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Polydeoxyribonucleotides (PDRNs) and polynucleotides (PNs) are similar DNA-derived biopolymers that have garnered significant scientific attention since the 1990s for their potential applications in wound healing and skin rejuvenation. These biopolymers exhibit a broad molecular weight (MW) range, typically spanning from 50 to 1500 kDa. However, recent studies have expanded this range to encompass fragments as small as 1 kDa and as large as 10,000 kDa. Clinically, PDRN/PN formulations, commercially available in various galenic forms (gels, creams, serums, masks, and injectables), have demonstrated promising effects in significantly promoting skin regeneration, reducing inflammation, improving skin texture, preventing scar formation, and mitigating wrinkles. Importantly, despite their widespread use in cosmetology and aesthetic dermatology, the interchangeable use of the terms “PDRN” and “PN” in the scientific literature (to describe polymers of varying lengths) has led to considerable confusion within the medical and scientific communities. To specifically address this PDRN/PN ambiguity, this narrative review proposes a standardized structure-based nomenclature for these DNA-derived polymers, the “Marques Polynucleotide Cutoff”, set at 1500 kDa. Thus, we propose that the term “PDRN” should be exclusively reserved for small- and medium-chain polymers (MW < 1500 kDa), while the term “PN” should specifically be used to denote longer-chain polymers (MW ≥ 1500 kDa). In a broader perspective, this classification is based on the distinct physicochemical properties and therapeutic effects of these DNA fragments of various MWs, which are comprehensively discussed in the present review.

Background Dermal fillers have gained widespread popularity for facial cosmetic enhancement and anti‐aging treatments. Recently, polycaprolactone (PCL) and polynucleotides (PN) fillers have emerged as promising options owing to their safety and long‐lasting effects. Objectives This study aimed to compare the efficacy and safety of a novel PCL‐based dermal filler (DLMR01) with purified PN filler (RJR: Rejuran) in correcting crow's feet wrinkles. Materials and Methods A randomized, evaluator‐blinded, prospective split‐face study was conducted with 218 healthy Asian participants. The primary outcome was in the improvement rate of the Crow's Feet Grading Scale (CFGS) at rest after 12 weeks. Secondary outcomes included the improvement rate of the CFGS at expression and rest at earlier time points, changes in CFGS, and the Global Aesthetic Improvement Scale (GAIS) assessment. Results The results showed that DLMR01 was not inferior to RJR in improving crow's feet wrinkles, with a significantly higher CGFS improvement rate at week 12. Both fillers demonstrated good safety profiles, with mild and tolerable adverse events. No serious adverse events were reported during the study period. Conclusion DLMR01, a PCL‐based dermal filler, showed effectiveness and safety in improving wrinkles described as crow's feet. The study suggests that DLMR01 could be a promising option for noninvasive anti‐aging treatments.

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin−1β (IL−1β) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL−1β induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.

Liquid phase separation into two or more coexisting phases has emerged as a new paradigm for understanding subcellular organization, prebiotic life, and the origins of disease. The design principles underlying biomolecular phase separation have the potential to drive the development of novel liquid-based organelles and therapeutics, however, an understanding of how individual molecules contribute to emergent material properties, and approaches to directly manipulate phase dynamics are lacking. Here, using microrheology, we demonstrate that droplets of poly-arginine coassembled with mono/polynucleotides have approximately 100 fold greater viscosity than comparable lysine droplets, both of which can be finer tuned by polymer length. We find that these amino acid-level differences can drive the formation of coexisting immiscible phases with tunable formation kinetics and can be further exploited to trigger the controlled release of droplet components. Together, this work provides a novel mechanism for leveraging sequence-level components in order to regulate droplet dynamics and multiphase coexistence. The design principles underlying biomolecular phase separation of membrane-less organelles remain poorly understood. Using model homopolymers, Fisher et al. show that the formation kinetics of coexisting liquid phases can be tuned by exploiting differences between arginine and lysine residues.

