Home Physical Sciences GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes
Article Open Access

GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes

  • Muhammad Naveed , Hamza Jamil , Tariq Aziz EMAIL logo , Syeda Izma Makhdoom , Abid Sarwar , Jasra Nasbeeb , Yang Zhennai EMAIL logo and Metab Alharbi
Published/Copyright: May 28, 2024
Download Article (PDF)
Open Chemistry
From the journal Open Chemistry Volume 22 Issue 1

Abstract

The purpose of this research was to examine the interaction between metabolites of Lactobacillus plantarum YW11, characterized through GC–mass spectra (MS) analysis, and the FN1 protein in cases of familial pulmonary fibrosis, found from hub genes analysis. GC–MS analysis was performed to identify metabolites in L. plantarum. Then, gene expression analysis and functional annotations were conducted to investigate the hub genes. A network of hub genes and transcription factors (TFs) was constructed, highlighting the significance of FN1 in the disease’s etiology. Molecular docking was employed to explore the interaction between the characterized metabolites and the FN1 protein. Toxicity analysis was also carried out. Thirty-two active compounds of L. plantarum YW11 were characterized by GC–MS. The gene expression analysis identified 295 differentially expressed genes, including 10 hub genes and 6 TFs, providing further support for the involvement of FN1 protein in the disease. The results of the molecular docking studies suggest the therapeutic potential of targeting FN1, with the best docking result observed for the interaction between FN1 and the 2,4-di-tert-butylphenol metabolite (energy of −6.9 kcal/mol). The toxicity analysis and molecular dynamic simulations support the suitability of 2,4-di-tert-butylphenol as a candidate for targeting FN1.

Keywords: L. plantarum YW11; DEGs; drug docking; TFs; simulations; hub genes

1 Introduction

The rare genetic illness familial pulmonary fibrosis (FPF) causes irreversible scarring and stiffness of lung tissue, resulting in respiratory failure [1]. Due to its quick progression compared to other types of pulmonary fibrosis, FPF can lead to respiratory collapse and death within a few years of diagnosis, it is particularly lethal [2]. The median survival period after FPF diagnosis was 3.6 years in a study of 22 families, and the overall survival rate at 5 years was only 20% [3]. Mutations in genes encoding surfactant proteins, telomerase, and extracellular matrix components are thought to be responsible for the heritable aspect of FPF. Signs of FPF include a progressive worsening of shortness of breath, cough, and exhaustion. Although FPF is uncommon, it nevertheless places a heavy burden on those who are diagnosed with it and their loved ones as there is no treatment and known cure yet. A ubiquitous bacteria Lactobacillus plantarum is a member of the Lactobacillus family found in the digestive tract. It is Gram-positive, facultative anaerobic bacteria. Both humans and animals can benefit from adding it to their diets as a supplement [4]. This microbe finds widespread application in the fermentation of many foods. The ability to stick strongly to the intestinal walls and resistance to the acidic or gastric environment of intestinal fluid have also been discovered [4]. In addition to its ability to aggregate in the intestines, L. plantarum also possesses antagonistic action against two bacterial species, namely Salmonella typhi and Escherichia coli [5,6]. L. plantarum is considered a probiotic because of this characteristic.

Hub genes are genes that act as central nodes in biological networks, typically controlling the expression of many other genes or processes. Disease-associated genes have the potential to serve as therapeutic targets or diagnostic/prognostic biomarkers and reveal previously unknown molecular mechanisms of disease. Large-scale gene expression data, like as microarray or RNA sequencing data, are often analyzed computationally to identify hub genes. These approaches seek to discover highly linked genes as well as those differently expressed between disease and health. Disease diagnosis, especially for diseases with complex or varied pathologies, is a key area of use for hub gene analysis. In cancer research, for instance, hub gene analysis has been used to pinpoint genes essential for tumor progression and metastasis, paving the way for the development of targeted medicines that selectively suppress these genes [7]. The outcomes for patients with a disease by discovering the central genes and pathways that are dysregulated in that disease can improve and then develop targeted treatments that are personalized to the individual patient.

Drug docking and simulations have emerged as a crucial component in modern drug research and development, providing a highly effective and efficient strategy for studying the molecular-level interaction between small molecules (drugs) and target proteins [8]. Employing computational algorithms and molecular modeling techniques, this methodology allows for the prediction and examination of the binding affinity and orientation of drugs within the binding pocket of their respective target proteins. Through the simulation of the dynamic behavior of drug–protein complexes using methods like molecular dynamics simulations, valuable insights can be obtained regarding the temporal stability, flexibility, and conformational alterations of these complexes [9].

This study aims to identify the metabolites of the L. plantarum YW11 from GC–MS analysis, find out the hub genes involved in FPF with the help of expression analysis, and find the best drug for these genes from L. plantarum metabolites. The metabolites were identified from the GC–mass spectra (MS) analysis of L. plantarum YW11, and then, the differentially expressed genes (DEGs) were identified from the Gene Expression Omnibus (GEO) database. The biological pathways associated with these DEGs were identified, and then, the hub genes network and transcription factors (TFs)-DEGs network were created with the help of Cytoscape. The identified metabolites’ structure was retrieved from PubChem and docking was done. Then, the toxicity analysis and molecular dynamic simulations were carried out.

2 Methods

2.1 Bacterial isolation and GC–MS analysis

The strain of L. plantarum YW11 used in this study was obtained from the culture bank at Beijing Technology and Business University in Beijing, China, with the GenBank ID CP035031.1. MRS broth (Beijing Aoboxing Co., Ltd) was used to culture L. plantarum YW11 [10]. The extraction process involved isolating the fatty acids from the culture medium. The upper hexane layer, enriched with fatty acid methyl esters (FAMEs), was carefully collected. To eliminate residual solvent, the collected layer underwent a drying procedure utilizing a liquid stream [11]. The analysis using GC–MS was conducted utilizing a Dual Stage TMP (Ultra) mass spectrometer and a Shimadzu GC2010 equipment. For the injection of 2 μL of FAME, a split mode with a 10:1 split ratio at 250°C was employed. Helium served as the transporter gas with a continuous flow rate of 1 mL/min. To achieve separation, highly polar (TR-Wax MS, 30 m length, 0.25 mm, i.e., 0.25 m thickness) and fused silica (Thermo Fisher Scientific) capillary columns were utilized. The oven temperature was initially set to 170°C for 1 min, followed by a gradual increase to 200°C at a rate of 0.8°C per minute. Line transmission was maintained at 250°C, while the ion source was held steady at 200°C. The MS sensor was employed operating under an electron ionization (EI) voltage of 70 eV and with a mass scan range of 33–450 amu (m/z) [10]. Chemical identification was performed by comparing the MS of the peaks with reference spectra available in the National Institute of Standards and Technology library [47].

2.2 Data collection and DEG identification

The expression patterns of FPF were investigated by utilizing the GEO data, curated by the National Center for Biotechnology Information (NCBI). A comprehensive search was conducted in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) using appropriate keywords (Human Pulmonary Fibrosis), filters (Expressions by array, Homo sapiens, and datasets), and search tools (GEO datasets), as described by Barrett et al. in 2012, to identify relevant datasets [12]. Two specific expression studies, namely GSE49072 and GSE208444, were carefully examined. The suitability of the identified datasets to address the research questions was assessed based on sample size, data quality, and relevance. Unfortunately, the GSE208444 dataset was excluded from further analysis due to insufficient data. In the GSE49072 dataset, which comprised a total of 84 samples, 61 samples were designated as controls, while the remaining 23 samples represented the experimental group. The gene expression data obtained were normalized and subjected to analysis using the dedicated GEO2R program (https://www.ncbi.nlm.nih.gov/geo/geo2r/). The analysis involved applying the Benjamini & Hochberg method to control the false discovery rate (FDR). This approach facilitated the identification of significant DEGs while minimizing the occurrence of false positives [13].

2.3 Functional annotation of DEGs for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway

The gene list of DEGs was uploaded into the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform for GO analysis. The DAVID provided by the National Institute of Allergy and Infectious Diseases was utilized in this investigation to identify the biological activities and pathways associated with the DEGs. The DAVID database (https://david.ncifcrf.gov/) offers comprehensive annotation tools for functional analysis [14]. This analysis aimed to identify enriched biological processes, molecular activities, and cellular components associated with the gene list. Then, the gene list was utilized to analyze the KEGG to determine significantly enriched pathways. The enriched GO terms and KEGG pathways were then visualized using SRplot (https://www.bioinformatics.com.cn/). The most significant groups were identified based on their enrichment scores.

2.4 Protein–protein network construction

The gene list was uploaded into the multiple protein section of the search bar, and a protein–protein interaction (PPI) network was constructed using the STRING database. For the construction of the PPI network, a minimum interaction score of 0.7, representing high confidence, was set. The STRING database (https://string-db.org/) is an online resource that compiles, evaluates, and integrates data from various sources to provide information on PPIs [15].

2.5 Protein network visualization and analysis

The PPI network, constructed using the STRING database, was visualized, and analyzed in Cytoscape software (v 3.9.1). Various plugin apps within Cytoscape (https://cytoscape.org/) were employed to perform different analyses based on specific requirements. In the network analysis conducted in Cytoscape, each gene was represented as a node, and the interactions were represented as edges.

2.6 Prediction of hub genes

CytoHubba, a plugin app in Cytoscape, was employed to the network of DEGs imported from STRING database to identify the top 10 hub genes. It employs the degree centrality method, which quantifies the number of adjacent interactions a protein has with its neighboring proteins in the network. A higher degree implies a greater number of interactions, and nodes with a higher number of interactions are considered hub genes, closely associated with the disease [16].

