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Background: The liver, a central organ in human metabolism, is often the primary target for drugs. However, conditions such as viral hepatitis, cirrhosis, non-alcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC) present substantial health challenges worldwide. Existing treatments, which suffer from the non-specific distribution of drugs, frequently fail to achieve desired efficacy and safety, risking unnecessary liver harm and systemic side effects. Purpose: The aim of this review is to synthesise the latest progress in the design of liver-targeted prodrugs, with a focus on passive and active targeting strategies, providing new insights into the development of liver-targeted therapeutic approaches. Methods: This study conducted an extensive literature search through databases like Google Scholar, PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI), systematically collecting and selecting recent research on liver-targeted prodrugs. The focus was on targeting mechanisms, including the Enhanced Permeability and Retention (EPR) effect, the unique microenvironment of liver cancer, and active targeting through specific transporters and receptors. Results: Active targeting strategies achieve precise drug delivery by binding specific ligands to liver surface receptors. Passive targeting takes advantage of the EPR effect and tumour characteristics to enrich drugs in liver tumours. The review details successful cases of using small molecule ligands, peptides, antibodies and nanoparticles as drug carriers. Conclusion: Liver-targeted prodrug strategies show great potential in enhancing the efficacy of drug treatment and reducing side effects for liver diseases. Future research should balance the advantages and limitations of both targeting strategies, focusing on optimising drug design and targeting efficiency, especially for clinical application. In-depth research on liver-specific receptors and the development of innovative targeting molecules are crucial for advancing the field of liver-targeted prodrugs. [ABSTRACT FROM AUTHOR]

Word-representable graphs were introduced in 2008 by Kitaev and Pyatkin in the context of semigroup theory. Graphs are called word-representable if there exists a word with the graph's nodes as letters such that the letters in the word alternate iff there is an edge between them in the graph. Until today numerous works investigated the word-representability of graphs but mostly from the graph perspective. In this work, we change the perspective to the words, i.e., we take classes of words and investigate the represented graphs. Our first subject of interest are the conjugates of words: we determine exactly which graphs are represented if we rotate the word. Afterwards, we look at k-local words introduced by Day et al. (FSTTCS LIPIcs, 2017) in order to gain more insights into this class of words. Here, we investigate especially which graphs are represented by 1-local words. Lastly, we prove that the language of all words representing a graph is regular. We were also able to characterise k-representable graphs, solving an open problem. [ABSTRACT FROM AUTHOR]

Abstract3-D multi-faceted, nano-globular PAMAM dendritic skeleton is a highly significant polymer that offers applications in biomedical, industrial, environmental and agricultural fields. This is mainly due to its enhanced properties, including adjustable surface functionalities, biocompatibility, non-toxicity, high uniformity and reduced cytotoxicity, as well as its numerous internal cavities. This trait inspires further exploration and advancements in tailoring approaches. The implementation of deliberate strategic modifications in the morphological characteristics of PAMAM is crucial through chemical and biological interventions, in addition to its therapeutic advancements. Thus, the production of peripheral groups remains a prominent and highly advanced technique in molecular fabrication, aimed at boosting the potential of PAMAM conjugates. Currently, there exist numerous dendritic-hybrid materials, despite the widespread use of PAMAM-conjugated frameworks as drug delivery systems, which are well regarded for their efficacy in enhancing potency through the incorporation of surface functions. This paper provides a comprehensive review of recent progress in the design and assembly of various components of PAMAM conjugates, focusing on their unique formulations. The review encompasses synthetic methodologies, a thorough evaluation of their applicability, and an analysis of their potential functions in the context of Drug Delivery Systems (DDS) in the current period. [ABSTRACT FROM AUTHOR]

Simple Summary: This review highlights the recent advances in the development and application of dual function kinase inhibitors that also bear fluorescent properties (fluorescent kinase inhibitors), thus can be used as theranostics in the field of cancer. This is a rapidly growing field with significant potential for cancer therapy and diagnosis. This work mainly focuses on the key design principles that guide the development of these multifunctional compounds, emphasizing the integration of essential components such as the kinase cytotoxic warhead, the fluorophore, the linkers, and additional modular elements to enhance the efficacy of the final assembled compound. We anticipate this review to propel the advancement of this field by improving the understanding of the design principles and ultimately leading to the development of more effective tools for the concurrent diagnosis and treatment of cancer. Kinase inhibitors are potent therapeutic agents in cancer treatment, but their effectiveness is frequently restricted by the inability to image the tumor microenvironment. To address this constraint, kinase inhibitor–fluorophore conjugates have emerged as promising theranostic agents, allowing for simultaneous cancer diagnosis and treatment. These conjugates are gaining attention for their ability to visualize malignant tissues and concurrently enhance therapeutic interventions. This review explores the design principles governing the development of multimodal inhibitors, highlighting their potential as platforms for kinase tracking and inhibition via bioimaging. The structural aspects of constructing such theranostic agents are critically analyzed. This work could shed light on this intriguing field and provide adequate impetus for developing novel theranostic compounds based on small molecule inhibitors and fluorophores. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the impact of varying ethanol concentrations on the functionality and structure of conjugates of gallic acid (GA) and whey protein isolate (WPI). The solubility, total phenolic content, and sulfhydryl group content of the conjugates significantly decreased with increasing ethanol concentration. The structure of the conjugates was altered as indicated by changes in their infrared and fluorescence spectra. By measuring the emulsification and foaming properties, we found that ethanol improved the functional properties of the conjugates. The study examined the influence of ethanol on the conjugates of polyphenolic compounds with whey protein, broadening the scope of research on protein modification. Furthermore, it provided a scientific basis for the future development of novel functional foods. [ABSTRACT FROM AUTHOR]

Summary: In this study, ultrasound‐assisted covalent binding method, free radical‐induced method, was used to prepare Moringa protein isolate (MPI) – gallic acid conjugates (MPI‐GAC) to examine the improvement of the sonication application. Additionally, the influence of polyphenol conjugation on functional and structural attributes of MPI was assessed thru spectral analysis, scanning electron microscopy, antioxidant activity, emulsification, foaming, and water and oil holding properties. The enhanced value of grafted polyphenol species was observed after introducing ultrasound treatment during free radical mediation process. The structural changes in protein by gallic acid conjugation were confirmed by using FT‐IR which illustrated the modification in MPI‐GAC with modified peak width of the amide‐I band. Scanning electron microscopy also showed a significant difference in the structure of MPI and MPI‐GAC. The grafting of gallic acid onto MPI directed under ultrasound‐assisted conditions conferred distinctive functional characteristics, containing elevated emulsification capacity (51.4 mg mL−1) along with enhanced water and oil holding capacity by 2.07 and 5.11 g g−1, respectively. Furthermore, conjugation also increased the protein solubility 89.3–97.6% and significant trend (68.04–88.06%) of antioxidant capacity was observed by increasing the concentration. The findings of this research work offer new insights on the effective fabrication of MPI‐GAC with multifaceted functionalities, thus broadening the scope and possibilities of high‐value Moringa seed protein. [ABSTRACT FROM AUTHOR]

