Kaempferol Alleviates Mitochondrial Damage by Reducing Mitochondrial Reactive Oxygen Species Production in Lipopolysaccharide-Induced Prostate Organoids.

Common prostate diseases such as prostatitis and benign prostatic hyperplasia (BPH) have a high incidence at any age. Cellular stresses, such as reactive oxygen species (ROS) and chronic inflammation, are implicated in prostate enlargement and cancer progression and development. Kaempferol is a flavonoid found in abundance in various plants, including broccoli and spinach, and has been reported to exhibit positive biological activities, such as antioxidant and anti-inflammatory properties. In the present study, we introduced prostate organoids to investigate the protective effects of kaempferol against various cellular stresses. The levels of COX-2, iNOS, p-IκB, a pro-inflammatory cytokine, and ROS were increased by LPS treatment but reversed by kaempferol treatment. Kaempferol activated the nuclear factor erythroid 2-related factor 2(Nrf2)-related pathway and enhanced the mitochondrial quality control proteins PGC-1α, PINK1, Parkin, and Beclin. The increase in mitochondrial ROS and oxygen consumption induced by LPS was stabilized by kaempferol treatment. First, our study used prostate organoids as a novel evaluation platform. Secondly, it was demonstrated that kaempferol could alleviate the mitochondrial damage in LPS-induced induced prostate organoids by reducing the production of mitochondrial ROS.

Polarization of THP-1-Derived Macrophage by Magnesium and MAGT1 Inhibition in Wound Healing.

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.

Chemoprevention of lotus leaf ethanolic extract through epigenetic activation of the NRF2-mediated pathway in murine skin JB6 P+ cell neoplastic transformation.

Background and aim: Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells. Experimental procedure: Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression. Results and conclusion: LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation.

The Cytoprotective Effects of Baicalein on H2O2-Induced ROS by Maintaining Mitochondrial Homeostasis and Cellular Tight Junction in HaCaT Keratinocytes.

Reactive oxygen species (ROS) promote oxidative stress, which directly causes molecular damage and disrupts cellular homeostasis, leading to skin aging. Baicalein, a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi has antioxidant, anticancer, anti-inflammatory, and other medicinal properties. We aimed to investigate the protective effect of baicalein on the disruption of tight junctions and mitochondrial dysfunction caused by H2O2-induced oxidative stress in HaCaT keratinocytes. The cells were pretreated with 20 and 40 µM baicalein followed by treatment with 500 µM H2O2. The results revealed that baicalein exerted antioxidant effects by reducing intracellular ROS production. Baicalein attenuated the degradation of the ECM (MMP-1 and Col1A1) and the disruption of tight junctions (ZO-1, occludin, and claudin-4). In addition, baicalein prevented mitochondrial dysfunction (PGC-1α, PINK1, and Parkin) and restored mitochondrial respiration. Furthermore, baicalein regulated the expression of antioxidant enzymes, including NQO-1 and HO-1, via the Nrf2 signaling pathway. Our data suggest that the cytoprotective effects of baicalein against H2O2-induced oxidative stress may be mediated through the Nrf2/NQO-1/HO-1 signaling pathway. In conclusion, baicalein exerts potent antioxidant effects against H2O2-induced oxidative stress in HaCaT keratinocytes by maintaining mitochondrial homeostasis and cellular tight junctions.

Aptamer-conjugated nano-liposome for immunogenic chemotherapy with reversal of immunosuppression.

