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1.
BMC Biotechnol ; 24(1): 27, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725019

ABSTRACT

Cyanobacteria represent a rich resource of a wide array of unique bioactive compounds that are proving to be potent sources of anticancer drugs. Selenium nanoparticles (SeNPs) have shown an increasing potential as major therapeutic platforms and led to the production of higher levels of ROS that can present desirable anticancer properties. Chitosan-SeNPs have also presented antitumor properties against hepatic cancer cell lines, especially the Cht-NP (Chitosan-NPs), promoting ROS generation and mitochondria dysfunction. It is proposed that magnetic fields can add new dimensions to nanoparticle applications. Hence, in this study, the biosynthesis of SeNPs using Alborzia kermanshahica and chitosan (CS) as stabilizers has been developed. The SeNPs synthesis was performed at different cyanobacterial cultivation conditions, including control (without magnetic field) and magnetic fields of 30 mT and 60 mT. The SeNPs were characterized by uv-visible spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), Dynamic light scattering (DLS), zeta potential, and TEM. In addition, the antibacterial activity, inhibition of bacterial growth, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC), as well as the antifungal activity and cytotoxicity of SeNPs, were performed. The results of uv-visible spectrometry, DLS, and zeta potential showed that 60 mT had the highest value regarding the adsorption, size, and stabilization in compared to the control. FTIR spectroscopy results showed consistent spectra, but the increased intensity of peaks indicates an increase in bond number after exposure to 30 mT and 60 mT. The results of the antibacterial activity and the inhibition zone diameter of synthesized nanoparticles showed that Staphylococcus aureus was more sensitive to nanoparticles produced under 60 mT. Se-NPs produced by Alborzia kermanshahica cultured under a 60 mT magnetic field exhibit potent antimicrobial and anticancer properties, making them a promising natural agent for use in the pharmaceutical and biomedical industries.


Subject(s)
Chitosan , Magnetic Fields , Selenium , Selenium/chemistry , Selenium/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/biosynthesis , Microbial Sensitivity Tests , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/metabolism , Antineoplastic Agents/chemistry , Metal Nanoparticles/chemistry
2.
J Med Chem ; 67(10): 7759-7787, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38716896

ABSTRACT

There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research.


Subject(s)
Selenium , Organoselenium Compounds/chemistry , Organoselenium Compounds/pharmacology , Selenium/chemistry , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology
3.
Int J Pharm ; 658: 124214, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38723732

ABSTRACT

The crucial demand to overcome the issue of multidrug resistance is required to refine the performance of antibiotics. Such a process can be achieved by fastening them to compatible nanoparticles to obtain effective pharmaceuticals at a low concentration. Thus, selenium nanoparticles (Se NPs) are considered biocompatible agents that are applied to prevent infections resulting from bacterial resistance to multi-antibiotics. The current evaluated the effectiveness of Se NPs and their conjugates with antibiotics such as amikacin (AK), levofloxacin (LEV), and piperacillin (PIP) against Pseudomonas aeruginosa (P. aeruginosa). In addition, the study determined the antibacterial and antibiofilm properties of Se NPs and their conjugates with LEV against urinary tract pathogens such as Staphylococcus aureus (S. aureus), Enterococcus faecalis (E. faecalis), P. aeruginosa, and Escherichia coli (E. coli). The result of minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) for eight isolates of P. aeruginosa revealed that the conjugation of Se NPs with AK, LEV, and PIP resulted in a reduction in the concentration of antibiotic-conjugated Se NPs. The concentration was found to be about 10-20 times lower than that of bare antibiotics. The MIC of the Se NPs with LEV (i.e., Se NPs:LEV) for S. aureus, E. faecalis, P. aeruginosa, and E. coli was found to be 1.4:0.5, 0.7:0.25, 22:8, and 11:4 µg/mL, respectively. The results of the half-maximal inhibitory concentration (IC50) demonstrated that Se NPs:LEV conjugate have inhibited 50 % of the mature biofilms of S. aureus, E. faecalis, P. aeruginosa, and E. coli at a concentration of 27.5 ± 10.5, 18.8 ± 3.1, 40.6 ± 10.7, and 21.6 ± 3.3 µg/mL, respectively compared to the control. It has been suggested that the antibiotic-conjugated Se NPs have great potential for biomedical applications. The conjugation of Se NPs with AK, LEV, and PIP increases the antibacterial potency against resistant pathogens at a low concentration.


