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Synthesis of the acetylcholinesterase inhibitor paraoxon (POX) as a carbon-11 positron emission tomography tracer ([11C]POX) and profiling in live rats is reported. Naïve rats intravenously injected with [11C]POX showed a rapid decrease in parent tracer to ∼1%, with an increase in radiolabeled serum proteins to 87% and red blood cells (RBCs) to 9%. Protein and RBC leveled over 60 minutes, reflecting covalent modification of proteins by [11C]POX. Ex vivo biodistribution and imaging profiles in naïve rats had the highest radioactivity levels in lung followed by heart and kidney, and brain and liver the lowest. Brain radioactivity levels were low but observed immediately after injection and persisted over the 60-minute experiment. This showed for the first time that even low POX exposures (∼200 ng tracer) can rapidly enter brain. Rats given an LD50 dose of nonradioactive paraoxon at the LD50 20 or 60 minutes prior to [11C]POX tracer revealed that protein pools were blocked. Blood radioactivity at 20 minutes was markedly lower than naïve levels due to rapid protein modification by nonradioactive POX; however, by 60 minutes the blood radioactivity returned to near naïve levels. Live rat tissue imaging-derived radioactivity values were 10%-37% of naïve levels in nonradioactive POX pretreated rats at 20 minutes, but by 60 minutes the area under the curve (AUC) values had recovered to 25%-80% of naïve. The live rat imaging supported blockade by nonradioactive POX pretreatment at 20 minutes and recovery of proteins by 60 minutes. SIGNIFICANCE STATEMENT: Paraoxon (POX) is an organophosphorus (OP) compound and a powerful prototype and substitute for OP chemical warfare agents (CWAs) such as sarin, VX, etc. To study the distribution and penetration of POX into the central nervous system (CNS) and other tissues, a positron emission tomography (PET) tracer analog, carbon-11-labeled paraoxon ([11C]POX), was prepared. Blood and tissue radioactivity levels in live rats demonstrated immediate penetration into the CNS and persistent radioactivity levels in tissues indicative of covalent target modification.

A series of new diterpene quinopimaric acid derivatives modified at the hydroxyl group with different pharmacophore fragments has been synthesised and their (along with previously obtained compounds) inhibitory properties towards cholinesterases were studied. Thereby an indole-3-acetyl derivative 7 and a propargyl substituted compound 28 were shown to be excellent and acetylcholinesterase-selective inhibitors. Both compounds inhibited the enzyme as a mixed type inhibitor, and Ki values of 0.41 and 0.44 µM and Ki' values of 0.98 and 2.26 µM were determined. The binding interactions between all active compounds and ligands protein were confirmed through molecular docking study. [ABSTRACT FROM AUTHOR]

Alzheimer's disease, is one of the irreversible neurodegenerative disorders among older people, causes behavior, memory, and thinking problems. This study aim is to synthesize of 4‐({8‐[3‐(dimethylamino)phenoxy]octyl}oxy)phthalonitrile, zinc(II) phthalocyanine and its water soluble derivative containing ({8‐[3‐(dimethylamino)phenoxy]octyl}oxy) substituents at the peripheral positions first time. To determine the potential of water soluble silicon(IV) and zinc(II) phthalocyanines for use in AD, spectrophotometric assays were performed to determine their acetylcholinesterase/butyrylcholinesterase inhibitory effects. In addition, their DNA nuclease properties were evaluated by agarose gel electrophoresis. The results showed that the compounds inhibited acetylcholinesterase/butyrylcholinesterase. They did not damage pBR322 plasmid DNA depending on time and concentration. As a result of the experiments, it is revealed that the compounds may be the potential for use as cholinesterase inhibitors, which is a promising approach for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The impact of environmental pollutants has been a focus of investigation in recent years. Studies assessing the effects of these pollutants are essential for understanding the challenges faced by non-target species. Among the many substances used for agricultural purposes, the herbicide glyphosate is one of the most widely marketed in recent years. This broad-spectrum herbicide is commonly used to protect a variety of crops. In this study, we evaluated the effects of chronic glyphosate exposure on a native amphibian species, Physalaemus gracilis. Amphibians, which develop in aquatic environments, are highly sensitive to pesticides. Because of this, we investigated morphological, physiological, behavioral, and biochemical parameters in the early stages of development. The animals were exposed to environmentally relevant concentrations of a glyphosate-based herbicide (0, 100, 350, and 700 µg L⁻¹) during their first seven days of life. As a result, we observed impairments in anti-predatory behavior, reduced body mass index, and scaled mass index, malformations of the mouth and intestine, increased acetylcholinesterase activity, cardiotoxicity, and oxidative stress. These findings underscore the importance of studying native non-target species and highlight the need to evaluate the effects of environmentally relevant concentrations, as well as to review legislation regarding permissible levels of glyphosate in surface water and public water supplies. [ABSTRACT FROM AUTHOR]

Wastewater effluents increase contaminant levels in the aquatic environment, leading to various disruptive effects. In this study, responses of Unio ravoisieri transplanted into wastewater from Wadi Guenniche were monitored using filtration rate, oxidative stress, lipo-peroxidation, neurotoxicity and histopathological markers. The filtration rate was significantly increased by exposure to diluted wastewater, rising from 35.13 mg indiv−1 h−1 in the control to 63.49 mg indiv−1 h−1 in the mussels after 96 h of exposure. In contrast, this exposure significantly reduces catalase, glutathione-S-transferase and acetylcholinesterase activities in both organs. This decrease is dependent on the effluent concentration and time exposure. The malondihaldehyde content showed an increasing profile in both organs. It is only in the gills that this increase is significant for mussels transplanted in situ for 48 h. Contamination by wastewater causes histopathological changes in both organs, marked by infiltration, vacuolisation, secretion of lipofuscins and cell necrosis. The intensity of these lesions depends on the duration of exposure and the degree of pollution. The mean incidence of lesions increases depending on effluent concentration and exposure time in both organs. Our study contributes to the database on behavioural, biochemical and histopathological effects in mussels following the discharge of wastewater effluent into a freshwater ecosystem. [ABSTRACT FROM AUTHOR]

Different species of aphids, responsible for severe yield losses of cereal crops including wheat, (Triticum aestivum L.) are managed by insecticides, which are harmful to organisms and the environment under field conditions. Therefore, an environment friendly aphidicidal product of plant origin is required. Mentha spicata oil was found to be rich in carvone (81.88%), but the use of its oil and carvone in crop protection is lacking due to their volatility, poor solubility, and stability. A nanoformulaton not only solves these problems but also improve the efficacy and dose of the bioactive compounds. Thus, nano-emulsions of the oil and carvone prepared were characterized, and evaluated against Rhopalosiphum maidis (corn aphid) and Sitobion avenae (wheat aphid) The average droplet size of nano-emulsions of the oil and carvone was found to be 22.1 and 41.21 nm. Nano-emulsion of carvone exhibited higher aphid mortality (LC50 = 0.87–1.94 mg/mL) at 24 h and acetylcholinesterase inhibitory activity (IC50 = 0.07–3.83 mg/mL) compared to the nano-emulsion of the oil (LC50 = 2.87–2.81 mg/mL; IC50 = 1.66–5.34 mg/mL). The repellence index (RI) in nano-emulsion of essential oil was found to be higher (84.73 and 81.72%) at the highest concentration (0.05 µL/cm2) than that of carvone (77.59 and 80.98%) for R. maidis and S. avenae. Further, in silico studies also revealed the favourable binding energy (− 6.6 to − 8.5 kcal/mol) of the main compounds in the oil with acetylcholinesterase, facilitated by hydrophobic interactions and hydrogen bonding. This study suggests that the nano-emulsions of the essential oil and carvone can be explored under field conditions to establish efficacy for their utilization as aphidicidal and repellent products against aphids. In the present study, aphidicial and repellent activities of its essential oil and carvone were reported for the first time against R.maidis and S.avenae. [ABSTRACT FROM AUTHOR]