Microbial infections are the most significant threats to human health, and there has been a recent increase in the number of deaths exclusively attributed to bacterial and fungal infections. The development of biofilms by bacterial and fungal pathogens has been identified as a key adaptive antimicrobial resistance (AMR) mechanism, in addition to intrinsic and extrinsic AMR. Various bioactive molecules have been isolated from marine organisms for use in biofilm therapies. These compounds are structurally complex, biocompatible, and economically viable. Studies have demonstrated that bioactive chemicals obtained from marine sources, marine-bioinspired nanomaterials, and marine polymer-antibiotic conjugates can control the biofilms and virulence factors of microbial pathogens. Microbial infections are major human health issues, and, recently, the mortality rate owing to bacterial and fungal infections has been increasing. In addition to intrinsic and extrinsic antimicrobial resistance mechanisms, biofilm formation is a key adaptive resistance mechanism. Several bioactive compounds from marine organisms have been identified for use in biofilm therapy owing to their structural complexity, biocompatibility, and economic viability. In this review, we discuss recent trends in the application of marine natural compounds, marine-bioinspired nanomaterials, and marine polymer conjugates as possible therapeutic agents for controlling biofilms and virulence factors. We also comprehensively discuss the mechanisms underlying biofilm formation and inhibition of virulence factors by marine-derived materials and propose possible applications of novel and effective antibiofilm and antivirulence agents. [ABSTRACT FROM AUTHOR]

The conjugates of gluten and polyphenols (naringin, hesperetin or curcumin) were produced by alkaline method and the effects of conjugation on physicochemical properties of gluten were investigated in this study. The results show that the conjugates possess lower content of free amino and sulfhydryl groups, and higher molecular mass, which indicate the covalent binding occurred. As compared with corresponding mixtures, the conjugates show lower intensity of the amide A, surface hydrophobicity, intermolecular β-sheets, interfacial and surface tension, as well as higher fluorescence intensity, antiparallel β-sheets and particle size (in the range of 130–150 μm). Furthermore, the conjugates also exhibit better emulsifying and foaming properties, higher storage modulus and lower degradation temperature than native gluten. However, the changes in physicochemical properties of conjugates depend on the type of polyphenols and curcumin-gluten conjugates possess the improved emulsifying, foaming and gelation properties among conjugates, due to their more flexible structure. [ABSTRACT FROM AUTHOR]

A series of twelve conjugates 9a-c, 10a-c, 11a-c, and 12a-c based on naturally occurring neo- and isocryptolepines I and II were synthesized and characterized. The synthetic pathways involved nucleophilic substitution reaction of the preprepared amines 4a-c and 5a-c with 1-(4-bromobutyl)indole derivatives 8a and 8b, respectively, in aprotic solvent under heating. The structures of the synthesized conjugates were elucidated by FTIR, 1H NMR, 13C NMR, and MS spectrometry and showed data consistence with the expected structures. The antiproliferative activity of 9a-c, 10a-c, 11a-c and 12a-c was evaluated against HepG-2 and HCT-116 cancer cell lines using normal cells and reference drug paclitaxel. The screening results revealed that 9b and 9c were the most active conjugates against HepG-2 and HCT-116 cancer cell lines with IC50: 8.49, 9.52, 16.87, 21.75 µM, respectively, using paclitaxel as a reference drug. It is worth noting that 9b and 9c were more selective toward cancer cells versus normal Vero cells. To rationalize the anticancer activity and selectivity of 9b and 9c, we have performed molecular docking study against human topoisomerases I and II for better understanding of their anticancer activities in atomic level. Molecular docking studies revealed that the presence of planar indoloquinoline fused four rings and a flexible side chain pharmacophores together improve DNA-intercalation and inhibition of DNA-Topo isomerases activity. [ABSTRACT FROM AUTHOR]

As per the World Health Organization (WHO), antimicrobial resistance (AMR) is a natural phenomenon whereby microbes develop or acquire genes that render them resistant. The rapid emergence and spread of this phenomenon can be attributed to human activity specifically, the improper and excessive use of antimicrobials for the treatment, prevention, or control of infections in humans, animals, and plants. As a result of this factor, many antibiotics have reduced effectiveness against microbes or may not work fully. Thus, there is a pressing need for the development of new antimicrobial agents in order to counteract antimicrobial resistance. Metallic nanoparticles (MNPs) are well known for their broad antimicrobial properties. Consequently, the use of MNPs with current antibiotics holds significant implications. MNPs, including silver nanoparticles (AgNPS), zinc oxide nanoparticles (ZnONPs), copper nanoparticles (CuNPs), and gold nanoparticles (AuNPs), have been extensively studied in conjunction with antibiotics. However, their mechanism of action is still not completely understood. The interaction between these MNPs and antibiotics can be either synergistic, additive, or antagonistic. The synergistic effect is crucial as it represents the desired outcome that researchers aim for and can be advantageous for the advancement of new antimicrobial agents. This article provides a concise and academic description of the recent advancements in MNP and antibiotic conjugates, including their mechanism of action. It also highlights their possible use in the biomedical field and major challenges associated with the use of MNP–antibiotic conjugates in clinical practice. [ABSTRACT FROM AUTHOR]

