ACHE Gene Research Articles

Preliminary exploration of the expression of acetylcholinesterase in normal human T lymphocytes and leukemic Jurkat T cells.

The classic enzymatic function of acetylcholinesterase (AChE) is the hydrolysis of acetylcholine (ACh) in the neuronal synapse. However, AChE is also present in nonneuronal cells such as lymphocytes. Various studies have proposed the participation of AChE in the development of cancer. The ACHE gene produces three mRNAs (T, H and R). AChE-T encodes amphiphilic monomers, dimers, tetramers (G1 A, G2 A and G4 A) and hydrophilic tetramers (G4 H). AChE-H encodes amphiphilic monomers and dimers (G1 A and G2 A). AChE-R encodes a hydrophilic monomer (G1 H). The present study considered the differences in the mRNA expression (T, H and R) and protein levels of AChE, as well as the molecular forms of AChE, the glycosylation pattern and the enzymatic activity of AChE present in normal T lymphocytes and leukemic Jurkat E6-1 cells. The results revealed that AChE enzymatic activity was higher in normal T lymphocytes than in Jurkat cells. Normal T cells expressed AChE-H transcripts, whereas Jurkat cells expressed AChE-H and AChE-T. The molecular forms identified in normal T cells were G2 A (5.2 S) and G1 A (3.5 S), whereas those in Jurkat cells were G2 A (5.2 S), G1 A (3.5 S) and G4 H (10.6S). AChE in Jurkat cells showed altered posttranslational maturation since a decrease in the incorporation of galactose and sialic acid into its structure was observed. In conclusion, the content and composition of AChE were altered in Jurkat cells compared with those in normal T lymphocytes. The present study opened new avenues for exploring the development of novel therapeutic strategies against T-cell leukemia and for identifying potential molecular targets for the early detection of this type of cancer.

Polluted water from a storage dam (Villa Victoria, méxico) induces oxidative damage, AChE activity, embryotoxicity, and behavioral changes in Cyprinus carpio larvae

The Villa Victoria dam is one of the most important storage reservoirs in Mexico since it distributes water to more than 20 million inhabitants in the Metropolitan Zone of Mexico City. In this dam, the common carp (Cyprinus carpio) is an important food resource for the inhabitants, so the aim of this work was to evaluate the oxidative damage (lipoperoxidation, oxidized proteins, antioxidant enzymes activity and gene expression), AChE, embryotoxicity and behavioral changes in C. carpio embryos and larvae exposed to water from Villa Victoria dam for 24, 48, 72 and 96 h. The embryotoxicity was evaluated trough the General Morphology Score (GMS) and the teratogenic index. Behavioral changes in basal locomotor activity and thigmotaxis were evaluated in a DanioVision, Noldus ™. An increase in lipid and protein oxidation as well as modification of CAT, SOD and GPx enzymatic activity was observed during the exposure times. The GMS indicated a low development in the embryos, the teratogenic index was less than 1, however teratogenic effects as yolk edema, fin malformation, head malformation and scoliosis were observed. In parallel, an increase in AChE activity and gene expression was observed reflecting changes in distance traveled of the basal locomotor activity and thigmotaxis at the sampling points. In conclusion, pollutants in water from Villa Victoria dam caused oxidative damage, changes in SOD, CAT, GPx and AChE activity as well as embryotoxicity and modifications in the behavior of C. carpio larvae. This study demonstrates the need to implement restoration programs for this reservoir since, contamination in the Villa Victoria dam could eventually endanger aquatic life and human health.

Biochemical and molecular evaluation of oxidative stress and mitochondrial damage in fruit fly exposed to carmoisine.

