Contrast-enhanced ultrasonography as an adjunctive method to ICG lymphography for functional lymphaticovenous anastomosis.

BACKGROUND AND OBJECTIVES: Indocyanine green (ICG) lymphography is the reference standard for evaluating lymphedema stage and identifying lymphatic vessels. However, the penetration depth was limited to 1-2 cm from the skin surface. This prospective study compares clinical outcomes following lymphaticovenous anastomoses (LVA) in patients with upper and lower limb lymphedema using contrast-enhanced ultrasonography (CEUS) with ICG as a preoperative imaging modality. METHODS: Under general anesthesia, Sonazoid® was injected subcutaneously to visualize functional lymphatic channels via CEUS. We analyzed the changes in limb circumference and inter-limb ratio (ILR) using bioimpedance to measure electrical resistance between the CEUS plus ICG group and the ICG-only group to see the effect of CEUS-assisted LVA. RESULTS: No significant demographic differences existed between the two groups (CEUS plus ICG group vs. ICG-only group). The ILR decrease of the Z1 value measured using bioimpedance was statistically significant (p = 0.042 for the upper limb, p = 0.002 for the lower limb)- CONCLUSIONS: CEUS allowed us to identify deep-lying, functional, and large lymphatic channels. In conclusion, the combination of CEUS and ICG for identifying lymphatic channels has the potential to lead to a more functional lymphovenous anastomosis.

Ethyl Pyruvate Decreases Collagen Synthesis and Upregulates MMP Activity in Keloid Fibroblasts and Keloid Spheroids.

Keloids, marked by abnormal cellular proliferation and excessive extracellular matrix (ECM) accumulation, pose significant therapeutic challenges. Ethyl pyruvate (EP), an inhibitor of the high-mobility group box 1 (HMGB1) and TGF-ß1 pathways, has emerged as a potential anti-fibrotic agent. Our research evaluated EP's effects on keloid fibroblast (KF) proliferation and ECM production, employing both in vitro cell cultures and ex vivo patient-derived keloid spheroids. We also analyzed the expression levels of ECM components in keloid tissue spheroids treated with EP through immunohistochemistry. Findings revealed that EP treatment impedes the nuclear translocation of HMGB1 and diminishes KF proliferation. Additionally, EP significantly lowered mRNA and protein levels of collagen I and III by attenuating TGF-ß1 and pSmad2/3 complex expression in both human dermal fibroblasts and KFs. Moreover, metalloproteinase I (MMP-1) and MMP-3 mRNA levels saw a notable increase following EP administration. In keloid spheroids, EP induced a dose-dependent reduction in ECM component expression. Immunohistochemical and western blot analyses confirmed significant declines in collagen I, collagen III, fibronectin, elastin, TGF-ß, AKT, and ERK 1/2 expression levels. These outcomes underscore EP's antifibrotic potential, suggesting its viability as a therapeutic approach for keloids.

Prediction of Enophthalmos in Medial Orbital Wall Fracture: Suggested Coordinate Plane for Making Surgical Decisions.

BACKGROUND: Enophthalmos is one of the most distressing complications of blowout orbital fractures. Although several studies have been conducted on the topic of indications of early surgical correction, none have been performed using a set of measurable parameters. METHODS: The study quantitatively examined orbital fracture areas (OFA) and volumes (OFV) retrospectively of 242 patients with isolated medial orbital wall fractures that were treated conservatively during a 12-year period (from 2009 to 2021). Three plastic surgeons measured enophthalmos >6 months after trauma. The correlations between parameters and enophthalmos in the study cohort were analyzed. In addition, patients treated operatively, and nonoperatively were compared with assess the suitability of the predictive model. RESULTS: Significant correlations were observed between several parameters and late enophthalmos. Total 2.59 cm 2 of OFA (ie, OFA >2.59 cm 2 ) or 1.45 cm 3 of OFV (ie, OFV >1.45 cm 3 ) corresponds to 2 mm of enophthalmos. Multiple regression analysis revealed the following coefficients: -0.208 is a constant ( P <0.001), with 0.695 and 0.372 for OFA and OFV, respectively ( P <0.001 for both OFA and OFV). CONCLUSIONS: The study shows that enophthalmos can be more accurately predicted when OFA and OFV are simultaneously considered in patients with isolated medial wall fractures. Finally, an algorithm and a "blowout fracture coordinate plane" was proposed to aid treatment decision-making in isolated medial wall fractures.

