Nevus Spilus, Partial Unilateral Lentiginosis, and Linear and Whorled Nevoid Hypermelanosis: A Comparison of Clinical Features, Course, and Treatment Response.

Skin diseases manifesting as agminated pigmented lesions have overlapping clinical manifestations. Therefore, accurate differentiation is challenging. The clinical characteristics, histopathological findings, and treatment response of patients diagnosed with partial unilateral lentiginosis, nevus spilus, or linear and whorled nevoid hypermelanosis were retrospectively analysed. Each disease demonstrated distinct demographic and clinical characteristics, and the responses to laser treatment varied. The median age at onset varied significantly among the groups: 0.1, 6.6, and 0.5 years in patients with nevus spilus, partial unilateral lentiginosis, and linear and whorled nevoid hypermelanosis, respectively. Regarding the locations of the skin lesions, partial unilateral lentiginosis occurred predominantly on the head and neck, while approximately half of nevus spilus and linear and whorled nevoid hypermelanosis were observed on the extremities. Although linear and whorled nevoid hypermelanosis and partial unilateral lentiginosis share a similar histological feature of basal hyperpigmentation, patients with linear and whorled nevoid hypermelanosis showed the best response to laser treatment, while patients with partial unilateral lentiginosis demonstrated a poor treatment response. The study's data may provide important clues for the differential diagnosis and clinical decision-making regarding the treatment of these agminated pigmented lesions.

The efficacy and safety of low- versus high-fluence fractional picosecond Nd:YAG 1064-nm laser in the treatment of acne scars: A randomized split-face comparison study.

BACKGROUND: Differences in clinical efficacy based on the fluence of fractional picosecond laser treatment for acne scars are unknown. OBJECTIVE: To compare the efficacy and safety of low-fluence versus high-fluence fractional picosecond Nd:YAG 1064-nm laser treatment in acne scar patients. METHODS: In this 12-week, investigator-blinded, randomized, split-face study, 25 patients with moderate-to-severe acne scars received three sessions of high-fluence laser treatment (1.0 J/cm2 ) on one side of their face and low-fluence (0.3 J/cm2 ) on the other side every 4 weeks. Patients were assessed using acne scar counts, the scar global assessment (SGA), and the ECCA scar grading scale every 4 weeks. The histological analysis compared the acne scars obtained before and 4 weeks after treatment. RESULTS: At their last visit, 88.00% and 92.00% of the subjects achieved >30% reduction in scar counts on the low- and high-fluence sides, respectively, without a significant difference between the two sides. On both sides, the scar counts, SGA, and ECCA score significantly improved 4 weeks after the last treatment. Although the high-fluence side showed a greater reduction in scar counts (-66.73%) than the low-fluence side (-62.13%), the two sides had no significant difference in the grading scores. The high-fluence side showed significantly more severe pain and higher side-effect scores immediately and 4 weeks after treatment. Histological analysis revealed a significantly increased collagen, elastin, and vimentin expression after treatment on the low-fluence side. CONCLUSIONS: The low-fluence setting demonstrated comparable efficacy and superior safety in treating acne scars compared with the high-fluence setting.

Exosomes from Human iPSC-Derived Retinal Organoids Enhance Corneal Epithelial Wound Healing.

This study investigated the therapeutic effects of exosomes derived from human-induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) on corneal epithelial wound healing. Exosomes were isolated from the culture medium of the hiPSC-derived ROs (Exo-ROs) using ultracentrifugation, and then they were characterized by a nanoparticle tracking analysis and transmission electron microscopy. In a murine model of corneal epithelial wounds, these exosomes were topically applied to evaluate their healing efficacy. The results demonstrated that the exosome-treated eyes showed significantly enhanced wound closures compared with the controls at 24 h post-injury. The 5-ethyl-2'-deoxyuridine assay and quantitative reverse transcription polymerase chain reaction revealed a substantial increase in cell proliferation and a decrease in inflammatory marker contents in the exosome-treated group. The RNA sequencing and exosomal microRNA analysis revealed that the Exo-RO treatment targeted various pathways related to inflammation and cell proliferation, including the PI3K-Akt, TNF, MAPK, and IL-17 signaling pathways. Moreover, the upregulation of genes related to retinoic acid and eicosanoid metabolism may have enhanced corneal epithelial healing in the eyes treated with the Exo-ROs. These findings suggest that hiPSC-derived RO exosomes could be novel therapeutic agents for promoting corneal epithelial wound healing.

Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden.

Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely unknown. This study investigated senescent fibroblasts in keloids and assessed the effects of dasatinib on these cells. Tissues acquired from keloid removal surgery were analysed for senescence-associated ß-galactosidase-positive cells, p16 expression, and the effects of dasatinib treatment on keloids. Keloid tissue was xenotransplanted into mice, and the effect of intralesional dasatinib injection on keloid growth was observed. The results showed that the numbers of ß-galactosidase-positive and p16-expressing cells were higher in the keloids compared with in the controls. Dasatinib induced selective clearance of senescent cells and decreased procollagen expression in cultured keloid fibroblasts. In this xenotransplant keloid mouse model, intralesional injection of dasatinib reduced gross keloid tissue weight and the expression of both procollagen and p16. In addition, dasatinib-treated keloid fibroblasts conditioned medium reduced procollagen and p16 expression in cultured keloid fibroblasts. In conclusion, these results suggest that an increased number of senescent fibroblasts may play an important role in the pathogenesis of keloids. Therefore, dasatinib could be an alternative treatment for patients with keloids.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Clinical features and natural course of pediatric longitudinal melanonychia: A retrospective cohort study in Korea.

