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Autophagy Jun 2024Dysregulation of melanin homeostasis is implicated in causing skin pigmentation disorders, such as melasma due to hyperpigmentation and vitiligo due to hypopigmentation....
Dysregulation of melanin homeostasis is implicated in causing skin pigmentation disorders, such as melasma due to hyperpigmentation and vitiligo due to hypopigmentation. Although the synthesis of melanin has been well studied, the removal of the formed skin pigment requires more research. We determined that β-mangostin, a plant-derived metabolite, induces the degradation of already-formed melanin in the mouse B16F10 cell line. The whitening effect of β-mangostin is mediated by macroautophagy/autophagy, as it was abolished by the knockdown of ATG5 or RB1CC1/FIP200, and by treatment with 3-methyladenine, a phosphatidylinositol 3-kinase complex inhibitor. However, the exact autophagy mechanism of melanosome degradation remains unknown. Selective autophagy for a specific cellular organelle requires specific E3-ligases and autophagic receptors for the target organelle. In this study, an E3-ligase, RCHY1, and an autophagy receptor, OPTN (optineurin), were identified as being essential for melanophagy in the β-mangostin-treated B16F10 cell line. As per our knowledge, this is the first report of a specific mechanism for the degradation of melanosomes, the target organelle of melanophagy. These findings are expected to broaden the scope of melanin homeostasis research and can be exploited for the development of therapeutics for skin pigmentation disorders.
PubMed: 38899611
DOI: 10.1080/15548627.2024.2370058 -
Skin Research and Technology : Official... Jun 2024Successful usage of autologous skin cell suspension (ASCS) has been demonstrated in some clinical trials. However, its efficacy and safety have not been verified. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Successful usage of autologous skin cell suspension (ASCS) has been demonstrated in some clinical trials. However, its efficacy and safety have not been verified. This latest systematic review and meta-analysis aim to examine the effects of autologous epidermal cell suspensions in re-epithelialization of skin lesions.
METHODS
Relevant articles were retrieved from PubMed, Embase, Cochrane Database, Web of Science, International Clinical Trials Registry Platform, China National Knowledge Infrastructureris, VIP Database for Chinese Technical Periodicals and Wanfang database. The primary output measure was the healing time, and the secondary outputs were effective rate, size of donor site for treatment, size of study treatment area, operation time, pain scores, repigmentation, complications, scar scale scores and satisfaction scores. Data were pooled and expressed as relative risk (RR), mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval (CI).
RESULTS
Thirty-one studies were included in this systematic review and meta-analysis, with 914 patients who received autologous epidermal cell suspensions (treatment group) and 883 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced healing time (SMD = -0.86; 95% CI: -1.59-0.14; p = 0.02, I= 95%), size of donar site for treatment (MD = -115.41; 95% CI: -128.74-102.09; p<0.001, I= 89%), operation time (MD = 25.35; 95% CI: 23.42-27.29; p<0.001, I= 100%), pain scores (SMD = -1.88; 95% CI: -2.86-0.90; p = 0.0002, I= 89%) and complications (RR = 0.59; 95% CI: 0.36-0.96; p = 0.03, I= 66%), as well as significantly increased effective rate (RR = 1.20; 95% CI: 1.01-1.42; p = 0.04, I= 77%). There were no significant differences in the size of study treatment area, repigmentation, scar scale scores and satisfaction scores between the two groups.
CONCLUSION
Our meta-analysis showed that autologous epidermal cell suspensions is beneficial for re-epithelialization of skin lesions as they significantly reduce the healing time, size of donar site for treatment, operation time, pain scores and complications, as well as increased effective rate. However, this intervention has minimal impact on size of treatment area, repigmentation, scar scale scores and satisfaction scores.
Topics: Humans; Randomized Controlled Trials as Topic; Epidermal Cells; Transplantation, Autologous; Re-Epithelialization; Treatment Outcome; Wound Healing; Skin Diseases
PubMed: 38898373
DOI: 10.1111/srt.13820 -
The Journal of Dermatology Jun 2024Autologous cultured pure melanocyte transplantation (CMT) can be utilized to treat stable vitiligo cases, but clinical data are insufficient to improve its efficacy. To...
