Search Results (1,332)

Currently, there are various approaches to the treatment of diabetes. Regarding type 2 diabetes (T2D), treatment focuses on blood glucose control. When changes in lifestyle do not achieve this glycemic control, the option is to start therapy with antidiabetic drugs such as metformin. However, long-term metformin use causes disturbances that may affect treatment approaches. This review examines recent advances in nanotechnology that have developed new forms of drug administration that can improve the efficacy of the treatment, where nanomaterials, nanostructures, and nanoparticle design are involved, so that they provide controlled and gradual release. The use of biopolymers (as drug delivery systems) has ensured biocompatibility, biodegradability, and low toxicity. There are several methods for obtaining a drug delivery system, including electrospinning, electrospraying, nanoprecipitation, etc. These systems improve drug delivery and can be used orally, transdermally, or intravenously, among means of administration. This review describes the new forms of the administration of metformin in the treatment of T2D, based on the encapsulation of metformin in polymeric matrices such as proteins, polysaccharides, and lipids, among others. Full article

This study developed a novel worm-assisted membrane bioelectrochemical reactor (W-MBER) that integrates aquatic worms and a single-chamber sediment microbial fuel cell into a membrane bioreactor (MBR) to address challenges in energy recovery, sludge reduction, and membrane fouling. The system achieved a stable output of 290 mV at an external resistance of 250 Ω and a maximum power density of 0.013 W/m² while maintaining high removal efficiencies for chemical oxygen demand (93.57%) and ammonia nitrogen (98.61%). Furthermore, the TN removal efficiency was 12.93% higher than that in the conventional MBR (C-MBR), attributed to the anodic anoxic microenvironment. The synergy of worm predation and the bioelectrochemical process reduced sludge production by 28.51% and extended the filtration cycle by 43.75%, indicating significant sludge reduction and membrane fouling mitigation. Mechanistic analysis revealed that the W-MBER system decreased protein content and protein/polysaccharide ratios in soluble microbial products (SMPs) and extracellular polymeric substances (EPSs), and the hydrophobicity of SMPs, EPSs, and sludge flocs was reduced, resulting in a lower free energy for their interaction with membrane. The foulants in the W-MBER encountered higher energy barriers and lower secondary energy minimums when approaching the membrane, indicating a lower membrane fouling propensity. These results demonstrate the promise of W-MBER for sustainable wastewater treatment. Full article

Granular copper oxide nanoparticles (CopOx NPs), synthesized via laser ablation (100 nm, ζ-potential +30 mV), were introduced into photolithographic polymethyl methacrylate (PMMA) resin at concentrations of 0.001–0.1%. The resulting composite material enables the fabrication of high-resolution (up to 50 μm) parts with a high degree of surface quality after polishing using the MSLA method. CopOx NPs increased the degree of resin polymerization (decrease by almost 4× in unpolymerized components at 0.1% CopOx NPs) and induced the in situ formation of self-organized periodic structures visible under a modulation interference microscope. The composite samples exhibit pronounced oxidative activity: they intensify the generation of hydrogen peroxide and hydroxyl radicals and cause the oxidative modification of biomolecules (formation of 8-oxoguanine in DNA and long-lived reactive forms of proteins). A key property of the materials is their selective biological activity. While lacking cytotoxicity for human fibroblasts, they exhibit a strong antibacterial effect against E. coli, leading to cell death within 24 h. Thus, the developed composite photolithographic resin combines improved technological characteristics (high printing resolution, degree of polymerization) with functional properties (selective antibacterial activity) and holds promise for application in biomedicine, as well as in the food and agricultural industries. Full article