2.7 TF regulatory network analysis of DEGs

To identify the TFs that target the DEGs, the iRegulon app within Cytoscape was employed. In this study, TF prediction was conducted with the following parameter settings: a minimum identity of 0.05 between orthologous genes, a maximum FDR of 0.001 for motif similarity, and a threshold of NES > 4 (normalized enrichment score). These parameters were utilized to estimate the TFs that potentially regulate the identified DEGs in the study. The iRegulon app assesses the enrichment of TF motifs based on direct targets, utilizing the position weight matrix method [17]. All the 6 TF-DEGs networks constructed were visualized using Cytoscape.

2.8 Protein 3D structure retrieval

Protein FN1’s three-dimensional structure was successfully retrieved using the AlphaFold. AlphaFold (https://alphafold.ebi.ac.uk/), created by DeepMind, is a web-based AI model that employs deep learning models to accurately predict the 3D structures of proteins. It has garnered a lot of attention from researchers in many different areas of biology because of its accuracy [18].

2.9 Identification of binding sites

To predict the binding sites of the FN1 protein, the protein data in PDB format was uploaded as input on the DeepSite. The identification of druggable binding sites is a crucial step in structure-based drug design. DeepSite (http://www.playmolecule.org/) is a machine learning-based method used to predict protein–ligand binding sites. DeepSite solely relies on machine learning algorithms to predict and identify potential binding sites within the FN1 protein [19]. To determine the atomic occupancy, it uses the least-squares approximation to the pair correlation function,

g ( r ) = exp ( β V ( r ) ) ,

where V(r) = (r vdw/r)12 is the repulsive component of a Lennard-Jones potential and r vdw is the van der Waals atom radius. So, to calculate the single-atom occupancy [19],

n ( r ) = 1 exp ( ( r vdw / r ) 12 )

2.10 Retrieval of bacterial metabolites

To retrieve the 2D and 3D structures of the metabolites obtained from L. plantarum YW11, PubChem database was utilized. PubChem (https://pubchem.ncbi.nlm.nih.gov/) is a comprehensive database that contains information about chemical compounds and their involvement in various biological processes [20].

2.11 Docking analysis

Docking analysis of multiple ligands was conducted using PyRx software. PyRx is a powerful computational tool widely utilized for molecular docking studies. The ligands and protein were prepared and processed within PyRx, employing appropriate force fields and algorithms. Then, to increase the validity of docking analysis, the best-docked molecules were again analyzed using WADDAICA. Input server molecular files were run to determine parameters. The protein FN1 with best-docked ligand 2,4-di-tert-butylphenol was uploaded to the input of the binding affinity by AI and job was submitted. The WADDAICA server (https://heisenberg.ucam.edu:5000/) was developed to take advantage of both deep learning and traditional drug design algorithms [21].

2.12 Toxicity screening

Toxicities of the compound were predicted with the help of ProTox-II (http://tox.charite.de/protox_II), a virtual laboratory that employs molecular correlation, pharmacophores, and machine learning algorithms [22]. The 2,4-di-tert-butylphenol was uploaded to the “load molecule” feature of Tox-Prediction. This platform provides predictions for various toxicological endpoints, including acute toxicity, hepatotoxicity, cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, unfavorable outcome pathways (Tox21), and toxicity targets. The models used in Tox-Prediction have demonstrated high performance, as validated by independent external validation sets for each specific toxicological endpoint.

2.13 MD simulations

In the input section on the iMOD server, the docked complex was uploaded and, then, the job was submitted. iMODs (http://imods.chaconlab.org/) is software that helps users interpret and visualize 3D biological imaging data [23]. It makes it easier to simulate the dynamics of complicated domains in macromolecules, uncovers potential conformational changes, and provides a number of methods for visualizing the simulated data.

3 Results

3.1 GC–MS characterization of bacterial metabolites

The metabolites characterized utilizing GC–MS analysis are given in Table S1, along with chromatograms of bioactive compounds of L. plantarum YW11 (Figure S1). There were 32 compounds found with the GC–MS results that included acetic acid, 4-methyl-2-hexanol, 2,4-decadienal, hexanoic acid, 2,4-di-tert-butylphenol, and many more. The molecular weight of the compounds was found from PubChem, an online database, and provided in Table S1.

3.2 Identification of DEGs

The 84 samples, split between 23 experimental and 61 control groups, were analyzed using GEO2R from the GEO NCBI to identify DEGs. Using the criteria p adj < 0.05 and log2FC > 0.5, a total of 295 DEGs were found that included 206 upregulated and 89 downregulated genes. In Figure 1(a), a volcano plot of the DEGs depicts the upregulated and downregulated genes. In the visualization, genes with increased expression are represented by red dots, while genes with decreased expression are represented by blue dots. On the other hand, genes whose expression levels did not show significant changes, based on the criteria of log2FC > 0.5 and p adj < 0.05, were depicted as black dots. Furthermore, a mean difference plot of the DEGs is displayed in Figure 1(b). In Figure 1(c), the Venn diagram represents the total number of DEGs. In the analysis, a total of 22,283 genes were examined. Among them, 295 genes met specific criteria (log2FC > 0.5 and p adj < 0.05). Conversely, the remaining 21,988 genes did not meet these criteria. The Venn diagram illustrates the distinction between genes that met the criteria and those that did not.

Figure 1 (a) Volcano plot of DEGs and (b) mean difference plot of DEGs. Blue dots represent downregulated genes and red are upregulated genes. (c) Venn diagram of the DEGs predicted from GEO2R.
Figure 1

(a) Volcano plot of DEGs and (b) mean difference plot of DEGs. Blue dots represent downregulated genes and red are upregulated genes. (c) Venn diagram of the DEGs predicted from GEO2R.

3.3 Functional enrichment analysis

The most significant DEGs were used in GO and a KEGG pathway analysis to identify key cellular components, molecular functions, biological pathways, and probable molecular mechanisms. The top 10 results for the most important gene ontologies and pathways were retrieved and displayed in Figure 2 based on the ranking and running enrichment scores. In these results, for primary biological processes, the DEG genes were enriched with leukocyte chemotaxis, cell junction assembly, and monocyte chemotaxis. For primary cellular components, the DEGs were enriched with endocytic vesicle, spindle midzone, and collagen-containing extracellular matrix. For primary molecular functions, the DEGs are enriched with low-density lipoprotein particle receptor activity, lipoprotein particle receptor activity, and chemokine activity. The KEGG pathway analysis revealed several pathways that were significantly enriched (p < 0.05) among the DEGs identified in this study. Among these, the most significant pathways were amebiasis, malaria, and axon guidance.

Figure 2 GO and KEGG pathway analyses from DAVID database. (a) enriched biological processes, (b) enriched cellular components, (c) enriched molecular functions, and (d) enriched KEGG pathway enriched functions.
Figure 2

GO and KEGG pathway analyses from DAVID database. (a) enriched biological processes, (b) enriched cellular components, (c) enriched molecular functions, and (d) enriched KEGG pathway enriched functions.

3.4 PPI network construction

The PPI network from STRING was analyzed with Cytoscape. It showed that the PPI had 227 nodes while it contained 185 edges. In Figure 3, the size of the nodes represents the adj p value of the PPI and the color represents the Log2FC expression values.

Figure 3 PPI network construction of DEGs. The red color represents the higher expression of genes with greater Log2FC value, while blue represents the genes with low expression and low Log2FC value. The sizes of the nodes vary based on adj p value.
Figure 3

PPI network construction of DEGs. The red color represents the higher expression of genes with greater Log2FC value, while blue represents the genes with low expression and low Log2FC value. The sizes of the nodes vary based on adj p value.

3.5 Hub genes identification

The STRING interaction network was subjected to analysis using CytoHubba. The results revealed the top 10 nodes ranked according to degree, closeness, and betweenness centrality measures. In the visualization, the first-stage nodes, which are considered more important, were highlighted in red color. As the ranking decreased, the node colors gradually transitioned from orange to yellow, representing the relative importance of the nodes in the network. This color scheme allows for easy identification and interpretation of the significance of different nodes based on their centrality measures in the network. The shortest paths were also displayed. The top ten genes listed as FN1, TLR2, CSF2, CCL2, CCR5, DLG4, TIMP3, FCGR2B, VCAN, and SPP1 in Table S3 (Figure 4).

Figure 4 The top ten hub genes identified by Cytoscape, and the top interacted network based on the degree.
Figure 4

The top ten hub genes identified by Cytoscape, and the top interacted network based on the degree.

Figure 5 Network of predicted TF-DEGs. Green circles represent TFs, purple represents DEGs interconnected with TFs, and blue represents DEGs not linked with TFs.
Figure 5

Network of predicted TF-DEGs. Green circles represent TFs, purple represents DEGs interconnected with TFs, and blue represents DEGs not linked with TFs.

3.6 TFs and DEGs in the network

The iRegulon app was employed to identify the TFs associated with the DEGs of interest. Through this analysis, six TFs were identified in the gene-TF regulatory network. The selection of these TFs was based on a threshold of NES > 4 (normalized enrichment score), indicating their strong regulatory potential and significance in the network. Forkhead box protein P2 (FOXP2), Chromodomain Helicase DNA Binding Protein 1 (CHD1), Early B-cell Factor1 (EBF1), RNA Polymerase II Subunit A (POLR2A), MAGE Family Member D4 (MAGED4), and interferon regulatory transcription factor 3 (IRF3) were the major TFs. Twenty-two genes were found to be targets of FOXP2, 18 genes as targets of CHD1, 57 genes as targets of EBF1, 10 genes as targets of POLR2A, 27 genes as target of MAGED4, and 12 genes as potential targets of IRF3 (Figure 5).

3.7 Protein retrieval

AlphaFold, a state-of-the-art computer approach for protein structure prediction, was used to determine the protein’s 3D structure. Discovery Studio, a robust program for molecular visualization and simulation, was then used to examine and analyze the 3D structure. Figure 6 displays the analysis’s findings, which provide light on the structural properties of FN1.

Figure 6 3D structure of FN1 protein generated by AlphaFold.
Figure 6

3D structure of FN1 protein generated by AlphaFold.

