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Thio- and cyano- modified single-stranded poly(dNTP) sequences of different molecular sizes (20–200 n) and the same lengths routine poly(dNTP) and poly(NTP) species were tested for their impact on catalytic activities of β-like DNA polymerases from chromatin of HL-60, WERI-1A and Y-79 cells as well as for the affinity patterns in DNApolβ-poly(dNTP)/(NTP) pairs, respectively. An essential link between the lengths of ultrashort (50–100 n) single-stranded poly(dNTP) sequences of different structures and their inhibitory effects towards the cancer-specific DNA polymerases β was found. A possible significance of this phenomenon for both DNA repair suppression in tumors and a consequent anti-cancer activity of the DNA repair related short poly(dNTP) fragments is under discussion.

[This corrects the article DOI: 10.3389/fphar.2016.00273.].[This corrects the article DOI: 10.3389/fphar.2016.00273.].

[This corrects the article DOI: 10.3389/fphar.2017.00558.].[This corrects the article DOI: 10.3389/fphar.2017.00558.].

[This corrects the article DOI: 10.3389/fphar.2017.00224.].

Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1β and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1β expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.

PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A 2A receptors. Besides engaging the A 2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A 2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A 2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects.

The present study evaluated the effects of polydeoxyribonucleotide (PDRN) on tissue regeneration, paying special attention to the molecular mechanisms that underlie its tissue remodeling actions to better identify its effective therapeutic potential in wound healing. Strategic searches were conducted through MEDLINE/PubMed, Google Scholar, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials, from their earliest available dates to March 2020. The studies were included with the following eligibility criteria: studies evaluating tissue regeneration, and being an , and clinical study. Out of more than 90 articles, 34 fulfilled the eligibility criteria. All data obtained proved the ability of PDRN in promoting a physiological tissue repair through salvage pathway and adenosine A2A receptor activation. Up to date PDRN has proved promising results in term of wound regeneration, healing time and absence of side effects.

[This corrects the article DOI: 10.3389/fphar.2016.00537.].[This corrects the article DOI: 10.3389/fphar.2016.00537.].

The normal wound healing process is characterized by a complex, highly integrated cascade of events, requiring the interactions of many cell types, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, as well as the involvement of growth factors and enzymes. However, several diseases such as diabetes, thermal injury and ischemia could lead to an impaired wound healing process characterized by wound hypoxia, high levels of oxygen radicals, reduced angiogenesis, decreased collagen synthesis and organization. Polydeoxyribonucleotide (PDRN) has been used to improve wound healing through local and systemic administration thanks to its ability to promote cell migration and growth, angiogenesis, and to reduce inflammation on impaired wound healing models in vitro, in vivo and clinical studies. In light of all these observations, the aim of this review is to provide a full overview of PDRN applications on skin regeneration. We reviewed papers published in the last 25 years on PubMed, inserting “polydeoxyribonucleotide and wound healing” as the main search term. All data obtained proved the ability of PDRN in promoting physiological tissue repair through adenosine A2A receptor activation and salvage pathway suggesting that PDRN has proven encouraging results in terms of healing time, wound regeneration and absence of side effects.

Background Polynucleotides (PDRN) have gained attention in aesthetic and regenerative medicine for their potential to enhance tissue regeneration, improve skin quality, and deliver superior aesthetic outcomes. However, the transition from theoretical benefits to proven clinical outcomes faces challenges due to inconsistencies and methodological shortcomings in the existing evidence base. This systematic review aims to critically evaluate the scientific basis and empirical evidence supporting the use of PDRN in aesthetic and regenerative medicine, highlighting the quality, reproducibility, and reliability of existing research, and identifying gaps and inconsistencies within the current literature. Methods Adhering to PRISMA guidelines and registered with PROSPERO, this review formulated a research question using the PICO framework to assess the efficacy of PDRN applications. A comprehensive literature search across PubMed–MEDLINE, EMBASE, and Web of Science was conducted. The inclusion criteria focused on clinical studies applying PDRN in regenerative or aesthetic medicine with clear outcome measures. Quality assessment utilized Cochrane Risk of Bias tool, ROBINS-I, and Newcastle Ottawa Scale. Data synthesis was qualitative due to anticipated heterogeneity. Results From 360 identified studies, 16 clinical trials met the inclusion criteria, encompassing various study designs and a total of 750 participants. The studies investigated PDRN's efficacy across different conditions and applications. Findings revealed a lack of specificity in PDRN sequencing, molecular targets, and dosage details, with a noted variability in source and manufacturing standards. Most studies demonstrated a low risk of bias, suggesting methodological rigor, yet the absence of comprehensive reporting on sequencing, targeted mechanisms, and molecular length was evident. The review underscores the embryonic stage of PDRN research and the necessity for more rigorous studies to validate clinical outcomes. Conclusions The potential of PDRN in aesthetic and regenerative medicine is significant, yet the current state of evidence necessitates a cautious and evidence-based approach to their clinical integration. Future research should focus on overcoming the highlighted gaps and inconsistencies, ensuring that the innovation in treatments does not compromise patient safety and efficacy. Regulatory frameworks must evolve to address the unique challenges presented by PDRN technologies, ensuring their safe and ethical application. Level of evidence: Level I, Therapeutic.