ABSTRACT
Meiosis is a critical process in sexual reproduction, and errors during this cell division can significantly impact fertility. Successful meiosis relies on the coordinated action of numerous genes involved in DNA replication, strand breaks, and subsequent rejoining. DNA topoisomerase enzymes play a vital role by regulating DNA topology, alleviating tension during replication and transcription. To elucidate the specific function of DNA topoisomerase 1α ( A t T O P 1 α ) in male reproductive development of Arabidopsis thaliana, we investigated meiotic cell division in Arabidopsis flower buds. Combining cytological and biochemical techniques, we aimed to reveal the novel contribution of A t T O P 1 α to meiosis. Our results demonstrate that the absence of A t T O P 1 α leads to aberrant chromatin behavior during meiotic division. Specifically, the top1α1 mutant displayed altered heterochromatin distribution and clustered centromere signals at early meiotic stages. Additionally, this mutant exhibited disruptions in the distribution of 45s rDNA signals and a reduced frequency of chiasma formation during metaphase I, a crucial stage for genetic exchange. Furthermore, the atm-2×top1α1 double mutant displayed even more severe meiotic defects, including incomplete synapsis, DNA fragmentation, and the presence of polyads. These observations collectively suggest that A t T O P 1 α plays a critical role in ensuring accurate meiotic progression, promoting homologous chromosome crossover formation, and potentially functioning in a shared DNA repair pathway with ATAXIA TELANGIECTASIA MUTATED (ATM) in Arabidopsis microspore mother cells.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Chromosome Segregation , DNA Topoisomerases, Type I , Meiosis , Arabidopsis/genetics , Arabidopsis/enzymology , Meiosis/physiology , Meiosis/genetics , DNA Topoisomerases, Type I/metabolism , DNA Topoisomerases, Type I/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Recombination, Genetic , MutationABSTRACT
Harmful elements in Egyptian phosphoric acid were identified by radiochemical neutron activation analysis. In the Second Egyptian Nuclear Research Reactor, precipitates were created and examined to identify many types of contaminants (Ce, Co, Cr, etc.). New bionanocomposite materials effectively removed with a high proportion each of Ce, Th, Pa, U, Np, Zn, and Co (100%) and a somewhat lower percentage (65-85%) for Cr, Sc, and Fe from simulated solutions, suggesting promise for purifying phosphoric acid.
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BACKGROUND: Chronic systemic anticoagulation use is prevalent for various thromboembolic conditions. Anticoagulation (usually through heparin products) is also recommended for the initial management of non-ST-elevation myocardial infarction (NSTEMI). AIMS: To evaluate the in-hospital outcomes of patients with NSTEMI who have been on chronic anticoagulation. METHODS: Using the National Inpatient Sample (NIS) years 2016-2020, NSTEMI patients and patients with chronic anticoagulation were identified using the appropriate International Classification of Diseases, 10th version (ICD-10) appropriate codes. The primary outcome was all-cause in-hospital mortality while the secondary outcomes included major bleeding, ischemic cerebrovascular accident (CVA), early percutaneous coronary intervention (PCI) (i.e., within 24 h of admission), coronary artery bypass graft (CABG) during hospitalization, length of stay (LOS), and total charges. Multivariate logistic or linear regression analyses were performed after adjusting for patient-level and hospital-level factors. RESULTS: Among 2,251,914 adult patients with NSTEMI, 190,540 (8.5%) were on chronic anticoagulation. Chronic anticoagulation use was associated with a lower incidence of in-hospital mortality (adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.65-0.73, p < 0.001). There was no significant difference in major bleeding (aOR: 0.95, 95% CI: 0.88-1.0, p = 0.15) or ischemic CVA (aOR: 0.23, 95% CI: 0.03-1.69, p = 0.15). Chronic anticoagulation use was associated with a lower incidence of early PCI (aOR: 0.78, 95% CI: 0.76-0.80, p < 0.001) and CABG (aOR: 0.43, 95% CI: 0.41-0.45, p < 0.001). Chronic anticoagulation was also associated with decreased LOS and total charges (adjusted mean difference [aMD]: -0.8 days, 95% CI: -0.86 to -0.75, p < 0.001) and (aMD: $-19,340, 95% CI: -20,692 to -17,988, p < 0.001). CONCLUSIONS: Among patients admitted with NSTEMI, chronic anticoagulation use was associated with lower in-hospital mortality, LOS, and total charges, with no difference in the incidence of major bleeding.
