Through a comprehensive analysis combining network pharmacology prediction and transcriptomics, this study systematically explained the multi-target mechanism of Cyanotis arachnoidea(CA) Gel in improving melasma. A melasma model was induced in female SD rats by progesterone injection combined with ultraviolet B(UVB) irradiation for 40 consecutive days, while the blank control group was only fed routinely. After successful model establishment, the rats were randomly divided into five groups and administered different doses of CA ethanol extract gel(high, medium, and low doses) or arbutin Gel(positive control), which were applied once daily for 28 consecutive days. Subsequently, the levels of superoxide dismutase(SOD), malondialdehyde(MDA), and tyrosinase(TYR) in the skin, serum, and liver tissues were measured. Hematoxylin-eosin(HE) staining and Masson-Fontana staining were used to observe the pathological changes in the tissues. Network pharmacology combined with transcriptomics was employed to identify core targets and pathways, and the differential gene expression was validated by quantitative real-time PCR(qPCR). Pharmacodynamic experiments showed that CA Gel significantly increased SOD activity and decreased MDA and TYR levels in the skin, serum, and liver of model rats. It also improved epidermal thickening, inflammatory infiltration, collagen loss, and melanin deposition. Network pharmacology analysis showed that CA mainly regulated core targets such as signal transducer and activator of transcription 3(STAT3), epidermal growth factor receptor(EGFR), and interleukin-6(IL-6), and modulated the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) and interleukin-17(IL-17) signaling pathways. Transcriptomic analysis showed that CA Gel significantly downregulated the gene expression of heat shock protein 90β family member 1(Hsp90b1), heat shock protein 90α family member 1(Hsp90aa1), and the key steroid synthesis enzyme cytochrome P450 family 17 subfamily A member 1(Cyp17a1), while upregulating thioredoxin 1(Txn1). qPCR results confirmed that CA Gel regulated oxidative stress and inflammatory response by inhibiting the IL-17 signaling pathway and steroid hormone synthesis. This study, for the first time, reveals the molecular mechanism of CA Gel in improving melasma through multi-target synergistic regulation of oxidative stress, inflammatory response, and hormone metabolism pathways, providing a scientific basis for the treatment of pigmentation diseases with traditional Chinese medicine.
Animals ; Rats ; Female ; Rats, Sprague-Dawley ; Network Pharmacology ; Drugs, Chinese Herbal/administration & dosage* ; Melanosis/metabolism* ; Transcriptome/drug effects* ; Humans ; Superoxide Dismutase/genetics* ; Signal Transduction/drug effects* ; Malondialdehyde/metabolism*

INTRODUCTION

Melasma, characterized by dark patches on the skin, predominantly affects individuals with Fitzpatrick skin types III-V and is more common among women. Hydroquinone 4% is traditionally the gold standard for melasma treatment due to its efficacy in reducing pigmentation, but alternatives like β-White™, Tyrostat™, and Melanostatine-5™ or a combination of all are being explored for their potentially better safety profiles.

This study aims to determine the efficacy and safety of β-White + Tyrostat, + Melanostatine-5™ creams versus hydroquinone 4% in the treatment of melasma.

A randomized, double-blind clinical trial compared β-White, Tyrostat, and Melanostatine-5 cream to hydroquinone 4% cream in 40 melasma patients. The intervention consisted of 12-week split-face (left-right) application of the said topical medications. Efficacy was measured using modified Melasma Area and Severity Index (mMASI) Score and the Physician’s and Patient’s Global Assessments (PGA). Safety was used by assessing side effects noted during the application. ANOVA and Post hoc tests were used to measure differences in scores.

Forty out of 42 patients were included in the analysis. The trial found that both treatment regimens were effective, with no significant difference in the reduction of melasma severity over 12 weeks. Initially, the experimental group showed more rapid improvement, but by the third month, both groups reported similar outcomes. The experimental group reported no side effects, making it a potentially safer option for long-term management of melasma.

