Exosomes Derived from Hypertrophic Scar Fibroblasts Suppress Melanogenesis in Normal Human Epidermal Melanocytes.

Post-burn hypertrophic scars often exhibit abnormal pigmentation. Exosomes play important roles in maintaining normal physiological homeostasis and in the pathological development of diseases. This study investigated the effects of the exosomes derived from hypertrophic scar fibroblasts (HTSFs) on melanocytes, which are pigment-producing cells. Normal fibroblasts (NFs) and HTSFs were isolated and cultured from normal skin and hypertrophic scar (HTS) tissue. Both the NF- and HTSF-exosomes were isolated from a cell culture medium and purified using a column-based technique. The normal human epidermal melanocytes were treated with both exosomes at a concentration of 100 µg/mL at different times. The cell proliferation, melanin content in the medium, apoptotic factors, transcription factors, melanin synthesis enzymes, signaling, signal transduction pathways, and activators of transcription factors (STAT) 1, 3, 5, and 6 were investigated. Compared with the Dulbecco's phosphate-buffered saline (DPBS)-treated controls and NF-exosomes, the HTSF-exosomes decreased the melanocyte proliferation and melanin secretion. The molecular patterns of apoptosis, proliferation, melanin synthesis, Smad and non-Smad signaling, and STATs were altered by the treatment with the HTSF-exosomes. No significant differences were observed between the DPBS-treated control and NF-exosome-treated cells. HTSF-derived exosomes may play a role in the pathological epidermal hypopigmentation observed in patients with HTS.

Sex differences in the skin microbiome of burn scars.

Sex differences are observed in various spectrums of skin diseases, and there are differences in wound healing rate. Herein, sex differences were identified for the newly healed skin microbiome of burn patients. Fifty-two skin samples (26 normal skin, 26 burn scars) were collected from 26 burn patients (12 male, 14 female) and microbiota analysis was performed. The correlation between skin microbiota and biomechanical properties of burn scars was also investigated. There were no significant differences in clinical characteristics between male and female patients. Considering the biomechanical properties of burn scars and normal skin around it performed before sample collection, the mean erythema level of men's normal skin was significantly higher than that of women, whereas the mean levels of melanin, transepidermal water loss and skin hydration showed no significant sex differences. The erythrocyte sedimentation rate was significantly higher in females than that in males. Alpha diversity showed no significant differences between normal skin and burn scars in the male group. However, the scar was significantly higher than that of normal skin in the female group. Microbial network analysis revealed that the male group had more complex microbial network than the female group. Additionally, in the male group, the edge density and clustering coefficient were higher in burn scars when compared to normal skin, than the female group. There were sex differences in the results of microbiome of normal skin and burn scars. Some of the altered microbiota have been correlated with the biomechanical properties of burn scars. In conclusion, sex difference in the burn scar microbiome was confirmed. These results suggest that burn treatment strategies should vary with sex.

Effects of Factors Influencing Scar Formation on the Scar Microbiome in Patients with Burns.

Skin microbiome dysbiosis has deleterious effects, and the factors influencing burn scar formation, which affects the scar microbiome composition, are unknown. Therefore, we investigated the effects of various factors influencing scar formation on the scar microbiome composition in patients with burns. We collected samples from the burn scar center and margin of 40 patients with burns, subgrouped by factors influencing scar formation. Scar microbiome composition-influencing factors were analyzed using univariate and multivariate analyses. Skin graft, hospitalization period, intensive care unit (ICU) admission, burn degree, sex, age, total body surface area burned (TBSA), time post-injury, transepidermal water loss, the erythrocyte sedimentation rate, and C-reactive protein levels were identified as factors influencing burn scar microbiome composition. Only TBSA and ICU admission were associated with significant differences in alpha diversity. Alpha diversity significantly decreased with an increase in TBSA and was significantly lower in patients admitted to the ICU than in those not admitted to the ICU. Furthermore, we identified microorganisms associated with various explanatory variables. Our cross-sectional systems biology study confirmed that various variables influence the scar microbiome composition in patients with burns, each of which is associated with various microorganisms. Therefore, these factors should be considered during the application of skin microbiota for burn scar management.

Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin.

Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell-cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 µg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.

Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts.