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Some heterocycles bearing a benzo[h]quinoline moiety were synthesized through treating a 3-((2-chlorobenzo[h]quinolin-3-yl)methylene)-5-(p-tolyl)furan-2(3H)-one with four nitrogen nucleophiles comprising ammonium acetate, benzylamine, dodecan-1-amine, and 1,2-diaminoethane. Also, thiation reactions of furanone and pyrrolinone derivatives were investigated. The insecticidal activity of these compounds against mosquito larvae (Culex pipiens L.) was evaluated. All tested compounds exhibited significant larvicidal activity, surpassing that of the conventional insecticide chlorpyrifos. In silico docking analysis revealed that these compounds may act as acetyl cholinesterase (AChE) inhibitors, potentially explaining their larvicidal effect. Additionally, interactions with other neuroreceptors, such as nicotinic acetylcholine receptor and sodium channel voltage-gated alpha subunit were also predicted. The results obtained from this study reflected the potential of benzo[h]quinoline derivatives as promising candidates for developing more effective and sustainable mosquito control strategies. The ADME (absorption, distribution, metabolism, and excretion) analyses displayed their desirable drug-likeness and oral bioavailability properties.
Subject(s)
Culex , Insecticides , Larva , Molecular Docking Simulation , Quinolines , Animals , Culex/drug effects , Insecticides/pharmacology , Insecticides/chemistry , Insecticides/chemical synthesis , Larva/drug effects , Structure-Activity Relationship , Quinolines/pharmacology , Quinolines/chemistry , Quinolines/chemical synthesis , Molecular Structure , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Dose-Response Relationship, Drug , Acetylcholinesterase/metabolismABSTRACT
OBJECTIVE: To evaluate histologically and radiographically the potential of dog's immature roots with apical periodontitis to regenerate after regenerative endodontic treatment using mesoporous silica nanoparticles (MSNs) with/without bone morphogenic protein (BMP-2) as scaffolds. METHODS: In 4 mongrel dogs, 56 immature teeth with 96 roots were infected, resulting in necrotic pulps and periapical pathosis. According to the evaluation time (Group I = 30 days and Group II = 90 days), 90 roots were divided into two equal groups (45 roots each) and 6 roots used to replace any lost root during the procedure. The two main groups were further divided according to treatment protocol into 5 subgroups (9 roots each): blood clot (BC subgroup), mesoporous silica nanoparticles scaffold only (MSNs subgroup), mesoporous silica nanoparticles impregnated with BMP2 (MSNs + BMP2 subgroup), infected teeth without treatment (+ ve control subgroup) and normal untouched teeth (-ve control subgroup). All teeth surfaces were coated with Tincture iodine and calcium hydroxide was applied prior to treatment protocols. Then, teeth were restored with glass ionomer filling to seal the remaining part of the access cavity. Radiography evaluation of the increase in root length, root thickness and occurrence of apical closure were performed. Following the sacrifice of the two dogs at each time of evaluation, histopathological analysis was performed and included the inflammatory cells count, bone resorption, tissue ingrowth, deposition of hard tissue, and closure of the apical part. All data were statistically analyzed. RESULTS: Compared to BC subgroup, MSNs and MSNs + BMP-2 subgroups exhibited significant higher increase in root length and thickness as well as higher vital tissue in-growth and new hard tissue formation in group II (P < 0.05). MSNs + BMP-2 subgroup had significant higher increase in root length and thickness as well as significant lower inflammatory cell count than MSNs subgroup in both groups (P < 0.05). There were no significant differences between MSNs and MSNs + BMP-2 subgroups regarding new hard tissue formation in both groups and apical closure in group I (P > 0.05). CONCLUSION: MSNs with/without BMP-2 scaffolds enabled the continuing growth of roots in immature teeth with necrotic pulps and periapical pathosis. Addition of BMP-2 to MSNs scaffold improved its outcome in regenerative endodontics. CLINICAL RELEVANCE: MSNs with/without BMP-2 scaffolds may alternate blood clot for regenerative endodontic treatment of immature teeth with necrotic pulps.
