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Clinics in Dermatology Jun 2024Frontal fibrosing alopecia (FFA) is characterized by a receding hairline in the frontotemporal region due to the gradual loss of hair follicles and then follicular stem...
Frontal fibrosing alopecia (FFA) is characterized by a receding hairline in the frontotemporal region due to the gradual loss of hair follicles and then follicular stem cells and follicular fibrosis. Follicular stem cells are crucial in skin healing after chemical peeling and other resurfacing procedures. Although there is a possible association of FFA with a history of facial and scalp surgical procedures, there is no information on the safety of cosmetic procedures in patients with FFA. We report five patients with FFA who experienced unusual and complicated outcomes after undergoing a deep chemical peel (phenol and croton oil). As the prevalence of FFA continues to increase globally, it is essential to raise awareness about the potential incompatibility of this dermatologic disorder with specific cosmetic procedures, such as deeper peels and other resurfacing modalities.
PubMed: 38942154
DOI: 10.1016/j.clindermatol.2024.06.024 -
Clinical Reviews in Allergy & Immunology Jun 2024Fibroblasts are crucial components of the skin structure. They were traditionally believed to maintain the skin's structure by producing extracellular matrix and other... (Review)
Review
Fibroblasts are crucial components of the skin structure. They were traditionally believed to maintain the skin's structure by producing extracellular matrix and other elements. Recent research illuminated that fibroblasts can respond to external stimuli and exhibit diverse functions, such as the secretion of pro-inflammatory factors, adipogenesis, and antigen presentation, exhibiting remarkable heterogeneity and plasticity. This revelation positions fibroblasts as active contributors to the pathogenesis of skin diseases, challenging the traditional perspective that views fibroblasts solely as structural entities. Based on their diverse functions, fibroblasts can be categorized into six subtypes: pro-inflammatory fibroblasts, myofibroblasts, adipogenic fibroblasts, angiogenic fibroblasts, mesenchymal fibroblasts, and antigen-presenting fibroblasts. Cytokines, metabolism, and epigenetics regulate functional abnormalities in fibroblasts. The dynamic changes fibroblasts exhibit in different diseases and disease states warrant a comprehensive discussion. We focus on dermal fibroblasts' aberrant manifestations and pivotal roles in inflammatory and autoimmune skin diseases, including psoriasis, vitiligo, lupus erythematosus, scleroderma, and atopic dermatitis, and propose targeting aberrantly activated fibroblasts as a potential therapeutic strategy for inflammatory and autoimmune skin diseases.
PubMed: 38940997
DOI: 10.1007/s12016-024-08997-1 -
Journal of Cardiothoracic Surgery Jun 2024Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is...
BACKGROUND
Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is required when treating patients with involvement of LSA. The best antiplatelet therapy after LSA reconstruction is presently uncertain.
METHODS
This study retrospectively analyzed 245 type B aortic dissection patients who underwent left subclavian artery revascularization during TEVAR. Out of 245 patients, 159 (64.9%) were in the single antiplatelet therapy (SAPT) group, receiving only aspirin, and 86 (35.1%) were in the dual antiplatelet therapy (DAPT) group, receiving aspirin combined with clopidogrel. During the 6-month follow-up, primary endpoints included hemorrhagic events (general bleeding and hemorrhagic strokes), while secondary endpoints comprised ischemic events (left upper limb ischemia, ischemic stroke, and thrombotic events), as well as death and leakage events. Both univariate and multivariate Cox regression analyses were performed on hemorrhagic and ischemic events, with the Kaplan-Meier method used to generate the survival curve.
