Comparing the biological activity and composition of Cerebrolysin with other peptide preparations.

Neurological disorders, ranging from acute forms such as stroke and traumatic brain injury to neurodegenerative diseases like dementia, are the leading cause of disability-adjusted life years (DALYs) worldwide. A promising approach to address these conditions and promote nervous system regeneration is the use of the neuropeptide preparation Cerebrolysin, which has been shown to be effective in both clinical and preclinical studies. Despite claims of similar clinical efficacy and safety by several peptide preparations, concerns regarding their generic composition and efficacy have been previously raised. Based on these reports, we analyzed the peptide composition and neurotrophic activity of several peptide preparations allegedly similar to Cerebrolysin and approved in some countries for treating neurological diseases. Our results demonstrate that these preparations lack relevant biological activity and that the peptide composition is significantly different from Cerebrolysin. peptide.

Effects of porcine somatotropin administration on the responses to dietary lysine and a near-ideal blend of amino acids on the amino acid composition of whole-body protein and amino acid accretion rate in growing pigs.

An experiment was conducted to assess the effects of porcine somatotropin (pST) on the responses to a near-ideal blend of AA on the AA composition of empty, whole-empty body (WEB) protein and WEB essential AA accretion rate in pigs from 22 to 60 kg BW. Forty Hampshire × Yorkshire gilts were individually penned and assigned to a 4 × 2 factorial arrangement of treatments consisting of four diets with and without pST injection. A fortified corn-soybean meal basal diet was formulated to contain 1.50% total Lys with Thr, Met, and Trp added to obtain a near-ideal blend of these AA relative to Lys. In three additional diets, Lys was reduced to 1.25%, 1.00%, and 0.75% by diluting the basal diet with cornstarch, cellulose, and sand such that the diets also contained the same ratios of AA. Pigs that received pST were administered a daily i.m. injection of 2 mg of pST. At 60 kg BW, the WEB (carcass, head, viscera, blood, nails, and hair) was ground and analyzed for proximate and AA composition. Administration of pST increased (P < 0.001) accretion rates of WEB protein and essential AA. Increasing dietary essential AA increased (quadratic, P < 0.03) accretion rate of WEB protein, His, Leu, Trp, and Val in pST-treated pigs, but not in untreated pigs. Lysine composition in the accreted WEB protein was not affected (P > 0.05) by dietary Lys. The efficiency of Lys utilization for WEB Lys accretion was linearly affected (P < 0.01) by dietary Lys. These results indicated that the dietary Lys needed to achieve maximum WEB Lys accretion is markedly increased by pST administration.

This study evaluated the effects of two factors, porcine somatotropin and graded levels of amino acids, on the total accumulation and the accretion rate of amino acids across a broad range of protein deposition rates in growing pigs. Treatments included 1) with or without a daily injection of porcine somatotropin and 2) graded levels of total dietary lysine from 0.75% to 1.50%. As expected, both the administration of porcine somatotropin and increased dietary lysine increased both the amount and the rate of amino acid accretion. However, the amount and rate of amino acid accretion from increased dietary amino acids were markedly greater in pigs treated with porcine somatotropin. Thus, the extent to which the genetic potential for protein deposition is achieved depends on both the anabolic capacity of the pig and the amino acid concentration of the diet provided.

Ultraviolet Protection From a Patented Amino Acid Complex Technology.

OBJECTIVE:   This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex). METHODS: I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2. RESULTS: I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment.  Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used.   J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.

Interactions between Gepotidacin and Escherichia coli Gyrase and Topoisomerase IV: Genetic and Biochemical Evidence for Well-Balanced Dual-Targeting.

Antimicrobial resistance is a global threat to human health. Therefore, efforts have been made to develop new antibacterial agents that address this critical medical issue. Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial in clinical development. Recently, phase III clinical trials for gepotidacin treatment of uncomplicated urinary tract infections caused by uropathogens, including Escherichia coli, were stopped for demonstrated efficacy. Because of the clinical promise of gepotidacin, it is important to understand how the compound interacts with its cellular targets, gyrase and topoisomerase IV, from E. coli. Consequently, we determined how gyrase and topoisomerase IV mutations in amino acid residues that are involved in gepotidacin interactions affect the susceptibility of E. coli cells to the compound and characterized the effects of gepotidacin on the activities of purified wild-type and mutant gyrase and topoisomerase IV. Gepotidacin displayed well-balanced dual-targeting of gyrase and topoisomerase IV in E. coli cells, which was reflected in a similar inhibition of the catalytic activities of these enzymes by the compound. Gepotidacin induced gyrase/topoisomerase IV-mediated single-stranded, but not double-stranded, DNA breaks. Mutations in GyrA and ParC amino acid residues that interact with gepotidacin altered the activity of the compound against the enzymes and, when present in both gyrase and topoisomerase IV, reduced the antibacterial activity of gepotidacin against this mutant strain. Our studies provide insights regarding the well-balanced dual-targeting of gyrase and topoisomerase IV by gepotidacin in E. coli.