Subject(s)
Dental Pulp , Nanoparticles , Silicon Dioxide , Tissue Scaffolds , Tooth Root , Animals , Dogs , Tooth Root/drug effects , Tooth Root/diagnostic imaging , Bone Morphogenetic Protein 2 , Periapical Periodontitis/therapy , Periapical Periodontitis/pathology , Dental Pulp Necrosis/therapy , Regeneration/drug effects , Regenerative Endodontics/methodsABSTRACT
Pieris rapae (Lepidoptera: Pieridae) poses a significant threat to Brassicaceae crops, leading to substantial losses annually. Repeated insecticide applications are widely used to protect crops and increase the resistance of P. rapae. Exploring the biochemical and molecular basis of insecticide tolerance in P. rapae is crucial for achieving effective insect suppuration and implementing resistance control strategies. In our research, emamectin benzoate (EBZ) resistance was developed in P. rapae strain through selective pressure over 15 generations. Moreover, the biochemical mechanisms underlying resistance to EBZ and its potential cross-resistance to other insecticides were studied. Additionally, the expression levels of cytochrome P450 (CYP450) and glutathione-s-transferase (GST) genes in P. rapae were quantitatively assessed upon exposure to EBZ using real-time PCR. Our data exhibited that the LC50 value of susceptible strain (Sus) and EBZ resistance strain (EBZ-R) were 0.009 and 8.09 mg/L, with a resistance ratio (RR) reaching 898.8-fold. The EBZ-R stain displayed notably low cross-resistance to lambda-cyhalothrin, spinetoram, and cypermethrin. However, it demonstrated a moderate level of cross-resistance to deltamethrin. Conversely, no cross-resistance was noted to chlorantraniliprole and indoxacarb. Notably, enzyme inhibitors of detoxification enzymes revealed that piperonyl butoxide (PBO) and diethyl maleate (DEM) enhanced the EBZ toxicity to the resistant strain, indicating the potential involvement of CYP450 and GST in avermectin resistance. A remarkable enhancement in CYP450 and GST activity was observed in the EBZ-R stain. CYP450 and GST genes are upregulated in the EBZ-R stain compared to the Sus strain, which serves as a basis for comprehending the mechanism behind P. rapae resistance to EBZ. The molecular docking analysis demonstrated that EBZ has a high binding affinity with CYP6AE120 and PrGSTS1 with docking energy values of -20.19 and -22.57 kcal/mol, respectively. Our findings offer valuable insights into crafting efficient strategies to monitor and manage resistance in P. rapae populations in Egypt.
Subject(s)
Cytochrome P-450 Enzyme System , Glutathione Transferase , Insecticide Resistance , Insecticides , Ivermectin , Animals , Ivermectin/analogs & derivatives , Ivermectin/toxicity , Ivermectin/pharmacology , Insecticide Resistance/genetics , Insecticides/toxicity , Insecticides/pharmacology , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Glutathione Transferase/metabolism , Glutathione Transferase/genetics , Pyrethrins/toxicity , Pyrethrins/pharmacology , Butterflies/drug effects , Butterflies/genetics , Nitriles/toxicity , Insect Proteins/genetics , Insect Proteins/metabolismABSTRACT
OBJECTIVE: This study aimed to clinically compare the accuracy of bracket positioning between three-dimensionally (3D) printed indirect bonding trays and vacuum-formed trays made over 3D-printed models. MATERIAL AND METHODS: Fourteen patients, planned for fixed orthodontic therapy, were randomly divided into two equal groups. For both groups, both dental arches were scanned, to acquire virtual models, brackets were virtually positioned from central incisors to second premolars, and scans for the final bracket positions were performed. In the first group, transfer trays were 3D-printed. In the second group, virtual models were 3D-printed, and vacuum-formed soft sheets were thermoformed on the printed model. Teeth were indirectly bonded and then scanned. Superimposition of the virtual and the final bracket positioning scans was performed to measure linear and angular deviations in brackets positions. RESULTS: The first group showed significantly less occlusogingival and buccolingual linear errors than the second group. No significant differences in angular deviations were found between both groups. The frequencies of clinically acceptable linear errors within 0.5 mm and angular errors within 2° showed no statistically significant difference between both groups (p> 0.05 for all measurements). The transfer errors in both groups showed linear directional biases toward the mesial, gingival and labial directions. There was no statistically significant difference in the rate of immediate debonding between both groups (10.7% and 7.1% for the first and the second groups, respectively, p=0.295). CONCLUSIONS: 3D-printed indirect bonding trays were more accurate than vacuum-formed trays, in terms of linear deviations. Both types of trays showed similar angular control.
