Favorable Interactions Research Articles

Ononin's Antagonistic Activity towards TRPV1: Insights from Molecular Dynamics and Capsaicin-Evoked Calcium Response in DRG Neurons.

The search for effective painkillers has led to intensive research, with a particular focus on the transient receptor potential vanilloid-1 (TRPV1) channel as a possible target. One promising candidate is ononin, which is investigated for its binding with TRPV1 through a 200-ns molecular dynamic simulation and analysed via root-meansquare deviation (RMSD), root-mean-square fluctuation (RMSF), hydrogen-bond interactions, radius of gyration (RadGyr), and MM-PBSA energy calculations. The results were further validated experimentally via calcium imaging studies. Molecular dynamics revealed that the ononin-TRPV1 complex achieved stable binding within a remarkably short time of approximately 38 ns while maintaining the degree of compactness of the receptor throughout a 200 ns simulation period. In contrast, the capsazepine-TRPV1 complex displayed more significant structural deviations during the whole simulation. Moreover, MM-PBSA energy calculations showed a relatively strong binding affinity between ononin and TRPV1, mainly attributed to favourable hydrophobic interactions. Pre-incubation of dorsal root ganglia (DRG) neurons with ononin (1 and 10 μM) or capsazepine (10 μM) for 4 min prior to stimulation with capsaicin significantly reduced capsaicin-evoked calcium responses. No significant difference between capsazepine and ononin was found at a concentration of 10 μM. Overall, this research demonstrates the potential of ononin as a potential antagonist for developing analgesics targeting TRPV1. Hence, and to our best knowledge, this study represents the first report of ononin's antagonistic activity towards TRPV1.

Targeting cyclin-dependent kinase 11: a computational approach for natural anti-cancer compound discovery.

Cancer, a leading global cause of death, presents considerable treatment challenges due to resistance to conventional therapies like chemotherapy and radiotherapy. Cyclin-dependent kinase 11 (CDK11), which plays a pivotal role in cell cycle regulation and transcription, is overexpressed in various cancers and is linked to poor prognosis. This study focused on identifying potential inhibitors of CDK11 using computational drug discovery methods. Techniques such as pharmacophore modeling, virtual screening, molecular docking, ADMET predictions, molecular dynamics simulations, and binding free energy analysis were applied to screen a large natural product database. Three pharmacophore models were validated, leading to the identification of several promising compounds with stronger binding affinities than the reference inhibitor. ADMET profiling indicated favorable drug-like properties, while molecular dynamics simulations confirmed the stability and favorable interactions of top candidates with CDK11. Binding free energy calculations further revealed that UNPD29888 exhibited the strongest binding affinity. In conclusion, the identified compound shows potential as a CDK11 inhibitor based on computational predictions, suggesting their future application in cancer treatment by targeting CDK11. These computational findings encourage further experimental validation as anti-cancer agents.

Optimized peptide inhibitor Aqs1C targets LasR to disrupt quorum sensing and biofilm formation in Pseudomonas aeruginosa: Insights from MD simulations and in vitro studies.

Pseudomonas aeruginosa (PA) is a critical pathogen, and its antibiotic resistance is largely driven by the quorum-sensing regulator LasR. Herein, we report the design, synthesis, and characterization of Aqs1C, a mutated peptide derivative of Aqs1, optimized to inhibit LasR and its quorum-sensing pathway. By introducing a targeted mutation, Aqs1C exhibited enhanced stability and binding affinity for LasR protein compared to its predecessor, Aqs1B. Using molecular dynamics simulations (MDS), the Aqs1C-LasR complex demonstrated a marked increase in structural stability, reflected in reduced root mean square deviation (RMSD) values and lower binding free energy. Electrostatic complementarity analysis showed stronger and more favorable interactions between Aqs1C and LasR. Further, GaMD experiments were able to reproduce the binding state between Aqs1C and LasR, indicating the binding mechanism between them. These molecular insights correlated with functional in vitro assays. Aqs1C effectively inhibited quorum-sensing-associated virulence factors in PA, involving biofilm formation (77.6 % inhibition), pyocyanin production (75.7 % inhibition), protease secretion (61.1 % inhibition), and rhamnolipid production (74.1 % inhibition), at a 100 μg/mL concentration, in a comparable or superior pattern to azithromycin (AZM). Molecular modelling, MDS, and GaMD insights and in vitro assays established Aqs1C as a promising candidate for therapeutic development to mitigate PA infections through targeted quorum-sensing disruption.