Silibinin Downregulates Types I and III Collagen Expression via Suppression of the mTOR Signaling Pathway.

Keloid scars are fibro-proliferative conditions characterized by abnormal fibroblast proliferation and excessive extracellular matrix deposition. The mammalian target of the rapamycin (mTOR) pathway has emerged as a potential therapeutic target in keloid disease. Silibinin, a natural flavonoid isolated from the seeds and fruits of the milk thistle, is known to inhibit the mTOR signaling pathway in human cervical and hepatoma cancer cells. However, the mechanisms underlying this inhibitory effect are not fully understood. This in vitro study investigated the effects of silibinin on collagen expression in normal human dermal and keloid-derived fibroblasts. We evaluated the effects of silibinin on the expressions of collagen types I and III and assessed its effects on the suppression of the mTOR signaling pathway. Our findings confirmed elevated mTOR phosphorylation levels in keloid scars compared to normal tissue specimens. Silibinin treatment significantly reduced collagen I and III expressions in normal human dermal and keloid-derived fibroblasts. These effects were accompanied by the suppression of the mTOR signaling pathway. Our findings suggest the potential of silibinin as a promising therapeutic agent for preventing and treating keloid scars. Further studies are warranted to explore the clinical application of silibinin in scar management.

Particulate matter-induced atmospheric skin aging is aggravated by UVA and inhibited by a topical l-ascorbic acid compound.

Ambient particulate matter (PM) is a major contributor to environmental air pollution-associated skin damage. However, most published studies are observational or epidemiologic and have not mechanistically investigated the effects of air pollutants on cellular senescence and aging, particularly in combination with ultraviolet (UV) radiation. Herein, we analyzed whether UVA aggravates the PM-induced inflammatory cascade, which contributes to the aging of skin-derived cells. We hypothesized that cellular senescence is involved in PM&UVA-induced aging and tested whether an l-ascorbic acid compound (LAC), containing vitamin E and ferulic acid, can inhibit PM&UVA-induced aging. PM&UVA-exposed HDFs showed further elevated reactive oxygen species (ROS) levels detected by flow cytometry. We then demonstrated that PM induces MAPK signaling activation and the expression of AhR and NF-κB, responses that are both exacerbated by UVA. The levels of inflammatory cytokines, IL-1ß and IL-6, were significantly higher in the PM&UVA-exposed group which resulted in increased transcription of MMPs, causing downregulation of type I collagen. Meanwhile, treatment with LAC reduced the levels of ROS and inflammatory cytokines. Additionally, PM&UVA-induced SA-ß-gal production (staining assay) was reduced by LAC. These findings suggest a role of atmospheric pollution and UVA radiation in cellular senescence induction. Our findings also suggest a possible role of AhR inhibition by topical antioxidants to prevent atmospheric pollution-induced skin aging.

Effect of Mortalin on Scar Formation in Human Dermal Fibroblasts and a Rat Incisional Scar Model.

Wound healing is a complicated cascading process; disequilibrium among reparative processes leads to the formation of pathologic scars. Herein, we explored the role of mortalin in scar formation and its association with the interleukin-1α receptor using in vitro and in vivo models. To investigate the effects of mortalin, we performed an MTT cell viability assay, qRT-PCR, and Western blot analyses, in addition to immunofluorescence and immunoprecipitation studies using cultured fibroblasts. A rat incisional wound model was used to evaluate the effect of a mortalin-specific shRNA (dE1-RGD/GFP/shMot) Ad vector in scar tissue. In vitro, the mortalin-treated human dermal fibroblast displayed a significant increase in proliferation of type I collagen, α-smooth muscle actin, transforming growth factor-ß, phospho-Smad2/3-complex, and NF-κB levels. Immunofluorescence staining revealed markedly increased mortalin and interleukin-1α receptor protein in keloid tissue compared to those in normal tissue, suggesting that the association between mortalin and IL-1α receptor was responsible for the fibrogenic effect. In vivo, mortalin-specific shRNA-expressing Ad vectors significantly decreased the scar size and type-I-collagen, α-SMA, and phospho-Smad2/3-complex expression in rat incisional scar tissue. Thus, dE1-RGD/GEP/shMot can inhibit the TGF-ß/α-SMA axis and NF-κB signal pathways in scar formation, and blocking endogenous mortalin could be a potential therapeutic target for keloids.