Subject(s)
Dental Bonding , Orthodontic Brackets , Printing, Three-Dimensional , Humans , Dental Bonding/methods , Models, Dental , Female , Vacuum , Male , Adolescent , Young Adult , Bicuspid/diagnostic imagingABSTRACT
Acetamiprid (ACDP) is a widely used neonicotinoid insecticide that is popular for its efficacy in controlling fleas in domestic settings and for pets. Our study aims to offer a comprehensive examination of the toxicological impacts of ACDP and the prophylactic effects of cinnamon nanoemulsions (CMNEs) on the pathological, immunohistochemical, and hematological analyses induced by taking ACDP twice a week for 28 days. Forty healthy rats were divided into four groups (n = 10) at random; the first group served as control rats; the second received CMNEs (2 mg/Kg body weight); the third group received acetamiprid (ACDP group; 21.7 mg/Kg body weight), and the fourth group was given both ACDP and CMNEs by oral gavage. Following the study period, tissue and blood samples were extracted and prepared for analysis. According to a GC-MS analysis, CMNEs had several bioactive ingredients that protected the liver from oxidative stress by upregulating antioxidant and anti-inflammatory agents. Our findings demonstrated that whereas ACDP treatment considerably boosted white blood cells (WBCs) and lymphocytes, it significantly lowered body weight gain (BWG), red blood cells (RBCs), hemoglobin (Hb), hematocrit (HCT), and platelets (PLT). ACDP notably reduced antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) and elevated hydrogen peroxide and malondialdehyde levels compared with other groups. ACDP remarkably raised alanine aminotransferase (ALT), aspartate amino transaminase (AST), and alkaline phosphatase (ALP) levels.Moreover, the histopathological and immunohistochemistry assays discovered a severe toxic effect on the liver and kidney following ACDP delivery. Furthermore, cyclooxygenase 2 (COX-2) + immunoexpression was enhanced after treatment with CMNEs. All of the parameters above were returned to nearly normal levels by the coadministration of CMNEs. The molecular docking of cinnamaldehyde with COX-2 also confirmed the protective potential of CMNEs against ACDP toxicity. Our findings highlighted that the coadministration of CMNEs along with ACDP diminished its toxicity by cutting down oxidative stress and enhancing antioxidant capacity, demonstrating the effectiveness of CMNEs in lessening ACDP toxicity.
Subject(s)
Cinnamomum zeylanicum , Emulsions , Insecticides , Liver , Molecular Docking Simulation , Neonicotinoids , Animals , Neonicotinoids/pharmacology , Cinnamomum zeylanicum/chemistry , Insecticides/toxicity , Rats , Emulsions/chemistry , Emulsions/pharmacology , Male , Liver/drug effects , Liver/pathology , Kidney/drug effects , Kidney/pathology , Oxidative Stress/drug effects , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/prevention & control , Antioxidants/pharmacology , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Kidney Diseases/pathology , Rats, Sprague-DawleyABSTRACT
OBJECTIVES: Effective disinfection of the root canals is the cornerstone of successful endodontic treatment. Diminishing the microbial load within the root canal system is crucial for healing in endodontically treated teeth. The aim of this study was to evaluate the effect of 2780 nm Er,Cr:YSGG and 940 nm diode lasers on the eradication of microorganisms from single-rooted teeth with asymptomatic apical periodontitis. MATERIALS AND METHODS: Thirty participants conforming to the inclusion criteria were randomly divided into 3 groups according to the disinfection protocol used; Conventional group: 2.5% Sodium Hypochlorite (NaOCl) and 17% EDTA solution NaOCl/EDTA, Dual laser group: 2780 nm Erbium, chromium: yttrium scandium-gallium-garnet (Er,Cr:YSGG) laser and 940 nm diode laser Er,CrYSGG/Diode, and Combined group: 17% EDTA and 940 nm diode laser EDTA/Diode. Bacterial samples were collected before and after intervention. The collected data were statistically analyzed using Friedman's test and Kruskal-Wallis test (P ≤ 0.05). RESULTS: The results of the study showed that both dual laser Er,CrYSGG/Diode and combined laser EDTA/Diode groups showed significantly less mean Log10 CFU/ml of aerobic and anaerobic bacterial counts than the conventional NaOCl/EDTA group. CONCLUSIONS: In this study we evaluated in vivo the bactericidal efficacy of three disinfection protocols for endodontic treatment of single-rooted teeth with apical periodontitis. The results indicated that both dual laser Er,CrYSGG/Diode and combined laser EDTA/Diode groups provide superior bactericidal effect compared to the conventional NaOCl/EDTA group. CLINICAL RELEVANCE: The integration of lasers into root canal disinfection protocols has demonstrated significant bacterial reduction which might promote healing and long-term success.