Post-burn hypertrophic scars are characterized by excessive accumulation of extracellular matrix secreted by fibroblasts. Exosomes are membrane lipid extracellular vesicles that play a pivotal role in cellular communication. Previous studies revealed the role of stem cell-derived exosomes in repairing damaged tissues, and also showed that cancer cell-derived exosomes could affect the disease pathogenesis. However, the functional properties of exosomes derived from hypertrophic scar fibroblasts (HTSFs) have not yet been studied extensively. In this study, we aimed to investigate whether HTSFs-derived exosomes can change the fibrosis-related signaling pathways in human normal fibroblasts (HNFs). HTSFs and HNFs were isolated from human hypertrophic scar tissues. HTSFs-derived exosomes were extracted and treated to HNFs. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect mRNA and protein expression, respectively, and cell proliferation and mobility were also assessed. Exosome treatment markedly increased cell proliferation and migration, and induced small mother against decapentaplegic (SMAD) signaling by increasing the levels of phosphorylated SMAD2 and SMAD1/5/8. The levels of TAK1 signaling components were also increased after exosome treatment to HNFs, including phosphorylated TAK1, p38, ERK, and JNK. HTSFs-derived exosomes further induced the epithelial-mesenchymal transition by decreasing the expression level of E-cadherin and increasing the expression levels of N-cadherin and vimentin. Consequently, the expression levels of fibronectin, type Ⅰ collagen, and type Ⅲ collagen were increased. Our results demonstrate the fibrotic property of HTSFs-derived exosomes, which suggests a potential functional role in hypertrophic scar development and a new therapeutic target.

CPEB1 or CPEB4 knockdown suppresses the TAK1 and Smad signalings in THP-1 macrophage-like cells and dermal fibroblasts.

Post-burn hypertrophic scar (HTS) is a form of excessive dermal fibrosis characterized by cutaneous scarring, which is common in patients following burn injury. Moreover, at least 50% of HTS are accompanied by inflammation. Cytoplasmic polyadenylation element binding (CPEB) proteins are key mRNA-binding proteins that control the translation of several mRNAs. However, their potential roles in treating dermal fibrosis and scarring remain unknown. Therefore, in this study, we aimed to investigate the effects of small interfering RNA (siRNA)-mediated knockdown of CPEB1 or CPEB4 in human THP-1 macrophages and dermal fibroblasts treated with LPS and TGF-ß1. We found significantly increased CPEB1 and CPEB4 mRNA and protein levels in LPS-treated THP-1 cells and TGF-ß1-treated fibroblasts. CPEB1 and CPEB4 knockdowns suppressed LPS-activated TAK1 signaling cascades by reducing the levels of TNF-α and phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65 in THP-1 cells. CPEB1 and CPEB4 knockdowns also attenuated TGF-ß1-activated Smad-dependent and -independent signaling cascades by reducing the levels of TAK1, p38, ERK, JNK, and phosphorylated Smad 2 and Smad 1/5/8 in fibroblasts. Furthermore, CPEB1 or CPEB4 knockdown markedly decreased the levels of fibrosis markers, including α-SMA, type I collagen, and fibronectin in fibroblasts. Our findings indicate that CPEB1 and CPEB4 are involved in the regulation of the TAK1 and Smad signalings in human macrophages and dermal fibroblasts. These activities may play a role in cutaneous scarring responses.

Effect of Combining Low Temperature Plasma, Negative Pressure Wound Therapy, and Bone Marrow Mesenchymal Stem Cells on an Acute Skin Wound Healing Mouse Model.

Low-temperature plasma (LTP; 3 min/day), negative pressure wound therapy (NPWT; 4 h/day), and bone marrow mesenchymal stem cells (MSCs; 1×106 cells/day) were used as mono- and combination therapy in an acute excisional skin wound-healing ICR mouse model. These therapies have been beneficial in treating wounds. We investigated the effectiveness of monotherapy with LTP, NPWT, and MSC and combination therapy with LTP + MSC, LTP + NPWT, NPWT + MSC, and LTP + NPWT + MSC on skin wounds in mice for seven consecutive days. Gene expression, protein expression, and epithelial thickness were analyzed using real time polymerase chain reaction (RT-qPCR), western blotting, and hematoxylin and eosin staining (H&E), respectively. Wound closure was also evaluated. Wound closure was significantly accelerated in monotherapy groups, whereas more accelerated in combination therapy groups. Tumor necrosis factor-α (TNF-α) expression was increased in the LTP monotherapy group but decreased in the NPWT, MSC, and combination therapy groups. Expressions of vascular endothelial growth factor (VEGF), α-smooth muscle actin (α-SMA), and type I collagen were increased in the combination therapy groups. Re-epithelialization was also considerably accelerated in combination therapy groups. Our findings suggest that combination therapy with LPT, NPWT, and MSC exert a synergistic effect on wound healing, representing a promising strategy for the treatment of acute wounds.

