The global emergence of monkeypox virus (MPXV) has created an urgent need for effective vaccines that induce robust immune responses. Here, we report a biomimetic nano-vaccine platform based on engineered dendritic cell membrane vesicles displaying M1R (M1R-CMVs), designed via genetic engineering with machine learning-assisted preliminary screening of physicochemical parameters including particle size (∼190 nm) and zeta potential (-18 mV). Subcutaneous delivery of M1R-CMVs with CpG adjuvant induced high titers of M1R-specific IgG and potent neutralizing antibodies. The vaccine promoted broad T cell activation, characterized by enhanced CD4+ and CD8+ T cell responses in spleen and lymph nodes, and established durable T cell memory. In vitro studies demonstrated that M1R-CMVs enhance dendritic cell maturation and T cell proliferation. Prime-boost immunization further amplified both humoral and cellular immunity, with significant increases in neutralizing antibody titers and effector T cell populations. Furthermore, the vaccine exhibited a favorable safety profile in vivo with no significant toxicity observed. Our findings demonstrate a biomimetic vaccine design strategy integrating engineered vesicles with machine learning-assisted physicochemical analysis, providing a promising approach to combat monkeypox.
Cancer cachexia affects up to 80 % of advanced cancer patients and contributes to significant mortality. Impaired wound healing in cachectic patients limits physical activity, leads to nutrient loss, and increases infection risk. This study develops multifunctional hydrogels composed of oxidized polysaccharides (TPS) from Radix Trichosanthis and carboxymethyl chitosan (termed CMOT) to enhance wound healing and mitigate scar hyperplasia. TPS, characterized by its immunomodulatory properties, was oxidized to create aldehyde derivatives (oTPS1 and oTPS2) with varying oxidation levels and crosslinked with carboxymethyl chitosan through Schiff base reactions to form hydrogels (CMOT1 and CMOT2). It indicates the ability to tailor the rheological and mechanical properties of CMOT hydrogels through controlled oxidation and cross-linking. These hydrogels exhibited excellent self-healing properties, biocompatibility, and immunoregulatory effects on macrophages and T lymphocytes. Notably, CMOT2 hydrogel, with higher aldehyde content, exhibited superior mechanical properties, enhanced water retention, and slower degradation than CMOT1, consequently, accelerating wound healing in cancer cachexia conditions and reducing scar hyperplasia. The therapeutic mechanisms were associated with promoting angiogenesis, collagen synthesis, and epithelial repair, while down-regulating En-1. It not only addresses the challenges of wound healing in cancer cachexia but also offers a potential therapeutic strategy for scar hyperplasia inhibition.
Leaves of Fagopyrum esculentum Moench were selected for their rich content of phytochemicals, offering potential biological activities. The aqueous residual fraction (AF) exhibited higher extraction yield (17.5%) compared with the other fractions. The highest content of phenols and flavonoids (84.27 ± 2.7 mg/g GAE and 42.57 ± 2.1 mg/g QUE, respectively) was found in AF among the different extracts. AF also showed the strong antioxidant properties (IC50 of DPPH: 61.43 ± 0.58 µg/mL; FRAP: 38.14 ± 0.59 µM Fe equivalents) and anti-inflammatory activity (IC50 = 69.87 ± 1.26 µg/mL). Furthermore, the α-amylase inhibition activity range varied from 19.39 ± 2.11to 55.35 ± 1.11% with an IC50 value of 40.59 ± 0.03 µg/mL, compared with standard metformin (IC50 = 19.88 ± 91.51 µg/mL). AF demonstrated significantly increased glucose uptake, range varied from 4.10 ± 2.32% to 60.30 ± 1.21%. AF are deemed non-toxic, as they preserve cell viability (HEK293) significantly above the IC50 threshold, with 75% of cells still viable at ≤ 10 µg/mL. LC-MS study of F. esculentum identified six major compounds (syringetin, pyrazinamide, glutaconic acid, 3-sulfolactic acid, gallic acid and kaempferol). Molecular docking study of kaempferol glucagon-like peptide-1 (GLP-1) showed good binding energies and interactions. Hence, F. esculentum possesses potential antidiabetic, antioxidant and cytotoxic activities.