Cancer cells have various immune evasion mechanisms that resist the immune cells by reprogramming the tumor microenvironment (TME), such as programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase-1 (IDO1) overexpression. One of the approaches to restore antitumor immune response by T-cells is through induction of immunogenic cell death (ICD). Thus, drug carrier containing IDO1 siRNA and ICD inducer would be effective anticancer regimen to modulate the immunosuppressive TME by reversing the IDO1-mediated immunosuppression in a synergistic combination with ICD induction. However, numerous nanocarrier platforms for co-delivery of multiple drugs mostly depend on the enhanced permeation and retention (EPR), which is insufficient to achieve selectivity in tumor sites harboring various types of cells. We designed a targeted drug delivery system using nano-sized liposomes functionalized with anti-CD44 and anti-PD-L1 DNA aptamers, which target breast cancer cells and inhibit PD-1/PD-L1 interaction between cancer cells and T-cells. To reverse immunosuppressive TME and reactivate immune response, cancer-targeting nano-liposomes were prepared to contain immunogenic cell death inducer (Doxorubicin, DOX) and IDO1 siRNA, namely Aptm[DOX/IDO1]. The Aptm[DOX/IDO1] specifically delivered the loaded DOX and IDO1 siRNA into target breast cancer cells through aptamer-mediated endocytosis. Cancer-targeted DOX/IDO1 siRNA delivery enhanced ICD and suppressed IDO1 expression with significantly high toxicity in cancer cells. We demonstrated that Aptm[DOX/IDO1] could achieve synergistic antitumor effects by facilitating ICD response and simultaneous reversal of the immunosuppressive TME with IDO1 knockdown in the subcutaneous breast cancer model mice, thus reducing tumor size. These antitumor effects were exerted with intratumoral infiltration of CD8+ cytotoxic T lymphocyte as well as attenuation of regulatory T-cell recruitment in the tumor sites. We further proved that our Aptm[DOX/IDO1] strategy significantly reduced tumor metastasis in tumor-xenograft mice through a synergistic combination of cancer cell-targeted ICD induction and reversal of the IDO1-mediated immunosuppressive TME. Our nanocarrier platform based on cationic liposomes containing DOX and IDO1 siRNA, which are conjugated with two DNA aptamers targeting the cancer cell surface, accomplished synergistic chemoimmunotherapy through tumor-specific immune modulation into immune-favorable TME in vivo.

Functional Graphene Nanomaterials-Based Hybrid Scaffolds for Osteogenesis and Chondrogenesis.

With the emerging trends and recent advances in nanotechnology, it has become increasingly possible to overcome current hurdles for bone and cartilage regeneration. Among the wide type of nanomaterials, graphene (G) and its derivatives (graphene-based materials, GBMs) have been highlighted due to the specific physicochemical and biological properties. In this review, we present the recent development of GBM-based scaffolds for bone and cartilage engineering, focusing on the formulation/shape/size-dependent characteristics, types of scaffold and modification, biocompatibility, bioactivity and underlying mechanism, drawback and prospect of each study. From the findings described herein, mechanical property, biocompatibility, osteogenic and chondrogenic property of GBM-based scaffolds could be significantly enhanced through various scaffold fabrication methods and conjugation with polymers/nanomaterials/drugs. In conclusion, the results presented in this review support the promising prospect of using GBM-based scaffolds for improved bone and cartilage tissue engineering. Although GBM-based scaffolds have some limitations to be overcome by future research, we expect further developments to provide innovative results and improve their clinical potential for bone and cartilage regeneration.

A Validated Grading Scale for Downturned Oral Commisure in Asian Faces.

BACKGROUND: Downturned oral commissures develop gradually with aging. Tools have been developed to evaluate the marionette line or the lower face. However, there is no validated and reproducible tool to evaluate the progress after oral commissure treatment in clinical practice. OBJECTIVE: The authors aimed to develop a scoring system to evaluate therapeutic interventions for downturned oral commissures and to verify its reliability, reproducibility, and clinical significance. METHODS AND MATERIALS: In the Scale Development Group, the Delphi method was used to establish a 5-graded scoring system to evaluate oral commissure position. The scoring system was applied to 50 participants. The authors recorded and compared the intrarater agreement, interrater agreement, and significance of the grade-dependent scale. RESULTS: Delphi analysis of the scoring system verified the grade description adequacy. Intrarater agreement showed almost perfect agreement, and the intraclass correlation coefficient of the interrater agreement had a significantly higher agreement rate. The differences between the clinical grades were significant. CONCLUSION: The Hugel Downturned Oral Commissure Scale is precise, reproducible, and reflective of the clinical differences for downturned oral commissure. Its novelty lies in the use of specific angles and ratio. This scale has clinical trial potential owing to its standardized and quantitative assessment.