Viral diseases of potatoes are among the main problems causing deterioration in the quality of tubers and loss of yield. The growth and development of potato plants largely depend on soil moisture. Prevention strategies require comprehensive protection against pathogens and abiotic stresses, including modeling the beneficial microbiome of agroecosystems combining microorganisms and immunostimulants. Chitosan and its derivatives have great potential for use in agricultural engineering due to their ability to induce plant immune responses. The effect of chitosan conjugate with caffeic acid (ChCA) in combination with Bacillus subtilis 47 on the transcriptional activity of PR protein genes and changes in the proteome of potato plants during potato virus Y (PVY) infection and drought was studied. The mechanisms of increasing the resistance of potato plants to PVY and lack of moisture are associated with the activation of transcription of genes encoding PR proteins: the main protective protein (PR-1), chitinase (PR-3), thaumatin-like protein (PR-5), protease inhibitor (PR-6), peroxidase (PR-9), and ribonuclease (PR-10), as well as qualitative and quantitative changes in the plant proteome. The revealed activation of the expression of marker genes of systemic acquired resistance and induced systemic resistance under the influence of combined treatment with B. subtilis and chitosan conjugate indicate that, in potato plants, the formation of resistance to viral infection in drought conditions proceeds synergistically. By two-dimensional electrophoresis of S. tuberosum leaf proteins followed by MALDI-TOF analysis, 10 proteins were identified, the content and composition of which differed depending on the experiment variant. In infected plants treated with ChCA, the synthesis of proteinaceous RNase P 1 and oxygen-evolving enhancer protein 2 was enhanced in conditions of normal humidity, and 20 kDa chaperonin and TMV resistance protein N-like was enhanced in conditions of lack of moisture. The virus coat proteins were detected, which intensively accumulated in the leaves of plants infected with potato Y-virus. ChCA treatment reduced the content of these proteins in the leaves, and in plants treated with ChCA in combination with Bacillus subtilis, viral proteins were not detected at all, both in conditions of normal humidity and lack of moisture, which suggests the promising use of chitosan derivatives in combination with B. subtilis bacteria in the regulation of plant resistance. [ABSTRACT FROM AUTHOR]

Plant proteins are promising sources of nutrition with enhanced health benefits due to their interaction with bioactive compounds like polyphenols. These interactions can form protein–polyphenol complexes with diverse properties and applications in the food, nutraceutical, and pharmaceutical industries. To exploit the potential of these conjugates, it is essential to understand how they are formed, characterized, and delivered. Various techniques such as spectroscopy, thermodynamics, and molecular docking simulations can reveal the mechanism and outcomes of protein–polyphenol binding. Moreover, the surface modification of protein–polyphenol conjugation can enhance the pharmacological effects of different drug molecules and enable their targeted delivery to specific tissues and organs. This review focuses on the systematic design and application of plant-based protein–polyphenol conjugates in diverse food systems and therapeutic interventions, with a focus on their antioxidation, anticancer, anti-allergy, anti-inflammatory, and antidiabetic effects. Additionally, the review aims to provide a comprehensive understanding of the binding mechanisms, conformational changes, and functional properties of these conjugates. The review brings forth the importance of exploring the intricate interplay between plant proteins and polyphenols, unlocking their potential in fostering sustainable and healthier food systems as well as versatile and effective drug delivery systems for human health. [ABSTRACT FROM AUTHOR]

Some properties of σ-convex functions are studied. Then some relations between the notions of σ-subdifferentials and σ-convex functions are established. Also, we present some results regarding the sum formula for the σ-subdifferential. Moreover, we obtain some particular relationships between the σ-subdifferential and the $ (\sigma,y) $ (σ , y) -conjugate. Finally, by imposing some assumptions on f and σ, the maximal $ 2\sigma $ 2 σ -monotonicity of σ-subdifferential is studied. Indeed, the maximality of the usual Fenchel subdifferentials of lower semicontinuous convex functions follows from our result. [ABSTRACT FROM AUTHOR]

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The interactions between proteins and chlorogenic acid (CGA) have gained significant attention in recent years, not only as a promising approach to modify the structural and techno-functional properties of proteins but also to enhance their bioactive potential in food systems. These interactions can be divided into covalent (chemical or irreversible) and non-covalent (physical or reversible) linkages. Mechanistically, CGA forms covalent bonds with nucleophilic amino acid residues of proteins by alkaline, free radical, and enzymatic approaches, leading to changes in protein structure and functionality, such as solubility, emulsification properties, and antioxidant activity. In addition, the protein–CGA complexes can be obtained by hydrogen bonds, hydrophobic and electrostatic interactions, and van der Waals forces, each offering unique advantages and outcomes. This review highlights the mechanism of these interactions and their importance in modifying the structural, functional, nutritional, and physiological attributes of animal- and plant-based proteins. Moreover, the potential applications of these protein–CGA conjugates/complexes are explored in various food systems, such as beverages, films and coatings, emulsion-based delivery systems, and so on. Overall, this literature review provides an in-depth overview of protein–CGA interactions, offering valuable insights for future research to develop novel protein-based food and non-food products with improved nutritional and functional characteristics. [ABSTRACT FROM AUTHOR]

Proteins and polysaccharides are two essential biopolymers, each with unique functional properties. Proteins are known for their foaming, emulsifying, and gelling abilities but often face stability and solubility challenges, making them sensitive to environmental factors like light, temperature, and pH. In contrast, polysaccharides are known for their solubility and strong mechanical properties. When combined, these biopolymers demonstrate enhanced functional characteristics, a phenomenon known as synergy, which opens up various opportunities in the nutraceutical, pharmaceutical, and food industries. This review explores the interactions between proteins and polysaccharides through both covalent and non-covalent bonds. It examines how these biopolymers respond to external conditions such as temperature, pH, humidity, pressure, and salt concentration. Additionally, it briefly addresses how variations in concentration, ratios, and types within the biopolymers influence protein-polysaccharide interactions. Moreover, protein-polysaccharide complexes are extensively utilized in various applications that involve both sophisticated and conventional treatments including gamma irradiation, high-pressure processing, microwave heating, UV radiation, electron beam irradiation, pulsed electric fields, fermentation, and ultrasonication. Therefore, studying their behaviour and changes in interactions under different treatments is crucial. This review offers a brief overview of how these interactions are affected by various treatment processes.