Due to the complex nature of Alzheimer’s disease (AD), it begins insidiously in the brain many years before the appearance of the first symptoms and is usually diagnosed, when the disease is progressive and symptoms have appeared. It can be said that AD’s emergence is almost untrackable and the straightforward mechanism of AD is still unclear for the most part. Therefore, any kind of research on the emergence of AD can lead to valuable results for predicting and treating AD. Previously, we proposed a novel mathematical model based on cellular automata for the study of Alzheimer’s disease progress. In this paper, cellular automata (CA) mathematical modeling is used as a tool for simulation and experimenting with drugs’ effects in this far-fetched situation. For this goal, immune system interactions and neuron-to-neuron communications are assumed to have prominent roles. We have used the CA network, pathophysiological process, and physiological realities to get a clear insight into neuron-to-neuron communications. Our simple model investigates the influence of three Acetylcholinesterase Inhibitor injections, including Donepezil, Rivastigmine, and Galantamine on the reduction of defined factors such as Alzheimer’s Rate (AR), Critical Rate (CR), and Warning Rate (WR). It is shown that using drugs has different effects on the betterment of neurons and can decrease AR and CR factors and enhance WR, many years before the appearance of symptoms. [ABSTRACT FROM AUTHOR]

\nHighlightsThe activity of liver catalase and brain acetylcholinesterase was assessed in rainbow trout (Oncorhynchus mykiss) after 7- and 14-day exposure to a six-metal mixture at the maximum permissible concentrations accepted for inland waters in the EU (2013/39/EU; 2008/105/EC) (Zn − 0.1, Ni − 0.034, Cu − 0.01, Cr − 0.01, Cd − 0.0015 and Pb − 0.014 mg L−1) and to the same six-metal mixtures with tenfold reduced concentration of Cu and Cr ions. A statistically significant increase of up to 26% of catalase and 52% of acetylcholinesterase activity was observed in rainbow trout after 7 days of exposure to the six-metal mixture at the maximum permissible concentrations in comparison to a control group. After 14-day treatment, neither CAT nor AChE showed significant response to all tested metal mixtures. The six-metal mixture with the tenfold reduced concentration of Cr increased brain AChE activity in O. mykiss after 7 days of exposure (35%). Enhancement of catalase activity caused by the mixture of the six metals at the maximum permissible concentrations and the increased acetylcholinesterase activity in response to the same metal mixture and mixture with tenfold reduced Cr concentration after 7 days of exposure indicates the induction of oxidative stress and disturbance of cholinergic system homeostasis respectively. The toxicity of different types of six-metal mixtures was assessed in liver and brain tissues of O. mykissA significant increase of CAT and AChE activity was observed in fish after 7 days of exposure to six-metal mixtureReduced Cr concentration significantly increased AChE activity after seven days of treatmentChanges of single-metal concentrations in the six-metal mixture have an impact on biomarker responsesThe toxicity of different types of six-metal mixtures was assessed in liver and brain tissues of O. mykissA significant increase of CAT and AChE activity was observed in fish after 7 days of exposure to six-metal mixtureReduced Cr concentration significantly increased AChE activity after seven days of treatmentChanges of single-metal concentrations in the six-metal mixture have an impact on biomarker responses [ABSTRACT FROM AUTHOR]

The current study focuses on evaluating the enzyme inhibition (acetylcholinesterase, α-amylase, α-glucosidase, pancreatin lipase), antioxidant, and antimicrobial activities of the "Modesto" apricot, "Stanley" plum, and their hybrid the "Stendesto" plum–apricot. The "Stendesto" is the only successful plum–apricot hybrid in Bulgaria. A spectrophotometric approach was used to evaluate the antioxidant activity following four complementary assays (DPPH, ABTS, FRAP, and CUPRAC). The "Stendesto" plum–apricot revealed its enhanced antioxidant potential compared to its parental lines. Apart from the free phenolics extraction, two other techniques (alkaline and acid hydrolysis) were applied to reveal the biological potential of the studied fruit. Not only free but also bound phenolic extracts were able to inhibit α-glucosidase and acetylcholinesterase, while none of the extracts inhibited lipase or α-amylase. None of the apricot extracts had antimicrobial activity, while the other fruit had limited antimicrobial activity. The proposed results undoubtedly reveal that hybrid fruits possess enhanced biological activity compared to their parents. This is a first comprehensive evaluation of hybrid fruits with reference to parental lines. This makes them an interesting research topic that should be better explored. [ABSTRACT FROM AUTHOR]

A series of benzothiazine derivatives (1–17) were synthesized via an intermolecular cyclocondensation reaction involving 2‐aminothiophenol (i) and substituted phenacyl bromide (ii). Structural elucidation of these synthetic derivatives utilized EI–MS, HR‐EIMS, 1H NMR, and 13C NMR spectroscopic techniques. The synthesized analogs were evaluated against key enzyme targets (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α‐glucosidase (α‐Glu)) and tested for cytotoxicity against various cancer cell lines. Six compounds were selected based on their inhibition profiles, exhibiting significant inhibitory potential against enzymes. In silico studies corroborated the observed inhibitory activities, aligning closely with experimental outcomes. Additionally, an ADME/T study provided insights into pharmacokinetic and safety profiles, identifying promising candidates for future drug development efforts. [ABSTRACT FROM AUTHOR]

Cyanobacteria, especially Arthrospira, are valuable resources of nutrients and natural pigments with many beneficial health-related properties. This study optimized the extraction conditions of Arthrospira to achieve high phenolic contents and antioxidant activities. Under optimized extraction conditions, the bioactive compounds (phenolics and pigment components), antioxidant activities, and inhibitions of the key enzymes relevant to some non-communicable diseases were compared between Arthrospira platensis and Arthrospira maxima. Optimized extraction conditions were determined as 2 h shaking time, 50 °C extraction temperature, and 1% (w/v) solid-to-liquid ratio, giving effective phenolic and phycocyanin contents using aqueous extraction, while 80% (v/v) aqueous ethanolic extraction provided high total chlorophyll content. Most antioxidant activities were higher using 80% (v/v) aqueous ethanolic extracts. Both Arthrospira species inhibited the key enzymes involved in controlling non-communicable diseases including hyperlipidemia (lipase), diabetes (α-amylase, α-glucosidase, and dipeptidyl peptidase-IV), Alzheimer's disease (acetylcholinesterase, butyrylcholinesterase and β-secretase), and hypertension (angiotensin-converting enzyme). High inhibitory activities were detected against β-secretase (BACE-1), the enzyme responsible for β-amyloid plaque formation in the brain that acts as a significant hallmark of Alzheimer's disease. Arthrospira extract and donepezil (Alzheimer's disease drug) synergistically inhibited BACE-1, suggesting the potential of Arthrospira extracts as effective BACE-1 inhibitors. Interestingly, A. maxima exhibited higher bioactive compound contents, antioxidant activities, and key enzyme inhibitions than A. platensis, indicating high potential for future food and medicinal applications. [ABSTRACT FROM AUTHOR]

Background and aims: This study aimed to investigate the effect of iron overload on acetylcholinesterase activity in the frontal lobe tissue of rats with minimal hepatic encephalopathy (MHE) and its relation to cognitive ability. By elucidating the potential mechanisms of cognitive impairment, this study may offer insights into novel therapeutic targets for MHE. Materials and methods: Twelve Sprague-Dawley rats were purchased and randomly assigned to either the experimental or control group with six rats in each group. Following the induction of MHE, the Morris Water Maze (MWM) was utilized to assess spatial orientation and memory capacity. Subsequently, Magnetic Resonance Imaging (MRI) scans were performed to capture Quantitative Susceptibility Mapping (QSM) images of all rats' heads. Results: Compared to the control group rats, the MHE model rats showed significantly reduced learning and memory capabilities as well as spatial orientation abilities (P < 0.05). Furthermore, the susceptibility values in the frontal lobe tissue of MHE model rats was significantly higher than that of the control group rats (P < 0.05), and the corresponding BuChE activity in the frontal lobe extract of model rats was significantly increased while BuChE activity in the peripheral blood serum was significantly decreased compared to the control group rats (P < 0.05). Meanwhile, our findings indicate a significant positive correlation between latency period and BuChE activity with susceptibility values in the MHE group. Conclusion: The changes in BuChE activity in frontal lobe extract may be related to changes in spatial orientation and behavioral changes in MHE, and iron overload in the frontal lobe tissue may regulate changes in BuChE activity, BuChE levels appear to be iron-dependent. [ABSTRACT FROM AUTHOR]