Subject(s)
Lasers, Solid-State , Periapical Periodontitis , Humans , Lasers, Semiconductor/therapeutic use , Disinfection/methods , Dental Pulp Cavity/microbiology , Edetic Acid/pharmacology , Edetic Acid/therapeutic use , Enterococcus faecalis , Root Canal Irrigants/pharmacology , Sodium Hypochlorite/pharmacology , Sodium Hypochlorite/therapeutic use , Lasers, Solid-State/therapeutic use , Anti-Bacterial Agents/therapeutic use , Periapical Periodontitis/drug therapyABSTRACT
STATEMENT OF PROBLEM: The influence of the ferrule thickness and post materials on the fracture resistance of endodontically treated teeth remains unclear. PURPOSE: The purpose of this laboratory study was to evaluate the influence of post material and ferrule thickness on the fracture resistance of endodontically treated mandibular premolars. MATERIAL AND METHODS: Sixty-four extracted and endodontically treated mandibular first premolars were used and divided into 4 test groups (n=16) depending on the ferrule thickness: F-0: without a ferrule, F-0.5: with a 0.5-mm ferrule thickness, F-1: with a 1-mm ferrule thickness, and F-1.5: with a 1.5-mm ferrule thickness. In groups with ferrules, the height ranged from 2 mm buccally/lingually to 1 mm proximally. Teeth in subgroups (n=8) were restored with either prefabricated glass fiber (FF) or titanium posts (FT) (ISO size 70 and length of 7.5 mm) and then adhesively restored with composite resin foundation materials. After foundation procedures, each specimen was restored with a cobalt chromium crown which was cemented with glass-ionomer cement. All specimens were subjected to dynamic loading in a masticatory simulator for 1 200 000 loading cycles with a nominal load of 5 Kg at 1.2 Hz and simultaneous thermocycling (5 to 55 °C). Specimens were then quasistatically loaded at 30 degrees in a universal testing machine until fracture. Fracture loads were analyzed by using 2-way ANOVA followed by the Tukey honestly significant difference test (α=.05). RESULTS: Fracture loads ranged from 610 ±45 N (no ferrule - glass fiber post) to 1216 ±169 N (1.5 mm ferrule thickness - glass fiber post). A statistically significant increase in fracture resistance was observed with increasing ferrule thickness (P<.001). However, post materials did not show a statistically significant influence (P=.977). CONCLUSIONS: Under the conditions of this laboratory study, increasing the ferrule thickness had a significant effect on the fracture resistance of endodontically treated teeth after thermomechanical fatigue, irrespective of post materials.
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ABSTRACT Objective: This study aimed to clinically compare the accuracy of bracket positioning between three-dimensionally (3D) printed indirect bonding trays and vacuum-formed trays made over 3D-printed models. Material and Methods: Fourteen patients, planned for fixed orthodontic therapy, were randomly divided into two equal groups. For both groups, both dental arches were scanned, to acquire virtual models, brackets were virtually positioned from central incisors to second premolars, and scans for the final bracket positions were performed. In the first group, transfer trays were 3D-printed. In the second group, virtual models were 3D-printed, and vacuum-formed soft sheets were thermoformed on the printed model. Teeth were indirectly bonded and then scanned. Superimposition of the virtual and the final bracket positioning scans was performed to measure linear and angular deviations in brackets positions. Results: The first group showed significantly less occlusogingival and buccolingual linear errors than the second group. No significant differences in angular deviations were found between both groups. The frequencies of clinically acceptable linear errors within 0.5 mm and angular errors within 2° showed no statistically significant difference between both groups (p> 0.05 for all measurements). The transfer errors in both groups showed linear directional biases toward the mesial, gingival and labial directions. There was no statistically significant difference in the rate of immediate debonding between both groups (10.7% and 7.1% for the first and the second groups, respectively, p=0.295). Conclusions: 3D-printed indirect bonding trays were more accurate than vacuum-formed trays, in terms of linear deviations. Both types of trays showed similar angular control.