Subject(s)
Anti-Bacterial Agents , Biofilms , Drug Resistance, Multiple, Bacterial , Escherichia coli , Microbial Sensitivity Tests , Nanoparticles , Pseudomonas aeruginosa , Selenium , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Selenium/chemistry , Selenium/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Nanoparticles/chemistry , Pseudomonas aeruginosa/drug effects , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Enterococcus faecalis/drug effects
4.
Food Chem ; 452: 139595, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38749143

ABSTRACT

Selenium nanospheres (SeNPs) show less toxicity and greater bioavailability than selenite salts. This research demonstrated the substantial tolerance and efficient conversion of Se(IV) into SeNPs by Lactiplantibacillus plantarum NML21. The bioreduction process of Se(IV) and the properties of SeNPs, including their morphology, particle size, and stability, were investigated with techniques including SEM, EDX, TEM, XPS, FT-IR, dynamic light scattering, XRD, and Raman spectroscopy. Under high selenium stress, certain cells displayed significant deformation and rupture, and released SeNPs as the main product of the bioreduction of Se(IV). These SeNPs were red, amorphous, zero-valent, and spherical, with an average diameter of 160 nm. Spectroscopic analysis highlighted that the functional groups of CO and CO are key to the bioreduction of Se(IV). The study suggested preliminary mechanisms for the bioreduction of Se(IV) and the formation and release of SeNPs by lactic acid bacteria. NML21 may therefore be a promising candidate for SeNPs synthesis.


Subject(s)
Nanospheres , Oxidation-Reduction , Selenium , Selenium/chemistry , Selenium/metabolism , Nanospheres/chemistry , Nanospheres/metabolism , Particle Size , Lactobacillus plantarum/metabolism , Lactobacillus plantarum/chemistry
5.
Nat Commun ; 15(1): 4041, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740794

ABSTRACT

Due to the complexity of the catalytic FeMo cofactor site in nitrogenases that mediates the reduction of molecular nitrogen to ammonium, mechanistic details of this reaction remain under debate. In this study, selenium- and sulfur-incorporated FeMo cofactors of the catalytic MoFe protein component from Azotobacter vinelandii are prepared under turnover conditions and investigated by using different EPR methods. Complex signal patterns are observed in the continuous wave EPR spectra of selenium-incorporated samples, which are analyzed by Tikhonov regularization, a method that has not yet been applied to high spin systems of transition metal cofactors, and by an already established grid-of-error approach. Both methods yield similar probability distributions that reveal the presence of at least four other species with different electronic structures in addition to the ground state E0. Two of these species were preliminary assigned to hydrogenated E2 states. In addition, advanced pulsed-EPR experiments are utilized to verify the incorporation of sulfur and selenium into the FeMo cofactor, and to assign hyperfine couplings of 33S and 77Se that directly couple to the FeMo cluster. With this analysis, we report selenium incorporation under turnover conditions as a straightforward approach to stabilize and analyze early intermediate states of the FeMo cofactor.


Subject(s)
Azotobacter vinelandii , Molybdoferredoxin , Nitrogenase , Selenium , Sulfur , Electron Spin Resonance Spectroscopy/methods , Azotobacter vinelandii/enzymology , Azotobacter vinelandii/metabolism , Nitrogenase/metabolism , Nitrogenase/chemistry , Molybdoferredoxin/metabolism , Molybdoferredoxin/chemistry , Selenium/metabolism , Selenium/chemistry , Sulfur/metabolism , Sulfur/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry
6.
Int J Biol Macromol ; 268(Pt 1): 131769, 2024 May.
Article in English | MEDLINE | ID: mdl-38692999