Arum maculatum, cuckoo‐pint in folk linguistics, is a poisonous but medicinal plant with tremendous properties that need investigation. This study subjected cuckoo‐pint's parts to in vitro antioxidant, enzyme inhibition, and antimicrobial susceptibility testing to investigate its biological activity. Further, phytochemistry was analyzed by both LC–MS/MS and total phenol, flavonoid, saponin, and reducing sugar content determination assays. Antioxidant activities were determined by Fe3+, Cu2+, Fe3+‐TPTZ metal‐reducing ability, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and 2,2ʹ‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) radical scavenging assays. According to the results, seeds and berries have remarkable metal‐reducing and radical‐scavenging effects as natural and synthetic analogs such as ascorbic acid, butylated hydroxyanisole, butylated hydroxytoluene, trolox, and α‐tocopherol. Inhibition studies over human carbonic anhydrase II (hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α‐amylase were performed, and IC50 values were determined for each enzyme inhibition. According to the results, the cuckoo‐pint seeds inhibited the AChE, BChE, and hCA II activity with greater IC50 values than reference inhibitors. Antimicrobial activity over pan‐resistant strains was achieved for each strain with the extracts, at least 20 mm zone diameter was obtained with the lowest concentrations. LC–MS/MS results revealed 24 bioactive metabolites associated with the extracts' biological activity. Notably, quinic acid and epicatechin correlated with cardioprotective, neuroprotective, antioxidant, and antidiabetic activity. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is characterized by cholinergic dysfunction, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) critical for improving cholinergic neurotransmission. However, the development of effective dual inhibitors remains challenging. Objective: This study aims to synthesize and evaluate novel pyridazine-containing compounds as potential dual inhibitors of AChE and BuChE for AD treatment. Methods: Ten novel pyridazine-containing compounds were synthesized and characterized using IR, 1H NMR, and 13C NMR. The inhibitory activities against AChE and BuChE were assessed in vitro, and pharmacokinetic properties were explored through in silico ADME studies. Molecular dynamics simulations were performed for the most active compound. Results: Compound 5 was the most potent inhibitor, with IC50 values of 0.26 µM for AChE and 0.19 µM for BuChE, outperforming rivastigmine and tacrine, and showing competitive results with donepezil. Docking studies revealed a binding affinity of −10.21 kcal/mol to AChE and −13.84 kcal/mol to BuChE, with stable interactions confirmed by molecular dynamics simulations. In silico ADME studies identified favorable pharmacokinetic properties for compounds 5, 8, and 9, with Compound 5 showing the best activity. Conclusions: Compound 5 demonstrates strong potential as a dual cholinesterase inhibitor for Alzheimer's disease, supported by both in vitro and in silico analyses. These findings provide a basis for further optimization and development of these novel inhibitors. [ABSTRACT FROM AUTHOR]

Despite the great effort that has gone into developing new molecules as multitarget compounds to treat Alzheimer's disease (AD), none of these have been approved to treat this disease. Therefore, it will be interesting to determine whether benzazoles such as benzimidazole, benzoxazole, and benzothiazole, employed as pharmacophores, could act as multitarget drugs. AD is a multifactorial disease in which several pharmacological targets have been identified—some are involved with amyloid beta (Aβ) production, such as beta secretase (BACE1) and beta amyloid aggregation, while others are involved with the cholinergic system as acetylcholinesterase (AChE) and butirylcholinesterase (BChE) and nicotinic and muscarinic receptors, as well as the hyperphosphorylation of microtubule-associated protein (tau). In this review, we describe the in silico and in vitro evaluation of benzazoles on three important targets in AD: AChE, BACE1, and Aβ. Benzothiazoles and benzimidazoles could be the best benzazoles to act as multitarget drugs for AD because they have been widely evaluated as AChE inhibitors, forming π–π interactions with W286, W86, Y72, and F338, as well as in the AChE gorge and catalytic site. In addition, the sulfur atom from benzothiazol interacts with S286 and the aromatic ring from W84, with these compounds having an IC50 value in the μM range. Also, benzimidazoles and benzothiazoles can inhibit Aβ aggregation. However, even though benzazoles have not been widely evaluated on BACE1, benzimidazoles evaluated in vitro showed an IC50 value in the nM range. Therefore, important chemical modifications could be considered to improve multitarget benzazoles' activity, such as substitutions in the aromatic ring with electron withdrawal at position five, or a linker 3 or 4 carbons in length, which would allow for better interaction with targets. [ABSTRACT FROM AUTHOR]

The identification of novel acetylcholinesterase inhibitors holds significant relevance in the treatment of Alzheimer's disease (AD), the prevailing form of dementia. The exploration of alternative inhibitors to the conventional acetylcholinesterase inhibitors is steadily gaining prominence. Quinones, categorized as plant metabolites, represent a specific class of compounds. In this study, the inhibitory effects of various naphthoquinone derivatives, along with anthraquinone and its derivatives, on the acetylcholinesterase (AChE) enzyme were investigated for this purpose. An in vitro investigation was conducted to examine the effects of these compounds in order to clarify the possible mechanism of inhibition in the interaction between the enzyme and chemicals. In addition, an in silico investigation was carried out to understand the conceivable inhibitor binding process to the enzyme's active site. The acquired outcomes corroborated the in vitro results. The AChE enzyme was found to be effectively inhibited by both naphthoquinones and anthraquinones, with inhibition constant (KI) values ranging from 0.014 to 0.123 μM (micormolar). The AChE enzyme was inhibited differently by this quinone and its derivatives. Although derivatives of naphthoquinone and anthraquinone exhibited a competitive inhibitory effect, derivatives of anthraquinone exhibited a noncompetitive inhibition effect. Furthermore, because it had the lowest KI value of any of these substances, 1,5‐dihydroxyanthraquinone (1c) was shown to be the most potent inhibitor. The findings will add to the body of knowledge on the creation of fresh, potent, and successful treatment approaches. [ABSTRACT FROM AUTHOR]

A series of phenyl, substituted phenyl and thiophene bearing dihydrofuropyrimidin‐4‐ones (3a‐p) were synthesized by Mn(OAc)3 mediated, microwave irradiated radical cyclizations of 2‐hydroxy‐pyridopyrimidin‐4‐one derivatives (1a‐j) with substituted phenylvinylthiophenes (2a‐c) at 70°C in 2 min. Compounds 3a‐j was obtained between 28% and 66% yields. Molecular structures of 3a‐p were determined by 1H NMR, 13C NMR, 19F NMR, FTIR and HRMS techniques. Inhibitory activity of 3a‐p were evaluated against Acetylcholinesterase (AChE) and inhibition results of these compounds showed that the compounds had good inhibition with IC50 values between 0.52 and 3.77 μM. In addition, molecular docking studies were carried out on the most potent inhibitory compounds 3d (IC50 = 0.64 μM), 3p (IC50 = 0.52 μM) and standart drug Donepezil. The binding energies for 3d, 3p and Donepezil are −9.12, −10.08 and −12.65 Kcal/mol, respectively. Based on these results, it was determined that, compounds 3d and 3p are promising AChE inhibitors. [ABSTRACT FROM AUTHOR]

The novel serious of tricyclicthiazolo[5,4‐d]pyrimidinone were designed and synthesized as acetylcholinesterase (AChE) inhibitor agents. The main factors affecting the reactions of syntheses and the structure–activity relationships (SARs) were investigated as well. All compounds were confirmed by 1H NMR, 13C NMR, and HRMS. The in vitro enzyme assays proved that most of the compounds effectively inhibited AChE in the micromolar range with little cytotoxicity. Especially the compound G15 exhibited the best inhibitory activity against AChE with IC50 values of 4.41 ± 0.46 μM. Furthermore, kinetic analysis and molecular modeling studies pointed out the competitive inhibition manner of G15 on AChE. Thus, the derivative G15 can be considered a promising leading compound on AChE. [ABSTRACT FROM AUTHOR]