TPPP (tubulin polymerization promoting protein)-like proteins are found throughout the living world. The individual members of this protein family are distinguished according to how many times and how completely their characteristic structural element, the p25alpha domain, is found in them. Phylogenomic occurrences of the members of the family differ from each other. Animals, fungi, algae, and various groups of unicellular organisms have their characteristic proteins. The two phylogenomic multi-supergroups, Opimoda+ and Diphoda+, show very different patterns in the occurrence of TPPP types. By using BLAST search in protein and nucleotide databases, we found that the previously known phylogenomic distribution is not strictly true, e.g., fungal type TPPPs are not only found in fungi. We primarily analyzed the Opisthokonta clade but also examined broader relationships. It was confirmed that the occurrence of TPPPs/genes is linked to the presence of the eukaryotic flagellum. A TPPP that contains the entire p25alpha domain twice and occurs only in Opisthokonta was identified. We also identified a TPPP in choanoflagellates and in the uncertainly classified Opisthokonta Tunicaraptor unikontis, which was previously known only in the Diphoda+ clade. On the other hand, we found an Opisthokonta (Opimoda+)-specific TPPP in a Heterolobosea (Diphoda+). Based on these results, we need to rethink the evolutionary history of TPPPs. Full article

Silicon dioxide (SiO₂) nanoparticles approximately 5 nm in size have been obtained. A method has been developed for introducing SiO₂ nanoparticles into photolithographic resin at concentrations up to 0.1%. Composite resins can be used to manufacture parts with complex geometries with a maximum achievable resolution of 50 μm. Parts made from composite resin with SiO₂ nanoparticles polish well. After polishing, areas of approximately 100 μm² with height differences of less than 10 nm are revealed on the surface of the parts. A relatively uniform distribution of SiO₂ nanoparticles is observed within the parts, and no optical defects are detected. However, areas differing in the phase shift of electromagnetic radiation are observed within the parts. Importantly, the presence of nanoparticles in the resin during MSLA printing increases the degree of resin polymerization. SiO₂ nanoparticles have been shown to have prooxidant properties, leading to the formation of 8-oxoguanine in DNA and long-lived reactive protein species. Components made from photolithographic resins with SiO₂ nanoparticles have been shown to inhibit the growth and development of E. coli bacteria, with a significant loss of viability. Despite their antimicrobial properties, components made from photolithographic resins with SiO₂ nanoparticles do not affect the growth and development of mammalian cells. Full article

Plasma cell myeloma (PCM) is classified as a blood cancer and is characterized by the abnormal proliferation of plasma cells in the bone marrow and the excessive production of monoclonal immunoglobulins, which lead to permanent damage to vital organs. Although treatment strategies have improved with the development of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), PCM remains an incurable disease due to its molecular heterogeneity and the development of drug resistance. In this review, we discuss the biochemical and molecular foundations underlying the diagnosis and treatment of PCM, emphasizing both traditional and advanced approaches. Classical methods such as serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain (sFLC) determination are highlighted alongside their integration with highly sensitive techniques like mass spectrometry (MS) and next-generation sequencing (NGS). Special attention is given to nanotechnology-based systems, including liposomes, polymeric nanoparticles (NPs), dendrimers, and hybrid nanocapsules, which enable controlled drug release, targeted delivery, and the minimization of systemic toxicity. Increasingly, nanomaterials are being shown to greatly enhance the biodistribution and pharmacokinetics of anticancer drugs, leading to improved therapeutic effects and escaping resistance mechanisms by employing multifunctional strategies that include dual drug co-encapsulation, pH-sensitive release and theranostic applications. Furthermore, the integration of nanotechnology with immunotherapy platforms represents a paradigm shift toward precision and personalized medicine for the treatment of PCM. Overall, this review views nanotechnology as an enabling technology to improve therapeutic effectiveness, minimize toxicity and open new avenues toward next-generation smart and personalized therapeutics for the treatment of PCM. Full article