Extracorporeal Shock Wave Therapy Alters the Expression of Fibrosis-Related Molecules in Fibroblast Derived from Human Hypertrophic Scar.

Extracorporeal shock wave therapy (ESWT) considerably improves the appearance and symptoms of post-burn hypertrophic scars (HTS). However, the mechanism underlying the observed beneficial effects is not well understood. The objective of this study was to elucidate the mechanism underlying changes in cellular and molecular biology that is induced by ESWT of fibroblasts derived from scar tissue (HTSFs). We cultured primary dermal fibroblasts derived from human HTS and exposed these cells to 1000 impulses of 0.03, 0.1, and 0.3 mJ/mm². At 24 h and 72 h after treatment, real-time PCR and western blotting were used to detect mRNA and protein expression, respectively, and cell viability and mobility were assessed. While HTSF viability was not affected, migration was decreased by ESWT. Transforming growth factor beta 1 (TGF-ß1) expression was reduced and alpha smooth muscle actin (α-SMA), collagen-I, fibronectin, and twist-1 were reduced significantly after ESWT. Expression of E-cadherin was increased, while that of N-cadherin was reduced. Expression of inhibitor of DNA binding 1 and 2 was increased. In conclusion, suppressed epithelial-mesenchymal transition might be responsible for the anti-scarring effect of ESWT, and has potential as a therapeutic target in the management of post-burn scars.

Gait Performance and Brain Activity Are Improved by Gait Automatization during Robot-Assisted Gait Training in Patients with Burns: A Prospective, Randomized, Single-Blinded Study.

Background: Patients with lower extremity burn injuries have decreased gait function. Gait dysfunctions are compensated by activation of executive areas such as the prefrontal cortex (PFC). Although robot-assisted gait training (RAGT) can improve gait function, the training mechanisms of RAGT are unknown. We aimed to determine the clinical effects of RAGT in patients with burns and investigate their underlying mechanisms. Methods: This single-blind, randomized controlled trial involved 54 patients with lower extremity burns. The RAGT group underwent RAGT using SUBAR® and conventional training. The control (CON) group underwent only conventional training. The primary outcome was cortical activity measured using a functional near-infrared spectroscopy device before and after 8 weeks of training to confirm the compensatory effect of gait dysfunction. The secondary outcomes were the functional ambulation category (FAC) to evaluate gait performance, 6-min walking test (6 MWT) distance to measure gait speed, isometric force and range of motion (ROM) of lower extremities to evaluate physical function, and the visual analog scale (VAS) score to evaluate subjective pain during gait. Results: PFC activation during the gait phase in the RAGT group decreased significantly compared with that of the CON. The VAS score decreased and FAC score improved after 8 weeks of training in both groups. The 6 MWT scores, isometric strengths (the left knee flexor and bilateral ankle plantar flexors), and the ROMs (the extensions of bilateral hip and bilateral knee) of the RAGT group were significantly improved compared with those of the CON. RAGT improved gait speed, lower extremity ROMs, and lower extremity muscles strengths in patients with burns. Conclusions: The improvement in gait speed and cerebral blood flow evaluation results suggests that the automatization of gait is related to the treatment mechanism during RAGT.

Clinical utility of extracorporeal shock wave therapy in restoring hand function of patients with nerve injury and hypertrophic scars due to burns: A prospective, randomized, double-blinded study.