Autologous cultured pure melanocyte transplantation (CMT) can be utilized to treat stable vitiligo cases, but clinical data are insufficient to improve its efficacy. To evaluate the influence of various factors on the therapeutic effect of CMT, this single-center retrospective study enrolled stable vitiligo patients who underwent CMT between 2009 and 2020. Univariate and multivariable analysis were used to determine the factors affecting the outcome of repigmentation. The study included 491 patients with long-term follow-up data (6-120 months). It was found that 69.7% of patients achieved an excellent re-color effect and 18.4% achieved a good re-color effect. There were statistically significant differences in pigmentation between patients with stable disease course, vitiligo type, and lesion site. Overall, a significant positive correlation between the target area treatment ratio of varied lesions and the percentage of repigmentation was found. CMT is effective and well tolerated in the treatment of stable vitiligo. Various factors, especially the target area treatment ratio of varied lesions, should be carefully assessed before using CMT. As the target area treatment ratio of varied lesions could further improve the post-operative repigmentation other than type of vitiligo. This clinic trial was approved by Hangzhou Third People's Hospital (number 2023KA015, national clinical record number MR-33-23-034502).
PubMed: 38895831
DOI: 10.1111/1346-8138.17320 -
Journal of Cosmetic Dermatology Jun 2024Vitiligo remains a challenging condition to treat. Fire needle therapy, a traditional Chinese medicine technique, has potential as an alternative therapeutic strategy....
BACKGROUND
Vitiligo remains a challenging condition to treat. Fire needle therapy, a traditional Chinese medicine technique, has potential as an alternative therapeutic strategy. However, rigorous evidence on its efficacy is lacking.
OBJECTIVE
We aimed to evaluate the efficacy and safety of fire needle therapy, alone and combined with topical tacrolimus ointment, for non-segmental stable vitiligo.
METHODS
In this 6-month randomized self-controlled trial, 35 vitiligo patients were enrolled, providing three similar lesions each. Lesions were randomly allocated to receive fire needle monotherapy, 0.1% tacrolimus ointment monotherapy, or combined fire needle and tacrolimus ointment therapy. The main outcome was change in vitiligo surface area.
RESULTS
In total, 29 patients completed the 6-month follow-up. The combination therapy group showed significantly greater reductions in vitiligo surface area compared to monotherapy groups starting at months 4 and 5. By the end of the study, combination therapy resulted in remarkably higher repigmentation responses, with 89.7% of lesions showing at least mild (≥25%) repigmentation and 51.7% showing good (≥50%) repigmentation. This significantly exceeded the outcomes with topical tacrolimus ointment alone, which only achieved 6.9% mild response and 6.9% good response. Fire needle monotherapy also demonstrated steady repigmentation over time, with 69% of lesions attaining a mild response by month 6. Importantly, no major adverse events occurred.
CONCLUSION
This study provides promising preliminary evidence supporting the use of fire needle therapy, alone or in combination with topical tacrolimus ointment, for inducing repigmentation in non-segmental stable vitiligo. As a non-pharmacological approach, fire needle therapy warrants further study as an alternative vitiligo treatment.
PubMed: 38894565
DOI: 10.1111/jocd.16428 -
Journal of Clinical Medicine May 2024Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune... (Review)
Review
Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune diseases seem to be particularly correlated with depressive comorbidity, raising the question of their possible common pathomechanism. The PubMed database was searched, focusing on results published after 2016. A particular reciprocal correlation of depressive disorders with psoriasis, atopic dermatitis, alopecia areata, impetigo, lupus and systemic scleroderma was found. One possible explanation for the co-occurrence of the above diseases is that the inflammatory theory may be applicable to depression, the various elements of which also apply to autoimmune diseases.