This study assessed the impact of stressors on marine bivalves from three Moroccan lagoons – Moulay Bousselham, Sidi Moussa, and Oualidia – using biomarkers like Acetylcholinesterase, Glutathione-S-Transferase, Catalase, and Metallothioneins. Biomarker variations indicated pollutant impacts, including pesticides and heavy metals. Results showed distinct biochemical responses, with Oualidia lagoon indicating improved water quality and significant alterations in Sidi Moussa. Seasonal variations in Moulay Bousselham highlighted the importance of temporal dynamics in pollution assessment. This study emphasises the importance of multibiomarker approaches in assessing and preserving the health of Moroccan lagoons. [ABSTRACT FROM AUTHOR]

Organophosphate (OP) poisoning, both accidental and with suicidal intent, is a global medical challenge. While the primary toxicity of these pesticides is based on the inhibition of acetylcholinesterase (AChE), case reports describe patients developing OP-mediated renal insufficiency. We set out to investigate possible pathomechanisms utilizing rat precision-cut kidney slices (PCKS). Depending on the method of investigation, PCKS were observed for a maximum of 10 days. PCKS exposed to OP compounds (malaoxon, malathion, paraoxon, parathion) showed a dose-dependent loss of viability and a reduction of total protein content over the course of 10 days. A concentration of 500 µM OP showed the most differences between OP compounds. After two days of incubation parathion showed a significantly lower level of viability than malathion. The respective effects of paraoxon and malaoxon were not significantly different from the control. However, effects of OP were only observed in concentrations exceeding those that were needed to achieve significant AChE inhibition in rat kidney tissue. In addition, we observed histological changes, without inducing LDH leakage. Overall, results suggest that OP exert effects in kidney tissue, that exceed those expected from the sole inhibition of AChE and vary between compounds. Without signs of necrosis, findings call for studies that address other possible pathomechanisms, including inflammatory response, oxidative stress or activation of apoptosis to further understand the nephrotoxicity of OP compounds. Monitoring oxon concentration over time, we demonstrated reduced enzyme-inhibiting properties in the presence of PCKS, suggesting interactions between OP compound and kidney tissue. [ABSTRACT FROM AUTHOR]

This study primarily aims to evaluate the phenolic content and biological activity of Salvia macrochlamys both in vitro and in silico. The antioxidant activities of Salvia macrochlamys were assessed using various methods. Additionally, cytotoxic effects and the α-amylase, α-glucosidase, and acetylcholinesterase (AChE) enzyme inhibitory abilities of ethanolic extract of the aerial parts of Salvia macrochlamys (EESM) were evaluated. Then, the molecular docking interactions and molecular dynamic calculations of EESM against α-amylase, α-glycosidase, and AChE enzymes were carried out. High antioxidant activity was determined in both ethanol and water extracts. The IC50 values of EESM against AChE (EC 3.1.1.7), α-glycosidase (E.C.3.2.1.20), and α-amylase (E.C.3.2.1.1) were determined as 1.622 μg/mL, 0.530 μg/mL, and 1.320 μg/mL, respectively. High enzyme-inhibiting properties of EESM were determined in also in silico. Rosmarinic acid was identified as one of the most abundant phenolic compounds in both EESM and water extract of the aerial parts of Salvia macrochlamys (WESM) (3919.65 mg/kg and 10520.77 mg/kg, respectively). Their high level of flavonoids and phenolics, as well as the potent antioxidant and enzyme-inhibitory properties displayed by extracts, may contribute to broadening the use of Salvia macrochlamys in both traditional and modern therapeutic applications. [ABSTRACT FROM AUTHOR]

In the search for new leads capable of interacting with multiple targets involved in NDD pathogenesis, a series of pyrazine-linked isoxazoline scaffolds were designed, synthesized and evaluated for their acetylcholinesterase and tyrosinase inhibitory potency and antioxidant activity. Isoxazolines 4a, 4d and 4h exhibited better molecular interaction with cholinesterases, tyrosinases and peroxiredoxin enzymes. Isoxazolines 4a, 4d and 4h interacted with acetylcholinesterase with the highest docking score of −9.083, −8.68 and −7.87 kcal/mol, respectively. Compound 4h ranked top when interacting with butyrylcholinesterase with a docking score of −7.926 kcal/mol, followed by 4a (−6.327 kcal/mol). 4a exhibited a robust interaction with 1HD2 with a docking score of −3.103 kcal/mol followed by 4d and 4h. 4a, 4d and 4h exhibited better docking scores of −5.47 kcal/mol, −4.63 kcal/mol and −5.157 kcal/mol with the enzyme tyrosinase. Based on the in-silico data, we have proceeded further to synthesis and in-vitro studies. Chalcones were synthesized by the Claisen-Schmidt reaction, which was cyclised to isoxazolines by the cycloaddition of hydroxylamine HCl. FTIR, 1HNMR, 13CNMR, and mass spectral studies further characterized the compounds. The prediction of pharmacokinetic parameters also supports the study, and all the compounds passed the screening. In-vitro studies were performed to evaluate acetylcholinesterase and tyrosinase inhibition. Compound 4h displayed excellent action against acetylcholinesterases and tyrosinase enzymes. Hydrogen peroxide assay determined the antioxidant effect, which found that 4h and 4d compounds exhibited higher strength as peroxide scavengers. Thus, the study shows that pyrazine-based isoxazolines with electron-withdrawing groups can be used as leads to develop a drug of choice for NDD, as it has excellent acetylcholinesterase and tyrosinase inhibitory action and tremendous peroxide scavenging effect. [ABSTRACT FROM AUTHOR]

The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC "Annex on Chemicals" some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman's assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed. [ABSTRACT FROM AUTHOR]

Assessment of acute toxicity of magnetic nanogel (MNG) is crucial to conclude the safe applicable dose and to warrant its application in aquaculture. Therefore, the current study is a novel step to assess behavior, neuro-stress response, hepato-renal, oxidative, and histopathological variations produced by MNG' acute toxicity in Clarias gariepinus. Two experiments were conducted: the first was a determination of the 96-h lethal concentration 50 (LC50) of MNG in C. gariepinus. Meanwhile, the second was an assessment of the toxicological impacts of three different concentrations of MNG in C. gariepinus following a 10-day exposure period and a subsequent 10-day depuration trial. One hundred and eighty fish were allotted to four groups exposed to 0, 1/10, 1/8, or 1/5 96-h LC50 of MNG. The outcomes exhibited that 96-h LC50 of MNG for C. gariepinus was 44 mg/L. The subjected group to MNG induced a concentration-dependent elevation in the serum values of cortisol, alanine transaminase, aspartate transaminase, urea, and creatinine following MNG exposure. Marked elevation in the oxidative stress indicators (catalase (CAT), glutathione S-transferase activity (GST), and superoxide dismutase (SOD)) was also evident. Meanwhile, the value of the neurological biomarker, acetylcholinesterase (AChE), was markedly reduced in a concentration-dependent way. These biochemical changes were complemented by pathological alterations in the hepato-renal architecture. Interestingly, in response to the 10-day depuration period, most of the tested parameters were eliminated in C. gariepinus exposed to 1/10 of LC50. Conclusively, MNG can induce numerous adverse effects only at higher doses (1/5 and 1/8 of LC50). Meanwhile, the lowest tested concentration of MNG (1/10 of LC50) was safe for application in aquaculture practices with only mild disruptions in the bio-indices. In addition, a retrieval period of 10 days was sufficient to renovate these alterations only in fish exposed to the same concentration. [ABSTRACT FROM AUTHOR]

A set of sesamol-derived acetamides was designed, synthesized, and evaluated against monoamine oxidases (MAO-A and MAO-B) and cholinesterases (AChE and BChE) for targeting neurodegenerative diseases. Most of the tested compounds showed inhibition activity at micromolar to nanomolar ranges. The 3,4-dichoro derivative (compound 19) was the most potent MAO-A inhibitor (IC50 = 0.053 ± 0.001 µM) while the 4-methyl analog (compound 16) emerged as a lead MAO-B inhibitor (IC50 = 0.019 ± 0.001 µM) compared to the reference inhibitors clorgyline (MAO-A IC50 = 0.096 ± 0.003 µM) and selegyline (MAO B IC50 = 0.021 ± 0.002 µM). Further, the 2,4-dichloro analog (compound 20) emerged as a potent dual MAO (MAO-A IC50 = 0.160 ± 0.009 µM, MAO-B IC50 = 0.071 ± 0.002 µM) and ChE (AChE IC50 = 2.611 ± 0.086 µM and BChE IC50 = 4.22 ± 0.162 µM) inhibitor. Moreover, molecular simulation studies revealed that H-bonding and hydrophobic interactions stabilize the virtual lead inhibitor-protein complex. Selected MAO-ChE inhibitors showed significant antioxidant and iron-chelation properties, suggesting their potential in treating neurological disorders characterized by impaired iron homeostasis. In summary, the structural modification attempted in the present study yielded a few nanomolar MAO (MAO-B) inhibitors and, thus, provided new insights into the linker requirements for dual MAO/ChE inhibitory properties. [ABSTRACT FROM AUTHOR]