ABSTRACT

This study investigates the synthesis of selenium nanoparticles (SeNPs), owing to the low cost and abundance of selenium. However, the toxicity of SeNP prompts the development of a selenium nanocomposite (SeNC) containing pectin, keratin, and ferulic acid to improve the bioactivity of Se[0]. Further, incorporating the SeNC in a suitable formulation for drug delivery as a transdermal patch was worth studying. Accordingly, various analytical techniques were used to characterize the SeNPs and the SeNC, confirming successful synthesis and encapsulation. The SeNC exhibited notable particle size of 448.2 ± 50.2 nm, high encapsulation efficiency (98.90 % ± 2.4 %), 28.1 ± 0.45 drug loading, and sustained drug release at pH 5.5. Zeta potential and XPS confirmed the zero-oxidation state. The supramolecular structure was evident from spectral analysis endorsing the semi-crystalline nature of the SeNC and SEM images showcasing flower-shaped structures. Further, the SeNC demonstrated sustained drug release (approx. 22 % at 48 h) and wound-healing potential in L929 fibroblast cells. Subsequently, the SeNC loaded into a gelling agent exhibited shear thinning properties and improved drug release by nearly 58 %. A 3D printed reservoir-type transdermal patch was developed utilizing the SeNC-loaded gel, surpassing commercially available patches in characteristics such as % moisture uptake, tensile strength, and hydrophobicity. The patch, evaluated through permeation studies and CAM assay, exhibited controlled drug release and angiogenic properties for enhanced wound healing. The study concludes that this patch can serve as a smart dressing with tailored functionality for different wound stages, offering a promising novel drug delivery system for wound healing.


Subject(s)
Drug Liberation , Keratins , Nanogels , Pectins , Printing, Three-Dimensional , Selenium , Transdermal Patch , Selenium/chemistry , Pectins/chemistry , Keratins/chemistry , Animals , Nanogels/chemistry , Mice , Oxidation-Reduction , Wound Healing/drug effects , Cell Line , Nanocomposites/chemistry , Drug Carriers/chemistry , Drug Delivery Systems , Particle Size
7.
ACS Nano ; 18(20): 13084-13097, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38727520

ABSTRACT

In the current work, the foliar application of selenium nanomaterials (Se0 NMs) suppressed sheath blight in rice (Oryza sativa). The beneficial effects were nanoscale specific and concentration dependent. Specifically, foliar amendment of 5 mg/L Se0 NMs decreased the disease severity by 68.8% in Rhizoctonia solani-infected rice; this level of control was 1.57- and 2.20-fold greater than that of the Se ions with equivalent Se mass and a commercially available pesticide (Thifluzamide). Mechanistically, (1) the controlled release ability of Se0 NMs enabled a wider safe concentration range and greater bioavailability to Se0 NMs, and (2) transcriptomic and metabolomic analyses demonstrated that Se0 NMs simultaneously promoted the salicylic acid- and jasmonic-acid-dependent acquired disease resistance pathways, antioxidative system, and flavonoid biosynthesis. Additionally, Se0 NMs improved rice yield by 31.1%, increased the nutritional quality by 6.4-7.2%, enhanced organic Se content by 44.8%, and decreased arsenic and cadmium contents by 38.7 and 42.1%, respectively, in grains as compared with infected controls. Human simulated gastrointestinal tract model results showed that the application of Se0 NMs enhanced the bioaccessibility of Se in grains by 22.0% and decreased the bioaccessibility of As and Cd in grains by 20.3 and 13.4%, respectively. These findings demonstrate that Se0 NMs can serve as an effective and sustainable strategy to increase food quality and security.