Mechanism of HJ11 Decoction in the Treatment of Atherosclerosis Based on Network Pharmacology and Experimental Validation.

HJ11 (HJ11 decoction), which is based on the traditional prescription Si-Miao-Yong-An decoction, has exerted a remarkable effect on atherosclerosis (AS). Nevertheless, the main components and underlying mechanisms of HJ11 for treating AS remain unclear. This study was designed to elucidate the mechanism of HJ11 in the treatment of AS through network pharmacology and in vivo experimental validation. Network pharmacology was employed to explore the primary bioactive components and targets of HJ11. AS-related genes were obtained from the GeneCards and DisGeNET databases and screened for intersections with HJ11. A herb-compound-target interaction network was constructed by Cytoscape 3.9.1, and molecular docking analyses were constructed on key targets. By using a mouse model, the mechanism of action of HJ11 was further confirmed. A total of 231 active components of HJ11, 1681 AS-related genes, and 156 common targets were identified. Through the establishment of numerous networks, it was discovered that the main association of the mechanism of HJ11 in AS therapy pertained to anti-inflammation. Important substances included quercetin, kaempferol, and luteolin, while TNF-α, AKT1, IL-6, and VEGFA were the main targets. Molecular docking demonstrated that there were favorable binding interactions between active drugs (quercetin, kaempferol, and luteolin) and targets (TNF-α, AKT1, IL-6, and VEGFA). In the in vivo study, HJ11 reduced the expression of TNF-α, AKT1, IL-6, and VEGFA at both the mRNA and protein levels, inhibited atherosclerotic lesions in AS mouse models, and retarded the development of retroarterioid sclerosis. HJ11 can inhibit inflammation and the progression of AS, and the mechanism might involve downregulating the expression of TNF-α, AKT1, IL-6, and VEGFA.

Study of the influence of ultra-high molecular weight polyethylene and high-density polyethylene on the properties and structure of ethylene propylene diene monomer rubber

Objectives. The study set out to examine the impact of pre-mixed ultra-high molecular weight polyethylene (UHMWPE) and high-density polyethylene (HDPE) on a range of properties and structural characteristics of SKEPT-50 ethylene propylene diene monomer (EPDM) rubber.Methods. The production of rubber mixtures involved the pre-mixing of rubber with UHMWPE and HDPE in a Brabender PL 2200-3 plasti-corder chamber (Germany) at a temperature of 160°C, for a period of 6 min, and with a rotor speed of 60 rpm. The polyethylene constituents were incorporated into the rubber compound at concentrations of 5, 10, and 15 pts. wt. The subsequent introduction of the principal constituents of the rubber mixture was conducted in an SYM laboratory mill (China) for a period of 30 min at a temperature of no more than 100°C. The vulcanization of the samples was conducted in an Y1000D vacuum hydraulic press (China) at a temperature of 185°C for a period of 35 min. The investigation of vulcanization and physical and mechanical properties was conducted in accordance with the established protocols. The analysis of the rubber supramolecular structure was conducted using a JEOL JSM-6840 LV scanning electron microscope (Japan).Results. The results demonstrate that an increase in the proportion of HDPE and UHMWPE to 15 pts. wt leads to a notable enhancement in the hardness of the rubbers by 10 and 5 Shore A units, respectively. The frost resistance coefficient at −45°C demonstrates an increase with the incorporation of 10 pts. wt of HDPE to reach a value of 0.229, and a further increase with the incorporation of 15 pts. wt of UHMWPE to reach a value of 0.260. The degree of swelling of rubbers in a DOT-4 brake fluid environment is observed to decrease to 13% for rubbers with HDPE and 19% with UHMWPE. The degree of swelling of rubbers in the DOT-4 brake fluid environment is observed to decrease to 13% for rubbers with HDPE and 19% with UHMWPE. While an increase in the HDPE content results in a 5% increase in volumetric wear, an increase in the UHMWPE content is associated with a 45% decrease in volumetric wear. The introduction of UHMWPE was observed to result in the formation of inclusions of varying shapes and sizes within a range of 50–100 µm. The transition zone between UHMWPE and rubber is characterized by a smooth surface. No evidence of cracks or micro-tears between the polymer phases, which could potentially form during low-temperature splitting, was observed. This finding indicates the presence of favorable interfacial interactions, which can be linked to the observed enhancements in resistance to aggressive liquids and abrasion, as well as the improved tensile frost resistance coefficient. The supramolecular structure of rubber samples combined with HDPE is more pronounced and exhibits greater relief than that of the original rubber. This is indicative of a more uniform distribution within the matrix volume, which can be attributed to the high fluidity of the HDPE melt.Conclusions. Rubbers modified with UHMWPE, in comparison with HDPE, exhibit enhanced resistance to wear, oil, and frost, while maintaining their elastic and strength properties. It was established that rubber containing 15 pts. wt of UHMWPE exhibits optimal properties and can thus be recommended for use in sealing rubber products.