In today's world, appearance is an important factor in almost all areas of our lives. Therefore, it has become common to use dyes to color foods to make them look appetizing and visually appealing. However, food additives have negative effects on biochemical processes in cells at both high and low doses. This study investigated the effect of carmoisine, a commonly used food coloring, on oxidative stress and damage parameters in Drosophila melanogaster in terms of both enzymatic and gene expression. The change in mitochondrial DNA copy number (mtDNA-CN), a marker of oxidative stress, was also examined. When the data obtained were analyzed, it was observed that carmoisine caused a significant decrease in GSH levels depending on the increase in dose. SOD, CAT, GPx, and AChE enzyme activities and gene expression levels were also found to be significantly decreased. All groups also showed a significant decrease in mtDNA-CN. The effect of carmoisine on Drosophila melanogaster morphology was also investigated in our study. However, no significant change was observed in terms of morphological development in any group. When all the findings were evaluated together, it was observed that carmoisin triggered oxidative stress and these effects became more risky at high doses. Therefore, we believe that the consumer should be made more aware of the side effects of azo dyes in food and that the type and concentration of each substance added to food should be specified.

Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria.

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in invivo and invitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.

Effects of thiamethoxam on physiological and molecular responses to potato plant (Solanum tuberosum), green peach aphid (Myzus persicae), and parasitoid (Aphidius gifuensis).

To improve integrated pest management (IPM) performance it is essential to assess pesticide side effects on host plants, insect pests, and natural enemies. The green peach aphid (Myzus persicae Sulzer) is a major insect pest that attacks various crops. Aphidius gifuensis is an essential natural enemy of M. persicae that has been applied effectively in controlling M. persicae. Thiamethoxam is a neonicotinoid pesticide widely used against insect pests. The current study showed the effect of thiamethoxam against Solanum tuberosum, M. persicae, and A. gefiuensis and the physiological and molecular response of the plants, aphids, and parasitoids after thiamethoxam application. Thiamethoxam affected the physical parameters of S. tuberosum and generated a variety of sublethal effects on M. persicae and A. gefiuensis, including nymph development time, adult longevity, and fertility. Our results showed that different thiamethoxam concentrations [0.1, 0.5, and 0.9 μm active ingredient (a.i.)/L] on different time durations (2, 6, and 10 days) increased the antioxidant enzyme activities SOD, POD, and CAT of S. tuberosum, M. persicae, and A. gefiuensis significantly compared with the control. Our results also showed that different thiamethoxam concentrations (0.1, 0.5, and 0.9 μm a.i./L) on different time durations (2, 6, and 10 days) increased the expression of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), acetylcholinesterase (AChE), carboxylesterase (CarE) and glutathione-S-transferase (GST) genes of S. tuberosum, M. persicae, and A. gefiuensis compared with the control. Our findings reveal that using thiamethoxam at suitable concentrations and time durations for host plants and natural enemies may enhance natural control through the conservation of natural enemies by overcoming any fitness disadvantages. © 2024 Society of Chemical Industry.

Genetic expressions and evaluation of insecticidal activity of some essential oil and methomyl lannate 90% against Spodopterafrugiperda

BackgroundFall armyworm (FAW) Spodopterafrugiperda is regarded as a major pest of various economic crops, their caterpillars are a highly destructive and have a wide host range. The application of traditional pesticides is the main strategies used for its control, that resulting to number of negative impacts of pesticides on the environment and development of pesticide resistance.MethodsThis study’s goal was to assess the insecticide potency of three essential oils [rosemary (Rosmarinusofficinalis L.), lemongrass (Cymbopogoncitratus) and Cinnamon (Cinnamomumzeylanicum)] and methomyl lannate 90% commercial insecticide to control S.frugiperda (fall armyworm) and their effects on expression of caspase-8 and inhibitor of apoptosis protein genes and expression of acetylcholinesterase (AChE) gene in fall armyworm (FAW).ResultsThe insecticidal activity against second larval instar of fall armyworm was evaluated with five concentrations (2.5%, 2%, 1.0%, 0.5% and 0.25%) for essential oil and four concentrations 0.4%, 0.2%, 0.15% and 0.05% for methomyl lannate 90%. The findings indicated that raising both essential oil concentrations and methomyl lannate 90% resulted in increased larval mortality at high concentration. The expression levels of Ache gene treated by low dose (0.3 µ/L) of methomyl lannate were increased (by 313%) significantly compared with the control but without significant differences.ConclusionsThe tested essential oils showed insecticidal activity against the second larval instar of S.frugiperda death as a result of treatment with the tested oils having an effect on the genes that the pest uses to express critical processes (genes of apoptosis).