Subject(s)
Nanostructures , Oryza , Plant Diseases , Rhizoctonia , Selenium , Oryza/microbiology , Oryza/metabolism , Oryza/drug effects , Selenium/pharmacology , Selenium/chemistry , Plant Diseases/microbiology , Plant Diseases/prevention & control , Humans , Rhizoctonia/drug effects , Nanostructures/chemistry , Nutritive Value , Disease Resistance/drug effects
8.
Biomed Mater ; 19(4)2024 May 30.
Article in English | MEDLINE | ID: mdl-38772390

ABSTRACT

Bacterial biofilm formation is associated with the pathogenicity of pathogens and poses a serious threat to human health and clinical therapy. Complex biofilm structures provide physical barriers that inhibit antibiotic penetration and inactivate antibiotics via enzymatic breakdown. The development of biofilm-disrupting nanoparticles offers a promising strategy for combating biofilm infections. Hence, polyethyleneimine surface-modified silver-selenium nanocomposites, Ag@Se@PEI (ASP NCs), were designed for synergistic antibacterial effects by destroying bacterial biofilms to promote wound healing. The results ofin vitroantimicrobial experiments showed that, ASP NCs achieved efficient antibacterial effects againstStaphylococcus aureus (S. aureus)andEscherichia coli (E. coli)by disrupting the formation of the bacterial biofilm, stimulating the outbreak of reactive oxygen species and destroying the integrity of bacterial cell membranes. Thein-vivobacterial infection in mice model showed that, ASP NCs further promoted wound healing and new tissue formation by reducing inflammatory factors and promoting collagen fiber formation which efficiently enhanced the antibacterial effect. Overall, ASP NCs possess low toxicity and minimal side effects, coupled with biocompatibility and efficient antibacterial properties. By disrupting biofilms and bacterial cell membranes, ASP NCs reduced inflammatory responses and accelerated the healing of infected wounds. This nanocomposite-based study offers new insights into antibacterial therapeutic strategies as potential alternatives to antibiotics for wound healing.


Subject(s)
Anti-Bacterial Agents , Biofilms , Escherichia coli , Nanocomposites , Polyethyleneimine , Selenium , Silver , Staphylococcus aureus , Wound Healing , Biofilms/drug effects , Animals , Nanocomposites/chemistry , Silver/chemistry , Mice , Polyethyleneimine/chemistry , Wound Healing/drug effects , Staphylococcus aureus/drug effects , Selenium/chemistry , Selenium/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Reactive Oxygen Species/metabolism , Humans , Microbial Sensitivity Tests , Metal Nanoparticles/chemistry , Wound Infection/drug therapy , Wound Infection/microbiology , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Male
9.
J Hazard Mater ; 472: 134491, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38703686

ABSTRACT

The microbial reduction of selenite to elemental selenium nanoparticles (SeNPs) is thought to be an effective detoxification process of selenite for many bacteria. In this study, Metasolibacillus sp. ES129 and Oceanobacillus sp. ES111 with high selenite reduction efficiency or tolerance were selected for systematic and comparative studies on their performance in selenite removal and valuable SeNPs recovery. The kinetic monitoring of selenite reduction showed that the highest transformation efficiency of selenite to SeNPs was achieved at a concentration of 4.24 mM for ES129 and 4.88 mM for ES111. Ultramicroscopic analysis suggested that the SeNPs produced by ES111 and ES129 had been formed in cytoplasm and subsequently released to extracellular space through cell lysis process. Furthermore, the transcriptome analysis indicated that the expression of genes involved in bacillithiol biosynthesis, selenocompound metabolism and proline metabolism were significantly up-regulated during selenite reduction, suggesting that the transformation of selenite to Se0 may involve multiple pathways. Besides, the up-regulation of genes associated with nucleotide excision repair and antioxidation-related enzymes may enhance the tolerance of bacteria to selenite. Generally, the exploration of selenite reduction and tolerance mechanisms of the highly selenite-tolerant bacteria is of great significance for the effective utilization of microorganisms for environmental remediation.