3.8 Binding site prediction

DeepSite was used to predict the binding sites of FN1 onco-proteins. The volume of the estimated binding sites was 1764.237 Å3, and their area was 1665.887 Å2. Figure 7(a) depicts the expected amino acids in the binding pocket and the binding sites (Figure 7(b)) in the red-highlighted region of the protein molecule.

Figure 7 (a) The binding site molecules predicted in chains and (b) 3D structure of FN1 protein predicted by AlphaFold.
Figure 7

(a) The binding site molecules predicted in chains and (b) 3D structure of FN1 protein predicted by AlphaFold.

3.9 Metabolites 2D and 3D conformers retrieval

The 2D and 3D structures of the metabolites were retrieved from PubChem and included in Table S2. A total of 32 metabolites were obtained from the GC–MS analysis of L. plantarum YW11.

3.10 Docking analysis

The “binding score” typically refers to the calculated affinity or strength of interaction between a ligand (in this case, the metabolite) and a receptor (FN1 oncoprotein) (Figure 8). Based on its high binding score of −6.9 kJ/mol against the FN1 oncoprotein (Figure 8), the 2,4-di-tert-butylphenol was the most promising therapeutic metabolite of L. plantarum YW11. It may have assessed various factors such as binding energy, hydrogen bonding, electrostatic interactions, and steric hindrance to validate the docking results obtained from PyRx (Table S4). WADDAICA likely confirmed the docking prediction by employing its algorithms to analyze the molecular interactions between the ligand (2,4-di-tert-butylphenol) and the receptor (FN1 protein). Four residues including ILE, TRP, TYR, and ILE of FN1 protein showed interactions with the 2,4-di-tert-butylphenol. Non-covalent interactions between the substrate (ligand) and the binding site (receptor) typically include hydrogen bonding, van der Waals forces, hydrophobic interactions, and electrostatic interactions. These interactions play crucial roles in stabilizing the ligand–receptor complex and determining the specificity and affinity of binding.

Figure 8 (a) Docked complex of FN1 protein with 2,4-di-tert-butylphenol with binding energy of −6.9 kJ/mol; (b) 3D-binding interactions; and (c) 2D-binding interactions.
Figure 8

(a) Docked complex of FN1 protein with 2,4-di-tert-butylphenol with binding energy of −6.9 kJ/mol; (b) 3D-binding interactions; and (c) 2D-binding interactions.

3.11 Toxicity prediction

Table S5 displays the results of computational examination of the hazardous characteristics of 2,4-di-tert-butylphenol. Based on the data shown in Figure 9, hepatotoxicity, mutagenicity, and cytotoxicity are highly unlikely to occur. Only, mitochondrial membrane potential had the active predicted score.

Figure 9 Radar score of toxicity predicted.
Figure 9

Radar score of toxicity predicted.

3.12 Molecular simulations

In Figure 10, the results of molecular dynamic simulations conducted using iMODs are presented. These simulations aimed to predict the stability of the docked complexes by analyzing the molecular mechanics MM field force, which refers to the forces acting on atoms or molecules within the complex. In Figure 10(a), the image depicts the deformability of the complex, indicating regions that are more or less flexible. Based on the deformability potential analysis, the interaction between 2,4-di-tert-butylphenol and the FN1 protein exhibited the highest stability over a duration of 200 ns. This suggests that the complex maintained its overall structural integrity without significant deformation. In Figure 10(b), the observation of stability is further supported by the calculated B-factor, which represents the atomic displacement or flexibility within the complex. A lower B-factor indicates less atomic movement and greater stability of the complex. Figure 10(c) highlights the stiffer regions of the complex, indicating areas with limited flexibility, while Figure 10(d) indicates the presence of correlated regions within the complex, where atomic movements are synchronized. Additionally, in Figure 10(e), the eigenvalues provided insights into the energy required to uniformly deform the complex, with a value of 4.463657 × 10−6 indicating minimal energy required for deformation. A lower eigenvalue suggests greater stability of the complex. Figure 10(f) depicts the variance of the complex, which measures the extent of atomic fluctuations. A lower variance indicates less fluctuation and greater stability of the complex. Taken together, these results suggest that the docked complex between 2,4-di-tert-butylphenol and the FN1 protein remained structurally stable throughout the duration of the molecular dynamic simulations. The low B-factor, minimal energy required for deformation, and limited atomic fluctuations indicate that the complex maintained its stability and structural integrity, further supporting its potential as a therapeutic agent for FPF.

Figure 10 The simulation of molecular dynamics for the best-docked complex: (a) deformability of the complex; (b) B-factor graph; (c) elastic network; (d) covariance map; (e) eigenvalue plot; and (f) variance.
Figure 10

The simulation of molecular dynamics for the best-docked complex: (a) deformability of the complex; (b) B-factor graph; (c) elastic network; (d) covariance map; (e) eigenvalue plot; and (f) variance.

4 Discussion

FPF is a condition characterized by missense mutations in the genetic content [24, 25]. Despite this knowledge, the complete underlying molecular mechanism involved in FPF remains elusive. The objective of this study is to shed light on the potential therapeutic implications of metabolites derived from L. plantarum YW11 in the context of FPF. This will be achieved by investigating their binding affinity and molecular interactions with the FN1 gene, which was identified through differential expression analysis and evaluation of hub genes. In addition, we aim to gain a deeper understanding of FN1’s role in the disease by analyzing biological annotations within FN1 in the context of FPF. Besides, we seek to identify the transcriptional factors associated with the DEGs, providing crucial insights into the underlying mechanisms of pulmonary fibrosis pathogenesis.

L. plantarum YW11 possesses a remarkable capacity for synthesizing diverse metabolites, which can be attributed to its intricate enzymatic machinery and intricate metabolic pathways. These pathways facilitate the utilization and conversion of a variety of substrates, including sugars, amino acids, and organic acids, leading to the production of a wide array of metabolites [26]. This extensive repertoire of metabolites reflects the adaptability and versatility of L. plantarum YW11, as it has evolved to efficiently exploit available resources and adapt to varying environmental conditions [27]. Thus, this strain can generate metabolites that have the potential to interact with biological systems and offer possible health benefits [10,28].

The results of our study provide valuable insights into the potential therapeutic applications of metabolites from L. plantarum YW11 in the context of FPF. Through GC–MS analysis, we identified 32 active compounds present in L. plantarum YW11, with notable compounds including 2,4-di-tert-butylphenol. These findings are consistent with previous research highlighting the diverse bioactive compounds produced by Lactobacillus species [29]. Importantly, our study elucidated the interaction between these metabolites and the FN1 protein, a key player in FPF pathology.

Gene expression analysis revealed 295 DEGs, including 10 hub genes such as FN1, TLR2, and CSF2. FN1, in particular, has been extensively studied in the context of pulmonary fibrosis and is known to play a crucial role in extracellular matrix deposition and tissue remodeling [30]. Our findings corroborate previous research implicating FN1 in the pathogenesis of pulmonary fibrosis, further emphasizing its potential as a therapeutic target. Functional enrichment analysis of DEGs highlighted biological processes such as leukocyte chemotaxis and cellular components like the collagen-containing extracellular matrix, which are known to be dysregulated in pulmonary fibrosis [31]. Moreover, pathway analysis identified significant enrichment in pathways related to immune response and extracellular matrix remodeling, consistent with the pathophysiology of pulmonary fibrosis.

The PPI network constructed from DEGs provided additional insights into the molecular mechanisms underlying FPF. The identification of hub genes and TFs further elucidated the regulatory networks associated with FPF pathogenesis. Notably, TFs such as FOXP2 and CHD1 have been implicated in pulmonary fibrosis and may serve as potential therapeutic targets [32]. Molecular docking analysis revealed 2,4-di-tert-butylphenol as a promising candidate for targeting FN1, with a high binding score indicating favorable interaction with the protein. This aligns with previous studies demonstrating the therapeutic potential of natural compounds in modulating FN1 activity [33]. Additionally, toxicity screening and molecular dynamic simulations supported the safety and stability of 2,4-di-tert-butylphenol as a potential therapeutic agent.

The L. plantarum metabolites were studied and employed in different diseases [34]. However, its impact on FPF is still not known. The metabolite 2,4-di-tert-butylphenol was identified as the best-docked metabolite against FN1 protein. In recent studies, the 2,4-di-tert-butylphenol has also been considered the best candidate against cancerous, bacterial, and other genetic diseases [35,36,37]. The observed antibacterial efficacy of 2,4-di-tert-butylphenol could be attributed to its ability to disrupt essential cellular processes or inhibit key bacterial enzymes, resulting in growth inhibition and bacterial cell death [38–40]. The compound exerts its anticancer effects through various mechanisms, such as inducing apoptosis, inhibiting cell proliferation, or interfering with signaling pathways essential for tumor growth and metastasis [41].

Several caveats should be noted, despite the fact that our investigation provides useful insights into the potential interaction between the metabolites of L. plantarum YW11 and FN1. The use of computer forecasts based on structural models and energy calculations is a serious restriction. These hypotheses serve as a springboard for additional experimental confirmation, but they do not prove that the predicted metabolites interact with FN1 in vivo [42]. Additional experimental studies are required to validate the expected interactions and assess the therapeutic benefits of L. plantarum YW11 metabolites on FN1 and pulmonary fibrosis. The binding between the metabolites and FN1 can be confirmed by cell-based assays or biochemical assays done in vitro, and the functional effects of this interaction can be evaluated [43]. L. plantarum YW11 metabolites can be studied in animal models of pulmonary fibrosis to learn more about their effects on fibrotic processes, ECM remodeling, and disease progression [44,45,46].

5 Conclusion

In conclusion, our study demonstrates the promising therapeutic potential of metabolites from L. plantarum YW11, particularly 2,4-di-tert-butylphenol, in targeting the FN1 protein associated with FPF. Through a combination of GC–MS analysis, gene expression profiling, network analysis, molecular docking, toxicity screening, and molecular dynamics simulations, we have elucidated the molecular mechanisms underlying FPF and identified 2,4-di-tert-butylphenol as a strong candidate for drug development. These findings underscore the importance of exploring natural compounds from probiotic bacteria as potential treatments for genetic lung diseases like FPF. Further research is warranted to validate the efficacy and safety of 2,4-di-tert-butylphenol in clinical settings.