Exploring the Affinity and Interactions of Piperine with Wild-Type and Mutated PTEN through Molecular Docking and Dynamics Simulations

Background: Phosphatase and tensin homolog (PTEN) gene dysfunction plays an essential role in the pathogenesis of cancer development. Piperine is a natural compound, popularized by its effective medicinal properties. In this investigation, we used in-silico techniques such as molecular docking and molecular dynamic simulation to assess the activating effect of piperine on PTEN which can guide the development of more personalized therapeutic strategies or to provide more effective therapies and interventions. Methods: The analysis was performed in Ghalib Bioinformatics Center, Kabul, Afghanistan in 2024. For molecular docking purposes, autodock 4.2.2 was applied to determine the interaction and binding affinity of Piperine with both Wild-type and Mutated-type PTEN. For molecular dynamics (MD) simulation purposes AMBER99SB force field within GROMACS 2019.6 software was utilized to find more molecular interaction and structural conformations. Results: Wild and mutated-type PTENs had favorable interaction and binding energy, with -6.99 (kcal/mol) for Wild-type PTEN and -6.35 (kcal/mol) for Mutated-type PTEN. The result of the MD simulation showed the stabilization and less fluctuation of wild-type PTEN in the presence of piperine. Conclusion: This study provides the details that piperine with its multi-health benefits and usage, could be likely as a potential activator for wild-type PTEN, offering valuable insights in generating new treatments to fight against cancers and reduce its development risk.

High levels of sinigrin trigger synthesis of fatty acids in Plutella xylostella (L.).

Diamondback moth (Lepidoptera: Plutellidae; Plutella xylostella L.) is a specialist insect of the Brassicaceae family, damaging economically important crops, such as cabbage and cauliflower. Glucosinolates, also known as 'mustard oil bombs' are present in all Brassicaceae members, of which sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate) is a major aliphatic compound. During herbivory, glucosinolates are converted to toxic isothiocyanates that deter insect pests. P. xylostella possesses glucosinolate sulfatases that desulfate them. Such a conversion renders them unfit for degradation to toxic products. Changes in the larval performance prompted us for RNA sequencing to understand probable adaptation mechanism under sinigrin stress. Differentially expressed genes were found to be related to larval cuticle proteins. Further, gene ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses depict genes belonging to the categories, integral component of membrane, cellular processes and those involved in biosynthesis of fatty acids. Upregulation of cuticular genes viz. larval cuticle protein-17 (LCP-17), cuticular protein-19 (2CP-19) and ATP binding cassette transporter C7 (ABCC7), ABCC16 was validated by qRT-PCR. Liquid chromatography quadrupole time of flight mass spectrometry analysis of whole larvae feeding on sinigrin and their separated cuticle, depicted abundance of fatty acids. Changes in the topography of the larval cuticle were evident by scanning electron microscopy. Expression of PxABCH1 was corroborated to its role in the transport of cuticular lipids. Notably, molecular docking of PxABCH1 with cuticular fatty acids showed favorable binding interactions. To summarize, integrated transcriptomic and metabolomic analyses suggest that in response to a diet containing a high dose of sinigrin, P. xylostella re-programs metabolic pathways related to fatty acid biosynthesis that directly influence insect development.