Subject(s)
Selenious Acid , Selenium , Soil Microbiology , Selenious Acid/metabolism , Selenium/metabolism , Selenium/chemistry , Oxidation-Reduction , Nanoparticles/chemistry , Biodegradation, Environmental , Soil Pollutants/metabolism , Bacteria/metabolism , Bacteria/genetics
10.
Int J Biol Macromol ; 269(Pt 1): 132073, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705328

ABSTRACT

Selenium nanoparticles (SeNPs) are a potential tumor therapeutic drug and have attracted widespread attention due to their high bioavailability and significant anticancer activity. However, the poor water solubility and degradability of selenium nanoparticles severely limit their application. In this study, spherical selenium nanoparticles with a particle size of approximately 50 nm were prepared by using Sargassum fusiforme polysaccharide (SFPS) as a modifier and Tween-80 as a stabilizer. The results of in vitro experiments showed that Sargassum fusiforme polysaccharide-Tween-80-Selenium nanoparticles (SFPS-Tw-SeNPs) had a significant inhibitory effect on A549 cells, with an IC50 value of 6.14 µg/mL, and showed antitumor cell migration and invasion ability against A549 cells in scratch assays and cell migration and invasion assays (transwell assays). Western blot experiments showed that SFPS-Tw-SeNPs could inhibit the expression of tumor migration- and invasion-related proteins. These results suggest that SFPS-Tw-SeNPs may be potential tumor therapeutic agents, especially for the treatment of human lung cancer.


Subject(s)
Cell Movement , Nanoparticles , Polysaccharides , Sargassum , Selenium , Sargassum/chemistry , Humans , Selenium/chemistry , Cell Movement/drug effects , Polysaccharides/chemistry , Polysaccharides/pharmacology , A549 Cells , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Particle Size , Cell Proliferation/drug effects , Edible Seaweeds
11.
J Hazard Mater ; 472: 134549, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38733789

ABSTRACT

Selenium nanoparticles (SeNPs) has been reported as a beneficial role in alleviating cadmium (Cd) toxicity in plant. However, underlying molecular mechanisms about SeNPs reducing Cd accumulation and alleviating Cd toxicity in wheat are not well understood. A hydroponic culture was performed to evaluate Cd and Se accumulation, cell wall components, oxidative stress and antioxidative system, and transcriptomic response of wheat seedlings after SeNPs addition under Cd stress. Results showed that SeNPs application notably reduced Cd concentration in root and in shoot by 56.9% and 37.3%, respectively. Additionally, SeNPs prompted Cd distribution in root cell wall by 54.7%, and increased lignin, pectin and hemicellulose contents by regulating cell wall biosynthesis and metabolism-related genes. Further, SeNPs alleviated oxidative stress caused by Cd in wheat through signal transduction pathways. We also observed that Cd addition reduced Se accumulation by downregulating the expression level of aquaporin 7. These results indicated that SeNPs alleviated Cd toxicity and reduced Cd accumulation in wheat, which were associated with the synergetic regulation of cell wall biosynthesis pathway, uptake transporters, and antioxidative system via signaling pathways.


Subject(s)
Cadmium , Cell Wall , Selenium , Transcriptome , Triticum , Triticum/drug effects , Triticum/metabolism , Cell Wall/drug effects , Cell Wall/metabolism , Cadmium/toxicity , Selenium/pharmacology , Selenium/chemistry , Transcriptome/drug effects , Oxidative Stress/drug effects , Nanoparticles/toxicity , Nanoparticles/chemistry , Plant Roots/drug effects , Plant Roots/metabolism , Metal Nanoparticles/toxicity , Metal Nanoparticles/chemistry , Gene Expression Regulation, Plant/drug effects , Soil Pollutants/toxicity
12.
Int Immunopharmacol ; 134: 112118, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38705029