Ginkgolic acid (GA) exhibits various biological activities, but its role in vascular restenosis remains unreported. GA (13:0) is a relatively abundant natural congener. This study aims to investigate and clarify the effects and mechanisms of GA (13:0) on vascular smooth muscle cell (VSMC) proliferation and migration in vitro, as well as on balloon injury-induced vascular restenosis in rats. The results showed that GA (13:0) significantly inhibited VSMC proliferation, migration, and intimal thickening both in vitro and in vivo. Moreover, GA (13:0) reduced the expression of cyclin D1, cyclin E1, CDK2, and CDK4, as well as cyclin D1-CDK4 and cyclin E1-CDK2 binding, leading to G0/G1 arrest. Additionally, GA (13:0) suppressed vimentin expression and actin cytoskeleton polymerization and altered F-actin morphology. Comparative proteomics identified tectonic family member 1 (TCTN1) as a potential molecular target of GA (13:0). GA (13:0) reduced TCTN1 expression both in vitro and in vivo. Crucially, TCTN1 overexpression notably reversed the inhibitory effects of GA (13:0) on VSMC proliferation, migration, intimal thickening, expression and binding of cell cycle-related proteins, and vimentin expression. Concurrently, TCTN1 overexpression also reversed GA (13:0)-induced F-actin depolymerization and rearrangement and G0/G1 arrest. GA (13:0) significantly inhibited TCTN1 co-localization with vimentin and actin in vitro and in vivo. Furthermore, we found that CCCTC binding factor (CTCF) binds to the 162–176 site of the TCTN1 promoter to regulate TCTN1 transcription, and CTCF knockout significantly down-regulated TCTN1 protein levels. This study reveals that GA (13:0) inhibits TCTN1 transcription and expression, hindering G1/S transition, vimentin expression, and F-actin rearrangement, thereby suppressing vascular restenosis. Full article

The epidermal cells of bracts, petals and sepals of Ornithogalum umbellatum L. (Star-of-Bethlehem, Asparagaceae) contain lipotubuloids, complex aggregates of lipid droplets (LDs) enmeshed by bundles of microtubules (MTs). We investigated lipotubuloid organization and stability through the transient expression of GFP fusion proteins targeted to different subcellular structures and with immunofluorescence and transmission electron microscopy (TEM). Live cell imaging confirmed that lipotubuloids contain LDs, organelles including endomembranes, mitochondria and peroxisomes, a tonoplast-defined vacuole, and that they move through actin microfilament-based streaming. Intriguingly, the different microscopy modes used showed different patterns of MT organization in the lipotubuloid. While MT sheets and bundles were visible by TEM, few MTs were seen with fusion proteins and immunofluorescence. Oryzalin-based MT depolymerization experiments suggest a possible resolution for this paradox: TEM showed that lipotubuloid MTs resisted depolymerization, even after 20 h in oryzalin, while MT polymerization was visible in lipotubuloids with fusion proteins during oryzalin wash-out. These results suggest that the Ornithogalum lipotubuloids contain hyperstable MTs, possibly formed with microtubule-associated proteins (MAPs) that normally occlude fusion protein and antibody binding sites. Full article

A common strategy for a protein’s functionality modification is the covalent binding of phenolic compounds (PCs) under alkaline conditions. Whether intentionally applied or arising during food processing and storage, such reactions are highly relevant, as alkaline pH promotes oxidation, covalent adduct formation, and polymerization, thereby altering both PC and protein properties. However, the interplay of these reactions and the impact of PC structure remain insufficiently understood. This study aimed at characterizing covalent binding products of structurally related PCs with tryptic peptides of the model protein β-lactoglobulin (β-Lg) at pH 9. Emphasis was given on substitution patterns and steric effects influencing polymerization and peptide adduct building. Hydroxycinnamic acid and flavonoid derivatives differing in hydroxyl substitution and carrying polar (glycosidic) groups were selected. Incubation products were characterized by HPLC–DAD and high-resolution mass spectrometry. Results showed that both mono- and dihydroxy PC undergo oxidation under alkaline conditions, but with distinct reactivity. Monohydroxy PCs form only limited peptide adducts due to resonance stabilization and steric hindrance. In contrast, dihydroxy PCs displayed a higher reactivity, producing more polymerization products and covalent adducts. Their enhanced reactivity is linked to the ability of quinone formation with reduced electrostatic repulsion, while additional polar substituents promote interactions with polar amino acids. At the same time, these substituents impose steric constraints on PC polymerization, modulating oligomer size and thereby influencing peptide binding. Overall, the findings highlight structural determinants of PC reactivity and provide mechanistic insight into the balance between polymerization and covalent peptide modification under alkaline conditions. Full article