Acknowledgments

The authors are thankful to the Researchers Supporting Project number (RSP2024R462), King Saud University, Riyadh, Saudi Arabia.

  1. Funding information: This research work was financially supported by Researchers Supporting Project number (RSP2024R462), King Saud University, Riyadh, Saudi Arabia.

  2. Author contributions: Conceptualization, M.N. and H.J.; methodology, A.S.; software, S.I.M.; validation, T.A.; formal analysis, H.J., investigation, Y.Z.; resources, T.A.; data curation, M.A.; writing – original draft preparation, M.N. and H.J.; writing – review and editing, J.N. and S.I.M.; visualization, A.F.A.; supervision, Y.Z.; project administration, T.H.A.

  3. Conflict of interest: The authors declare no conflict of interest.

  4. Ethical approval: The conducted research is not related to either human or animal use.

  5. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

[1] Borie R, Kannengiesser C, Nathan N, Tabèze L, Pradère P, Crestani B. Familial pulmonary fibrosis. Respir Med Rev. 2015;32:413–34. 10.1016/j.rmed.2015.09.001.Search in Google Scholar

[2] Wilson M, Wynn TJ. Pulmonary fibrosis: Pathogenesis, etiology and regulation. Immunol Rev. 2009;2:103–21. 10.1111/j.1600-065X.2008.00736.x.Search in Google Scholar

[3] Copeland CR, Donnelly EF, Mehrad M, Ding G, Markin CR, Douglas K, et al. The association between exposures and disease characteristics in familial pulmonary fibrosis. Annals of the American Thoracic. Society. 2022;19(11):2003–12. 10.1513/AnnalsATS.202104-437OC.Search in Google Scholar

[4] Seddik HA, Bendali F, Gancel F, Fliss I, Spano G, Drider D. Lactobacillus plantarum and its probiotic and food potentialities. Pathogens. 2017;9(3):111–22. 10.3390/pathogens9030111.Search in Google Scholar

[5] Jambo T, Chingwaru C, Alufasi R, Chingwaru RS, Chingwaru W. Removal of pathogens (Escherichia coli O157: H7 and Salmonella typhi), and nutrients from wastewater by lactic acid bacteria. Adv Biotechnol. 2020;2(2):60–83. 10.1002/adbi.201900055.Search in Google Scholar

[6] Kadhom UA, Saleem AJ, Kareem AA. The effect of supernatant of Lactobacillus plantarum against Salmonella Typhi biofilm formation. J Microbiol Infect Dis. 2022;12(2):703–12. 10.5799/jmid.844849.Search in Google Scholar

[7] Zhang C, Zhang W, Cui H, Zhang B, Miao P, Yang Q, et al. Role of hub genes in the occurrence and development of testicular cancer based on bioinformatics. Int J Gen Med. 2022;15:645–60. 10.2147/IJGM.S323643.Search in Google Scholar

[8] Stanzione F, Giangreco I, Cole JC. Use of molecular docking computational tools in drug discovery. Prog Mol Biol Transl Sci. 2021;60:273–343. 10.1016/bs.pmbts.2021.05.001.Search in Google Scholar

[9] Salo-Ahen OM, Alanko I, Bhadane R, Bonvin AM, Honorato RV, Hossain S, et al. Molecular dynamics simulations in drug discovery and pharmaceutical development. Drug Discovery Today. 2020;25(1):71–83. 10.1016/j.drudis.2019.07.010.Search in Google Scholar

[10] Aziz T, Sarwar A, Fahim M, Al Dalali S, Din JU, Din ZU, et al. In silico characterization of linoleic acid biotransformation to rumenic acid in food derived Lactobacillus plantarum YW11. Adv Bioprocess Eng Food Technol. 2020;67:99–109. 10.1007/978-981-15-2569-8_8.Search in Google Scholar

[11] Shantha NC, Decker EA, Hennig B. Comparison of methylation methods for the quantitation of conjugated linoleic acid isomers. J Agric Food Chem. 1993;76(3):644–9. 10.1021/jf00028a031.Search in Google Scholar

[12] Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: Archive for functional genomics data sets – Update. Nucleic Acids Res. 2012;41(D1):D991–5. 10.1093/nar/gks1193.Search in Google Scholar

[13] Clough E, Barrett T. The gene expression omnibus database. Stat Genomics: Methods Protoc. 2016;93:110–7. 10.1016/j.ymeth.2015.06.030.Search in Google Scholar

[14] Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, et al. DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 2003;4(5):1–11. 10.1186/gb-2003-4-5-p3.Search in Google Scholar

[15] T15imalsina P, Charles K, Mondal AM. STRING PPI score to characterize protein subnetwork biomarkers for human diseases and pathways. In 2014 IEEE International Conference on Bioinformatics and Bioengineering. IEEE; 2014. p. 251–6. 10.1109/BIBM.2014.6999293.Search in Google Scholar

[16] Chin C-H, Chen S-H, Wu H-H, Ho C-W, Ko M-T, Lin C-Y. CytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8(Suppl 4):S11. 10.1186/1752-0509-8-S4-S11.Search in Google Scholar

[17] Janky R, Verfaillie A, Imrichová H, Van de Sande B, Standaert L, Christiaens V, et al. iRegulon: From a gene list to a gene regulatory network using large motif and track collections. PLOS Comput Biol. 2014;10(7):e1003731. 10.1371/journal.pcbi.1003731.Search in Google Scholar

[18] Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–9. 10.1038/s41586-021-03819-2.Search in Google Scholar

[19] Jiménez J, Doerr S, Martínez-Rosell G, Rose AS, De Fabritiis G. DeepSite: Protein-binding site predictor using 3D-convolutional neural networks. Bioinformatics. 2017;33(19):3036–42. 10.1093/bioinformatics/btx350.Search in Google Scholar

[20] Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, et al. PubChem substance and compound databases. Nucleic Acids Res. 2016;44(D1):D1202–13. 10.1093/nar/gkv951.Search in Google Scholar

[21] Bai Q, Ma J, Liu S, Xu T, Banegas-Luna AJ, Pérez-Sánchez H, et al. WADDAICA: A webserver for aiding protein drug design by artificial intelligence and classical algorithm. Comput Struct Biotechnol J. 2021;19:3573–9. 10.1016/j.csbj.2021.11.018.Search in Google Scholar

[22] Banerjee P, Eckert AO, Schrey AK, Preissner RJ. ProTox-II: A webserver for the prediction of toxicity of chemicals. Bioinformatics. 2018;34(24):W257–63. 10.1093/bioinformatics/bty612.Search in Google Scholar

[23] López-Blanco JR, Aliaga JI, Quintana-Ortí ES, Chacón PJ. iMODS: Internal coordinates normal mode analysis server. Nucleic Acids Res. 2014;42(W1):W271–6. 10.1093/nar/gku378.Search in Google Scholar

[24] Stearman RS, Cornelius AR, Young LR, Conklin DS, Mickler EA, Lu X, et al. Familial pulmonary fibrosis and Hermansky-Pudlak syndrome rare missense mutations in context. Am J Respir Crit Care Med. 2019;200(2):253–6. 10.1164/rccm.201812-2312LE.Search in Google Scholar

[25] Wang H, Xie Q, Ou‐Yang W, Zhang MB. Integrative analyses of genes associated with idiopathic pulmonary fibrosis. J Cell Biochem. 2019;120(5):8648–60. 10.1002/jcb.28047.Search in Google Scholar

[26] Aziz T, Naveed M, Jabeen K, Shabbir MA, Sarwar A, Zhennai Y, et al. Integrated genome based evaluation of safety and probiotic characteristics of Lactiplantibacillus plantarum YW11 isolated from Tibetan kefir. Food Res Int. 2023;148:1157615. 10.1016/j.foodres.2021.11157615.Search in Google Scholar

[27] Krieger-Weber S, Heras JM, Suarez CJ. Lactobacillus plantarum, a new biological tool to control malolactic fermentation: A review and an outlook. J Microbiol, Biotechnol Food Sci. 2020;6(2):23. 10.15414/jmbfs.2020.9.2.23-31.Search in Google Scholar

[28] Min Z, Xiaona H, Aziz T, Jian Z, Zhennai Y. Exopolysaccharides from Lactobacillus plantarum YW11 improve immune response and ameliorate inflammatory bowel disease symptoms. Adv Bioprocess Eng Food Technol. 2020;67:485–93. 10.1007/978-981-15-2569-8_44.Search in Google Scholar

[29] Shi Y, Gochuico BR, Yu G, Tang X, Osorio JC, Fernandez IE, et al. Syndecan-2 exerts antifibrotic effects by promoting caveolin-1–mediated transforming growth factor-β receptor I internalization and inhibiting transforming growth factor-β1 signaling. Am J Respir Cell Mol Biol. 2013;48(6):831–41. 10.1165/rcmb.2012-0393OC.Search in Google Scholar

[30] Zhou Y, Cao G, Cai H, Huang H, Zhu X. The effect and clinical significance of FN1 expression on biological functions of gastric cancer cells. Cell Biol Int. 2020;44(1):191–8. 10.1002/cbin.11342.Search in Google Scholar

[31] Bukhari SA, Salman M, Numan M, Javed MR, Zubair M, Mustafa GR. Characterization of antifungal metabolites produced by Lactobacillus plantarum and Lactobacillus coryniformis isolated from rice rinsed water. Microb Pathog. 2020;147:1871–81. 10.1016/j.micpath.2020.104286.Search in Google Scholar

[32] Sentürk M, Ercan F, Yalcin S. The secondary metabolites produced by Lactobacillus plantarum downregulate BCL-2 and BUFFY genes on breast cancer cell line and model organism Drosophila melanogaster: Molecular docking approach. Cancer Chemother Pharmacol. 2020;28(1):33–45. 10.1016/j.jsps.2019.11.018.Search in Google Scholar