Beyond analgesia: repurposing NSAIDs as a novel strategy in antivenom therapy against Naja nigricollis envenomation

ObjectiveThis study aimed to explore the potential of repurposing non-steroidal anti-inflammatory drugs (NSAIDs) as antisnake venom agents using experimental and computational approaches.Data descriptionVirtual screening of 20 NSAIDs alongside Varespladib was conducted to obtain three top-scoring drugs (celecoxib, ketorolac, and ketoprofen); the antisnake venom efficacy of the three NSAIDs was evaluated using a combination of in vivo, ex vivo, in vitro and in silico approaches. In vivo and ex vivo experiments in mice, demonstrated that all three drugs exhibited significant (p < 0.05) antisnake venom activity against Naja nigricollis venom in a dose-dependent manner. Ketorolac provided complete protection with a 100% survival rate at doses of 100, 200, and 400 mg/kg, while celecoxib and ketoprofen showed survival rates ranging from 25 to 75%. The standard antivenom (ASV) also achieved a 100% survival rate at 0.6 mg/mL. Ex vivo results mirrored these findings, with ketorolac showing the highest survival rate (100%) and celecoxib exhibiting the lowest (50%). In vitro, the drugs demonstrated significant (p < 0.05) phospholipase A2 enzyme (PLA2) inhibition, with ketorolac achieving 96.65–99.86% inhibition at 1–0.0125 mg/mL. Molecular docking studies further supported these findings, revealing favorable binding affinities and interactions with key amino acid residues implicated in envenomation. In conclusion, these findings suggest that NSAIDs, particularly ketorolac, hold promise as potential antivenom therapies against Naja nigricollis envenomation, warranting further investigation in clinical studies.

RuIII-Morpholine-Derived Thiosemicarbazone-Based Metallodrugs: Lysosome-Targeted Anticancer Agents.

The idea of coordinating biologically active ligand systems to metal centers to exploit their synergistic effects has gained momentum. Therefore, in this report, three RuIII complexes 1-3 of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of 2 through a single-crystal X-ray diffraction study. The solution stability of 1-3 was tested using conventional techniques such as UV-vis and HRMS. Further, the anticancer activity of 1-3 was tested in HT-29 and HeLa cancer cell lines. To gain insight into their mechanism of action, the cytotoxicity, hydrophobicity, and the interaction of 1-3 with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, 1-3 revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, 1 has the highest cytotoxicity among all in the group, against both cells, respectively. Additionally, the fluorescence-active ruthenium complexes selectively target lysosomes, which is evaluated by live-cell imaging. 1-3 disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.

From Antipsychotic to Neuroprotective: Computational Repurposing of Fluspirilene as a Potential PDE5 Inhibitor for Alzheimer's Disease.

Phosphodiesterase 5 (PDE5) inhibitors have shown great potential in treating Alzheimer's disease by improving memory and cognitive function. In this study, we evaluated fluspirilene, a drug commonly used to treat schizophrenia, as a potential PDE5 inhibitor using computational methods. Molecular docking revealed that fluspirilene binds strongly to PDE5, supported by hydrophobic and aromatic interactions. Molecular dynamics simulations confirmed that the fluspirilene-PDE5 complex is stable and maintains its structural integrity over time. Binding energy calculations further highlighted favorable interactions, indicating that the drug forms a strong and stable bond with PDE5. Additional analyses, including studies of protein dynamics and energy landscape mapping, revealed how the drug interacts dynamically with PDE5, adapting to different conformations and maintaining stability. These findings suggest that fluspirilene may modulate PDE5 activity, potentially offering therapeutic benefits for Alzheimer's disease. This study provides strong evidence for repurposing fluspirilene as a treatment for Alzheimer's and lays the foundation for further experimental and clinical investigations.

Nanoscale self-assembly and water retention properties of silk fibroin-riboflavin hydrogel.

Silk-fibroin hydrogels have gained considerable attention in recent years for their versatile biomedical applications. The physical properties of a complex hydrogel, comprising silk fibroin and riboflavin, surpass those of the silk fibroin-hydrogel without additives. This study investigates silk fibroin-riboflavin (silk-RIB) hydrogel at the atomistic level to uncover molecular structures and chemical characteristics specific to silk fibroin and riboflavin molecules in an aqueous medium. The interplay between hydrophilic riboflavin and hydrophobic silk fibroin polymers facilitates the formation of solubilized silk fiber, which subsequently evolves into a nano-scale hydrogel over time. Eventually, the interlinked RIB stacks form a scaffold that not only accommodates silk fibroin aggregates but also encloses water pockets, preserving the moisture level and enhancing the thermal conductivity of the hydrogel. To explore water retention properties and the role of ions, two sets of simulations of semi-hydrated hydrogel in the presence and absence of ions are conducted. The presence of ions significantly influences the dynamics of RIB and silk fibroin. Favorable interactions with the ions impede the unrestricted diffusion of these larger molecules, potentially leading to a stable structure capable of retaining water for a prolonged duration. The complete removal of water results in further shrinkage of the anhydrous silk-RIB hydrogel or xerogel (XG), yet its porosity and structural integrity remain intact. These findings offer valuable insights into the behavior of silk fibroin hydrogel and XG, paving the way for materials engineering in aqueous environments to develop biomedical devices with customized functional properties.