Tire microplastics (TMPs) are a widespread pollutant with growing concern due to their diverse sources, persistence, and potential risks to the environment and human health. This study investigated the impact of TMPs (50–500 mg/L) on the sludge structure, activity, and extracellular polymeric substance (EPS) dynamics in granular sequencing batch reactors (GSBRs) under continuous aeration (CA) and intermittent aeration (IA) conditions. Increased TMP concentration reduced granule size and increased the specific surface area under CA, but under IA, it increased granule size and lowered specific surface area. Total EPS declined as TMP concentration increased in both aeration regimes, but the reduction was more pronounced under CA. Protein levels in the soluble EPS fraction were consistently higher during IA than CA across all GSBRs. Aeration regimes had contrasting effects on EPS polysaccharides, as TMP dose increased; polysaccharide content increased during IA and decreased during CA. During CA, TMP presence enhanced dehydrogenase activity to over five times that of the control, while during IA, activity remained stable despite TMP addition. Overall, biomass under IA showed greater tolerance to TMP stress than CA, as evidenced by enhanced granulation, stable dehydrogenase activity, and preserved EPS. Full article

This study aimed to create a unique WPI film formulation that would help maintain strawberry quality. Therefore, an edible coating from WPI was developed, and its physical, mechanical, and rheological characteristics were analysed. WPI is a biopolymer residue with attractive barrier characteristics, biodegradability, and neutral taste that can be used as an edible coating on fragile fruits such as strawberries. Key innovations from this research include a comprehensive evaluation of whey as the sole polymeric component in edible coatings for strawberries, assessing its standalone protective potential; improvement of film formulation based on whey proportion; and an inferred shelf-life extension of whey-coated strawberries aligned with commercial acceptability standards, bridging the gap between research and practical application. This study showed that increasing protein proportion reduced the film’s solubility from 47.6% to 22.4%, thus enhancing its water resistance by up to 2-fold. Still, the film became tensile stiffer and more elastic modulus at 50% RH than at 70% RH. The filmogenic solution’s viscosity enhanced from 2.25 at 25 °C to 4.19 Pa.sⁿ at 4 °C, indicating homogeneous coating of the fruit surface at room temperature and its adhesion at storage temperature. During cold storage, WPI coating reduced the mass loss of strawberries from a range of 5.83–16.71% in the control to a range of 2.56–13.22%, thus decreasing the mass loss by up to 2-fold compared to uncoated fruit from the control treatment, which resulted in better visual quality and a 33% extension of the shelf life of commercial strawberries. Overall, WPI films and coatings have the potential to offer a sustainable and effective protective layer for highly perishable and delicate fruits, extending shelf life and, consequently, reducing waste. Together, these properties can revolutionise the fresh produce industry to enhance global supply chain efficiency. Full article

The SARS-CoV-2 pandemic caused tremendous loss of life and long-term health effects for many. The virus continues to evolve, and new variants have the potential to cause widespread physical and economic impacts. Long-chain carboxylic acids featuring two conjugated acetylenes midway along the chain easily self-assemble onto various substrates, particularly polyvinylidene fluoride, and then polymerize to form a deep blue film. COVID-19 nucleocapsid or spike protein antibodies can be conjugated to the film, and upon exposure to appropriate trigger proteins, they turn pink or red. Certain additives commonly found in commercial preparations of COVID-19 proteins can trigger false positives. The addition of small amounts of surfactants can increase detector sensitivity, though this must be carefully controlled to avoid false positives. Sensing systems based on both nucleocapsid and ACE2 antibodies can detect authentic samples of the virus in human saliva. The platform is readily adaptable to antibodies from new variants. Full article

