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1.
Foods ; 13(12)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38928779

ABSTRACT

Curcumin is a naturally occurring hydrophobic polyphenolic compound with a rapid metabolism, poor absorption, and low stability, which severely limits its bioavailability. Here, we employed a starch-protein-based nanoparticle approach to improve the curcumin bioavailability. This study focused on synthesizing nanoparticles with a zein "core" and a carboxymethylated short-chain amylose (CSA) "shell" through anti-solvent precipitation for delivering curcumin. The zein@CSA core-shell nanoparticles were extensively characterized for physicochemical properties, structural integrity, ionic stability, in vitro digestibility, and antioxidant activity. Fourier-transform infrared (FTIR) spectroscopy indicates nanoparticle formation through hydrogen-bonding, hydrophobic, and electrostatic interactions between zein and CSA. Zein@CSA core-shell nanoparticles exhibited enhanced stability in NaCl solution. At a zein-to-CSA ratio of 1:1.25, only 15.7% curcumin was released after 90 min of gastric digestion, and 66% was released in the intestine after 240 min, demonstrating a notable sustained release effect. Furthermore, these nanoparticles increased the scavenging capacity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH•) free radical compared to those composed solely of zein and were essentially nontoxic to Caco-2 cells. This research offers valuable insights into curcumin encapsulation and delivery using zein@CSA core-shell nanoparticles.

2.
Mol Pharm ; 21(7): 3674-3683, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38838194

ABSTRACT

The efficacy of nanostructured lipid carriers (NLC) for drug delivery strongly depends on their stability and cell uptake. Both properties are governed by their compositions and internal structure. To test the effect of the lipid composition of NLC on cell uptake and stability, three kinds of liquid lipids with different degrees of unsaturation are employed. After ensuring homogeneous size distributions, the thermodynamic characteristics, stability, and mixing properties of NLC are characterized. Then the rates and predominant pathways of cell uptake are determined. Although the same surfactant is used in all cases, different uptake rates are observed. This finding contradicts the view that the surface properties of NLC are dominated by the surfactant. Instead, the uptake rates are explained by the structure of the nanocarrier. Depending on the mixing properties, some liquid lipids remain inside the nanocarrier, while other liquid lipids are present on the surface. Nanocarriers with liquid lipids on the surface are taken up more readily by the cells. This shows that the engineering of efficient lipid nanocarriers requires a delicate balance of interactions between all components of the nanocarrier on the molecular level.


Subject(s)
Drug Carriers , Drug Delivery Systems , Lipids , Nanostructures , Lipids/chemistry , Drug Carriers/chemistry , Nanostructures/chemistry , Drug Delivery Systems/methods , Humans , Surface-Active Agents/chemistry , Nanoparticles/chemistry , Thermodynamics , Particle Size , Surface Properties
3.
J Sci Food Agric ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38925572

ABSTRACT

BACKGROUND: Proteins and anionic octenyl succinic anhydride (OSA)-modified starch (OSA-starch) are common ingredients in food systems. The interactions between OSA-starch and protein are found to alter the structural and functional properties of the protein-OSA-starch complexes. In this regard, the close understanding of the relationship among the molecular interactions between whey protein isolate (WPI) and OSA-high amylose corn starch (HAS), structure changes and rheological, digestibility and release properties of WPI-OSA-HAS was investigated. RESULTS: The molecular interactions of WPI-OSA-HAS were significant for increasing the surface rough, solubility, storage modulus and loss modulus, but decreasing the R1047/1022 values. For the nutritional evaluation, the anti-digestibility of WPI-OSA-HAS was enhanced with increased resistant starch + slowly digestible starch contents and decreased equilibrium hydrolysis percentage and kinetic constant. During the digestion, part of the starch granule, OSA groups and WPI were lost, but the loss was lower than for OSA-HAS. Furthermore, the results of curcumin-loaded WPI-OSA-HAS in simulated gastrointestinal fluids demonstrated that curcumin could be gradually released to simulate colonic fluid. Notably, the interaction between WPI and OSA-HAS depended on the WPI concentration with the stronger molecular interactions obtained at 35% concentration. CONCLUSION: These results provided important information concerning how to adjust the rheological, anti-digestibility and release properties of WPI-OSA-HAS through altering the electrostatic interactions and hydrophobic interactions of WPI-OSA-HAS. © 2024 Society of Chemical Industry.