A Single-Center, Randomized, Double-Blind Clinical Trial to Compare the Efficacy and Safety of a New Monophasic Hyaluronic Acid Filler and Biphasic Filler in Correcting Nasolabial Fold.

BACKGROUND: Hyaluronic acid (HA) fillers have been widely used in humans since 1958 because of their biomedical safety. Restylane® was introduced in the1990s as a favorable temporary filler option for facial augmentation. Subsequently, many new HA filler products, including the Sardenyashape®, have been introduced, but comparative studies of these products are limited. Here, we compared tolerability (wrinkle severity rating scale, WSRS), pain (visual analog scale, VAS score), satisfaction (global esthetic improvement scale, GAIS), and safety of a new monophasic HA (MHA) filler (Sardenyashape®) containing lidocaine, used to correct nasolabial folds (NLFs), with those of biphasic HA (BHA) filler (Restylane LYFT®) containing lidocaine. METHODS: We enrolled 96 participants with visible NLFs in this randomized, double-blind, single-center clinical study. Participants were injected with a new MHA filler in one NLF and a BHA filler and were reassessed for cosmetic changes at 8 and 24 weeks. Wrinkle severity was assessed using the 5-point WSRS. RESULTS: At week 24, the mean improvement in WSRS compared to baseline was 1.92 ± 0.75 and 2.24 ± 0.66 for MHA and BHA fillers, respectively, and corresponding average pain values using the VAS score 30 min after the procedure were 0.04 ± 0.25 and 0.02 ± 0.15, respectively, showing no significant difference. Average GAIS values 8 weeks after the procedure with MHA and BHA fillers were 1.89 ± 0.77 and 1.40 ± 0.82, respectively (p < 0.001). Both fillers were well tolerated, with mild adverse reactions. CONCLUSION: The evaluation of the effect of Sardenyashape® with lidocaine on NLF in this study proved its effectiveness and safety for use in correcting NLF. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Extracellular Vesicles From a Three-Dimensional Culture of Perivascular Cells Accelerate Skin Wound Healing in a Rat.

BACKGROUND: Soluble proteins and extracellular vesicles (EVs) are crucial wound repair mediators in cell-based therapy. Previous studies reported that EVs of perivascular cells stimulated migration and proliferation of cell types involved in the dermatological wound healing process. However, these studies only show effects of EVs from perivascular cells (PVCs) for in vitro models. METHODS: EVs were collected from 3D-cultured PVC (PVC-3D-EV) and compared with EVs from 2D-culture PVC (PVC-2D-EV) to investigate effects on wound contraction, angiogenesis, activation of myofibroblast, and collagen deposition. RESULTS: PVC-3D-EV was significantly improved in terms of wound contraction compared with PVC-2D-EV and the control. Activation of myofibroblast and collagen deposition in a rat skin wound model was significantly stimulated by PVC-3D-EV. In addition, angiogenesis and vascular endothelial growth factor expression were also highly stimulated by PVC-3D-EV. These results suggest that PVC-3D-EV was regulated in granulation tissue formation, angiogenesis, and wound contraction in healing of a rat skin wound. These results indicate a pivotal role of PVC-3D-EV in wound healing through multiple mechanisms. CONCLUSIONS: 3D-culture using a polystyrene scaffold is demonstrated to be a better system for providing better physiological conditions than the 2D-culture system, and EVs from 3D-cultured PVC could be a promising option for healing skin wound. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Carbon Nanomaterials for Biomedical Application.

The use of carbon-based nanomaterials (CNs) with outstanding properties has been rising in many scientific and industrial application fields. These CNs represent a tunable alternative for applications with biomolecules, which allow interactions in either covalent or noncovalent way. Diverse carbon-derived nanomaterial family exhibits unique features and has been widely exploited in various biomedical applications, including biosensing, diagnosis, cancer therapy, drug delivery, and tissue engineering. In this chapter, we aim to present an overview of CNs with a particular interest in intrinsic structural, electronic, and chemical properties. In particular, the detailed properties and features of CNs and its derivatives, including carbon nanotube (CNT), graphene, graphene oxide (GO), and reduced GO (rGO) are summarized. The interesting biomedical applications are also reviewed in order to offer an overview of the possible fields for scientific and industrial applications of CNs.

