Search Results (130)

Arsenic (As) is a toxic trace element with neurodevelopmental, carcinogenic, and other adverse effects. Meanwhile, selenium (Se) is an antioxidant trace element with essential physiological roles in humans. The preterm neonate is the most heavily transfused patient. The multiple blood transfusions could expose this vulnerable group to trace elements with variable effects. This study aimed to quantify As and Se in various blood products that were used in neonatal blood transfusions alongside an estimate of a dose per transfusion. In addition to exposure quantification, database mining and molecular docking analysis were performed to explore potential detoxification strategies. Samples from transfusion bags: N = 120; 30 samples of each type of blood product (plasma, platelets, packed RBCs (pRBCs), and whole blood “WB”) were analyzed for As and Se by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The As and Se medians of all blood units were 0.6 and 74 μg/L, respectively. About 20% of donors have As levels above 1 μg/L. In addition, 74% of donors have Se levels less than 100 μg/L (the level of sub-optimal activity of the antioxidant enzyme glutathione peroxidase), and 60% of the donors have Se levels below the accepted minimum Se level (80 μg/L). The pRBCs were the units with the highest As and Se content. Meanwhile, WBs were the units with the highest dose per transfusion. Key methyl donors—folic acid, S-adenosylmethionine (SAM), and glutathione (GSH)—showed strong binding affinity to the active site of arsenite methyltransferase (AS3MT), a crucial enzyme in As metabolism. These ligands interacted with conserved catalytic residues such as ASN173, ASP115, and CYS92, suggesting a supportive role in enhancing As methylation and clearance. The present study highlights that neonates are exposed to As and Se via different blood product transfusions with high potential to increase As and decrease Se after transfusion. It is recommended to select donors and screen blood units with optimal Se levels and minimal As content for neonatal transfusions. The integration of in silico docking with exposure assessment adds mechanistic insight and highlights the potential for targeted nutritional interventions to reduce As toxicity in vulnerable neonatal populations. Full article

Background/Objectives: In the last few decades, the dengue virus, a prevalent flavivirus, has demonstrated various epidemiological, economic, and health impacts around the world. Dengue virus serotype 2 (DENV2) plays a vital role in dengue-associated mortality. The RNA-dependent RNA polymerase (RdRp) of DENV2 is a charming druggable target owing to its crucial function in viral reproduction. In recent years, streptomycetes natural products (NPs) have attracted considerable attention as a potential source of antiviral drugs. Methods: Seeking prospective inhibitors that inhibit the DENV2 RdRp allosteric site, in silico mining of the Streptome database was executed. AutoDock4.2.6 software performance in predicting docking poses of the inspected inhibitors was initially conducted according to existing experimental data. Upon the assessed docking parameters, the Streptome database was virtually screened against DENV2 RdRp allosteric site. The streptomycetes NPs with docking scores less than the positive control (68T; calc. −35.6 kJ.mol⁻¹) were advanced for molecular dynamics simulations (MDS), and their binding affinities were computed by employing the MM/GBSA approach. Results: SDB9818 and SDB4806 unveiled superior inhibitor activities against DENV2 RdRp upon MM/GBSA//300 ns MDS than 68T with ΔG_binding values of −246.4, −242.3, and −150.6 kJ.mol⁻¹, respectively. A great consistency was found in both the energetic and structural analyses of the identified inhibitors within the DENV2 RdRp allosteric site. Furthermore, the physicochemical characteristics of the identified inhibitors demonstrated good oral bioavailability. Eventually, quantum mechanical computations were carried out to evaluate the chemical reactivity of the identified inhibitors. Conclusions: As determined by in silico computations, the identified streptomycetes NPs may act as DENV2 RdRp allosteric inhibitors and mandate further experimental assays. Full article