Combined transcriptome and metabolome analysis reveals breed-specific regulatory mechanisms in Dorper and Tan sheep

BackgroundDorper and Tan sheep are renowned for their rapid growth and exceptional meat quality, respectively. Previous research has provided evidence of the impact of gut microbiota on breed characteristics. The precise correlation between the gastrointestinal tract and peripheral organs in each breed is still unclear. Investigating the metabolic network of the intestinal organ has the potential to improve animal growth performance and enhance economic benefits through the regulation of intestinal metabolites.ResultsIn this study, we identified the growth advantage of Dorper sheep and the high fat content of Tan sheep. A transcriptome study of the brain, liver, skeletal muscle, and intestinal tissues of both breeds revealed 3,750 differentially expressed genes (DEGs). The genes PPARGC1A, LPL, and PHGDH were found to be highly expressed in Doper, resulting in the up-regulation of pathways related to lipid oxidation, glycerophospholipid metabolism, and amino acid anabolism. Tan sheep highly express the BSEP, LDLR, and ACHE genes, which up-regulate the pathways involved in bile transport and cholesterol homeostasis. Hindgut content analysis identified 200 differentially accumulated metabolites (DAMs). Purines, pyrimidines, bile acids, and fatty acid substances were more abundant in Dorper sheep. Based on combined gene and metabolite analyses, we have identified glycine, serine, and threonine metabolism, tryptophan metabolism, bile secretion, cholesterol metabolism, and neuroactive ligand-receptor interaction as key factors contributing to the differences among the breeds.ConclusionsThis study indicates that different breeds of sheep exhibit unique breed characteristics through various physiological regulatory methods. Dorper sheep upregulate metabolic signals related to glycine, serine, and threonine, resulting in an increase in purine and pyrimidine substances. This, in turn, promotes the synthesis of amino acids and facilitates body development, resulting in a faster rate of weight gain. Tan sheep accelerate bile transport, reduce bile accumulation in the intestine, and upregulate cholesterol homeostasis signals in skeletal muscles. This promotes the accumulation of peripheral and intramuscular fat, resulting in improved meat quality. This work adopts a joint analysis method of multi-tissue transcriptome and gut metabolome, providing a successful case for analyzing the mechanisms underlying the formation of various traits.

Effects of trichlorfon on ecotoxicological biomarkers in farmed Colossoma macropomum (tambaqui).

Producers of fish have been looking for viable alternatives for the management of Colossoma macropomum (tambaqui) in confinement systems in order to avoid the harm and subsequent losses caused by parasitic diseases. One alternative used by farmers is pesticides, such as trichlorfon, which has a genotoxic effect. Thus, this study aimed to evaluate the changes in gene expression due to the side effects of trichlorfon in tambaqui. Two treatments were used based on LC50-96h of 0.870 mg/L using 30% and 50% trichlorfon with exposure periods of 48, 72 and 96 h. For differential expression of the genes in the liver, real-time PCR was performed for the AChE, GST, CYP2J6, CYP2C8, 18S and GAPDH genes. After 96 h of exposure to trichlorfon, an alteration in the gene expression profile of the antioxidant defense system (GST) of the tambaqui was observed. It was also observed that this organophosphate did not affect the expression of genes related to the isoenzymes that are responsible for the biotransformation of xenobiotics in phase I (2J6 and 2C8) and cholinesterase AChE. It was concluded that the reduction in gene expression of GST suggests a decrease in metabolization capacity in phase II.

