs to estimate the blood–brain barrier permeability. Our results can be applied in the design of new molecules with a lesser impact on humans and the environment. [ABSTRACT FROM AUTHOR]

GC/MS analysis of Murraya koenigii (L.) Spreng. and Murraya paniculata (L.) Jacq. leaves revealed the identification of 73 components, with an evident greater contribution of monoterpenes hydrocarbons to their total volatiles. α-Pinene (37.5%) and β-caryophyllene (27.4%) were the most abundant compounds in M. koenigii leaves and β-phellandrene (40.7%) in M. paniculata leaves, using headspace. β-Phellandrene (33.7%) was the major constituent by M. koenigii leaves where germacrene D (23.8%), and δ-elemene (22.0%) were predominant in M. paniculata leaves, using steam distillation. M. koenigii leaves oil showed quite remarkable cholinesterase inhibitory activity, where oil of M. paniculata leaves showed strong inhibitory activity against AChE (IC50=13.2 ± 0.9 µg/mL) and BChE (IC50=5.1 ± 0.3 µg/mL). Germacrene D, α-zingiberene, and δ-elemene showed higher affinity to BChE than AChE as revealed from docking scores (S = −5.65 to −6.03 Kcal/mol) for BChE and (S = −5.56 to −6.25 Kcal/mol) for AChE. [ABSTRACT FROM AUTHOR]

In this study, the inhibition effects of aniline molecules of 1-(2-Furylmethyl) piperidine-3-carboxylic acid hydrochloride (molecule 1), and 3-Chloro-4-(3,5-dimethyl-1-piperidinyl) aniline (molecule 2), which contain piperidine ring, on the enzymes of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and glutathione s-transferase (GST) were investigated. The studies of IC50 and Ki were performed for the inhibitors. All the molecules were found to be good inhibitors for the three enzymes. Molecule 2 was detected to be an effective inhibitory with Ki values of 2.9987±0.2555 for the AChE enzyme and 1.9301±0.2563 for the BChE enzyme. Molecule 1 was found to be another effective molecule with a Ki value of 4.217±0.3759 for the GST enzyme. Ethacrynic acid (EA) and tacrine (TAC) were used as positive inhibitions for enzymes of GST and cholinesterases, respectively. The studied molecules were detected to be more effective compared to the standard compounds. Additionally, enzyme inhibitor interaction was examined theoretically by molecular docking. [ABSTRACT FROM AUTHOR]

In Kars-Sarıkamış-Soğanlı, Angelica purpurascens (A. purpurascens) emerges as a promising natural antioxidant source. Extracts from its leaves, branches, and flowers underwent thorough bioanalytical assessments. The leaf extract exhibited the highest concentrations of herbal flavonoids (45.22 µg QE/mg extract) and total phenolics (28.96 µg GAE/mg extract). Branch extracts demonstrated significant enzymatic activity against AChE and BChE with IC50 values of 37.26 mg/mL and 9.08 mg/mL respectively. The flower extract displayed notable antibacterial properties. This study sheds light on the therapeutic potential of A. purpurascens ethanol extracts, suggesting benefits for Alzheimer's, cell damage-induced diseases, and diabetes mellitus. It pioneers new enzymatic and antioxidant insights and contributes to understanding this abundant Türkiye species. A. purpurascens holds promise for pharmaceutical exploration, offering potential solutions for challenging health conditions. [ABSTRACT FROM AUTHOR]

Boesenbergia albosanguinea is a member of the genus Boesenbergia, which traditionally serves a range of purposes, including food, medicinal applications, ornamental use, and ritualistic practices. It is found growing in wet, shady forest areas on sandstone or quartz-derived soils. This study aims to characterize the essential oils from the rhizomes of B. albosanguinea, assessing their activity against acetylcholinesterase using in vitro methods, along with molecular docking analysis. The essential oil was obtained through hydrodistillation and the volatile components were analysed using gas chromatography (GC-FID) and gas chromatography mass spectrometry (GC-MS) techniques. A total of 34 chemical components, which constitute 96.7% of the oil content, were successfully identified. The most abundant components were elemicin (44.0%), α-gurjunene (9.3%), β-caryophyllene (4.5%), and safrole (4.1%). Anticholinesterase activity was assessed using Ellman method. A moderate inhibitory effect was observed for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes with IC50 values of 90.5 ± 0.2 and 110.8 ± 0.2 μg/mL, respectively. The molecular docking studies of elemicin against the cholinesterase target revealed a robust docking score (-7.0 kcal/mol), but it also showed important interactions with some key amino acid residues, providing crucial insights into its potential as a cholinesterase inhibitor. [ABSTRACT FROM AUTHOR]