ABSTRACT

This study aims to explore the protective machinery of pegylated polymeric micelles of boswellic acid-selenium (PMBS) against secondary neuronal damage triggered by mild repetitive traumatic brain injury (RTBI). After PMBS characterization in terms of particle size, size distribution, zeta potential, and transmission electronic microscopy, the selected formula was used to investigate its potency against experimental RTBI. Five groups of rats were used; group 1 (control) and the other four groups were subjected to RTBI. Groups 2 was RTBI positive control, while 3, 4, and 5 received boswellic acid (BSA), selenium (SEL), and PMBS, respectively. The open-field behavioral test was used for behavioral assessment. Subsequently, brain tissues were utilized for hematoxylin and eosin staining, Nissl staining, Western blotting, and ELISA in addition to evaluating microRNA expression (miR-155 and miR-146a). The behavioral changes, oxidative stress, and neuroinflammation triggered by RTBI were all improved by PMBS. Moreover, PMBS mitigated excessive glutamate-induced excitotoxicity and the dysregulation in miR-155 and miR-146a expression. Besides, connexin43 (Cx43) expression as well as klotho and brain-derived neurotrophic factor (BDNF) were upregulated with diminished neuronal cell death and apoptosis because of reduced Forkhead Box class O3a(Foxo3a) expression in the PMBS-treated group. The current study has provided evidence of the benefits produced by incorporating BSA and SEL in PEGylated polymeric micelles formula. PMBS is a promising therapy for RTBI. Its beneficial effects are attributed to the manipulation of many pathways, including the regulation of miR-155 and miR-146a expression, as well as the BDNF /Klotho/Foxo3a signaling pathway.


Subject(s)
Brain-Derived Neurotrophic Factor , Forkhead Box Protein O3 , Klotho Proteins , Micelles , MicroRNAs , Polyethylene Glycols , Selenium , Triterpenes , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Forkhead Box Protein O3/metabolism , Forkhead Box Protein O3/genetics , Male , Rats , Selenium/chemistry , Triterpenes/pharmacology , Triterpenes/therapeutic use , Signal Transduction/drug effects , Rats, Sprague-Dawley , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Disease Models, Animal , Oxidative Stress/drug effects , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/metabolism , Brain/drug effects , Brain/metabolism , Brain/pathology , Polymers/chemistry
13.
Bioorg Chem ; 148: 107459, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761707

ABSTRACT

Lung cancer is a malignant tumor with high mortality and drug resistance. Therefore, it is urgent to explore natural and nontoxic drugs to treat lung cancer. In this study, the natural active ingredient AANL extracted from Agrocybe aegirita was used to modify nanoselenium by an oxidation-reduction method. Transmission electron microscope detection and infrared spectroscopy showed that a novel selenium nanocomposite named AANL-SeNPs was successfully prepared. The results of nanoscale characterization showed that AANL-SeNPs had good stability and uniform dispersion in aqueous solution by zeta potential and spectrum analysis. At the cellular level, we found that AANL-SeNPs significantly inhibited the cell viability of lung cancer cells, and the cell inhibition rate of 60 nM AANL-SeNPs was 39 % in H157 cells, 67 % in H147 cells, and 62 % in A549 cells. The IC50 value of AANL-SeNPs was 51.85 nM in A549 cells and 81.57 nM in H157 cells. Moreover, AANL-SeNPs could inhibit the cell proliferation and migration, and enhance the sensitivity of lung cancer cells to osimertinib and has no toxic to normal cells. In vivo, AANL-SeNPs significantly slowed tumor growth in tumor-bearing mice by establishing a subcutaneous transplantation tumor model for lung cancer, and the tumor size was smaller and was reduced about 79 % in 2 mg/kg AANL-SeNPs group compared with PBS group. Mechanistically, a total of 38 differentially expressed proteins were identified by data-independent acquisition mass spectrometry. A significantly upregulated protein, CDC-like kinase 2 (CLK2), was screened and validated for further analysis, which showed that the expression levels of CLK2 were increased in H157 and H1437 cells after AANL-SeNPs treatment. The results obtained in this study suggest that a novel selenium nanocomposite AANL-SeNPs, which inhibits lung cancer by upregulating the expression of CLK2.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Lung Neoplasms , Nanocomposites , Protein-Tyrosine Kinases , Selenium , Up-Regulation , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Nanocomposites/chemistry , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Animals , Selenium/chemistry , Selenium/pharmacology , Mice , Up-Regulation/drug effects , Drug Screening Assays, Antitumor , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/antagonists & inhibitors , Dose-Response Relationship, Drug , Molecular Structure , Structure-Activity Relationship , Cell Survival/drug effects , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Neoplasms, Experimental/metabolism , Cell Line, Tumor , Mice, Inbred BALB C , Mice, Nude
14.
J Agric Food Chem ; 72(22): 12566-12581, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38770928