A critical review on genotoxicity potential of low dimensional nanomaterials.

Low dimensional nanomaterials (LDNMs) have earned attention among researchers as they exhibit a larger surface area to volume and quantum confinement effect compared to high dimensional nanomaterials. LDNMs, including 0-D and 1-D, possess several beneficial biomedical properties such as bioimaging, sensor, cosmetic, drug delivery, and cancer tumors ablation. However, they threaten human beings with the adverse effects of cytotoxicity, carcinogenicity, and genotoxicity when exposed for a prolonged time in industry or laboratory. Among different toxicities, genotoxicity must be taken into consideration with utmost importance as they inherit DNA related disorders causing congenital disabilities and malignancy to human beings. Many researchers have performed NMs' genotoxicity using various cell lines and animal models and reported the effect on various physicochemical and biological factors. In the present work, we have compiled a comparative study on the genotoxicity of the same or different kinds of NMs. Notwithstanding, we have included the classification of genotoxicity, mechanism, assessment, and affecting factors. Further, we have highlighted the importance of studying the genotoxicity of LDNMs and signified the perceptions, future challenges, and possible directives in the field.

Clinical courses and degradation patterns of absorbable plates in facial bone fracture patients.

BACKGROUND: Absorbable plates are widely used in open reduction and internal fixation surgeries for facial bone fractures. Absorbable plates are made of polyglycolic acid (PGA), polylactic acid (PLA), polydioxane (PDS), or various combinations of these polymers. The degradation patterns of absorbable plates made from different polymers and clinical courses of patients treated with such plates have not been fully identified. This study aimed to confirm the clinical courses of facial bone fracture patients using absorbable plates and compare the degradation patterns of the plates. METHODS: A retrospective chart review was conducted for 47 cases in 46 patients who underwent open reduction and internal fixation surgery using absorbable plates to repair facial bone fractures. All surgeries used either PLA/PGA composite-based or poly-L-lactic acid (PLLA)/hydroxyapatite (HA) composite-based absorbable plates and screws. Clinical courses were confirmed and comparisons were conducted based on direct observation. RESULTS: There were no naturally occurring foreign body reactions. Post-traumatic inflammatory responses occurred in eight patients (nine cases), in which six recovered naturally with conservative treatment. The absorbable plates were removed from two patients. PLA/PGA composite-based absorbable plates degraded into fragments with non-uniform, sharp surfaces whereas PLLA/HA composite-based absorbable plates degraded into a soft powder. CONCLUSION: PLA/PGA composite-based and PLLA/HA composite-based absorbable plates showed no naturally occurring foreign body reactions and showed different degradation patterns. The absorbable plate used for facial bone fracture surgery needs to be selected in consideration of its degradation patterns.

A novel photonumeric hand grading scale for hand rejuvenation.

BACKGROUND: Few scales are currently available to evaluate changes in hand volume. We aimed to develop a hand grading scale for quantitative assessments of dorsal hand volume with additional consideration of changes in skin texture; to validate and prove the precision and reproducibility of the new scale; and to demonstrate the presence of clinically significant differences between grades on the scale. METHODS: Five experienced plastic surgeons developed the Hand Volume Rating Scale (HVRS) and rated 91 images. Another five plastic surgeons validated the scale using 50 randomly selected images. Intra- and inter-rater agreement was calculated using the weighted kappa statistic and intraclass correlation coefficients (ICCs). Paired images were also evaluated to verify whether the scale reflected clinical differences. RESULTS: The intra-rater agreement was 0.95 (95% confidence interval, 0.922-0.974). The interrater ICCs were excellent (first rating, 0.94; second rating, 0.94). Image pairs that differed by 1, 2, and 3 grades were considered to contain clinically relevant differences in 80%, 100%, and 100% of cases, respectively, while 84% of image pairs of the same grade were found not to show clinically relevant differences. This confirmed that the scale of the HVRS corresponded to clinically relevant distinctions. CONCLUSIONS: The scale was proven to be precise, reproducible, and reflective of clinical differences.

