Glycogen synthase kinase-3 is a fascinating enzyme involved in a series of physiological processes, and its activity is associated with the pathological features of various diseases, such as type 2 diabetes, Alzheimer's disease, chronic inflammation, cancer, and bipolar affective disorder. GSK-3 inhibitors are currently being tested for their therapeutic effects on these diseases. In this work, the inhibition of GSK-3/3 by aloisines is investigated by structure-activity correlation studies, the best model obtained being characterized by R2 = 0.8865. The identification of the molecular fragments that contribute most to the formation of biological activity is carried out using fingerprint descriptors, such as the electronegativity of the OMO/UMO quantum molecular states. For an even better understanding of the relationship between chemical structure and observed biological activity, an aloisine/GSK-3/3 complex structure was obtained using molecular docking. The two types of studies (correlation and docking) are in good and complementary agreement. Therefore, our study suggests that the aloisine molecules are potent and selective for GSK-3/3.

Combination analgesic therapy is commonly used to improve pain control, yet conventional molecular docking approaches typically evaluate individual ligands and provide limited insight into potential intermolecular associations between co-administered drugs. In this study, paracetamol, codeine, and their proposed 1:1 and 2:1 non-covalent assemblies were investigated using lipophilicity analysis, molecular docking, short molecular dynamics relaxation, electrostatic potential surface mapping, and HOMO-LUMO analysis. Docking simulations were performed against cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and the μ-opioid receptor (MOR). The proposed assemblies produced docking scores that differed from those of the individual compounds, with the most pronounced differences observed for the cyclooxygenase targets. The 2:1 assemblies generally exhibited the most favorable docking scores, whereas the predicted interaction profiles at MOR appeared to be more dependent on molecular orientation. Molecular dynamics relaxation and electronic structure analyses further revealed differences in the energetic and electronic characteristics of the investigated configurations. These findings support the theoretical feasibility of distinct interaction patterns among the proposed paracetamol-codeine assemblies within the applied computational framework. However, the reported docking scores represent relative computational values rather than experimentally validated binding affinities, and the short-timescale molecular dynamics simulations provide only preliminary information regarding conformational stability. Furthermore, the existence and biological relevance of the proposed assemblies under physiological conditions remain to be established. This study provides a computational basis for future investigations of intermolecular associations in multicomponent drug systems.

Cyclodextrins (CDs) have revolutionized the pharmaceutical industry with their ability to enhance the stability, solubility, and bioavailability of a wide range of active substances. These cyclic oligosaccharides, with a unique hydrophilic exterior and hydrophobic cavity, form inclusion complexes with poorly soluble drugs, improving their pharmacokinetic profiles and therapeutic efficacy. This review explores the multifaceted roles of cyclodextrins in pharmaceutical formulations, ranging from oral, ophthalmic, parenteral, and topical applications to their emerging use in targeted therapies, gene delivery, and treatment of neurodegenerative, cardiovascular, and infectious diseases. Cyclodextrins not only improve drug solubility and controlled release but also reduce toxicity and side effects, leading to safer and more effective treatments. Recent advancements, such as cyclodextrin-based nanoparticles, offer promising pathways for cancer therapy, chronic disease management, and personalized medicine. As research continues, cyclodextrins remain at the forefront of innovation in drug delivery systems, ensuring better patient outcomes and expanding the possibilities of modern therapeutics.

The paracetamol-propyphenazone combination is one of the classic analgesic formulations used for the treatment of acute pain of mild to moderate intensity. By combining the antipyretic and analgesic properties of paracetamol with the rapid analgesic and anti-inflammatory effects of propyphenazone, this association provides an enhanced therapeutic response, characterized by a fast onset of action and effective symptom relief. It is frequently used in the management of tension-type headaches, migraines, and other forms of acute pain, being appreciated for its relatively favorable tolerability profile. The main objective of this study is to determine whether the interactions between paracetamol, propyphenazone, and cyclooxygenase enzymes are influenced by the combination of these two drugs. This was achieved using the HEX 8.0 docking program. Binding energy was used as a measure to assess the strength of the interactions. Our analysis shows that the strongest interaction with COX-2 was observed for the propyphenazone-paracetamol complex, indicating that when propyphenazone is assigned as the receptor and paracetamol as the ligand, the resulting complex achieves optimal accommodation within the COX-2 active site. These findings highlight the importance of understanding drug-drug interactions. Therefore, a solid comprehension of these dynamics is essential to ensure the efficacy of therapeutic combinations.