Overall, while hydroquinone remains effective, β-White + Tyrostat + Melanostatine-5 cream offers a viable alternative with potentially fewer side effects, making it an attractive option for patients seeking long-term melasma management.

Humans ; Melanocytes ; Melanosis ; Fibroblasts ; Skin

14 workers in the 1, 8-diaminonaphthalene workshop of a chemical company in Nantong City had symptoms or signs of varying degrees of pruritus and pigmentation of the face, neck and waist. Pathological examination of skin biopsies showed hyperkeratosis, the basal cells were liquefied and denatured. Seven workers were eventually diagnosed with occupational melanosis. To explore the causes of occupational melanosis caused by exposure to 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene, and to provide reference for the prevention and treatment of occupational melanosis in the future, this paper reported 14 cases of melanosis in the skin of workers in chemical industry.
Humans ; Melanosis/pathology* ; Pigmentation ; Skin/pathology*

INTRODUCTION: Pigmented contact dermatitis (PCD) is characterized by non-eczematous pigmentation associated with contact sensitizers, usually without any active or preceding pruritus and erythema. PCD was first described by Riehl, who identified patients with brown to gray facial pigmentation concentrated on the face most commonly associated with sensitizing chemical such as cosmetics, fragrances, and textiles. CASE REPORT: This is a case of a 48-year-old female Filipino who presents with blue-grey to brown patches on the forehead of 1-year duration with no significant pathologic history. Clinical examination, dermoscopy and histology were consistent with a variant of pigmented contact dermatitis known as Riehl melanosis. Since anamnesis was unremarkable, patch testing was done to identify the contact allergen triggering the symptom. Results obtained a positive reaction to nickel, potassium dichromate, and textile dye. CONCLUSION:Treatment includes the elimination of trigger factors, hence the importance of patch testing in the investigation of its cause. Alongside adequate photoprotection, a combination treatment of 1,064 nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, 20% tricholoacetic acid (TCA) peel and oral retinoids, were found safe and effective in the management of facial melanosis. Three-dimensional imaging and dermoscopy were utilized to obtain a more standard and objective pre- and post-treatment comparison.
Lasers, Solid-State ; Patch Tests ; Melanosis ; Skin Abnormalities ; Dermatitis, Contact

No abstract available.
Cheek ; Melanosis ; Neck

We present 9-year-old fraternal twins from a family with piebaldism, having congenital depigmented macules and meeting the diagnostic criteria for neurofibromatosis type 1 (NF1) due to the multiple café-au-lait macules (CALMs) and intertriginous freckling at the same time. It's still a debatable issue that CALMs and intertriginous freckling may be seen in the clinical spectrum of piebaldism or these patients should be regarded as coexistence of piebaldism and NF1. However, based on recent literature and our patients' findings, we suggest that this rare phenotypic variant of piebaldism may not need the careful clinical follow-up and molecular testing for NF1. Besides, it may be suitable that these individuals with piebaldism showing NF1-like clinical phenotypes should be further tested for KIT and SPRED1 gene mutations.
Cafe-au-Lait Spots ; Child ; Follow-Up Studies ; Humans ; Melanosis ; Neurofibromatoses ; Neurofibromatosis 1 ; Phenotype ; Piebaldism ; Skin Diseases, Genetic ; Twins, Dizygotic