Benign High Prevalence Antibody Yta

Abstract Introduction/Objective The Yt system, also known as the Cartwright system, discovered in 1964, consists of five antigens encoded by the ACHE gene on chromosome 7. Yta and Ytb are antithetical antigens on the GPI – linked red cell glycoprotein, acetylcholinesterase (AChE). About 8-10% of individuals of European ancestry are Yt(b+); Yta is highly prevalent in all populations. The other three high-prevalence antigens, YTEG, YTLI, and YTOT, were added to this system in 2018. Yta is not affected by trypsin but is destroyed by α-chymotrypsin treatment of reagent red cells. Yta and Ytb are sensitive to disulfide bond-reducing agents 2-aminoethylisothiouronium bromide (AET) and dithiothreitol (DTT). Yt antibodies are mostly IgG and require Indirect Antiglobulin Test (IAT) for detection. Yt antibodies are not clinically significant, although anti-Yta may cause accelerated destruction of Yt(a+) transfused red cells. Monocyte Monolayer Assay (MMA) is often used to determine whether the anti-Yta is predicted to cause destruction of transfused Yt(a+) red cells. Methods/Case Report A 50 year old female of Hispanic/Latino descent with a BRCA2 mutationand a history of scoliosis and severe migraineswas admitted for robotic-assisted bilateral salpingo-oophorectomy, cystoscopy, and dilation and curettage. A type and screen was ordered preoperatively, and her antibody screen was positive. In her profile, the origin of anti-Yta was identified from an outside facility since 2008, but written documentation of anti-Yta identification could not be located. On antibody identification, the patient’s plasma was reactive with all cells (1+ AHG in PEG) except the auto control. Rare frozen anti-Yta antisera were used for phenotyping the patient for Yta and she was found to be Yta negative. Yta antigens are sensitive or weakened by DTT, so DTT-treated panel screen cells were used to rule out all clinically significant alloantibodies except for the Kell system. Anti-K and anti-k were ruled out by testing the patient’s plasma against SCARF (Serum, Cells, and Rare Fluid Exchange) Yta negative with homozygous K positive and homozygous k positive cells. Anti-Yta was reconfirmed at our facility. Results (if a Case Study enter NA) NA Conclusion Yta-negative blood is so rare that anti-Yta reacts > 99.8% of most populations. In some cases, autologous transfusion may be recommended for a patient. However, anti-Yta is often benign, and antigen-negative blood may not need to be transfused. The patient had uncomplicated procedures, and blood transfusion was not indicated at that time.

Transcriptome Changes Reveal the Toxic Mechanism of Cadmium and Lead Combined Exposure on Silk Production and Web-Weaving Behavior of Spider A. ventricosus.

The combined exposure of multiple metals imposes a substantial burden on the ecophysiological functions in organisms; however, the precise mechanism(s) remains largely unknown. Here, adult female A. ventricosus were exposed to single and combined exposure to cadmium (Cd) and lead (Pb) through the food chain. The aim was to explore the combined toxicity of these metals on silk production and web-weaving behavior at physiological, cellular morphological, and transcriptomic levels. The Cd and Pb combined exposure significantly inhibited the ability of silk production and web-weaving, including reduced silk fiber weight and diameter of single strands, lowered weaving position, induced nocturnal weaving, and increased instances of no-web, and showed a dose-response relationship on the Cd and Pb bioaccumulation. Concurrently, severe oxidative stress and degenerative changes in cells were observed. In addition, the combined pollution of Cd and Pb demonstrated synergistic effects, influenced by variations in concentration, on the enrichment of metals, inhibition of silk weight, oxidative damage, and cellular degeneration. At the transcriptome level, the upregulated ampullate spidroin genes and downregulated amino acid anabolic genes, upregulated Far genes and downregulated cytoskeleton-related TUBA genes, and overexpressed AChE and Glu genes may tend to present promising potential as biomarkers for silk protein synthesis, cellular degeneration, and neurotransmitter induction. This study offers an enormous capability for a comprehensive understanding of the eco-toxicological effects and mechanisms of multiheavy metals pollution.