Inhibiting cholinesterase (ChE) such as AChE and BChE is thought to be one of the most effective treatments for Alzheimer’s disease (AD) and dementia. In the present work, a new facile method for (1S,4S)-4-(3,4-dichlorophenyl)-n-methyl-1,2,3,4-tetrahydronaphthalen-1-amine based analogues 4 (a–p) in good yield (66–93 %) were synthesized by refluxing demethylsertraline (2) with different aldehydes and ketones 3 (a–p). The newly synthesized analogues 4 (a–p) were characterized by physical and spectroscopic techniques for instance FTIR, LR-MS and HR-MS. The synthesized demethylsertraline based analogues 4 (a–p) were examined for their biological activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In case of AChE activity, electron donating substituents have shown more inhibition as 4–hydroxyphenyl– (4b, IC50, 0.98 ± 0.99 µM) and 3,4–dimethoxyyphenyl– (4c, IC50, 1.0 ± 0.98 µM) and exhibited excellent binding affinity. In case of BChE activity, 4e consisting of electron withdrawing substituent has shown potent inhibition (1.26 ± 0.34 µM). Similarly, 4i and 4n depicted good inhibition with IC50 values 1.66 ± 0.78 µM and 1.66 ± 0.98 µM respectively as they possess weakly donating substituents. The structure activity relationship of BChE inhibition has shown opposite trend than AChE inhibition. It has been scrutinized that strong electron donating substituent decrease the BChE inhibitory activities whereas electron withdrawing groups greatly enhance the enzyme inhibition activity. In silico study of the synthesized compounds 4 (a–p) of the series was carried out. Compound 4b demonstrated excellent interaction with AChE compare with Eserine (standard) with a score of 6228 and an ACE value of –101.33 kcal/mol. Compound 4e demonstrated potent interaction with BChE compare with Eserine (standard) with a score of 6028 and ACE value of –258.53 kcal/mol. Compound 4b has the potential to serve as a lead molecule in medication development for Alzheimer’s disease treatment.

The use of the cholinesterase enzyme as a component of the analytical system has made it possible to develop a new kinetic-spectrophotometric method, which is alternative to the pharmacopoeial method, for determining the quaternary ammonium salt – ethonium in the substance and a dosage form. This method is characterized by high sensitivity and specificity, and is relatively cheap. The relative standard deviation of the procedure does not exceed 2.7 %, and the limit of quantification is 17 ng/mL.

Abstract Introduction Lung cancer is a prevalent malignancy globally, and immunotherapy has revolutionized its treatment. However, resistance to immunotherapy remains a challenge. Abnormal cholinesterase (ChE) activity and choline metabolism are associated with tumor oncogenesis, progression, and poor prognosis in multiple cancers. Yet, the precise mechanism underlying the relationship between ChE, choline metabolism and tumor immune microenvironment in lung cancer, and the response and resistance of immunotherapy still unclear. Methods Firstly, 277 advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy in Sun Yat-sen University Cancer Center were enrolled in the study. Pretreatment and the alteration of ChE after 2 courses of immunotherapy and survival outcomes were collected. Kaplan–Meier survival and cox regression analysis were performed, and nomogram was conducted to identify the prognostic and predicted values. Secondly, choline metabolism-related genes were screened using Cox regression, and a prognostic model was constructed. Functional enrichment analysis and immune microenvironment analysis were also conducted. Lastly, to gain further insights into potential mechanisms, single-cell analysis was performed. Results Firstly, baseline high level ChE and the elevation of ChE after immunotherapy were significantly associated with better survival outcomes for advanced NSCLC. Constructed nomogram based on the significant variables from the multivariate Cox analysis performed well in discrimination and calibration. Secondly, 4 choline metabolism-related genes (MTHFD1, PDGFB, PIK3R3, CHKB) were screened and developed a risk signature that was found to be related to a poorer prognosis. Further analysis revealed that the choline metabolism-related genes signature was associated with immunosuppressive tumor microenvironment, immune escape and metabolic reprogramming. scRNA-seq showed that MTHFD1 was specifically distributed in tumor-associated macrophages (TAMs), mediating the differentiation and immunosuppressive functions of macrophages, which may potentially impact endothelial cell proliferation and tumor angiogenesis. Conclusion Our study highlights the discovery of ChE as a prognostic marker in advanced NSCLC, suggesting its potential for identifying patients who may benefit from immunotherapy. Additionally, we developed a prognostic signature based on choline metabolism-related genes, revealing the correlation with the immunosuppressive microenvironment and uncovering the role of MTHFD1 in macrophage differentiation and endothelial cell proliferation, providing insights into the intricate workings of choline metabolism in NSCLC pathogenesis.