This paper examines the performance of feed concentrates based on bovine skin collagen and their effect on fish feeding efficiency.Because of research, it was possible to obtain a protein concentrate containing up to 50 and 70%.When these concentrates are added to fish feed for 10%, it was observed that they have a positive effect on the growth of fish, and it was found that the concentrates have no side effects on the parenchymatous organs of fish.
А method has been developed for extracting modified pectin from plant raw materials by using microwave radiation at the stage of washing. The rheological properties of 5.0% aqueous solutions of apple PV obtained by exposure to microwave radiation of various powers: 300, 450 and 600 W, as well as PV obtained by the traditional method at temperatures of 25, 40, 55, 70 °C were investigated. It is shown that the use of microwave radiation makes it possible to improve the method of obtaining pectins with the possibility of increasing the yield of pectin substances and regulating their structure and properties. The rheological properties of concentrated aqueous solutions of pectins obtained by exposure to microwave radiation of various powers have been studied. It is shown, that all the studied systems of PV solutions are non-Newtonian fluids with a pseudoplastic type of viscous flow anomaly, determined by the values of the microwave energy. The values of the apparent activation energies of the viscous flow of solutions, which are an indirect characteristic of the strength of the structures of the system, have been estimated. Information was obtained on the structure and changes in the structure of their concentrated solutions under the action of external forces and temperature in the course of a viscous flow. It is shown that the power values оf microwave radiation are the main factor determining the structure of molecular matrices of pectin substances and the structure of their concentrated aqueous solutions.
As a result of the study, branched polysaccharides were isolated from the basidiomycete raw materials of Ganoderma lucidum. It has been established that the isolated fractions contain branched polysaccharides in the form of complexes with melanin. After purification of polysaccharides by ion-exchange chromatography, two fractions were obtained from basidial raw materials: neutral polysaccharides GW-1 with a yield of 25.71% and anionic polysaccharides GW-2, the yield of which was 5.26%, respectively. The physicochemical properties of the obtained samples were studied by IR and UV spectroscopy. The degree of purity of the obtained fractions of branched polysaccharides was established. Using gas chromatography, one-dimensional (13C NMR, 1H NMR) and two-dimensional (COSY, TOCSY, HSQC, HMBC, NOESY) NMR spectroscopy, the composition and molecular structure of the obtained polysaccharide samples were determined. The results showed that the isolated and purified polysaccharides are branched glucans with 1,4,6- and 1,3,6-bonds between glucopyranose units. Pharmacotoxicological studies were carried out on white outbred mice and it was found that the resulting polysaccharides belong to class V, practically non-toxic compounds (LD50 ≥ 2000 mg/kg). Isolated polysaccharides (GW) are promising biologically active components, on the basis of which it is possible to create drugs with hepatoprotective and antitumor activity.
Peroral administration to mice of melanin isolated from horse chestnut (Aesculus hippocastanum L.) seed shells as an aqueous solution (10%) at doses of 2000, 2500, 3000, 4000, and 5000 mg/kg produced no symptoms of acute toxicity in all experimental animals. The mortality corresponded to class VI relatively harmless compounds (LD50 > 5000 mg/kg). Melanin administered intragastrically at doses of 0.5 and 5.0 mg/kg had an induced effect on humoral immunity. The maximum effectiveness was manifested at a dose of 5.0 mg/kg, where the content of antibody-forming cells in the spleen increased by 4.1 times and was 1.7 times greater than that induced by Immunal. Melanin at the studied doses reliably stimulated the formation of a clone of antigen-specific T-lymphocytes and had a stimulating effect on central and peripheral immunity organs, increasing the number of nucleated cells of the thymus by a maximum of 2.8 times; of the spleen, by 1.7 times; and of the lymph nodes, by 5.7 times, like Immunal.
