Dysregulated tryptophan metabolism and AhR pathway contributed to CXCL10 upregulation in stable non-segmental vitiligo.

BACKGROUND: Tryptophan metabolism dysregulation has been observed in vitiligo. However, drawing a mechanistic linkage between this metabolic disturbance and vitiligo pathogenesis remains challenging. OBJECTIVE: Aim to reveal the characterization of tryptophan metabolism in vitiligo and investigate the role of tryptophan metabolites in vitiligo pathophysiology. METHODS: LC-MS/MS, dual-luciferase reporter assay, ELISA, qRT-PCR, small interfering RNA, western blotting, and immunohistochemistry were employed. RESULTS: Kynurenine pathway activation and KYAT enzyme-associated deviation to kynurenic acid (KYNA) in the plasma of stable non-segmental vitiligo were determined. Using a public microarray dataset, we next validated the activation of kynurenine pathway was related with inflammatory-related genes expression in skin of vitiligo patients. Furthermore, we found that KYNA induced CXCL10 upregulation in keratinocytes via AhR activation. Moreover, the total activity of AhR agonist was increased while the AhR concentration per se was decreased in the plasma of vitiligo patients. Finally, higher KYAT, CXCL10, CYP1A1 and lower AhR expression in vitiligo lesional skin were observed by immunohistochemistry staining. CONCLUSION: This study depicts the metabolic and genetic characterizations of tryptophan metabolism in vitiligo and proposes that KYNA, a tryptophan-derived AhR ligand, can enhance CXCL10 expression in keratinocytes.

The role of aryl hydrocarbon receptor in vitiligo: a review.

Vitiligo is an acquired autoimmune dermatosis characterized by patchy skin depigmentation, causing significant psychological distress to the patients. Genetic susceptibility, environmental triggers, oxidative stress, and autoimmunity contribute to melanocyte destruction in vitiligo. Due to the diversity and complexity of pathogenesis, the combination of inhibiting melanocyte destruction and stimulating melanogenesis gives the best results in treating vitiligo. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that can regulate the expression of various downstream genes and play roles in cell differentiation, immune response, and physiological homeostasis maintenance. Recent studies suggested that AhR signaling pathway was downregulated in vitiligo. Activation of AhR pathway helps to activate antioxidant pathways, inhibit abnormal immunity response, and upregulate the melanogenesis gene, thereby protecting melanocytes from oxidative stress damage, controlling disease progression, and promoting lesion repigmentation. Here, we review the relevant literature and summarize the possible roles of the AhR signaling pathway in vitiligo pathogenesis and treatment, to further understand the links between the AhR and vitiligo, and provide new potential therapeutic strategies.

The efficiency and safety of low-dosage isotretinoin therapy for Chinese acne vulgaris patients.

BACKGROUND: Acne vulgaris is one of the most common skin conditions in dermatology clinics. Accumulating evidence has implicated oral low-dosage isotretinoin was an effective treatment for acne with fewer side effects. Currently, the data on low-dosage isotretinoin use in Chinese is limited. AIMS: To investigate the efficiency and safety of low-dosage isotretinoin therapy for Chinese acne patients. METHODS: Three hundred and eighty-eight patients treated with low-dosage isotretinoin (0.2-0.4 mg/kg/d) and who completed the course (120 mg/kg) were enrolled. Medical information on the severity, duration, adverse effects, and outcome of acne was reviewed. RESULTS: The majority (90.2%, n = 350) of patients achieved complete remission, and on average, patients received 13.5 months of treatment. The time between isotretinoin start and the clear date between the mild and moderate groups was not significantly different (74 ± 24 vs. 84 ± 24 days). However, it took longer to resolve for the severe acne group (112 ± 25 days). Follow-up 1 year after completion of the isotretinoin course, 37/350 (10.6%) patients relapsed, but there was no difference in the severity of acne. There were 133 (34.3%), 40 (10.3%), and 14 (2.6%) patients who developed hypercholesterolemia, hypertriglyceridemia, and high LDL, respectively. Thirty-two (8.2%) and 28 patients (7.2%) had elevated serum levels of alanine and aspartate aminotransferases. No values above grade 2 were detected. CONCLUSIONS: This study reaffirms the efficacy and safety of low-dosage oral isotretinoin in Chinese patients with acne vulgaris. Lab investigation could be performed after 2 months of therapy in healthy patients with normal baseline liver function and lipid panel tests.

Enhanced removal of Cr(VI) by polyethyleneimine-modified bamboo hydrochar.