Abstract Acute compartment syndrome (ACS) is a severe orthopedic issue that, if left untreated, can result in lasting nerve and muscle damage or even necessitate amputation. The association between admission laboratory blood test indicators and the occurrence of ACS in patients with tibial diaphysis fractures is currently a subject of debate. The objective of this research was to identify the contributing factors for ACS in individuals suffering from tibial diaphysis fractures. In this retrospective study, we collected data on a total of 705 individuals from our hospital, comprising 86 ACS patients and 619 non-ACS patients with tibial diaphysis fractures. These participants were categorized into two distinct groups: the ACS group and the non-ACS group. Despite the inherent limitations associated with retrospective analyses, such as potential biases in data collection and interpretation, we conducted a comprehensive analysis of demographics, comorbidities, and admission lab results. Our analytical approach included univariate analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis techniques, aiming to mitigate these limitations and provide robust findings. The statistical analysis revealed several predictors of ACS, including gender (p = 0.011, OR = 3.200), crush injuries (p = 0.004, OR = 4.622), lactic dehydrogenase (LDH) levels (p

Glyphosate has remained the leading herbicide on the global market to date, despite the continuous debate between consumers, scientific community, and regulatory agencies over its carcinogenicity, genotoxicity, environmental persistence, and the role in the development of neurodegenerative disorders. Chemically, glyphosate belongs to a large family of organophosphorus pesticides, which exert a neurotoxic effect by inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes of the cholinergic system essential for maintaining neurotransmission. Although research shows that glyphosate is a weak cholinesterase inhibitor in fish and mammals compared to other OP compounds, no conclusive data exist concerning the inhibition of human AChE and BChE. In our study we analysed its inhibitory potency on human AChE and BChE, by establishing its IC50 and reversible inhibition in terms of dissociation inhibition constants. Glyphosate concentration of 40 mmol/L caused near total inhibition of enzyme activity (approx. 10 % activity remaining). Inhibition dissociation constants (Ki) of glyphosate-AChE and -BChE complexes were 28.4±2.7 mmol/L and 19.3±1.8 mmol/L, respectively. In conclusion, glyphosate shows a slight binding preference for BChE but exhibits inhibition only in a high concentration range. Our results are in line with studies reporting that its neurotoxic effect is not primarily linked to the cholinergic system.

Background: Studies suggest that medicinal plant extracts can help reduce the neuron degeneration associated with diabetes. In this study, the neuroprotective effect of the alkaloid-rich extract from the leaves of Lannea egregia was assessed in rats with diabetes induced by streptozotocin (STZ). Methods: Lannea egregia alkaloid-rich analysis was carried out via a known procedure. The rats were randomly assigned into five treatment groups (n = 8): normal control, diabetic-induced rats (45 mg/kg STZ), and diabetic rats treated with low doses of Lannea egregia leaf alkaloid-rich extract (50 mg/kg b.w, LEL) and high (100 mg/kg b.w, LEH) (300 mg/kg and 150 mg/kg), and metformin (200 mg/kg). On 22nd day of the experiment, animals were sacrificed, and their blood and brains were collected for neuro-biomarker analysis. Results: Diabetic-induced rats that received metformin, LEL and LEH exhibited considerably reduced levels of dopamine, serotonin, norepinephrine, NO, MDA, and AChE, BChE activities when compared to untreated diabetic animals. Additionally, rats with diabetes that received treatment with metformin, LEL and LEH displayed a noticeable increase in ENTPDase, Na/K ATPase, GST, CAT, GPx, and SOD activities when compared to the untreated diabetic rats. Histological examination revealed improved brain architecture in the treated groups in contrast to those in diabetic-induced rats. Conclusion: The alkaloid-rich extracts of Lannea egregia might be effective in normalizing brain damage caused by complications of diabetes mellitus.

The scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, were explored in the search for appropriate inhibitors. Thus, to test their inhibitory effect on AChE and BChE, we synthesized a short series of derivatives derived from vanillylamide. Consequently, it was discovered that compounds 12, 34, and 35, which have Ki values in the sub-micromolar concentration range, are especially effective inhibitors. Compound 12 demonstrated dual mixed-type (competitive/uncompetitive) inhibitory activity for both enzymes; compound 34 showed selective mixed-type inhibitory activity for AChE, and compound 35 was found to have selective uncompetitive activity for AChE.

