Caffeine weakens the astringency of epigallocatechin gallate by inhibiting its interaction with salivary proteins.

The astringency of green tea is an integrated result of the synergic and antagonistic effects of individual tea components, whose mechanism is highly complex and not completely understood. Herein, we used an epigallocatechin gallate (EGCG)/caffeine (CAF)/saliva model to simulate the oral conditions during tea drinking. The effect of CAF on the interaction between EGCG and salivary proteins was first investigated using molecular docking and isothermal titration calorimetry (ITC). Then, the rheological properties and the micro-network structure of saliva were studied to relate the molecular interactions and perceived astringency. The results revealed that CAF partially occupied the binding sites of EGCG to salivary proteins, inhibiting their interaction and causing changes in the elastic network structure of the salivary film, thereby reducing astringency.

Enhancement of the gelling properties of Aristichthys nobilis: Insights into intermolecular interactions between okra polysaccharide and myofibrillar protein.

The effects of various contents of okra polysaccharide (OP) (0%-1%) on myofibrillar protein (MP) gelation and the interaction mechanism between OP and MP were investigated. OP improved the gelling properties of MP with an additive limitation of 0.75%. Rheological analysis demonstrated that the addition of OP enhanced the interactions between MPs, resulting in a denser intermolecular gel network structure. The addition of OP shifted the I850/I830 of Fourier transform infrared spectroscopy, indicating that hydrogen bonds were formed between OP and MP. Adding OP promoted the transition from α-helix to ß-sheet in the MP. OP exposed the hydrophobic groups of MPs and increased the number of hydrophobic interactions between them, favoring the formation of a dense gel network. Molecular docking predicted that hydrogen bonds were the main force involved in the binding of OP and MP. Moderate OP promoted the aggregation of MPs and improved their functional properties, facilitating heat-induced gelation.

Assessing the influences of ß-glucan on highland barley starch: Insights into gelatinization and molecular interactions.

Developing highland barley products is complex, possibly due to the presence of ß-glucan in highland barley. This study aims to investigate the impact of ß-glucan on the physicochemical properties, microstructure, and molecular interactions of highland barley starch (HBS) during gelatinization and aging. Increasing the ß-glucan content significantly reduced peak viscosity, setback viscosity, and breakdown viscosity, indicating altered gelatinization behavior. The ß-glucan content increase caused a significant drop in peak viscosity. With 20% ß-glucan addition, it reduced by 883 mPa·s, nearly 38%. Rheological analysis showed a transition from a solid-like to a liquid-like texture or quality, ultimately leading to a shear-thinning behavior. Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) confirmed the interaction between HBS and ß-glucan via intermolecular hydrogen bonding, promoting the formation of double helical structures in starch. These findings provide a deeper understanding of the role of ß-glucan in the processing of highland barley, highlighting its influence on the starch's properties.

Larvicidal activity of ß-Citral: An In-vitro and In-silico study to understand its potential against mosquito.

Tropical and subtropical regions face millions of deaths from mosquito-borne illnesses yearly. Insecticides prevent transmission but pose health risks like dermatitis and allergies. The primary objective was to mitigate the recurring dependence on synthetic insecticides, thereby curbing the development of mosquito resistance. Leaves of Cymbopogon flexuosus (lemongrass) was collected from Mayurbhanj, India, processed, then extracted by steam distillation for essential oils & analyzed spectroscopically. Larvicidal assays were performed across varying concentrations, revealing the significant mortality induced by the Cymbopogon flexuosus extract against Anopheles stephensi larvae. 3D structure was modelled by using G protein-coupled receptors (GPCR) sequence and structural stability was also validated. After docking the binding free energy was determined from GPCR protein with ß-citral complex. Molecular dynamics (MD) study was conducted on the docked pose that displayed an optimal interactome profile. The larvicidal assay at the 12th and 24th hour revealed the highest LC50 (lethal concentration) of 23.493 ppm and 19.664 ppm . ß-Citral has a high binding affinity and an identifiable binding site, which suggests that it may play a larvicidal role in regulating the receptor's function by creating stable complexes with it. ß-Citral from lemongrass oils has potential larvicidal activity and effective against GPCR family 1 of mosquito and highly effective repellents against mosquito-borne diseases.