Background Atopic dermatitis (AD) is a chronic inflammatory dermatological disorder characterized by skin barrier dysfunction, dry skin, pruritus, and aberrant immune responses to external stimuli. Although polynucleotides (PNs) have anti‐inflammatory properties, their effect on AD remains unexplored. Materials and Methods This study investigated the effects of PNs on a 2,4‐dinitrochlorobenzene (DNCB)‐induced AD mouse model. The effects were evaluated by the dermatitis severity score (DSS), the spleen index, the serum immunoglobulin E (IgE) concentration, trans‐epidermal water loss (TEWL), histological findings, and the expression levels of cytokine mRNA and filaggrin protein in skin tissue. Results Topical application of PNs significantly reduced the DSS, the spleen index, the serum IgE concentration, and TEWL compared with the control. Additionally, histopathological analysis showed that PNs reduced epidermal and dermal thickness, the mast cell count, collagen deposition, and eosinophil infiltration in the dermis. Moreover, PNs significantly downregulated the expression of key inflammatory cytokines, including interleukin (IL)‐4, IL‐5, IL‐13, IL‐25, IL‐33, and thymic stromal lymphopoietin (TSLP), in affected skin tissue. Immunohistochemical (IHC) staining and Western blot revealed that PNs inhibited DNCB‐induced suppression of filaggrin. A combination of hyaluronic acid (HA) and PNs showed enhanced efficacy compared with PNs alone, particularly for reducing the serum IgE concentration and TEWL and increasing filaggrin expression. Conclusion These results suggest that PNs are potential candidates to treat AD because they possess anti‐inflammatory properties and improve skin barrier function.

Polynucleotides (PN) are becoming more prominent in aesthetic medicine. However, the structural characteristics of PN have not been published and PN from different companies may have different structural characteristics. This study aimed to elucidate the structural attributes of DOT™ PN and distinguish differences with polydeoxyribonucleotides (PDRN) using high-resolution scanning electron microscopy (SEM) imaging. DOT™ PN was examined using a Quanta 3-D field emission gun (FEG) Scanning Electron Microscope (SEM). Sample preparation involved cryogenic cooling, cleavage, etching, and metal coating to facilitate high-resolution imaging. Cryo-FIB/SEM techniques were employed for in-depth structural analysis. PDRN exhibited an amorphous structure without distinct features. In contrast, DOT™ PN displayed well-defined polyhedral shapes with smooth, uniformly thick walls. These cells were empty, with diameters ranging from 3 to 8 micrometers, forming a seamless tessellation pattern. DOT™ PN's distinct geometric tessellation design conforms to the principles of biotensegrity, providing both structural reinforcement and integrity. The presence of delicate partitions and vacant compartments hints at possible uses in the field of pharmaceutical delivery systems. Within the realms of beauty enhancement and regenerative medicine, DOT™ PN's capacity to bolster cell growth and tissue mending could potentially transform approaches to rejuvenation treatments. Its adaptability becomes apparent when considering its contributions to drug administration and surgical procedures. This study unveils the intricate structural scaffold features of DOT™ PN for the first time, setting it apart from PDRN and inspiring innovation in biomedicine and materials science. DOT™ PN's unique attributes open doors to potential applications across healthcare and beyond.

Life as we know it requires three basic types of polymers: polypeptide, polynucleotide, and polysaccharide. Here we evaluate both universal and idiosyncratic characteristics of these biopolymers. We incorporate this information into a model that explains much about their origins, selection, and early evolution. We observe that all three biopolymer types are pre-organized, conditionally self-complementary, chemically unstable in aqueous media yet persistent because of kinetic trapping, with chiral monomers and directional chains. All three biopolymers are synthesized by dehydration reactions that are catalyzed by molecular motors driven by hydrolysis of phosphorylated nucleosides. All three biopolymers can access specific states that protect against hydrolysis. These protected states are folded, using self-complementary interactions among recurrent folding elements within a given biopolymer, or assembled, in associations between the same or different biopolymer types. Self-association in a hydrolytic environment achieves self-preservation. Heterogeneous association achieves partner-preservation. These universal properties support a model in which life’s polymers emerged simultaneously and co-evolved in a common hydrolytic milieu where molecular persistence depended on folding and assembly. We believe that an understanding of the structure, function, and origins of any given type of biopolymer requires the context of other biopolymers.