[33] Song YW, Lim Y, Cho SK. 2, 4‑Di‑tert‑butylphenol, a potential HDAC6 inhibitor, induces senescence and mitotic catastrophe in human gastric adenocarcinoma AGS cells. Arch Med Res. 2018;49(6):675–83. 10.1016/j.arcmed.2018.11.005.Search in Google Scholar

[34] Zhang J, Zhao X, Jiang Y, Zhao W, Guo T, Cao Y, et al. Antioxidant status and gut microbiota change in an aging mouse model as influenced by exopolysaccharide produced by Lactobacillus plantarum YW11 isolated from Tibetan kefir. J Dairy Sci. 2017;100(8):6025–41. 10.3168/jds.2016-12353.Search in Google Scholar

[35] Kaari M, Joseph J, Manikkam R, Kalyanasundaram R, Sivaraj A, Anbalmani S, et al. A novel finding: 2, 4-Di-tert-butylphenol from streptomyces bacillaris ANS2 effective against mycobacterium tuberculosis and cancer cell lines. J Adv Biotechnol Exp Therapeutics. 2023;34:1–14.Search in Google Scholar

[36] Mishra R, Kushveer J, Khan MIK, Pagal S, Meena CK, Murali A, et al. 2, 4-Di-tert-butylphenol isolated from an endophytic fungus, Daldinia eschscholtzii, reduces virulence and quorum sensing in Pseudomonas aeruginosa. Fungal Genet Biol. 2020;11:1668. 10.1016/j.fgb.2020.103388.Search in Google Scholar

[37] Nair RV, Jayasree DV, Biju PG, Baby S. Anti-inflammatory and anticancer activities of erythrodiol-3-acetate and 2, 4-di-tert-butylphenol isolated from Humboldtia unijuga. Nat Product Res. 2020;34(16):2319–22. 10.1080/14786419.2018.1544658.Search in Google Scholar

[38] Aissaoui N, Mahjoubi M, Nas F, Mghirbi O, Arab M, Souissi Y, et al. Antibacterial potential of 2, 4-di-tert-butylphenol and calixarene-based prodrugs from thermophilic Bacillus licheniformis isolated in Algerian hot spring. J Genet Eng Biotechnol. 2019;17(1):53–62. 10.1016/j.jgeb.2018.12.001.Search in Google Scholar

[39] Chen Y, Bertrand C, Dai G, Yuan JJ. Biochemical mechanisms of acaricidal activity of 2, 4-di-tert-butylphenol and ethyl oleate against the carmine spider mite Tetranychus cinnabarinus. J Pesticide Sci. 2018;91(2):405–19. 10.1007/s12600-018-0630-5.Search in Google Scholar

[40] Padmavathi AR, Bakkiyaraj D, Thajuddin N, Pandian SK. Effect of 2, 4-di-tert-butylphenol on growth and biofilm formation by an opportunistic fungus Candida albicans. J Biofilm. 2015;31(7):565–74. 10.1016/j.jbiosc.2015.06.006.Search in Google Scholar

[41] Seenivasan A, Manikkam R, Kaari M, Sahu AK, Said M, Dastager SG. 2, 4-Di-tert-butylphenol (2, 4-DTBP) purified from Streptomyces sp. KCA1 from Phyllanthus niruri: Isolation, characterization, antibacterial and anticancer properties. J Biosci Agric Res. 2022;34:102088.Search in Google Scholar

[42] Yang M, Yan Q, Luo Y, Wang B, Deng S, Luo H, et al. Molecular mechanism of Ganji Fang in the treatment of hepatocellular carcinoma based on network pharmacology, molecular docking and experimental verification technology. Front Pharmacol. 2023;14. 10.3389/fphar.2023.01234.Search in Google Scholar

[43] Rahman M, Browne JJ, Van Crugten J, Hasan MF, Liu L, Barkla BJ. In silico, molecular docking and in vitro antimicrobial activity of the major rapeseed seed storage proteins, 2S albumins and 12S cruciferins. PLoS One. 2020;15(8):e0235314. 10.1371/journal.pone.0235314.Search in Google Scholar

[44] Tawfike AF, Viegelmann C, Edrada-Ebel R, Lin W, Wray V, Proksch P. Metabolomic tools to assess the chemistry and bioactivity of endophytic Aspergillus strain. Bioorg Med Chem. 2020;28(1):115228. 10.1016/j.bmc.2019.115228.Search in Google Scholar

[45] Balhara M, Misra HS. Antimutagenic and genoprotective effect of p-coumaric acid against mitomycin C-induced genotoxicity in Vibrio harveyi. Toxicol Rep. 2020;7:872–8. 10.1016/j.toxrep.2020.07.004.Search in Google Scholar

[46] Machuca LM, Suárez PA, Dalla Rizza M. Antibacterial activity of p-coumaric acid against Staphylococcus aureus: Mechanisms of action and synergistic effects with oxacillin. Curr Microbiol. 2019;76(10):1137–43. 10.1007/s00284-019-01704-6.Search in Google Scholar

[47] Fernández-Arrojo L, Marqués S, Polaina J, Plou FJ, Jiménez-Barbero J, Fernández-Lobato M, et al. Structural insights into the catalytic mechanism of a family 43 β-D-xylosidase from Bifidobacterium longum. J Biol Chem. 2011;286(3):2285–94. 10.1074/jbc.M110.185124.Search in Google Scholar
Received: 2023-10-18
Revised: 2024-03-11
Accepted: 2024-03-31
Published Online: 2024-05-28