Hydrochar is an environmentally friendly and cheap adsorbent, but its adsorption amounts for anions is very limited. The functionalized hydrochar can overcome this shortcoming. Herein, polyethyleneimine-modified hydrochar (PEI-HC) was synthesized from hydrothermal carbonization (HTC) of methyl acrylate and bamboo after addition of initiator ammonium persulfate, and then modified by polyethyleneimine (PEI), which was used to treat Cr(VI). PEI-HC was tested by XANES, EXAFS, SEM-EDS, XPS, FTIR, N2 sorption isotherms, zeta potential, and elemental analyses. The characterizations showed that PEI was successfully grafted onto hydrochar, and the PEI-HC was rich in N and O functional groups, which presented high Cr(VI) sorption ability (528.41 mg·g-1 at pH 2). The bath experiments found the pseudo-second-order kinetic and Freundlich equations can well describe the adsorption kinetics and isotherm of the Cr(VI) adsorption onto PEI-HC, respectively. Electrostatic interaction, reduction, complexation, and H-bonding are the main removal mechanisms as supported by XANES, EXAFS, XPS, and FTIR. This study provides a strategy of combining HTC and free radical graft polymerization to convert agricultural and forestry wastes into functionalized hydrochar, showing highly efficient removal of Cr(VI).

TMT-Based Quantitative Proteomic and Physiological Analyses on Serums of Chinese Patients with Active Vitiligo.

Purpose: Vitiligo is an acquired depigmented skin disorder. Though genetic background, autoimmune dysregulation, and oxidative stress were reported involved in the development of vitiligo, the exact pathogenesis remains largely unknown. This study aimed to investigate potential functional proteins, pathways, and serum biomarkers involved in active vitiligo. Patients and Methods: Tandem Mass Tags (TMT) method was used to determine differentially expressed proteins (DEPs) in serum samples between 11 active vitiligo patients and 7 healthy controls of Chinese Han population. Results: A total of 31 DEPs were identified (P < 0.05, fold change >1.2), with 21 proteins upregulated and 10 proteins downregulated in the vitiligo group. DEPs were enriched in GO terms such as "extracellular exosome" and "immunoglobulin receptor binding", as well as KEGG pathways including "cysteine and methionine metabolism" and other immune-related pathways. Furthermore, ALDH1A1 and EEF1G achieved areas under receiver-operating characteristic (ROC) curve of 0.9221 and 0.8571, respectively. The expression levels of these 2 proteins were validated in another active vitiligo patient group. Conclusion: Our research provided novel insight into serum proteomic profile for vitiligo patients, detecting ALDH1A1 and EEF1G as potential biomarkers for active vitiligo and therapeutic intervention. Our work also detected several DEPs and associated pathways in the serum of active vitiligo patients, reinforcing the roles of retinoic acid and exosome processes in vitiligo pathogenesis.

Roflumilast enhances the melanogenesis and attenuates oxidative stress-triggered damage in melanocytes.

BACKGROUND: The management of vitiligo is challenging due to limited treatment options, and therapeutic strategy varies according to the active or stable stage of vitiligo. PDE4 inhibitor has been used to treat various skin diseases, but the efficacy in vitiligo treatment is mixed. OBJECTIVE: In this study, we aimed to investigate whether roflumilast, a PDE4 inhibitor, induces melanogenesis and attenuates oxidative stress-triggered damage in melanocytes, and if so, what is the mechanism. METHODS: Melanin content assay, qRT-PCR, western blotting, ELISA, immunofluorescence assays, immunohistochemistry, small interfering RNA, flow cytometry, and transmission electron microscopy were employed. RESULTS: Our results demonstrated that roflumilast alone only slightly increased melanogenesis, however, the combination of roflumilast and forskolin could boost cAMP levels, hence promoting melanogenesis more significantly. Moreover, roflumilast attenuated H2O2-induced apoptosis and mitochondrial morphological changes in melanocytes by reducing ROS levels. Furthermore, roflumilast activated AhR/Nrf2 pathway via cAMP whereas AhR silencing blocked roflumilast-induced Nrf2 nuclear translocation and reversed the inhibitory effect of roflumilast on H2O2-induced ROS production. Finally, we observed that the lesional skin of active vitiligo patients exhibited higher PDE4 expression levels. CONCLUSION: roflumilast enhances the melanogenesis effect of forskolin and protects melanocytes from H2O2-induced apoptosis by cAMP/AhR/Nrf2-activated ROS inhibition, highlighting its therapeutic potential in vitiligo treatment.

Atrophic dermatofibrosarcoma protuberans: Two case reports and literature review.

Dermatofibrosarcoma protuberans is a rare, locally aggressive, slowly growing cutaneous fibroblastic sarcoma with a high recurrence rate and low metastatic potential. Atrophic dermatofibrosarcoma protuberans is a rare variant usually presents as atrophic plaques, easily neglected and misdiagnosed as benign lesions by patients and dermatologists. Here we report two cases of atrophic dermatofibrosarcoma protuberans, one of which was accompanied by pigment, and review other cases have been reported in the literature. Understanding the most up-to-date literature and early identification of these dermatofibrosarcoma protuberans variants can help clinicians avoid delayed diagnosis and improve prognosis.