The article focused on a study of the release of melanin from its gel dosage form and the toxicological properties of the gel. The recorded release of melanin from the gel was fastest during the first 3 h (50.8
The results of the development of a technology for the isolation of melanins from the basidiomycete mushroom Bovista plumbea collected in the territory of Tashkent and the Tashkent region of the Republic of Uzbekistan are presented. A technological scheme for obtaining melanins from basidiomycetes has been developed, which includes the following stages: drying, grinding of raw materials, purification, water extraction, filtration, concentration, acidification, centrifugation, dissolution, washing, drying. By water extraction, melanins were isolated, which are dark brown, alkali-soluble powder, with a molecular weight of 55686 Da, the content of which in the extract was 15.35%, respectively, which indicates the prospects of this type of raw material for obtaining drugs based on them. When studying the elemental composition of melanins obtained from the fruiting bodies of basidiomycetes by the method of water extraction, it was found that they contain 9.706% nitrogen, 55.831% carbon and 7.203% hydrogen. UV and IR spectroscopy was used to confirm that the obtained samples belonged to the category of melanins. The IR spectra of melanin isolated from the fruiting body of the basidiomycete were studied. Melanins are characterized by absorption bands in the region of 1690-1590 cm-1, indicating the presence of conjugated aromatic bonds in their structure. There is also a wide absorption band in the region of 3430-3100 cm-1, which is due to the presence of polyphenolic and OH groups. UV spectral analysis for the content of melanin in fractions of basidiomycete raw materials showed the presence of absorption bands in the region of 320-380 nm, corresponding to the characteristic absorption bands of melanin.
Viruses transmitted through the respiratory tract tend to have short incubation periods and are highly contagious, thus being one of the main triggers of acute respiratory illnesses. Vaccines are important tools for reducing viral infections and preventing serious illness, hospitalization, and death. However, vaccines are still not widely accessible in some areas, particularly in low-income countries, because of limited production capacity and inadequate medical personnel, resulting in high morbidity and mortality rates during pandemics. Therefore, there is an urgent need for the development of vaccines that can be rapidly manufactured and self-administered in response to pandemics caused by respiratory-transmitted viruses. In this work, we developed an inhalable vaccine platform consisting of antigen-engineered cell membrane vesicles (CMVs) and cholesterolized CpG anchoring to the vesicle surface to establish an “all-in-one” vaccine platform (antigen/CpG-CMVs), which could induce mucosal immunity upon oropharyngeal inhalation to protect against viral infections in the respiratory tract. Its antigen, adjuvant, and particle size can be adjusted as needed through gene editing, cholesterol modification, and extrusion process, respectively. The lyophilized antigen/CpG-CMVs can be distributed without cold-chain transportation and can be self-administered by inhalation upon reconstitution. We found that this inhalable “all-in-one” vaccine induced not only systemic immunity but also mucosal immunity in the respiratory tract, as reflected by the enhanced levels of systemic immunoglobulin G (IgG) and respiratory secreted immunoglobulin A (sIgA). This work may validate engineered cell membrane vesicles as an inhalable vaccine platform and a promising avenue for future vaccine development to protect against pandemics.
Smart designs beyond the limitations of the biosensors present fascinating opportunities for portable, flexible, versatile, and effective performance that allow for the rapid in-vivo, and real-time detection of potential targets. Conjugated polythiophenes (CPTs) are particularly valuable as biosensors because of their remarkable brightness, excellent photostability, and low toxicity. CPTs potentially molecularly self-assemble using an imprinted method resulting in imprinted conjugated polythiophenes (ICPTs). ICPTs combined the distinctive characteristics of CPTs with the excellent selectivity arising from robustly particular binding sites of molecular imprinting. ICPT-based biomimetic sensors represent a specialized subset within this extensive field. An overview of various types of CPT-based sensors was described to achieve a systematic analysis. These included biosensors based on printing technologies, microfluidic systems, film transistors, colorimetric methods, and electrochemical approaches. Additionally, we discussed the optical-electrical properties, and sub-types of polythiophene derivatives examining their specific applications and advantages in biosensor technology. The final section provided an in-depth exploration of the imprinted techniques employed in developing ICPTs-based sensors, with particular emphasis on applications in biochemical sensing.