Background/Objectives: Oncogenic KRAS drives ~30% of solid tumours, yet the only approved G12C-specific drugs benefit ≈ 13% of KRAS-mutant patients, leaving a major clinical gap. We sought mutation-agnostic natural ligands from Ziziphus lotus, whose stereochemically rich phenolics may overcome this limitation by occupying the SI/II (Switch I/Switch II) groove and locking KRAS in its inactive state. Methods: Phytochemical mining yielded five recurrent phenolics, such as (+)-catechin, hyperin, astragalin, eriodictyol, and the prenylated benzoate amorfrutin A, benchmarked against the covalent inhibitor sotorasib. An in silico cascade combined SI/II docking, multi-parameter ADME/T (Absorption, Distribution, Metabolism, Excretion, and Toxicity) filtering, and 100 ns explicit solvent molecular dynamics simulations. Pharmacokinetic modelling predicted oral absorption, Lipinski compliance, mutagenicity, and acute-toxicity class. Results: Hyperin and astragalin showed the strongest non-covalent affinities (−8.6 kcal mol⁻¹) by forging quadridentate hydrogen-bond networks that bridge the P-loop (Asp30/Glu31) to the α3-loop cleft (Asp119/Ala146). Catechin (−8.5 kcal mol⁻¹) balanced polar anchoring with entropic economy. ADME ranked amorfrutin A the highest for predicted oral absorption (93%) but highlighted lipophilic solubility limits; glycosylated flavonols breached Lipinski rules yet remained non-mutagenic with class-5 acute-toxicity liability. Molecular dynamics trajectories confirmed that hyperin clamps the SI/II groove, suppressing loop RMSF below 0.20 nm and maintaining backbone RMSD stability, whereas astragalin retains pocket residence with transient re-orientation. Conclusions: Hyperin emerges as a low-toxicity, mutation-agnostic scaffold that rigidifies inactive KRAS. Deglycosylation, nano-encapsulation, or soft fluorination could reconcile permeability with durable target engagement, advancing Z. lotus phenolics toward broad-spectrum KRAS therapeutics. Full article

Spore-forming Bacilli have been explored due to their potential biotechnological features and applications in human health and functional food research. This study focuses on the genetic and phenotypical characterization of the functional probiotic properties of Bacillus velezensis P45, a strain isolated from fish intestines. B. velezensis P45 exhibited antimicrobial activity against Gram-positive and Gram-negative pathogens and demonstrated strong autoaggregation and biofilm formation properties in vitro. The strain also showed tolerance to gastrointestinal conditions and ability to metabolize and adhere to mucin. In silico analysis confirmed the absence of virulence factors and antibiotic resistance genes, reinforcing its safety as a probiotic candidate. Genome mining revealed the presence of genes related to adhesion, such as fibronectin-binding protein and enolases, and for the synthesis of secondary metabolites, including the antimicrobial lipopeptides fengycin, surfactin, and bacillibactin. In addition, phylogenetic comparison using the yloA (rqcH) gene associated with gut adhesion clustered strain P45 with other probiotic Bacillus and B. velezensis strains, while separating it from pathogenic bacteria. Thus, the strain B. velezensis P45 could be a valuable candidate as a probiotic due to its functional properties and safety. Full article

Breast, colon, and ovarian cancers are among the most prevalent malignancies worldwide, with distinct clinical features. This study aims to identify key proteins as common biomarkers for breast, colon, and ovarian cancer through protein analysis, molecular mechanisms, and patient sample validation. Data mining from curated databases identified 483 proteins for breast cancer, 521 for colon cancer, and 223 for ovarian cancer. Interaction network analysis revealed shared clusters involved in cancer progression, DNA repair, and cell proliferation. A core set of 27 proteins was found to be common across all three cancer types, participating in key biological processes such as DNA damage response, cell proliferation, and apoptosis. Notably, these proteins are implicated in KEGG pathways linked to multiple cancers. Differential gene expression analysis revealed significant alterations in the expressions of MSH2 and KIT across the three cancers, suggesting their potential as common biomarkers. The high expression of these proteins was associated with better survival outcomes, highlighting their potential as common biomarkers for breast, colon, and ovarian cancers. The in-silico methodology integrated various bioinformatic tools—including cluster identification, gene expression profiling, protein network visualization, and biomarker prediction—enhancing the understanding of shared molecular mechanisms and potential therapeutic targets. Full article

Background: Lung adenocarcinoma is one of the major subtype of non-Small Cell Lung Cancer and biomarkers are essential to be identified for early diagnosis. The study aims to find in silico and preliminary in vitro analysis of potential biomarkers for lung adenocarcinoma. Methods: Bioinformatics analysis in parallel to data mining analysis was performed on microarray data with lung adenocarcinoma samples to identify potent gene biomarkers associated with lung cancer type. Afterwards, these genes were then validated in vitro using RT-qPCR analysis in cancerous (Calu-3) and non-cancerous (MRC-5) cell lines. Moreover, these genes were used in machine learning-based analysis to classify lung adenocarcinoma samples from controls. The analysis includes three experiments—the bioinformatic (in silico), in vitro, and machine learning analyses. Results: The three experiments identified four genes, namely, SLC15A1, GPR123 (ADGRA1), KCNAB2, and KNDC1, as key biomarkers and the most relevant gene features for distinguishing lung adenocarcinoma from control. Conclusions: This study identifies four biomarkers associated with lung adenocarcinoma through bioinformatics, in vitro and machine learning analyses. These four genes shows strong potential for further investigation in clinical research. Full article

