In recent times mucoadhesive drug delivery systems are gaining popularity in oral cancer. It is a malignancy with high global prevalence. Despite significant advances in cancer therapeutics, improving the prognosis of late-stage oral cancer remains challenging. Targeted therapy using mucoadhesive polymers can improve oral cancer patients' overall outcome by offering enhanced oral mucosa bioavailability, better drug distribution and tissue targeting, and minimizing systemic side effects. Mucoadhesive polymers can also be delivered via different formulations such as tablets, films, patches, gels, and nanoparticles. These polymers can deliver an array of medicines, making them an adaptable drug delivery approach. Drug delivery techniques based on these mucoadhesive polymers are gaining traction and have immense potential as a prospective treatment for late-stage oral cancer. This review examines leading research in mucoadhesive polymers and discusses their potential applications in treating oral cancer.

The development of subunit vaccine platforms has been of considerable interest due to their good safety profile and ability to be adapted to new antigens, compared to other vaccine typess. Nevertheless, subunit vaccines often lack sufficient immunogenicity to fully protect against infectious diseases. A wide variety of subunit vaccines have been developed to enhance antigen immunogenicity by increasing antigen multivalency, as well as stability and delivery properties, via presentation of antigens on protein nanoparticles. Increasing multivalency can be an effective approach to provide a potent humoral immune response by more strongly engaging and clustering B cell receptors (BCRs) to induce activation, as well as increased uptake by antigen presenting cells and their subsequent T cell activation. Proper orientation of antigen on protein nanoparticles is also considered a crucial factor for enhanced BCR engagement and subsequent immune responses. Therefore, various strategies have been reported to decorate highly repetitive surfaces of protein nanoparticle scaffolds with multiple copies of antigens, arrange antigens in proper orientation, or combinations thereof. In this review, we describe different chemical bioconjugation methods, approaches for genetic fusion of recombinant antigens, biological affinity tags, and enzymatic conjugation methods to effectively present antigens on the surface of protein nanoparticle vaccine scaffolds.

Coevolution between protein residues is normally interpreted as direct contact. However, the evolutionary record of a protein sequence contains rich information that may include long-range functional couplings, couplings that report on homo-oligomeric states or even conformational changes. Due to the complexity of the sequence space and the lack of structural information on various members of a protein family, it has been difficult to effectively mine the additional information encoded in a multiple sequence alignment (MSA). Here, taking advantage of the recent release of the AlphaFold (AF) database we attempt to identify coevolutionary couplings that cannot be explained simply by spatial proximity. We propose a simple computational method that performs direct coupling analysis on a MSA and searches for couplings that are not satisfied in any of the AF models of members of the identified protein family. Application of this method on 2012 protein families suggests that ~12% of the total identified coevolving residue pairs are spatially distant and more likely to be disordered than their contacting counterparts. We expect that this analysis will help improve the quality of coevolutionary distance restraints used for structure determination and will be useful in identifying potentially functional/allosteric cross-talk between distant residues.

In this study, effective transport of small interfering RNAs (siRNAs) via hyaluronic acid (HA) receptor was carried out with biodegradable HA and low-molecular weight polyethyleneimine (PEI)-based transport systems. Gold nanoparticles (AuNPs) capable of giving photothermal response, and their conjugates with PEI and HA, were also added to the structure. Thus, a combination of gene silencing, photothermal therapy and chemotherapy, has been accomplished. The synthesized transport systems ranged in size, between 25 and 690 nm. When the particles were applied at a concentration of 100 μg mL-1 (except AuPEI NPs) in vitro, cell viability was above 50%. Applying radiation after the conjugate/siRNA complex (especially those containing AuNP) treatment, increased the cytotoxic effect (decrease in cell viability of 37%, 54%, 13%, and 15% for AuNP, AuPEI NP, AuPEI-HA, and AuPEI-HA-DOX, respectively) on the MDA-MB-231 cell line. CXCR4 gene silencing via the synthesized complexes, especially AuPEI-HA-DOX/siRNA was more efficient in MDA-MB-231 cells (25-fold decrease in gene expression) than in CAPAN-1 cells. All these results demonstrated that the synthesized PEI-HA and AuPEI-HA-DOX conjugates can be used as siRNA carriers that are particularly effective, especially in the treatment of breast cancer.

Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional DNA repair protein localized in different subcellular compartments. The mechanisms responsible for the highly regulated subcellular localization and "interactomes" of this protein are not fully understood but have been closely correlated to the posttranslational modifications in different biological context. In this work, we attempted to develop a bio-nanocomposite with antibody-like properties that could capture APE1 from cellular matrices to enable the comprehensive study of this protein. By fixing the template APE1 on the avidin-modified surface of silica-coated magnetic nanoparticles, we first added 3-aminophenylboronic acid to react with the glycosyl residues of avidin, followed by addition of 2-acrylamido-2-methylpropane sulfonic acid as the second functional monomer to perform the first step imprinting reaction. To further enhance the affinity and selectivity of the binding sites, we carried out the second step imprinting reaction with dopamine as the functional monomer. After the polymerization, we modified the nonimprinted sites with methoxypoly (ethylene glycol) amine (mPEG-NH2 ). The resulting molecularly imprinted polymer-based bio-nanocomposite showed high affinity, specificity, and capacity for template APE1. It allowed for the extraction of APE1 from the cell lysates with high recovery and purity. Moreover, the bound protein could be effectively released from the bio-nanocomposite with high activity. The bio-nanocomposite offers a very useful tool for the separation of APE1 from various complex biological samples.

The regulation of the biodegradation rate of 3D-regenerated silk fibroin scaffolds and the avoidance of premature collapse are important concerns for their effective applications in tissue engineering. In this study, bromelain, which is specific to sericin, was used to remove sericin from silk, and high molecular weight silk fibroin was obtained after the fibroin fibers were dissolved. Afterwards, a 3D scaffold was prepared via freeze-drying. The Sodium dodecyl sulfate-polyacrylamide gel electrophoresis results showed that the average molecular weight of the regenerated silk fibroin prepared by using the bromelain-degumming method was approximately 142.2 kDa, which was significantly higher than that of the control groups prepared by using the urea- and Na2 CO3 -degumming methods. The results of enzyme degradation in vitro showed that the biodegradation rate and internal three-dimensional structure collapse of the bromelain-degumming fibroin scaffolds were significantly slower than those of the two control scaffolds. The proliferation activity of human umbilical vein vascular endothelial cells inoculated in bromelain-degumming fibroin scaffolds was significantly higher than that of the control scaffolds. This study provides a novel preparation method for 3D-regenerated silk fibroin scaffolds that can effectively resist biodegradation, continuously guide cell growth, have good biocompatibility, and have the potential to be used for the regeneration of various connective tissues.

Mucilage, a polysaccharide-containing hydrogel, is hypothesized to play a key role in the rhizosphere as a self-organized system because it may vary its supramolecular structure with changes in the surrounding solution. However, there is currently limited research on how these changes are reflected in the physical properties of real mucilage. This study examines the role of solutes in maize root, wheat root, chia seed, and flax seed mucilage in relation to their physical properties. Two purification methods, dialysis and ethanol precipitation, were applied to determine the purification yield, cation content, pH, electrical conductivity, surface tension, viscosity, transverse 1 H relaxation time, and contact angle after drying of mucilage before and after purification. The two seed mucilage types contain more polar polymers that are connected to larger assemblies via multivalent cation crosslinks, resulting in a denser network. This is reflected in higher viscosity and water retention ability compared to root mucilage. Seed mucilage also contains fewer surfactants, making them better wettable after drying compared to the two root mucilage types. The root mucilage types, on the other hand, contain smaller polymers or polymer assemblies and become less wettable after drying. However, wettability not only depends on the amount of surfactants but also on their mobility, as well as the strength and mesh size of the network structure. The changes in physical properties and cation composition observed after ethanol precipitation and dialysis suggest that the polymer network of seed mucilage is more stable and specialized in protecting the seeds from unfavorable environmental conditions. In contrast, root mucilage is characterized by fewer cationic interactions and its network relies more on hydrophobic interactions. This allows root mucilage to be more flexible in responding to changing environmental conditions, facilitating nutrient and water exchange between root surfaces and the rhizosphere soil.