PubMed: 38892934
DOI: 10.3390/jcm13113224 -
International Journal of Molecular... May 2024Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss.... (Review)
Review
Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient's quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis.
Topics: Alopecia Areata; Humans; Animals; Hair Follicle
PubMed: 38891839
DOI: 10.3390/ijms25115652 -
JMIR Dermatology Jun 2024Vitiligo, a common dermatological disorder in Saudi Arabia, is associated with significant psychological impacts. This study explores the relationship between vitiligo...
BACKGROUND
Vitiligo, a common dermatological disorder in Saudi Arabia, is associated with significant psychological impacts. This study explores the relationship between vitiligo and the severity of Major Depressive Disorder (MDD), highlighting the broader implications on mental health among affected individuals.
OBJECTIVE
To assess the prevalence and predictors of depression among adult vitiligo patients, and to examine the relationship between MDD severity and vitiligo.
METHODS
Employing a cross-sectional design, the research utilized the Vitiligo Area Severity Index (VASI) and the Patient Health Questionnaire-9 (PHQ-9) to measure the extent of vitiligo and depression severity respectively. The study involved 340 diagnosed vitiligo patients from various healthcare settings. Logistic and ordinal regression analysis were applied to evaluate the impact of sociodemographic variables and vitiligo types on MDD severity.
RESULTS
The prevalence of MDD was 58.8% (200 out of 340 participants). Depression severity varied notably: 24.7% of patients experienced mild depression, 31.1% moderate, 22.6% moderately severe, and 21.6% severe depression. Female patients had higher odds of severe depression compared to males (aOR = 3.14, 95% CI: 1.93-5.1, P < .001). Age was inversely related to depression severity, with patients over 60 years showing significantly lower odds (aOR = 0.1, 95% CI: 0.03-0.39, P < .001). Lower income was associated with higher depression severity (aOR = 10.2, 95% CI: 3.25-31.8, P < .001). Vitiligo types also influenced depression severity; vulgaris (aOR = 5.3, 95% CI: 2.6-10.9, P < .001) and acrofacial vitiligo (aOR = 2.8, 95% CI: 1.5-5.1, P < .001) were significantly associated with higher depression levels compared to focal vitiligo.
CONCLUSIONS
The findings suggest that vitiligo contributes to an increased risk of severe depression, highlighting the need for integrated dermatological and psychological treatment approaches to address both the physical and mental health aspects of the disease.
PubMed: 38888950
DOI: 10.2196/60686 -
Advanced Science (Weinheim,... Jun 2024Vitiligo is an autoimmune disease characterized by epidermal melanocyte destruction, with abnormal autoimmune responses and excessive oxidative stress as two cardinal...
Vitiligo is an autoimmune disease characterized by epidermal melanocyte destruction, with abnormal autoimmune responses and excessive oxidative stress as two cardinal mechanisms. Human umbilical mesenchymal stem cells-derived exosomes (hUMSCs-Exos) are regarded as promising therapeutic choice for autoimmune diseases due to potent immunosuppressive and anti-oxidative properties, which can be potentiated under 3D cell culture condition. Nevertheless, whether exosomes derived from 3D spheroids of hUMSCs (3D-Exos) exhibit considerable therapeutic effect on vitiligo and the underlying mechanism remain elusive. In this study, systemic administration of 3D-Exos showed a remarkable effect in treating mice with vitiligo, as revealed by ameliorated skin depigmentation, less CD8T cells infiltration, and expanded Treg cells in skin, and 3D-Exos exerted a better effect than 2D-Exos. Mechanistically, 3D-Exos can prominently facilitate the expansion of Treg cells in vitiligo lesion and suppress HO-induced melanocytes apoptosis. Forward miRNA profile analysis and molecular experiments have demonstrated that miR-132-3p and miR-125b-5p enriched in 3D-Exos greatly contributed to these biological effects by targeting Sirt1 and Bak1 respectively. In aggregate, 3D-Exos can efficiently ameliorate vitiligo by simultaneously potentiating Treg cells-mediated immunosuppression and suppressing oxidative stress-induced melanocyte damage via the delivery of miR-132-3p and miR-125b-5p. The employment of 3D-Exos will be a promising treament for vitiligo.