Small molecule inhibitor binds to NOD-like receptor family pyrin domain containing 3 and prevents inflammasome activation.

Despite recent advances in the mechanism of oxidized DNA activating NLRP3, the molecular mechanism and consequence of oxidized DNA associating with NLRP3 remains unknown. Cytosolic NLRP3 binds oxidized DNA which has been released from the mitochondria, which subsequently triggers inflammasome activation. Human glycosylase (hOGG1) repairs oxidized DNA damage which inhibits inflammasome activation. The fold of NLRP3 pyrin domain contains amino acids and a protein fold similar to hOGG1. Amino acids that enable hOGG1 to bind and cleave oxidized DNA are conserved in NLRP3. We found NLRP3 could bind and cleave oxidized guanine within mitochondrial DNA. The binding of oxidized DNA to NLRP3 was prevented by small molecule drugs which also inhibit hOGG1. These same drugs also inhibited inflammasome activation. Elucidating this mechanism will enable the design of drug memetics that treat inflammasome pathologies, illustrated herein by NLRP3 pyrin domain inhibitors which suppressed interleukin-1ß (IL-1ß) production in macrophages.

The molecular mechanisms underlying optical isomer arbutin permeating the skin: The molecular interaction between arbutin and skin components.

Arbutin, a typical optical isomer, has garnered widespread acclaim in the whitening cosmetics for its favorable efficacy and safety. However, the molecular mechanisms underlying α-arbutin and ß-arbutin permeating across the skin have not elucidated clearly yet. Herein we aimed to unveil how α-arbutin and ß-arbutin interacted with keratin or SC lipids, further demonstrating their relationship with their drug permeability. We found that α-arbutin displayed significantly higher drug accumulation into the porcine skin than ß-arbutin within 24 h through in vitro permeation test. Moreover, α-arbutin predominantly induced the alternations of secondary structure of amide II during the drug permeation, which was favorable for α-arbutin permeation. On the contrary, ß-arbutin exhibited an observable effect on the stretching vibration of SC lipids, possessing a significantly stronger mixing energy, binding energy and compatibility with ceramide (Cer) than that of α-arbutin, which ultimately restricted its permeation. Interestingly, free fatty acids and ceramides of the SC lipids specifically utilized its oxygen atom of carboxyl group to dock the arbutin molecules, enhancing their affinity with ß-arbutin, as confirmed by molecular simulation and 13Carbon Nuclear Magnetic Resonance. Nevertheless, a favorable compatibility between α-arbutin and keratin was observed. It was emphasized that the distinct spatial configuration and opposite optical rotation of arbutin was the leading factor impacting the intermolecular force between arbutin and the SC, and resulted in a diverse drug permeation. In cellular and in vivo skin pharmacokinetic studies, α-arbutin also possessed a higher cellular uptake and topical bioavailability than ß-arbutin. This study revealed the transdermal permeation mechanisms of optical isomer arbutin at the molecular levels, providing methodological reference for the investigations of permeation behaviors of other isomers with similar spatial configuration.

Cytochrome c prompts the recruitment of its nuclear partners SET/TAF-Iß and NPM1 into biomolecular condensates.