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Regular Articles
  2. Porous silicon nanostructures: Synthesis, characterization, and their antifungal activity
  3. Biochar from de-oiled Chlorella vulgaris and its adsorption on antibiotics
  4. Phytochemicals profiling, in vitro and in vivo antidiabetic activity, and in silico studies on Ajuga iva (L.) Schreb.: A comprehensive approach
  5. Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents
  6. Sonochemical synthesis of gold nanoparticles mediated by potato starch: Its performance in the treatment of esophageal cancer
  7. Computational study of ADME-Tox prediction of selected phytochemicals from Punica granatum peels
  8. Phytochemical analysis, in vitro antioxidant and antifungal activities of extracts and essential oil derived from Artemisia herba-alba Asso
  9. Two triazole-based coordination polymers: Synthesis and crystal structure characterization
  10. Phytochemical and physicochemical studies of different apple varieties grown in Morocco
  11. Synthesis of multi-template molecularly imprinted polymers (MT-MIPs) for isolating ethyl para-methoxycinnamate and ethyl cinnamate from Kaempferia galanga L., extract with methacrylic acid as functional monomer
  12. Nutraceutical potential of Mesembryanthemum forsskaolii Hochst. ex Bioss.: Insights into its nutritional composition, phytochemical contents, and antioxidant activity
  13. Evaluation of influence of Butea monosperma floral extract on inflammatory biomarkers
  14. Cannabis sativa L. essential oil: Chemical composition, anti-oxidant, anti-microbial properties, and acute toxicity: In vitro, in vivo, and in silico study
  15. The effect of gamma radiation on 5-hydroxymethylfurfural conversion in water and dimethyl sulfoxide
  16. Hollow mushroom nanomaterials for potentiometric sensing of Pb2+ ions in water via the intercalation of iodide ions into the polypyrrole matrix
  17. Determination of essential oil and chemical composition of St. John’s Wort
  18. Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus
  19. Anti-parasitic activity and computational studies on a novel labdane diterpene from the roots of Vachellia nilotica
  20. Microbial dynamics and dehydrogenase activity in tomato (Lycopersicon esculentum Mill.) rhizospheres: Impacts on growth and soil health across different soil types
  21. Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives
  22. Spatial mapping of indoor air quality in a light metro system using the geographic information system method
  23. Iron indices and hemogram in renal anemia and the improvement with Tribulus terrestris green-formulated silver nanoparticles applied on rat model
  24. Integrated track of nano-informatics coupling with the enrichment concept in developing a novel nanoparticle targeting ERK protein in Naegleria fowleri
  25. Cytotoxic and phytochemical screening of Solanum lycopersicum–Daucus carota hydro-ethanolic extract and in silico evaluation of its lycopene content as anticancer agent
  26. Protective activities of silver nanoparticles containing Panax japonicus on apoptotic, inflammatory, and oxidative alterations in isoproterenol-induced cardiotoxicity
  27. pH-based colorimetric detection of monofunctional aldehydes in liquid and gas phases
  28. Investigating the effect of resveratrol on apoptosis and regulation of gene expression of Caco-2 cells: Unravelling potential implications for colorectal cancer treatment
  29. Metformin inhibits knee osteoarthritis induced by type 2 diabetes mellitus in rats: S100A8/9 and S100A12 as players and therapeutic targets
  30. Effect of silver nanoparticles formulated by Silybum marianum on menopausal urinary incontinence in ovariectomized rats
  31. Synthesis of new analogs of N-substituted(benzoylamino)-1,2,3,6-tetrahydropyridines
  32. Response of yield and quality of Japonica rice to different gradients of moisture deficit at grain-filling stage in cold regions
  33. Preparation of an inclusion complex of nickel-based β-cyclodextrin: Characterization and accelerating the osteoarthritis articular cartilage repair
  34. Empagliflozin-loaded nanomicelles responsive to reactive oxygen species for renal ischemia/reperfusion injury protection
  35. Preparation and pharmacodynamic evaluation of sodium aescinate solid lipid nanoparticles
  36. Assessment of potentially toxic elements and health risks of agricultural soil in Southwest Riyadh, Saudi Arabia
  37. Theoretical investigation of hydrogen-rich fuel production through ammonia decomposition
  38. Biosynthesis and screening of cobalt nanoparticles using citrus species for antimicrobial activity
  39. Investigating the interplay of genetic variations, MCP-1 polymorphism, and docking with phytochemical inhibitors for combatting dengue virus pathogenicity through in silico analysis
  40. Ultrasound induced biosynthesis of silver nanoparticles embedded into chitosan polymers: Investigation of its anti-cutaneous squamous cell carcinoma effects
  41. Copper oxide nanoparticles-mediated Heliotropium bacciferum leaf extract: Antifungal activity and molecular docking assays against strawberry pathogens
  42. Sprouted wheat flour for improving physical, chemical, rheological, microbial load, and quality properties of fino bread
  43. Comparative toxicity assessment of fisetin-aided artificial intelligence-assisted drug design targeting epibulbar dermoid through phytochemicals
  44. Acute toxicity and anti-inflammatory activity of bis-thiourea derivatives
  45. Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.
  46. GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes
  47. Green formulation of copper nanoparticles by Pistacia khinjuk leaf aqueous extract: Introducing a novel chemotherapeutic drug for the treatment of prostate cancer
  48. Improved photocatalytic properties of WO3 nanoparticles for Malachite green dye degradation under visible light irradiation: An effect of La doping
  49. One-pot synthesis of a network of Mn2O3–MnO2–poly(m-methylaniline) composite nanorods on a polypyrrole film presents a promising and efficient optoelectronic and solar cell device
  50. Groundwater quality and health risk assessment of nitrate and fluoride in Al Qaseem area, Saudi Arabia
  51. A comparative study of the antifungal efficacy and phytochemical composition of date palm leaflet extracts
  52. Processing of alcohol pomelo beverage (Citrus grandis (L.) Osbeck) using saccharomyces yeast: Optimization, physicochemical quality, and sensory characteristics
  53. Specialized compounds of four Cameroonian spices: Isolation, characterization, and in silico evaluation as prospective SARS-CoV-2 inhibitors
  54. Identification of a novel drug target in Porphyromonas gingivalis by a computational genome analysis approach
  55. Physico-chemical properties and durability of a fly-ash-based geopolymer
  56. FMS-like tyrosine kinase 3 inhibitory potentials of some phytochemicals from anti-leukemic plants using computational chemical methodologies
  57. Wild Thymus zygis L. ssp. gracilis and Eucalyptus camaldulensis Dehnh.: Chemical composition, antioxidant and antibacterial activities of essential oils
  58. 3D-QSAR, molecular docking, ADMET, simulation dynamic, and retrosynthesis studies on new styrylquinolines derivatives against breast cancer
  59. Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
  60. Determination of heavy elements in agricultural regions, Saudi Arabia
  61. Synthesis and characterization of antioxidant-enriched Moringa oil-based edible oleogel
  62. Ameliorative effects of thistle and thyme honeys on cyclophosphamide-induced toxicity in mice
  63. Study of phytochemical compound and antipyretic activity of Chenopodium ambrosioides L. fractions
  64. Investigating the adsorption mechanism of zinc chloride-modified porous carbon for sulfadiazine removal from water
  65. Performance repair of building materials using alumina and silica composite nanomaterials with electrodynamic properties
  66. Effects of nanoparticles on the activity and resistance genes of anaerobic digestion enzymes in livestock and poultry manure containing the antibiotic tetracycline
  67. Effect of copper nanoparticles green-synthesized using Ocimum basilicum against Pseudomonas aeruginosa in mice lung infection model
  68. Cardioprotective effects of nanoparticles green formulated by Spinacia oleracea extract on isoproterenol-induced myocardial infarction in mice by the determination of PPAR-γ/NF-κB pathway
  69. Anti-OTC antibody-conjugated fluorescent magnetic/silica and fluorescent hybrid silica nanoparticles for oxytetracycline detection
  70. Curcumin conjugated zinc nanoparticles for the treatment of myocardial infarction
  71. Identification and in silico screening of natural phloroglucinols as potential PI3Kα inhibitors: A computational approach for drug discovery
  72. Exploring the phytochemical profile and antioxidant evaluation: Molecular docking and ADMET analysis of main compounds from three Solanum species in Saudi Arabia
  73. Unveiling the molecular composition and biological properties of essential oil derived from the leaves of wild Mentha aquatica L.: A comprehensive in vitro and in silico exploration
  74. Analysis of bioactive compounds present in Boerhavia elegans seeds by GC-MS
  75. Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases
  76. LncRNA MIR17HG alleviates heart failure via targeting MIR17HG/miR-153-3p/SIRT1 axis in in vitro model
  77. Development and validation of a stability indicating UPLC-DAD method coupled with MS-TQD for ramipril and thymoquinone in bioactive SNEDDS with in silico toxicity analysis of ramipril degradation products
  78. Biosynthesis of Ag/Cu nanocomposite mediated by Curcuma longa: Evaluation of its antibacterial properties against oral pathogens
  79. Development of AMBER-compliant transferable force field parameters for polytetrafluoroethylene
  80. Treatment of gestational diabetes by Acroptilon repens leaf aqueous extract green-formulated iron nanoparticles in rats
  81. Development and characterization of new ecological adsorbents based on cardoon wastes: Application to brilliant green adsorption
  82. A fast, sensitive, greener, and stability-indicating HPLC method for the standardization and quantitative determination of chlorhexidine acetate in commercial products
  83. Assessment of Se, As, Cd, Cr, Hg, and Pb content status in Ankang tea plantations of China
  84. Effect of transition metal chloride (ZnCl2) on low-temperature pyrolysis of high ash bituminous coal
  85. Evaluating polyphenol and ascorbic acid contents, tannin removal ability, and physical properties during hydrolysis and convective hot-air drying of cashew apple powder
  86. Development and characterization of functional low-fat frozen dairy dessert enhanced with dried lemongrass powder
  87. Scrutinizing the effect of additive and synergistic antibiotics against carbapenem-resistant Pseudomonas aeruginosa
  88. Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat
  89. Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches
  90. Anti-melanoma cancer activity and chemical profile of the essential oil of Seseli yunnanense Franch
  91. Molecular docking analysis of subtilisin-like alkaline serine protease (SLASP) and laccase with natural biopolymers
  92. Overcoming methicillin resistance by methicillin-resistant Staphylococcus aureus: Computational evaluation of napthyridine and oxadiazoles compounds for potential dual inhibition of PBP-2a and FemA proteins
  93. Exploring novel antitubercular agents: Innovative design of 2,3-diaryl-quinoxalines targeting DprE1 for effective tuberculosis treatment
  94. Drimia maritima flowers as a source of biologically potent components: Optimization of bioactive compound extractions, isolation, UPLC–ESI–MS/MS, and pharmacological properties
  95. Estimating molecular properties, drug-likeness, cardiotoxic risk, liability profile, and molecular docking study to characterize binding process of key phyto-compounds against serotonin 5-HT2A receptor
  96. Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation
  97. Phyto-mediated synthesis of ZnO nanoparticles and their sunlight-driven photocatalytic degradation of cationic and anionic dyes
  98. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218
  99. Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity
  100. Eco-friendly synthesis of silver nanoparticles using Phyllanthus niruri leaf extract: Assessment of antimicrobial activity, effectiveness on tropical neglected mosquito vector control, and biocompatibility using a fibroblast cell line model
  101. Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats
  102. Quality changes of durian pulp (Durio ziberhinus Murr.) in cold storage
