Comparative study on the age-related incidence of seborrheic keratosis and verruca plana in patients with verruca plana-like lesions.

Seborrheic keratosis (SK) is a common skin disease in the elderly. However, in cases where SK presenting as multiple skin-colored or clustered lesions can be easily misdiagnosed as verruca plana (VP), especially in the young population. This retrospective study investigated the prevalence of SK and VP in the lesions that appear clinically similar to VP according to age. We examined the pathology slides of the skin tissue and photographs of patients who were clinically suspected to have VP. A total of 503 patients were included in the study, out of which 174 patients were finally diagnosed with SK (34.6%) and 132 with VP (26.2%). The mean ages of the SK- and VP-diagnosed group were 39.3 and 35.4 years, respectively. SK had a higher prevalence among individuals older than 30 years, and relative frequency of SK should not be ignored in patients with a grouped distribution in their 20 s and 30 s. Therefore, our study suggests that multiple verrucous skin-colored to brownish plaques are also commonly diagnosed as SK in young people as well as VP, and the prevalence of SK and VP may not always depend solely on chronological aging, and the prevalence of SK among young people may be higher than commonly believed stereotypes suggest.

Multiple Eruptive Epithelioid Hemangiomas on the Right Upper Extremity in an Asian Man.

Epithelioid hemangioma is a rare benign vascular neoplasm. Recently, the term "multiple eruptive epithelioid hemangioma" has been proposed for epithelioid hemangioma with distinct features. It is different from usual epithelioid hemangioma because of the multifocal distributions in various body regions with an eruptive onset. In addition, the histopathology of multiple eruptive epithelioid hemangioma shows increased cellular proliferation, mitosis, and nuclear pleomorphism and positive findings for FOS-B compared to classic epithelioid hemangioma. Herein, we report the case of a 59-year-old man with unusual manifestations suitable for multiple eruptive epithelioid hemangioma. He had multiple erythematous to purple-red dome-shaped nodules on the right hand, arm, and shoulder. The initial lesion was a solitary erythematous nodule on the right hand that abruptly extended to the right arm and shoulder. Microscopically, the tumor was a well-demarcated dermal nodule and showed capillary sized vascular structures. Vascular structures had epithelioid endothelial cells with abundant eosinophilic cytoplasm and vesicular nuclei. The tumor cells showed mild nuclear pleomorphism and a few mitosis and feature of resembling cobble stone was observed. In immunohistochemistry, CD31 and CD34 were positive in the endothelial cells. The endothelial cells showed nuclear positivity in FOS-B. Based on the clinical and histopathological findings, the final diagnosis was multiple eruptive epithelioid hemangiomas. This is the first report of multiple eruptive epithelioid hemangiomas in an Asian man after the term had been introduced.

Pulsed-dye laser as an effective treatment for recalcitrant granulomatous rosacea and a potential regulator of CXCL9 expression.

Granulomatous rosacea (GR) is a rare and distinct variant of rosacea. We report three cases of recalcitrant GR successfully treated with pulsed-dye laser (PDL) and provide experimental evidence supporting its potential as a treatment option. PDL treatment demonstrated remarkable efficacy in the three clinical cases, despite their resistance to conventional therapies. Chemokine ligand 9 (CXCL9), a key chemokine involved in inflammation and granuloma formation, was found to be increased in skin sections from all three patients. In vitro experiments using human monocytes and dermal fibroblasts demonstrated that PDL treatment significantly reduced CXCL9 expression in fibroblasts. These findings suggest that PDL may modulate CXCL9 secretion in fibroblasts, potentially limiting the recruitment of immune cells to the lesion. Although further research is needed to fully understand the precise mechanisms underlying the role of CXCL9 in GR, PDL may be a promising therapeutic approach for refractory GR.

Mid-old cells are a potential target for anti-aging interventions in the elderly.

The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed "mid-old status" cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

Comparison of Melanocyte-Associated Immunohistochemical Markers in Acral Lentiginous Melanoma and Acral Benign Nevi.