Evaluation of GSTP1, GSTA4 and AChE Gene Methylation in Bovine Lymphocytes Cultured In Vitro with Miconazole Alone and in Combination with Mospilan 20SP.

5-methylcytosine (5mC) is one of the most important epigenetic modifications. Its increased occurrence in regulatory sequences of genes, such as promoters and enhancers, is associated with the inhibition of their expression. Methylation patterns are not stable but are sensitive to factors such as the environment, diet, and age. In the present study, we investigated the effects of fungicide miconazole, both alone and in combination with the insecticide Mospilan 20SP, on the methylation status of bovine GSTP1, GSTA4, and AChE genes in bovine lymphocytes cultured in vitro. The methylation-specific PCR technique was used for the objectives of this study. We found that miconazole alone at concentrations of 1.25, 2.5, 5, 10, 25, and 50 µg/mL after 24 h exposure probably did not induce changes in methylation for all three genes analysed. The same results were found for the combination of pesticides at 24 h exposure and the following concentrations for each of them: 0.625, 1.25, 2.5, 5, and 12.5 µg/mL. Thus, we can conclude that the fungicide miconazole alone, as well as in combination with the insecticide Mospilan 20SP, was unlikely to cause changes to the methylation of bovine GSTP1, GSTA4, and AChE genes.

Association of NOTCH4 and ACHE gene polymorphism in Alzheimer’s disease of Gujarat cohort

BackgroundAlzheimer's Disease (AD) is the most common form of dementia, affecting cognitive and behavioral functions. AD is a complex disease resulting from the modest effect of gene interaction and environmental factors, as a result of which the exact pathogenesis is still unknown. AimThe aim of the present study was to investigate the association between variants of 98 targeted genes with Alzheimer's disease phenotype. MethodA total of 98 genes from 32 AD cases and 11 controls were genotyped using the Haloplex target enrichment method and the PCR-RFLP approach.Association analysis was performed using the PLINK tool to identify the variant significantly associated with AD. Functional enrichment analysis and network analysis was performed using ClueGo and String database respectively. The Expression Quantitative Trait Loci (eQTL) analysis using the Genotype Tissue Expression (GTEx) dataset to explore the possible implication of the variant on the expression of one or more genes in different brain regions and whole blood. ResultAssociation analysis showed significant association of 19 variant assigned to 16 genes with Alzheimer’s with p-value < 0.05 with rs367398/NOTCH4 only variant that passed multiple test corrections. Functional enrichment analysis showed association of these genes with AD. ClueGo and network analysis utilizing the String database suggested that genes are directly and indirectly linked to the AD pathogenesis. eQTL analysis revealed that the rs367398/NOTCH4 and rs1799806/ACHE variant showed significant eQTL for the neighbouring genes. ConclusionThe present study showed the possible role of 16 genes in AD pathogenesis, especially highlighting the role of rs367398/NOTCH4 and rs1799806/ACHE. However further investigation with large cohort is required to study and validate the implication of these variants in the AD pathogenesis.

Abelmoschus eculentus Seed Extract Exhibits In Vitro and In Vivo Anti-Alzheimer's Potential Supported by Metabolomic and Computational Investigation.

Abelmoschus esculentus Linn. (okra, F. Malvaceae) is a fruit widely consumed all over the world. In our study, the anti-Alzheimer's potential of A. esculentus was evaluated. An in vitro DPPH free radical assay on A. esculentus seed's total extract and AChE inhibition potential screening indicated a significant anti-Alzheimer's activity of the extract, which was confirmed through an in vivo study in an aluminum-intoxicated rat model. Additionally, in vivo results demonstrated significant improvement in Alzheimer's rats, which was confirmed by improving T-maze, beam balance tests, lower serum levels of AChE, norepinephrine, glycated end products, IL-6, and MDA. The levels of dopamine, BDNF, GSH, and TAC returned to normal values during the study. Moreover, histological investigations of brain tissue revealed that the destruction in collagen fiber nearly returns back to the normal pattern. Metabolomic analysis of the ethanolic extract of A. esculentus seeds via LC-HR-ESI-MS dereplicated ten compounds. A network pharmacology study displayed the relation between identified compounds and 136 genes, among which 84 genes related to Alzheimer's disorders, and focused on AChE, APP, BACE1, MAPT and TNF genes with interactions to all Alzheimer's disorders. Consequently, the results revealed in our study grant potential dietary elements for the management of Alzheimer's disorders.