Metformin Inhibits Transforming Growth Factor ß-Induced Fibrogenic Response of Human Dermal Fibroblasts and Suppresses Fibrosis in Keloid Spheroids.

ABSTRACT: Accumulation of excessive extracellular matrix (ECM) and aberrant transforming growth factor ß (TGF-ß) signaling pathway function can be potential therapeutic targets for keloid treatment. In this study, we examined the antifibrotic effect of metformin as a suppressor of TGF-ß signaling pathways in human dermal fibroblasts (HDFs) and keloid spheroids. Human dermal fibroblasts were stimulated with TGF-ß (10 ng/mL) and treated with metformin (10 mM). The mRNA and protein expression of ECM components were evaluated by quantitative polymerase chain reaction, western blot, and immunofluorescence assay. In addition, we immunohistochemically examined the expression levels of ECM proteins in keloid spheroids. After addition of metformin (10 mM), collagen types I and III and elastin mRNA levels were significantly decreased in HDFs, and collagen type I protein level was significantly decreased. In addition, the expression levels of collagen types I and III, fibronectin, and elastin were significantly reduced in keloid spheroids after treatment with metformin (100 mM). Collagen types I and III and p-Smad2/3 complex proteins were decreased in metformin-treated keloid spheroids. These findings indicated that metformin inhibits the expression of ECM components in TGF-ß-stimulated HDFs and keloid spheroids. Therefore, we suggest the potential of metformin as an effective agent for the treatment of keloids.

Synergistic Effect of 300 µm Needle-Depth Fractional Microneedling Radiofrequency on the Treatment of Senescence-Induced Aging Hyperpigmentation of the Skin.

Aging-associated dermatological pigmentary diseases are associated with accumulation of senescence cells and the disruption of basement membrane due to chronic ultraviolet radiation (UVR) exposure. Our study is on the synergistic effect of the novel 300 µm needle-depth fractional microneedling radiofrequency (FMR) treatment and conventional Q-switched ND:YAG laser on aging-associated hyperpigmentation of the skin. The prospective controlled clinical trial of 25 Asian women revealed significantly higher improvements not only on wrinkles, but also on hyperpigmentation. Additional ex vivo study revealed significant reduction of pro-melanogenic markers as well as senescent keratinocytes, while increased expression of collagen type IV on the epidermal basement membrane, after additional FMR treatment on UV-irradiated human tissues. These results demonstrate that 300 µm needle-depth FMR might effectively remove senescent keratinocytes that secrete pro-melanogenic markers, and repair disrupted basement membrane, therefore preventing constant hyperpigmentation of the aged skin.

Tissue-remodelling M2 Macrophages Recruits Matrix Metallo-proteinase-9 for Cryotherapy-induced Fibrotic Resolution during Keloid Treatment.

Cryotherapy is used to treat keloid scars; however, the molecular and pathological mechanisms are not clearly understood. This study retrospectively evaluated the efficacy of combined treatment with cryotherapy and intralesional triamcinolone injection (Cryo+TA) or intralesional TA monotherapy (TA) in 40 Asian patients with keloid scars. Scar improvement was assessed using the Vancouver Scar Scale and Global Improvement Scale. Clinical improvement in scars, especially reduced vascularity and redness, was significantly greater in the Cryo+TA group than in the TA group. Cryotherapy-treated and untreated keloid tissue was collected from six patients for analysis. Histo-logically, collagen bundles from cryotherapy-treated keloid tissue were more fibrillar and abnormal thickness was reduced. Immunohistochemical staining showed a reduced number of dermal vessels after cryotherapy. Moreover, CD163+ M2 macrophages and matrix metalloproteinase-9 (MMP-9) were significantly increased in cryotherapy-treated tissue. Double immunofluorescence staining revealed co-expression of CD163 and MMP-9. These data indicate that cryotherapy recruits tissue-remodelling M2 macrophages with accompanying MMP-9, suggesting that cryotherapy-recruited M2 macrophages function in fibrotic resolution during keloid treatment.