Nowadays, many studies have been carried out to develop new eco-friendly alternatives consequently, the essential oils (EOs) have acquired more interest due to their insecticidal activities, low harmfulness, and rapid degradation in the environment. Following this approach, herein we tried to improve the insecticidal activities of Pelargonium graveolens (G) through using the geranium oil in nano-emulsion (GN) form and in combination with sesame seed oil (SO). Different concentrations ranged from 0.313 to 10% were prepared from GN and the combination of G with S and tested for their larvicidal and pupicidal activities against Musca domestica and Culex pipiens, while their adulticidal activities were tested against red flour beetle Tribolium castaneum. The LC50 of G alone was 4.29% against house fly larvae. The values of LC50 decreased to 1.50% for GN and 0.32% for the combination of G+S. GO and GN form induced (pupal toxicity) 100% inhibition rate (PIR) in the treated housefly pupae at the concentration of 10%. Meanwhile, GO+SO combination showed 100% PIR at the concentration of 2.5%. Furthermore, the LC50 for GO, GN and GO+SO was 0.22, 0.19 and 0.079 % respectively against larvae of C. pipiens, while it was 1.04 % for sesame oil. Regarding the contact and fumigant assays against adult T. castaneum, the combination of G and S achieved the best results when compared with GO alone or GN form. All treatments exhibited inhibition in the activity of acetylcholinesterase enzyme in the house fly larvae 24h post application. In addition, all the treatments induced significant increase in the malondialdehyde activity. In conclusion, nanoemulsion tech and mixing GO+SO increased their insecticidal potency against house fly, C. pipiens and T. castenum. This is a useful method in the integrated pest management. [ABSTRACT FROM AUTHOR]

Copyright of Retos: Nuevas Perspectivas de Educación Física, Deporte y Recreación is the property of Federacion Espanola de Asociaciones de Docentes de Educacion Fisica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We have developed a bienzymatic biosensor that contains acetylcholinesterase together with butyrylcholinesterase co-immobilized on the same electrode modified with a stabilized copper containing Prussian blue electrodeposited on electrodes coated with 4-aminothiophenol monolayer using diazonium chemistry and copper nanoparticles for improved sensitivity. There are organophosphorus and carbamate neurotoxic insecticides that inhibit only one of the two enzymes, e.g., pirimicarb inhibits butyrylcholinesterase at much lower concentrations than acetylcholinesterase while methomyl inhibits only acetylcholinesterase. Our system is simple and in a single measurement provides a sensitive signal for insecticides' presence based on the inhibition of the enzyme with the highest affinity for each toxic compound. The limits of detection are 50 ng/mL pirimicarb for the bienzymatic biosensor in comparison with 400 ng/mL pirimicarb for the acetylcholinesterase biosensor and 6 ng/mL methomyl for the bienzymatic biosensor, while inhibition is obtained for the butyrylcholinesterase biosensor at 700 ng/mL. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is one of the leading causes of distorted social communication, impaired speech, hyperactivity, anxiety, and stereotyped repetitive behaviour. The aetiology of ASD is complex; therefore, multiple drugs have been suggested to manage the symptoms. Studies with histamine H3 receptor (H3R) blockers and acetylcholinesterase (AchE) blockers are considered potential therapeutic agents for the management of various cognitive impairments. Therefore, the aim of this study was to evaluate the neuro-behavioural effects of Betahistine, an H3R antagonist, and Donepezil, an acetylcholinesterase inhibitor on Swiss albino mouse model of autism. The mice were intraperitoneally injected with valproic acid (VPA) on the embryonic 12.5th day to induce autism-like symptoms in their offspring. This induced autism-like symptoms persists throughout the life. After administration of different experimental doses, various locomotor tests: Open Field, Hole-Board, Hole Cross and behavioural tests by Y-Maze Spontaneous Alternation and histopathology of brain were performed and compared with the control and negative control (NC1) groups of mice. The behavioural Y-Maze test exhibits significant improvement (p <0.01) on the short term memory of the test subjects upon administration of lower dose of Betahistine along with MAO-B inhibitor Rasagiline once compared with the NC1 group (VPA-exposed mice). Furthermore, the tests showed significant reduction in locomotion in line crossing (p <0.05), rearing (p <0.001) of the Open Field Test, and the Hole Cross Test (p <0.01) with administration of higher dose of Betahistine. Both of these effects were observed upon administration of acetylcholinesterase inhibitor, Donepezil. Brain-histopathology showed lower neuronal loss and degeneration in the treated groups of mice in comparison with the NC1 VPA-exposed mice. Administration of Betahistine and Rasagiline ameliorates symptoms like memory deficit and hyperactivity, proving their therapeutic effects. The effects found are dose dependent. The findings suggest that H3R might be a viable target for the treatment of ASD. [ABSTRACT FROM AUTHOR]

Norbelladine derivatives have garnered attention in recent years due to their diverse biological activities and pivotal role in the biosynthetic pathway of Amaryllidaceae alkaloids. This study reports the synthesis and biological evaluation of four O,N-methylated derivatives of norbelladine. These derivatives were synthesized through a three-step process: forming imine intermediates from benzaldehydes with tyramine, hydrogenating them to secondary amines, and N-methylating these amines. The products were purified and characterized by 1H and 13C NMR spectroscopy. Their biological activities were assessed by evaluating their ability to inhibit Alzheimer's disease-related enzymes acetylcholinesterase and butyrylcholinesterase. Additionally, the cytotoxic activity of the novel derivatives was tested against cancer cell lines derived from hepatocarcinoma (Huh7), adenocarcinoma (HCT-8), and acute myeloid leukemia (THP-1) cells, and their antiviral properties against a human coronavirus (HCoV-OC43), a flavivirus (dengue virus), and a lentivirus (pseudotyped HIV-1). Docking analysis was performed to understand the impact of the N-methylation on their pharmacological relevance. The results indicate that while N-methylation does not significantly affect antiviral activity, it enhances butyrylcholinesterase inhibition for N-methylnorbelladine and 4′-O,N-dimethylnorbelladine. Overall, this work enhances our understanding of norbelladine derivatives, provides new tools for Alzheimer's disease research, and lays the groundwork for future pharmaceutical developments. [ABSTRACT FROM AUTHOR]