The search for selective anticholinergic agents stems from varying cholinesterase levels as Alzheimer's Disease progresses from the mid to late stage. In this computational study, we probed the selectivity of FDA-approved and metabolite compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with molecular-docking-based virtual screening. The results were evaluated using locally developed codes for the statistical methods. The docking-predicted selectivity for AChE and BChE was predominantly the consequence of differences in the volume of the active site and the narrower entrance to the bottom of the active site gorge of AChE. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of cholinesterase (ChE), procalcitonin (PCT) and D-dimer (D-D) in monitoring pulmonary infection in patients with acute organophosphorus poisoning (AOPP) . Methods 104 cases of AOPP patients admitted to our hospital from March 2021 to June 2022 were selected as the study objects, and were divided into the infected group (39 cases) and the uninfected group (65 cases) according to whether they had pulmonary infection. The general clinical data of the two groups were compared, and the correlation between ChE, PCT, D-D levels and other clinical differential indicators and pulmonary infection was analyzed. The risk factors and protective factors of pulmonary infection in AOPP patients were analyzed by logistic regression model. The receiver operating characteristic curve was drawn to analyze the diagnostic value of combined detection of each index in AOPP patients complicated with pulmonary infection. Results Organophosphorus intake, white blood cell count (WBC), acute physiology and chronic health status evaluation Ⅱ (APACHEⅡ) scores, PCT and D-D levels in the infected group were significantly higher than those in the non-infected group, and ChE activity was significantly lower than that in the non-infected group, with statistical significance (P＜0. 05) . ChE activity was negatively correlated with organophosphorus intake, WBC, APACHEⅡ score and pulmonary infection, while PCT and D-D levels were positively correlated, with statistical significance (P＜0. 05) . Organophosphorus intake, WBC, APACHEⅡ scores, and PCT and D-D levels were all risk factors for pulmonary infection in AOPP patients, and ChE activity was the protective factor, with statistical significance (P＜0. 05) . The area under the curve of AOPP patients complicated with pulmonary infection detected by the combination of ChE, PCT and D-D was 0. 803. Conclusion In patients with AOPP complicated with pulmonary infection, the expression of ChE in serum is down-regulated, while the expression of PCT and D-D is up-regulated. The combined detection in patients with AOPP complicated with pulmonary infection has diagnostic value, and can be used as an effective indicator for the diagnosis of pulmonary infection in patients with AOPP. [ABSTRACT FROM AUTHOR]

Probiotics are defined as “live microorganisms that provide health benefits to the host when administered in adequate amounts.” Probiotics have beneficial effects on human health, including antibacterial activity against intestinal pathogens, regulation of blood cholesterol levels, reduction of colitis and inflammation incidence, regulation of the immune system, and prevention of colon cancer. In addition to probiotic bacteria, some phenolic compounds found in foods we consume (both food and beverages) have positive effects on human health. p-coumaric acid (p-CA) is one of the most abundant phenolic compounds in nature and human diet. The interactions between these two different food components (phenolics and probiotics), resulting in more beneficial combinations called synbiotics, are not well understood in terms of how they will affect the gut microbiota by promoting the probiotic properties and growth of probiotic bacteria. Thus, this study aimed to investigate synbiotic relationship between p-CA and Lactobacillus acidophilus LA-5 (LA-5), Lacticaseibacillus rhamnosus GG (LGG). Probiotic bacteria were grown in the presence of p-CA at different concentrations, and the effects of p-CA on probiotic properties, as well as its in vitro effects on AChE and BChE activities, were investigated. Additionally, Surface analysis was conducted using FTIR. The results showed that treatment with p-CA at different concentrations did not exhibit any inhibitory effect on the growth kinetics of LA-5 and LGG probiotic bacteria. Additionally, both probiotic bacteria demonstrated high levels of antibacterial properties. It showed that it increased the auto-aggregation of both probiotics. While p-CA increased co-aggregation of LA-5 and LGG against Escherichia coli, it decreased co-aggregation against Staphylococcus aureus. Probiotics grown with p-CA were more resistant to pepsin. While p-CA increased the resistance of LA-5 to bile salt, it decreased the resistance of LGG. The combinations of bacteria and p-CA efficiently suppressed AChE and BChE with inhibition (%) 11.04–68.43 and 13.20-65.72, respectively. Furthermore, surface analysis was conducted using FTIR to investigate the interaction of p-coumaric acid with LA-5 and LGG, and changes in cell components on the bacterial surface were analyzed. The results, recorded in range of 4000 –600 cm-1 with resolution of 4 cm-1, demonstrated that p-CA significantly affected only the phosphate/CH ratio for both bacteria. These results indicate the addition of p-CA to the probiotic growth may enhance the probiotic properties of bacteria. [ABSTRACT FROM AUTHOR]