EWS is a member of the FET family of RNA/DNA binding proteins that regulate crucial phases of nucleic acid metabolism. EWS comprises an N-terminal low-complexity domain (LCD) and a C-terminal RNA-binding domain (RBD). The RBD is further divided into three RG-rich regions, which flank an RNA-recognition motif (RRM) and a zinc finger (ZnF) domain. Recently, EWS was shown to regulate R-loops in Ewing sarcoma, a pediatric bone and soft-tissue cancer in which a chromosomal translocation fuses the N-terminal LCD of EWS to the C-terminal DNA binding domain of the transcription factor FLI1. Though EWS was shown to directly bind R-loops, the binding mechanism was not elucidated. In the current study, the RBD of EWS was divided into several constructs, which were subsequently assayed for binding to various nucleic acid structures expected to form at R-loops, including RNA stem-loops, DNA G-quadruplexes, and RNA:DNA hybrids. EWS interacted with all three nucleic acid structures with varying affinities and multiple domains contributed to binding each substrate. The RRM and RG2 region appear to bind nucleic acids promiscuously while the ZnF displayed more selectivity for single-stranded structures. With these results, the structural underpinnings of EWS recognition and binding of R-loops and other nucleic acid structures is better understood.

In the CryoEM-structure of the hSkMNaV1.4 ion channel (PDB:6AGF), the 59-residue DIS5-S6 linker peptide was omitted due to absence of electron density. This peptide is intriguing - comprised of unique sequence and found only in mammalian skeletal muscle sodium ion channels. To probe potential physiological and evolutionary significance, we constructed an homology model of the complete hSkMNaV1.4 channel. Rather than a flexible random coil potentiating drift across the channel, the linker folds into a compact configuration through self-assembling secondary structural elements. Analogous sequences from 48 mammalian organisms show hypervariability with between 40% and 100% sequence similarity. To investigate structural implications, sequences from 14 representative organisms were additionally modelled. All showed highly conserved N-and C-terminal residues closely superimposed, suggesting a critical functional role. An optimally located asparagine residue within the conserved region was investigated for N-linked glycosylation and MD simulations carried out. Results suggest a complex glycan added at this site in the linker may form electrostatic interactions with the DIV voltage sensing domain and be mechanistically involved in channel gating. The relationship of unique sequence, compact configuration, potential glycosylation and MD simulations are discussed relative to SkMNaV1.4 structure and function.

In this work, hydrogels based on semi-interpenetrating polymeric networks (semi-IPN) based on collagen-polyurethane-alginate were studied physicochemically and from different approaches for biomedical application. It was determined that the matrices in the hydrogel state are crosslinked by the formation of urea and amide bonds between the biopolymer chains and the polyurethane crosslinker. The increment in alginate content (0-40 wt%) significantly increases the swelling capacity, generating semi-crystalline granular structures with improved storage modulus and resistance to thermal, hydrolytic, and proteolytic degradation. The in vitro bioactivity results indicated that the composition of these novel hydrogels stimulates the metabolic activity of monocytes and fibroblasts, benefiting their proliferation; while in cancer cell lines, it was determined that the composition of these biomaterials decreases the metabolic activity of breast cancer cells after 48 h of stimulation, and for colon cancer cells their metabolic activity decreases after 72 h of contact for the hydrogel with 40 wt% alginate. The matrices show a behavior of multidose release of ketorolac, and a higher concentration of analgesic is released in the semi-IPN matrix. The inhibition capacity of Escherichia coli is higher if the polysaccharide concentration is low (10 wt%). The in vitro wound closure test (scratch test) results indicate that the hydrogel with 20 wt% alginate shows an improvement in wound closure at 15 days of contact. Finally, the bioactivity of mineralization was evaluated to demonstrate that these hydrogels can induce the formation of carbonated apatite on their surface. The engineered hydrogels show biomedical multifunctionality and they could be applied in soft and hard tissue healing strategies, anticancer therapies, and drug release devices.

Bioplastics were developed to overcome environmental problems that are difficult to decompose in the environment. This study analyzes Thai cassava starch-based bioplastics' tensile strength, biodegradability, moisture absorption, and thermal stability. This study used Thai cassava starch and polyvinyl alcohol (PVA) as matrices, whereas Kepok banana bunch cellulose was employed as a filler. The ratios between starch and cellulose are 10:0 (S1), 9:1 (S2), 8:2 (S3), 7:3 (S4), and 6:4 (S5), while PVA was set constant. The tensile test showed the S4 sample's highest tensile strength of 6.26 MPa, a strain of 3.85%, and a modulus of elasticity of 166 MPa. After 15 days, the maximum soil degradation rate in the S1 sample was 27.9%. The lowest moisture absorption was found in the S5 sample at 8.43%. The highest thermal stability was observed in S4 (316.8°C). This result was significant in reducing the production of plastic waste for environmental remediation.