Compartmentalization of proteins by liquid-liquid phase separation (LLPS) is used by cells to control biochemical reactions spatially and temporally. Among them, the recruitment of proteins to DNA foci and nucleolar trafficking occur by biomolecular condensation. Within this frame, the oncoprotein SET/TAF-Iß plays a key role in both chromatin remodeling and DNA damage response, as does nucleophosmin (NPM1) which indeed participates in nucleolar ribosome synthesis. Whereas phase separation by NPM1 is widely characterized, little is known about that undergone by SET/TAF-Iß. Here, we show that SET/TAF-Iß experiences phase separation together with respiratory cytochrome c (Cc), which translocates to the nucleus upon DNA damage. Here we report the molecular mechanisms governing Cc-induced phase separation of SET/TAF-Iß and NPM1, where two lysine-rich clusters of Cc are essential to recognize molecular surfaces on both partners in a specific and coordinated manner. Cc thus emerges as a small, globular protein with sequence-encoded heterotypic phase-separation properties.

SPI1-KLF1/LYL1 axis regulates lineage commitment during endothelial-to-hematopoietic transition from human pluripotent stem cells.

PU.1 (SPI1) is pivotal in hematopoiesis, yet its role in human endothelial-to-hematopoietic transition (EHT) remains unclear. Comparing human in vivo and in vitro EHT transcriptomes revealed SPI1's regulatory role. Knocking down SPI1 during in vitro EHT led to a decrease in the generation of hematopoietic progenitor cells (HPCs) and their differentiation potential. Through multi-omic analysis, we identified KLF1 and LYL1 - transcription factors specific to erythroid/myeloid and lymphoid cells, respectively - as downstream targets of SPI1. Overexpressing KLF1 or LYL1 partially rescues the SPI1 knockdown-induced reduction in HPC formation. Specifically, KLF1 overexpression restores myeloid lineage potential, while LYL1 overexpression re-establishes lymphoid lineage potential. We also observed a SPI1-LYL1 axis in the regulatory network in in vivo EHT. Taken together, our findings shed new light on the role of SPI1 in regulating lineage commitment during EHT, potentially contributing to the heterogeneity of hematopoietic stem cells (HSCs).

A hybrid evaluation of the intestinal absorption performance of compounds from molecular structure.

Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure-property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P-glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well.

Interaction of plants and metal nanoparticles: Exploring its molecular mechanisms for sustainable agriculture and crop improvement.

Metal nanoparticles offer promising prospects in agriculture, enhancing plant growth and ensuring food security. Silver, gold, copper, and zinc nanoparticles possess unique properties making them attractive for plant applications. Understanding molecular interactions between metal nanoparticles and plants is crucial for unlocking their potential to boost crop productivity and sustainability. This review explores metal nanoparticles in agriculture, emphasizing the need to understand these interactions. By elucidating mechanisms, it highlights the potential for enhancing crop productivity, stress tolerance, and nutrient-use efficiency, contributing to sustainable agriculture and food security. Quantifying benefits and risks reveal significant advantages. Metal nanoparticles enhance crop productivity by 20% on average and reduce disease incidence by up to 50% when used as antimicrobial agents. They also reduce nutrient leaching by 30% and enhance soil carbon sequestration by 15%, but concerns about toxicity, adverse effects on non-target organisms, and nanoparticle accumulation in the food chain must be addressed. Metal nanoparticles influence cellular processes including sensing, signaling, transcription, translation, and post-translational modifications. They act as signaling molecules, activate stress-responsive genes, enhance defense mechanisms, and improve nutrient uptake. The review explores their catalytic role in nutrient management, disease control, precision agriculture, nano-fertilizers, and nano-remediation. A bibliometric analysis offers insights into the current research landscape, highlighting trends, gaps, and future directions. In conclusion, metal nanoparticles hold potential for revolutionizing agriculture, enhancing productivity, mitigating environmental stressors, and promoting sustainability. Addressing risks and gaps is crucial for their safe integration into agricultural practices.

Regulation of the DLC3 tumor suppressor by a novel phosphoswitch.