ABSTRACT

Dietary deficiency of selenium is a global health hazard. Supplementation of organic selenopeptides via food crops is a relatively safe approach. Selenopeptides with heterogeneous selenium-encoded isotopes or a poorly fragmented peptide backbone remain unidentified in site-specific selenoproteomic analysis. Herein, we developed the Se-Pair Search, a UniProtKB-FASTA-independent peptide-matching strategy, exploiting the fragmentation patterns of shared peptide backbones in selenopeptides to optimize spectral interpretation, along with developing new selenosite assignment schemes (steps 1-3) to standardize selenium-localization data reporting for the selenoproteome community and thereby facilitating the discovery of unexpected selenopeptides. Using selenium-biofortified rice under cooking, fermentation, and high-temperature and high-pressure processing conditions as a pyrolysis-thermolysis dietary model, we probed the single-molecule-level kinetic evolution of the novel selenopeptide "KKSe(M)R" with qual-quantitative information on graph-theory-oriented localization calculations, abundance patterns, activation energy, and rate constants at a selenoproteome-wide scale. We ground-truth-annotated thirteen pyrolysis-thermolysis products and inferred four pyrolysis-thermolysis pathways to characterize the formation reactivity of the main intermediate variables of KKSe(M)R and constructed an advanced probe-type ultrasound technique prior to pyrolysis-thermolysis conditions for minimizing loss of KKSe(M)R during processing. Importantly, we reveal the unappreciated pyro-excitation diversion of KKSe(M)R at pyrolysis-thermolysis time and temperature matrices. These findings provide pioneering theoretical guidance for controlling dietary selenium supplementation within the safety thresholds.


Subject(s)
Hot Temperature , Oryza , Peptides , Pyrolysis , Selenium , Selenium/chemistry , Selenium/metabolism , Peptides/chemistry , Peptides/metabolism , Oryza/chemistry , Oryza/metabolism , Cooking , Food Handling/methods , Plant Proteins/chemistry , Plant Proteins/metabolism , Kinetics
15.
J Agric Food Chem ; 72(22): 12673-12684, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38772747

ABSTRACT

Biogenic selenium nanoparticles (SeNPs) are the most favorable Se form for nutritional supplementation due to their high stability, low toxicity, and high activity. However, the interaction between the surface-binding proteins and their stable biogenic SeNPs, as well as their impact on the stability and bioavailability of SeNPs, remains to be understood. In vitro stabilization experiments revealed an amino acid segment (F(235-386)) in Rahnella aquatilis' flagellin FliC, with surfactant-like properties, stabilizing SeNPs under harsh conditions. FliC and F(235-386) were employed as stabilizers to synthesize SeNPs (FliC@SeNPs and F(235-386)@SeNPs), and surface chemistry analysis revealed coordination reactions between the proteins and Se atoms on the surface of SeNPs. Both FliC and F(235-386) enhanced SeNPs uptake in wheat seedlings but reduced it in bacteria and yeast. This study highlights FliC's core function in stabilizing SeNPs and enhancing their bioavailability, paving the way for agricultural and nutritional applications.


Subject(s)
Biological Availability , Flagellin , Nanoparticles , Selenium , Surface-Active Agents , Selenium/chemistry , Selenium/metabolism , Flagellin/chemistry , Flagellin/metabolism , Surface-Active Agents/chemistry , Surface-Active Agents/metabolism , Nanoparticles/chemistry , Triticum/chemistry , Triticum/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/genetics
16.
J Nanobiotechnology ; 22(1): 250, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750519

ABSTRACT

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.