Background/Objectives: MicroRNAs (miRNAs) are molecules involved in biological regulation processes, including type 2 diabetes and its complications development. Single nucleotide polymorphisms (SNPs) can alter miRNA mechanisms, resulting in loss or gain effects. VEGFA is recognized for its role in angiogenesis. However, its overexpression can lead to deleterious effects, such as disorganized and inefficient vasculature. Under hyperglycemic conditions, VEGFA expression seems to increase, which may contribute to the development of microvascular and macrovascular diabetic complications. Several miRNAs are associated with VEGFA regulation and seem to act in the prevention of dysregulated expression. This study aimed to investigate SNPs in miRNA regions related to the loss effect in VEGFA regulation, examining their frequency and potential physiological effects in the development of diabetic complications. Methods: VEGFA-targeting miRNAs were identified using the R package multimiR, with validated and predicted results. Tissue expression analysis and SNP search were data-mined with Python 3 for miRNASNP-v3 SNP raw databases. Allele frequencies were obtained from dbSNP. The miRNA–mRNA interaction comparison was obtained in the miRmap tool through Python 3. MalaCards were used to infer physiological disease association. Results: The variant rs371699284 was selected in hsa-miR-654-3p among 103 potential VEGFA-targeting miRNAs. This selected SNP demonstrated promising results in bioinformatics predictions, tissue-specific expression, and population frequency, highlighting its potential role in miRNA regulation and the resulting loss in VEGFA-silencing efficiency. Conclusions: Our findings suggest that carriers of rs1238947970 may increase susceptibility to diabetic microvascular and macrovascular complications. Furthermore, in vitro and in silico studies are necessary to better understand these processes. Full article

In our previous study, Lentzea sp. JNUCC 0626 was isolated from Hwasun Gotjawal on Jeju Island, and its melanogenic effects were confirmed in B16F10 melanoma cells through the identification of 1-acetyl-β-carboline. In this study, we conducted a comprehensive taxonomic characterization of Lentzea sp. JNUCC 0626, including enzymatic activities, carbohydrate metabolism, growth conditions, and cellular composition. Major fatty acids identified were iso-C16:0, iso-C15:0, and C15:0 anteiso, with polar lipids such as diphosphatidylglycerol, phosphatidylethanolamine, and several unidentified lipids. Ubiquinone Q-9 was determined as the predominant respiratory quinone. Enzymatic activity analysis (API ZYM) showed alkaline phosphatase, esterase (C4), esterase lipase (C8), and leucine arylamidase activities, while carbohydrate metabolism analysis (API 50CHB) indicated acid production from esculin alone. Complete genome sequencing revealed a 10,602,950 bp linear chromosome and a 177,940 bp plasmid. This plasmid encodes essential plasmid-related genes, including a Type IV secretion system and ParA proteins critical for plasmid transfer and stability. These findings suggest that the plasmid in Lentzea sp. JNUCC 0626 could be utilized for developing host–vector systems to facilitate the combinatorial biosynthesis of novel bioactive compounds. Comparative genomic analysis identified Lentzea pudingi CGMCC 4.7319 as the closest relative, but significant genetic divergence (dDDH 46.7%, ANI 88.02%) strongly supports the classification of Lentzea sp. JNUCC 0626 as a novel species. AntiSMASH analysis revealed 34 biosynthetic gene clusters (BGCs), highlighting the strain’s capacity to produce diverse bioactive compounds. Finally, the JNUCC 0626 extract exhibited concentration-dependent NO inhibition in LPS-stimulated RAW 264.7 cells, demonstrating significant anti-inflammatory activity. This suggests that the secondary metabolites inferred from genomic analysis may contribute to these observed bioactivities. Full article