ABSTRACT: Acral lentiginous melanoma (ALM) is a relatively rare clinicopathologic subtype of cutaneous malignant melanoma, but it is the most common type of melanoma among Asians. Although the research to identify immunohistochemical (IHC) markers to differentiate nevi from melanoma is being conducted, specific markers for ALM are not well-known. Therefore, we aimed to analyze and compare the differences in the expression of melanocyte-associated IHC markers between ALM and acral benign nevi (ABN). Two independent groups of 53 and 19 paraffin-embedded specimens (from patients with pathologically confirmed ALM and ABN, respectively) were subjected to IHC staining for MART-1, preferentially expressed antigen in melanoma (PRAME), SOX10, HMB-45, Ki-67, and p16. We performed a quantitative analysis of PRAME, SOX10, KI-67, and p16 expression and gradient pattern analysis of HMB-45 expression for each specimen. The PRAME (60.1% and 28.5%, P < 0.05) and Ki-67 (7.8% and 3.5%, P < 0.05) expression levels were significantly higher in the ALM group than in the ABN group. The p16 expression was significantly lower (14.2% and 19.4%, P < 0.05), and the absence of HMB-45 gradient was more frequent in the ALM group than in the ABN group. However, no statistical significance was noted in SOX10 (54.8% and 44.7%). Receiver operating characteristic curves showed that PRAME had the highest area under the curve value. In summary, among various IHC markers, PRAME was the most valuable marker for the diagnosis of ALM; however, further large-scale studies are needed to validate these findings.

Aureobasidium pullulans Treatment Mitigates Drought Stress in Abies koreana via Rhizosphere Microbiome Modulation.

The Korean fir tree Abies koreana, an endangered species in Korea, faces threats primarily from climate change-induced stress and drought. This study proposed a sustainable method to enhance A. koreana drought tolerance using a black yeast-like fungus identified as Aureobasidium pullulans (AK10). The 16S/ITS metabarcoding analysis assessed the impact of drought and AK10 treatment on the seedlings' rhizosphere microbiome. Results revealed a profound drought influence on the microbiome, particularly affecting fungal mycobiota. Drought-stressed seedlings exhibited elevated Agaricaceae levels, opportunistic fungi generally associated with decomposition. AK10 treatment significantly mitigated this proliferation and increased the relative abundance of beneficial fungi like Cystofilobasidium and Mortierella, known biocontrol agents and phosphate solubilizers. A notable reduction in the phytopathogenic Fusarium levels was observed with AK10, alongside an increase in beneficial bacteria, including Azospirillum and Nitrospirillum. Furthermore, the conducted correlation analysis shed light on microbial interrelationships within the rhizosphere, elucidating potential co-associations and antagonisms. Taken together, the isolated A. pullulans AK10 identified in this study serves as a potential biostimulant, enhancing the drought tolerance in A. koreana through beneficial alterations in the rhizosphere microbiome. This approach presents a promising strategy for the conservation of this endangered species.

Progression of Pre-Existing Vitiligo during Secukinumab Treatment for Psoriasis.

Vitiligo has been considered an unexplained paradoxical phenomenon during biologics use. Herein, we report an adult case of progression of pre-existing vitiligo during secukinumab treatment for psoriasis, and we also examined the immunohistochemical changes in relation to biologics use. He was being administered monthly secukinumab of 300 mg dose for 2 years, and all psoriatic lesions were cleared, but pre-existing hypopigmented lesions became more distinct and larger than before unlike when using adalimumab. A skin biopsy of the hypopigmented lesion showed loss of epidermal melanocytes and absence of gp100 immune activities, and he was finally diagnosed with progression of pre-existing vitiligo. Immunohistochemical staining of vitiligo lesion showed decrease in interleukin-17 and tumor necrosis factor-α and increase in CD8+ T cells, interferon-γ, and CXCL10 after the use of secukinumab. In this study, we suggest that biologics-induced cytokine imbalance play a critical role in vitiligo progression in patients with chronic inflammatory diseases, including psoriasis.

Intramuscular administration of recombinant Newcastle disease virus expressing SARS-CoV-2 spike protein protects hACE-2 TG mice against SARS-CoV-2 infection.