Dual Targeting of MEK1 and Akt Kinase Identified SBL-027 as a Promising Lead Candidate to Control Cell Proliferations in Gastric Cancer.

Dual inhibition of Akt and MEK1 pathways offers a promising strategy to enhance treatment efficacy in gastric cancer. In this study, we employed computational approaches followed by in vitro validations. Our results demonstrate that SBL-027 exhibits robust and enduring interactions with Akt and MEK1 kinases, as evidenced by atomistic molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) based binding free energy estimates. The predicted Gibbs binding free energies indicate highly favorable interactions between SBL-027 and both Akt and MEK1 kinases. In vitro, SBL-027 displayed an IC50 value of 195.20nM against Akt and 239.10nM against MEK1 enzymes. The compound exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells, with GI50 values of 490.70 and 615.14nM, respectively. Moreover, SBL-027 induced an increase in the sub G0/G1 population during the cell cycle of KATOIII and SNU-5 cells, while facilitating early and late-phase apoptosis in these cell lines. Notably, the compound significantly reduced the percentage of dual-positive cells expressing both MEK1 and Akt in gastric cancer cells. The strong binding affinity, stability, and favorable thermodynamics of SBL-027 along with the established in vitro efficacy highlight its potential as a lead compound for further preclinical and clinical development.

Understanding Folding of bFGF and Potential Cellular Protective Mechanisms of Neural Cells.

Traumatic brain injury (TBI) is a serious health condition that affects an increasing number of people, especially veterans and athletes. TBI causes serious consequences because of its long-lasting impact on the brain and its alarming frequency of occurrence. Although the brain has some natural protective mechanisms, the processes that trigger them are poorly understood. Fibroblast growth factor (FGF) proteins interact with receptor proteins to protect cells. Gaps in the literature include how basic-FGF (bFGF) is activated by heparin, can heparin-like molecules induce neural protection, and the effect of allosteric binding on bFGF activity. To fill the gap in our understanding, we applied temperature replica exchange to study the influence of heparin binding to bFGF and how mutations in bFGF influence stability. A new favorable binding site was identified by comparing free energies computed from the potential of mean force (PMF). Although the varied sugars studied resulted in different interactions with bFGF compared to heparin, they each produced structural effects similar to those of bFGF that likely facilitate receptor binding and signaling. Our results also demonstrate how point mutations can trigger the same conformational change that is believed to promote favorable interactions with the receptor. A deeper atomic-level understanding of how chemicals are released during TBI is needed to improve the development of new treatments for TBI and could contribute to a better understanding of other diseases.

Substantially Improving CO2 Permeability and CO2/CH4 Selectivity of Matrimid Using Functionalized-Ti3C2Tx.

Mixed-matrix membranes (MMMs) with favorable interfacial interactions between dispersed and continuous phases offer a promising approach to overcome the traditional trade-off between permeability and selectivity in membrane-based gas separation. In this study, we developed free-standing MMMs by embedding pristine and surface-modified Ti3C2Tx MXenes into Matrimid 5218 polymer for efficient CO2/CH4 separation. Two-dimensional Ti3C2Tx with adjustable surface terminations provided control over these critical interfacial interactions. Characterization (Raman spectroscopy, XPS, DSC, FTIR) indicated the formation of hydrogen bonds between the termination groups on Ti3C2Tx and the carbonyl groups of Matrimid, promoting enhanced compatibility and dispersion of MXenes within the polymer matrix. The resulting MMMs with 5 wt % Ti3C2Tx showed a 67% increase in CO2 permeability and an 84% enhancement in CO2/CH4 selectivity compared to pristine Matrimid membranes. Surface modification of Ti3C2Tx using [3-(2-aminoethylamino)propyl]trimethoxysilane (AEAPTMS) further enhanced compatibility, leading to MMMs with 140% higher CO2 permeability and 130% greater CO2/CH4 selectivity. Molecular simulations suggested that AEAPTMS functionalization improved interfacial interactions with Matrimid chains, increasing the affinity of MXenes toward CO2 molecules. Additionally, the elongation of gas pathways, polymer chain disruption, and the presence of interlayer nanogalleries contributed positively to the enhanced separation performance. This work provides insights into tailoring nanomaterial-polymer interfaces to address the challenges of gas separation, paving the way for environmentally friendly CO2 separation technologies.