Apurinic/apyrimidinic (AP) sites are ubiquitous DNA lesions that are highly mutagenic and cytotoxic if not repaired. In addition, clusters of two or more abasic lesions within one to two turns of DNA, a hallmark of ionizing radiation, are repaired much less efficiently and thus present greater mutagenic potential. Abasic sites are chemically labile, but naked DNA containing them undergoes strand scission slowly with a half-life on the order of weeks. We find that independently generated AP sites within nucleosome core particles are highly destabilized, with strand scission occurring ∼60-fold more rapidly than in naked DNA. The majority of core particles containing single AP lesions accumulate DNA—protein cross-links, which persist following strand scission. The N-terminal region of histone protein H4 contributes significantly to DNA—protein cross-links and strand scission when AP sites are produced approximately 1.5 helical turns from the nucleosome dyad, which is a known hot spot for nucleosomal DNA damage. Reaction rates for AP sites at two positions within this region differ by ∼4-fold. However, the strand scission of the slowest reacting AP site is accelerated when it is part of a repair resistant bistranded lesion composed of two AP sites, resulting in rapid formation of double strand breaks in high yields. Multiple lysine residues within a single H4 protein catalyze double strand cleavage through a mechanism believed to involve a templating effect. These results show that AP sites within the nucleosome produce significant amounts of DNA—protein cross-links and generate double strand breaks, the most deleterious form of DNA damage.

Background Polynucleotides (PN), popular in biorevitalization, show promise in the current sphere of esthetic medicine due to their regenerative properties, previously used in wound healing. Currently, research investigates their use in esthetic medicine. The aim of this review was to synthesize the existing literature, focusing on the effectiveness of PN in esthetic medicine, which is concentrated on skin rejuvenation by providing patients with multiple benefits and the least side effects. Methods A systematic electronic search was conducted in Embase, Medline, and Cochrane to identify primary research studies evaluating the effectiveness of polynucleotides in esthetic medicine, published in English between January 01, 2010, and January 01, 2024. A narrative synthesis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. The quality of evidence was assessed using the Critical Appraisal Skills Programme checklists. PROSPERO Registration: CRD42024588712. Results Nine studies, of low and moderate quality, were included in this review, describing a population of 219 patients receiving PN treatment. A variation was present regarding procedural characteristics, such as injection areas and techniques. Polynucleotide injections have shown promising outcomes in reducing wrinkles, improving skin texture, and enhancing elasticity, with statistically significant results in several studies. While side effects are generally mild and transient, patient satisfaction is moderate to high, suggesting PN treatment as a well‐tolerated and effective cosmetic intervention. Conclusion Polynucleotides offer promising potential in esthetic medicine; however, there is limited consensus regarding their optimal use. Rigorous, high‐quality studies are essential to validate the effectiveness and safety of PN.

A study of the fluorescent properties of MB complexes with ss-poly(dA), poly(rU), poly(rA), and poly(dT), as well as hybrid ds-structures poly(rA)-poly(dT) and poly(dA)-poly(rU), was carried out. Based on changes in fluorescence and absorption spectra, it was revealed that this ligand exhibits unequal affinity for homopolynucleotide sequences. Particularly, it was found that MS binds to poly(rA) with pronounced specificity, compared to ss-poly(dA), poly(rU), and poly(dT). The difference was also obtained for the interaction of MB with hybrid ds-polynucleotides poly(rA)-poly(dT) and poly(dA)-poly(rU).