Longan fruit increase bone mineral density in zebrafish and ovariectomized rat by suppressing RANKL-induced osteoclast differentiation.

BACKGROUND: The receptor activator of nuclear factor-kappa B ligand (RANKL)-induced nuclear factor-kappa B (NF-κB) signaling pathway plays essential roles in osteoclast differentiation and may serve as an attractive target for the development of therapeutics for osteoporosis. PURPOSE: This study aimed to identify plant extracts that attenuated RANKL-induced NF-κB signaling pathway and examine their anti-osteoporotic effects in animal model systems. METHODS: Osteoclast differentiation was determined by western blot analysis, RT-PCR, and tartrate-resistant acid phosphatase (TRAP) assay. The effect of Longan (Dimocarpus longan Lour.) fruit extract (LFE) on bone mineral density was evaluated by calcein staining in zebrafish and micro-CT analysis in ovariectomized (OVX) rat. RESULTS: LFE nullified RANKL-induced down-regulation of inhibitor of NF-κB, which keeps NF-κB sequestered in the cytosol, thereby inhibiting translocation of NF-κB to the nucleus, in RAW264.7 cells. In addition, LFE decreased the nuclear levels of c-Fos and nuclear factor of activated T-cells c1, which play crucial roles in RANKL-induced osteoclast differentiation, in RAW264.7 cells. LFE repressed RANKL-activated cathepsin K and TRAP expression in RAW264.7 cells, resulting in a reduction of the number of TRAP-positive multinucleated cells, without cytotoxicity. Furthermore, LFE increased bone mineralization in zebrafish and prevented bone loss in OVX rat. CONCLUSION: Collectively, our findings suggest that LFE exerts its anti-osteoporotic activity through inhibition of osteoclast differentiation and may have potential as a herbal therapeutic or preventive agent for the treatment of osteoporosis.

Pueraria montana var. lobata root extract inhibits photoaging on skin through Nrf2 pathway.

Pueraria montana var. lobata is a bioactive substance, in possession of a variety of beneficial health effects, which has long been extensively used as a traditional medication for the treatment of fever, acute dysentery, diabetes, and cardiovascular diseases in North-East Asian countries. The purpose of this study was to evaluate the cytoprotective activity of Pueraria montana var. lobata ethanol extract (PLE) for ultraviolet B (UVB) induced oxidative stress in human dermal fibroblasts (HDF). It was hypothesized that PLE treatment (25-100 µg/mL) would reduce intracellular reactive oxygen species (ROS) levels as well as increase collagen production in UVB-irradiated HDF. The results confirmed this theory, with collagen production increasing in the PLE treatment group in a dose-dependent manner. In addition, regulators of cellular ROS accumulation, including HO-1 and NOQ-1, were activated by Nrf2, which was mediated by PLE. Hence, intracellular levels of ROS were also reduced in the PLE treatment group in a dose-dependent manner. In conclusion, PLE increases collagen production and maintains hyaluronic acid (HA) levels in human dermal fibroblasts exposed to UVB-irradiation, thereby inhibiting photoaging.

Intravascular papillary endothelial hyperplasia (Masson's hemangioma) of the face.

Intravascular papillary endothelial hyperplasia or Masson's hemangioma is a rare vascular tumor. The reactive proliferation of endothelial cells in this disease mimics other benign or malignant vascular proliferation such as angiosarcoma or Kaposi's sarcoma. It is important to make an accurate distinction to avoid confusion with these malignant tumors. This would facilitate a proper diagnosis, which is essential so that the patient is not subjected to unnecessarily aggressive or inappropriate treatment.

Experimental Investigation on the Tissue Response Induced by Face-Lifting Mesh Suspension Thread in Rats.

