Search Results (13)

Polynucleotide (PN) and polydeoxyribonucleotide (PDRN) are DNA-derived biopolymers increasingly recognized for their potential in dermatology. Despite their structural similarities, PN and PDRN exhibit distinct functions due to differences in polymer length and molecular weight. PN, composed of longer DNA fragments, plays a key role in extracellular matrix remodeling. Conversely, PDRN, composed of relatively shorter oligonucleotide sequences than those of PN, enhances skin condition through adenosine receptor activations and supports nucleotide synthesis via both the salvage and de novo pathways. This review provides a critical comparison of the molecular characteristics and functions of PN and PDRN with particular emphasis on their dermatological applications. By delineating their respective roles in esthetic and regenerative medicine, we aim to highlight recent advances that may guide the development of optimized treatment strategies and foster evidence-based clinical practice. Full article

Ultraviolet (UV) radiation stimulates melanogenesis, leading to various esthetic problems. UV increases oxidative stress and nuclear factor-kappa B (NF-κB), which increase the nucleotide-binding oligomerization domain (NOD) or leucine-rich repeat and pyrin do-main containing 3 (NLRP3) inflammasome. Given that polydeoxyribonucleotides reduce melanogenesis and polynucleotide (PN) has molecular similarity to polydeoxyribonucleotides, we hypothesized that PN can decrease melanogenesis. We compared the anti-melanogenic effect of PN with that of a PN mixture (PNM) that contained other antioxidants, such as glutathione and hyaluronic acid, in UVB-irradiated keratinocytes and animal skin. PN and PNM both decreased oxidative stress, which was evaluated according to the expression of NADPH oxidase (NOX) 1/2/4, the glutathione (GSH):oxidized glutathione (GSSG) ratio, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in UVB-irradiated keratinocytes. The expression of NLRP3 inflammasome components (NLRP3, ASC, and pro-caspase-1) and IL-18 was increased by UVB radiation and reduced by PN and PNM. When conditioned media from PN or PNM were administered to UVB-radiated keratinocytes, melanogenesis-related signals (MITF, tyrosinase, and tyrosinase-related protein1/2) were decreased. These effects were similar in the UVB-irradiated animal skin. Both PN and PNM decreased melanin accumulation and increased skin lightness in UVB-irradiated skin. The anti-melanogenic effect of PNM was greater than that of PN. In conclusion, PN and PNM decreased melanogenesis by decreasing oxidative stress, NF-κB, and NLRP3 inflammasome activation. Full article

Background/Objectives: Natural-origin PN HPT™ (Polynucleotides High Purification Technology) protect and revitalize chondrocytes, synoviocytes, and cartilage with a regenerative medicine perspective following intra-articular injection. This six-month, open-label data collection aimed to validate the benefits documented in previous studies of a single intra-articular injection of a proprietary PN HPT™/HA-based medical device in improving both subjective and objective manifestations of knee osteoarthritis in real-life ambulatory patients of both genders with unilateral or bilateral knee osteoarthritis. Methods: Efficacy and safety assessments, conducted at baseline before a single PN HPT™/HA injection and after three and six months of follow-up, included the Lequesne index and the patient-assessed Numeric Pain Rating Scale (NPRS), which focuses on pain intensity, as primary endpoints. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was a secondary endpoint. Results: After three and six months, the mean baseline Lequesne index score improved by 43.8% and 51.4%, respectively. Concurrently, the mean NPRS score improvements were 42.2% and 54.7%. Furthermore, 32% of investigators and 15.5% of treated patients deemed optimal the clinical outcomes with no clinical worsening. Conclusions: With some limitations due to the uncontrolled design and relying on subjective rating scales only, the study confirms all previous findings about the benefits of combining PN HPT™ and HA in the same medical device for intra-articular injection in knee osteoarthritis. Full article

Skin aging is a complex and multifactorial process influenced by both intrinsic and extrinsic factors. The periorbital area of the face is particularly susceptible to premature aging signs due to its delicate skin structure, and is a major concern for many individuals. While hyaluronic acid (HA)-based dermal filler products are commonly used for periorbital rejuvenation, novel approaches to effectively locally address the visible signs of aging are available. This study aimed to investigate Innovyal Regenerative Action (IRA), an injectable polynucleotide–HA (PN-HA) regenerative complex designed for periocular prejuvenation. Firstly, PN-HA was compared to other commercially available HA-based dermbooster products (Profhilo^®, Suisselle Cellbooster^® Glow, and NCTF^® 135 HA) in terms of rheological properties, in vitro antioxidant capacity, and total collagen production stimulation in human fibroblasts. Secondly, the clinical effects of the IRA PN-HA complex were evaluated in two case reports (monotherapy for periorbital prejuvenation). It was shown that the PN-HA complex outperformed its comparators in terms of relative rheological behavior (biophysical attributes normalized to polymer contents), intrinsic antioxidant activity (CUPRAC, FRAP, and ORAC assays), as well as total collagen level induction (72-h in vitro dermal fibroblast induction model). Generally, the results of this study provided mechanistic and preliminary clinical insights into the potential benefits of the IRA PN-HA complex for periocular cutaneous treatment. Overall, it was underscored that combining the structural support and regenerative properties of PN with the hydrating and volumizing effects of HA bares tangible potential for multifactorial skin quality enhancement and for periocular prejuvenation in particular. Full article