Conjugates of chlorins with β‐cyclodextrin connected either directly or via a flexible linker were prepared. In aqueous medium these amphiphilic conjugates were photostable, produced singlet oxygen at a rate similar to clinically used temoporfin and formed irregular nanoparticles via aggregation. Successful loading with the chemotherapeutic drug tamoxifen was evidenced in solution by the UV‐Vis spectral changes and dynamic light scattering profiles. Incubation of MCF‐7 cells with the conjugates revealed intense spotted intracellular fluorescence suggestive of accumulation in endosome/lysosome compartments, and no dark toxicity. Incubation with the tamoxifen‐loaded conjugates revealed also practically no dark toxicity. Irradiation of cells incubated with empty conjugates at 640 nm and 4.18 J/cm2 light fluence caused >50 % cell viability reduction. Irradiation following incubation with tamoxifen‐loaded conjugates resulted in even higher toxicity (74 %) indicating that the produced reactive oxygen species had triggered tamoxifen release in a photochemical internalization (PCI) mechanism. The chlorin‐β‐cyclodextrin conjugates displayed less‐lasting effects with time, compared to the corresponding porphyrin‐β‐cyclodextrin conjugates, possibly due to lower tamoxifen loading of their aggregates and/or their less effective lodging in the cell compartments' membranes. The results suggest that further to favorable photophysical properties, other parameters are important for the in vitro effectiveness of the photodynamic systems. [ABSTRACT FROM AUTHOR]

Small molecules are significant risk factors for causing food safety issues, posing serious threats to human health. Sensitive screening for hazards is beneficial for enhancing public security. However, traditional detection methods are unable to meet the requirements for the field screening of small molecules. Therefore, it is necessary to develop applicable methods with high levels of sensitivity and specificity to identify the small molecules. Aptamers are short−chain nucleic acids that can specifically bind to small molecules. By utilizing aptamers to enhance the performance of recognition technology, it is possible to achieve high selectivity and sensitivity levels when detecting small molecules. There have been several varieties of aptamer target recognition techniques developed to improve the ability to detect small molecules in recent years. This review focuses on the principles of detection platforms, classifies the conjugating methods between small molecules and aptamers, summarizes advancements in aptamer−based conjugate recognition techniques for the detection of small molecules in food, and seeks to provide emerging powerful tools in the field of point−of−care diagnostics. [ABSTRACT FROM AUTHOR]

MXenes are two-dimensional transition metal carbides, nitrides, and carbonitrides that have become important materials in nanotechnology because of their remarkable mechanical, electrical, and thermal characteristics. This review emphasizes how crucial MXene conjugates are for several biomedical applications, especially in the field of cancer. These two-dimensional (2D) nanoconjugates with photothermal, chemotherapeutic, and photodynamic activities have demonstrated promise for highly effective and noninvasive anticancer therapy. MXene conjugates, with their distinctive optical capabilities, have been employed for bioimaging and biosensing, and their excellent light-to-heat conversion efficiency makes them perfect biocompatible and notably proficient nanoscale agents for photothermal applications. The synthesis and characterization of MXenes provide a framework for an in-depth understanding of various fabrication techniques and their importance in the customized formation of MXene conjugates. The following sections explore MXene-based conjugates for nanotheranostics and demonstrate their enormous potential for biomedical applications. Nanoconjugates, such as polymers, metals, graphene, hydrogels, biomimetics, quantum dots, and radio conjugates, exhibit unique properties that can be used for various therapeutic and diagnostic applications in the field of cancer nanotheranostics. An additional layer of understanding into the safety concerns of MXene nanoconjugates is provided by detailing their toxicity viewpoints. Furthermore, the review concludes by addressing the opportunities and challenges in the clinical translation of MXene-based nanoconjugates, emphasizing their potential in real-world medical practices. [ABSTRACT FROM AUTHOR]

Biobased natural polymers, including polymers of natural origin such as casein, are growing rapidly in the light of the environmental pollution caused by many mass‐produced commercial synthetic polymers. Although casein has interesting intrinsic properties, especially for the food industry, numerous chemical reactions have been carried out to broaden the range of its properties, most of them preserving casein's nontoxicity and biodegradability. New conjugates and graft copolymers have been developed especially by Maillard reaction of the amine functions of the casein backbone with the aldehyde functions of sugars, polysaccharides, or other molecules. Carried out with dialdehydes, these reactions lead to the cross‐linking of casein giving three‐dimensional polymers. Acylation and polymerization of various monomers initiated by amine functions are also described. Other reactions, far less numerous, involve alcohol and carboxylic acid functions in casein. This review provides an overview of casein‐based conjugates and graft copolymers, their properties, and potential applications. [ABSTRACT FROM AUTHOR]

Elastin is a functional protein of the dermal extracellular matrix and a critical component of skin wound healing. In severe wounds, skin cells do not produce enough elastin; therefore, the ability to transfer elastin to tissue is highly advantageous. This study aims to develop and characterize the bovine elastin/tannic acid (E/T) conjugate for wound healing applications. A simple conjugation method between the extracted bovine elastin (E) and tannic acid (T) was applied herein. The developed E/T conjugate showed the best binding efficiency besides controlled delivery of T content up to 7 days in acidic, alkaline, and aqueous media. The E/T conjugate exhibited great T content stability when stored at 40 °C for 60 days. The incorporation of T into E significantly improved the moisture, swelling, and solubility properties of the E/T conjugate. The micro-morphological study of the E/T conjugate confirmed the deposition of T on E fibers, whereas FTIR spectra of the E/T conjugate demonstrated the interaction between E and T functional groups. Markedly improved thermal stability was demonstrated for E/T conjugate over native E via thermogravimetric analysis. In vivo studies on Wistar rats demonstrated that the E/T conjugate considerably impacts the wound closure rate, scar disappearance, and acceleration of the wound healing process compared to the native E. According to these findings, the newly developed E/T conjugate can be used as a potential biomedical product in wound healing applications. [ABSTRACT FROM AUTHOR]

Mucosal vaccines are highly attractive due to high patient compliance and their suitability for mass immunizations. However, all currently licensed mucosal vaccines are composed of attenuated/inactive whole microbes, which are associated with a variety of safety concerns. In contrast, modern subunit vaccines use minimal pathogenic components (antigens) that are safe but typically poorly immunogenic when delivered via mucosal administration. In this study, we demonstrated the utility of various functional polymer-based nanostructures as vaccine carriers. A Group A Streptococcus (GAS)-derived peptide antigen (PJ8) was selected in light of the recent global spread of invasive GAS infection. The vaccine candidates were prepared by either conjugation or physical mixing of PJ8 with rod-, sphere-, worm-, and tadpole-shaped polymeric nanoparticles. The roles of nanoparticle shape and antigen conjugation in vaccine immunogenicity were demonstrated through the comparison of three distinct immunization pathways (subcutaneous, intranasal, and oral). No additional adjuvant or carrier was required to induce bactericidal immune responses even upon oral vaccine administration. [ABSTRACT FROM AUTHOR]