4.
Food Chem ; 454: 139742, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38795623

ABSTRACT

This study investigated the effects of octenyl succinic anhydride (OSA)-starch-fatty acid (FA) interactions on the structural, digestibility and release characteristics of high amylose corn starch (HAS). FTIR and XRD analysis showed that the hydrophobic interaction between HAS and FA promoted the covalent binding between OSA and HAS. With the increasing of the FA chain length, the complex index, degree of substitution, R1047/1022 and relative crystallinity of OSA-HAS-FA increased first and then decreased, whereas the first-order rate coefficient and percentage of digested in infinite time showed an opposite trend. Structural changes and the molecular interactions of OSA-HAS-FA with 12­carbon FA resulted in highest resistant starch content (45.43%) and encapsulation efficiency of curcumin (Cur) (47.98%). In vitro release test revealed that Cur could be gradually released from OSA-HAS-FA in simulated gastric, intestinal and colonic fluids. Results provided novel insights into HAS-FA complex grafted with OSA as carrier for colon-specific of functional materials.


Subject(s)
Amylose , Digestion , Fatty Acids , Starch , Zea mays , Amylose/chemistry , Amylose/metabolism , Starch/chemistry , Starch/metabolism , Starch/analogs & derivatives , Fatty Acids/chemistry , Fatty Acids/metabolism , Zea mays/chemistry , Zea mays/metabolism , Succinic Anhydrides/chemistry , Humans
5.
Food Chem X ; 22: 101405, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38694543

ABSTRACT

This study investigated the effect of inulin with different polymerization degrees (DP), including L-inulin (DP 2-6), M-inulin (DP 10-23) and H-inulin (DP 23-46), on the structural and gelation properties of potato protein isolate (PPI). Results revealed that textural properties (hardness, cohesiveness, springiness and chewiness) and water-holding capacity (WHC) of PPI-inulin composite gels were positively correlated with the inulin DP and addition content at 0-1.5% (w/v), but deteriorated at 2% due to phase separation. The addition of 1.5% H-inulin showed the most significant increment effects on the WHC (18.65%) and hardness (2.84 N) of PPI gel. Furthermore, M-/H-inulin were more effective in increasing the whiteness and surface hydrophobicity, as well as in strengthening hydrogen bonds and hydrophobic interactions than L-inulin. Fourier transform infrared spectroscopy analysis and microstructural observation indicated that inulin with higher DP promoted more generation of ß-sheet structures, and leading to the formation of stronger and finer network structures.

6.
J Mol Graph Model ; 130: 108780, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38692128

ABSTRACT

One of the easier methods of wastewater treatment is adsorption due to its simplicity in implementation, environmental friendliness, and economic feasibility. Polyvinyl alcohol (PVA) looks promising as an adsorbent due to its biocompatible, non-toxic, water-soluble and eco-friendly nature. The investigation of PVA for its potential in the adsorption of pollutants has been reported in many studies but the mechanistic understanding of the adsorption is poor. The present study used a theoretical approach through density functional theory and Monte Carlo with molecular dynamics simulations to investigate the adsorption mechanism behaviors of model organic molecules (bromothymol blue (BTB), methylene blue (MB), metronidazole (MNZ) and tetracycline (TC)) on PVA surface. The quantum chemical calculations result showed that with the increase in PVA chains (2, 4, 8, 16, and 32 units), the zero-point energy decreases (from -308.79 to -4922.93 kcal/mol) while the dipole moment increases (from 4.37 to 87.52 Debye). Temperature effect on the PVA chain structures showed the same trends for all the chain units and with the increase in temperature (50-600 K), there are no appreciable changes in zero-point energy, enthalpy energy increases while Gibbs free energy decreases. Considering PVA-pollutant complexes, the effects of temperature on the structures showed that there are no appreciable changes in the zero-point energy, Gibbs free and thermal energies increase with an increase in temperature while the kinetic rate of reactions decreases with an increase in temperature. The enthalpy of the reaction showed different trends with antibiotic and dye complexes. In all the thermodynamic properties investigated and the rate of reaction, the order of affinity of the pollutants with PVA followed TC > MNZ > MB > BTB. Monte Carlo simulation was used to investigate the adsorption behavior of the pollutants on the surface of PVA. The negative adsorption energies (-366.56 to -2266.81 kcal/mol) in terms of affinity towards the pollutants on the surface of PVA followed the sequence TC > MNZ > BTB > MB and the molecular dynamic simulation results followed the same order. The obtained results give valuable insights into the mechanism and performance of PVA as an adsorbent. Most of these computational observations are in good agreement with the available experimental results.