Safety of Combined Fractional Microneedle Radiofrequency and CO2 as an Early Intervention for Inflammatory Acne and Scarring Treated With Concomitant Isotretinoin.

BACKGROUND: Fractional microneedle radiofrequency (FMRF) systems are popular options for treating acne scars. However, treatment efficacy when used in combination with traditional ablative fractional laser (AFL) and the safety profile with concomitant use of isotretinoin remain unknown. OBJECTIVE: The aim of this study was to assess the safety and efficacy of an early intervention combination treatment protocol for inflammatory acne and acne scars. MATERIALS AND METHODS: The electronic records of 71 patients with inflammatory acne and acne scars were included in this retrospective observational study. Data were collected for all patients who received combination FMRF and AFL. Within the study group, 43 patients were receiving low-dose isotretinoin or had completed isotretinoin within the past 3 weeks. RESULTS: The mean Scar Global Assessment score significantly decreased after 3 sessions of combination treatment (n = 71). Patients with inflammatory acne showed a significant decrease in the number of inflammatory lesions (n = 30). Patients with concomitant low-dose isotretinoin use reported a further decrease in Scar Global Assessment score (n = 43). There were no reported persistent side effects, including prolonged inflammatory reaction or scarring. CONCLUSION: Combination treatment with FMRF and AFL is an effective and well-tolerated treatment modality for acne scars and inflammatory acne.

Dickkopf 2-Expressing Adenovirus Increases the Survival of Random-Pattern Flaps and Promotes Vasculogenesis in a Rat Model.

BACKGROUND: Dickkopf 2 (DKK2) has important roles in vertebrate development; it inhibits Wnt signaling-related processes, such as axial patterning, limb development, somitogenesis, and eye formation. However, DKK2 also acts as a Wnt signaling agonist. Dickkopf 2, induced during endothelial cell morphogenesis, promotes angiogenesis in cultured human endothelial cells. In this study, we explored the effect of DKK2-expressing adenovirus on random-pattern flaps using a rodent model. METHODS: A DKK2-expressing (dE1-RGD/DKK2) adenovirus was generated and 20 Sprague-Dawley rats were randomly divided into 2 groups: a DKK2 group and a control group. Each group was intradermally injected with 1 × 10 plaque-forming units of DKK2-expressing adenovirus (DKK2 group) or control virus (control group) 48 hours before and immediately before surgery. Then, random-pattern dorsal cutaneous flaps of 3 × 9 cm were elevated. Flap survival rates and cutaneous blood flow were measured over time, and immunohistochemical staining was performed 10 days after surgery to detect CD31 and vascular endothelial growth factor (VEGF). RESULTS: Immunofluorescence staining confirmed the expression of DKK2 in the DKK2 group. The flap survival rate was higher in the DKK2 group (80.0 ± 4.49%) than in the control group (57.5 ± 4.21%; P < 0.05). Blood flow to the most distal compartment was higher in the DKK2 group than the control group during the early postoperative period. Although vascular density was greater in the DKK2 group, there was no difference in the VEGF concentration between groups. CONCLUSIONS: The findings of the present study suggest that the DKK2-expressing adenovirus increases the survival of the random-pattern cutaneous flap independently of VEGF. The administration of the DKK2-expressing adenovirus into elevated skin flaps increased the number of capillaries and blood flow, thereby improving skin flap survival.

Demographic Factors of Nasal Bone Fractures and Social Reflection.