Branched polysaccharides have been isolated from basidiomycete raw materials of locally growing and cultivated Ganoderma lucidum . It has been found that the isolated fractions contain branched polysaccharides in the form of complexes with melanin. After purification of polysaccharides by ion exchange chromatography from locally growing and cultivated basidial raw materials, two fractions have been obtained: neutral polysaccharides of locally growing Ganoderma lucidum (GW-1), cultivated Ganoderma lucidum (GWL-1) with a yield of 25.71 and 29.85%, respectively, and anionic polysaccharides of locally growing Ganoderma lucidum (GW-2), cultivated Ganoderma lucidum (GWL-2), with a yield of 5.26 and 4.19%. The physicochemical properties of the obtained samples have been studied by IR and UV spectroscopies. The purity degree of fractions of branched polysaccharides has been determined. Using gas chromatography, one-dimensional ( 13 C NMR, 1 H NMR), and two-dimensional (COSY, TOCSY, HSQC, HMBC, NOESY) NMR spectroscopies, the compositions and molecular structures of the obtained polysaccharide samples have been determined. The results showed that the isolated and purified polysaccharides are β-glucan-type branched polysaccharides that have branch point (1,4,6)- and (1,3,6)-linked glucopyranose residues.
Paper-based surface-enhanced Raman scattering (SERS) optical nanoprobes provide ultrasensitive analyte detection; however, they lack selectivity, making them difficult to use in real-world sample analysis without a pretreatment process. This work describes the design of a microfluidic paper-based SERS substrate based on molecularly imprinted nanogels decorated with silver nanoparticles to simultaneously detect bisphenol A (BPA) and bisphenol S (BPS) traces in plastic toys and receipts. The synthesized nanogels have two characteristics that boost SERS performance: molecularly imprinted cavities that allow for selective adsorption and a wrinkled surface that creates uniformly distributed hot spots. Simple paper-based sensor devices were built as 'drop and read' SERS substrates with a separate reservoir to detect a single target, while advanced SERS platforms were designed as a microfluidic chip with two reservoirs connected by a channel for simultaneous detection of BPA and BPS. The SERS platform with a single reservoir showed outstanding analytical performance for the detection of BPA and BPS, with low detection limits of 0.38 pM and 0.37 pM, respectively. The microfluidic paper-based sensor allowed simultaneous and selective detection of BPA and BPS with detection limits estimated at 0.68 nM and 0.47 nM, respectively. The developed sensors are successfully applied to detect BPA and BPS in plastic products and receipts. Finally, the results obtained with our method showed greater sensitivity than those of commercially available ELISA kits, and the acquired values within the ELISA detection range were in excellent agreement.
Sodium cellulose sulfates were prepared in various degrees of substitution (DS) and degree of polymerization (DP) by directly sulfating cotton and microcrystalline cellulose. Molecular parameters of the prepared samples were characterized using elemental analysis, IR spectroscopy, and 13C NMR spectroscopy techniques. The antibacterial activities of the sodium cellulose sulfates were assayed against both gram-negative and gram-positive bacteria. The study examined the dependence of antimicrobial properties on molecular weight (Mw) and DS. The samples showed DS- and DP-dependent antibacterial activity against both gram-negative and gram-positive pathogenic microorganisms. Samples with DS ≥2.0 exhibited the highest antibacterial activity, indicating the presence of sulfate groups in C-2 and/or C-3 carbon atoms in cellulose anhydroglucose unit (AGU) induces the antibacterial activity. Additionally, SCS samples with DP around 340 showed the highest antibacterial activity against all species of bacteria. The mechanism of antimicrobial effect of SCS derivatives is most likely directed at the destruction of bacterial membranes.
The article presents the results of the compatibility of collagen and Na-CMC at various ratios. The study of the structure of the biopolymer composition collagen/Na-CMC/glycerol showed their full compatibility. For the first time, films were obtained from a collagen/Na-CMC/glycerol solution in an aqueous medium, which simplifies the technology for obtaining medicinal films and improves their bioavailability. Using electron microscopy and viscometric studies, the optimal ratio of collagen and Na-CMC 70/30 was chosen, at which materials with strength and viscosity suitable for the formation of a film material were obtained. The optimal concentration of the plasticizer glycerin – 17% – was selected and the physicochemical properties of the films were studied. It has been established that with a decrease in the concentration of glycerol below 17%, the elastic properties of the film deteriorate; an increase in the concentration of more than 17% does not improve the elasticity of the film, but leads to an overuse of the plasticizer. As a result of double plasticization, it is possible to obtain films with good plasticity, which is achieved due to the good compatibility of glycerol with Na-CMC. The microstructure of the films was studied by atomic force microscopy. It has been established that when Na-CMC and glycerol are added to the collagen mass in the established ratios, the uniformity of the films is observed due to the loosening of the collagen microstructure. The biological efficiency of the obtained films was evaluated under the conditions of the development of adhesions in laboratory animals in vivo. The results of the study of anti-adhesion activity indicate the high efficiency of the developed P-3 film for preventing adhesion formation after surgical interventions.