RESULTS
During the six-month follow-up, the incidence of hemorrhagic events in the DAPT group was higher (8.2% vs. 30.2%, P < 0.001). No significant differences were observed in ischemic events, death, or leakage events among the different antiplatelet treatment schemes. Multivariate Cox regression analysis showed that DAPT (HR: 2.22, 95% CI: 1.07-4.60, P = 0.032) and previous chronic conditions (HR:3.88, 95% CI: 1.24-12.14, P = 0.020) significantly affected the occurrence of hemorrhagic events. Chronic conditions in this study encompassed depression, vitiligo, and cholecystolithiasis. Carotid subclavian bypass (CSB) group (HR:0.29, 95% CI: 0.12-0.68, P = 0.004) and single-branched stent graft (SBSG) group (HR:0.26, 95% CI: 0.13-0.50, P < 0.001) had a lower rate of ischemic events than fenestration TEVAR (F-TEVAR). Survival analysis over 6 months revealed a lower risk of bleeding associated with SAPT during hemorrhagic events (P = 0.043).
CONCLUSIONS
In type B aortic dissection patients undergoing LSA blood flow reconstruction after synchronous TEVAR, the bleeding risk significantly decreases with the SAPT regimen, and there is no apparent ischemic compensation within 6 months. Patients with previous chronic conditions have a higher risk of bleeding. The CSB group and SBSG group have less ischemic risk compared to F-TEVAR group.
Topics: Humans; Male; Female; Retrospective Studies; Platelet Aggregation Inhibitors; Subclavian Artery; Middle Aged; Aortic Dissection; Endovascular Procedures; Aortic Aneurysm, Thoracic; Aged; Clopidogrel; Aspirin; Aorta, Thoracic; Treatment Outcome; Blood Vessel Prosthesis Implantation; Postoperative Complications; Endovascular Aneurysm Repair
PubMed: 38937841
DOI: 10.1186/s13019-024-02932-3 -
Clinical, Cosmetic and Investigational... 2024Vitiligo is an autoimmune disease characterized by loss of skin pigmentation and currently has no effective treatment. This study aimed to investigate the function of...
BACKGROUND
Vitiligo is an autoimmune disease characterized by loss of skin pigmentation and currently has no effective treatment. This study aimed to investigate the function of SIRT7, being an important desuccinylase mediating multiple disease progression, and its mechanism in vitiligo progression.
METHODS
Normal human melanocytes (NHM) PIG1 and vitiligo human melanocytes (VHM) PIG3V were utilized in this research. The role of sirtuin 7 (SIRT7) and Ezrin (EZR) on melanin synthesis was investigated by detecting tyrosinase activity, melanin content, α-MSH levels, and the protein levels of melanin-related markers. The function of EZR was identified via rescue experiments, while the underlying mechanism was investigated via bioinformatic analysis, co-immunoprecipitation (co-IP), immunoprecipitation (IP), and Western blot techniques.
RESULTS
Results showed that only SIRT7 was highly expressed in vitiligo human melanocytes, where knockingdown SIRT7 translated into increased melanin synthesis in melanocytes. Mechanistically, SIRT7 knockdown promoted the succinylation of EZR at the Lys (K)60 site. Moreover, overexpressing EZR induced higher melanin synthesis in melanocytes, while its knocking down exerted the opposite effect by inhibiting SIRT7 knockdown-induced melanin synthesis.
CONCLUSION
SIRT7 inhibited melanin synthesis in melanocytes by suppressing the succinylation of EZR. These findings are envisaged to provide a novel theoretical basis for vitiligo treatment.
PubMed: 38933605
DOI: 10.2147/CCID.S462280 -
Dermatology and Therapy Jun 2024There is currently a lack of research regarding disease course and burden as well as treatment patterns and goals in patients with non-segmental vitiligo (NSV). The aim...
INTRODUCTION
There is currently a lack of research regarding disease course and burden as well as treatment patterns and goals in patients with non-segmental vitiligo (NSV). The aim of this analysis was to evaluate disease course, treatment patterns and goals in patients with NSV.