Structural and electronic features enabling delocalized charge-carriers in CuSbSe2

Inorganic semiconductors based on heavy pnictogen cations (Sb3+ and Bi3+) have gained significant attention as potential nontoxic and stable alternatives to lead-halide perovskites for solar cell applications. A limitation of these novel materials, which is being increasingly commonly found, is carrier localization, which substantially reduces mobilities and diffusion lengths. Herein, CuSbSe2 is investigated and discovered to have delocalized free carriers, as shown through optical pump terahertz probe spectroscopy and temperature-dependent mobility measurements. Using a combination of theory and experiment, the critical enabling factors are found to be: 1) having a layered structure, which allows distortions to the unit cell during the propagation of an acoustic wave to be relaxed in the interlayer gaps, with minimal changes in bond length, thus limiting deformation potentials; 2) favourable quasi-bonding interactions across the interlayer gap giving rise to higher electronic dimensionality; 3) Born effective charges not being anomalously high, which, combined with the small bandgap (≤1.2 eV), result in a low ionic contribution to the dielectric constant compared to the electronic contribution, thus reducing the strength of Fröhlich coupling. These insights can drive forward the rational discovery of perovskite-inspired materials that can avoid carrier localization.

SBL-JP-0004: A promising dual inhibitor of JAK2 and PI3KCD against gastric cancer.

Gastric cancer (GC) remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies. The phosphoinositide 3-kinase and PI3K and Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathways play pivotal roles in GC progression, making them attractive targets for therapeutic interventions. This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases. KATOIII and SNU-5 GC cells were used for in vitro evaluation. SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases, as evidenced by molecular docking scores and molecular dynamics simulations. Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins. SBL-JP-0004 displayed an half-maximal inhibitory concentration (IC50) value of 118.9 nM against JAK2 kinase and 200.9 nM against PI3KCD enzymes. SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells, with half-maximal growth inhibitory concentration (GI50) values of 250.8 and 516.3 nM, respectively. A significant elevation in the early phase apoptosis (28.53% in KATOIII cells and 26.85% in SNU-5 cells) and late phase apoptosis (17.37% in KATOIII cells and 10.05% in SNU-5 cells) were observed with SBL-JP-0004 treatment compared to 2.1% and 2.83% in their respective controls. The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

Comparison in vitro and in silico studies of phenolic acids and flavonoids on α-glucosidase inhibition

Context: Inhibiting α-glucosidase activity has been proven to regulate hyperglycemia for treating diabetes, particularly type 2 diabetes mellitus (T2DM). Plant secondary metabolites consist of phenolic acids and flavonoids, which have been identified as α-glucosidase inhibitory agents. Aims: To assess the ability of the tested phenolic acids and flavonoids as α-glucosidase inhibitors and to predict their binding interactions with α-glucosidase, as well as their pharmacokinetic properties. Methods: The tested phenolic acids and flavonoids were evaluated for α-glucosidase inhibition by in vitro study, and their binding interactions were observed by an in silico molecular docking study utilizing AutoDock 4.2 software, while their pharmacokinetic properties were predicted using SwissADME and pkCSM online software. Results: The results displayed that quercetin (QE; IC50 = 0.85 μg/mL) and gallic acid (GA; IC50 = 26.19 μg/mL) significantly inhibited α-glucosidase activity than acarbose (IC50 = 139.4 μg/mL). Molecular docking analysis revealed that QE exhibited a higher binding affinity (ΔG; -7.53 kcal/mol) compared to acarbose (ΔG; -7.00 kcal/mol). This suggested that QE formed more favorable interactions with the enzyme, as evidenced by its binding to catalytic residues D215 and D352. In contrast, acarbose interacted with only one catalytic amino acid, i.e., D215. Furthermore, GA displayed a lower binding affinity (ΔG; -4.63 kcal/mol) than acarbose and bound to a distinct site on the α-glucosidase involving amino acids K156, S241, and D242. The pharmacokinetic properties predictions revealed that the potential compounds could bind and inhibit the α-glucosidase and were not toxic. Conclusions: Therefore, this study is useful for modifying the structures of phenolic acids and flavonoids to improve their ability to inhibit the α-glucosidase activity.