Acetylcholinesterase, pro-inflammatory cytokines, and association of ACHE SNP rs 17228602 with male infertility.

Male infertility is a complex and polygenic reproductive disease. 10-15% of the males are affected by idiopathic infertility conditions. Acetylcholine (ACh), a major neurotransmitter has been reported to play a non-neuronal role as well. Acetylcholinesterase (AChE) is the primary ACh hydrolyzing enzyme whose over or lower expression influence the availability of ACh for physiological roles. The purpose of the study was to find the possible impact and association of acetylcholinesterase, ACHE gene variant rs 17228602, and pro-inflammatory cytokines in clinically diagnosed infertile males. The study includes clinically diagnosed fifty non-infertile (control) and forty-five infertile males. Whole blood AChE enzymatic activity was measured. Genotyping of rs17228602 was carried out from peripheral blood by standard molecular methods. Pro-inflammatory cytokines were determined by the ELISA method. AChE enzyme was found to be significantly elevated in infertile than non-infertile males. ACHE SNP rs17228602 had shown significant association in dominant model (odd ratio = 0.378, 95% CI = 0.157-0.911, p-value 0.046). Pro-inflammatory cytokine IL-1β was notably increased with statistical significance (p ≤0.05) in male infertile patients. The study concludes and speculates that AChE plays role in the pathogenesis of male infertility through the modulation of inflammatory pathways. Further studies in this direction may resolve the idiopathic cases of male infertility. Other variants of ACHE and the association of miRNA for the regulation of AChE in male infertility are suggested for further insight.

Influence of the chronic groundwater fluoride consumption on cholinergic enzymes, ACHE and BCHE gene SNPs and pro-inflammatory cytokines: A study with Pakistani population groups

Fluoride is one of the abundant elements found in the Earth's crust and is a global environmental issue. The present work aimed to find the impact of chronic consumption of fluoride contained groundwater on human subjects. Five hundred and twelve volunteers from different areas of Pakistan were recruited. Cholinergic status, acetylcholinesterase and butyrylcholinesterase gene SNPs and pro-inflammatory cytokines were examined. Association analysis, regression and other standard statistical analyses were performed. Physical examination of the fluoride endemic areas' participants revealed the symptoms of dental and skeletal fluorosis. Cholinergic enzymes (AChE and BChE) were significantly increased among different exposure groups. ACHE gene 3′-UTR variant and BCHE K-variant showed a significant association with risk of fluorosis. Pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were found to be increased and have a significant correlation in response to fluoride exposure and cholinergic enzymes. The study concludes that chronic consumption of high fluoride-contained water is a risk factor for developing low-grade systemic inflammation through the cholinergic pathway and the studied cholinergic gene SNPs were identified to be associated with the risk of flurosis.