BACKGROUND: Large studies on the clinical features and natural course of pediatric longitudinal melanonychia (LM) are lacking. OBJECTIVE: To investigate the clinical features and natural course of pediatric LM. METHODS: Retrospective cohort analysis of pediatric patients (age ≤ 18 years) with LM. RESULTS: We examined 703 LM lesions in 381 children. Single, narrow, and homogeneously pigmented fingernail lesions were most frequently observed. Our results suggested that within 3, 4.5, and 9.5 years after onset, approximately 3%, 5%, and 10% of LM lesions, respectively, will completely regress and that single, left-sided, and homogeneously pigmented lesions are more likely to disappear completely. The age of onset, sex, finger/toe position, Hutchinson's sign, and nail dystrophy were not associated with complete regression. During follow-up, most cases demonstrated no change in color or width between the first and last visit, and early darkening/widening before stabilization or lightening/narrowing was common. The lightning of pigmentation was associated with complete regression, whereas change in width was not. LIMITATIONS: Retrospective study at a tertiary center. CONCLUSION: Our results suggest that clinicians ought to follow pediatric patients with LM without intervention for several years even if lesions grow darker or wider. Single, left-sided, and homogeneously colored lesions are more likely to regress.

Smart Roads for Autonomous Accident Detection and Warnings.

An increasing number of vehicles on the roads increases the risk of accidents. In bad weather (e.g., heavy rainfall, strong winds, storms, and fog), this risk almost doubles due to bad visibility as well as road conditions. If an accident happens, especially in bad weather, it is important to inform approaching vehicles about it. Otherwise, there might be another accident, i.e., a multiple-vehicle collision (MVC). If the Emergency Operations Center (EOC) is not informed in a timely fashion about the incident, fatalities might increase because they do not receive immediate first aid. Detecting humans or animals would undoubtedly provide us with a better answer for reducing human fatalities in traffic accidents. In this research, an accident alert light and sound (AALS) system is proposed for auto accident detection and alerts with all types of vehicles. No changes are required in non-equipped vehicles (nEVs) and EVs because the system is installed on the roadside. The idea behind this research is to make smart roads (SRs) instead of equipping each vehicle with a separate system. Wireless communication is needed only when an accident is detected. This study is based on different sensors that are used to build SRs to detect accidents. Pre-saved locations are used to reduce the time needed to find the accident's location without the help of a global positioning system (GPS). Additionally, the proposed framework for the AALS also reduces the risk of MVCs.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation.

The activation of transcriptional coactivators YAP and its paralog TAZ has been shown to promote resistance to anti-cancer therapies. YAP/TAZ activity is tightly coupled to actin cytoskeleton architecture. However, the influence of actin remodeling on cancer drug resistance remains largely unexplored. Here, we report a pivotal role of actin remodeling in YAP/TAZ-dependent BRAF inhibitor resistance in BRAF V600E mutant melanoma cells. Melanoma cells resistant to the BRAF inhibitor PLX4032 exhibit an increase in actin stress fiber formation, which appears to promote the nuclear accumulation of YAP/TAZ. Knockdown of YAP/TAZ reduces the viability of resistant melanoma cells, whereas overexpression of constitutively active YAP induces resistance. Moreover, inhibition of actin polymerization and actomyosin tension in melanoma cells suppresses both YAP/TAZ activation and PLX4032 resistance. Our siRNA library screening identifies actin dynamics regulator TESK1 as a novel vulnerable point of the YAP/TAZ-dependent resistance pathway. These results suggest that inhibition of actin remodeling is a potential strategy to suppress resistance in BRAF inhibitor therapies.

Adiponectin-Based Peptide (ADP355) Inhibits Transforming Growth Factor-ß1-Induced Fibrosis in Keloids.

Keloids, benign cutaneous overgrowths of dermal fibroblasts, are caused by pathologic scarring of wounds during healing. Current surgical and therapeutic modalities are unsatisfactory. Although adiponectin has shown an antifibrotic effect, its large size and insolubility limit its potential use in keloid treatment. We investigated the effect of a smaller and more stable adiponectin-based peptide (ADP355) on transforming growth factor ß1 (TGF-ß1)-induced fibrosis in a primary culture of keloid fibroblasts prepared from clinically obtained keloid samples. Xenograft of keloid tissues on athymic nude mice was used to investigate the effect of intralesional injection of ADP355. ADP355 significantly attenuated the TGF-ß1-induced expression of procollagen type 1 in keloid fibroblasts (p < 0.05). Moreover, it inhibited the TGF-ß1-induced phosphorylation of SMAD3 and ERK, while amplifying the phosphorylation of AMP-activated protein kinase (p < 0.05). Knockdown of adiponectin receptor 1 reversed the attenuation of procollagen expression in ADP355-treated TGF-ß1-induced fibrosis (p < 0.05). ADP355 also significantly reduced the gross weight and procollagen expression of keloid tissues in xenograft mice compared to control animals. These results demonstrate the therapeutic potential of the adiponectin peptide ADP355 for keloids.