Subject(s)
Molecular Dynamics Simulation , Polyvinyl Alcohol , Temperature , Thermodynamics , Water Pollutants, Chemical , Polyvinyl Alcohol/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Water Purification/methods , Monte Carlo Method
7.
BMC Bioinformatics ; 25(1): 187, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741200

ABSTRACT

MOTIVATION: Long non-coding RNAs (lncRNAs) are a class of molecules involved in important biological processes. Extensive efforts have been provided to get deeper understanding of disease mechanisms at the lncRNA level, guiding towards the detection of biomarkers for disease diagnosis, treatment, prognosis and prevention. Unfortunately, due to costs and time complexity, the number of possible disease-related lncRNAs verified by traditional biological experiments is very limited. Computational approaches for the prediction of disease-lncRNA associations allow to identify the most promising candidates to be verified in laboratory, reducing costs and time consuming. RESULTS: We propose novel approaches for the prediction of lncRNA-disease associations, all sharing the idea of exploring associations among lncRNAs, other intermediate molecules (e.g., miRNAs) and diseases, suitably represented by tripartite graphs. Indeed, while only a few lncRNA-disease associations are still known, plenty of interactions between lncRNAs and other molecules, as well as associations of the latters with diseases, are available. A first approach presented here, NGH, relies on neighborhood analysis performed on a tripartite graph, built upon lncRNAs, miRNAs and diseases. A second approach (CF) relies on collaborative filtering; a third approach (NGH-CF) is obtained boosting NGH by collaborative filtering. The proposed approaches have been validated on both synthetic and real data, and compared against other methods from the literature. It results that neighborhood analysis allows to outperform competitors, and when it is combined with collaborative filtering the prediction accuracy further improves, scoring a value of AUC equal to 0966. AVAILABILITY: Source code and sample datasets are available at: https://github.com/marybonomo/LDAsPredictionApproaches.git.


Subject(s)
Computational Biology , RNA, Long Noncoding , RNA, Long Noncoding/genetics , Humans , Computational Biology/methods , Algorithms , MicroRNAs/genetics , MicroRNAs/metabolism , Genetic Predisposition to Disease/genetics
8.
J Comput Aided Mol Des ; 38(1): 23, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814371

ABSTRACT

In this work, we present the frontend of GeoMine and showcase its application, focusing on the new features of its latest version. GeoMine is a search engine for ligand-bound and predicted empty binding sites in the Protein Data Bank. In addition to its basic text-based search functionalities, GeoMine offers a geometric query type for searching binding sites with a specific relative spatial arrangement of chemical features such as heavy atoms and intermolecular interactions. In contrast to a text search that requires simple and easy-to-formulate user input, a 3D input is more complex, and its specification can be challenging for users. GeoMine's new version aims to address this issue from the graphical user interface perspective by introducing an additional visualization concept and a new query template type. In its latest version, GeoMine extends its query-building capabilities primarily through input formulation in 2D. The 2D editor is fully synchronized with GeoMine's 3D editor and provides the same functionality. It enables template-free query generation and template-based query selection directly in 2D pose diagrams. In addition, the query generation with the 3D editor now supports predicted empty binding sites for AlphaFold structures as query templates. GeoMine is freely accessible on the ProteinsPlus web server ( https://proteins.plus ).


Subject(s)
Databases, Protein , Protein Binding , Proteins , User-Computer Interface , Ligands , Binding Sites , Proteins/chemistry , Proteins/metabolism , Software , Search Engine , Protein Conformation , Models, Molecular
9.
J Agric Food Chem ; 72(15): 8372-8379, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38579274

ABSTRACT

Self-assembling peptides are rapidly gaining attention as novel biomaterials for food and biomedical applications. Peptides self-assemble when triggered by physical or chemical factors due to their versatile physicochemical characteristics. Peptide self-assembly, when combined with the health-promoting bioactivity of peptides, can also result in a plethora of biofunctionalities of the biomaterials. This perspective highlights current developments in the use of food-derived self-assembling peptides as biomaterials, bioactive nutraceuticals, and potential dual functioning bioactive biomaterials. Also discussed are the challenges and opportunities in the use of self-assembling bioactive peptides in designing biocompatible, biostable, and bioavailable multipurpose biomaterials.


