miR-25-5p in exosomes derived from UVB-induced fibroblasts regulates melanogenesis via TSC2-dominated cellular organelle dysfunction.

BACKGROUND: Few reports have confirmed whether exosomes derived from fibroblasts can regulate the process of melanogenesis. We wondered whether exosomes derived from fibroblasts could have a potent regulatory effect on melanogenesis and explored the underlying mechanisms. OBJECTIVE: This study aimed to find the role of fibroblasts in melanocytes and revealed the related mechanisms. METHODS: RT-qPCR, Western blot analysis were conducted to measure the RNA and protein expression level of various related genes. miRNA sequencing, mass spectrum analysis and subsequent bioinformatics analysis were employed to find the underlying targets. Zebrafish were employed to measure the melanin synthesis related process in vivo. Furthermore, electron microscopy, ROS measurement and dual-luciferase reporter assay were adopted to investigate the relationship between these processes. RESULTS: We found that exosomes derived from human primary dermal fibroblasts were internalized by human primary melanocytes and MNT1 cells and that the melanin content and the expression of melanin synthesis-related proteins TYR and MITF was inhibited by exosomes derived from UVB-induced human primary dermal fibroblasts. The miRNA expression profile in secreted exosomes changed significantly, with miR-25-5p identified as capable of regulating TSC2 expression via the CDS region. The miR-25-5p-TSC2 axis could affect the melanin content through subsequent cellular organelle dysfunction, such as mitochondrial dysfunction, endoplasmic reticulum stress and dysregulation of lysosomal cysteine proteases. CONCLUSION: We unveiled a novel regulatory role of fibroblasts in melanocytes, facilitated by the secretion of exosomes. miR-25-5p within exosomes plays a pivotal role in regulating melanogenesis via TSC2-induced cellular organelle dysfunction.

Blue Nevus Hidden within the Nevus of Ota.

A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.

Automatic identification of benign pigmented skin lesions from clinical images using deep convolutional neural network.

OBJECTIVE: We aimed to develop a computer-aided detection (CAD) system for accurate identification of benign pigmented skin lesions (PSLs) from images captured using a digital camera or a smart phone. METHODS: We collected a total of 12,836 clinical images which had been classified and location-labeled for training and validating. Four models were developed and validated; you only look once, v4 (YOLOv4), you only look once, v5 (YOLOv5), single shot multibox detector (SSD) and faster region-based convolutional neural networks (Faster R-CNN). The performance of the models was compared with three trained dermatologists, respectively. The accuracy of the best model was further tested and validated using smartphone-captured images. RESULTS: The accuracies of YOLOv4, YOLOv5, SSD and Faster R-CNN were 0.891, 0.929, 0.852 and 0.874, respectively. The precision, sensitivity and specificity of YOLOv5 (the best model) were 0.956, 0.962 and 0.952, respectively. The accuracy of YOLOv5 model for images captured using a smart-phone was 0.905. The CAD based YOLOv5 system can potentially be used in clinical identification of PSLs. CONCLUSION: We developed and validated a CAD system for automatic identification of benign PSLs using digital images. This approach may be used by non-dermatologists to easily diagnose by taking a photo of skin lesion and guide on management of PSLs.

A deep learning-based hybrid artificial intelligence model for the detection and severity assessment of vitiligo lesions.

Background: We aimed to establish and validate a deep learning-based hybrid artificial intelligence (AI) model for the objective morphometric and colorimetric assessment of vitiligo lesions. Methods: Two main datasets containing curated images of vitiligo lesions from Chinese patients (Fitzpatrick skin types III or IV) were established, including one with 2,720 images for lesion localization study and the other with 1,262 images for lesion segmentation study. Besides, an additional test set containing 145 images of vitiligo lesions from other Fitzpatrick skin types (I, II, or V) was also generated. A 3-stage hybrid model was constructed. YOLO v3 (You Only Look Once, v3) architecture was trained and validated to classify and localize vitiligo lesions, with sensitivity and error rate as primary performance outcomes. Then a segmentation study comparing 3 deep convolutional neural networks (DCNNs), Pyramid Scene Parsing Network (PSPNet), UNet, and UNet++, was carried out based on the Jaccard index (JI). The architecture with the best performance was integrated into the model. Three add-on metrics, namely VAreaA, VAreaR, and VColor were finally developed to measure absolute, relative size changes and pigmentation, respectively. Agreement between the AI model and dermatologist evaluators were assessed. Results: The sensitivity of the YOLO v3 architecture to detect vitiligo lesions was 92.91% with an error rate of 14.98%. The UNet++ architecture outperformed the others in the segmentation study (JI, 0.79) and was integrated into the model. On the additional test set, however, the model achieved a lower detection sensitivity (72.41%) and a lower segmentation score (JI, 0.69). With respect to size changes, no difference was observed between the AI model, trained dermatologists (W=0.812, P<0.05), and Photoshop analysis (P=0.075, P=0.212 respectively), which all displayed good concordance. Conclusions: We developed a novel, convenient, objective, and quantitative deep learning-based hybrid model which simultaneously evaluated both morphometric and colorimetric vitiligo lesions from patients with Fitzpatrick skin types III or IV, rendering it suitable for the assessment of severity of vitiligo lesions in Asians in both clinic and research scenarios. More work is also warranted for its use in other ethnic skin groups.