Fragment-based drug design of new bioactive scaffolds is a recent aspect of medicinal chemistry that provides a faster and more efficient road in drug discovery. Phenoxyethyl piperidine and morpholine derivatives have various pharmacological activities, from antitussive to anticancer properties. They are also widely used in selective estrogen receptor modulator (SERM) drugs and can be used to prevent osteoporosis in postmenopausal women. Also, other recent findings suggest that these compounds exhibit high anticholinergic and H3 inverse agonistic activities. We outlined the process of developing novel medications for Alzheimer's disease, malaria, cancer, and various other illnesses, which could entail modifying or incorporating these structures into a different biologically active framework. Pharmacokinetic assessment and organic pathways for synthesizing these scaffolds are also indicated. This review will discuss the recent pharmaceutical advances of phenoxyethyl cyclic amine derivatives in experimental, investigational, and FDA-approved drugs to draw an apparent viewpoint for future drug research and discovery. [ABSTRACT FROM AUTHOR]

Cholinesterases (ChEs) are pivotal in the pathophysiology of various neuromuscular diseases, including Parkinson's disease, Alzheimer's disease, myasthenia gravis, and vascular dementia. The involvement of ChEs in open-angle glaucoma establishes them as promising drug targets. This study employed hierarchical virtual screening (HVS) to identify lead compounds against cholinesterase drug targets. A four-step, knowledge-based, and time-efficient HVS protocol was implemented, resulting in the identification of 41 novel scaffolds capable of evolving into diverse functional ChE inhibitors. This includes inhibitors with selectivity for acetylcholinesterase (AChE) or butyrylcholinesterase (BChE), dual-target, and dual-binding-site inhibitors. The proposed HVS scheme integrates structure-based pharmacophores, docking methodologies, and physicochemical-descriptor-based filters. Among the identified scaffolds, 13 potential ChE inhibitors were selected based on their non-covalent interactions with key binding site residues of both AChE and BChE. Furthermore, an assessment of the physicochemical and pharmacokinetic profiles of these compounds was conducted. The selected potential inhibitors are recommended for further evaluation through in vitro and in vivo assay studies. This comprehensive approach enhances the prospects of identifying effective therapeutic agents targeting cholinesterases in neuromuscular diseases. [ABSTRACT FROM AUTHOR]