  103. Study on recrystallization process of nitroguanidine by directly adding cold water to control temperature
  104. Determination of heavy metals and health risk assessment in drinking water in Bukayriyah City, Saudi Arabia
  105. Larvicidal properties of essential oils of three Artemisia species against the chemically insecticide-resistant Nile fever vector Culex pipiens (L.) (Diptera: Culicidae): In vitro and in silico studies
  106. Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates
  107. The impact of drying and extraction methods on total lipid, fatty acid profile, and cytotoxicity of Tenebrio molitor larvae
  108. A zinc oxide–tin oxide–nerolidol hybrid nanomaterial: Efficacy against esophageal squamous cell carcinoma
  109. Research on technological process for production of muskmelon juice (Cucumis melo L.)
  110. Physicochemical components, antioxidant activity, and predictive models for quality of soursop tea (Annona muricata L.) during heat pump drying
  111. Characterization and application of Fe1−xCoxFe2O4 nanoparticles in Direct Red 79 adsorption
  112. Torilis arvensis ethanolic extract: Phytochemical analysis, antifungal efficacy, and cytotoxicity properties
  113. Magnetite–poly-1H pyrrole dendritic nanocomposite seeded on poly-1H pyrrole: A promising photocathode for green hydrogen generation from sanitation water without using external sacrificing agent
  114. HPLC and GC–MS analyses of phytochemical compounds in Haloxylon salicornicum extract: Antibacterial and antifungal activity assessment of phytopathogens
  115. Efficient and stable to coking catalysts of ethanol steam reforming comprised of Ni + Ru loaded on MgAl2O4 + LnFe0.7Ni0.3O3 (Ln = La, Pr) nanocomposites prepared via cost-effective procedure with Pluronic P123 copolymer
  116. Nitrogen and boron co-doped carbon dots probe for selectively detecting Hg2+ in water samples and the detection mechanism
  117. Heavy metals in road dust from typical old industrial areas of Wuhan: Seasonal distribution and bioaccessibility-based health risk assessment
  118. Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects
  119. Investigating dye adsorption: The role of surface-modified montmorillonite nanoclay in kinetics, isotherms, and thermodynamics
  120. Antimicrobial activity, induction of ROS generation in HepG2 liver cancer cells, and chemical composition of Pterospermum heterophyllum
  121. Study on the performance of nanoparticle-modified PVDF membrane in delaying membrane aging
  122. Impact of cholesterol in encapsulated vitamin E acetate within cocoliposomes
  123. Review Articles
  124. Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives
  125. Biosurfactants in biocorrosion and corrosion mitigation of metals: An overview
  126. Stimulus-responsive MOF–hydrogel composites: Classification, preparation, characterization, and their advancement in medical treatments
  127. Electrochemical dissolution of titanium under alternating current polarization to obtain its dioxide
  128. Special Issue on Recent Trends in Green Chemistry
  129. Phytochemical screening and antioxidant activity of Vitex agnus-castus L.
  130. Phytochemical study, antioxidant activity, and dermoprotective activity of Chenopodium ambrosioides (L.)
  131. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria
  132. Study of the phytotoxicity of margines on Pistia stratiotes L.
  133. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part III
  134. Impact of biogenic zinc oxide nanoparticles on growth, development, and antioxidant system of high protein content crop (Lablab purpureus L.) sweet
  135. Green synthesis, characterization, and application of iron and molybdenum nanoparticles and their composites for enhancing the growth of Solanum lycopersicum
  136. Green synthesis of silver nanoparticles from Olea europaea L. extracted polysaccharides, characterization, and its assessment as an antimicrobial agent against multiple pathogenic microbes
  137. Photocatalytic treatment of organic dyes using metal oxides and nanocomposites: A quantitative study
  138. Antifungal, antioxidant, and photocatalytic activities of greenly synthesized iron oxide nanoparticles
  139. Special Issue on Phytochemical and Pharmacological Scrutinization of Medicinal Plants
  140. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats
  141. Chemical composition and biological properties of Thymus capitatus plants from Algerian high plains: A comparative and analytical study
  142. Chemical composition and bioactivities of the methanol root extracts of Saussurea costus
  143. In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract
  144. Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property
  145. A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas
  146. A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
  147. Assessment of anti-diabetic properties of Ziziphus oenopolia (L.) wild edible fruit extract: In vitro and in silico investigations through molecular docking analysis
  148. Optimization of polyphenol extraction, phenolic profile by LC-ESI-MS/MS, antioxidant, anti-enzymatic, and cytotoxic activities of Physalis acutifolia
  149. Phytochemical screening, antioxidant properties, and photo-protective activities of Salvia balansae de Noé ex Coss
  150. Antihyperglycemic, antiglycation, anti-hypercholesteremic, and toxicity evaluation with gas chromatography mass spectrometry profiling for Aloe armatissima leaves
  151. Phyto-fabrication and characterization of gold nanoparticles by using Timur (Zanthoxylum armatum DC) and their effect on wound healing
  152. Does Erodium trifolium (Cav.) Guitt exhibit medicinal properties? Response elements from phytochemical profiling, enzyme-inhibiting, and antioxidant and antimicrobial activities
  153. Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2
  154. 6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies
  155. Simultaneous extraction and quantification of hydrophilic and lipophilic antioxidants in Solanum lycopersicum L. varieties marketed in Saudi Arabia
  156. Biological evaluation of CH3OH and C2H5OH of Berberis vulgaris for in vivo antileishmanial potential against Leishmania tropica in murine models
https://doi.org/10.1515/chem-2024-0019
Keywords for this article
L. plantarum YW11; DEGs; drug docking; TFs; simulations; hub genes
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
  2. Porous silicon nanostructures: Synthesis, characterization, and their antifungal activity
  3. Biochar from de-oiled Chlorella vulgaris and its adsorption on antibiotics
  4. Phytochemicals profiling, in vitro and in vivo antidiabetic activity, and in silico studies on Ajuga iva (L.) Schreb.: A comprehensive approach
  5. Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents
  6. Sonochemical synthesis of gold nanoparticles mediated by potato starch: Its performance in the treatment of esophageal cancer
  7. Computational study of ADME-Tox prediction of selected phytochemicals from Punica granatum peels
  8. Phytochemical analysis, in vitro antioxidant and antifungal activities of extracts and essential oil derived from Artemisia herba-alba Asso
  9. Two triazole-based coordination polymers: Synthesis and crystal structure characterization
  10. Phytochemical and physicochemical studies of different apple varieties grown in Morocco
  11. Synthesis of multi-template molecularly imprinted polymers (MT-MIPs) for isolating ethyl para-methoxycinnamate and ethyl cinnamate from Kaempferia galanga L., extract with methacrylic acid as functional monomer
  12. Nutraceutical potential of Mesembryanthemum forsskaolii Hochst. ex Bioss.: Insights into its nutritional composition, phytochemical contents, and antioxidant activity
  13. Evaluation of influence of Butea monosperma floral extract on inflammatory biomarkers
  14. Cannabis sativa L. essential oil: Chemical composition, anti-oxidant, anti-microbial properties, and acute toxicity: In vitro, in vivo, and in silico study
  15. The effect of gamma radiation on 5-hydroxymethylfurfural conversion in water and dimethyl sulfoxide
  16. Hollow mushroom nanomaterials for potentiometric sensing of Pb2+ ions in water via the intercalation of iodide ions into the polypyrrole matrix
  17. Determination of essential oil and chemical composition of St. John’s Wort
  18. Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus
  19. Anti-parasitic activity and computational studies on a novel labdane diterpene from the roots of Vachellia nilotica
  20. Microbial dynamics and dehydrogenase activity in tomato (Lycopersicon esculentum Mill.) rhizospheres: Impacts on growth and soil health across different soil types
  21. Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives
  22. Spatial mapping of indoor air quality in a light metro system using the geographic information system method
  23. Iron indices and hemogram in renal anemia and the improvement with Tribulus terrestris green-formulated silver nanoparticles applied on rat model
  24. Integrated track of nano-informatics coupling with the enrichment concept in developing a novel nanoparticle targeting ERK protein in Naegleria fowleri
  25. Cytotoxic and phytochemical screening of Solanum lycopersicum–Daucus carota hydro-ethanolic extract and in silico evaluation of its lycopene content as anticancer agent
  26. Protective activities of silver nanoparticles containing Panax japonicus on apoptotic, inflammatory, and oxidative alterations in isoproterenol-induced cardiotoxicity
  27. pH-based colorimetric detection of monofunctional aldehydes in liquid and gas phases
  28. Investigating the effect of resveratrol on apoptosis and regulation of gene expression of Caco-2 cells: Unravelling potential implications for colorectal cancer treatment
  29. Metformin inhibits knee osteoarthritis induced by type 2 diabetes mellitus in rats: S100A8/9 and S100A12 as players and therapeutic targets
  30. Effect of silver nanoparticles formulated by Silybum marianum on menopausal urinary incontinence in ovariectomized rats
  31. Synthesis of new analogs of N-substituted(benzoylamino)-1,2,3,6-tetrahydropyridines
  32. Response of yield and quality of Japonica rice to different gradients of moisture deficit at grain-filling stage in cold regions
  33. Preparation of an inclusion complex of nickel-based β-cyclodextrin: Characterization and accelerating the osteoarthritis articular cartilage repair
  34. Empagliflozin-loaded nanomicelles responsive to reactive oxygen species for renal ischemia/reperfusion injury protection
  35. Preparation and pharmacodynamic evaluation of sodium aescinate solid lipid nanoparticles
  36. Assessment of potentially toxic elements and health risks of agricultural soil in Southwest Riyadh, Saudi Arabia
  37. Theoretical investigation of hydrogen-rich fuel production through ammonia decomposition
  38. Biosynthesis and screening of cobalt nanoparticles using citrus species for antimicrobial activity
  39. Investigating the interplay of genetic variations, MCP-1 polymorphism, and docking with phytochemical inhibitors for combatting dengue virus pathogenicity through in silico analysis
  40. Ultrasound induced biosynthesis of silver nanoparticles embedded into chitosan polymers: Investigation of its anti-cutaneous squamous cell carcinoma effects
  41. Copper oxide nanoparticles-mediated Heliotropium bacciferum leaf extract: Antifungal activity and molecular docking assays against strawberry pathogens
  42. Sprouted wheat flour for improving physical, chemical, rheological, microbial load, and quality properties of fino bread
  43. Comparative toxicity assessment of fisetin-aided artificial intelligence-assisted drug design targeting epibulbar dermoid through phytochemicals
  44. Acute toxicity and anti-inflammatory activity of bis-thiourea derivatives
  45. Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.
  46. GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes
  47. Green formulation of copper nanoparticles by Pistacia khinjuk leaf aqueous extract: Introducing a novel chemotherapeutic drug for the treatment of prostate cancer
  48. Improved photocatalytic properties of WO3 nanoparticles for Malachite green dye degradation under visible light irradiation: An effect of La doping
  49. One-pot synthesis of a network of Mn2O3–MnO2–poly(m-methylaniline) composite nanorods on a polypyrrole film presents a promising and efficient optoelectronic and solar cell device
  50. Groundwater quality and health risk assessment of nitrate and fluoride in Al Qaseem area, Saudi Arabia
  51. A comparative study of the antifungal efficacy and phytochemical composition of date palm leaflet extracts