BACKGROUND: Face-lifting procedures are often performed to hide the effects of aging. Thread-lifting, a minimally invasive technique for the correction of facial aging, has become increasingly popular, and various materials for the procedure have been developed. OBJECTIVE: This study compared tissue responses to two types of threading sutures placed under rat skin: polypropylene (PP) monofilament mesh suspension thread (a novel face-lifting material) and polydioxanone (PDO) barbed thread. METHODS: Eight rats each were assigned to the PP monofilament mesh suspension, PDO barbed thread, and control groups. Tissue reactions were evaluated 28 days after subcutaneous loading of the materials. RESULTS: Significant increases in tensile strength and the mean area occupied by collagen fibers were evident in skin loaded with PDO barbed thread and PP monofilament mesh suspension thread compared to control skin (p<0.05). Compared to sites loaded with PDO barbed thread, those loaded with PP monofilament mesh suspension thread showed a significant increase in the number of collagen fibers and a lower grade of inflammation (p<0.05). CONCLUSION: PP monofilament mesh suspension thread has skin-rejuvenating effects comparable to those of PDO barbed thread, but induces a less severe inflammatory response. This indicates that it is a safe and effective material for use in thread-lifting procedures on aging skin.

A Prospective Observational Study of the Effectiveness and Safety of Botulinum Toxin in the Horizontal Neck Lines.

BACKGROUND: Botulinum toxin is used extensively, and its use for aesthetic indications in the lower face and neck is now becoming increasingly popular. It is the ideal alternative to surgical procedures for patients who are too young for facelift surgery or who are unwilling to take recuperation time. We review current approaches to BTX A treatment for horizontal neck lines. METHODS: Subjects were 20 women with an average age of 43 with mild to moderate horizontal neck lines but have had no treatment by BTX A for the past 3 months. Injections are performed at points 1-1.5 cm apart along the horizontal lines with 1-2 U in each injection site, for a total of 15-30 U. Patients were followed up 3 and 8 days after treatment and then every 4 weeks after initial treatment for 16 weeks. RESULTS: Except day 3 in the first neck line, the mean resulting from evaluation by the actual physician who performed the injection and two blinded physicians has statistical significance as shown by the maximum results at 8 weeks after injection. However, the patient improvement rate and satisfaction level did not exceed 50%. Adverse reactions were mild and transitory. CONCLUSIONS: The overall results of applying BTX A are excellent, and the satisfaction level of treated patients is high to a certain extent. Moreover, smoothening of the neck skin was observed due to the intradermal effect. It is also a safe and effective therapeutic modality for any patient desiring rejuvenation of his or her neck, but who at the same time does not desire any recuperation time or is unwilling to undertake the potential risks associated with surgical procedures. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparison of wound healing effects between Oncorhynchus keta-derived polydeoxyribonucleotide (PDRN) and Oncorhynchus mykiss-derived PDRN.

BACKGROUND: Polydeoxyribonucleotide (PDRN) influencing cellular growth and differentiation is recognized to promote wound healing by stimulating tissue repair. Although PDRN can be extracted from human placentas, PDRN medications have recently been extracted from the semen of trout (Oncorhynchus mykiss) and salmon (Oncorhynchus keta). The present study was designed to evaluate the wound healing effects of O. keta-derived PDRN for injection (Rejuvenex) and PDRN cream (Rejuvenex Cream) in comparison with those of O. mykiss-derived PDRN injection (Placentex). METHODS: Full-thickness skin defects were made on the back of mice (n=60). The mice were divided into the following four groups according to the dressing used for the wounds: O. mykiss-derived PDRN injection group, O. keta-derived PDRN injection group, O. keta-derived PDRN cream group, and normal saline soaked dressing group (control group). We analyzed the gross findings, wound sizes, histological findings, immunohistochemistry and enzyme-linked immunosorbent assays for the groups immediately after the treatment, and again after 4, 7, and 10 days of treatment. RESULTS: The wound healing effects were the greatest in the O. keta-derived PDRN injection and O. mykiss-derived PDRN injection groups, which showed similar scores, followed by the O. keta-derived cream and normal saline soaked dressing groups. CONCLUSION: The injection of PDRN extracted from O. keta was found to be as effective at healing full-thickness skin defects as the O. mykiss-derived PDRN injection, which is currently used in the clinic. Moreover, the O. keta-derived PDRN injection was also found to reduce the time required for wound healing.