Precision nutrition-targeted gut microbiota (GM) may have therapeutic potential not only for age-related diseases but also for slowing the aging process and promoting longer healthspan. Recent studies have shown that restoring a healthy symbiosis of GM by counteracting dysbiosis (DYS) through precise nutritional intervention is becoming a major target for extending healthspan. Microbiota-accessible borate (MAB) complexes, such as boron (B)–pectins (rhamnogalacturonan–borate) and borate–phenolic esters (diester chlorogenoborate), have a significant impact on healthy host–microbiota symbiosis (HMS). The mechanism of action of MABs involves the biosynthesis of the autoinducer-2–borate (AI-2B) signaling molecule, B fortification of the mucus gel layer by the MABs diet, inhibition of pathogenic microbes, and reversal of GM DYS, strengthening the gut barrier structure, enhancing immunity, and promoting overall host health. In fact, the lack of MAB complexes in the human diet causes reduced levels of AI-2B in GM, inhibiting the Firmicutes phylum (the main butyrate-producing bacteria), with important effects on healthy HMS. It can now be argued that there is a relationship between MAB-rich intake, healthy HMS, host metabolic health, and longevity. This could influence the deployment of natural prebiotic B-based nutraceuticals targeting the colon in the future. Our review is based on the discovery that MAB diet is absolutely necessary for healthy HMS in humans, by reversing DYS and restoring eubiosis for longer healthspan.

The aim of this study was to investigate the molecular interactions of heparin, diclofenac, and their supramolecular complexes with cyclooxygenase enzymes (COX-1 and COX-2) using computational docking techniques. Diclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX isoforms, whereas heparin is a polyanionic glycosaminoglycan with established anticoagulant and emerging anti-inflammatory properties. Supramolecular association between these agents may modulate their physicochemical behavior and target engagement. Molecular modeling, dual-drug docking, and molecular dynamics (MD) simulations were employed to characterize the interactions of heparin, diclofenac, and pre-formed heparin-diclofenac complexes with COX-1 and COX-2. Geometry optimization and lipophilicity (logP) estimates were obtained using HyperChem, while protein-ligand docking was performed in HEX using crystallographic COX structures from the Protein Data Bank. Docking poses were analyzed in Chimera, and selected complexes were refined through short MD simulations. Pre-formed heparin-diclofenac assemblies exhibited markedly enhanced docking scores toward both COX isoforms compared with single ligands. Binding orientation strongly influenced affinity: for COX-1, the heparin-diclofenac configuration yielded the most favorable interaction, whereas for COX-2 the diclofenac-heparin configuration was preferred. Both assemblies adopted binding modes distinct from free diclofenac, suggesting cooperative electrostatic and hydrophobic contacts at the enzyme surface. Supramolecular complexation also altered calculated logP values relative to the individual compounds. MD simulations supported the relative stability of the top-ranked complex-COX assemblies. These findings indicate that heparin-diclofenac assemblies may enhance and reorganize predicted COX interactions in a configuration-dependent manner and illustrate the utility of dual-drug docking for modeling potential synergistic effects. Such insights may inform the design of localized or topical formulations, potentially incorporating non-anticoagulant heparin derivatives, to achieve effective COX inhibition with reduced systemic exposure. However, the results rely on simplified heparin fragments, legacy docking tools, and short MD simulations, and should therefore be interpreted qualitatively. Experimental studies will be essential to confirm whether such supramolecular assemblies form under physiological conditions and whether they influence COX inhibition in vivo.

The study investigates the characteristics of PLGA-based particles encapsulating doxorubicin (Doxo) and functionalised with alendronate (Aln) for controlled drug delivery. Zeta potential measurements indicated moderate colloidal stability of both PLGA-Doxo and PLGA-Doxo-Aln particles, with values of-7 mV andA-10 mV, respectively. This negative charge suggests weak electrostatic repulsion between particles, potentially promoting aggregation in complex biological environments. Numerical and volumetric distributions showed that most particles were in the 550-822 nm size range, with a predominant particle size of 817.2 nm for PLGA-Doxo-Aln. AThe morphology of the particles revealed a porous structure, which could influence the gradual release of Doxo. Antibacterial activity tests showed significant inhibition of S. aureus by PLGA-Doxo, while PLGA-Doxo-Aln showed no activity against E. coli due to functionalization with Aln. Release studies indicated a controlled release of both Aln and Doxo, with gradual degradation of the PLGA matrix contributing to prolonged drug release. The results suggest that PLGA-Doxo-Aln particles could serve as a promising system for targeted drug delivery, particularly for bone-related cancers.