Overcoming the growing challenge of antimicrobial resistance (AMR), which affects millions of people worldwide, has driven attention for the exploration of marine-derived antimicrobial peptides (AMPs) for innovative solutions. Cnidarians, such as corals, sea anemones, and jellyfish, are a promising valuable resource of these bioactive peptides due to their robust innate immune systems yet are still poorly explored. Hence, we employed an in silico proteolysis strategy to search for novel AMPs from omics data of 111 Cnidaria species. Millions of peptides were retrieved and screened using shallow- and deep-learning models, prioritizing AMPs with a reduced toxicity and with a structural distinctiveness from characterized AMPs. After complex network analysis, a final dataset of 3130 Cnidaria singular non-haemolytic and non-toxic AMPs were identified. Such unique AMPs were mined for their putative antibacterial activity, revealing 20 favourable candidates for in vitro testing against important ESKAPEE pathogens, offering potential new avenues for antibiotic development. Full article

In our large-scale search for antimicrobial-producing bacteria, we isolated an actinomycete strain from rhizospheric soil of Bambusa vulgaris. The strain designated BP-8 showed noticeable antibacterial activity. BP-8 was subjected to a whole-genome analysis via a polyphasic taxonomy approach, and its antibacterial metabolite was identified by HRLS-MS. The results of the physiological and morphological analyses indicated that BP-8 is an aerobic, neutrophilic, mesophilic organism that is tolerant to 8% NaCl and can use a wide range of carbohydrates. It forms curly sporophores with a warty surface. The results of the phylogenetic and average nucleotide identity analyses and in silico DNA–DNA hybridization calculation indicated that BP-8 represents the type strain of a novel Streptomyces species. A comparative in silico analysis of the genome sequences of BP-8 and its closest related strains revealed the presence of genes encoding chemotaxonomic markers characteristic of Streptomyces. The antibacterial compound was identified as amicetin. Genomic mining also revealed more than 10 biosynthetic gene clusters that have not been described previously and may lead to the discovery of new valuable compounds. On the basis of these results, strain BP-8^T (=VKM Ac-3066^T = CCTCC AA 2024094^T) is proposed as the type strain of the novel species Streptomyces sirii sp. nov. Full article

Fungal infections pose a growing public health threat, creating an urgent clinical need for new antifungals. Natural products (NPs) from organisms in extreme environments are a promising source for novel drugs. Streptomyces albidoflavus CBMAI 1855 exhibited significant potential in this regard. This study aimed to (1) assess the antifungal spectrum of the CBMAI 1855 extract against key human pathogens, (2) elicit NP production through co-cultivation with fungi, correlating the metabolites with the biosynthetic gene clusters (BGCs), and (3) perform in silico toxicity predictions of the identified compounds to analyze their suitability for drug development. The crude extract of CBMAI 1855 exhibited broad-spectrum antifungal activity. The metabolomic analysis identified antifungal NPs such as antimycin A, fungimycin, surugamides, 9-(4-aminophenyl)-3,7-dihydroxy-2,4,6-trimethyl-9-oxo-nonoic acid, and ikarugamycin, with the latter two predicted to be the most suitable for drug development. Genome mining revealed three cryptic BGCs potentially encoding novel antifungals. These BGCs warrant a detailed investigation to elucidate their metabolic products and harness their potential. CBMAI 1855 is a prolific producer of multiple antifungal agents, offering a valuable source for drug discovery. This study highlights the importance of exploring microbial interactions to uncover therapeutics against fungal infections, with a detailed exploration of cryptic BGCs offering a pathway to novel antifungal compounds. Full article

Anoectochilus roxburghii is a rare and precious medicinal and ornamental plant of Orchidaceae. Abundant morphological characteristics have been observed among cultivated accessions. Our understanding of the genetic basis of morphological diversity is limited due to a lack of sequence data and candidate genes. In this study, a high-quality de novo transcriptome assembly of A.roxburghii was generated. A total of 138,385 unigenes were obtained, and a BUSCO (Benchmarking Universal Single-Copy Orthologs) analysis showed an assembly completeness of 98.8%. Multiple databases were used to obtain a comprehensive annotation, and the unigenes were functionally categorized using the GO (Gene Ontology), KOG (Eukaryotic Orthologous Groups), KEGG (Kyoto Encyclopedia of Genes and Genomes), and Nr databases. After comparing the phenotypic characteristics of five representative cultivars, a set of cultivar-specific, highly expressed unigenes was identified based on a comparative transcriptome analysis. Then, a WGCNA (Weighted Gene Co-expression Network Analysis) was performed to generate gene regulatory modules related to chlorophyll content (red) and sucrose synthase activity (black). In addition, the expression of six and four GO enrichment genes in the red and black modules, respectively, was analyzed using qRT-PCR to determine their putative functional roles in the leaves of the five cultivars. Finally, in silico SSR (Simple Sequence Repeat) mining of the assembled transcriptome identified 44,045 SSRs. Mononucleotide was the most dominant class of SSRs, followed by complex SSRs. In summary, this study reports on the phenomic and genomic resources of A. roxburghii, combining SSR marker development and validation. This report aids in morphological diversity assessments of Anoectochilus roxburghii. Full article