Activation of mGlu 2/3 receptors with the orthosteric agonist LY-404,039 alleviates dyskinesia in experimental parkinsonism.

LY-404,039 is an orthosteric agonist at metabotropic glutamate 2 and 3 (mGlu 2/3 ) receptors, with a possible additional agonist effect at dopamine D 2 receptors. LY-404,039 and its pro-drug, LY-2140023, have previously been tested in clinical trials for psychiatric indications and could therefore be repurposed if they were shown to be efficacious in other conditions. We have recently demonstrated that the mGlu 2/3 orthosteric agonist LY-354,740 alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat without hampering the anti-parkinsonian action of L-DOPA. Here, we seek to take advantage of a possible additional D 2 -agonist effect of LY-404,039 and see if an anti-parkinsonian benefit might be achieved in addition to the antidyskinetic effect of mGlu 2/3 activation. To this end, we have administered LY-404,039 (vehicle, 0.1, 1 and 10 mg/kg) to 6-OHDA-lesioned rats, after which the severity of axial, limbs and oro-lingual (ALO) AIMs was assessed. The addition of LY-404,039 10 mg/kg to L-DOPA resulted in a significant reduction of ALO AIMs over 60-100 min (54%, P  < 0.05). In addition, LY-404,039 significantly enhanced the antiparkinsonian effect of L-DOPA, assessed through the cylinder test (76%, P  < 0.01). These results provide further evidence that mGlu 2/3 orthosteric stimulation may alleviate dyskinesia in PD and, in the specific case of LY-404,039, a possible D 2 -agonist effect might also make it attractive to address motor fluctuations. Because LY-404,039 and its pro-drug have been administered to humans, they could possibly be advanced to Phase IIa trials rapidly for the treatment of motor complications in PD.

Microplate-Based Cryopreservation of Adherent-Cultured Human Cell Lines Using Amino Acids and Proteins.

With the progression of regenerative medicine and cell therapy, the importance of cryopreservation techniques for cultured cells continues to rise. Traditional cryoprotectants, such as dimethyl sulfoxide and glycerol, are effective in cryopreserving suspended cells, but they do not demonstrate sufficient efficacy for two-dimensional (2D)-cultured cells. In the past decade, small molecules and polymers have been studied as cryoprotectants. Some L-amino acids have been reported to be natural and biocompatible cryoprotectants. However, the cryoprotective effects of D-amino acids have not been investigated for such organized cells. In the present study, the cryoprotective effects of D- and L-amino acids and previously reported cryoprotectants were assessed using HepG2 cells cultured on a microplate without suspending the cells. d-Proline had the highest cryoprotective effect on 2D-cultured cells. The composition of the cell-freezing solution and freezing conditions were then optimized. The d-proline-containing cell-freezing solution also effectively worked for other cell lines. To minimize the amount of animal-derived components, fetal bovine serum in the cell freezing solution was substituted with bovine serum albumin and StemFit (a commercial supplement for stem cell induction). Further investigations on the mechanism of cryopreservation suggested that d-proline protected enzymes essential for cell survival from freeze-induced damage. In conclusion, an effective and xeno-free cell-freezing solution was produced using d-proline combined with dimethyl sulfoxide and StemFit for 2D-cultured cells.

Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids.

Four series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC50 values of 0.017 and 0.025 µM, respectively. Compounds 15g and 18c efficiently inhibited extracellular matrix (ECM) deposition in TGF-ß-induced hepatic stellate cells (HSCs), and eventually suppressed HSC activation. Moreover, compound 15g showed a good pharmacokinetic (PK) profile with a favorable half-life (t1/2 = 9.14 h). The results indicated that these compounds exhibited activity targeting ALK5 and may have potential in the treatment of liver fibrosis; thus they are worthy of further study.

Metabolomic insights into the browning inhibition of fresh-cut apple by hydrogen sulfide.