Nodular and diffuse spindle cell infiltration in keloidal scleroderma: a case report.

Keloidal scleroderma is a variant of scleroderma that presents as firm keloidal nodules or plaques. Due to the similarity in morphology and pathology, it is often distinguished from a hypertrophic scar or keloid. We report a case of keloidal scleroderma with rare nodular and diffuse spindle cell infiltration in histopathology. Recognition of this unusual histopathological feature may help clinicians improve their knowledge and avoid misdiagnosis.

Eyebrow tattoo-associated sarcoidosis: A case report.

Cutaneous sarcoidosis can manifest after doing a permanent makeup (PMU), such as tattooed eyebrows. A 41-year-old Chinese woman, with a tattoo in the eyebrows, developed yellow-brown plaques in her eyebrows for several months. A dermatopathological examination revealed non-caseating granulomas consistent with cutaneous sarcoidosis. For months, topical corticosteroids were applied, which showed little effect. Furthermore, a physical evaluation of the patient revealed no apparent involvement of other body organs except bilateral hilar lymphadenopathy with few diffuse reticulonodular opacities. On the basis of fully informed consent, the patient agreed to a 6-month initial follow-up to avoid unnecessary PMU.

[Material design and temperature field simulation analysis of tumor radiofrequency ablation needle].

To solve the problems of small one-time ablation range and easy charring of the tissue around the electrode associated with the tumor radiofrequency ablation needle, based on the multiphysical field coupling analysis software COMSOL, the effects of needle material, the number of sub needles and the bending angle of sub needles on the ablation effect of radiofrequency ablation electrode needle were studied. The results show that compared with titanium alloy and stainless steel, nickel titanium alloy has better radiofrequency energy transmission efficiency and it is the best material for electrode needle. The number of sub needles has a great influence on the average necrosis depth and the maximum necrosis diameter. Under the same conditions, the more the number of sub needles, the larger the volume of coagulation necrosis area. The bending angle of the needle has a great effect on the maximum diameter of the coagulated necrotic area, but has little effect on the average necrotic depth. Under the same other conditions, the coagulation necrosis area formed by ablation increased with the increase of the bending angle of the sub needle. For the three needles with bending angles of 60 °, 90 ° and 120 ° analyzed in this paper, the one with bending angle of 120 ° can obtain the largest coagulation necrosis area. In general, the design of nickel titanium alloy with 120 ° bending 8-pin is the optimal. The average depth of radiofrequency ablation necrosis area is 32.40 mm, and the maximum necrosis diameter is 52.65 mm. The above optimized design parameters can provide guidance for the structure and material design of tumor radiofrequency ablation needle.

Four-Octyl Itaconate Attenuates UVB-Induced Melanocytes and Keratinocytes Apoptosis by Nrf2 Activation-Dependent ROS Inhibition.

Vitiligo is an acquired skin depigmentation disease in which excessive reactive oxygen species (ROS) play a critical pathogenic role in melanocyte destruction. The complex crosstalk between melanocytes and keratinocytes in vitiligo suggests that treatments aimed at protecting both the cells might be meaningful. In this study, we investigated the effect of 4-octyl itaconate (4-OI), an itaconate derivative, on ultraviolet B- (UVB-) induced apoptosis in HaCaT and PIG1 cells and the underlying mechanisms. HaCaT and PIG1 cells were pretreated with 4-OI (50 or 100 µM) for 24 h and then exposed to 300 mJ/cm2 UVB (emission range 290-320 nm, emission peak 310 nm). ROS levels and cell apoptosis were investigated using fluorescence microscopy and flow cytometry 24 h after irradiation. In addition, nuclear translocation and the expression of pathway-related proteins and mRNAs were detected using confocal microscopy, western blotting, and qRT-PCR, respectively. Our results demonstrated that UVB induced apoptosis in HaCaT and PIG1 cells, whereas inhibition of ROS production could reverse this effect. Furthermore, 4-OI attenuated UVB-induced apoptosis in HaCaT and PIG1 cells in a concentration-dependent manner by reducing the ROS levels. Moreover, 4-OI induced nuclear translocation and activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and Nrf2 silencing reversed the inhibitory effect of 4-OI on the UVB-induced increase in ROS production and apoptosis in HaCaT and PIG1 cells. In addition, in vivo experiments using the Institute of Cancer Research mouse model showed that 4-OI via tail vein injection (10 mg/kg/day for six consecutive days) could reduce skin damage induced by UVB (400 mJ/cm2/day for five consecutive days). In conclusion, 4-OI can protect melanocytes and keratinocytes from UVB-induced apoptosis by Nrf2 activation-dependent ROS inhibition and can potentially treat skin disorders associated with oxidative stress, such as vitiligo.