Flavonoids are a diverse group of polyphenolic compounds widely distributed in the plant kingdom, known for their antioxidant, anti-inflammatory, and anticancer properties. This study focuses on flavonoids identified in Aloe vera, a medicinal plant with numerous bioactive compounds, and investigates their potential as inhibitors of Glycogen Synthase Kinase-3β (GSK-3β)—a key enzyme implicated in various inflammatory and neurodegenerative diseases. A total of ten flavonoid compounds (six hydroxyflavones and four glycosylated flavones) were analyzed using computational methods. Geometry optimization and physicochemical property calculations were performed using HyperChem software, while molecular docking studies were conducted with Hex 8.0 to evaluate interactions with GSK-3β (PDB ID: 1q4l). The results revealed two main docking sites on the enzyme, specific to the structural group of each compound. Key descriptors such as HOMO-LUMO energy levels, dipole moments, polarizability, and molecular hardness were also assessed to understand reactivity and stability. These findings highlight the structural and electronic characteristics that govern flavonoid binding and support the potential of Aloe vera-derived flavonoids as therapeutic agents targeting GSK-3β.

Malignant melanoma remains one of the most aggressive forms of skin cancer, underscoring the need for improved therapeutic strategies. In this study, a analysis and molecular docking was employed to investigate the molecular determinants of anticancer activity against the human melanoma cell line. A set of ten drug molecules with reported growth inhibition data (pGI50) was selected for analysis. QSAR analysis revealed that both geometric parameters and frontier molecular orbital descriptors significantly influence biological activity, highlighting the importance of molecular size, flexibility, and electron-donating/accepting capabilities. Molecular docking simulations were subsequently performed against the target protein associated with the SK-MEL-5 cell line (PDB ID: 3OG7) to evaluate binding affinity and interaction patterns. The docking results showed distinct differences in binding energies and interaction profiles among the compounds, with methotrexate, rhodomycin A, and triazinate exhibiting the most favorable binding characteristics. Overall, the integrated QSAR and docking approach provides mechanistic insight into ligand-receptor interactions and supports the rational interpretation of structure-activity relationships in melanoma.

Microbiota-accessible nutritional complexes (MAC), a formulation comprising prebiotics, postbiotics, autophagy stimulators, senolytic activators, and natural probiotics, may influence systemic biomarkers and biological aging in healthy individuals. This pilot interventional study aimed to evaluate the effects of a 60-day MAC supplementation on serum biomarkers and biological age (BioAge) in medically healthy adults. Methods: Of 13 screened, 12 enrolled; 3 were excluded from the final analysis. Nine participants (five females, four males; mean age 61 ± 9.29 years) completed 60 days of daily MAC supplementation and were included in the analyses. Serum biomarkers were measured at baseline and post-intervention. BioAge was estimated using three machine-learning regressors: Support Vector Regression (SVR), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost). Feature importance analysis was conducted to identify key predictors of BioAge. Results: No adverse events occurred. A significant reduction in high-sensitivity C-reactive protein (hs-CRP) levels was observed from 2.66 ± 4.65 to 0.84 ± 0.54 mg/L (-69