Hydrogen sulfide (H2S) is known to effectively inhibit the browning of fresh-cut apples, but the mechanism at a metabolic level remains unclear. Herein, non-targeted metabolomics was used to analyze metabolic changes in surface and internal tissues of fresh-cut apple after H2S treatment. The results showed that prenol lipids were the most up-accumulated differential metabolites in both surface and inner tissue of fresh-cut apple during browning process, which significantly down-accumulated by H2S treatment. H2S treatment reduced the consumption of amino acid in surface tissue. Regarding inner tissue, H2S activated defense response through accumulation of lysophospholipid signaling and induced the biosynthesis of phenolic compounds. We therefore propose that H2S inhibited the surface browning of fresh-cut apple by reducing the accumulation of prenol lipids, directly delaying amino acid consumption in surface tissue and indirectly regulating defense response in inner tissue, which provides fundamental insights into browning inhibition mechanisms by H2S.

The effect of valproate on the amino acids, monoamines, and kynurenic acid concentrations in brain structures involved in epileptogenesis in the pentylenetetrazol-kindled rats.

BACKGROUND: The study aimed to assess the influence of a single valproate (VPA) administration on inhibitory and excitatory neurotransmitter concentrations in the brain structures involved in epileptogenesis in pentylenetetrazol (PTZ)-kindled rats. METHODS: Adult, male Wistar rats were kindled by repeated intraperitoneal (ip) injections of PTZ at a subconvulsive dose (30 mg/kg, three times a week). Due to the different times required to kindle the rats (18-22 injections of PTZ), a booster dose of PTZ was administrated 7 days after the last rats were kindled. Then rats were divided into two groups: acute administration of VPA (400 mg/kg) or saline given ip. The concentration of amino acids, kynurenic acid (KYNA), monoamines, and their metabolites in the prefrontal cortex, hippocampus, amygdala, and striatum was assessed by high-pressure liquid chromatography (HPLC). RESULTS: It was found that a single administration of VPA increased the gamma-aminobutyric acid (GABA), tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and KYNA concentrations and decreased aspartate (ASP) levels in PTZ-kindled rats in the prefrontal cortex, hippocampus, amygdala and striatum. CONCLUSIONS: Our results indicate that a single administration of VPA in the PTZ-kindled rats restored proper balance between excitatory (decreasing the level of ASP) and inhibitory neurotransmission (increased concentration GABA, KYNA) and affecting serotoninergic neurotransmission in the prefrontal cortex, hippocampus, amygdala, and striatum.

Effect of sodium hypochlorite gel on bacteria associated with periodontal disease.

OBJECTIVES: An adjunct in non-surgical periodontal therapy might be sodium hypochlorite (NaOCl)-based agents. The purpose of the present in vitro study was to get deeper knowledge on the influence of different parameters as time after mixing, pH, and chemical composition of an amino acid 0.475% NaOCl (AA-NaOCl) gel consisting of two components on its anti-biofilm activity. MATERIALS AND METHODS: Six-species biofilms were cultured for 5 days, before AA-NaOCl gel was applied. In the different series, the influence of the time after mixing of the two components before application, of the concentration of NaOCl in the gel mixture, of the pH of the gel mixture, and of an exchange of the amino acid component by hyaluronic acid (HA), was analyzed. RESULTS: Mixing time point experiments showed that the AA-NaOCl gel is capable of statistically significantly reducing colony-forming unit (cfu) counts up to 30 min after mixing, but only up to 20 min after mixing the reduction was more than 2 log10 cfu. The pH experiments indicate that a reduced pH results in a reduced activity of the NaOCl formulation. NaOCl concentrations in the formulation in the range from 0.475 to 0.2% provide adequate activity on biofilms. A HA/NaOCl gel was equally active against the biofilm as the AA-NaOCl gel. CONCLUSION: Mixing of the components should be made in a timeframe of 20 min before applications. An optimization of the composition of the NaOCl formulation might be possible and should be a topic in further in vitro studies. CLINICAL RELEVANCE: The AA-NaOCl gel formulation can be mixed up to 20 min before application. Further, the study indicates that the composition of the NaOCl gel formulation can be optimized.

Design, synthesis, in silico, and in vitro evaluation of novel benzyloxybenzene substituted (S)-α-amino amide derivatives as cholinesterases and monoaminoxidases inhibitor.