BACKGROUND: Joint contractures and nerve injuries are common after hand burns. Extracorporeal shock wave therapy (ESWT) is effective not only for the regeneration of various tissues, including scar tissues, but also for reducing pain and pruritus in patients with burns. Researchers have attempted to explore the effects of ESWT on hand dysfunction caused by nerve injury following burns. MATERIALS AND METHODS: We evaluated the effects of ESWT (compared to sham stimulation) on hands with nerve injury and hypertrophic scars and thereby on hand function. The current study was a double-blind randomized controlled trial involving 120 patients. The ESWT parameters were as follows: energy flux density, 0.05-0.30 mJ/mm2; frequency, 4 Hz; 1000 to 3000 impulses per treatment; and 12 treatments, one/week for 12 weeks. Outcome measures were as follows: 10-point visual analog scale for pain, Jebsen-Taylor hand function test, grip strength, Purdue Pegboard test, ultrasound measurement of scar thickness, and skin characteristics before and immediately after 12 weeks of treatment. RESULTS: No significant inter-group difference was noted after the initial evaluation (P>0.05). More significant improvements were found in the ESWT group than in the sham group in terms of the VAS score (P=0.004), extension ROMs of hand joints (P=0.02), the JTT scores (writing, small, and light) (P<0.001, P<0.001, and P=0.002), and skin characteristics (melanin, skin distensibility, and biologic skin elasticity) (P=0.004, P<0.001, and P<0.001). Other measured outcomes did not differ between the two groups after the treatment. CONCLUSION: We identified the clinically beneficial effects of ESWT in promoting hand function, improving scarring, and alleviating scarring-related pain, thereby highlighting its advantages in improving hand function that has been impaired due to nerve injury and hypertrophic scars after burns.

Effect of extracorporeal shock wave therapy on the microbial community in burn scars: retrospective case-control study.

BACKGROUND: The effectiveness of extracorporeal shock wave therapy (ESWT) has been demonstrated in various medical fields, including burn medicine. It promotes wound healing, improves blood flow, and modulates the inflammatory responses. The recovery speed and outcomes of skin diseases are influenced by the skin microbiome; however, studies examining the effects of specific treatments on the skin microbiome are lacking. This study investigated the impact of ESWT on the skin microbiome of burn patients, focusing on the microbial diversity and community structure within burn scars. MATERIALS AND METHODS: In the retrospective case-control study, nineteen patients with burn scars were treated with ESWT, and changes in their skin microbiome were evaluated. ESWT was administered weekly for three months, and samples were collected from the ESWT-treated burn scars and untreated normal skin. Blood chemistry, and pain and itching scores were evaluated during sample collection. The collected samples were then subjected to 16S rRNA sequencing. Microbial community analysis was conducted using the QIIME2 and R packages. RESULTS: After ESWT, changes in alpha diversity indices were observed in burn scars. Faith phylogenetic diversity (P<0.05) and observed features (P<0.01) increased, whereas the evenness index decreased (P<0.01); no marked changes were noted in untreated skin. Beta diversity analysis showed stable microbial community structures in both the treated and untreated areas. A considerable increase in Micrococcus and Staphylococcus abundance was observed. Network analysis revealed a more open microbial network structure after ESWT, indicating adaptive changes in the microbial community. CONCLUSION: ESWT enhances microbial diversity and modifies microbial community structure in burn scars, promoting a more balanced and functionally supportive microbiome. ESWT aids in scar remodeling and positively influences skin microbiome dynamics, contributing to improved skin health and recovery.

Utility of customized 3D compression mask with pressure sensors on facial burn scars: A single-blinded, randomized controlled trial.

PURPOSE: A pressure of approximately 15-25 mmHg is used for effective compression therapy to prevent and treat hypertrophic scar formation in patients with burns. However, conventional facial compression garments present challenges owing to inadequate pressure distribution in curved areas such as the cheeks, around the mouth, and the slope of the nose. This study aimed to evaluate the utility of a custom-made 3D compression mask equipped with pressure sensors to treat facial burn scars. METHODS: This single-blinded, prospective randomized controlled trial was conducted between May and October 2023, involving 48 burn scars in 12 inpatients with facial burns. We created the custom-made 3D compression mask equipped with pressure sensors, inner lined with biocompatible silicon, and a harness system using 3D printing technology, which can continuously monitor whether an appropriate pressure of 15-25 mmHg maintains. The biological scar properties, Vancouver Scar Scale (VSS), and Patient and Observer Scar Assessment Scale (POSAS) scores in patients with facial burns were assessed before applying the compression mask and garment and at 4 and 12 weeks after application. RESULTS: Pre-application assessment of biological scar properties, VSS, and POSAS revealed no statistically significant differences between the 3D mask and control groups (p > 0.05 for all). Throughout the 12-week application, skin hydration and scar thickness significantly increased (p < 0.001) and reduced (p = 0.010), respectively, in the 3D mask group compared to the control group. Additionally, significant improvements in scar pliability (p = 0.004) and height (p = 0.009) of VSS, itching (p = 0.047), scar stiffness (p = 0.001), thickness (p = 0.011), and irregularity (p < 0.001) of POSAS-patient component, and scar thickness (p = 0.001), pliability (p = 0.012), and surface area (p = 0.027) of the POSAS-observer component were observed in 3D mask group throughout the 12-week application compared to the control group. CONCLUSION: The customized 3D compression mask equipped with pressure sensors significantly improved scar thickness, skin hydration, and various assessment scale parameters throughout the 12-week application.