INTRODUCTION: The nose is the most protruding central part of the face, and nasal bone fractures are the most common of facial bone fractures, leading up to 39%. Despite its high frequency, not many studies handled the etiology of nasal bone fractures, leading to the necessity of a recent demographic study. MATERIALS AND METHODS: A total of 1111 patients diagnosed with nasal bone fracture from 2013 to 2018 at our institute were evaluated. A retrospective review of the various demographic and etiologic characteristics was done. RESULTS: Numerous factors associated with nasal bone fractures were analyzed. Male patients were 3.3 times greater than the number of female patients, and twenties were the most common age range. Violence was the overall most common cause of injury, while slip down was the most common cause for females. Upon monthly distribution, the highest incidence of nasal bone fractures occurred in September, followed by March and December. The authors further divided the patients by time zone of the fractures, and male patients were most commonly injured from midnight to 3 AM, while female patients were 6 PM to 9 PM. CONCLUSION: Our findings represent a recent urban data of various etiologic factors of nasal bone fracture. The concept of school violence has been widely used since 1990s, and our data reflects that violence of the youth is a serious issue of the society. The mechanism of injury differed among sexes and age groups, and such discrepancies will aid physicians to better understand facial bone fracture patients and educate them in the future.

Huge Anterior Skull Base Defect Reconstruction on Communicating Between Cranium and Nasal Cavity: Combination Flap of Galeal Flap and Reverse Temporalis Flap.

INTRODUCTION: Traditionally, galeal flap or cranialization was often used to reconstruct the skull base defect caused by trauma or tumor removal. However, in the case of huge skull base defect, galeal flap is not enough to block the communication between nasal cavity and intracranial space. In this study, authors suggest combination flap of galea and reverse temporalis muscle as a method for reconstruction of huge skull base defect. MATERIALS AND METHODS: From 2016 to 2019, retrospective review was conducted, assessing 7 patients with bone defect which is not just opening of frontal sinus but extends to frontal sinus and cribriform plate. Reconstructions were done by combination of galeal flap and reverse temporalis muscle flap transposition. RESULTS: Defects were caused by nasal cavity tumor with intracranial extension or brain tumor with nasal cavity extension. There was no major complication in every case. During the follow up period, no patient had signs of complication such as ascending infection, herniation and CSF rhinorrhea. Postoperative radiologic images of all patients that were taken at least 6 months after the surgery showed that flaps maintained the lining and the volume well. DISCUSSION: Conventional reconstruction of skull base defect with galeal flap is not effective enough to cover the large sized defect. In conclusion, galeal flap in combination with reverse temporalis muscle flap can effectively block the communication of nasal cavity and intracranium.

Sustained Release of Decoy Wnt Receptor (sLRP6E1E2)-Expressing Adenovirus Using Gel-Encapsulation for Scar Remodeling in Pig Model.

An adenoviral vector (Ad) expressing a Wnt decoy receptor (sLRP6E1E2) is known to induce an anti-fibrotic effect by inhibiting Wnt signaling. We evaluated its effects in vivo using pig models and attempted to introduce an alginate gel-matrix system to prolong the effect of the Ad. Transduction efficiency as to the biological activity of Ad in different forms was evaluated. Then, 50 days after the formation of full-thickness skin defects on the backs of Yorkshire pigs, scars were treated with each form of Ad. Therapeutic efficacy and various factors influencing scar formation and collagen rearrangement were analyzed. Inflammatory cell infiltration within the scar tissues was also evaluated. Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus treatment improved scar quality in a pig model. Loading this construct in alginate gel allows sustained virus release into local tissues and prolongs Ad activity, thus maintaining its therapeutic effect longer in vivo.

Combined Therapeutic Strategies for Keloid Treatment.

