Introduction/ Objective During aging, numerous pathological changes occur in the brain, including changes in its lipid composition. This leads to impaired memory and cognitive function. All existing geriatric drugs cause side effects. N-acylethanolamines (NAE) are a class of biologically active lipids that are part of the body's endocannabinoid system and play an important role in the functioning of the central nervous system. This study aimed to investigate the effects of NAE18:0 N-stearoylethanolamine (NSE) on memory, exploration activity, neuronal state, and lipid composition, choline, acetylcholine content, and acetylcholinesterase (AChE) activity in the brain and blood plasma in 18-month-old aging rats. Methods All animals were tested using a “New object recognition test” and “Hole board test” to assess rats’ memory and exploration activity. Old rats in the experimental group were orally administered a water suspension of NSE for 10 days. Thin-layer chromatography, ELISA, and mass spectrometry were used. Results The use of NSE led to changes in the phospholipid composition and cholesterol content in the frontal cortex and hippocampus, AChE activity, and a slight increase in acetylcholine in the hippocampus and frontal cortex, a decrease in the number of hyperchromic and vacuolated forms of neurons in brain structures, as well as improved memory and exploratory activity in aging rats. Discussion The neuroprotective effect of NSE in aged rats may be due to its influence on fatty acid amide hydrolase (FAAH) activity, modulation of the PPARγ/NF-κB signaling pathway, activation of PPAR receptors and α7 nicotinic acetylcholine receptors, and the ability of NSE to influence the initial stages of inflammation characteristic of old age. These hypotheses require further research in the future. Conclusion Thus, the results of this study suggest that NSE has a pronounced neuroprotective and antiamnestic effect in age-related changes in the brain. The use of NSE in old rats leads to an improvement in cognitive functions, as well as to a decrease in the severity of morphofunctional disorders in brain structures, including a decrease in signs of age-related neuronal degeneration. The data obtained confirm the participation of NSE as a component of the endocannabinoid system in regulating the cholinergic system and highlight the prospects for further studies of this compound in correcting age-related neurodegenerative processes. These results could be used to develop a new geriatric drug, taking into account the absence of known adverse reactions in NSE.
IntroductionIn recent years, the management of advanced Non–Small-Cell Lung Cancer (NSCLC) has increasingly relied on molecular testing for key driver alterations, particularly Epidermal Growth Factor Receptor (EGFR) mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements. This study aimed to estimate the prevalence of EGFR mutations in NSCLC, characterize the spectrum of EGFR variants across NSCLC subtypes, and compare mutation frequencies between smokers and non-smokers. MethodsThis hospital-based observational study utilized DNA extracted from Formalin-Fixed Paraffin-Embedded (FFPE) tumor samples. Polymerase Chain Reaction (PCR) followed by reverse hybridization was performed using oligonucleotide probe–based EGFR strip assays capable of detecting 16 distinct mutations spanning exons 18–21 of the EGFR gene. Data analysis was conducted using Microsoft Excel 2013 and SPSS version 17. Associations between EGFR mutation status and clinicopathologic variables were examined using the chi-square test. A p-value < 0.05 was considered statistically significant. ResultsEGFR mutations were identified in 18 cases (66.7%). Among patients with adenocarcinoma, the mutation frequency was 52.6%, whereas all squamous cell carcinoma cases demonstrated EGFR mutations. Within the adenocarcinoma subgroup, EGFR alterations were more frequently observed in females (60%) than in males (50%). Exon 19 in-frame deletions were the most prevalent mutation type detected. DiscussionThe EGFR Strip-Assay represents a sensitive, cost-effective, and less labor-intensive approach with a rapid turnaround time. ConclusionThis assay may serve as a practical alternative to direct sequencing for EGFR mutation analysis, particularly when working with limited tissue samples in resource-constrained settings such as those in developing countries, including India.