This current study aims to analyze the potential bioactivities possessed by the enzymatic hydrolysates of commercial bovine, porcine, and tilapia gelatins using bioinformatics in combination with in vitro and in vivo studies. The hydrolysate with superior inhibition of angiotensin converting enzyme (ACE) activity was used to treat the D-galactose (DG)-induced amnesic mice. In silico digestion of the gelatins led to the identification of peptide sequences with potential antioxidant, ACE-inhibitory, and anti-amnestic properties. The results of in vitro digestion revealed that the <1 kDa peptide fraction of porcine gelatin hydrolysate obtained after 1 h digestion with papain (PP) (PP1, <1 kDa) potently inhibited ACE, acetylcholinesterase, and prolyl endopeptidase activities at 87.42%, 21.24%, and 48.07%, respectively. Administering the PP1 to DG-induced amnesic mice ameliorated the spatial cognitive impairment and Morris water maze learning abilities. The dentate area morphology in the PP1-treated mice was relatively similar to the control group. In addition, PP1 enhanced the antioxidant capacity in the DG-induced amnesic mice. This study suggests that PP1 could serve as a potential treatment tool against oxidative stress, hypertension, and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most common causes of dementia, accounting for more than 60% of all cases. It is a neurodegenerative disease in which symptoms such as a decline in memory, thinking, learning, and organizing skills develop gradually over many years and eventually become more severe. To date, there is no effective treatment for the cause of Alzheimer's disease, and the existing pharmacological options primarily help manage symptoms. Treatment is mainly based on acetylcholinesterase (AChE) inhibitors such as donepezil, rivastigmine, and galantamine, which exhibit numerous adverse cardiovascular and gastrointestinal effects due to excessive stimulation of peripheral cholinergic activity involving muscarinic receptors. Therefore, in addition to the obvious drugs that act on the cause of the disease, new drugs based on AChE inhibition that show the fewest side effects are needed. One potential drug could be a new compound under study, tetrahydroacridine derivative (CHDA), which showed significant potential to inhibit the AChE enzyme in previous in vitro studies. The present study shows that while having very potent AChE inhibitory properties, CHDA is a compound with low toxicity to nerve cell culture and living organisms. In addition, it exhibits dissociative activity against amyloid β fibrils, which is extremely important for applications in Alzheimer's disease therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT In this study, novel chlorine‐thymol derivatives (1,3‐bis(4‐chloro‐2‐isopropyl‐5 methylphenoxy)propan‐2‐ol (Thy‐OHI) and 2‐[2‐(4‐chloro‐2‐isopropyl‐5‐methylphenoxy)ethoxy]ethanol (Thy‐OHII)) and axially di‐4‐chloro‐2‐isopropyl‐5‐methylphenoxy (Thy‐SiPc), 1,3‐bis(4‐chloro‐2‐isopropyl‐5‐methylphenoxy)propanoxy (Thy‐OHI‐SiPc), and 2‐[2‐(4‐chloro‐2‐isopropyl‐5‐methylphenoxy)ethoxy]ethanoxy (Thy‐OHII‐SiPc) substituted silicon phthalocyanine compounds were obtained, and their structures were elucidated by the combination of various methods such as NMR, IR, UV–Vis, and MS. The inhibitory effects of these compounds (Thy‐OHI, Thy‐OHII, Thy‐SiPc, Thy‐OHI‐SiPc and Thy‐OHII‐SiPc), synthesized for the first time, on cholinesterase enzymes (AChE and BChE) were investigated in the laboratory environment. In the studies, notably Thy‐OHI‐Si and thymol derivative ligand Thy‐OHII displayed significant inhibition against AChE and BChE. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects the elderly population globally and there is an urgent demand for developing novel anti-AD agents. In this study, a new series of indole-isoxazole carbohydrazides were designed and synthesized. The structure of all compounds was elucidated using spectroscopic methods including FTIR, 1H NMR, and 13C NMR as well as mass spectrometry and elemental analysis. All derivatives were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Out of all synthesized compounds, compound 5d exhibited the highest potency as AChE inhibitor with an IC50 value of 29.46 ± 0.31 µM. It showed significant selectivity towards AChE, with no notable inhibition against BuChE. A kinetic study on AChE for compound 5d indicated a competitive inhibition pattern. Also, 5d exhibited promising BACE1 inhibitory potential with an IC50 value of 2.85 ± 0.09 µM and in vitro metal chelating ability against Fe3+. The molecular dynamic studies of 5d against both AChE and BACE1 were executed to evaluate the behavior of this derivative in the binding site. The results showed that the new compounds deserve further chemical optimization to be considered potential anti-AD agents. [ABSTRACT FROM AUTHOR]

Current clinical management of pregnancies at risk of preterm delivery includes maternal antenatal corticosteroid (ACS) treatment. ACS activate the glucocorticoid receptor (GR) in all fetal tissues, maturing the lungs at the cost of impaired brain development, creating a need for novel treatments. The prodrug ciclesonide (CIC) activates the GR only when converted to des-CIC by specific enzymes, including acetylcholinesterase (ACHE) and carboxylesterase 1 and 2 (CES1, CES2). Importantly, the human placenta expresses ACHE and CES, and could potentially produce des-CIC, resulting in systemic fetal exposure and GR activation in all fetal tissues. We therefore investigated CES gene expression and conversion of CIC to des-CIC in human placentae collected during the second trimester (Tri2), and at preterm and term birth. Differential expression analysis was performed in Tri2 (n = 27), preterm (n = 34), and term (n = 40) placentae using the DESeq2 R -package. Conversion of CIC to des-CIC was measured in a subset of placenta samples (Tri2 n = 7, preterm n = 26, term n = 20) using functional assays. ACHE mRNA expression was higher in Tri2 male than preterm and term male placentae only, whereas CES1 mRNA expression was higher in Tri2 than preterm or term placentae of both sexes. Conversion of CIC to des-CIC did not differ between gestational ages. Conversion of CIC to des-CIC by the human placenta may preclude its use as a novel GR-agonist in threatened preterm birth. In vivo studies are required to confirm the extent to which placental activation occurs after maternal treatment. • Human placental ciclesonide activation decreased with increasing gestational age. • Human placenta activated ciclesonide at rates greater than reported in human lung. • Placental CES1 and ACHE expression was higher at Tri2 than later gestations. • Placental activation of ciclesonide may expose the fetus to active metabolite. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative condition brought on by aging and characterised by progressive decline in cognitive function and abnormalities in the central cholnergic system. β-amyloid deposits, neurofibril tangle aggregation, oxidative stress or reduced level of acetylcholine are a few causes that have been linked to AD. In this study, the bioassay-guided isolation from ethyl acetate (EtOAc) extract of Horsfieldia polyspherula bark led to the isolation of nine compounds namely, 16-phenylhexadecanoic acid (1), undecylbenzene (2), 3,4-dihydroxybenzoic acid (3), dodecanoic acid (4), tetradecanoic acid (5), pentadecanoic acid (6), 1-tridecene (7), stigmasterol (8) and trimyristin (9). Phytochemical analysis revealed the presence of flavonoids, steroids, lignin, alkaloids, phytosterol and triterpenoids. The DPPH scavenging activity of EtOAc extract was related to the phenolic content (116.67 ± 16.98 GAE mg/g) and other non-phenolics such as lower fatty acids. Meanwhile, the DPPH scavenging activity was found to be concentration-dependent and correlated with both flavonoid and phenolic content. Furthermore, EtOAc and methanol (MeOH) extracts of H. polyspherula bark showed significant inhibitory activity at 100 µg/mL on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), with EtOAc extract showing 77.2% and 64.1% inhibition and MeOH extract showing 37.5% and 39.2% inhibition, respectively. Additionally, the IC50 for BuChE and AChE of the EtOAc extract were found to be effective, with 15.41 ± 0.78 µg/mL and 7.67 ± 0.13 µg/mL, respectively. Compound 1 exhibited dual inhibition of 40.99 ± 1.99 µM (BuChE) and 46.83 ± 2.44 µM (AChE), while compounds 2 and 3 showed IC50 values above 200 µM. This study revealed that this plant shows a significant potential as a nti-cholinesterase focusing on acetylcholinesterase (AchE) and butyrylcholinesterase (BuChE). This is the first report on Horsfieldia polyspherula and their biological activity. [ABSTRACT FROM AUTHOR]

Although the clinical diagnosis or exclusion of Hirschsprung's disease is a frequent task in pediatric practice, the final diagnosis is based on the histopathological conclusion of a rectal biopsy. However, ancillary diagnostic tests such as acetylcholinesterase histochemistry or immunohistochemistry are extremely useful in some cases. The differential histological diagnosis of Hirschsprung's disease can be challenging, as other conditions can present with similar histological features. In this article, we consider the pathological features of Hirschsprung's disease, highlight the main pathohistological manifestations of this disease, as well as auxiliary methods of morphological diagnosis, which are important in solving particularly difficult cases of diagnostic search. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the benefit of verapamil on stress-induced memory impairment in mice. Methods: Forty-eight (48) mice were used in this study. They were divided into two equal groups based on the two models of stress used in this study (sleep deprivation and hypoxia). Each model was further divided into 4 groups of six animals each. The mice in the sleep deprivation model were suspended on a platform above water while in the hypoxic model, mice were locked in an airless container for 20 min daily throughout the experiment. As for the intervention, 25 and 50 mg/kg verapamil were preadministered via the oral route to study groups, except the normal control group and negative control group in both models. After seven-day stress and intervention, the mice were subjected to behavioural tests (Y-maze and object recognition tests), biochemical assays (for acetylcholinesterase activity) and histochemical analysis. Results: Stress caused a significant (p < 0.05) impairment in the consolidation and retrieval of working and recognition memories. Also, acetylcholinesterase activity was significantly (p < 0.05) enhanced in the stressed groups when compared to control groups. Similarly, the histological analysis revealed a significant decline in population (p < 0.05), distribution and density of viable neurons in specific areas of the hippocampus and prefrontal cortex. These alterations were significantly (p < 0.05) attenuated in verapamil-treated groups almost in a dose-dependent pattern. Conclusion: Verapamil displays significant memory-enhancing effects in two (2) murine models of stress. Antihypertensives should therefore be considered a viable prospect in the management of stress-related memory disorders after additional studies have been done to establish the mechanisms of action. [ABSTRACT FROM AUTHOR]