Background/Objectives: Subunit vaccines composed of purified proteins and adjuvants offer excellent safety, but often generate short-lived immunity due to rapid antigen clearance and limited antigen-presenting cell engagement. Sustained, localized delivery of antigen and adjuvant may improve the magnitude and durability of the immune response without compromising safety. This study evaluated an in-situ polymerizing type I oligomeric collagen (Oligomer) scaffold to localize antigen/adjuvant at the injection site and prolong antigen presentation. Methods: Mice were immunized intramuscularly with ovalbumin (OVA) and CpG oligonucleotide adjuvant delivered alone or co-formulated with Oligomer. Antibody response and inflammation at the injection site were assessed post-booster at early (Day 32) and late (Day 68) time points. Antigen retention and dendritic cell trafficking to draining lymph nodes were evaluated using fluorescently labeled OVA. Results: The Oligomer scaffold retained vaccine antigen at the injection site without eliciting a material-mediated foreign body response. Co-delivery of OVA and CpG within the scaffold enhanced germinal center activity, increased follicular helper T cells and germinal center B cells, and skewed CD4⁺ T cells toward a Th1 phenotype. Humoral responses were greater and more durable, with higher OVA-specific IgG, IgG1, and IgG2a titers and an increased number of bone marrow antibody-secreting cells persisting through Day 68. Antigen-positive dendritic cells, including both resident and migratory subsets, were elevated in draining lymph nodes, indicating enhanced antigen transport. No anti-mouse collagen I antibodies were detected, confirming the maintenance of collagen self-tolerance. Conclusions: The Oligomer delivery platform functioned as a localized, immunotolerant vaccine depot, sustaining antigen availability and immune cell engagement. This spatiotemporal control enhanced germinal center responses and generated a more robust, durable humoral immune response, supporting its potential to improve subunit vaccine efficacy while maintaining an excellent safety profile. Full article

Polymeric micelles are widely studied as nanocarriers for hydrophobic drugs, yet their structural stability under physiological conditions remains a major limitation. This review provides a comparative evaluation of synthetic and natural polymeric micelles with a focus on their stability under dilution and in protein-rich environments. The discussion integrates thermodynamic and kinetic factors governing micelle integrity and examines how molecular composition, hydrophobic segment length, and core–shell modifications influence disintegration behavior. While synthetic micelles commonly collapse below their critical micelle concentration during intravenous administration, natural polymeric micelles, such as those derived from chitosan, alginate, or heparin, exhibit improved resistance to dilution but remain vulnerable to protein-induced destabilization. Strategies such as core or shell cross-linking, surface functionalization, and natural polymer coatings are reviewed as promising approaches to enhance circulation stability and controlled drug release. The work provides a framework for designing micellar systems with balanced biocompatibility, biodegradability, and robustness suitable for clinical drug-delivery applications. Full article

Strain-promoted azide–alkyne cycloaddition (SPAAC) is widely used in solution-phase bioconjugation. However, its application in surface chemistry remains limited because substrate-independent azide films that remain stable upon reaction with bulky strained alkynes have not yet been developed. In this study, we address this challenge using a melanin-inspired coating based on tyrosine–azide derivatives with different linkers. In particular, we investigated how differences in linker length and hydrophilicity affect the hydrophobic interactions within the film network and, ultimately, determine film stability. Specifically, Tyr-3-N₃, a tyrosine–azide derivative having an azide group tethered to tyrosine through a short three-carbon alkyl linker, was identified as optimal, forming azide-presenting films via tyrosinase-mediated oxidation and retaining integrity during SPAAC with external dibenzocyclooctyne (DBCO) ligands. The optimized poly(Tyr-3-N₃) coatings enabled efficient methoxypolyethylene glycol (mPEG) immobilization, thereby exhibiting excellent antifouling performance against protein adsorption, and further supported spatially controlled protein patterning through soft lithography techniques such as micromolding in capillaries (MIMIC) and microcontact printing (µCP). The approach was broadly applicable with a range of inorganic and polymeric substrates, as well as living cell surfaces; even after encapsulation and SPAAC-based functionalization, the cells remained viable. Collectively, these findings establish a substrate-independent and biocompatible coating platform that preserves film stability through SPAAC functionalization, supporting applications in antifouling coatings, biosensing, and cell surface engineering. Full article