Caffeine is a widely consumed psychoactive compound known to influence drug metabolism and efficacy through interactions with key enzymes such as cytochrome P450 3A4 (CYP3A4). This study investigates the molecular impact of caffeine on the binding behavior of imatinib, a first-line BCR-ABL tyrosine kinase inhibitor, using molecular docking simulations. Structural optimization and lipophilicity analyses were conducted using HyperChem, while docking was performed with HEX software (Version 8.0.0) against the CYP3A4 receptor (PDB ID: 1W0E). Two administration scenarios were evaluated: concurrent caffeine–imatinib complex formation and sequential administration with caffeine pre-bound to CYP3A4. The caffeine–imatinib complex exhibited a predicted increase in lipophilicity (logP = 3.09) compared to imatinib alone (logP = −1.29), which may indicate the potential for enhanced membrane permeability and tissue distribution. Docking simulations revealed stronger binding affinity of the complex to CYP3A4 (−350.53 kcal/mol) compared to individual compounds, and improved imatinib binding when CYP3A4 was pre-complexed with caffeine (−294.14 kcal/mol vs. −288.19 kcal/mol). Frontier molecular orbital analysis indicated increased reactivity of the complex (ΔE = 7.74 eV), supporting the hypothesis of altered pharmacodynamic behavior. These findings suggest that caffeine may modulate imatinib’s metabolic profile and therapeutic efficacy by enhancing receptor binding and altering drug distribution. The study underscores the importance of evaluating dietary components during drug development and therapeutic planning, particularly for agents metabolized by CYP3A4.

Recently, we discovered and proved the essentiality of organic boron species (OBS), such as borate–pectic polysaccharides and borate–phenolic esters, for healthy symbiosis (HS) between microbiota and human/animal (H/A) host. The essentiality of OBS will provide new options for B supplementation in H/A nutrition for a healthy and long life. New knowledge on the essentiality of naturally occurring microbiota-accessible borate species for HS between microbiota and H/A host will allow the use of natural B-based dietary supplements to target the H/A microbiome (the gut, skin, oral, scalp, and vaginal microbiome). In the literature, there is evidence that certain bacteria need B (autoinducer-2 borate) for communication and our preliminary data show that HS takes place when the colonic mucus gel layer contains B. Subsequently, OBS become novel prebiotic candidates and target the colon as novel colonic foods.

The current strategy for treating osteomyelitis includes surgical procedures for complete debridement of the formed biofilm and necrotic tissues, systemic and oral antibiotic therapy, and the clinical use of cements and three-dimensional scaffolds as bone defect fillers and delivery systems for therapeutic agents. The aim of our research was to formulate a low-cost hybrid nanoparticulate biomaterial using poly(lactic-co-glycolic acid) (PLGA), in which we incorporated the therapeutic agent (ciprofloxacin), and to deposit this material on titanium plates using the matrix-assisted pulsed laser evaporation (MAPLE) technique. The deposited material demonstrated antibacterial properties, with all analyzed samples inhibiting the growth of tested bacterial strains, confirming the release of active substances from the investigated biocomposite. The poly(lactic-co-glycolic acid)-ciprofloxacin (PLGA-CIP) nanoparticle scaffolds displayed a prolonged local sustained release profile over a period of 45 days, which shows great promise in bone infections. Furthermore, the burst release ensures a highly efficient concentration, followed by a constant sustained release which allows the drug to remain in the implant-adjacent area for an extended time period.

Boron (B) has many roles in the plant kingdom, being an essential element for fundamental metabolic pathways, with reference to carbohydrates, ribonucleic acid, phenolic compounds, indole acetic acid derivatives, respiration, as well as for the structure of cell wall and integrity of plasma membrane, cell division, differentiation, and elongation at the level of meristematic tissues, growth of the pollen tube, grain maturation. It has also been shown that the low amount of B can cause sterility during herbal reproductive stage.For identification and quantitative determination of some natural B-containing compounds (BCCs), such as boric acid, fructoboric acid and its derivatives (Ca–fructose–B complex and Zn–fructose–B complex), sodium tetraborate, high-performance thin-layer chromatography (HPTLC)–ultraviolet (UV) densitometry method was used, based on the following experimental conditions: stationary phase HPTLC silica gel G 60 F254 precoated glass plates, mobile phase 2-propanol–water 8:2 (v/v), derivatization with chlorogenic acid.The phytobiological assessment of natural BCCs was carried out using Triticum test. A slight stimulation of the mean radicular elongation of wheat-germinated caryopses, compared to the reference, was recorded for fructoboric acid and its derivatives at a concentration of 0.1% expressed in B.