RESUMO Objetivo: Esse estudo teve como objetivo comparar clinicamente a precisão no posicionamento de braquetes usando guias de colagem indireta impressas tridimensionalmente (3D) e guias termoformadas a vácuo em cima de modelos impressos em 3D. Material e Métodos: Quatorze pacientes, planejados para tratamento ortodôntico fixo, foram divididos aleatoriamente em dois grupos de igual tamanho. Em ambos os grupos, as duas arcadas dentárias foram escaneadas para a criação dos modelos virtuais, os braquetes foram posicionados virtualmente dos incisivos centrais aos segundos pré-molares, e foram feitos os escaneamentos das posições finais dos braquetes. No primeiro grupo, as guias de transferência foram impressas em 3D. No segundo grupo, os modelos virtuais foram impressos em 3D e as guias foram termoformadas a vácuo em cima dos modelos impressos. Os braquetes foram colados de forma indireta e depois feitos os escaneamentos. Uma sobreposição das posições planejadas virtualmente e do escaneamento com os braquetes na posição final foi realizada para medir os desvios lineares e angulares nas posições dos braquetes. Resultados: O primeiro grupo apresentou significativamente menos erros lineares oclusogengivais e vestibulolinguais do que o segundo grupo. Não foram encontradas diferenças significativas nos desvios angulares entre os dois grupos. As frequências de erros lineares clinicamente aceitáveis menores que 0,5 mm e de erros angulares menores que 2° não apresentaram diferença estatisticamente significativa entre os dois grupos (p > 0,05 para todas as medições). Os erros de transferência em ambos os grupos mostraram tendências a desvios lineares nas direções mesial, gengival e labial. Não houve diferença estatisticamente significativa entre os dois grupos para a taxa de descolagem imediata (10,7% e 7,1% para o primeiro e o segundo grupos, respectivamente, p=0,295). Conclusões: As guias de colagem indireta impressas em 3D foram mais precisas em termos de desvios lineares do que as guias termoformadas a vácuo. Os dois tipos de guias apresentaram controle angular semelhante.
ABSTRACT
In this study, we aimed to develop hybrid antitumor compounds by synthesizing and characterizing novel N-substituted acrididine-1,8-dione derivatives, designed as hybrids of phthalimide and acridine-1,8-diones. We employed a three-step synthetic strategy and characterized all compounds using IR, 1H NMR, 13C NMR, and LC-MS. The cytotoxicity and antitumor activity of five compounds (8c, 8f, 8h, 8i, and 8L) against four cancer cell lines (H460, A431, A549, and MDA-MB-231) compared to human skin fibroblast cells were evaluated. Among the synthesized compounds, compound 8f showed promising activity against skin and lung cancers, with favorable IC50 values and selectivity index. The relative changes in mRNA expression levels of four key genes (p53, TOP2B, p38, and EGFR) in A431 cells treated with the five synthesized compounds (8c, 8f, 8h, 8i, and 8L) were also investigated. Additionally, molecular docking studies revealed that compound 8f exhibited high binding affinity with TOP2B, p38, p53, and EGFR, suggesting its potential as a targeted anticancer therapy. The results obtained indicate that N-substituted acrididine-1,8-dione derivatives have the potential to be developed as novel antitumor agents with a dual mechanism of action, and compound 8f is a promising candidate for further investigation.
Subject(s)
Antineoplastic Agents , Tumor Suppressor Protein p53 , Humans , Molecular Docking Simulation , Antineoplastic Agents/pharmacology , Phthalimides/pharmacology , ErbB ReceptorsABSTRACT
Insect glutathione S-transferases (GSTs) serve critical roles in insecticides and other forms of xenobiotic chemical detoxification. The fall armyworm, Spodoptera frugiperda (J. E. Smith), is a major agricultural pest in several countries, especially Egypt. This is the first study to identify and characterize GST genes in S. frugiperda under insecticidal stress. The present work evaluated the toxicity of emamectin benzoate (EBZ) and chlorantraniliprole (CHP) against the third-instar larvae of S. frugiperda using the leaf disk method. The LC50 values of EBZ and CHP were 0.029 and 1.250 mg/L after 24 h of exposure. Moreover, we identified 31 GST genes, including 28 cytosolic and 3 microsomal SfGSTs from a transcriptome analysis and the genome data of S. frugiperda. Depending on the phylogenetic analysis, sfGSTs were divided into six classes (delta, epsilon, omega, sigma, theta, and microsomal). Furthermore, we investigated the mRNA levels of 28 GST genes using qRT-PCR under EBZ and CHP stress in the third-instar larvae of S. frugiperda. Interestingly, SfGSTe10 and SfGSTe13 stood out with the highest expression after the EBZ and CHP treatments. Finally, a molecular docking model was constructed between EBZ and CHP using the most upregulated genes (SfGSTe10 and SfGSTe13) and the least upregulated genes (SfGSTs1 and SfGSTe2) of S. frugiperda larvae. The molecular docking study showed EBZ and CHP have a high binding affinity with SfGSTe10, with docking energy values of -24.41 and -26.72 kcal/mol, respectively, and sfGSTe13, with docking energy values of -26.85 and -26.78 kcal/mol, respectively. Our findings are important for understanding the role of GSTs in S. frugiperda regarding detoxification processes for EBZ and CHP.