Acute compartment syndrome (ACS) is a severe orthopedic issue that, if left untreated, can result in lasting nerve and muscle damage or even necessitate amputation. The association between admission laboratory blood test indicators and the occurrence of ACS in patients with tibial diaphysis fractures is currently a subject of debate. The objective of this research was to identify the contributing factors for ACS in individuals suffering from tibial diaphysis fractures. In this retrospective study, we collected data on a total of 705 individuals from our hospital, comprising 86 ACS patients and 619 non-ACS patients with tibial diaphysis fractures. These participants were categorized into two distinct groups: the ACS group and the non-ACS group. Despite the inherent limitations associated with retrospective analyses, such as potential biases in data collection and interpretation, we conducted a comprehensive analysis of demographics, comorbidities, and admission lab results. Our analytical approach included univariate analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis techniques, aiming to mitigate these limitations and provide robust findings. The statistical analysis revealed several predictors of ACS, including gender (p = 0.011, OR = 3.200), crush injuries (p = 0.004, OR = 4.622), lactic dehydrogenase (LDH) levels (p < 0.001, OR = 1.003), and white blood cell (WBC) count (p < 0.001, OR = 1.246). Interestingly, the study also found that certain factors, such as falls on the same level (p = 0.007, OR = 0.334) and cholinesterase (CHE) levels (p < 0.001, OR = 0.721), seem to provide a degree of protection against ACS. In order to better predict ACS, the ROC curve analysis was employed, which determined threshold values for LDH and WBC. The established cut-off points were set at 266.26 U/L for LDH and 11.7 × 109 cells per liter for WBC, respectively. Our research has successfully pinpointed gender, crush injuries, LDH levels, and white blood cell (WBC) count as crucial risk factors for the development of ACS in patients experiencing tibial diaphysis fractures. Furthermore, by establishing the cut-off values for LDH and WBC, we have facilitated a more personalized assessment of ACS risk, enabling clinical doctors to implement targeted early interventions and optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Cholinesterase is a classical marker that reflects nutritional and inflammatory status. The aim of the present study was to evaluate the association between serum cholinesterase levels and postoperative infectious complications in patients undergoing gastrectomy for gastric cancer. This retrospective study comprised 108 patients who underwent gastrectomy for gastric cancer. We comprehensively investigated the association between clinicopathological variables and postoperative infectious complications after gastrectomy. Then patients were divided into the cholinesterase-high and -low groups to analyze their clinicopathological variables. Finally, we analyzed the types of infectious complications that were most associated with preoperative serum cholinesterase levels. Twenty-six patients (24%) developed postoperative infectious complications. Multivariate analysis revealed that serum cholinesterase levels (P = 0.026) and N stage (P = 0.009) were independent risk factors for postoperative infectious complications. In particular, the incidence of pneumonia (P = 0.001) was significantly higher in the cholinesterase-low group. Age (P = 0.023), cerebrovascular comorbidities (P = 0.006), serum cholinesterase levels (P = 0.013), and total gastrectomy (P = 0.017) were identified as independent risk factors for postoperative pneumonia. Preoperative serum cholinesterase levels were associated with postoperative pneumonia after gastrectomy for gastric cancer, suggesting the importance of preoperative nutritional assessment in gastric cancer surgery. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum amyloid A (SAA), cholinesterase (CHE), apolipoprotein A1 (ApoA1) levels and cognitive function in patients with Alzheimer's disease (AD). Methods: 103 AD patients who were treated in our hospital from December 2020 to May 2023 were selected as case group, and 80 healthy volunteers who underwent physical examination in our hospital during the same period were selected as control group. The levels of serum SAA, CHE and ApoA1 in two groups were detected by enzyme-linked immunosorbent assay. The cognitive function in two groups was evaluated by Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Serum SAA, CHE, ApoA1 levels and MMSE, MoCA scores were compared between two groups. AD patients were divided into mild group, moderate group and severe group according to the MMSE score, the levels of serum SAA, CHE and ApoA1 in mild group, moderate group and severe group were observed and compared. The correlation between serum SAA, CHE, ApoA1 levels and MMSE score were analyzed by Pearson test. The serum SAA in case group was higher than that in control group, and the serum CHE and ApoA1 levels were lower than those in control group (P<0.05). The scores of MoCA and MMSE in case group were lower than those in control group (P<0.05). Results: The serum SAA levels in severe group and moderate group were higher than those in mild group, and severe group was higher than that of moderate group (P<0.05). The levels of serum CHE and ApoA1 in severe group and moderate group were lower than those in mild group, and severe group was lower than that of moderate group (P<0.05). Pearson test analysis showed that serum CHE, ApoA1 and MMSE scores were positively correlated, and serum SAA and MMSE scores were negatively correlated (P<0.05). Conclusions: The abnormal increase of serum SAA and the abnormal decrease of serum CHE and ApoA1 levels in AD patients may be relate to the occurrence of cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Cognitive impairment is one of the main complications of diabetes and patients with cognitive impairment are considered to be in an intermediate stage of decreased cognition with higher risk of developing dementia and Alzheimer's disease. This study aimed at evaluating serum activity of two esterase enzymes including cholinesterase and paraoxonase 1 (PON 1) in diabetic patients and association with cognitive performance and metabolic parameters. In this crosssectional study, 128 diabetic patients were enrolled. Cognitive performance was evaluated using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Body mass index, fasting blood glucose, fasting blood insulin, insulin resistance, serum cholinesterase and paraoxonase 1 activity were measured. Prevalence of cognitive impairment was found to be 77% in the study population. Serum cholinesterase activity was found to be higher in diabetic patients with cognitive impairment than the patients with normal cognitive performance (p < 0.04). Further, a negative correlation was found between cognitive performance and cholinesterase activity, albeit statistically non-significant. Alteration in the activity of cholinesterase enzyme was shown to be associated with cognitive impairment in diabetic patients and future studies are required to find the pathophysiological mechanisms of diabetic cognitive dysfunction. [ABSTRACT FROM AUTHOR]