Numerous types of oligonucleotide modifications have been developed since automated synthesis of DNA/RNA became a common instrument in the creation of synthetic oligonucleotides. Despite the growing number of types of oligonucleotide modifications under development, only a few of them and, moreover, their combinations have been studied widely enough in terms of their influence on the properties of corresponding NA constructions. In the present study, a number of oligonucleotides with combinations of 3′-end lipophilic (a single cholesteryl or a pair of dodecyl residues) and phosphate backbone modifications were synthesized. The influence of the combination of used lipophilic groups with phosphate modifications of various natures and different positions on the efficiency of cell penetration was evaluated. The obtained results indicate that even a couple of phosphate modifications are able to affect a set of oligonucleotide properties in a complex manner and can remarkably change cellular uptake. These data clearly show that the strategy of using different patterns of modification combinations has great potential for the rational design of oligonucleotide structures with desired predefined properties. [ABSTRACT FROM AUTHOR]

Dendritic architectures have potential use as excellent carriers for drug delivery due to their multifunctionality, biopermeability, and biodegradability properties. Furthermore, their conjugation with non‐steroidal anti‐inflammatory drugs (NSAIDs) results in a synergetic effect improving their anticancer activity. Here we report the synthesis and cytotoxic activity of novel Janus dendrimer conjugates with naproxen and mefenamic acid moieties at the periphery. Diethanolamine dendrons were convergently synthesized through a protection‐deprotection sequence with naproxen as a terminal group and finally coupled to triethylene glycol as a linker. On the other hand, mefenamic acid was covalently joined to the L‐lysine. The dendron and dendrimer‐conjugates with naproxen and mefenamic acid showed high inhibition and selectivity against PC‐3 (human prostatic adenocarcinoma), and K‐562 (human chronic myelogenous leukemia) cell lines, but low cytotoxicity against normal cell lines. To explain the molecular mechanisms involved in the anticancer activity of dendrimer conjugates, our research will be continued. [ABSTRACT FROM AUTHOR]

Viral diseases of potatoes are among the main problems causing deterioration in the quality of tubers and loss of yield. The growth and development of potato plants largely depend on soil moisture. Prevention strategies require comprehensive protection against pathogens and abiotic stresses, including modeling the beneficial microbiome of agroecosystems combining microorganisms and immunostimulants. Chitosan and its derivatives have great potential for use in agricultural engineering due to their ability to induce plant immune responses. The effect of chitosan conjugate with caffeic acid (ChCA) in combination with Bacillus subtilis 47 on the transcriptional activity of PR protein genes and changes in the proteome of potato plants during potato virus Y (PVY) infection and drought was studied. The mechanisms of increasing the resistance of potato plants to PVY and lack of moisture are associated with the activation of transcription of genes encoding PR proteins: the main protective protein (PR-1), chitinase (PR-3), thaumatin-like protein (PR-5), protease inhibitor (PR-6), peroxidase (PR-9), and ribonuclease (PR-10), as well as qualitative and quantitative changes in the plant proteome. The revealed activation of the expression of marker genes of systemic acquired resistance and induced systemic resistance under the influence of combined treatment with B. subtilis and chitosan conjugate indicate that, in potato plants, the formation of resistance to viral infection in drought conditions proceeds synergistically. By two-dimensional electrophoresis of S. tuberosum leaf proteins followed by MALDI-TOF analysis, 10 proteins were identified, the content and composition of which differed depending on the experiment variant. In infected plants treated with ChCA, the synthesis of proteinaceous RNase P 1 and oxygen-evolving enhancer protein 2 was enhanced in conditions of normal humidity, and 20 kDa chaperonin and TMV resistance protein N-like was enhanced in conditions of lack of moisture. The virus coat proteins were detected, which intensively accumulated in the leaves of plants infected with potato Y-virus. ChCA treatment reduced the content of these proteins in the leaves, and in plants treated with ChCA in combination with Bacillus subtilis, viral proteins were not detected at all, both in conditions of normal humidity and lack of moisture, which suggests the promising use of chitosan derivatives in combination with B. subtilis bacteria in the regulation of plant resistance.

The analytical applications of antibodies are often associated with their immobilization on different carriers, which is accompanied by a loss of antigen-binding activity for a sufficient proportion of the bound antibodies. In contrast to data on plain carriers, minimal data are available on the properties of antibodies on the surfaces of nanoparticles. Protein antigens have been predominantly investigated, for which space restrictions do not allow them to occupy all active sites of immobilized antibodies. This study considered a low-molecular-weight compound, fluorescein, as an antigen. Spherical gold nanoparticles with five different sizes, two differently charged forms of fluorescein, and three different levels of surface coverage by immobilized antibodies were tested. For gold nanoparticles with diameters from 14 to 35.5 nm with monolayers of immobilized antibodies, the percentage of molecules capable of binding carboxyfluorescein varied from 6% to 17%. The binding of aminofluorescein was more efficient; for gold nanoparticles with an average diameter of 21 nm, the percentage of active binding sites for the immobilized antibodies reached 27% compared with 13% for the carboxyfluorescein case. A fourfold reduction in the coverage of the nanoparticles' surface compared with that of the monolayer did not lead to reliable changes in the percentage of active binding sites. The obtained data demonstrate that an antigen's binding to immobilized antibodies is limited even for small antigens and depends on the size of the nanoparticles and the electrostatic repulsion near their surface. [ABSTRACT FROM AUTHOR]

A series of new conjugates of tacrine with ethyl 2-aminomethylidene-3-oxobutanoate with a spacer length of 4, 6, and 8 methylene groups was synthesized. The synthesized conjugates were shown to be effective inhibitors of acetylcholinesterase (IC50 up to 0.143 µmol L−1) and butyrylcholinesterase (IC50 up to 0.024 µmol L−1), with the inhibitory activity increasing with the spacer elongation. The new conjugates, as their diethyl malonate analogs, demonstrated a potential ability to block the AChE-induced β-amyloid aggregation and inhibited the self-aggregation of β-amyloid (1–42) with maximum activity at the level of the standard compound myricetin for derivatives with the octamethylene spacer. For the lead compound, a conjugate of tacrine with ethyl 2-aminomethylidene-3-oxobutanoate with the (CH2)8 spacer, the ability to bind the biometal ions CuII, FeII and ZnII was also demonstrated. The obtained characteristics indicated the synthesized conjugates as promising multitarget agents for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