Introduction: Vitex negundo has a myriad of medicinal uses, such as antioxidant, analgesic and anthelminthic properties, and it is used for dysmenorrhoea. The plant contains various phytochemicals, such as flavonoids, vitamins and casticin. All components of the plant are utilised medicinally due to the minimal occurrence of adverse drug reactions, making it a potential drug target for various chronic diseases. However, the role of this plant in neurodegenerative disorders, such as Alzheimer's Disease (AD), has not yet been extensively studied. Aim: To evaluate the in-silico and in-vitro activity of the anti-Alzheimer properties of the Methanolic Extract of Vitex negundo (MEVN) leaves. Materials and Methods: The present in-silico docking study and in-vitro study were conducted in the Department of Pharmacology at Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu, India, over a period of two months. The in-silico analysis was performed to determine the intermolecular interactions between the ligand and protein of the top five scored molecules using PyMol software. To assess the Acetylcholinesterase (AChE) inhibitory property, the findings were presented as docking scores. Cell viability and cytotoxicity were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with results expressed as percentages for various concentrations: 6.25 µg/mL, 12.5 µg/mL, 25 µg/mL, 50 µg/mL, 75 µg/mL, and 100 µg/mL of MEVN. Results: The MEVN exhibited competitive inhibition of the AChE enzyme. There were active interactions between Agnuside, Isochlorogenic Acid B, Isochlorogenic Acid C, Kaempferol-3-O-rutinoside, and Quercetin found in the MEVN with AChE. The percentage of cell viability for the concentrations of 6.25 µg/mL, 12.5 µg/mL, 25 µg/mL, 50 µg/mL, 75 µg/mL, and 100 µg/mL, as determined by the MTT assay, was 98.62%, 98.86%, 97.19%, 96.66%, 91.86%, and 78.82%, respectively. The results indicated that MEVN does not exhibit any toxicity. Conclusion: The findings demonstrated that MEVN possesses AChE inhibitory properties and maintains cell viability, both of which are indicative of anti-Alzheimer activity. Therefore, MEVN can be further evaluated for its potential in preventing cell cytotoxicity and treating AD. [ABSTRACT FROM AUTHOR]

New triheteroyclic compounds containing quinazolinone, thiophene, andthiadiazole /thiazolidinone structureswere synthesized and characterized by FT-IR, 1H–NMR, and13C–NMRspectral data. The new compounds' inhibitory activities on urease and acetylcholinesterase were assessed. All triheterocyclic compounds with thiadiazole ring have urease and acetylcholinesteraseinhibitory activities.Especially compound 5a; 3-[(5-(phenylamino)-1,3,4-thiadiazol-2-yl]methyl-2-(thiophen-3-ylmethyl)quinazolin-4(3H)-onehas the best urease inhibition result with 13.30 ± 0.15 µg/mL IC50 value, and it also has the best acetylcholinesterase inhibition with 20.30 ± 0.15 µg/mL IC50 value. [ABSTRACT FROM AUTHOR]

In this study, the effects of various lichen and usnic acid applications on seizure scores and biochemical parameters in brain tissue in rats with epilepsy model was investigated. For this aim, 91 rats were divided into 13 groups, each containing 7 rats, which were: control, pentylenetetrazole (PTZ) (35 mg/kg), PTZ + Valproic acid (100 mg/kg), PTZ + Dolichousnea longissima (200 mg/kg), PTZ + Dolichousnea longissima (400 mg/kg), PTZ + Xanthoparmelia somloensis (50 mg/kg), PTZ + Xanthoparmelia somloensis (200 mg/kg), PTZ + Cetraria islandica (250 mg/kg), PTZ + Cetraria islandica (500 mg/kg), PTZ + Pseudevernia furfuracea (250 mg/kg), PTZ + Pseudevernia furfuracea (500 mg/kg), PTZ + usnic acid (50 mg/kg), and PTZ + usnic acid (200 mg/kg). All items were applied with an interval of 120 minutes for a period of one week. Seizure detection, seizure scores and total seizure duration of each group was recorded. After the applications, oxidative stress parameters and acetylcholinesterase enzyme activity in the brain tissue of rats were measured. There was no difference between the groups in the 1st, 2nd, and 3rd injections (p>0.05). Starting from the 4th injection, the seizure score was significantly higher in the PTZ group compared to the control group (p<0.05). When the effects on locomotor activity were evaluated, no difference was found between any group (p>0.05). In PTZ applied groups, an increase in lipid and protein oxidation as well as a decrease in antioxidant and acetylcholine esterase levels were observed (p<0.05). Valproic acid, high concentration of lichen extract applications and high and low concentration of usnic acid applications were found to reverse this situation (p<0.05). As a result, various lichen extracts and usnic acid were shown to reduce behavioral symptoms and oxidative stress of epilepsy, with a preventive effect on the complications of epilepsy. [ABSTRACT FROM AUTHOR]

• TMA+ exposure significantly inhibited the swimming activities of larval zebrafish. • Swimming path angle is the most sensitive endpoint in response to TMA+ exposure. • Neurobehavior endpoints of larvae were significantly related with oxidative stress. • The calculated 96 h-LC 50 of TMA+ was lower for zebrafish juveniles than larvae. • TMA+ evoked greater inhibitions on multi-biomarkers of juveniles than larvae. Tetramethylammonium hydroxide (TMAH) is an important compound that utilized and released by the rapidly expanding semiconductor industry, which could hardly be removed by the conventional wastewater treatment techniques. As a cholinergic agonist, the tetramethylammonium ion (TMA+) has been reported to induce toxicity to muscular and respiratory systems of mammals and human, however the toxicity on aquatic biota remains poorly known. We investigated the neurotoxic effects of TMA+ exposure on zebrafish, based on neurobehavior tests and a series of biomarkers. Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L, and significant alterations on swimming path angles (straight and deflective movements) occurred even at 10 mg/L. The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species (ROS) and malondialdehyde (MDA), significantly negatively related with the activities of antioxidant enzymes, but not significantly correlated with the level of acetylcholinesterase (AChE). Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress, rather than the alterations of neurotransmitter. At the highest exposure concentration (200 mg/L), TMA+ evoked more severe toxicity on zebrafish juveniles, showing significantly stronger elevation on the MDA activity, and greater inhibitions on the activities of antioxidant enzymes and AChE, suggesting juveniles were more susceptible to TMA+ exposure than larval zebrafish. [Display omitted] [ABSTRACT FROM AUTHOR]

Knema elegans Warb. is an evergreen tree belonging to the Myristicaceae family, primarily native to Southeast Asia. This study examined the chemical composition and assessed the antioxidant and anti-acetylcholinesterase properties of the essential oil from the leaves of K. elegans in Vietnam. Gas chromatography/mass spectrometry analysis revealed the main compounds in the essential oil, including bicyclogermacrene (23.8%), germacrene D (17.1%), β-caryophyllene (15.4%), δ-cadinene (8.2%), and α-cadinol (7.9%). Antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'- azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, with halfmaximum inhibitory concentration (IC50) values of 93.11 ± 1.95 μg/mL and 114.95 ± 2.41 μg/mL, respectively, indicating moderate antioxidant potential. Additionally, the essential oil exhibited significant anti-acetylcholinesterase effects, with an IC50 value of 87.44 ± 2.52 μg/mL. These findings highlight the biological significance of K. elegans essential oil and suggest avenues for further investigation, particularly in elucidating its mechanisms of action in antioxidant and anti-acetylcholinesterase activities. Notably, this research represents the first comprehensive exploration of the chemical composition, antioxidant activity, and acetylcholinesterase inhibition effects of K. elegans essential oil from its leaves. [ABSTRACT FROM AUTHOR]