Coronavirus disease 2019 (Covid-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) became a pandemic, causing significant burden on public health worldwide. Although the timely development and production of mRNA and adenoviral vector vaccines against SARS-CoV-2 have been successful, issues still exist in vaccine platforms for wide use and production. With the potential for proliferative capability and heat stability, the Newcastle disease virus (NDV)-vectored vaccine is a highly economical and conceivable candidate for treating emerging diseases. In this study, a recombinant NDV-vectored vaccine expressing the spike (S) protein of SARS-CoV-2, rK148/beta-S, was developed and evaluated for its efficacy against SARS-CoV-2 in K18-hACE-2 transgenic mice. Intramuscular vaccination with low dose (106.0 EID50) conferred a survival rate of 76 % after lethal challenge of a SARS-CoV-2 beta (B.1.351) variant. When administered with a high dose (107.0 EID50), vaccinated mice exhibited 100 % survival rate and reduced lung viral load against both beta and delta variants (B.1.617.2). Together with the protective immunity, rK148/beta-S is an accessible and cost-effective SARS-CoV-2 vaccine.

Darier Disease with Psoriasis.

Darier disease is an autosomal dominant disorder with dark crusty patches and is classified as hereditary acantholytic dermatosis. Keratotic papules and crust are often present on the scalp, forehead, chest, back, upper arms, elbows, groin, and behind the ears, predominantly in seborrheic areas. A 48-year-old male patient presented skin lesions with pruritus on the trunk and both upper and lower extremities. He first noticed the lesion 15 years before. On physical examination, there were multiple erythematous papules with crust on the trunk and red-brown colored keratotic plaque on both extremities. The suspected histopathological diagnosis was psoriasis vulgaris. The patient's skin lesions and pruritus were significantly improved after the psoriasis treatment. While continuing psoriasis treatment, the patient showed sudden worsening of the skin lesions on the scalp, abdomen, and fingernails (V-shaped nicks) with pruritus. Punch biopsy was performed on the abdominal lesion again and the final diagnosis was Darier disease. The patient was then treated using alitretinoin while maintaining the use of guselkumab for psoriasis. There are only a few cases that we found in which patients with Darier disease also had psoriasis. We report this rare case of Darier disease with psoriasis and propose that an additional biopsy might be necessary for accurate diagnosis and proper treatment.

A prospective study to evaluate the treatment effect of pulsed dye laser on thyroidectomy hypertrophic scars using 3D imaging analysis.

OBJECTIVES: The pulsed dye laser (PDL) is an effective modality for preventing and improving hypertrophic scars (HSs). However, the heterogeneity of the parameter settings of the laser and subjective scar assessment methods used in most studies resulting in uncertainty with treatment plans. Therefore, we investigated the treatment effect of the PDL (V-beam; Candela Laser Corporation) on HSs in post-thyroidectomy patients using three-dimensional imaging analysis and intended to provide a systemic and optimal treatment protocol. METHODS: Nineteen patients with HS after thyroidectomy underwent eight treatment sessions with the 595 nm PDL (with the dose gradually increased by 0.5 J/cm2 ) at 4- to 6-week intervals. Patients with an elevated lesion also received intralesional corticosteroid (ICS) treatment. After every two treatment sessions, we assessed the patients' HS using the Vancouver Scar Scale (VSS), a patient satisfaction questionnaire, and with a three-dimensional (3D) skin imaging device (Antera 3D™; Miravex Limited). RESULTS: In repeated-measures analysis of variance, the mean VSS and patient satisfaction significantly improved (p < 0.001), with significant differences in these values observed until the sixth and eighth treatment sessions, respectively. In the quantitative analysis using Antera 3D™, the mean height, pigmentation, and vascularity scores were observed to be significantly improved (p < 0.001). Significant differences in these values were observed until the fourth, second, and eighth treatment sessions, respectively. Subgroup analysis according to ICS treatment showed no significant differences in scar characteristics between those with and without ICS treatment. CONCLUSIONS: In this study, we found that the PDL was effective in reducing scar height, vascularity, and pigmentation in patients with thyroidectomy HS using 3D imaging analysis. Furthermore, we have suggested a cost-effective treatment plan with the 595 nm PDL.