Deleted in liver cancer 3 (DLC3) is a Rho GTPase-activating protein (RhoGAP) that plays a crucial role in maintaining adherens junction integrity and coordinating polarized vesicle transport by modulating Rho activity at the plasma membrane and endomembranes. By employing bioinformatical sequence analysis, in vitro experiments, and in cellulo assays we here identified a polybasic region (PBR) in DLC3 that facilitates the association of the protein with cellular membranes. Within the PBR, we mapped two serines whose phosphorylation can alter the electrostatic character of the region. Consequently, phosphomimetic mutations of these sites impaired the membrane association of DLC3. Furthermore, we found a new PBR-dependent localization of DLC3 at the midbody region, where the protein locally controlled Rho activity. Here, the phosphorylation-dependent regulation of DLC3 appeared to be required for proper cytokinesis. Our work thus provides a novel mechanism for spatiotemporal termination of Rho signaling by the RhoGAP protein DLC3.

Infection of Phytophthora palmivora Isolates on Arabidopsis thaliana.

Phytophthora palmivora, a hemibiotrophic oomycete, causes diseases in several economically important tropical crops, such as oil palm, which it is responsible for a devastating disease called bud rot (BR). Despite recent progress in understanding host resistance and virulence mechanisms, many aspects remain unknown in P. palmivora isolates from oil palm. Model pathosystems are useful for understanding the molecular interactions between pathogens and hosts. In this study, we utilized detached leaves and whole seedlings of Arabidopsis thaliana Col-0 to describe and evaluate the infection process of three P. palmivora isolates (CPPhZC-05, CPPhZC-04, CPPhZOC-01) that cause BR in oil palm. Two compatible isolates (CPPhZC-05 and CPPhZOC-01) induced aqueous lesions at 72 h post-inoculation (hpi), with microscopic visualization revealing zoospore encysting and appressorium penetration at 3 hpi, followed by sporangia generation at 72 hpi. In contrast, an incompatible isolate (CPPhZC-04) exhibited cysts that could not penetrate tissue, resulting in low leaf colonization. Gene expression of ten P. palmivora infection-related genes was quantified by RT-qPCR, revealing overexpression in compatible isolates, but not in the incompatible isolate. Additionally, key genes associated with salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) in Arabidopsis exhibited regulation during interaction with the three isolates. These findings demonstrate that P. palmivora can infect Arabidopsis Col-0, and variability is observed in the interaction between Arabidopsis-Col-0 and P. palmivora isolates. Establishing this pathosystem is expected to enhance our understanding of P. palmivora's pathology and physiology.

Incorporation of cross-linked/acetylated tapioca starches on the gelling properties, rheological behaviour, and microstructure of low-salt myofibrillar protein gels: Perspective on phase transition.

This study investigated the gelling properties, rheological behaviour, and microstructure of heat-induced, low-salt myofibrillar protein (MP) gels containing different levels (2%, 4%, 6%, and 8%, w/w) of cross-linked (CTS) or acetylated (ATS) tapioca starch. The results indicated that either CTS or ATS significantly enhanced the gel strength and water-holding capacity of low-salt MP gels (P < 0.05), an outcome verified by the rheological behaviour test results under different modes. Furthermore, iodine-staining images indicated that the MP-dominated continuous phase gradually transited to a starch-dominated phase with increasing CTS or ATS levels, and 4% was the critical point for this phase transition. In addition, hydrophobic interactions and disulphide bonds constituted the major intermolecular forces of low-salt MP gels, effectively promoting phase transition. In brief, modified tapioca starches possess considerable potential application value in low-salt meat products.

Exo1 cooperates with Tel1/ATM in promoting recombination events at DNA replication forks.

Tel1/ataxia telangiectasia mutated (ATM) kinase plays multiple functions in response to DNA damage, promoting checkpoint-mediated cell-cycle arrest and repair of broken DNA. In addition, Saccharomyces cerevisiae Tel1 stabilizes replication forks that arrest upon the treatment with the topoisomerase poison camptothecin (CPT). We discover that inactivation of the Exo1 nuclease exacerbates the sensitivity of Tel1-deficient cells to CPT and other agents that hamper DNA replication. Furthermore, cells lacking both Exo1 and Tel1 activities exhibit sustained checkpoint activation in the presence of CPT, indicating that Tel1 and Exo1 limit the activation of a Mec1-dependent checkpoint. The absence of Tel1 or its kinase activity enhances recombination between inverted DNA repeats induced by replication fork blockage in an Exo1-dependent manner. Thus, we propose that Exo1 processes intermediates arising at stalled forks in tel1 mutants to promote DNA replication recovery and cell survival.