α-mangostin (AM) is a promising natural anticancer agent that can be used in cancer research. However, its effectiveness can be limited by poor solubility and bioavailability. To address this issue, chitosan-based nanoparticles (CSNPs) have been investigated as a potential delivery system to enhance the cytotoxicity to cancer cells and improve selectivity against normal cells. In this study, we developed folate-conjugated chitosan nanoparticles (F-CS-NPs) using a carbodiimide-based conjugation method to attach folate to chitosan (CS), which have different molecular weights. The NPs were crosslinked using tripolyphosphate (TPP) via ionic gelation. To characterize the F-CS-NPs, we utilized various analytical techniques, including transmission electron microscopy (TEM) to evaluate the particle size and morphology, Fourier-transform infrared spectroscopy (FTIR) to confirm the presence of functional groups, and ultraviolet-visible spectroscopy (UV-Vis) to measure the absorption spectrum and confirm the presence of folate. The particle size of AM-F-CS-NPs ranged from 180 nm to 250 nm, with many having favorable charges ranging from +40.33 ± 3.4 to 10.69 ± 1.3 mV. All NPs exhibited the same spherical morphology. The use of F-CS-NPs increased drug release, followed by a sustained release pattern. We evaluated the cytotoxicity of AM, AM-F-CS-HMW, and AM-F-CS-LMW NPs against MCF-7 cells and found IC50 values of 8.47 ± 0.49, 5.3 ± 0.01, and 4.70 ± 0.11 µg/mL, respectively. These results confirm the improved cytotoxicity of AM in MCF-7 cells when delivered via F-CS-NPs. Overall, our in vitro study demonstrated that the properties of F-CS-NPs greatly influence the cytotoxicity of AM in MCF-7 breast cancer cells (significantly different (p < 0.05)). The use of F-CS-NPs as a drug-delivery system for AM may have the potential to develop novel therapies for breast cancer. [ABSTRACT FROM AUTHOR]

The evolution of a physical system occurs through a set of variables, and the problems can be treated based on an approach employing multivariable Hermite polynomials. These polynomials possess beneficial properties exhibited in functional and differential equations, recurring and explicit relations as well as symmetric identities, and summation formulae, among other examples. In view of these points, comprehensive schemes have been developed to apply the principle of monomiality from mathematical physics to various mathematical concepts of special functions, the development of which has encompassed generalizations, extensions, and combinations of other functions. Accordingly, this paper presents research on a novel family of multivariable Hermite polynomials associated with Frobenius–Genocchi polynomials, deriving the generating expression, operational rule, differential equation, and other defining characteristics for these polynomials. Additionally, the monomiality principle for these polynomials is verified, as well as establishing the series representations, summation formulae, operational and symmetric identities, and recurrence relations satisfied by these polynomials. This proposed scheme aims to provide deeper insights into the behavior of these polynomials and to uncover new connections between these polynomials, to enhance understanding of their properties. [ABSTRACT FROM AUTHOR]

Cold plasma technology is gaining attention as a promising approach to enhancing the bioactivity of plant extracts. However, its impact on green coffee bean extracts (GCBEs) still needs to be explored. In this study, an innovative underwater plasma jet system was employed to investigate the effects of cold plasma on Coffea arabica GCBEs, focusing on the conjugation reflected by the change in composition and bioactivity. The DPPH radical scavenging antioxidant activity exhibited a gradual increase with plasma treatment up to 35 min, followed by a decline. Remarkably, at 35 min, the plasma treatment resulted in a significant 66% increase in the DPPH radical scavenging activity of the GCBE. The total phenolic compound content also displayed a similar increasing trend to the DPPH radical scavenging activity. However, the phenolic profile analysis indicated a significant decrease in chlorogenic acids and caffeine. Furthermore, the chemical composition analysis revealed a decrease in free amino acids, while sucrose remained unchanged. Additionally, the SDS-PAGE results suggested a slight increase in protein size. The observed enhancement in antioxidant activity, despite the reduction in the two major antioxidants in the GCBE, along with the increase in protein size, might suggest the occurrence of conjugation processes induced by plasma, particularly involving proteins and phenolic compounds. Notably, the plasma treatment exhibited no adverse effects on the extract's safety, as confirmed by the MTT assay. These findings indicate that cold plasma treatment holds significant promise in improving the functional properties of GCBE while ensuring its safety. Incorporating cold plasma technology into the processing of natural extracts may offer exciting opportunities for developing novel and potent antioxidant-rich products. [ABSTRACT FROM AUTHOR]

Lipophilic oligonucleotide conjugates represent a powerful tool for nucleic acid cellular delivery, and many methods for their synthesis have been developed over the past few decades. In the present study, a number of chemical approaches for the synthesis of different fork- and comb-like dodecyl-containing oligonucleotide structures were performed, including use of non-nucleotide units and different types of phosphate modifications such as alkyl phosphoramidate, phosphoryl guanidine, and triazinyl phosphoramidate. The influence of the number of introduced lipophilic residues, their mutual arrangement, and the type of formed modification backbone on cell penetration was evaluated. The results obtained indicate great potential in the developed chemical approaches, not only for the synthesis of complex oligonucleotide structures but also for the fine-tuning of their properties. [ABSTRACT FROM AUTHOR]

Purpose: modeling of experimental antibiotic-resistant endophthalmitis on laboratory animals model describing the interaction of quantum dots and a biological organism and its physicochemical and kinetic aspects.Material and methods. The object of the study is laboratory New Zealand rabbits (2 male, age 4 months, weight 3.5 kg). The inflammation inductor is the culture of Methicillin-Resistant Staphylococcus Aureus (MRSA). 1 mg/0.05 ml of vancomycin in combination with 0.5 μg (0.01 %)/0.05 ml by a solution of quantum dots InP/ZnSe/ZnS 660 was intravitreally administrated to the first rabbit. 1 mg/0.1 ml of vancomycin was intravitreally administrated to the second rabbit. Dynamic observation of the clinical process was performed daily by photo registration of the front segment and ultrasonic sonography.Results. The conjugate based on 1 mg/0.05 ml vancomycin coupled with 0.5 μg (0.01 %)/0.05 ml quantum dots InP/ZnSe/ZnS 660 demonstrated high anti-infectious activity against vancomycin-resistant MRSA. It was shown that the effect of the above solution on MRSA is described by the one-time ability of quantum dots by using electron microscopy. The presence of superoxide radicals O2–• generation in an aqueous solution of quantum dots under the action of blue light has also been proven by spectrophotometric method.Conclusion. Conjugates based on quantum dots can be considered as one of the promising directions of treatment of antibiotic-resistant endophthalmitis.