RETRACTED ARTICLE: Evaluating the neuroprotective effect of Spirulina platensis–loaded niosomes against Alzheimer’s disease induced in rats

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by memory loss, changes in behavior, and avoidance of social bonds. Aluminum is one of the main risk factors in the development of AD. Spirulina platensis (SP) is a microalga that improves motor and cognitive skills and prevents cerebral endothelial damage. SP could be delivered in a more controlled and targeted manner using nanoparticles like niosomes. The purpose of this research was to develop a SP-loaded niosome (SPLN) formulation as a drug delivery system to investigate the effectiveness and toxicity of SP as an AD therapy using the AlCl3-induced AD rat model. A niosomal formulation that consists of Tween 60, cholesterol, and dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation. AD was induced in rats by orally administering AlCl3. Compared with the AlCl3 control, the group treated with the SPLN formulation showed enhancement of the recognition and working memories by increasing the difference score, the discrimination ratio, and the spontaneous alternation behavior. Additionally, it revealed a significant increase in AchE genes, restored the reduced brain neurotransmitters, and improved brain oxidative status. In conclusion, SPLN formulation could be considered an effective AD therapy.

Neuroprotective Effects of Virgin Coconut Oil Supplemented Diet against Sodium Benzoate-induced Acetylcholinesterase Dysfunction and Cognitive Impairment: Role of Nrf2/NfKb Signaling Pathway.

The effect of virgin coconut oil (VCO) supplemented diet on sodium benzoate (SB) - induced neurotoxicity in male Wistar rats was investigated. Twenty (20) male Wistar rats weighing 160-180g were divided into four (4) groups: Control which received 1ml of normal saline, SB-treated; received 200 mg/kg b.w, SB + Low Dose VCO-treated (SB + 5% VCO mixed with 95g of rat chow), and SB + High Dose VCO-treated (SB+ 15% VCO mixed with 85g of rat chow). The brain was processed for NRF-2, NF-kB, and acetylcholine esterase (AchE) gene expression levels. Also, the blood sample was processed for assessment of superoxide dismutase (SOD), catalase (CAT), and IL1B levels. One-way ANOVA and Tukey post hoc tests were used to analyze data. SB-treated rats with no intervention showed anxiety-like behavior and impaired memory as depicted by a significant (p<0.0001) increase in anxiety index, increase in brain NF-KB, increase in serum IL1B and increase in AchE gene expression level, reduction in the recognition ratio, decreased spontaneous alternation performance, decreased CAT and SOD levels and decreased NRF-2 expression level when compared to other groups (especially control and SB + 5% VCO). VCO supplemented diet (both 5% and 15%) significantly (p<0.0001) increased the CAT and SOD levels, increased the NRF-2 gene expression level, and significantly (p <0.0001) decreased the IL1-B level. Moreover, 5% VCO significantly (p<0.0001) decreased the anxiety index, decreased AchE and NFkB gene expression levels, increased spontaneous alternation performance, and increased recognition ratio compared to 15% VCO. VCO shows a neuroprotective effect in attenuating cognitive impairment and anxiety-like behavior in SB-induced model by modulating oxidative stress and inflammatory pathways, and also enhancing cholinergic neurotransmission. Keywords: Virgin coconut oil; sodium benzoate; acetylcholinesterase; catalase; superoxide dismutase; oxidative stress.

The Protective and Therapeutic Anti-Alzheimer Potential of Olea europaea L. cv. Picual: An In Silico and In Vivo Study.

LC-HRESIMS metabolomic profiling of Olea europaea L. cv. Picual (OEP) (Saudi Arabian olive cultivar, F. Oleacea) revealed 18 compounds. Using pharmacology networking to specify the targets of the identified compounds with a relationship to Alzheimer's disease, it was possible to identify the VEGFA, AChE, and DRD2 genes as the top correlated genes to Alzheimer's disease with 8, 8, and 6 interactions in the same order. The mechanism of action on cellular components, biological processes, and molecular functions was determined by gene enrichment analysis. A biological pathway comparison revealed 13 shared pathways between the identified genes and Alzheimer protein genes (beta-amyloid band tau proteins). The suggested extract's anti-Alzheimer potential in silico screening was confirmed through in vivo investigation in regressing the neurodegenerative features of Alzheimer's dementia in an aluminum-intoxicated rat model (protective and therapeutic effects, 100 mg/kg b.w.). In vivo results suggested that OEP extract significantly improved Alzheimer's rats, which was indicated by the crude extract's ability to improve T-maze performance; lower elevated serum levels of AChE, AB peptide, and Ph/T ratio; and normalize the reduced level of TAC during the study. The results presented in this study may provide potential dietary supplements for the management of Alzheimer's disease.