  52. Processing of alcohol pomelo beverage (Citrus grandis (L.) Osbeck) using saccharomyces yeast: Optimization, physicochemical quality, and sensory characteristics
  53. Specialized compounds of four Cameroonian spices: Isolation, characterization, and in silico evaluation as prospective SARS-CoV-2 inhibitors
  54. Identification of a novel drug target in Porphyromonas gingivalis by a computational genome analysis approach
  55. Physico-chemical properties and durability of a fly-ash-based geopolymer
  56. FMS-like tyrosine kinase 3 inhibitory potentials of some phytochemicals from anti-leukemic plants using computational chemical methodologies
  57. Wild Thymus zygis L. ssp. gracilis and Eucalyptus camaldulensis Dehnh.: Chemical composition, antioxidant and antibacterial activities of essential oils
  58. 3D-QSAR, molecular docking, ADMET, simulation dynamic, and retrosynthesis studies on new styrylquinolines derivatives against breast cancer
  59. Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
  60. Determination of heavy elements in agricultural regions, Saudi Arabia
  61. Synthesis and characterization of antioxidant-enriched Moringa oil-based edible oleogel
  62. Ameliorative effects of thistle and thyme honeys on cyclophosphamide-induced toxicity in mice
  63. Study of phytochemical compound and antipyretic activity of Chenopodium ambrosioides L. fractions
  64. Investigating the adsorption mechanism of zinc chloride-modified porous carbon for sulfadiazine removal from water
  65. Performance repair of building materials using alumina and silica composite nanomaterials with electrodynamic properties
  66. Effects of nanoparticles on the activity and resistance genes of anaerobic digestion enzymes in livestock and poultry manure containing the antibiotic tetracycline
  67. Effect of copper nanoparticles green-synthesized using Ocimum basilicum against Pseudomonas aeruginosa in mice lung infection model
  68. Cardioprotective effects of nanoparticles green formulated by Spinacia oleracea extract on isoproterenol-induced myocardial infarction in mice by the determination of PPAR-γ/NF-κB pathway
  69. Anti-OTC antibody-conjugated fluorescent magnetic/silica and fluorescent hybrid silica nanoparticles for oxytetracycline detection
  70. Curcumin conjugated zinc nanoparticles for the treatment of myocardial infarction
  71. Identification and in silico screening of natural phloroglucinols as potential PI3Kα inhibitors: A computational approach for drug discovery
  72. Exploring the phytochemical profile and antioxidant evaluation: Molecular docking and ADMET analysis of main compounds from three Solanum species in Saudi Arabia
  73. Unveiling the molecular composition and biological properties of essential oil derived from the leaves of wild Mentha aquatica L.: A comprehensive in vitro and in silico exploration
  74. Analysis of bioactive compounds present in Boerhavia elegans seeds by GC-MS
  75. Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases
  76. LncRNA MIR17HG alleviates heart failure via targeting MIR17HG/miR-153-3p/SIRT1 axis in in vitro model
  77. Development and validation of a stability indicating UPLC-DAD method coupled with MS-TQD for ramipril and thymoquinone in bioactive SNEDDS with in silico toxicity analysis of ramipril degradation products
  78. Biosynthesis of Ag/Cu nanocomposite mediated by Curcuma longa: Evaluation of its antibacterial properties against oral pathogens
  79. Development of AMBER-compliant transferable force field parameters for polytetrafluoroethylene
  80. Treatment of gestational diabetes by Acroptilon repens leaf aqueous extract green-formulated iron nanoparticles in rats
  81. Development and characterization of new ecological adsorbents based on cardoon wastes: Application to brilliant green adsorption
  82. A fast, sensitive, greener, and stability-indicating HPLC method for the standardization and quantitative determination of chlorhexidine acetate in commercial products
  83. Assessment of Se, As, Cd, Cr, Hg, and Pb content status in Ankang tea plantations of China
  84. Effect of transition metal chloride (ZnCl2) on low-temperature pyrolysis of high ash bituminous coal
  85. Evaluating polyphenol and ascorbic acid contents, tannin removal ability, and physical properties during hydrolysis and convective hot-air drying of cashew apple powder
  86. Development and characterization of functional low-fat frozen dairy dessert enhanced with dried lemongrass powder
  87. Scrutinizing the effect of additive and synergistic antibiotics against carbapenem-resistant Pseudomonas aeruginosa
  88. Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat
  89. Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches
  90. Anti-melanoma cancer activity and chemical profile of the essential oil of Seseli yunnanense Franch
  91. Molecular docking analysis of subtilisin-like alkaline serine protease (SLASP) and laccase with natural biopolymers
  92. Overcoming methicillin resistance by methicillin-resistant Staphylococcus aureus: Computational evaluation of napthyridine and oxadiazoles compounds for potential dual inhibition of PBP-2a and FemA proteins
  93. Exploring novel antitubercular agents: Innovative design of 2,3-diaryl-quinoxalines targeting DprE1 for effective tuberculosis treatment
  94. Drimia maritima flowers as a source of biologically potent components: Optimization of bioactive compound extractions, isolation, UPLC–ESI–MS/MS, and pharmacological properties
  95. Estimating molecular properties, drug-likeness, cardiotoxic risk, liability profile, and molecular docking study to characterize binding process of key phyto-compounds against serotonin 5-HT2A receptor
  96. Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation
  97. Phyto-mediated synthesis of ZnO nanoparticles and their sunlight-driven photocatalytic degradation of cationic and anionic dyes
  98. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218
  99. Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity
  100. Eco-friendly synthesis of silver nanoparticles using Phyllanthus niruri leaf extract: Assessment of antimicrobial activity, effectiveness on tropical neglected mosquito vector control, and biocompatibility using a fibroblast cell line model
  101. Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats
  102. Quality changes of durian pulp (Durio ziberhinus Murr.) in cold storage
  103. Study on recrystallization process of nitroguanidine by directly adding cold water to control temperature
  104. Determination of heavy metals and health risk assessment in drinking water in Bukayriyah City, Saudi Arabia
  105. Larvicidal properties of essential oils of three Artemisia species against the chemically insecticide-resistant Nile fever vector Culex pipiens (L.) (Diptera: Culicidae): In vitro and in silico studies
  106. Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates
  107. The impact of drying and extraction methods on total lipid, fatty acid profile, and cytotoxicity of Tenebrio molitor larvae
  108. A zinc oxide–tin oxide–nerolidol hybrid nanomaterial: Efficacy against esophageal squamous cell carcinoma
  109. Research on technological process for production of muskmelon juice (Cucumis melo L.)
  110. Physicochemical components, antioxidant activity, and predictive models for quality of soursop tea (Annona muricata L.) during heat pump drying
  111. Characterization and application of Fe1−xCoxFe2O4 nanoparticles in Direct Red 79 adsorption
  112. Torilis arvensis ethanolic extract: Phytochemical analysis, antifungal efficacy, and cytotoxicity properties
  113. Magnetite–poly-1H pyrrole dendritic nanocomposite seeded on poly-1H pyrrole: A promising photocathode for green hydrogen generation from sanitation water without using external sacrificing agent
  114. HPLC and GC–MS analyses of phytochemical compounds in Haloxylon salicornicum extract: Antibacterial and antifungal activity assessment of phytopathogens
  115. Efficient and stable to coking catalysts of ethanol steam reforming comprised of Ni + Ru loaded on MgAl2O4 + LnFe0.7Ni0.3O3 (Ln = La, Pr) nanocomposites prepared via cost-effective procedure with Pluronic P123 copolymer
  116. Nitrogen and boron co-doped carbon dots probe for selectively detecting Hg2+ in water samples and the detection mechanism
  117. Heavy metals in road dust from typical old industrial areas of Wuhan: Seasonal distribution and bioaccessibility-based health risk assessment
  118. Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects
  119. Investigating dye adsorption: The role of surface-modified montmorillonite nanoclay in kinetics, isotherms, and thermodynamics
  120. Antimicrobial activity, induction of ROS generation in HepG2 liver cancer cells, and chemical composition of Pterospermum heterophyllum
  121. Study on the performance of nanoparticle-modified PVDF membrane in delaying membrane aging
  122. Impact of cholesterol in encapsulated vitamin E acetate within cocoliposomes
  123. Review Articles
  124. Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives
  125. Biosurfactants in biocorrosion and corrosion mitigation of metals: An overview
  126. Stimulus-responsive MOF–hydrogel composites: Classification, preparation, characterization, and their advancement in medical treatments
  127. Electrochemical dissolution of titanium under alternating current polarization to obtain its dioxide
  128. Special Issue on Recent Trends in Green Chemistry
  129. Phytochemical screening and antioxidant activity of Vitex agnus-castus L.
  130. Phytochemical study, antioxidant activity, and dermoprotective activity of Chenopodium ambrosioides (L.)
  131. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria
  132. Study of the phytotoxicity of margines on Pistia stratiotes L.
  133. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part III
  134. Impact of biogenic zinc oxide nanoparticles on growth, development, and antioxidant system of high protein content crop (Lablab purpureus L.) sweet
  135. Green synthesis, characterization, and application of iron and molybdenum nanoparticles and their composites for enhancing the growth of Solanum lycopersicum
  136. Green synthesis of silver nanoparticles from Olea europaea L. extracted polysaccharides, characterization, and its assessment as an antimicrobial agent against multiple pathogenic microbes
  137. Photocatalytic treatment of organic dyes using metal oxides and nanocomposites: A quantitative study
  138. Antifungal, antioxidant, and photocatalytic activities of greenly synthesized iron oxide nanoparticles
  139. Special Issue on Phytochemical and Pharmacological Scrutinization of Medicinal Plants
  140. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats
  141. Chemical composition and biological properties of Thymus capitatus plants from Algerian high plains: A comparative and analytical study
  142. Chemical composition and bioactivities of the methanol root extracts of Saussurea costus
  143. In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract
  144. Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property
  145. A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas
  146. A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
  147. Assessment of anti-diabetic properties of Ziziphus oenopolia (L.) wild edible fruit extract: In vitro and in silico investigations through molecular docking analysis
  148. Optimization of polyphenol extraction, phenolic profile by LC-ESI-MS/MS, antioxidant, anti-enzymatic, and cytotoxic activities of Physalis acutifolia
  149. Phytochemical screening, antioxidant properties, and photo-protective activities of Salvia balansae de Noé ex Coss
  150. Antihyperglycemic, antiglycation, anti-hypercholesteremic, and toxicity evaluation with gas chromatography mass spectrometry profiling for Aloe armatissima leaves
  151. Phyto-fabrication and characterization of gold nanoparticles by using Timur (Zanthoxylum armatum DC) and their effect on wound healing
  152. Does Erodium trifolium (Cav.) Guitt exhibit medicinal properties? Response elements from phytochemical profiling, enzyme-inhibiting, and antioxidant and antimicrobial activities
  153. Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2
  154. 6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies
  155. Simultaneous extraction and quantification of hydrophilic and lipophilic antioxidants in Solanum lycopersicum L. varieties marketed in Saudi Arabia
  156. Biological evaluation of CH3OH and C2H5OH of Berberis vulgaris for in vivo antileishmanial potential against Leishmania tropica in murine models
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 21.1.2026 from https://www.degruyterbrill.com/document/doi/10.1515/chem-2024-0019/html
Scroll to top button