The interactions between proteins and chlorogenic acid (CGA) have gained significant attention in recent years, not only as a promising approach to modify the structural and techno-functional properties of proteins but also to enhance their bioactive potential in food systems. These interactions can be divided into covalent (chemical or irreversible) and non-covalent (physical or reversible) linkages. Mechanistically, CGA forms covalent bonds with nucleophilic amino acid residues of proteins by alkaline, free radical, and enzymatic approaches, leading to changes in protein structure and functionality, such as solubility, emulsification properties, and antioxidant activity. In addition, the protein–CGA complexes can be obtained by hydrogen bonds, hydrophobic and electrostatic interactions, and van der Waals forces, each offering unique advantages and outcomes. This review highlights the mechanism of these interactions and their importance in modifying the structural, functional, nutritional, and physiological attributes of animal- and plant-based proteins. Moreover, the potential applications of these protein–CGA conjugates/complexes are explored in various food systems, such as beverages, films and coatings, emulsion-based delivery systems, and so on. Overall, this literature review provides an in-depth overview of protein–CGA interactions, offering valuable insights for future research to develop novel protein-based food and non-food products with improved nutritional and functional characteristics.

Small molecules are significant risk factors for causing food safety issues, posing serious threats to human health. Sensitive screening for hazards is beneficial for enhancing public security. However, traditional detection methods are unable to meet the requirements for the field screening of small molecules. Therefore, it is necessary to develop applicable methods with high levels of sensitivity and specificity to identify the small molecules. Aptamers are short−chain nucleic acids that can specifically bind to small molecules. By utilizing aptamers to enhance the performance of recognition technology, it is possible to achieve high selectivity and sensitivity levels when detecting small molecules. There have been several varieties of aptamer target recognition techniques developed to improve the ability to detect small molecules in recent years. This review focuses on the principles of detection platforms, classifies the conjugating methods between small molecules and aptamers, summarizes advancements in aptamer−based conjugate recognition techniques for the detection of small molecules in food, and seeks to provide emerging powerful tools in the field of point−of−care diagnostics.

This study is based on the premise of investigating antibacterial activity through a novel conjugate of silver nanoparticles (AgNPs) and antimicrobial peptides (AMPs) in line with a green synthesis approach by developing antimicrobial-coated implants to prevent bacterial resistance. The AMPs were obtained from Bellamya Bengalensis (BB), a freshwater snail, to prepare the nanocomposite conjugate, e.g., AgNPs@BB extract, by making use of UV-Visible spectroscopy. The antimicrobial assessment of AgNPs@BB extract conjugate was performed using the Resazurin Microtiter Assay Method (REMA), followed by the use of three biocompatible implant materials (titanium alloys, Ti 6AL-4V stainless steel 316L, and polyethylene). Finally, the coating was analyzed under confocal microscopy. The results revealed a significant reduction of biofilm formation on the surfaces of implants coated with conjugate (AgNPs@BB extract) in comparison to uncoated implants. For the MTT assay, no significant changes were recorded for the cells grown on the AgNPs/AMP++ sample in high concentrations. Staphylococcus epidermidis, however, showed more prominent growth on all implants in comparison to Staphylococcus aureus. It is evident from the results that Staphylococcus epidermidis is more susceptible to AgNPs@BB extract, while the minimum inhibitory concentration (MIC) value of AgNPs@BB extract conjugates and biosynthesized AgNPs was also on the higher side. This study indicates that AgNPs@BB extract carries antibacterial activity, and concludes that an excessive concentration of AgNPs@BB extract may affect the improved biocompatibility. This study recommends using robust, retentive, and antimicrobial coatings of AgNPs@BB extract for implantable biocompatible materials in accordance with the novel strategy of biomaterial applications. [ABSTRACT FROM AUTHOR]

This study investigated concentration levels of ten bisphenols (BPs) in 13 Chinese commercial fresh low temperature dairy milk samples (fresh milk) of main local and national brands with or without enzyme hydrolysis. The results showed that at least two BPs were detected in each fresh milk sample without enzyme hydrolysis and the respective mean concentrations of bisphenol AF (BPAF), bisphenol B (BPB), bisphenol C (BPC), bisphenol F (BPF), bisphenol A (BPA), bisphenol S (BPS), bisphenol AP (BPAP), bisphenol PP (BPP), bisphenol Z (BPZ), and bisphenol E (BPE) were 0.73, 0.61, 1.86, 0.87, 0.42, 0.11, 1.06, 1.42, 1.5, and 0.04 ng/mL, while their respective detection frequencies ranged from 23.1–92.3%. These results indicated the frequent detection of BPs in fresh milk samples. With enzyme hydrolysis, the respective mean concentrations of BPAF, BPA, BPB, BPC, BPF, BPS, and BPAP were increased 7.1–107.1%, indicating the long-ignored importance of enzyme hydrolysis. The respective average estimated daily intakes (EDIs) of BPA by adult and children in China via fresh milk were 32.5 and 37.5 ng/kg bw/d, indicating that BPA in fresh milk was a crucial source to human. Six out of nine other BPs had higher average EDIs than that of BPA, among which the EDI of BPAP was almost three times that of BPA, suggesting the widespread contamination of other BPs in Chinese fresh milk. [ABSTRACT FROM AUTHOR]

A series of 4-thiazolidinone conjugates bearing quinoline/indole/furan scaffolds were designed as potential anti-breast cancer agents, synthesized, and investigated for their anti-breast cancer, and anti-oxidant activity. The anticancer activity was performed using MTT assay against breast cancer cell lines such as MCF-7 and MDA-MB-231 and the results demonstrated that most of the compounds were sensitive to cancer cell lines. Compounds GT1, GT2 and GT5 showed remarkable potency against MCF-7 cell lines with IC50 values of 11.64 µM, 11.27 µM and 11.37 µM respectively in comparison to standard drug doxorubicin with IC50 value of 11.80 µM. Compounds GT2 and GT5 exerted higher cytotoxic activity against the MDA-MD-231 cell line with IC50 value of 17.60 µM and 15.09 µM respectively than doxorubicin (IC50: 18.35 µM). The anti-oxidant activity was also performed by DPPH and hydrogen peroxide scavenging assay. Compounds GT2 and GT7 showed higher free radical scavenging activity with IC50 value of 11.39 µM and 11.28 µM respectively against DPPH assay and 10.99 µM and 11.20 µM respectively against hydrogen peroxide assay. The molecular docking study was carried out against estrogen receptor alpha (PDB ID: 4IVY) to identify the mechanism of action of synthesized compounds using molecular docking and molecular dynamics simulation. The results showed that compounds GT1, GT2, and GT5 showed higher docking score −110.922 kcal/mol, −124.618 kcal/mol and-116.029 kcal/mol respectively as compared to reference (doxorubicin) drug (-109.847 kcal/mol). The ADME and toxicity profile was predicated by Schrodinger QikProp program. All the synthesized compounds showed no violation of Lipinski's rule except GT2. The molecule insight behavior was predicted by using MD simulation. According to in silico and in vitro studies GT1, GT2, and GT5 showed anti-cancerous activity against MCF-7. [ABSTRACT FROM AUTHOR]