Identification of new targets for glioblastoma therapy based on a DNA expression microarray.

This study provides a comprehensive perspective on the deregulated pathways and impaired biological functions prevalent in human glioblastoma (GBM). In order to characterize differences in gene expression between individuals diagnosed with GBM and healthy brain tissue, we have designed and manufactured a specific, custom DNA microarray. The results obtained from differential gene expression analysis were validated by RT-qPCR. The datasets obtained from the analysis of common differential expressed genes in our cohort of patients were used to generate protein-protein interaction networks of functionally enriched genes and their biological functions. This network analysis, let us to identify 16 genes that exhibited either up-regulation (CDK4, MYC, FOXM1, FN1, E2F7, HDAC1, TNC, LAMC1, EIF4EBP1 and ITGB3) or down-regulation (PRKACB, MEF2C, CAMK2B, MAPK3, MAP2K1 and PENK) in all GBM patients. Further investigation of these genes and enriched pathways uncovered in this investigation promises to serve as a foundational step in advancing our comprehension of the molecular mechanisms underpinning GBM pathogenesis. Consequently, the present work emphasizes the critical role that the unveiled molecular pathways likely play in shaping innovative therapeutic approaches for GBM management. We finally proposed in this study a list of compounds that target hub of GBM-related genes, some of which are already in clinical use, underscoring the potential of those genes as targets for GBM treatment.

Formation of pea protein amyloid-like nanofibrils-derived hydrogels mediated by epigallocatechin gallate.

This study investigated the interaction between pea protein amyloid-like nanofibril and epigallocatechin gallate, constructed and characterized the novel pea protein nanofibrils-derived hydrogel mediated by epigallocatechin gallate, and researched the functionalities of the hydrogel. Epigallocatechin gallate remodeled the structure of pea protein nanofibrils, and a stable and strong hydrogel was formed at a relatively low protein concentration (4.5%). Additionally, the hydrogels exhibited various surface structures and hydrogel properties dependent on the mass ratio. Strongest gel strength (51 g) was attained at 0.25 epigallocatechin gallate/pea protein nanofibrils mass ratio. Whereas, the hydrogels exhibited the highest water holding capacity (87%) at 0.05 mass ratio. The primary driving forces in the formation and maintaining of the hydrogels were hydrophobic interactions and ionic bonds. Progressive rise of ß-sheet content of pea protein nanofibrils occurred increasing epigallocatechin gallate concentration. This hydrogel holds great potential for applications in food processing, targeted delivery of nutraceuticals and biomedicine.

Characterization of size-tuneable aescin-lipid nanoparticles as platform for stabilization of membrane proteins.

Disc-like lipid nanoparticles stabilized by saponin biosurfactants display fascinating properties, including their temperature-driven re-organization. ß-Aescin, a saponin from seed extract of the horse chestnut tree, shows strong interactions with lipid membranes and has gained interest due to its beneficial therapeutic implications as well as its ability to decompose continuous lipid membranes into size-tuneable discoidal nanoparticles. Here, we characterize lipid nanoparticles formed by aescin and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine. We present site-resolved insights into central molecular interactions and their modulations by temperature and aescin content. Using the membrane protein bacteriorhodopsin, we additionally demonstrate that, under defined conditions, aescin-lipid discs can accommodate medium-sized transmembrane proteins. Our data reveal the general capability of this fascinating system to generate size-tuneable aescin-lipid-protein particles, opening the road for further applications in biochemical, biophysical and structural studies.