Subject(s)
Biocompatible Materials , Peptides , Hydrogels , Dietary Supplements
10.
Materials (Basel) ; 17(7)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38612054

ABSTRACT

The application of low-density polyethylene (LDPE) has been confined to packaging applications due to its inadequate mechanical and tribological characteristics. We propose enhancing LDPE by integrating hard carbon spheres (CSs) to improve its strength, frictional characteristics, and wear resistance. LDPE/CS composites were created by blending LDPE with varying CS amounts (0.5-8 wt.%). Analysis using scanning electron microscopy and Raman spectroscopy confirmed CS presence in the LDPE matrix, with X-ray diffraction showing no microstructural changes post-blending. Thermal characterization exhibited notable improvements in thermal stability (~4%) and crystallinity (~7%). Mechanical properties such as hardness and Young's modulus were improved by up to 4% and 24%, respectively. Tribological studies on different composite samples with varying surface roughness under various load and speed conditions revealed the critical role of surface roughness in reducing friction by decreasing real contact area and adhesive interactions between asperities. Increased load and speed amplified shear stress on asperities, possibly leading to deformation and failure. Notably, integrating CSs into LDPE, starting at 1 wt.%, effectively reduced friction and wear. The composite with the highest loading (8 wt.%) displayed the most significant tribological enhancement, achieving a remarkable 75% friction reduction and a substantial 78% wear reduction.

11.
J Biomol Struct Dyn ; : 1-13, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38686915

ABSTRACT

Leucine is the native known ligand of Sestrin2 (Sesn2) and its interaction with Sesn2 is particularly important, as it influences the activity of mTOR in aging and its associated pathologies. It is important to find out how leucine interacts with Sesn2 and how mutations in the binding pocket of leucine affect the binding of leucine. Therefore, this study was committed to investigating the impact of non-synonymous mutations by incorporating a broad spectrum of simulation techniques, from molecular dynamics to free energy calculations. Our study was designed to model the atomic-scale interactions between leucine and mutant forms of Sesn2. Our results demonstrated that the interaction paradigm for the mutants has been altered thus showing a significant decline in the hydrogen bonding network. Moreover, these mutations compromised the dynamic stability by altering the conformational flexibility, sampling time, and leucine-induced structural constraints that consequently caused variation in the binding and structural stability. Molecular dynamics-based flexibility analysis revealed that the regions 217-339 and 371-380 demonstrated a higher fluctuation. Noteworthy, these regions correspond to a linker (217-339) and a loop (371-380) that cover the leucine binding cavity that is critical for the 'latch' mechanism in the N-terminal, which is essential for leucine binding. Further validation of reduced binding and modified internal motions caused by the mutants was obtained through binding free energy calculations, principal components analysis (PCA), and free energy landscape (FEL) analysis. By unraveling the molecular intricacies of Sesn2-leucine interactions and their mutations, we hope to pave the way for innovative strategies to combat the inevitable tide of aging and its associated diseases.Communicated by Ramaswamy H. Sarma.

12.
Cell Mol Life Sci ; 81(1): 162, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38568213

ABSTRACT

Spatiotemporal-controlled second messengers alter molecular interactions of central signaling nodes for ensuring physiological signal transmission. One prototypical second messenger molecule which modulates kinase signal transmission is the cyclic-adenosine monophosphate (cAMP). The main proteinogenic cellular effectors of cAMP are compartmentalized protein kinase A (PKA) complexes. Their cell-type specific compositions precisely coordinate substrate phosphorylation and proper signal propagation which is indispensable for numerous cell-type specific functions. Here we present evidence that TAF15, which is implicated in the etiology of amyotrophic lateral sclerosis, represents a novel nuclear PKA substrate. In cross-linking and immunoprecipitation experiments (iCLIP) we showed that TAF15 phosphorylation alters the binding to target transcripts related to mRNA maturation, splicing and protein-binding related functions. TAF15 appears to be one of multiple PKA substrates that undergo RNA-binding dynamics upon phosphorylation. We observed that the activation of the cAMP-PKA signaling axis caused a change in the composition of a collection of RNA species that interact with TAF15. This observation appears to be a broader principle in the regulation of molecular interactions, as we identified a significant enrichment of RNA-binding proteins within endogenous PKA complexes. We assume that phosphorylation of RNA-binding domains adds another layer of regulation to binary protein-RNAs interactions with consequences to RNA features including binding specificities, localization, abundance and composition.