Aberrant APOBEC3C expression induces characteristic genomic instability in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a well-known lethal and heterogeneous disease. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) is an important mutagenic driver that has seldom been investigated in PDAC. Therefore, this study investigated the significance of APOBEC3C in PDAC. First, cytosine deamination-associated mutation signatures were identified in the PDAC cohorts from TCGA and Fudan University Shanghai Cancer Center (FUSCC) datasets, and C > X-enriched kataegis regions were identified in the FUSCC cohort (12 to 27 counts per sample). Patients were stratified according to APOBEC3C expression, and high APOBEC3C expression was found to correlate with a higher motif enrichment score of 5’-CC-3’ and an elevated kataegis count within PCSK5 and NES genes. Second, we compared APOBEC expression in PDAC and normal pancreatic tissues and found that APOBEC3C was substantially upregulated in PDAC. APOBEC3C-overexpressing cell lines were generated to substantiate the effects of APOBEC3C on PDAC genome, including alterations in single-nucleotide variant (SNV) classes (higher proportion of C > T conversions) and the formation of kataegis regions (newly occurring kataegis regions detected in ACHE and MUC6 genes). Three different PDAC cohorts (FUSCC, TCGA, and QCMG) were analysed to evaluate the prognostic value of APOBEC3C, and APOBEC3C overexpression predicted shorter survival. Finally, the APOBEC3C overexpression correalted with the PDAC tumour microenvironment (TME) remodelling, APOBEC3C expression was associated with the invasion of CD4 + T lymphocytes and CD8 + T lymphocytes (cytotoxic T lymphocytes, CTLs), indicating enhanced immune activity and validating the practicality of APOBEC3C for guiding immunotherapy.

ZIF-8 nanoparticles induce neurobehavioral disorders through the regulation of ROS-mediated oxidative stress in zebrafish embryos

Zeolite imidazolate framework-8 (ZIF-8) is a nanomaterial of metal-organic frameworks (MOFs), which have various applications in drug delivery and water pollution remediation. However, little is known about its developmental neurotoxicity in aquatic organisms, especially on the low-level exposure. In the present study, we investigated the toxic effects of ZIF-8 NPs on the neuron development, behavioral traits, oxidative stress and gene expression in zebrafish embryos. Firstly, our results showed that ZIF-8 induced significantly embryonic malformations and abnormal development of nervous system in zebrafish embryos with a concentration-dependent manner. Meanwhile, the locomotor behavior was obviously inhibited while the anxiety behavior was greatly increased after ZIF-8 exposure. Secondly, the levels of ROS and antioxidant enzyme activities (CAT, SOD and MDA) together with AChE and ATPase were substantially increased in the ZIF-8 exposed groups. At the molecular level, ZIF-8 NPs could down-regulate the expression profiles of neural development-related genes (gap43, synapsin 2a and neurogenin 1) and PD-like related genes (dj-1, dynactin and parkin), but up-regulate the expression levels of neuro-inflammatory genes (nox-1, glip1a and glip1b) in larval zebrafish. In addition, we further explored the molecular mechanism of neurotoxicity induced by ZIF-8 with pharmacological experiments. The results showed that specific inhibition of ROS-mediated oxidative stress by the astaxanthin could reverse the expression patterns of ATPase, AChE and neurodevelopmental genes. Moreover, astaxanthin can partially rescue the ZIF-8-modulated locomotor behavior. Taken together, our results demonstrated that ZIF-8 had the potential to cause neurotoxicity in zebrafish embryos. These informations presented in this study will help to elucidate the molecular mechanisms of ZIF-8 nanoparticles exposure in zebrafish, which providing a scientific evaluation of its safety to aquatic ecosystems.