Introduction Diabetes mellitus is a chronic metabolic condition characterized by hyperglycemia due to either insulin resistance, lack of insulin production, and/or secretion. The global rates of infection are increasing, especially in low- and middle-income countries; thus, exploring novel and safer therapeutic options has become essential. This review aims to compile and analyze existing data on the anti-diabetic properties of selected medicinal plants, focusing on their phytochemical composition, molecular mechanisms of action, and potential therapeutic roles in glucose homeostasis. Methods A comprehensive literature search was conducted using databases such as Scopus, ScienceDirect, and Google Scholar. Sixteen medicinal plants traditionally used for diabetes management were identified and examined based on multiple experimental studies. Results Phytochemicals such as flavonoids, polyphenols, saponins, and terpenoids from these plants exhibit anti-diabetic effects through multiple mechanisms: modulation of glucose transporters ( e.g. , GLUT4), activation of insulin signaling pathways ( e.g. , PI3K/Akt), inhibition of digestive enzymes ( e.g. , α-amylase, α-glucosidase), promotion of insulin secretion, and mitigation of oxidative stress. Discussion Notably, compounds like quercetin, kaempferol, berberine, and gymnemic acid have shown significant promise. Conclusion Medicinal plants present a rich source of bioactive compounds with multi-targeted mechanisms relevant to diabetes management. Further pharmacological investigations are necessary to establish their therapeutic efficacy and safety, enabling the development of phytochemical-based interventions for diabetes.
IntroductionPoly ADP-ribose polymerase 1 (PARP-1) plays a crucial role in the gene repair process and thus attracts significant attention in the development of anti-cancer drugs. Although some FDA-approved compounds, including Olaparib, are effective in BRCA-mutated cancers, they face the obstacle of resistance and adverse reactions. Among these, Arenobufagin, a bufadienolide extracted from Bufo gargarizans, has been shown to be a potential PARP-1 inhibitor. Although the specific process of molecular inhibition is not fully understood, the investigation focused on the binding and molecular interactions between compound 30 and Olaparib to assesstheir potential as a novel PARP-1 inhibitory drug. MethodsMolecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy (BFE) analyses were employed to explore the interactions between the ligands and the protein. Structural stability and key residues involved in the interactions mediated by the ligands were determined through conformational and per-residue energy decomposition (PRED) analyses. ResultsArenobufagin 30 showed a binding affinity of –51.88 kcal/mol, which was similar to that of Olaparib (- 52.99 kcal/mol). This affinity was primarily supported by strong electrostatic and van der Waals interactions. Conformational analysis revealed that arenobufagin 30 induced specific dynamic changes in the PARP-1 molecule without disrupting its secondary structures. PRED showed improved binding with the crucial residues of the catalytic domain, suggesting an unusual mode of stabilization and inhibition. DiscussionThe similarity in binding affinity and unique conformational modification presented by arenobufagin 30 indicates an unconventional PARP-1 inhibitory mechanism. The atomistic information provided for the inhibitory actions of naturally occurring bufadienolides can be used to suggest their potential role in counteracting the limitations presented by existingPARP-1 inhibitors. ConclusionThis study provides mechanistic insight into the inhibition of PARP-1 by Arenobufagin, suggesting it as a candidate for the development of novel anti-PARP-1 agents.
IntroductionThe critical importance of controlling antibiotic residues in milk for human health necessitates advanced monitoring methods, as these residues can induce allergies, contribute to bacterial resistance, and disrupt gut microflora. Milk safety is key to preventing human health risks worldwide. The aim of the work is to identify consistent patterns and search for informative parameters and ranges in spectral diagnostics of tetracycline interaction with milk. MethodsThe absorption and luminescence spectra of milk were measured using a CM2203 spectrofluorimeter. Initial milk parameters were assessed with an “Expert Profi” ultrasonic analyzer, and antibiotic content was verified using “BIOEASY 4in1 BSCT” test kits. ResultsAnalysis of milk contaminated with tetracycline across the 230-600 nm range revealed four distinct absorption peaks at 290, 324, 360, and 445 nm, with the peak at 445 nm exhibiting twice the intensity of the others. The integral and statistical parameters of the spectra were calculated, leading to the derivation of approximate dependencies of these parameters on antibiotic concentration. This process enabled the proposal of specific informative ranges and parameters for detecting and quantifying tetracycline. While the complex matrix of cow's milk renders the 230–310 nm and 310–340 nm ranges ineffective for analysis due to minimal parameter changes, the constructed dependencies identified two key diagnostic ranges: 340-400 nm and 400-520 nm. DiscussionApproximate dependences of the spectrum parameters on the concentration of the antibiotic are obtained. Informative ranges and parameters for diagnosing the presence and tracking the concentration of tetracycline in milk are proposed. ConclusionThese findings confirm that the 340-400 nm range (associated with nucleotide, protein, and flavonoid absorption) and the 400-520 nm range (associated with riboflavin absorption) are diagnostically informative, with the latter enabling qualitative detection of tetracycline based on parameters H, As, and Ex. The results pave the way for developing rapid, spectral-based methods for dairy product safety monitoring.