Background/Objectives: Tendinopathy is the preferred term to describe various tendon pathologies, including paratendinitis, tendinitis, and tendinosis, in the absence of histopathological evidence in biopsy specimens. The management of tendinopathies is challenging; rest, physiotherapy (such as eccentric training), injections, shock waves, orthotics, medical therapy, and surgery are the main therapeutic options offered to the patient. The conservative treatment of tendinopathies is still difficult, but several options have been proposed, including the use of anti-inflammatory molecules. In this retrospective study, we aimed to assess the efficacy of a conservative approach in improving pain and functional improvement in hip bursitis (HB) and biceps tendinitis (BT) patients. Methods: A series of data concerning the application of Polynucleotides High Purification Technology (PN HPT^TM) in 47 patients with BT and HB was analyzed. All patients received three bi-weekly injections of PN HPT^TM (T0–T2). Follow-up visits were performed at T3 (8 weeks from T2) and T4 (24 weeks from T2). Both the visual analog scale (VAS) for pain assessment and functional impairment (FI) scores were processed in the form of anonymized series for clinical improvement evaluations. Results: Statistically significant differences (p < 0.001) in pain reduction (−85%) and functional improvement (+86%) were found at the end of treatment. The levels of patient satisfaction (PS) and Clinical Global Improvement—Impression (CGI-I) were equal to 93% and 98%, respectively. According to the analyses, other patient data (e.g., gender, age, and BMI) did not appear to influence the positive treatment outcomes. Conclusions: The application of High Purification Technology (PN HPT^TM) was shown to improve both pain and functional deterioration in patients with tendonitis in a similar manner to other conservative treatments. These retrospective analyses may open up new avenues for the implementation of conservative approaches in patients with tendinitis. Full article

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. Full article

Aims: Intra-articular (IA) injection therapy, particularly IA hyaluronic acid (HA), is a common treatment for knee osteoarthritis, but it does have limitations. The injection of IA polynucleotide (PN) has emerged as an alternative, potentially offering superior clinical outcomes. This study investigates current practice patterns and the perceived effectiveness of PN among clinicians for treating knee osteoarthritis in the Republic of Korea. Methods: Based on a survey conducted among clinicians who use PN in clinical practice, we explored the current practices and assessed the perceived effectiveness of IA PN in treating knee osteoarthritis. Results: A total of 265 clinicians who used IA PN for knee osteoarthritis participated in the survey. Most clinicians (73.3%) used PN therapy for the treatment of chronic pain, with varying administration frequencies. In addition, 25.8% of clinicians used PN for the treatment of acute flare-ups. In cases of knee effusion, 55.5% of clinicians removed the effusion prior to administering PN. Clinicians rated PN as more effective than HA for both chronic pain and acute flare-ups, with higher scores for cushioning, anti-inflammatory effects, and delaying joint degeneration. The clinicians stated that patients expressed a higher satisfaction with IA PN compared with IA HA, noting improvement in joint smoothness, noise reduction, pain relief, and a reduction in heat sensation and swelling. Conclusions: The results of the present study highlight the extensive use and perceived benefits among clinicians of IA PN for knee osteoarthritis in the Republic of Korea. Further research is warranted to explore the effectiveness of PN in acute flare-ups and to validate these findings in broader populations. Full article

Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNFα levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade. Full article

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. Full article

Angiogenesis promotes rejuvenation in multiple organs, including the skin. Heat shock protein 90 (HSP90), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) are proangiogenic factors that stimulate the activities of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase 1/2 (ERK1/2). Poly-D,L-lactic acid (PDLLA), polynucleotide (PN), and calcium hydroxyapatite (CaHA) are dermal fillers that stimulate the synthesis of dermal collagen. However, it is not yet known whether these compounds promote angiogenesis, which leads to skin rejuvenation. Here, we evaluated whether PDLLA, PN, and CaHA stimulate angiogenesis and skin rejuvenation using H₂O₂-treated senescent macrophages and endothelial cells as an in vitro model for skin aging, and we used young and aged C57BL/6 mice as an in vivo model. Angiogenesis was evaluated via endothelial cell migration length, proliferation, and tube formation after conditioned media (CM) from senescent macrophages was treated with PDLLA, PN, or CaHA. Western blot showed decreased expression levels of HSP90, HIF-1α, and VEGF in senescent macrophages, but higher expression levels of these factors were found after treatment with PDLLA, PN, or CaHA. In addition, after exposure to CM from senescent macrophages treated with PDLLA, PN, or CaHA, senescent endothelial cells expressed higher levels of VEGF receptor 2 (VEGFR2), PI3K, phosphorylated AKT (pAKT), and phosphorylated ERK1/2 (pERK1/2) and demonstrated greater capacities for cell migration, cell proliferation, and tube formation. Based on the levels of 4-hydroxy-2-nonenal, the oxidative stress level was lower in the skin of aged mice injected with PDLLA, PN, or CaHA, while the tumor growth factor (TGF)-β1, TGF-β2, and TGF-β3 expression levels; the density of collagen fibers; and the skin elasticity were higher in the skin of aged mice injected with PDLLA, PN, or CaHA. These effects were greater in PDLLA than in PN or CaHA. In conclusion, our results are consistent with the hypothesis that PDLLA stimulates angiogenesis, leading to the rejuvenation of aged skin. Our study is the first to show that PDLLA, PN, or CaHA can result in angiogenesis in the aged skin, possibly by increasing the levels of HSP90, HIF-1α, and VEGF and increasing collagen synthesis. Full article