Treatment of acne scars with fractional carbon dioxide laser in Asians: a retrospective study to search for predicting factors associated with efficacy.

Ablative fractional laser treatment has been extensively used for resurfacing atrophic acne scars. However, few studies have investigated how the parameters set during laser procedures affect efficacy. In this retrospective study, we examined the relationship between efficacy and Fitzpatrick skin type, gender, age, follow-up duration, energy, and treatment sessions utilizing ablative fractional carbon dioxide (CO2) laser in Asians with Fitzpatrick skin types III-IV. We then analyzed the relationship between outcome and adverse effects including hyperpigmentation. Three blinded dermatologists used the ECCA (Echelle d'Evaluation Clinique des Cicatrices d'Acnluation Clinique des Cicospectively review 82 of 1034 patients who presented at our institution for atrophic acne scar treatment between August 2013 and August 2019. Factors associated with efficacy, including age, gender, Fitzpatrick skin type, energy, treatment sessions, follow-up duration, and pigmentation, were analyzed. 82 patients met inclusion criteria. Patients underwent one to three CO2 laser treatment sessions. Parameter settings for individual patients were consistent across treatments. Mean ECCA scores decreased from 102.70 ± 24.95 to 87.28 ± 24.48 (p ≤ 0.001). The number of treatment sessions and duration of pigmentation lasting shorter than 3 months positively correlated with better outcomes. All patients had erythema, which lasted longer than 3 months in 16 patients (19.51%). Post-inflammatory hyperpigmentation (PIH) affected 60 patients (73.17%) and lasted longer than 3 months in 26 patients (31.71%). One patient experienced hypopigmentation (1.22%), while 8 experienced acne flare-up (9.76%). Post-laser scars occurred in 2 patients (2.44%). Our data suggest that in atrophic acne scar treatment in Asians using fractional CO2 laser, 3 treatment sessions and duration of hyperpigmentation within 3 months have better outcomes regardless of energy, gender, age, Fitzpatrick skin type, follow-up duration, and disease course.

Treatment of nevus of Ota with 1064 nm picosecond Nd:YAG laser: A retrospective study.

Nevus of Ota has been successfully treated by lasers. Currently, 1064 nm picosecond Nd:YAG lasers have become available for the treatment of pigmented disorders. However, there are few studies concerning the application of 1064 nm picosecond Nd:YAG laser in nevus of Ota. This study aimed to evaluate the efficacy and safety of a 1064 nm picosecond Nd:YAG laser for the treatment of nevus of Ota. We conducted a retrospective analysis of Chinese patients with nevus of Ota who had been treated with a 1064 nm picosecond Nd:YAG laser. Those who had any other laser treatment during the period of picosecond laser treatment were excluded. Via a visual analog scale for percentage of pigmentary clearance in standard photographs, the treatment efficacy was assessed by three blinded physician evaluators. A total of 16 subjects were included in this retrospective study. The average age at the beginning of treatment was 16.87 years old (range of 4 months to 59 years), and all patients were of Fitzpatrick skin type IV. Total treatment ranged from 1 to 5 sessions. A 1064 nm picosecond Nd:YAG laser with a mean fluence of 1.8-4.3 J/cm2 was used at 3-12 month intervals. The mean efficacy score for all 16 patients was 2.56 after one session, and the mean efficacy score of 13 patients who completed two sessions and nine patients who completed three sessions were 3.15 and 3.51, respectively. Postinflammatory hyperpigmentation after treatment was only observed in 1 (1/16, 6.25%) patient. The 1064 nm picosecond Nd:YAG laser is an effective and safe approach for treating nevus of Ota.