Stabilization of zein nanoparticles with tween-80 and fucoidan for encapsulation of eugenol via a nozzle simulation chip.

Eugenol (EU), a natural bioactive compound found in various plants, offers numerous health benefits, but its application in the food and pharmaceutical industry is limited by its high volatility, instability, and low water solubility. Therefore, this study aimed to utilize the surface coating technique to develop zein-tween-80-fucoidan (Z-T-FD) composite nanoparticles for encapsulating eugenol using a nozzle simulation chip. The physicochemical characteristics of the composite nanoparticles were examined by varying the weight ratios of Z, T, and FD. Results showed that the Z-T-FD weight ratio of 5:1:15 exhibited excellent colloidal stability under a range of conditions, including pH (2-8), salt concentrations (10-500 mmol/L), heating (80 °C), and storage (30 days). Encapsulation of EU into Z-T-FD nanoparticles (0.5:5:1:15) resulted in an encapsulation efficiency of 49.29 ± 1.00%, loading capacity of 0.46 ± 0.05%, particle size of 205.01 ± 3.25 nm, PDI of 0.179 ± 0.006, and zeta-potential of 37.12 ± 1.87 mV. Spherical structures were formed through hydrophobic interaction and hydrogen bonding, as confirmed by Fourier transform infrared spectroscopy and molecular docking. Furthermore, the EU-Z-T-FD (0.5:5:1:15) nanoparticles displayed higher in vitro antioxidant properties (with DPPH and ABTS radical scavenging properties at 75.28 ± 0.16% and 39.13 ± 1.22%, respectively), in vitro bioaccessibility (64.78 ± 1.37%), and retention rates under thermal and storage conditions for EU compared to other formulations. These findings demonstrate that the Z-T-FD nanoparticle system can effectively encapsulate, protect, and deliver eugenol, making it a promising option for applications in the food and pharmaceutical industries.

Pregnant Women with Multiple Sclerosis: An Overview of Gene Expression and Molecular Interaction Using Bioinformatics Analysis.

Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients' genetic and biological phenomena and formulate new questions about MS during pregnancy.

Discovery of azaleatin as a potential allosteric inhibitor for dengue NS2B-NS3 protease using in vitro and in silico studies.

The rise in dengue cases in tropical and sub-tropical areas has become a significant health concern. At present, there is no definitive cure for dengue fever, which underscores the importance of identifying potent inhibitors. Dengue NS2B-NS3 protease is the prime drug target due to its vital function for replication. Quercetin, a flavone, has anti-dengue virus properties but is limited by low bioavailability. Previous studies have shown that methoxy substitution in flavones improves bioavailability and metabolic stability. Azaleatin is a derivative of quercetin with a methoxy substitution at the C5 position, however its ability to inhibit dengue is unknown. In this study, azaleatin was investigated for its inhibition against dengue NS2B-NS3 protease using in vitro and in silico techniques. The fluorescence assay was used to determine the IC50 value and inhibition kinetics. The molecular interaction between azaleatin and NS2B-NS3 was studied using CB-Dock2 and AutoDock Vina. The complex's stability was then analysed using GROMACS. Besides, the ADMETlab 2.0 was utilized to predict pharmacokinetic of the azaleatin. Results showed that azaleatin inhibits dengue NS2B-NS3 protease non-competitively with a Ki of 26.82 µg/ml and an IC50 of 38 µg/ml. Molecular docking indicated binding of the azaleatin to the allosteric pocket of NS2B-NS3 with a docking score of -8.2 kcal/mol. Azaleatin was found stable in the pocket along 100 ns, supporting its inhibitory mode. The compound has favourable pharmacokinetic profiles and conformed to Lipinski's Rule of Five. Taken together, azaleatin inhibits NS2B-NS3 protease in a non-competitive mode, suggesting its potential as safer anti-dengue compound.Communicated by Ramaswamy H. Sarma.