Clinical Utility of Robot-Assisted Gait Training in Patients with Spinal Cord Injury Caused by Electrical Burns: A Case Report.

Robot-assisted gait training (RAGT) has been proven effective in improving gait function in not only patients with central nervous system damage, but also in patients who have undergone musculoskeletal surgery. Nevertheless, evidence supporting the efficacy of such training in burn patients remains insufficient. This report aimed to evaluate the effect of RAGT in burn patients with spinal cord injuries (SCI) caused by electrical trauma. We reported a case of two patients. The total duration of each session was about 1 h 30 min. This included 10 min to put on the exoskeleton, 30 min of robot-assisted training using SUBAR®, 10 min to remove the exoskeleton, 10 min to observe whether complications such as skin abrasion, ulcer, or pain occur in the scar area after RAGT, and 30 min of conventional physiotherapy, at a rate of 5 days a week for 12 weeks. All measurements were assessed before training (0 week) and after training (12 weeks). The American Spinal Cord Injury Association (ASIA) lower extremity motor score (LEMS), passive range of motions (ROMs) of different joints (hip, knee, and ankle), ambulatory motor index (AMI), functional ambulation categories (FAC), and 6 min walking (6 MWT) distances were evaluated to measure the degree of gait function through training. In both patients, manual muscle test measurement and joint ROM in the lower extremities improved after 12 weeks training. The first patient scored 0 in the FAC before training. After 12 weeks of training, he could walk independently indoors, improving to an FAC score of 4. He also reached 92.16 m in the 6 MWT. LEMS improved from 22 before training to 30 after training, and AMI score improved from 12 before training to 16 after training. In the second patient, an independent walking function was not acquired. LEMS improved from 10 before training to 26 after training. AMI scores were the same at 10 points before and after training. The results suggested the possibility of achieving clinical effects in terms of improving lower extremity muscle strength, joint ROMs, and gait performance in patients with SCI caused by electrical trauma.

Regenerative effect of combined laser and human stem cell-conditioned medium therapy on hypertrophic burn scar.

PURPOSE: This study aimed to determine the effect of combined treatment with non-ablative laser and human stem cell-conditioned medium (HSCM) on tissue regeneration after burn-induced hypertrophic scar (HTS) formation. METHODS: Fourteen patients with HTSs on both sides of the same body part were subjected to three sessions of non-ablative laser treatment, with an interval of four weeks between each treatment. Following laser treatment, HSCM and normal saline were applied to the HTSs of the right (experimental) and left side (control), respectively. Over the next 6 days, HSCM and moisturizer were applied to experimental scars, while only moisturizer was applied to control scars. Skin characteristics were evaluated before laser treatment and on the seventh day after the third laser treatment. RESULTS: No significant intergroup differences were noted in the initial evaluation (P > 0.05). We found significant differences between the pre- and post-treatment measurements of erythema (P < 0.001), trans-epidermal water loss (TEWL; P < 0.001), and Cutometer® parameters (all parameters; P <0.05) of experimental scars. Control scars also showed significant differences between pre- and post-treatment measurements of thickness (P = 0.01), erythema (P < 0.001), TEWL (P < 0.001), and Cutometer® parameters (all parameters; P < 0.05). Changes (pre- to post-treatment) in scar thickness between the experimental (-0.003 ± 0.09) and control scars (0.04 ± 0.12) were significant (P = 0.01). CONCLUSION: These results suggest that HSCM has a positive effect on short-term results when applied after laser treatment of hypertrophic scars.

The Intra-rater reliability and validity of ultrasonography in the evaluation of hypertrophic scars caused by burns.