FACILE HYDROTHERMAL SYNTHESIS OF NIOBIUM PENTOXIDE SEMICONDUCTOR AND THEIR APPLICATION IN THE PHOTODEGRADATION OF DYES AND REDUCTION OF FREE FAT ACIDS IN WASTE OIL

We report a facile hydrothermal method for the synthesis of niobium pentoxide (Nb2O5) under two different temperatures, 120 °C (Nb2O5-120) and 150 °C (Nb2O5-150). The obtained materials were characterized by structural, optical and morphological techniques. Also, the photocatalytic properties of the Nb2O5 samples were evaluated in two reactions under ultraviolet (UVC) irradiation: degradation of methylene blue (MB) and indigo carmine (IC) dyes; and esterification of free fatty acids (FFA) present in waste cooking oil (WCO). The Nb2O5 was formed at different temperatures of synthesis, and the increase in temperature did not cause significant changes in the structural and optical characteristics, but resulted in an increased surface area of the synthesized materials. Both synthesized materials showed excellent efficiency for dye photodegradation. The sample Nb2O5-150 presented the best performance for the MB photodegradation, with almost 85% of the removal efficiency. In this case, the adsorption of MB molecules on the surface of the material was high due to the favorable electrostatic interaction and also because of its high surface area. For the IC photodegradation, the adsorption was insignificant, and both samples presented approximately 100% of the removal efficiency. These materials were also promising for the reduction of free fat acids in waste oil by photoesterification.

Syntheses of differentially fluorinated triazole-based 1-deoxysphingosine analogues en route to SphK inhibitors.

This study focuses on the stereoselective syntheses of 1-deoxysphingosine analogues as potential inhibitors of sphingosine kinase (SphK), particularly targeting its isoforms SphK1 and SphK2, which are implicated in cancer progression and therapy resistance. The research builds on previous work by designing a series of analogues featuring systematic structural modifications like the incorporation of a triazole ring, varying degrees of fluorination, and different head groups (e.g., guanidino, N-methylamino, and N,N-dimethylamino). These modifications aimed to enhance polar and hydrophobic interactions especially with SphK2. The synthesized compounds were evaluated for their inhibitory activity, revealing that certain derivatives, particularly those with guanidino groups and heptafluoropropyl fragments at the lipidic tail, exhibited significant potency and selectivity towards SphK2. Docking studies supported these findings by showing favorable binding interactions within the SphK2 active site, which were less pronounced in SphK1, correlating with the observed selectivity. This work contributes to the development of novel 1-deoxysphingosine analogues targeting SphK inhibition, as well as to the knowledge of the differential topology of the active sites in SphK1 and SphK2.

Biophysiochemically favorable, antithrombotic and pro-endothelial coordination compound nanocoating of copper (II) with protocatechuic acid & nattokinase on flow-diverting stents.

Neurovascular flow-diverting stents (FDSs) are revolutionizing the paradigm for treatment of intracranial aneurysms, but they still face great challenges like post- implantation acute thrombosis and delayed reendothelialization. Surface modification is of crucial relevance in addressing such key issues. In this study, we fabricated an ultrathin nanocoating out of copper (II) together with protocatechuic acid (PCA) and nattokinase (NK) bioactive molecules on NiTi FDSs via a coordination chemistry approach, with favorable biophysiochemical interactions, to fulfill this goal. This coating was identified as covalently-anchored and compactly covering the FDSs substrate, with unique nano-structured morphology as well as superhydrophilicity. The in vitro coagulation and whole blood assays demonstrated that the modified FDS's surfaces showed improved antithrombogenicity, with reduced platelet and fibrinogen adhesion, as well as their aggregation and activation, and consequently prolonged clotting time leading to decreased thrombosis occurrence. Human umbilical vein endothelial cell cultures confirmed the modified capability of FDSs to promote endothelial cell proliferation and migration. The ex vivo experiments verified that modified FDSs had clearly in-stent patency without thrombi formation, as compared to the bare FDSs bearing thromboembolic blockage. It was postulated that these enhanced biocompatibilities can be attributable to the copper-catalyzed nitric oxide (NO) released as a functional mediator, the nature of the PCA and NK molecules, as well as the synergic biophysiochemical surface/interface interactions. Our strategy may not only open a new avenue for surface-functionalizing neurovascular FDSs for medical purpose but also help better-understand interfacial phenomena on the advanced biomaterials.