METHODS
This analysis used secondary data from the Adelphi Real World Vitiligo Disease Specific Programme 2021, specifically, a survey of physicians and their adult and adolescent patients with NSV. Physicians categorized patients by the extent of NSV at time of survey completion as mild, moderate or severe/very severe. Physician-reported patient information included demographics, current/previously prescribed NSV therapies, treatment satisfaction and the Vitiligo Noticeability Scale (VNS). Patients completed a survey on treatment satisfaction and the VNS. Treatment pattern data were stratified by disease extent and Fitzpatrick skin type.
RESULTS
At survey completion, physicians reported that 38, 50 and 12% of patients (N = 1865) had improving, stable and deteriorating/progressing disease, respectively. Most patients (96%) with mild disease at treatment initiation still had mild disease at the time of survey completion. More than half of patients with moderate disease (62%) or severe/very severe disease (57%) at treatment initiation still had moderate or severe/very severe disease at survey completion. Topical calcineurin inhibitors (TCIs) were the most common treatment in 40% of patients followed by phototherapy in 30%. Patients hoped for re-pigmentation (mild 56%, moderate 62%, severe/very severe 66%), reduction (mild 50%, moderate 56%, severe/very severe 49%) or cessation of affected areas with vitiligo (mild 48%, moderate 54%, severe/very severe 43%).
CONCLUSION
The study findings indicate that a significant proportion of patients with NSV are not improving on current treatments, most commonly TCIs and phototherapy. The results highlight the unmet need for novel and effective therapies to substantially improve re-pigmentation, an important treatment goal for patients with NSV.
PubMed: 38926302
DOI: 10.1007/s13555-024-01212-1 -
International Journal of Cosmetic... Jun 2024Methylsulfonylmethane (MSM), which contains organic sulphur, has been used for a long time as a medicinal ingredient because of its benefits to human health. MSM is...
OBJECTIVE
Methylsulfonylmethane (MSM), which contains organic sulphur, has been used for a long time as a medicinal ingredient because of its benefits to human health. MSM is reported to be protective against certain skin disorders, but it is unknown whether it affects melanin synthesis. Therefore, in our current research, we examined the possibility of MSM controlling the production of melanin in Mel-Ab melanocytes.
METHODS
In Mel-Ab cells, melanin contents and tyrosinase activities were assessed and quantified. The expression of microphthalmia-associated transcription factor (MITF) and tyrosinase was evaluated using western blot analysis, while MSM-induced signalling pathways were investigated.
RESULTS
The MSM treatment significantly resulted in a dose-dependent increase in melanin production. Furthermore, MSM elevated melanin-related proteins, including MITF and tyrosinase. However, the rate-limiting enzyme of melanin production, tyrosinase, was not directly influenced by it. Therefore, we investigated potential melanogenesis-related signalling pathways that may have been triggered by MSM. Our findings showed that MSM did not influence the signalling pathways associated with glycogen synthase kinase 3β, cAMP response-element binding protein, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase. However, MSM phosphorylated c-Jun N-terminal kinases/stress-activated protein kinase (JNK/SAPK), which is known to induce melanogenesis. SP600125, a specific JNK inhibitor, inhibited MSM-induced melanogenesis.
CONCLUSION
Taken together, our study indicates that MSM induces melanin synthesis and may serve as a therapeutic option for hypopigmentary skin disorders such as vitiligo.
PubMed: 38924609
DOI: 10.1111/ics.12988 -
Annals of the New York Academy of... Jun 2024This study aimed to investigate the protective effect of NAcM-OPT, a small molecule inhibitor of defective in cullin neddylation 1 (DCN1), on HO-induced oxidative damage...