PURPOSE: Acanthosis nigricans (AN) is a hyperpigmented dermatosis associated with obesity and insulin resistance (IR). There is no consensus whether AN extension scoring offers added value to the clinical estimation of IR. In this study we aimed to assess and score AN using both a short and an extended version of the scale proposed by Burke et al. and analyze the relationships of both versions with hyperinsulinemia and IR. METHODS: We analyzed data from 139 overweight adolescents (body mass index ≥85th percentile) aged 12–18 with (n=67) or without (n=72) AN who were followed at a pediatric obesity clinic. RESULTS: Adolescents with AN had higher levels of insulin (d=0.56, P=0.003) and HOMA-IR (d=0.55, P=0.003) compared to those without. Neither the short nor the extended versions of AN scores explained either hyperinsulinemia (β=1.10, P=0.316; β=1.15, P=0.251) or IR (β=1.07, P=0.422; β=1.10, P=0.374). The presence of AN alone predicted hyperinsulinemia and the presence of IR in 7.3% (β=2.68, P=0.008) and 7.1% (β=2.59, P=0.009) of adolescents, respectively. CONCLUSIONS: Screening for AN at the neck and axilla is a noninvasive and cost-effective way to identify asymptomatic overweight adolescents with or at risk of developing IR.
Acanthosis Nigricans ; Adolescent ; Axilla ; Biomarkers ; Consensus ; Humans ; Hyperinsulinism ; Insulin Resistance ; Insulin ; Mass Screening ; Neck ; Obesity ; Overweight ; Pediatric Obesity ; Skin Diseases

Noonan syndrome (NS) and NS-related disorders (cardio-facio-cutaneous syndrome, Costello syndrome, NS with multiple lentigines, or LEOPARD [lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and sensory neural deafness] syndrome) are collectively named as RASopathies. Clinical presentations are similar, featured with typical facial features, short stature, intellectual disability, ectodermal abnormalities, congenital heart diseases, chest & skeletal deformity and delayed puberty. During past decades, molecular etiologies of RASopathies have been growingly discovered. The functional perturbations of the RAS-mitogen-activated protein kinase pathway are resulted from the mutation of more than 20 genes (PTPN11, SOS1, RAF1, SHOC2, BRAF, KRAS, NRAS, HRAS, MEK1, MEK2, CBL, SOS2, RIT, RRAS, RASA2, SPRY1, LZTR1, MAP3K8, MYST4, A2ML1, RRAS2). The PTPN11 (40–50%), SOS1 (10–20%), RAF1 (3–17%), and RIT1 (5–9%) mutations are common in NS patients. In this review, the constellation of overlapping clinical features of RASopathies will be described based on genotype as well as their differential diagnostic points and management.
Congenital Abnormalities ; Costello Syndrome ; Diagnosis ; Ectoderm ; Electrocardiography ; Genitalia ; Genotype ; Heart Diseases ; Humans ; Hypertelorism ; Intellectual Disability ; Lentigo ; Noonan Syndrome ; Panthera ; Protein Kinases ; Puberty, Delayed ; Pulmonary Valve Stenosis ; Thorax

Primary malignant melanoma (PMM) of the gastrointestinal tract is rare. Reported cases of PMM of the lower gastrointestinal tract typically describe anal and rectal involvement rather than colonic lesions. This report describes a rare case of a 50-year-old woman with PMM originating in the colon. The patient presented to Inje University Busan Paik Hospital with a 3-day history of blood-tinged stools. She underwent colonoscopy for a diagnosis of hematochezia. The colonoscopic examination revealed a large-sized semi-pedunculated sigmoid colon polyp with a reddish-colored mucosal surface. Endoscopic mucosal resection was performed, and the final histopathological findings were consistent with a diagnosis of malignant melanoma. Systemic work-up was performed for assessment of metastasis and to identify the primary tumor considering the high metastatic rate of gastrointestinal malignant melanoma; however, no other malignant lesion was detected. Thus, she was diagnosed with colonic PMM. She underwent laparoscopic low anterior resection and lymph node dissection and has been recurrence-free for > 2 years.
Busan ; Colon ; Colon, Sigmoid ; Colonoscopy ; Diagnosis ; Female ; Gastrointestinal Hemorrhage ; Gastrointestinal Tract ; Humans ; Lower Gastrointestinal Tract ; Lymph Node Excision ; Melanoma ; Melanosis ; Middle Aged ; Neoplasm Metastasis ; Polyps