BACKGROUND: Recent advances in keloid management favor the administration of combination therapy over monotherapy. OBJECTIVE: The authors evaluated the safety and efficacy of combination therapy to treat keloids using fractional lasers, cryotherapy, and intralesional corticosteroids. MATERIALS AND METHODS: The authors performed a retrospective study involving 35 Korean patients. Each patient underwent treatment using the 1,550 nm nonablative fractional erbium-glass laser, followed by the 10,600 nm ablative fractional carbon dioxide laser. Laser treatment was immediately followed by the administration of superficial cryotherapy and intralesional triamcinolone injection. Therapeutic efficacy was assessed using the Vancouver Scar Scale (VSS) score and the 7-point patient self-assessment score. RESULTS: The mean total and subcategory VSS scores showed statistically significant improvements. The height and pliability scores showed the most significant and quickest responses to the combination therapy. The patients reported remarkable improvement in itching, pain, and limitations of motion after a single combination therapy session. Twenty patients were followed up for 1 year after the discontinuation of the combination treatment, and the recurrence was observed only in one patient. No significant adverse effects were observed throughout the follow-up period. CONCLUSION: Combination keloid therapy using fractional lasers, superficial cryotherapy, and intralesional triamcinolone injection is safe and more effective than individual monotherapies.

A Novel Technique of Asian Tip Plasty: Rein-Shaped Columellar Strut Graft.

BACKGROUND: The columellar strut graft is one of the most commonly used invisible grafts in tip plasty techniques for nasal tip projection. However, the columellar strut graft induces cephalic rotation of the dome with nasal tip projection. This is an effective change in Western people with a long nose; however, this change should be avoided in Asians who have a relatively short nose and visible nostrils. We designed a more convenient and effective technique using a rein-shaped columellar strut graft that can prevent cephalic rotation of the dome. METHODS: A total of 32 patients underwent surgery with a rein-shaped columellar strut graft with a septal cartilage. The projection and location of the nasal tip, nasal length, and nasolabial angle were measured after taking a photograph of the lateral view, and the preoperative and postoperative results were compared. RESULTS: There were statistically significant differences between the preoperative and postoperative values of the nasal tip projection ratio and nasal tip location ratio. There were no revision surgeries and no direct complications associated with the use of the columellar strut graft. CONCLUSION: We performed tip plasty with a modified columellar strut graft-the rein-shaped columellar strut graft. In most cases of using this method, the tip projection was increased and the cephalic rotation of the tip was prevented. This surgical procedure can also be used for lengthening (rotating caudally) of the nose in some cases, as well as for the purpose of preventing the cephalic rotation of the tip. 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 .

Antifibrotic Effects of High-Mobility Group Box 1 Protein Inhibitor (Glycyrrhizin) on Keloid Fibroblasts and Keloid Spheroids through Reduction of Autophagy and Induction of Apoptosis.

Overabundance of extracellular matrix resulting from hyperproliferation of keloid fibroblasts (KFs) and dysregulation of apoptosis represents the main pathophysiology underlying keloids. High-mobility group box 1 (HMGB1) plays important roles in the regulation of cellular death. Suppression of HMGB1 inhibits autophagy while increasing apoptosis. Suppression of HMGB1 with glycyrrhizin has therapeutic benefits in fibrotic diseases. In this study, we explored the possible involvement of autophagy and HMGB1 as a cell death regulator in keloid pathogenesis. We have highlighted the potential utility of glycyrrhizin as an antifibrotic agent via regulation of the aberrant balance between autophagy and apoptosis in keloids. Higher HMGB1 expression and enhanced autophagy were observed in keloids. The proliferation of KFs was decreased following glycyrrhizin treatment. While apoptosis was enhanced in keloids after glycyrrhizin treatment, autophagy was significantly reduced. The expressions of ERK1/2, Akt, and NF-κB, were enhanced in HMGB1-teated fibroblasts, but decreased following glycyrrhizin treatment. The expression of extracellular matrix (ECM) components was reduced in glycyrrhizin-treated keloids. TGF-ß, Smad2/3, ERK1/2, and HMGB1 were decreased in glycyrrhizin-treated keloids. Treatment with the autophagy inhibitor 3-MA resulted in a decrease of autophagy markers and collagen in the TGF-ß-treated fibroblasts. The results indicated that autophagy plays an important role in the pathogenesis of keloids. Because glycyrrhizin appears to reduce ECM and downregulate autophagy in keloids, its potential use for treatment of keloids is indicated.