In this study, a series of novel benzyloxybenzene substituted (S)-α-amino acid methyl esters and their amide derivatives were synthesized and evaluated for their inhibitory actions against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase A (MAO-A), and monoamine oxidase B (MAO-B). The synthetic strategy was based on starting from benzyl bromide (5) and 4-hydroxybenzaldehyde (6). The reaction of 5 and 6 in the presence of K2 CO3 gave benzyloxybenzaldehyde 7. Benzyloxybenzene substituted (S)-α-amino acid methyl esters 11, 12, 13, (±)-19, and (±)-20 were obtained from the reaction of  L-amino acid methyl esters with benzyloxybenzaldehyde (7) followed by in situ reduction with NaBH4 . The reaction of (S)-11, (S)-12, 13, (±)-19, and (±)-20 with excess ammonia gave amides (S)-14, (S)-15, 16, (±)-21, and (±)-22. The in vitro inhibitory activities of compounds against MAO-A, MAO-B, AChE, and BChE were investigated. Within the α-amino acid methyl ester series, 13 (21.32 ± 0.338 µM) showed selectivity by inhibiting the MAO-B better than MAO-A. 13 emerged as the most active member of this series, exhibiting a 12-fold selectivity for MAO-B. 14 (4.501 ± 0.295 µM) demonstrated a pronounced selectivity for MAO-A over MAO-B, with a selectivity ratio of 110-fold. In addition, it was determined that compound 15 (95.65 ± 3.09 µM) had high selectivity for BChE inhibition. 21 was demonstrated the most potent inhibition (18.36 ± 1.36 µM) against AChE.

Effect of tryptophan position and lysine/arginine substitution in antimicrobial peptides on antifungal action.

Every year, the overprescription, misuse, and improper disposal of antibiotics have led to the rampant development of drug-resistant pathogens and, in turn, a significant increase in the number of patients who die of drug-resistant fungal infections. Recently, researchers have begun investigating the use of antimicrobial peptides (AMPs) as next-generation antifungal agents to inhibit the growth of drug-resistant fungi. The antifungal activity of alpha-helical peptides designed using the cationic amino acids containing lysine and arginine and the hydrophobic amino acids containing isoleucine and tryptophan were evaluated using 10 yeast and mold fungi. Among these peptides, WIK-14, which is composed of a 14-mer with tryptophan sequences at the amino terminus, showed the best antifungal activity via transient pore formation and ROS generation. In addition, the in vivo antifungal effects of WIK-14 were investigated in a mouse model infected with drug-resistant Candida albicans. The results demonstrate the potential of AMPs as antifungal agents.

Protection against ß-N-methylamino-l-alanineꟷinduced vesicular monoamine transporter 2 inhibition by hydroxyl-containing proteinogenic amino acids.

ß-N-methylamino-l-alanine (BMAA) has been shown to inhibit vesicular monoamine transporter 2 (VMAT2), thereby preventing the uptake of monoaminergic neurotransmitters into platelet dense granules and synaptic vesicles. The inhibition is hypothesized to be through direct association of BMAA with hydroxyl groupꟷcontaining amino acid residues in VMAT2. This study evaluated whether BMAA-induced inhibition of VMAT2 could be prevented directly by co-incubation of BMAA with amino acids, and if this protection was specific for BMAA inhibition of VMAT2. l-tyrosine, and to a lesser extent l-serine, was able to prevent BMAA-induced VMAT2 inhibition in a concentration-dependent manner, whereas neither l-threonine nor amino acids without side chain hydroxyl groups could reduce this inhibition. Reserpine-induced VMAT2 inhibition was unaffected by any of the amino acids. These data support the hypothesized interaction between BMAA and hydroxyl groupꟷcontaining amino acids and suggests that this interaction might be leveraged to protect against the toxicity of BMAA.

Genetic loss of Nrf1 and Nrf2 leads to distinct metabolism reprogramming of HepG2 cells by opposing regulation of the PI3K-AKT-mTOR signalling pathway.

As a vital hallmarker of cancer, the metabolic reprogramming has been shown to play a pivotal role in tumour occurrence, metastasis and drug resistance. Amongst a vast variety of signalling molecules and metabolic enzymes involved in the regulation of cancer metabolism, two key transcription factors Nrf1 and Nrf2 are required for redox signal transduction and metabolic homeostasis. However, the regulatory effects of Nrf1 and Nrf2 (both encoded by Nfe2l1 and Nfe2l2, respectively) on the metabolic reprogramming of hepatocellular carcinoma cells have been not well understood to date. Here, we found that the genetic deletion of Nrf1 and Nrf2 from HepG2 cells resulted in distinct metabolic reprogramming. Loss of Nrf1α led to enhanced glycolysis, reduced mitochondrial oxygen consumption, enhanced gluconeogenesis and activation of the pentose phosphate pathway in the hepatocellular carcinoma cells. By striking contrast, loss of Nrf2 attenuated the glycolysis and gluconeogenesis pathways, but with not any significant effects on the pentose phosphate pathway. Moreover, knockout of Nrf1α also caused fat deposition and increased amino acid synthesis and transport, especially serine synthesis, whilst Nrf2 deficiency did not cause fat deposition, but attenuated amino acid synthesis and transport. Further experiments revealed that such distinctive metabolic programming of between Nrf1α-/- and Nrf2-/- resulted from substantial activation of the PI3K-AKT-mTOR signalling pathway upon the loss of Nrf1, leading to increased expression of critical genes for the glucose uptake, glycolysis, the pentose phosphate pathway, and the de novo lipid synthesis, whereas deficiency of Nrf2 resulted in the opposite phenomenon by inhibiting the PI3K-AKT-mTOR pathway. Altogether, these provide a novel insight into the cancer metabolic reprogramming and guide the exploration of a new strategy for targeted cancer therapy.