PURPOSE: Hypertrophic scars that occur after burns are less flexible and less elastic than normal skin. Objective measurement tools are required to assess hypertrophic scars after thermal injury. Cutometer® MPA 580 has been widely used for evaluating the properties of hypertrophic scars. Ultrasonography can evaluate elasticity, stiffness, and structure of tissues simultaneously using elastography and B-mode. This study aimed to investigate the intra-rater reliability and validity of elastography to visualize hypertrophic scars. METHODS: Sixteen participants with a total of 96 scars were evaluated. The measurement sequence was elastography, Cutometer®, and elastography every 10 min. We then analyzed the intra-rater reliability using intraclass correlation coefficients (ICC). The results measured using elastography on the hypertrophic scars and surrounding normal skin were compared. The relationships between the elastographic and Cutometer® measurements using the 2-and 8-mm probes were compared. RESULTS: The intra-rater reliability of elastographic measurements was acceptable for clinical use in terms of strain ratio (SR), shear-wave elastography (SWE), shear-wave speed (SWS), and SWE ratio ( ICC = 0.913, ICC=0.933, ICC = 0.842, and ICC = 0.921). The average SWS and SWE in hypertrophic scars were significantly greater than that for normal skin ( p < 0.001 and p < 0.001). SWE showed correlations with the R0 (r = -0.32, p = 0.002) and R8 (r = -0.30, p = 0.003) measured with the 8-mm probe. The SWE ratio was correlated with the R7 (r = -0.34, p = 0.001) measured with the 2-mm probe. The thickness of hypertrophic scars showed correlations with the R5 (r = 0.33, p < 0.001), R6 (r = 0.44, p < 0.001) and R8 (r = -0.35, p < 0.001) measured with the 8-mm probe. R0-R9 measured with 2-mm Cutometer® probes were not correlated with scar thickness ( r < 0.30, P > 0.05). The total scores of mVSS showed correlations with the R0 (r = 0.35, p < 0.001), R1(r = 0.32., p = 0.001), R3 (r = 0.38, p < 0.001), R4 (r = 0.38, p < 0.001), R8 (r = 0.34, p = 0.001), and R9 (r = 0.34, p = 0.001) measured with the 2-mm probe. R0-R9 measured with 8-mm Cutometer® probes were not correlated with mVSS ( r < 0.30, P > 0.05). The thickness of hypertrophic scars showed correlations with the SWE (r = 0.38, p < 0.001) and SWE ratio (r = 0.35, p < 0.001). Elastographic findings were not correlated with mVSS ( r < 0.30, P > 0.05). CONCLUSION: In this study, together with the Cutometer®, ultrasound was confirmed as an evaluation tool that can objectively compare and analyze the difference between normal skin and hypertrophic scars.

Knockdown of CPEB1 and CPEB4 Inhibits Scar Formation via Modulation of TAK1 and SMAD Signaling.

BACKGROUND: Cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study. OBJECTIVE: This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing. METHODS: CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively. RESULTS: Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased. CONCLUSION: CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.

Predictive validity of the Cornell Scale for depression in dementia among older adults with and without dementia: A systematic review and meta-analysis.

This review analyzes the predictive validity of the Cornell Scale for Depression in Dementia (CSDD), considering cognitive function. Electronic searches were performed using MEDLINE, EMBASE, CINAHL, and PsycINFO databases. Overall, 20 studies were reviewed, including 3,499 older adults, with and without dementia, who satisfied the selection criteria. Participants were stratified into the dementia, non-dementia, and mixed groups, and the diagnostic performance of the CSDD was assessed using receiver operating characteristic (ROC) curves. In the dementia and non-dementia groups, the area under the curve was ≥ 0.9, confirming high accuracy of the test. The pooled sensitivity was the highest in the dementia group (0.87), followed by the mixed group (0.84) and non-dementia group (0.82). In the subgroup analysis based on the Mini-Mental State Examination (MMSE), the ROC curve was 0.90 for older adults with MMSE scores < 15 and 0.87 for those with an MMSE score ≥ 15. Therefore, the CSDD can be considered excellent tool for assessing depression in all older adults, although its predictive ability is better for older adults with dementia compared to that in those without dementia. It can be used as a first-line screening tool for depression, regardless of cognitive function.

Effect of robot-assisted gait training on the biomechanical properties of burn scars: a single-blind, randomized controlled trial.