Hypoxia-Induced Epithelial-To-Mesenchymal Transition Mediates Fibroblast Abnormalities via ERK Activation in Cutaneous Wound Healing.

Previous studies described the involvement of extracellular signal-related kinase (ERK) in systemic fibrotic diseases, but the role of ERK in cutaneous scarring is unknown. Although hypoxia drives tissue fibrosis by activating hypoxia-inducible factor-1α (HIF-1α), the specific roles of hypoxia and associated ERK phosphorylation in abnormal fibroblast activity during cutaneous scarring are unclear. Here, we investigated whether pathologic myofibroblast-like keloid fibroblast activity is promoted by hypoxia-induced epithelial-mesenchymal transition mediated by ERK activation. ERK phosphorylation was significantly increased in keloid tissue and fibroblasts. Human dermal fibroblasts cultured under hypoxia (1% O2) expressed phosphorylated ERK and exhibited activation of p38 mitogen-activated protein kinase signaling. Hypoxic human dermal fibroblasts showed increased protein and mRNA levels of epithelial-mesenchymal transition markers. Furthermore, administration of an ERK inhibitor (SCH772984) reduced the hypoxia-induced elevation of collagen type I levels in human dermal fibroblasts. Therefore, ERK may be a promising therapeutic target in profibrogenic diseases.

Comparison of the efficacy and safety of povidone-iodine foam dressing (Betafoam), hydrocellular foam dressing (Allevyn), and petrolatum gauze for split-thickness skin graft donor site dressing.

We evaluated the efficacy and safety of a povidone-iodine (PVP-I) foam dressing (Betafoam) for donor site dressing versus a hydrocellular foam dressing (Allevyn) and petrolatum gauze. This prospective Phase 4 study was conducted between March 2016 and April 2017 at eight sites in Korea. A total of 106 consenting patients (aged ≥ 19 years, scheduled for split-thickness skin graft) were randomised 1:1:1 to PVP-I foam, hydrocellular, or petrolatum gauze dressings for up to 28 days after donor site collection. We assessed time to complete epithelialisation, proportion with complete epithelialisation at Day 14, and wound infection. Epithelialisation time was the shortest with PVP-I foam dressing (12.74 ± 3.51 days) versus hydrocellular foam dressing (16.61 ± 4.45 days; P = 0.0003) and petrolatum gauze (15.06 ± 4.26 days, P = 0.0205). At Day 14, 83.87% of PVP-I foam dressing donor sites had complete epithelialisation, versus 36.36% of hydrocellular foam dressing donor sites (P = 0.0001) and 55.88% of petrolatum gauze donor sites (P = 0.0146). There were no wound infections. Incidence rates of adverse events were comparable across groups (P = 0.1940). PVP-I foam dressing required less time to complete epithelialisation and had a good safety profile.

Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3.

BACKGROUND/AIMS: Radiation-induced skin fibrosis is a common side effect of clinical radiotherapy. Our previous next-generation sequencing (NGS) study demonstrated the reduced expression of the regulatory α subunit of phosphatidylinositol 3-kinase (PIK3r1) in irradiated murine skin. Metformin has been reported to target the PIK3-FOXO3 pathway. In this study, we investigated the effects of metformin on radiation-induced skin fibrosis. METHODS: Metformin was orally administered to irradiated mice. Skin fibrosis was analyzed by staining with H&E and Masson's trichrome stain. The levels of cytokines and chemokines associated with fibrosis were analyzed by immunohistochemistry and quantitative RT-PCR. The roles of PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl and transfecting FOXO3 siRNA in NIH3T3 cells and mouse-derived dermal fibroblasts (MDF). RESULTS: The oral administration of metformin significantly reduced radiation-induced skin thickening and collagen accumulation and significantly reduced the radiation-induced expression of FOXO3 in murine skin. Additionally, the overexpression of PIK3r1 reduced the radiation-induced expression of FOXO3, while FOXO3 silencing decreased the radiation-induced expression of TGFß in vitro. CONCLUSIONS: The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1. Collectively, the data obtained in this study suggested that metformin could be a potent therapeutic agent for alleviating radiation-induced skin fibrosis.