Subject(s)
Bone Regeneration , Calcium Phosphates , Osteogenesis , Osteosarcoma , Tissue Scaffolds , Osteosarcoma/drug therapy , Osteosarcoma/pathology , Animals , Bone Regeneration/drug effects , Tissue Scaffolds/chemistry , Rabbits , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Osteogenesis/drug effects , Polyesters/chemistry , Humans , Cell Differentiation/drug effects , Bone Neoplasms/pathology , Bone Neoplasms/drug therapy , Bone Neoplasms/therapy , Cell Line, Tumor , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Schwann Cells/drug effects , Nanofibers/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Selenium/chemistry , Selenium/pharmacology
19.
Food Res Int ; 187: 114428, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763678

ABSTRACT

In this study, blackberry polysaccharide-selenium nanoparticles (BBP-24-3Se) were first prepared via Na2SeO3/Vc redox reaction, followed by coating with red blood cell membrane (RBC) to form core-shell structure polysaccharide-selenium nanoparticles (RBC@BBP-24-3Se). The particle size of BBP-24-3Se (167.1 nm) was increased to 239.8 nm (RBC@BBP-24-3Se) with an obvious core-shell structure after coating with RBC. FT-IR and XPS results indicated that the interaction between BBP-24-3 and SeNPs formed a new C-O···Se bond with valence state of Se0. Bioassays indicated that RBC coating markedly enhanced both the biocompatibility and bioabsorbability of RBC@BBP-24-3Se, and the absorption rate of RBC@BBP-24-3Se in HepG2 cells was 4.99 times higher than that of BBP-24-3Se at a concentration of 10 µg/mL. Compared with BBP-24-3Se, RBC@BBP-24-3Se possessed significantly heightened protective efficacy against oxidative damage and better regulation of glucose/lipid metabolism disorder induced by palmitic acid in HepG2 cells. Mechanistic studies demonstrated that RBC@BBP-24-3Se could effectively improve PI3K/AKT signaling pathway to promote glucose metabolism, inhibit the expression of lipid synthesis genes and up-regulate the expression of lipid-decomposing genes through AMPK signaling pathway to improve lipid metabolism. These results provided a theoretical basis for developing a new type of selenium supplement for the treatment of insulin resistance.


Subject(s)
Glucose , Lipid Metabolism , Nanoparticles , Polysaccharides , Rubus , Selenium , Humans , Selenium/chemistry , Hep G2 Cells , Polysaccharides/pharmacology , Polysaccharides/chemistry , Lipid Metabolism/drug effects , Glucose/metabolism , Nanoparticles/chemistry , Rubus/chemistry , Particle Size , Oxidative Stress/drug effects , Antioxidants/pharmacology , Signal Transduction/drug effects
20.
Mol Biol Rep ; 51(1): 688, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796570

ABSTRACT

Selenium nanoparticles (SeNPs) are an appealing carrier for the targeted delivery. The selenium nanoparticles are gaining global attention because of the potential therapeutic applications in several diseases e.g., rheumatoid arthritis (RA), inflammatory bowel disease (IBD), asthma, liver, and various autoimmune disorders like psoriasis, cancer, diabetes, and a variety of infectious diseases. Despite the fact still there is no recent literature that summarises the therapeutic applications of SeNPs. There are some challenges that need to be addressed like finding targets for SeNPs in various diseases, and the various functionalization techniques utilized to increase SeNP's stability while facilitating wide drug-loaded SeNP distribution to tumor areas and preventing off-target impacts need to focus on understanding more about the therapeutic aspects for better understanding the science behind it. Keeping that in mind we have focused on this gap and try to summarize all recent key targeted therapies for SeNPs in cancer treatment and the numerous functionalization strategies. We have also focused on recent advancements in SeNP functionalization methodologies and mechanisms for biomedical applications, particularly in anticancer, anti-inflammatory, and anti-infection therapeutics. Based on our observation we found that SeNPs could potentially be useful in suppressing viral epidemics, like the ongoing COVID-19 pandemic, in complement to their antibacterial and antiparasitic uses. SeNPs are significant nanoplatforms with numerous desirable properties for clinical translation.


Subject(s)
Nanoparticles , Selenium , Humans , Selenium/therapeutic use , Selenium/chemistry , Nanoparticles/chemistry , Neoplasms/drug therapy , Animals , COVID-19 , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , SARS-CoV-2/drug effects , Drug Delivery Systems/methods
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