In traditional medicine, people commonly consume Bryoria capillaris (BC) as flour and tea, particularly in Northeast Anatolia, where it is one of the most prevalent lichen species. This study aimed to obtain an acetone extract of BC and investigate its inhibitory effects on carbonic anhydrase (CA) I, CA II, acetylcholine esterase (AChE), and butyrylcholine esterase (BChE) enzymes. We determined IC50 values of BC for each enzyme to measure the level of inhibition. The IC50 values for CA I and CA II were 8.77 µg/mL and 7.56 µg/mL, respectively. Acetazolamide, a specific CA I and II inhibitor, had IC50 values of 1.65 and 0.016 µg/mL, respectively. The IC50 values of BC for AChE and BChE were 7.96 and 8.58 µg/mL, respectively. Galantamine had IC50 values of 4.68 and 16.07 µg/mL for AChE and BChE, respectively. These results indicate that BC extract has a high potential to provide new drug candidates for all the tested enzymes, particularly for BChE. [ABSTRACT FROM AUTHOR]

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Background and purpose: Alzheimer's disease (AD) is a common neurodegenerative disease and the fifth leading cause of death among the elderly. The development of drugs for AD treatment is based on inhibiting cholinesterase (ChE) activity and inhibiting amyloid-beta peptide and tau protein aggregations. Many in vitro findings have demonstrated that thiazole- and thiazolidine-based compounds have a good inhibitory effect on ChE and other elements involved in the AD pathogenicity cascade. Experimental approach: In the present review, we collected available documents to verify whether these synthetic compounds can be a step forward in developing new medications for AD. A systematic literature search was performed in major electronic databases in April 2021. Twenty-eight relevant in vitro and in vivo studies were found and used for data extraction. Findings/Results: Findings demonstrated that thiazole- and thiazolidine-based compounds could ameliorate AD's pathologic condition by affecting various targets, including inhibition of ChE activity, amyloid-beta, and tau aggregation in addition to cyclin-dependent kinase 5/p25, beta-secretase-1, cyclooxygenase, and glycogen synthase kinase-3β. Conclusion and implications: Due to multitarget effects at micromolar concentration, this review demonstrated that these synthetic compounds could be considered promising candidates for developing anti-Alzheimer drugs.

Shu-Tong Huang,1,2,&ast; Jin-Chong Luo,1,3,&ast; Guo-Hui Zhong,1,2 Li-Ping Teng,4 Cai-Yan Yang,4 Chun-Li Tang,1 Lin Jing,1 Zhong-Bo Zhou,4 Jing Liu,1,3 Neng Jiang1,2 1Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 2Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China; 4School of Pharmacy, Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Liu, School of Pharmacy, Jiangxi University of Chinese Medicine, No. 56, Yangming Road, Donghu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Email liujing860828@163.com Neng Jiang, Department of Pharmacy, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +86-17307711726, Email cpujnh@163.comPurpose: Alzheimer’s disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs.Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo.Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC50 = 1.57 μM, hBuChE: IC50 = 0.43 μM) and MAOs (hMAO-A: IC50 = 2.30 μM, hMAO-B: IC50 = 4.75 μM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics.Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD. Keywords: Alzheimer’s disease, cholinesterase, monoamine oxidase, multi-target, designed

This study was designed to examine the essential oils compositions of Litsea glauca Siebold and Litsea fulva Fern.-Vill. growing in Malaysia. The essential oils were achieved by hydrodistillation and fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The study identified 17 and 19 components from the leaf oils from L. glauca (80.7%) and L. fulva (81.5%), respectively. The major components of L. glauca oil were β-selinene (30.8%), β-calacorene (11.3%), tridecanal (7.6%), isophytol (4.8%) and β-eudesmol (4.5%); whereas in L. fulva oil gave β-caryophyllene (27.8%), caryophyllene oxide (12.8%), α-cadinol (6.3%), (E)-nerolidol (5.7%), β-selinene (5.5%) and tridecanal (5.0%). Anticholinesterase activity was evaluated using Ellman method. The essential oils showed moderate inhibitory activity on acetylcholinesterase and butyrylcholinesterase assays. Our findings demonstrate that the essential oil could be very useful for the characterization, pharmaceutical, and therapeutic applications of the essential oil from the genus Litsea. [ABSTRACT FROM AUTHOR]