Subject(s)
Amyotrophic Lateral Sclerosis , TATA-Binding Protein Associated Factors , Humans , Cyclic AMP-Dependent Protein Kinases , Phosphorylation , Cyclic AMP , RNA
13.
Int J Pharm ; 657: 124175, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38685442

ABSTRACT

Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong molecular interactions with drugs. Polymers tailored to fit the physicochemical properties of the drug molecule to be incorporated, for instance by allowing the incorporation of specific functional groups, would be highly sought-for in this regard. For this purpose, the novel allyl-terminated polymer methoxy(polyethylene glycol)-block-poly(jasmine lactone) (mPEG-b-PJL) has been synthesized and functionalized to potentially enhance specific drug-polymer interactions. This study investigated the use of mPEG-b-PJL in ASDs, using carvedilol (CAR), a weakly basic model drug. The findings revealed that the acidic functionalized form of the polymer (mPEG-b-PJL-COOH) indeed established stronger molecular interactions with CAR compared to its non-functionalized counterpart mPEG-b-PJL. Evaluations on polymer effectiveness in forming ASDs demonstrated that mPEG-b-PJL-COOH outperformed its non-functionalized counterpart in miscibility, drug loading ability, and stability, inferred from reduced molecular mobility. However, dissolution tests indicated that ASDs with mPEG-b-PJL-COOH did not significantly improve the dissolution behaviour compared to amorphous CAR alone, despite potential solubility enhancement through micelle formation. Overall, this study confirms the potential of functionalized polymers in ASD formulations, while the challenge of improving dissolution performance in these ASDs remains an area of further development.


Subject(s)
Polyethylene Glycols , Polyethylene Glycols/chemistry , Solubility , Carvedilol/chemistry , Drug Stability , Polymers/chemistry , Lactones/chemistry , Chemistry, Pharmaceutical/methods , Drug Compounding/methods
14.
Int J Mol Sci ; 25(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38673722

ABSTRACT

The human Vitamin K Epoxide Reductase Complex (hVKORC1), a key enzyme that converts vitamin K into the form necessary for blood clotting, requires for its activation the reducing equivalents supplied by its redox partner through thiol-disulphide exchange reactions. The functionally related molecular complexes assembled during this process have never been described, except for a proposed de novo model of a 'precursor' complex of hVKORC1 associated with protein disulphide isomerase (PDI). Using numerical approaches (in silico modelling and molecular dynamics simulation), we generated alternative 3D models for each molecular complex bonded either covalently or non-covalently. These models differ in the orientation of the PDI relative to hVKORC1 and in the cysteine residue involved in forming protein-protein disulphide bonds. Based on a comparative analysis of these models' shape, folding, and conformational dynamics, the most probable putative complexes, mimicking the 'precursor', 'intermediate', and 'successor' states, were suggested. In addition, we propose using these complexes to develop the 'allo-network drugs' necessary for treating blood diseases.


Subject(s)
Molecular Dynamics Simulation , Protein Disulfide-Isomerases , Vitamin K Epoxide Reductases , Protein Disulfide-Isomerases/metabolism , Protein Disulfide-Isomerases/chemistry , Vitamin K Epoxide Reductases/chemistry , Vitamin K Epoxide Reductases/metabolism , Vitamin K Epoxide Reductases/genetics , Humans , Disulfides/chemistry , Disulfides/metabolism , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/metabolism , Models, Molecular , Protein Conformation , Oxidation-Reduction , Protein Binding
15.
J Sci Food Agric ; 104(10): 6157-6165, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38456778