This study aimed to investigate the protective effect of NAcM-OPT, a small molecule inhibitor of defective in cullin neddylation 1 (DCN1), on HO-induced oxidative damage in keratinocytes. Immortalized human keratinocytes (HaCaT cells) were treated with NAcM-OPT and exposed to oxidative stress. CCK-8 assays were used to measure cell viability. The mGFP-RFP-LC3 dual fluorescent autophagy indicator system was utilized to evaluate changes in autophagic flux. Western blotting was used to measure the expression of the autophagy-related proteins LC3 and Beclin 1. Keratinocytes were treated with the autophagy activator rapamycin, and HaCaT cell supernatant was added to PIG1 cells (immortalized human melanocytes), followed by evaluation of tyrosinase (TYR) expression via qRT-PCR. NAcM-OPT increased cell viability and cell proliferation. Furthermore, this molecule promoted autophagic flux through increased expression of autophagy-related proteins under HO-induced oxidative stress. Additionally, rapamycin increased the mRNA levels of TYR in PIG1 cells. Moreover, NAcM-OPT alleviated mitochondrial damage, restored mitochondrial function, and upregulated the expression of NFE2L2, HO1, NQO1, and GCLM. Importantly, NAcM-OPT also increased epidermal thickness, follicle length, and melanin synthesis under oxidative stress in vivo. These findings suggest that NAcM-OPT may be a promising small molecule antioxidant drug for the treatment of vitiligo.
PubMed: 38922711
DOI: 10.1111/nyas.15173 -
Hematology Reports Jun 2024Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the... (Review)
Review
Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the clinical presentations related to hypopigmentation in hematological disorders, focusing on vitiligo, morphea, and syndromic albinism. Vitiligo, an autoimmune disorder targeting melanocytes, involves interactions between genetic polymorphisms and immune responses, particularly regarding CD8+ T cells and IFN-γ. Drug-induced vitiligo, notably by immune checkpoint inhibitors and small-molecule targeted anticancer therapies, underscores the importance of immune dysregulation. Morphea, an inflammatory skin disorder, may signal hematological involvement, as seen in deep morphea and post-radiotherapy lesions. Syndromic albinism, linked to various genetic mutations affecting melanin production, often presents with hematologic abnormalities. Treatment approaches focus on targeting the immune pathways specific to the condition, and when that is not possible, managing symptoms. Understanding these dermatological manifestations is crucial for the timely diagnosis and management of hematological disorders.
PubMed: 38921184
DOI: 10.3390/hematolrep16020036 -
Clinical, Cosmetic and Investigational... 2024Vitiligo, a condition characterized by depigmented skin, has been observed to have a higher incidence in patients with a family history of the disease. This study...
BACKGROUND
Vitiligo, a condition characterized by depigmented skin, has been observed to have a higher incidence in patients with a family history of the disease. This study investigates the relationship between parental consanguinity, family medical history, and the onset of childhood vitiligo, hypothesizing that genetic factors play a significant role.
METHODS
A cross-sectional study was conducted involving 382 people diagnosed with vitiligo in Saudi Arabia. The study assessed the prevalence of parental consanguinity and its correlation with the disease's onset, employing statistical analysis to evaluate the data collected through medical records and family history questionnaires.
RESULTS
The findings reveal a significant association between parental consanguinity, particularly among first cousins, and the incidence of childhood-onset vitiligo. Additionally, a notable correlation was found between family medical history and the onset of the condition, with familial vitiligo being more prevalent in patients with adult-onset vitiligo.
CONCLUSION
This study underscores the critical role of genetic predispositions in the development of childhood-onset vitiligo, highlighting the influence of parental consanguinity. The results advocate for increased awareness and screening in populations with high rates of consanguinity to facilitate early detection and management of vitiligo. Future research should focus on exploring the genetic mechanisms underlying this association to develop targeted interventions.
PubMed: 38919171
DOI: 10.2147/CCID.S470937 -
Scientific Reports Jun 2024Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are... (Randomized Controlled Trial)
Randomized Controlled Trial
Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.
Topics: Humans; Vitiligo; Atorvastatin; Simvastatin; Male; Female; Double-Blind Method; Adult; Pilot Projects; Middle Aged; Administration, Topical; Young Adult; Treatment Outcome; Adolescent
PubMed: 38918590
DOI: 10.1038/s41598-024-65722-w