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Non-alcoholic fatty liver disease (NAFLD) and its progressive form (non-alcoholic steatohepatitis; NASH) are the main reason for chronic liver disease in the general population, characterized by fat accumulation in hepatocytes (steatosis) and anomalies in liver biochemical analyses. To date, no pharmacological agents have been approved for NAFLD or NASH treatment. However, silymarin, the active ingredient in milk thistle, has been used in the last decades for the treatment of several liver diseases. In this case report, treatment with silymarin 140 mg three-times daily highlighted moderate efficacy and a good safety profile in the management of NASH and liver function, as it decreased serum AST and ALT levels over the treatment period with no side-effects, supporting silymarin as a promising supplemental intervention that can normalize liver activity in NAFLD and NASH. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series. Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.
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Surface coating has become an effective approach to improve the electrochemical performance of Ni-rich cathode materials. In this study, we investigated the nature of an Ag coating layer and its effect on electrochemical properties of the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode material, which was synthesized using 3 mol.% of silver nanoparticles by a facile, cost-effective, scalable and convenient method. We conducted structural analyses using X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy, which revealed that the Ag nanoparticle coating did not affect the layered structure of NCM811. The Ag-coated sample had less cation mixing compared to the pristine NMC811, which could be attributed to the surface protection of Ag coating from air contamination. The Ag-coated NCM811 exhibited better kinetics than the pristine one, which is attributed to the higher electronic conductivity and better layered structure provided by the Ag nanoparticle coating. The Ag-coated NCM811 delivered a discharge capacity of 185 mAh·g-1 at the first cycle and 120 mAh·g-1 at the 100th cycle, respectively, which is better than the pristine NMC811.
ABSTRACT
OBJECTIVE: To evaluate the degree of postoperative pain and rate of analgesic intake in patients with symptomatic irreversible pulpitis in mandibular first molar teeth at 6 h, 12 h, 24 h, 48 h, and 72 h after using different irrigation activation techniques in single-visit endodontic treatment. METHODS: A total of 78 patients with symptomatic irreversible pulpitis with no signs of periapical pathology were randomly divided into 3 groups according to the final irrigation activation technique; Group XP-endo Finisher, Group Ultra X ultrasonic device, and Group side-vented needle. The teeth underwent standardised single-visit root canal treatment procedures using 2.5% sodium hypochlorite for irrigation. Each patient was given a chart to record postoperative pain at 6, 12, 24, 48 and 72 hours intervals. Ibuprofen, 400 mg tablets, was prescribed to be taken when the pain was unbearable. The incidence and number of analgesic tablets taken were recorded. Data were analysed using a Kruskal-Wallis test followed by a pairwise Mann-Whitney U test with Bonferroni correction for intergroup comparisons and Freidman's test followed by Dunn's post hoc test for intragroup comparisons. RESULTS: No statistically significant difference was found between all groups regarding the incidence and intensity of pain at different time intervals (p>0.05). There was no significant difference in analgesic intake between different groups, with most cases in all groups not taking analgesics (p>0.05). CONCLUSION: Adding XP-endo Finisher or passive ultrasonic irrigation to the final irrigation protocol in singlevisit endodontic treatment had no significant effect on postoperative pain or analgesic intake. (EEJ-2021-11-185).
Subject(s)
Pulpitis , Humans , Pulpitis/therapy , Dental Pulp Cavity , Root Canal Therapy/adverse effects , Root Canal Therapy/methods , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Analgesics/therapeutic useABSTRACT
In the United States, allyl isothiocyanate (AITC) has been registered as an insecticide, bactericide, and nematicide. And it has been confirmed that AITC has significant insecticidal activities against four stored product pests including Sitophilus zeamais Mostchulky (Coleoptera: Curculionidae). This study aimed to verify the mechanism of action of AITC on cytochrome c oxidase core subunits II in S. zeamais. Enzyme - catalyzed reactions and Fourier transform infrared spectrometer (FTIR) analysis revealed that the expressed COX II proteins could competitively bind and inhibit the activity of COX II. Furthermore, molecular docking results showed that a sulfur atom of AITC could form a 2.9 Å hydrogen bond with Ile-30, having a binding energy of -2.46 kcal/mol.