ABSTRACT

BACKGROUND: Solid fats are critical to obtaining a wide range of food texture and quality characteristics, but their consumption is strongly associated with higher cardiovascular disease risks. Structuring unsaturated oils with natural waxes into oleogels (OG) is an innovative solution to develop fat mimics with a healthier profile. RESULTS: Soy wax (SW), beeswax (BW) and carnauba wax (CW), have been used in binary mixtures of waxes, aiming to understand their interactions and influence on OG quality properties and microstructural characteristics. In the present study, OGs were produced using binary wax mixtures and analyzed for texture, color, smoke point, microstructure, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Wax combinations led to antagonistic (mixtures with SW) and synergistic interactions (BW/CW) based on their mechanical properties. At the microstructural level BW/CW blends showed a reduction in crystal size and with a more compact structure. XRD and FTIR spectra revealed a packing of orthorhombic perpendicular subcell for most OGs, whereas SW produced samples with an arrangement with ß' crystals, characteristic of edible solid fats. Additionally, when compared to commercial beef fat, BW/CW mixtures showed similar quality attributes indicating that they could act as fat mimic. CONCLUSION: The combined analysis of microstructure, spectroscopic and mechanical properties enhanced the understanding of how the nature of the interactions between waxes and lipid phases impact in the final quality of the structured oils. The study's insights indicate that binary wax combinations can efficiently replace solid fats, offering healthier alternatives at the same time as preserving desired sensory characteristics. © 2024 Society of Chemical Industry.


Subject(s)
Organic Chemicals , Waxes , Waxes/chemistry , Organic Chemicals/chemistry , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
16.
Int J Mol Sci ; 25(5)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38474085

ABSTRACT

Mowat-Wilson syndrome (MWS) is a rare genetic neurodevelopmental congenital disorder associated with various defects of the zinc finger E-box binding homeobox 2 (ZEB2) gene. The ZEB2 gene is autosomal dominant and encodes six protein domains including the SMAD-binding protein, which functions as a transcriptional corepressor involved in the conversion of neuroepithelial cells in early brain development and as a mediator of trophoblast differentiation. This review summarizes reported ZEB2 gene variants, their types, and frequencies among the 10 exons of ZEB2. Additionally, we summarized their corresponding encoded protein defects including the most common variant, c.2083 C>T in exon 8, which directly impacts the homeodomain (HD) protein domain. This single defect was found in 11% of the 298 reported patients with MWS. This review demonstrates that exon 8 encodes at least three of the six protein domains and accounts for 66% (198/298) of the variants identified. More than 90% of the defects were due to nonsense or frameshift changes. We show examples of protein modeling changes that occurred as a result of ZEB2 gene defects. We also report a novel pathogenic variant in exon 8 in a 5-year-old female proband with MWS. This review further explores other genes predicted to be interacting with the ZEB2 gene and their predicted gene-gene molecular interactions with protein binding effects on embryonic multi-system development such as craniofacial, spine, brain, kidney, cardiovascular, and hematopoiesis.


Subject(s)
Facies , Hirschsprung Disease , Intellectual Disability , Microcephaly , Repressor Proteins , Female , Humans , Child, Preschool , Repressor Proteins/genetics , Zinc Finger E-box Binding Homeobox 2/genetics , Intellectual Disability/genetics , Homeodomain Proteins/genetics , Transcription Factors
17.
Food Chem ; 447: 139031, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38513491

ABSTRACT

The present study was aimed to investigate the interactions between soybean protein isolate (SPI) with resveratrol (RESV) and lutein (LUT). The binding forces, molecular interactions and functional properties were explored by multi-spectroscopic analysis, molecular docking and functional property indexes between SPI and RESV/LUT. The RESV/LUT quenched SPI chromophore residues with static mechanism and the endothermic reaction. The SPI- RESV/LUT complexes were formed through hydrogen bond, electrostatic and hydrophobic interactions. Molecular docking confirmed van-der-Waals force as one of the important forces. The interaction of RESV/LUT led to SPI's secondary structure alterations with a decrease in α-helix and random coil and an increase in ß-sheet and ß-turns. RESV/LUT developed foaming and emulsifying properties of SPI and showed a significant decrease of the surface hydrophobicity with RESV/LUT concentrations increase attributed to SPI's partial unfolding. Our study exposed molecular mechanisms and confirmations to understand the interactions in protein- RESV/LUT complexes for protein industrial base promotion.