Copyright of Mersin University School of Medicine Lokman Hekim Journal of History of Medicine & Folk Medicine is the property of Mersin University School of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this paper, the lipid classes, compositions of the neutral lipids, phospholipids and fatty acids, acetylcholinesterase inhibition and cytotoxic activity of two brown algae Lobophora tsengii D. Tien & Z. Sun and Lobophora australis Z. Sun, F. C. Gurgel & H. Kawai have been investigated. The polar lipid class had the highest content in total lipid (TL) (43.47% in L. tsengii and 48.95% in L. australis). Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were the main components in the phospholipids of two studied brown algae with contents varied from 32.27% to 52.33%. Total lipids were rich in PUFA (42.54% of total fatty acids for L. australis and 32.98% for L. tsengii), with EPA (11.46%, 14.30%) and AA (8.0%, 11.96%). L. tsengii methanol extract inhibited acetylcholinesterase (AChE) in in vitro assay with an IC50 value of 25.45 µg/mL. Both Lobophora methanol extracts display cytotoxic effects against four human cancer cell lines (KB, MCF7, HepG2 and A549) with IC50 in the range of 21.11-83.61 µg/mL. Especially, L. australis extract showed a strong cytotoxicity against KB cell lines with IC50 value of 21.11±0.39 µg/mL. [ABSTRACT FROM AUTHOR]

Thermal and mechanical treatments may affect the structure of hydrolyzed proteins, thus influencing the obtaining of peptides with improved bioactivity. In this work, tilapia muscle was treated by thermal sterilization or homogenization with ultra‐turrax (UT) and hydrolyzed with alcalase to obtain FPHs with antioxidant properties in salad dressing. To evaluate the bioactive potential of FPHs, the acetylcholinesterase inhibition assay was applied, resulting in up to 45.87% inhibition for the UT sample (60 mg/mL). Also, no cytotoxicity was detected by Allium cepa model for all FPHs. The emulsifying activity index and emulsifying stability index of FPHs indicated better emulsifying capacity in basic pH. As a proof of concept, FPHs were used as an emulsifying/antioxidant agent to prepare a salad dressing. FPHs increased the formulation's protein content, pseudoplastic behavior, color, and texture. In addition, FPHs aided the oxidative stability of salad dressing (evaluated by oil's extinction coefficient), demonstrating potential application in emulsified foods by acting on the elimination of radicals generated in lipid oxidation. Practical applications: Fish protein hydrolysates (FPHs) offer diverse bioactive properties such as antioxidant, antimicrobial, anticancer, antihypertensive, and acetylcholinesterase (associated with Alzheimer's disease) inhibitory effects. However, optimizing their technological properties poses a challenge, affecting applicability and bioactivity. Industrial processes such as thermal and mechanical treatments can alter protein structures, influencing peptide bioactivity post enzymatic hydrolysis. This study investigates the impact of substrate pre‐treatments, sterilization via thermal heating, and homogenization using a rotor‐stator system (ultra‐turrax) on FPHs' technological properties after hydrolysis with alcalase, including emulsifying capacity and acetylcholinesterase inhibitory capacity. In addition, it explores the application of pre‐treated FPHs in a real food system (French salad dressing), assessing rheological properties, texture, and oxidative stability. Such evaluations are crucial for ensuring the feasibility of industrial FPHs production and their application. [ABSTRACT FROM AUTHOR]

Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I (1), and one new phloroglucinol derivative, speradine J (8), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro. [ABSTRACT FROM AUTHOR]

Synthesis of novel unnatural amino acids (UAAs) from 4‐oxo‐4‐phenylbut‐2‐enoic acid derivatives with intramolecular aza‐Michael addition reaction in the presence of chlorosulfonyl isocyanate (CSI) was reported in soft conditions without any metal catalyst. Acids and base as a catalyst, and solvents effects were investigated for the synthesis of novel UAAs. This novel method provides inexpensive, practicable, and efficient approach to generate UAAs. The use of UAAs has attracted great interest in the development of therapeutic agents and drug discovery to improve their properties. In this context, in addition to the synthesis of new UAAs, their inhibition effects on important metabolic enzymes of acetylcholinesterase (AChE) and carbonic anhydrases I and II (hCA I and II) enzymes were investigated. The compound 2g showed the best inhibition for CA I and AChE enzymes, while compound 2i exhibited the best inhibition profile against CA II isoenzyme. The inhibition values of these compounds were found as 1.85 ± 0.64 for AChE, 0.53 ± 0.07 for hCA I, 0.44 ± 0.15 µM for hCA II, respectively, and they showed a stronger inhibitory property than acetazolamide (standard inhibitor for hCA I and II) and tacrine (standard inhibitor for AChE) molecules. The activity of the studied molecule against different proteins that are hCA I (PDB ID: 2CAB), hCA II (PDB ID: 5AML), and AChE (PDB ID: 1OCE) was examined. Finally, the drug properties of the studied molecule were examined by performing absorption, distribution, metabolism, excretion, and toxicity analysis. [ABSTRACT FROM AUTHOR]

The rapid expansion of agriculture in the Souss Massa region has been accompanied by a significant increase in pesticide usage to protect and increase crop yields. Unfortunately, these pesticides leave behind residues that can have detrimental effects on both human health and the environment. To investigate the impact of pesticide contamination on the coasts of Agadir Bay, our study focuses on the bivalve Perna perna (Linnaeus, 1758) as a biomonitoring sentinel species. Between autumn 2009 and summer 2010, we conducted measurements of pesticide residue concentrations and assessed two biomarkers of pollution the Glutathion-S-transferase (GST) and acetylcholinesterase (AChE) in the soft tissues of P. perna. These bivalves were seasonally collected from two different locations along the Agadir Bay coast. The results revealed that Glutathion-S-transferase and acetylcholinesterase showed seasonal variations, likely influenced by the species' reproductive cycle. In terms of pesticide concentrations, the levels of organochlorines were found to range from 13.40 to 109.76 ng g−1 of dry weight (dw) for Dichlofluanide, not-detected (ND) to 38.66 ng g−1 dw for Endosulfan S, ND to 15.76 ng g−1 dw for Lindane, ND to 33.66 ng g−1 dw for Fenarimol, and 0.26–35.02 ng g−1 dw for Buperimate. It should be noted that these levels of pesticide contamination are relatively low compared to values reported in similar studies conducted in other regions of the world. The contamination of Agadir Bay by pesticides can be attributed to their extensive use in agricultural practices in the Souss Massa region. [ABSTRACT FROM AUTHOR]

Two monophyletic Daphnia species (Daphnia magna and D. similis) were exposed to a sub-lethal concentration of Pb (50 µg/L) for nine generations under two food regimes (usual and restricted) and analyzed for acetylcholinesterase (AChE) activity, first reproduction delay, lifespan, and net reproductive rate (R0) at the subcellular, individual, and population levels, respectively. In the sixth generation, Pb-acclimated neonates were moved to clean media for three more generations to check for recovery. The net reproductive rate (R0) of D. magna was not affected by Pb. However, Pb stimulated reproduction, reduced lifespan, and decreased AChE activity. First reproduction delay and lifespan did not improve during the recovery process, suggesting a possible genetic adaptation. Food restriction reduced R0, lifespan, delayed hatching, and increased AChE activity; the opposite outcomes were observed for D. similis. The full recovery shown by R0 suggests the physiological acclimation of D. similis. Under food restriction, the animals exhibited a reduction of R0 and lifespan, delayed first reproduction, and increased AChE activity; however, there was no effect of Pb. The recovery process under food restriction showed that D. similis might not cope with Pb exposure, indicating a failed recovery. Such outcomes indicate that one model species' sensitivity may not represent another's sensitivity. [ABSTRACT FROM AUTHOR]