Human hair is characterised by variability, determined by genetic and macromolecular factors. Whilst the European hair type has been a focus of extensive research, Afro-textured hair care faces challenges created by insufficient knowledge of its properties. Applications of hair care products that are incompatible with Afro-textured hair frequently have detrimental effects on the scalp. This highlights the need for partnerships to bridge the gap between research and hair care practices and address challenges related to Afro-textured hair. In this review, we performed data mining of the existing literature and in silico network analysis of the biomarkers relevant to Afro-textured hair. The approaches to hair maintenance are highlighted in the context of hair anatomy and growth cycles, organisation of keratins, surface lipids, and chemical bonds. We discuss a range of biomarkers affecting hair fibre’s shape and mechanical strength, with the gene interactive network pointing to the hierarchical organisation of important traits, notably hair shaft diameter, keratinization, and hair follicle patterning, which likely contribute to the increased sensitivity of hair to extrinsic factors. We propose that a better understanding of the genetic traits, molecular structure, and biomechanics of Afro-textured hair is required to initiate more effective hair care solutions that would benefit the wider population. Full article

Background: The abuse of psychoactive substances presents challenges in clinical and forensic toxicology. The emergence of novel and potent drugs that pose significant health risks, in particular towards frequent abusers and users unaware of the ingredients, further complicates the situation. Designer benzodiazepines have become a fast-growing subgroup of these new psychoactive substances (NPSs), and their overdose may potentially turn fatal, especially when combined with other central nervous system depressants. In 2021, flubrotizolam, a potent thieno-triazolo designer benzodiazepine, emerged on the illicit market, available online as a “research chemical”. The identification of markers of consumption for this designer benzodiazepine is essential in analytical toxicology, especially in clinical and forensic cases. Methods: We therefore aimed to identify biomarkers of flubrotizolam uptake in ten-donor-pooled human hepatocytes, applying liquid chromatography high-resolution mass spectrometry and software-aided data mining supported by in silico prediction tools. Results: Prediction studies resulted in 10 and 13 first- and second-generation metabolites, respectively, mainly transformed through hydroxylation and sulfation, methylation, and glucuronidation reactions. We identified six metabolites after 3 h human hepatocyte incubation: two hydroxylated metabolites (α- and 6-hydroxy-flubrotizolam), two 6-hydroxy-glucuronides, a reduced-hydroxy-N-glucuronide, and an N-glucuronide. Conclusions: We suggest detecting flubrotizolam and its hydroxylated metabolites as markers of consumption after the glucuronide hydrolysis of biological samples. The results are consistent with the in vivo metabolism of brotizolam, a medically used benzodiazepine and a chloro-phenyl analog of flubrotizolam. Full article

Multidrug-resistant bacteria present a significant public health challenge; such pathogens exhibit reduced susceptibility to conventional antibiotics, limiting current treatment options. Cationic non-ribosomal peptides (CNRPs) such as brevicidine and polymyxins have emerged as promising candidates to block Gram-negative bacteria. To investigate the capability of bacteria to biosynthesize CNRPs, and specifically polymyxins, over 11,000 bacterial genomes were mined in silico. Paenibacillus polymyxa was identified as having a robust biosynthetic capacity, based on multiple polymyxin gene clusters. P. polymyxa biosynthetic competence was confirmed by metabolite characterization via HPLC purification and MALDI TOF/TOF analysis. When grown in a selected medium, the metabolite yield was 4 mg/L with a 20-fold specific activity increase. Polymyxin B (PMB) was assayed with select nosocomial pathogens, including Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumaii, which exhibited minimum inhibitory concentrations of 4, 1, and 1 µg/mL, respectively. Full article