Unlocking Antibacterial Potential: Key-Site-Based Regulation of Antibacterial Spectrum of Peptides.

In the pursuit of combating multidrug-resistant bacteria, antimicrobial peptides (AMPs) have emerged as promising agents; however, their application in clinical settings still presents challenges. Specifically, the exploration of crucial structural parameters that influence the antibacterial spectrum of AMPs and the subsequent development of tailored variants with either broad- or narrow-spectrum characteristics to address diverse clinical therapeutic needs has been overlooked. This study focused on investigating the effects of amino acid sites and hydrophobicity on the peptide's antibacterial spectrum through Ala scanning and fixed-point hydrophobic amino acid substitution techniques. The findings revealed that specific amino acid sites played a pivotal role in determining the antibacterial spectrum of AMPs and confirmed that broadening the spectrum could be achieved only by increasing hydrophobicity at certain positions. In conclusion, this research provided a theoretical basis for future precise regulation of an antimicrobial peptide's spectrum by emphasizing the intricate balance between amino acid sites and hydrophobicity.

Compounds Consisting of Quinazoline, Ibuprofen, and Amino Acids with Cytotoxic and Anti-Inflammatory Effects.

In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) and cyclooxygenase-2 (COX-2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A-431, MCF-7, MDA-MB-231) and epithelial non-tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC50) than gefitinib (reference drug) on three cancer cell lines (0.034 µM in A-431, 2.67 µM in MCF-7, and 3.64 µM in AGS) without showing activity on the non-tumorigenic cell line (>100 µM). Furthermore, assessment of EGFR-TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an in vivo anti-inflammatory assay using the 12-O-tetradecanoylphorbol-3-acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR-TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX-2, involving S531. The RMSD graph indicated that the ligand remained stable in 50 ns.

IR76b-expressing neurons in Drosophila melanogaster are necessary for associative reward learning of an amino acid mixture.

Learning where to find nutrients while at the same time avoiding toxic food is essential for survival of any animal. Using Drosophila melanogaster larvae as a study case, we investigate the role of gustatory sensory neurons expressing IR76b for associative learning of amino acids, the building blocks of proteins. We found surprising complexity in the neuronal underpinnings of sensing amino acids, and a functional division of sensory neurons. We found that the IR76b receptor is dispensable for amino acid learning, whereas the neurons expressing IR76b are specifically required for the rewarding but not the punishing effect of amino acids. This unexpected dissociation in neuronal processing of amino acids for different behavioural functions provides a study case for functional divisions of labour in gustatory systems.

Selenium Improves the Control Efficacy of Phytophthora nicotianae by Damaging the Cell Membrane System and Promoting Plant Energy Metabolism.

Tobacco black shank (TBS), caused by Phytophthora nicotianae, poses a significant threat to tobacco plants. Selenium (Se), recognized as a beneficial trace element for plant growth, exhibited inhibitory effects on P. nicotianae proliferation, disrupting the cell membrane integrity. This action reduced the energy supply and hindered hyphal transport through membrane proteins, ultimately inducing hyphal apoptosis. Application of 8 mg/L Se through leaf spraying resulted in a notable decrease in TBS incidence. Moreover, Se treatment preserved chloroplast structure, elevated chitinase activities, ß-1,3-GA, polyphenol oxidase, phenylalanine ammonia-lyase, and increased hormonal content. Furthermore, Se enhanced flavonoid and sugar alcohol metabolite levels while diminishing amino acid and organic acid content. This shift promoted amino acid degradation and flavonoid synthesis. These findings underscore the potential efficacy of Se in safeguarding tobacco and potentially other plants against P. nicotianae.