7-Hydroxy-2-octenoic acid-ethyl ester mixture as an UV protectant secondary metabolite of an endolichenic fungus isolated from Menegazzia terebrata.

Enodolichenic fungi (ELF) are considered a promising bio-resource since they produce a variety of novel secondary metabolites with bioactivities. Ultraviolet (UV) radiation in sunlight containing UVA and UVB can cause acute and chronic skin diseases, and the demand for UV protectants in sunscreens has been increasing. Such situations evoke the strong interest of researchers in seeking effective UV protectants from natural products. In this study, we obtained partially purified 7-hydroxy-2-octenoic acid-ethyl ester (7E) from the secondary metabolites of ELF000548, which has UVA absorption activity. The antioxidant properties were performed by in vitro tests. The superoxide anion scavenging activity and inhibition of linoleic acid peroxidation of the 7E mixture were higher than ascorbic acid (ASA) and butyl hydroxyl anisole (BHA). Furthermore, the compound recovered the damage caused by UVB irradiation and inhibited melanin synthesis. Additionally, the 7E mixture exhibited no cytotoxicity toward the mouse melanoma cell lines, B16F1 and B16F10, except for the normal cell line, HaCaT. In general, these results are the first report about bioactivities of 7E, and those demonstrated that this compound might be a UV protectant to go further study.

Effect of changes in Breslow thickness between the initial punch biopsy results and final pathology reports in acral lentiginous melanoma patients.

Acral lentiginous melanoma (ALM) is the most common subtype of cutaneous melanoma among Asians; punch biopsy is widely performed for its diagnosis. However, the pathologic parameters evaluated via punch biopsy may not be sufficient for predicting disease prognosis compared to the parameters evaluated via excisional biopsy. We investigated whether changes in Breslow thickness (BT) between initial punch biopsy results and final pathology reports can affect the prognosis of ALM. Pathologic parameters were recorded from specimens acquired through the initial punch biopsy and wide excision. Patients were classified into two groups based on a change in Breslow depth: the BT increased or decreased on comparing the samples from the initial punch biopsy and final wide excision. We compared clinical characteristics, and a Cox regression model was used to identify independent prognostic factors influencing melanoma-specific death (MSD). Changes in BT did not affect MSD (hazard ratio [HR]: 0.55, P = 0.447). In multivariate analysis, a higher BT (> 2 mm) (HR: 9.93, P = 0.046) and nodal metastasis (HR: 5.66, P = 0.041) were significantly associated with an increased MSD risk. The use of punch biopsy did not affect MSD despite the inaccuracy of BT measurement as long as ALM was accurately diagnosed.

Bone Response to Conventional Titanium Implants and New Zirconia Implants Produced by Additive Manufacturing.

The aim of the present study was to evaluate the in vivo bone response to an additively manufactured zirconia surface compared to osseointegration into titanium (Ti) surfaces. Scanning electron microscopy, confocal laser scanning microscopy, and electron spectroscopy for chemical analysis were performed to assess the surface characteristics of implant specimens. For the in vivo evaluation, eight Ti implants and eight 3D-printed zirconia implants were used. The surface of four Ti implants was sandblasted, large-grit, and acid-etched (Ti-SLA group), while those of the other four Ti implants were left untreated (Ti-turned group). The zirconia implants had no further surface modification. Implants were placed into the tibiae of four rabbits; two received the Ti-SLA and zirconia implants and the other two received Ti-turned and zirconia implants. The experimental animals were sacrificed after four weeks of surgery, and the undecalcified microscopic slides were prepared. The bone-implant interface was analyzed by histomorphometry to evaluate the bone response. The degree of surface roughness showed that Ti-SLA was the highest, followed by zirconia and Ti-turned surfaces. The 3D-printed zirconia surface showed similar bone-to-implant contact to the Ti-turned surface, and Ti-SLA had the most bone-to-implant contact. The additively manufactured zirconia implant surface is biocompatible with respect to osseointegration compared to the commercially pure Ti surface.