The presence of reactive aldehyde groups in the elementary units of dialdehyde polysaccharides enables to enter easily into a condensation reaction with reagents containing primary amino groups in the structure. This naturally expands the possibilities of obtaining new derivatives of polysaccharides with physiologically active properties. In this study, we synthesized azomethine derivatives of cellulose and pectin differing in the degree of substitution and the content of the nucleophilic reagent in the composition of the reaction products through chemical interaction of guanidine with macromolecules of dialdehyde polysaccharides. Therefore, regularities of the reaction of nucleophilic substitution of aldehyde groups of oxidized polysaccharides with guanidine were revealed. It was found that the interaction of guanidine amino groups with oxidized pectin in contrast to dialdehyde cellulose occurs through the formation of azomethine and ionic bonds. Moreover, the possibility of obtaining guanidine-containing derivatives of cellulose and pectin with different structural characteristics by varying the molar ratio of the nucleophile and the oxidation state of the starting polysaccharides was proved. The composition and structure of the reaction products were studied by physicochemical methods of analysis. The stability and rate of cleavage of guanidine groups from the macromolecules of dialdehyde cellulose and dialdehyde pectin were studied by hydrolysis of the synthesized samples in acidic and alkaline media.
Introduction. Up to the present time, there are practically no studies on the relationship between the structural characteristics and biological activity of antimicrobial polymers synthesized by the chemical addition of guanidine groups to polysaccharide macromolecules. Therefore, there is a need to carry out the chemical modification of guanidine with natural polymers, in particular polyaldehyde pectin, and to conduct comparative studies of the antimicrobial activity of the obtained samples with different physicochemical characteristics.Aim. To conduct the synthesis of guanidine-containing pectin derivatives. In addition, to determine the influence of structural variations in the obtained samples on exhibiting antimicrobial properties.Materials and methods. The synthesis of guanidine-containing pectin derivatives consisted of the following stages: periodate oxidation of the polysaccharide, modification of guanidine using polyaldehyde pectin, and chemical reduction of azomethine bonds. The amount of guanidine in the obtained samples was calculated by acidimetric titration, the nitrogen content (N, %) was determined using a Eura EA (Italy) elemental analyzer. The рКα values of the synthesized compounds were found by the back titration method. Absorption spectra were analyzed on a "UV 1280" spectrophotometer (Shimadzu, Japan) in the range λ = 180–400 nm. IR spectra were recorded on a Vector-22 spectrometer in the wavelength range of 400–4000 cm-1 in KBr tablets (3 mg sample / 300 mg KBr). The molecular weight characteristics of the synthesized derivatives were determined by high-performance gel permeation chromatography on an Agilent 1260 Infiniti liquid chromatograph. The acute toxicity of guanidine-containing pectin derivatives was calculated by the Prozorovsky method. Comparative assessment of antimicrobial activity was conducted by agar diffusion method.Results and discussion. By varying the oxidation level of polyaldehyde pectin, synthesized compounds differ in the degree of substitution, guanidine content, molecular weight, and pKα value. It was found that the levels of the antibacterial and antifungal activity of the studied samples depend on the degree of substitution and the nature of the counterion. The antimicrobial effect increases with an increase in the quantitative content of guanidine groups in the macromolecular chain of pectin. Moreover, it was found that the change of low molecular weight Cl–, NO3– , F–, I– counterions by carboxylate anions leads to a sharp decrease in antimicrobial properties. Upon oral injection of the synthesized compounds to mice, it was found that all samples belong to the category of practically non-toxic substances (V-class).Conclusion. Comparative analysis of guanidine-containing pectin derivatives with different characteristics showed that the severity of the antimicrobial action of the synthesized compounds against bacteria and fungi of the genus Candida depends on the quantitative content of cationic groups and the nature of the counterion.