(1) Background: Three-dimensional cultures are useful tools to evaluate regenerative approaches in vitro, as they may mimic the spatial arrangement of cells more closely to natural tissues than routine 2D culture methods. (2) Methods: We investigated the effects of a polynucleotide, hyaluronic acid (PN, HA) compound on 3D spheroid cultures of primary gingival fibroblasts, by measuring their morphology over time, cell viability with Calcein-AM, a fluorescent marker, and cell growth potential by re-plating spheroids in attachment-permissive regular culture plates under routine conditions and following them up for 15 days. (3) Results: PN + HA induced an increase in spheroid size and perimeter and a decrease in spheroid circularity, as cells tended to grow and form small peripheral stacks around the spheroid. Levels of cell viability were also higher in this group. After re-plating, only the spheroids previously stimulated with PN + HA dissolved completely during the second week of culture and colonized the plate, thus indicating the retention of a higher level of viability by the cells forming the whole spheroid with this stimulus. (4) Conclusions: Taken together, our data support the idea that the combination of PN and HA has synergic effects on primary fibroblasts and promotes their viability, the growth of 3D cellular constructs, and the retention of a remarkable proliferative potential over the course of the experimental period, making it a promising compound for further investigations. Full article

Knee osteoarthritis (OA) is one of the most common degenerative diseases in old age. Recent studies have suggested new treatment approaches dealing with subchondral remodeling, which is a typical feature of OA progression. However, diagnostic tools or therapeutic approaches related to such a process are still being researched. The automated artificial intelligence (AI) algorithm-based texture analysis is a new method used for OA-progression detection. We designed a prospective case series study to examine the efficacy of the AI algorithm-based texture analysis in detecting the restoration of the subchondral remodeling process, which is expected to follow therapeutic intervention. In this study, we used polynucleotide (PN) filler injections as the therapeutic modality and the treatment outcome was verified by symptom improvement, as well as by the induction of subchondral microstructural changes. We used AI algorithm-based texture analysis to observe these changes in the subchondral bone with the bone structure value (BSV). A total of 51 participants diagnosed with knee OA were enrolled in this study. Intra-articular PN filler (HP cell Vitaran J) injections were administered once a week and five times in total. Knee X-rays and texture analyses with BSVs were performed during the screening visit and the last visit three months after screening. The Visual Analogue Scale (VAS) and Korean-Western Ontario MacMaster (K-WOMAC) measurements were used at the screening visit, the fifth intra-articular injection visit, and the last visit. The VAS and K-WOMAC scores decreased after PN treatment and lasted for three months after the final injection. The BSV changed in the middle and deep layers of tibial bone after PN injection. This result could imply that there were microstructural changes in the subchondral bone after PN treatment, and that this change could be detected using the AI algorithm-based texture analysis. In conclusion, the AI- algorithm-based texture analysis could be a promising tool for detecting and assessing the therapeutic outcome in knee OA. Full article

Polynucleotides (PN) have long been known as an effective supportive therapy for wound healing. The present study investigated whether a hydrogel formulation containing PN and hyaluronic acid (PN + HA) could promote wound healing in an in vitro model of gingival fibroblasts. PN promoted cell growth and viability as assessed by different assays, and PN + HA, though not significantly further increasing cell growth as compared to PN, supported the formation of dense multilayered cell nodules. PN promoted fibroblasts’ clonogenic efficiency and PN + HA further enhanced the formation of more numerous dense colonies. PN + HA appeared to significantly increase the expression of collagen 1a1 and 3a1, while not affecting proteoglycans deposition. Interestingly, when tested in a scratch assay, PN + HA achieved gap closure after 48 h, while cells in the comparison groups had not completely bridged the scratch even after 96 h. Taken together, these results demonstrate that PN + HA is a promising candidate for a supportive therapy to promote soft tissue healing in the oral cavity. Full article