PubMed: 38887870
DOI: 10.1002/advs.202404064 -
Skin Research and Technology : Official... Jun 2024The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined...
BACKGROUND
The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined with oral mini-pulse therapy (OMP) and narrow-band ultraviolet B (NB-UVB) in treating active nonsegmental vitiligo (NSV).
MATERIALS AND METHODS
The combination therapy was contrasted against those from a group treated solely with OMP and NB-UVB. Data from 62 patients undergoing TGP combination treatment and 55 without were analyzed over a 3-month period. After 6 months, the differences in recurrence rate were investigated by follow-up.
RESULTS
The findings indicate that integrating TGP may yield superior outcomes compared to OMP + NB-UVB alone. Moreover, the patient's oxidative stress makers were significantly reduced after the treatment. The majority of patients in the TGP cohort exhibited enhanced skin pigmentation over the duration. Notably, no increase in side effects or recurrence was observed in this group. Especially, patients with vitiligo on their head and neck experienced pronounced improvements.
CONCLUSION
The efficacy of the combination treatment group was better than that of the control group at 2 and 3 months, and there was no difference in recurrence rate and side effects, suggesting that TGP may continue to show efficacy in NSV for a longer period of time by reducing the level of oxidative stress, and is especially suitable for patients with head and neck lesions.
Topics: Humans; Vitiligo; Female; Male; Adult; Ultraviolet Therapy; Retrospective Studies; Paeonia; Glucosides; Combined Modality Therapy; Middle Aged; Young Adult; Adrenal Cortex Hormones; Treatment Outcome; Administration, Oral; Plant Extracts; Adolescent; Skin Pigmentation
PubMed: 38887837
DOI: 10.1111/srt.13769 -
Frontiers in Immunology 2024The pathogenesis of vitiligo remains elusive. Emerging evidence suggests that vitiligo is an immune-mediated disorder, in which a plethora of immune cells play pivotal...
BACKGROUND
The pathogenesis of vitiligo remains elusive. Emerging evidence suggests that vitiligo is an immune-mediated disorder, in which a plethora of immune cells play pivotal roles. However, the association between circulating immune cells and vitiligo continues to be enigmatic.
MATERIALS AND METHODS
We extracted single nucleotide polymorphisms (SNPs) associated with immune circulating cells at a genome-wide significance level from the BLOOD CELL CONSORTIUM's genome-wide association study (GWAS) dataset. Summary data for 385,801 cases of vitiligo were obtained from a large-scale Finnish genome-wide association study (ncases=292, ncontrols=385,509). The inverse variance weighted (IVW) method was employed as the primary analytical approach for Mendelian randomization (MR) analysis. Additionally, heterogeneity was assessed using Cochran's Q value, and horizontal pleiotropy was evaluated using MR-Egger Mendelian Randomization Pleiotropy RESidual Sum and Outlier and leave-one-out analyses.
RESULTS
The risk of vitiligo was found to increase with the elevation of 4 circulating immune cells, as evidenced by the odds ratios (ORs) and 95% confidence intervals (CIs): basophils (OR=1.81; 95% CI: 1.01-3.24, p=0.0450), monocytes (OR=1.67; 95% CI: 1.23-2.26, p=0.0009), eosinophils (OR=1.78; 95% CI: 1.22-2.59, p=0.0028), and neutrophils (OR=1.65; 95% CI: 1.08-2.54, p=0.0208). After removing outliers, the sensitivity analysis of the above indicators did not show heterogeneity and pleiotropy.
CONCLUSION
Our findings illuminate the association between circulating immune cells and vitiligo, offering insights that could guide clinical practices in the treatment of vitiligo.
Topics: Vitiligo; Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38887286
DOI: 10.3389/fimmu.2024.1391186