Phytophthora infestans is, worldwide, one of the main causal agents of epiphytotics in potato plantings. Prevention strategies demand integrated pest management, including modeling of beneficial microbiomes of agroecosystems combining microorganisms and natural products. Chitooligosaccharides and their derivatives have great potential to be used by agrotechnology due to their ability to elicit plant immune reactions. The effect of combining Bacillus subtilis 26D and 11VM and conjugates of chitin with hydroxycinnamates on late blight pathogenesis was evaluated. Mechanisms for increasing the resistance of potato plants to Phytophthora infestans were associated with the activation of the antioxidant system of plants and an increase in the level of gene transcripts that encode PR proteins: basic protective protein (PR-1), thaumatin-like protein (PR-5), protease inhibitor (PR-6), and peroxidase (PR-9). The revealed activation of the expression of marker genes of systemic acquired resistance and induced systemic resistance under the influence of the combined treatment of plants with B. subtilis and conjugates of chitin with hydroxycinnamates indicates that, in this case, the development of protective reactions in potato plants to late blight proceeds synergistically, where B. subtilis primes protective genes, and chitosan composites act as a trigger for their expression. [ABSTRACT FROM AUTHOR]

A series of copper(II) complexes with the formula [Cu2+Hy(x)Car%] varying the molecular weight (MW) of Hyaluronic acid (Hy, x = 200 or 700 kDa) conjugated with carnosine (Car) present at different loading were synthesized and characterized via different spectroscopic techniques. The metal complexes behaved as Cu, Zn-superoxide dismutase (SOD1) mimics and showed some of the most efficient reaction rate values produced using a synthetic and water-soluble copper(II)-based SOD mimic reported to date. The increase in the percentage of Car moieties parallels the enhancement of the I50 value determined via the indirect method of Fridovich. The presence of the non-functionalized Hy OH groups favors the scavenger activity of the copper(II) complexes with HyCar, recalling similar behavior previously found for the copper(II) complexes with Car conjugated using β-cyclodextrin or trehalose. In keeping with the new abilities of SOD1 to activate protective agents against oxidative stress in rheumatoid arthritis and osteoarthritis diseases, Cu2+ interaction with HyCar promotes the nuclear translocation of erythroid 2-related factor that regulates the expressions of target genes, including Heme-Oxigenase-1, thus stimulating an antioxidant response in osteoblasts subjected to an inflammatory/oxidative insult. [ABSTRACT FROM AUTHOR]

Disease monitoring in free-ranging wildlife is a challenge and often relies on passive surveillance. Alternatively, proactive surveillance that relies on the detection of specific antibodies could give more reliable and timely insight into disease presence and prevalence in a population, especially if the evidence of disease occurs below detection thresholds for passive surveillance. Primary binding assays, like the indirect ELISA for antibody detection in wildlife, are hampered by a lack of species-specific conjugates. In this study, we developed anti-kudu (Tragelaphus strepsiceros) and anti-impala (Aepyceros melampus) immunoglobulin-specific conjugates in chickens and compared them to the binding of commercially available protein-G and protein-AG conjugates, using an ELISA-based avidity index. The conjugates were evaluated for cross-reaction with sera from other wild herbivores to assess future use in ELISAs. The developed conjugates had a high avidity of >70% against kudu and impala sera. The commercial conjugates (protein-G and protein-AG) had significantly low relative avidity (<20%) against these species. Eighteen other wildlife species demonstrated cross-reactivity with a mean relative avidity of >50% with the impala and kudu conjugates and <40% with the commercial conjugates. These results demonstrate that species-specific conjugates are important tools for the development and validation of immunoassays in wildlife and for the surveillance of zoonotic agents along the livestock-wildlife-human interface. [ABSTRACT FROM AUTHOR]

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Proteins act as a primary food component obtained from different food sources. In contrast, polyphenols are metabolites and are abundantly present in plants, so their combination plays a crucial role in defining the functional properties of a food product. In the current review, the protein-polyphenol interactions have been briefly reviewed, along with the changes that occur because of their interaction. The mechanisms and the factors affecting the functionalities of the protein-polyphenol conjugates, e.g., the solubility, antioxidant, and gelling properties, have also been briefly reviewed. In addition, the interaction of polyphenols with whey proteins was been reviewed with various applications within the food industry, e.g., emulsifiers, foaming agents, and antioxidants. To end the review, future challenges were also highlighted.

Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide synthesized via the activity of the ATP-dependent enzyme carnosine synthetase 1 and can be found at a very high concentration in tissues with a high metabolic rate, including muscles (up to 20 mM) and brain (up to 5 mM). Because of its well-demonstrated multimodal pharmacodynamic profile, which includes anti-aggregant, antioxidant, and anti-inflammatory activities, as well as its ability to modulate the energy metabolism status in immune cells, this dipeptide has been investigated in numerous experimental models of diseases, including Alzheimer's disease, and at a clinical level. The main limit for the therapeutic use of carnosine is related to its rapid hydrolysis exerted by carnosinases, especially at the plasma level, reason why the development of new strategies, including the chemical modification of carnosine or its vehiculation into innovative drug delivery systems (DDS), aiming at increasing its bioavailability and/or at facilitating the site-specific transport to different tissues, is of utmost importance. In the present review, after a description of carnosine structure, biological activities, administration routes, and metabolism, we focused on different DDS, including vesicular systems and metallic nanoparticles, as well as on possible chemical derivatization strategies related to carnosine. In particular, a basic description of the DDS employed or the derivatization/conjugation applied to obtain carnosine formulations, followed by the possible mechanism of action, is given. To the best of our knowledge, this is the first review that includes all the new formulations of carnosine (DDS and derivatives), allowing a decrease or complete prevention of the hydrolysis of this dipeptide exerted by carnosinases, the simultaneous blood–brain barrier crossing, the maintenance or enhancement of carnosine biological activity, and the site-specific transport to different tissues, which then offers perspectives for the development of new drugs. [ABSTRACT FROM AUTHOR]