Subject(s)
Soybean Proteins , Soybean Proteins/chemistry , Molecular Docking Simulation , Protein Structure, Secondary , Spectrum Analysis , Protein Conformation, alpha-Helical
18.
Foods ; 13(6)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38540852

ABSTRACT

Since the initial findings that food tannin/salivary protein interaction and subsequent precipitation is the main cause of the astringency development, numerous studies have concentrated on the supramolecular characterization of these bindings. Most of these works have focused on the low-molecular-weight salivary proteins, in particular proline-rich proteins, hardly considering the involvement of the high-molecular-weight salivary proteins (HMWSPs). Herein, different techniques such as fluorescence quenching, Isothermal Titration Calorimetry and HPLC-MS-DAD were employed to determine the occurrence of molecular interactions between three HMWSPs, namely, mucin, α-amylase and albumin, and a complex extract of tannins composed mainly of flavan-3-ols. The obtained results prove the capability of the three HMWSPs to effectively interact with the flavan-3-ol extract, involving different forces and action mechanisms. Flavan-3-ols are capable of interacting with mucins by a mechanism that includes the formation of stable ground-state complexes that led to approximately 90% flavan-3-ol precipitation, while for albumin and α-amylase, the interaction model of a "sphere of action" was established, which represented only 20% flavan-3-ol precipitation. These data highlight the relevance of including HMWSPs in astringency analyses, paying special heed to the role of mucins in the interaction and subsequent precipitation of dietary tannins.

19.
Trends Plant Sci ; 29(7): 770-785, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38368122

ABSTRACT

The plant long noncoding (lnc)RNA field is on the brink of transitioning from large-scale identification of lncRNAs to their functional characterization. Due to the cross-kingdom conservation of interaction types and molecular functions, there is much to be learned from mammalian lncRNA research. Here, we discuss the different molecular processes involving lncRNAs from the regulation of chromatin to splicing. Furthermore, we discuss the lncRNA interactome, which includes proteins, other RNAs, and DNA. We explore and discuss how mammalian lncRNA functionalities could be reflected in similar pathways in plants and hypothesize that several breakthroughs in mammalian research could lead to the discovery of novel plant lncRNA molecular functions. Expanding our knowledge of the biological role of lncRNAs and their multiple applications paves the way for future agricultural applications.


Subject(s)
RNA, Long Noncoding , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Animals , Plants/genetics , Plants/metabolism , RNA, Plant/genetics , RNA, Plant/metabolism , Chromatin/metabolism , Chromatin/genetics , RNA Splicing , Humans
20.
Brief Bioinform ; 25(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38348746

ABSTRACT

The prediction of molecular interactions is vital for drug discovery. Existing methods often focus on individual prediction tasks and overlook the relationships between them. Additionally, certain tasks encounter limitations due to insufficient data availability, resulting in limited performance. To overcome these limitations, we propose KGE-UNIT, a unified framework that combines knowledge graph embedding (KGE) and multi-task learning, for simultaneous prediction of drug-target interactions (DTIs) and drug-drug interactions (DDIs) and enhancing the performance of each task, even when data availability is limited. Via KGE, we extract heterogeneous features from the drug knowledge graph to enhance the structural features of drug and protein nodes, thereby improving the quality of features. Additionally, employing multi-task learning, we introduce an innovative predictor that comprises the task-aware Convolutional Neural Network-based (CNN-based) encoder and the task-aware attention decoder which can fuse better multimodal features, capture the contextual interactions of molecular tasks and enhance task awareness, leading to improved performance. Experiments on two imbalanced datasets for DTIs and DDIs demonstrate the superiority of KGE-UNIT, achieving high area under the receiver operating characteristics curves (AUROCs) (0.942, 0.987) and area under the precision-recall curve ( AUPRs) (0.930, 0.980) for DTIs and high AUROCs (0.975, 0.989) and AUPRs (0.966, 0.988) for DDIs. Notably, on the LUO dataset where the data were more limited, KGE-UNIT exhibited a more pronounced improvement, with increases of 4.32$\%$ in AUROC and 3.56$\%$ in AUPR for DTIs and 6.56$\%$ in AUROC and 8.17$\%$ in AUPR for DDIs. The scalability of KGE-UNIT is demonstrated through its extension to protein-protein interactions prediction, ablation studies and case studies further validate its effectiveness.


Subject(s)
Learning , Pattern Recognition, Automated , Drug Discovery , Area Under Curve , Neural Networks, Computer , Drug Interactions
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