This study explores the molecular interactions between two drugs, diclofenac, and heparin, through computational docking to understand the impact of complex formation on binding affinity, orientation, and pharmacological properties. Using molecular modeling and docking simulations, we analyzed how diclofenac and heparin bind individually and as complexes to target receptor Factor Xa, critical in coagulation pathways. Results demonstrate that forming diclofenac-heparin complexes significantly enhances binding affinity, with lower binding energies compared to individual drugs, indicating more stable interactions. Notably, the orientation of the complex (diclofenac_heparin versus heparin_diclofenac) affected the binding site and binding energy, suggesting that sequence and orientation in complex formation are crucial factors in drug-target interaction. Additionally, differences in lipophilicity (logP values) between the complexes suggest that binding orientation may influence bioavailability and membrane permeability. These findings underscore the potential for dual-drug complex formation to enhance pharmacological efficacy, paving the way for optimized drug combinations in therapeutic applications

Combining polimers with polyphenols such as gallic acid opens up new directions in healthcare system. By encapsulating secondary metabollites within PLGA nanoparticles, we tried to enhance their stability, solubility, and obtain a targeted delivery system. In this study, we synthesized a PLGA-gallic acid sustained release system, using the solvent evaporation method. This approach improved the therapeutic efficacy of gallic acid. The numerical distribution showed that most PLGA-GA nanoparticles have a size of 10 nm. Through the method of solvent evaporation, an incorporation efficiency of 49% was obtained.

The aim of our study was to develop a more advanced method of using some already existing drugs by synthesizing a multicomponent biopolymeric nanocomposite material, which would function as a local drug release system. Thus, we started from simple polylactic-co-glycolic acid (PLGA) nanoparticles, synthesized by the double emulsion method. Then we functionalized the surface of the obtained material with polydopamine (PDA) to which we bound bisphosphonates (used in the current medical practice for the treatment of osteosarcoma). This resulted in a composite material with improved properties compared to constituent materials. The synthesized polymer biocomposites were characterized by SEM (morphological aspects) and Diffusion Light Scattering (DLS) (granulometric dimensions, zeta potential). The chosen synthesis method is simple, inexpensive, with easily adjustable parameters. The theoretical studies carried out regarding the bisphosphonate-polydopamine interaction showed a better stability for the risedronate interaction complex which agrees with the experimental data obtained for it.

NAD+ is known classically as a metabolite that participates in catabolic and anabolic pathways throughout the metabolism that is taught to students in introductory biochemistry courses. However, non-classical studies starting over a decade ago found that NAD+ is also involved in higher order functions, in part because of its involvement in the activation of SIRTs and the support of the mitochondrial unfolded protein response. Many studies since have suggested that NAD+ is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes, Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including NAR and NMN. Together, these studies show that this system has value as a dietary supplement to improve general health overall, as well as mitigating specific disease conditions. Accordingly, many are now recommending the consumption of materials in this system as dietary supplements. Nicotinamide riboside (NAR) appears to have special value in this regard. It appears to be better tolerated than other molecules in this system, as well as better pharmacodynamics and greater potency. Unfortunately, NAR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Indeed, HPLC analyses of many commercial samples of NAR shows that they contain substantial amounts of material that are not, in fact, NAR. In some of these commercial preparations, NAR is a minority component. Therefore, more stable derivatives of NAR that are easily converted upon consumption into NAR are therefore desired. Recently work related to prebiotic chemistry provided the borate derivative of NAR. NARB is considerably more stable than NAR itself. However, immediately upon consumption, the borate dissociates from NARB, and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NAR left behind is expected to behave pharmacologically in ways identical to NAR itself. This review provides a comprehensive summary (through Q1 of 2023) of literature that makes the case for the consumption of NAR as a dietary supplement. It then summarizes the challenges of delivering quality NAR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NAR-borate in these processes.

Salvia genus, representative for the Lamiaceae family as it comprises approximately one thousand different species, is considered for a wide plethora of therapeutic actions, such as antioxidant, anti-inflammatory, hepatoprotective, antitumoral and antidiabetic activity. The paper presents the preliminary chromatographic investigations of the polyphenols in the aerial parts of some Salvia spp. Using high-performance thin-layer chromatography (HPTLC) coupled with photodensitometry, caffeic acid was identified and quantified in the 20% methanolic extracts of Salviaeherba, in descending order, as follows: S. nemorosa (3.096%) > S. verticillata (3.041%) > S. sclarea (2.663%) > S. glutinosa (1.962%) > S. aethiopis (0.926%).