Background: Robot-assisted gait training (RAGT) is more effective in the range of motion (ROM) and isometric strength in patients with burns than conventional training. However, concerns have been raised about whether RAGT might negatively affect the scars of patients with burns. Therefore, we investigated the effects of RAGT-induced mechanical load on the biomechanical properties of burn scars. Methods: This was a single-blind, randomized clinical trial conducted on inpatients admitted to the Department of Rehabilitation Medicine between September 2020 and August 2021. RAGT was conducted for 30 min per day, five days a week for 12 weeks and the control group received conventional gait training for 12 weeks. The pre-training ROM of lower extremity joints was evaluated and the levels of melanin, erythema, trans-epidermal water loss, scar distensibility and elasticity were assessed before training and at 4 and 12 weeks after training. Finally, 19 patients in the gait assistance robot (GAR) group and 20 patients in the control group completed the 12-week trial and all evaluations. Results: There were no significant differences in the epidemiologic characteristics, pre-training ROM of joints and pre-training biomechanical properties of the burn scar between the groups (p > 0.05 for all). None of the patients experienced skin abrasion around the burn scar where the fastening belts were applied or musculoskeletal or cardiovascular adverse events during the training. Scar thickness significantly increased in both groups (p = 0.037 and p = 0.019) and scar distensibility significantly decreased in the control group (p = 0.011) during the training. Hysteresis was significantly decreased in the GAR group during the training (p = 0.038). The GAR and control groups showed significant difference in the change in the values of hysteresis between pre-training and 12 weeks after training (p = 0.441 and p = 0.049). Conclusions: RAGT significantly decreased hysteresis in hypertrophic burn scars and did not cause a significant decrease in skin distensibility. Moreover, no skin complications around the burn scars were detected during RAGT. Trial registration: This study registered on the Clinical Research Information Service (KCT0005204).

Respiratory Characteristics in Patients With Major Burn Injury and Smoke Inhalation.

This study aimed to evaluate pulmonary function measurements and respiratory muscle parameters in patients with major burn injury and smoke inhalation. The inclusion criteria included patients who were diagnosed with a smoke inhalation burn or a major burn of more than 20% of total body surface area (TBSA). All subjects underwent a pulmonary function test, respiratory muscle strength test, peak cough flow and fluoroscopic diaphragmatic movement measurement, and 6-minute walk test before starting pulmonary rehabilitation. Evaluations were conducted on the 88th day after the injury, the average time of admission to the Department of the Rehabilitation Medicine for burn rehabilitation after the completion of the acute treatment. The average degree of burns of the total 67 patients was 34.6% TBSA. All parameters in the patient group were significantly lower than the healthy controls, and a mild restrictive pattern of impairment with a reduction in diffusing capacity and more reduced expiratory muscle, than inspiratory muscle strength were observed. Peak cough flow, respiratory muscle strength, and forced vital capacity in the patient group with inhalation burn were significantly lower than in those without inhalation burn. The conditions of the majority of patients with major burn and inhalation injury were consistent with restrictive impairment and significant reduction in diffusion capacity. The patients had expiratory muscle weakness, decreased diaphragmatic movement, and exercise capacity impairment.

Clinical Utility of the Portable Pressure-Measuring Device for Compression Garment Pressure Measurement on Hypertrophic Scars by Burn Injury during Compression Therapy.

Compression therapy for burn scars can accelerate scar maturation and improve clinical symptoms (pruritus and pain). This study objectively verified the effect of pressure garment therapy in maintaining a therapeutic pressure range for hypertrophic scars. Sixty-five participants (aged 20~70 years) with partial- or full-thickness burns, Vancouver scar scale score of ≥4, and a hypertrophic scar of ≥4 cm × 4 cm were enrolled. Compression pressure was measured weekly using a portable pressure-monitoring device to regulate this pressure at 15~25 mmHg for 2 months. In the control group, the compression garment use duration and all other burn rehabilitation measures were identical except for compression monitoring. No significant difference was noted in the initial evaluations between the two groups (p > 0.05). The improvements in the amount of change in scar thickness (p = 0.03), erythema (p = 0.03), and sebum (p = 0.02) were significantly more in the pressure monitoring group than in the control group. No significant differences were noted in melanin levels, trans-epidermal water loss, or changes measured using the Cutometer® between the two groups. The efficacy of compression garment therapy for burn-related hypertrophic scars can be improved using a pressure-monitoring device to maintain the therapeutic range.