Efficacy of combined treatment with intense pulsed light and fractional erbium:YAG Laser in scar prevention: A randomized split wound trial.

Various methods have been used for scar prevention; however, the optimal method remains unclear. We investigated the efficacy of combinational intense pulsed light (IPL)/fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser treatment in early wound healing. This was a prospective, randomized, controlled split wound trial. Scars were divided into three sites: the combined IPL/fractional Er:YAG treatment, fractional Er:YAG laser treatment, and untreated control sites. Treatment was conducted in three sessions: at removal of stitches and after 4 and 8 weeks. Treatment efficacy was evaluated using the Patient Observer Scar Assessment Scale (POSAS) and Vancouver Scar Scale (VSS) scores. The erythema index (EI) and melanin index (MI) were measured. In the total POSAS score, the IPL/fractional Er:YAG site showed steady and significant improvement, in contrast to the other sites. At week 8, the combined treatment sites had better POSAS scores than the fractional Er:YAG laser alone sites (p = 0.001) and the control sites (p = 0.000). The effect of combinational treatment was maintained until the follow-up period by comparing the Er:YAG (p = 0.015) and control sites (p = 0.007). In terms of VSS scores, the IPL/fractional Er:YAG combined treatment sites had consistent improvement at week 8 (p = 0.005) and week 20 (p = 0.02) compared to that at week 4, while the other sites showed no such improvement. In conclusion, the combination of IPL and Er:YAG showed more favorable effects on scar prevention than Er:YAG or no treatment. IPL/Er:YAG therapy could be an effective and safe strategy in the early wound healing process for reducing scar formation.

Tetrahydrocurcumin Ameliorates Skin Inflammation by Modulating Autophagy in High-Fat Diet-Induced Obese Mice.

Obesity can induce chronic low-grade inflammation via oxidative stress. Tetrahydrocurcumin (THC) is a major curcumin metabolite with anti-inflammatory and antioxidant effects, but little is known about its effects on the skin of obese individuals. Thus, the aim of this study was to investigate the effects of THC on inflammatory cytokine production, oxidative stress, and autophagy in the skin of mice with high-fat diet- (HFD-) induced obesity. Eight-week-old C57BL/6J mice were fed a regular diet, HFD (60% of total calories from fat), or HFD supplemented with THC (100 mg/kg/day orally) for 12 weeks. We measured their body weights during the experimental period. After 12-week treatments, we performed western blotting and real-time polymerase chain reaction analyses on skin samples to evaluate the expression of inflammatory cytokines, oxidative stress markers, and autophagy markers. We observed higher tumor necrosis factor-α (TNF-α), NADPH oxidase 2 (Nox2), Nox4, and phosphorylated p65 levels; lower nuclear factor erythroid 2-related factor 2 (Nrf2) expression; and higher light chain 3 (LC3), autophagy-related 5 (Atg5), and Beclin 1 expression in the skin of HFD mice compared to the corresponding levels in the skin of mice fed with regular diet. THC administration decreased TNF-α, Nox2, Nox4, and phosphorylated p65 levels and activated the Nrf2 pathway. Interestingly, THC administration suppressed the expression of the autophagy markers LC3, Atg5, and Beclin 1. Overall, HFD-fed mice exhibited an elevation in inflammation, oxidative stress, and autophagy in their skin. THC ameliorated obesity-related skin pathology, and therefore, it is a potential therapeutic agent for obesity-related inflammatory skin diseases.

In Vitro and In Vivo Antibacterial Activity of Serratamid, a Novel Peptide-Polyketide Antibiotic Isolated from Serratia plymuthica C1, against Phytopathogenic Bacteria.