Subject(s)
Insecticides , Weevils , Animals , Weevils/genetics , Electron Transport Complex IV/genetics , Electron Transport Complex IV/metabolism , Molecular Docking Simulation , Insecticides/pharmacology , Insecticides/metabolism , Cloning, MolecularABSTRACT
OBJECTIVE: The pulpal response to Hoffmann's Pulpine mineral (PMIN) and Pulpine NE (PNE) was compared to mineral trioxide aggregate (MTA) when used as pulpotomy materials in immature permanent teeth in dogs. MATERIALS AND METHODS: Immature premolars were randomly divided according to the observation period into three equal groups (n = 24) (10 days, 30 days, and 90 days) then furtherly subdivided into 3 subgroups according to the material used. Histopathological analysis regarding inflammatory cell infiltration and dentin bridge (DB) formation was done. Immunohistochemical analysis was performed using osteopontin marker. RESULTS: The results showed that after 90 days, both MTA and PMIN subgroups had 100% complete thick DB without inflammation in 87.5% of the samples, while the PNE subgroup failed to form DB in 37.5% of the samples and 50% of samples showed thin initial DB with heavy inflammation in 62.5% of the samples. There was no significant difference between MTA and PMIN, while there was a statistically significant difference between PNE and the two other subgroups in DB formation and inflammatory cell infiltration (P > 0.05). After 90 days, MTA showed the highest mean value of osteopontin positive fraction area followed by PMIN without statistically significant differences, while the least value was recorded in PNE subgroup with statistically significant difference with the remaining subgroups (P < 0.05). CONCLUSION: PMIN is a promising alternative to MTA when used for pulpotomy. CLINICAL RELEVANCE: Vital pulp therapy in immature teeth can be done using PMIN as an alternative to MTA.
Subject(s)
Osteopontin , Pulpotomy , Animals , Dogs , Pulpotomy/methods , Calcium Compounds/therapeutic use , Silicates/therapeutic use , Inflammation/drug therapy , Oxides/therapeutic use , Drug Combinations , Aluminum Compounds/therapeutic useABSTRACT
BACKGROUND: To assess the response of CNV secondary to chorioretinal diseases to IVA and to explore the adequate dosing regimen and the long-term results. METHODS: A retrospective study including patients with treatment-naïve active CNV secondary to chorioretinal diseases. All patients received an initial IVA injection followed by a PRN regimen. The main outcome measures were improvement of BCVA, improvement of anatomical morphology and vascularity of the CNV on SS-OCT, and SS-OCTA, respectively, and ocular or systemic complications attributed to IVA. RESULTS: The study included 17 eyes of 15 patients. Nine patients (60%) were females. The median age was 20 years. The main primary chorioretinal disease was vitelliform macular dystrophy (29%). The mean baseline BCVA was 0.16. The mean follow-up period was 15 months. Final BCVA improved by a mean of 6 lines. The CNV regressed or became inactive in all eyes. The median number of IVA injections was 2. There were no ocular or systemic complications attributed to IVA. CONCLUSION: The customized IVA regimen is effective in inducing long-term regression of secondary CNV and in improving BCVA. Multimodal imaging is fundamental in establishing the diagnosis of CNV, and in monitoring its response to IVA.
ABSTRACT
OBJECTIVE: No diagnostic gold standard for keratoconus in children and adolescents exists. Our objective was investigating the diagnostic accuracy of various indices for keratoconus (KC) detection in paediatric eyes. METHODS: All retrievable data of significance from 432 normal right paediatric eyes and 48 eyes of paediatric KC and forme fruste KC (FFKC), imaged by use of a rotating Scheimpflug camera (Oculyzer II, Pentacam HR) between December 2013 and October 2018 at Watany Eye Hospitals, Cairo, Egypt, including Scheimpflug images data, were collected. The area under the receiver operating characteristic curve (AUROC) was calculated for different indices in this retrospective descriptive study. RESULTS: All 36 tested indices showed discriminative power differentiating KC and FFKC from normal corneas (AUROC P-value <0.05), except AC volume, AC angle, and horizontal decentrations of the steepest and thinnest points. The 32 indices showed variable degrees of diagnostic accuracy. The highest AUROC was that of the corneal assessment index from the relational thickness and other OCULUS values (CAIRO 8). Only 8 indices showed non-inferiority to it, namely, Ambrosio's relational thickness maximum (ART max) and avg, the pachymetric progression index maximum (PPI max) and avg, the back elevation from the best-fit toric ellipsoid (BE BFTE), the KC index (KI), the topographic KC indices (TKC), and the index of height decentration (IHD) (P > 0.05). CONCLUSIONS: The 8 most useful rotating Scheimpflug imaging indices for KC detection in paediatric eyes are CAIRO 8 followed by ART max and avg, PPI max and avg, BE BFTE, KI, TKC, and IHD.