This study focused on the synthesis and evaluation of the biological activity of ten novel acetohydrazide hybrid derivatives, having furfuryloxy‐1,2,3‐triazole ring. All the target compounds were tested in vitro and in silico for their inhibitory potential against key enzymes: hAChE, hBChE, hCAI, and hCAII, all involved in significant physiological processes. Remarkably, two compounds, namely (E)‐2‐(4‐((furan‐2‐ylmethoxy)methyl)‐1H‐1,2,3‐triazol‐1‐yl)‐N′‐(4‐hydroxy‐3‐methoxybenzylidene)acetohydrazide (9) and (E)‐N′‐(4‐chlorobenzylidene)‐2‐(4‐((furan‐2‐ylmethoxy)methyl)‐1H‐1,2,3‐triazol‐1‐yl)acetohydrazide (11), exhibited strong inhibitory activity. Compound 9 emerged as the top‐performing inhibitor for both hAChE (IC50 of 0.23 μM) and hBChE (IC50 of 0.74 μM). Additionally, compounds 9 and 11 displayed potent inhibitory effects on hCAI and hCAII, with IC50 values of 0.18 μM and 0.15 μM, respectively. Furthermore, in silico studies provided valuable insights into the interaction mechanisms and stability of the ligand‐protein complexes. Compound 9 demonstrated strong binding scores of −12.063 kcal/mol for hAChE and −9.359 kcal/mol for hBChE, while Compound 11 exhibited substantial scores of −7.040 kcal/mol for hCAI and −8.216 kcal/mol for hCAII. In conclusion, they stand out as promising inhibitors of hAChE, hBChE, hCAI and hCAII enzymes. Their inhibitory activity, supported by low IC50 values, indicated their potential to inhibit enzymes associated with neurological and metabolic processes. [ABSTRACT FROM AUTHOR]

The EtOH extracts of the leaves of two new cultivars (Uysal-SFU and Turgut-SFT) of Salvia fruticosa Mill. was tested against acetylcholinesterase (IC50: 30.62 ± 3.27 and 32.97 ± 2.33 µg/mL for SFU and SFT, respectively) and butyrylcholinesterase (IC50: 69.91 ± 1.08 µg/mL and 86.55 ± 1.26 µg/mL), respectively, relevant to Alzheimer's disease. The essential oils showed a stumpy inhibition against AChE and no inhibition against BChE. DPPH radical scavenging activity of the extracts (86.70 ± 0.17% and 86.14 ± 1.13% for SFU and SFT, respectively) was stronger than that of quercetin (85.51 ± 0.17%): Their (1.24 ± 0.05 and 1.04 ± 0.16 for SFU and SFT, respectively) ferric-reducing antioxidant power were close to that of the reference (e.g. quercetin, 1.42 ± 0.14). Molecular docking simulations were performed on their major monoterpenes. Our findings revealed that the leaf EtOH extracts of two cultivars are promising inhibitors of both AChE and BChE. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic disease that is multifactorial. Its underlying cause and mechanisms are yet to be fully understood and numerous research are underway to develop more effective drug candidates. This research explores the synthesis of an indazole-containing novel drug targeting AD, particularly by inhibiting cholinesterase activity. Among the 17 indazole derivatives synthesized in this study, compound 4q was demonstrated to have potent and selective butyrylcholinesterase (BChE) inhibitory activity. Molecular docking simulations revealed that the binding of 4q with BChE was through hydrophobic and polar interactions. It was also found to easily permeate through the blood-brain-barrier via an in vitro model and is non-toxic when tested against SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

Introduction: Tobacco production is increasing in certain regions of Indonesia due to its high economic value. Tobacco and its products can have harmful effects on the health of consumers, producers and processing workers. Analysis of blood samples has shown that tobacco farmers are at risk of developing occupational diseases related to pesticide exposure and nicotine absorption through the epidermis of wet tobacco leaves. The aim of this study was to compare blood cholinesterase levels in tobacco plantation workers in relation to their working hours and use of personal protective equipment (PPE). Methods: This cross-sectional observational study was conducted in ten subdistricts in Jember district, Indonesia, and included 50 participants selected using proportional sampling. Spearman's test was used to analyse the relationship between variables. Results: The significance value of the relationship based on Spearman's test between working hours and blood cholinesterase levels of tobacco farmers in Jember was 0.058 > a (0.05). Meanwhile, the significance value of the relationship between working hours and complete blood count, specifically mean corpuscular haemoglobin concentration (MCHC), was 0.00 < a (0.05), and between PPE use and blood cholinesterase levels was 0.035 < a (0.05). Conclusion: Working hours were not associated with blood cholinesterase levels, but were associated with blood MCHC levels. Meanwhile, the use of PPE was found to be associated with cholinesterase levels in tobacco farmers. [ABSTRACT FROM AUTHOR]

The use of the cholinesterase enzyme as a component of the analytical system has made it possible to develop a new kineticspectrophotometric method, which is alternative to the pharmacopoeial method, for determining the quaternary ammonium salt – ethonium in the substance and a dosage form. This method is characterized by high sensitivity and specificity, and is relatively cheap. The relative standard deviation of the procedure does not exceed 2.7 %, and the limit of quantification is 17 ng mL–1. [ABSTRACT FROM AUTHOR]