A new hybrid non-ribosomal peptide-polyketide antibiotic (serratamid) for phytoprotection was isolated from the ethyl acetate layer of tryptic soy agar culture of the soil bacterium Serratia plymuthica C1 through bioassay-guided fractionation. Its chemical structure was elucidated using instrumental analyses, such as mass and nuclear magnetic resonance spectrometry. Serratamid showed antibacterial activity against 15 phytopathogenic bacteria, with minimum inhibitory concentration (MIC) values ranging from 0.244 to 31.25 µg/mL. In vitro, it displayed strong antibacterial activity against Ralstonia solanacearum and four Xanthomonas spp., with MIC values (0.244-0.488 µg/mL) superior to those of streptomycin sulfate, oxolinic acid, and oxytetracycline. Further, serratamid and the ethyl acetate layer of S. plymuthica C1 effectively reduced bacterial wilt caused by R. solanacearum on tomato seedlings and fire blight caused by Erwinia on apple fruits in a dose-dependent manner. These results suggest that serratamid is a promising candidate as a potent bactericide for controlling bacterial diseases.

Nonviral gene delivery using PAMAM dendrimer conjugated with the nuclear localization signal peptide derived from human papillomavirus type 11 E2 protein.

Polyamidoamine (PAMAM) dendrimers are biocompatible polymers utilized in multiple biomedical applications including tissue engineering, medical diagnosis, drug and gene delivery systems, and biosensors. Normally, high-generation PAMAM dendrimers are advantageous for use in gene therapy research because they have a relatively high transfection efficiency. A high-generation PAMAM dendrimer has a high charge density, which induces greater damage to the membranous organelles than that induced by a low-generation PAMAM dendrimer. In this study, we added NLS sequences derived from the human papillomavirus (HPV) type 11 E2 protein to the low-generation PAMAM generation 2 (PAMAM G2) dendrimer and simultaneously introduced histidine residues to reduce cytotoxicity. RKRARH-PAMAM G2 showed similar and high transfection efficiencies in Neuro-2A and NIH3T3 cell lines and relatively low cytotoxicities relative to that of polyethylenimine 25 kDa (PEI 25 kDa).

Hypopigmented Mycosis Fungoides Mimicking Vitiligo.

ABSTRACT: Hypopigmented mycosis fungoides (HMF) is a clinical variant of MF with a presentation similar to other hypopigmented diseases, especially vitiligo. In this article, we report an adult case of HMF mimicking vitiligo. A 53-year-old man presented with an asymptomatic well-defined focal and hypopigmented patch with erythematous to brownish macules on the flank which had been developing over several months without other cutaneous findings. He had no past medical or trauma history. Skin biopsy from the hypopigmented patch indicated a slightly band-like, superficial dermal infiltrate of lymphocytes with mild cytologic atypia and epidermotropism. Fontana-Masson and Mart-1 stains showed a decrease in the epidermal pigment and the number of basal melanocytes. In addition, CD4 and CD8 stains were positive, predominantly the CD8 stain, and loss of CD7 stain was noted in the epidermal atypical lymphocytes. A T-cell receptor gene rearrangement study from the hyperpigmented area showed monoclonality. Finally, we diagnosed the patient with HMF. After about 17 months of treatment with narrow-band ultraviolet B, the hypopigmented lesion had notably improved in both the clinical and histological aspects. The clinical appearance of our case was similar to vitiligo while clinical improvement was also exceptionally similar to the skin findings from follicular repigmentation after narrow-band ultraviolet B treatment in vitiligo. Therefore, dermatologists should consider the clinical differential diagnosis of HMF in patients with an asymptomatic hypopigmentation, especially in dark-skinned Asian patients.

Senescent Fibroblast-Derived GDF15 Induces Skin Pigmentation.

Senescent fibroblasts play a role in aging pigmentation. In this study, we found that GDF15 expression levels are increased in UV-irradiated senescent fibroblasts and photoaged hyperpigmented skin. To investigate the effects of GDF15 on melanogenesis, normal human melanocytes were cocultured with fibroblasts infected with the GDF15 lentivirus or GDF15 short hairpin RNA. It was found that GDF15 stimulates melanogenesis in melanocytes through MITF/tyrosinase upregulation via ß-catenin signaling. The stimulatory action of GDF15 during pigmentation was further confirmed in ex vivo cultured skin and in a reconstituted human skin sample. These results suggest that senescent fibroblast-derived GDF15 stimulates skin pigmentation and may play a role in aging-associated pigmentation.