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Aikaterini I Liakou, Christos C Zouboulis Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Centre, Dessau, Germany Introduction: Psoriasis has long been considered a systemic inflammatory disease. Lately, it has been strongly associated with obesity, as well as other components of metabolic syndrome, such as dyslipidemia, insulin resistance, and arterial hypertension. Methods: We reviewed the literature of the last decade by using the keywords: psoriasis, metabolic syndrome, and/or obesity in PubMed and Medline. Results: Obesity and psoriasis seem to share similar profiles of systemic inflammation. Serum cytokines such as TNF-α, CRP, IL-6, and IL-12 are elevated in both disorders. The more severely an individual is affected with psoriasis, the more likely it is to be obese. This makes the disease an important health care issue, which requires the cooperation of dermatologists with other medical specialists. Discussion: This review attempts to summarize the links and risks that associate psoriasis with obesity, and highlight the concerns and queries for both disorders in the future. Keywords: psoriasis, obesity, metabolic, syndrome, inflammation

Chinese translation BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults. OBJECTIVE: To evaluate the efficacy and safety of adalimumab, an anti-tumor necrosis factor-[alpha] antibody, in patients with moderate to severe HS. DESIGN: Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study. (ClinicalTrials.gov: NCT00918255) SETTING: 26 academic and private practice medical centers in the United States and Europe. PATIENTS: 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics. INTERVENTION: Patients were assigned in a 1:1:1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimumab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Physician's Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31. MEASUREMENTS: The primary outcome measure (clinical response) was the proportion of patients achieving an HS-PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16. RESULTS: At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. placebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted difference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group. A decrease in response was seen after the switch from weekly to EOW dosing in period 2. LIMITATIONS: Weeks 16 to 52 of the study were open-label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders. CONCLUSION: Adalimumab dosed once per week alleviates moderate to severe HS. PRIMARY FUNDING SOURCE: Abbott Laboratories. [ABSTRACT FROM AUTHOR]

Background: The American Joint Committee on Cancer (AJCC) method of staging melanoma is dated and inaccurate. It ignores important prognostic melanoma features, especially the patient's age. BAUSSS is more accurate in determining survival risk for primary cutaneous melanoma patients who have no clinical or imaging evidence of nodal or distant metastases. BAUSSS is an algorithm incorporating analysis of Breslow thickness, Age, Ulceration, Subtype of melanoma, Sex and Site. These are the six features from the patient history along with the details from the melanoma pathology report that are most predictive of mortality outcome., Objective: To develop a single-page document that allows the clinician to determine BAUSSS biomarker-predicted prognosis in consultation with the patient., Method: From various data sources, we developed an algorithm to predict melanoma mortality using the BAUSSS biomarker system. The single-page algorithm was made available to download at https://globalmelanoma.net/bausss-survival-chart, thus being readily available without charge to all clinicians and their patients., Results: BAUSSS method of determining melanoma prognosis is more accurate and less costly than the AJCC staging system. The only surgery the patient requires is wide local excision of the primary tumour. This method of ascertaining melanoma risk does not require added surgery, costs, hospitalization, tests and anaesthesia, such as would be required if sentinel lymph node biopsy was undertaken. BAUSSS can be a useful tool in determining which primary melanoma patients are at sufficiently high risk to be considered for adjuvant drug therapy., Conclusion: We encourage clinicians to download and print in colour this single-page BAUSSS mortality prediction tool, laminate it, and use it face to face with the patient in consultations. Not only will the patient be able to recognize his/her long-term prognosis but will also be able to see how their tumour severity compares with others., (© 2024 European Academy of Dermatology and Venereology.)

Background : Hidradenitis suppurativa (HS) is a persistent, recurring skin inflammatory condition linked to various comorbidities. Management involves antibiotics, hormone therapy, immune-modulating drugs, surgery, and treatment of comorbidities. The objectives of the study were to assess the comorbidities, clinical presentation subtypes, and applied treatment of patients with HS. Methods : Patients with HS who visited the Centre of Dermatovenereology at Vilnius University Hospital Santaros Klinikos in Lithuania underwent evaluation based on the guidelines of the European Hidradenitis Suppurativa Foundation Registry questionnaire. Results : The study included 49 patients, and 61.22% ( n = 30) had comorbidities. A strong positive correlation was found between a family history of inflammatory diseases (69.38% ( n = 34)) and the severity of HS according to Hurley stage (r = 0.71 p < 0.05). A statistically significant correlation (r = 0.944, p = 0.02) was found between metabolic comorbidities and Hurley stage. Patients on biologic treatment had a mean IHS4 of 7.38 at the beginning of treatment and 3.22 at follow-up ( p < 0.05). For patients not on biologics, the initial IHS4 score was 6.21 and 5.42 at follow-up ( p > 0.05). Conclusions : A family history of inflammatory diseases and metabolic comorbidities showed a strong correlation with HS severity. Treatment with biologics showed significant improvement in HS scores compared to systemic antibiotics.

Sebaceous glands (SG) and their oily secretion (sebum) are indispensable for maintaining skin structure and function, and their deregulation causes skin disorders including but not limited to acne. Recent studies also indicate that sebum may have important immunomodulatory activities and may influence whole-body energy metabolism. However, the progressive transcriptional changes of sebocytes that lead to sebum production have never been characterized in detail. Here, we exploited the high cellular resolution provided by sebaceous hyperplasia and integrated spatial transcriptomics, pseudo time analysis, RNA velocity, and functional enrichment to map the landscape of sebaceous differentiation. Our results were validated by comparison with published SG transcriptome data and further corroborated by assessing the protein expression pattern of a subset of the transcripts in the public repository Human Protein Atlas. Departing from four sebocyte differentiation stages generated by unsupervised clustering, we demonstrate consecutive modulation of cellular functions associable with specific gene sets, from cell proliferation and oxidative phosphorylation via lipid synthesis to cell death. Both validation methods confirmed the biological significance of our results. Our report is complemented by a freely available and browsable online tool. Our data provide the first high-resolution spatial portrait of the SG transcriptional landscape and deliver starting points for experimentally assessing novel candidate molecules for regulating SG homeostasis in health and disease., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Branched gold and silver nanoparticles coated with polydopamine (Au-Ag-PDA) demonstrate high photothermal conversion efficiency. Utilizing umbilical cord mesenchymal stem cell membranes (MSCM) as an effective drug delivery system, our preliminary studies investigated the suppression of sebum secretion in sebaceous glands using MSCM-coated Au-Ag-PDA nano-particles (Au-Ag-PDA@MSCM) combined with 808 nm laser irradiation, showing potential for dermatological applications in acne treatment., Methods: This study employs proteomic analysis, complemented by subsequent techniques such as Western blotting (WB), small interfering RNA (siRNA), and transmission electron microscopy, to further investigate the differential mechanisms by which Au-Ag-PDA and Au-Ag-PDA@MSCM-mediated photothermal therapy (PTT) suppress sebum secretion., Results: Our proteomic analysis indicated mitochondrial respiratory chain damage in sebaceous gland tissues post-PTT, with further validation revealing ferroptosis in sebaceous cells and tissues. Acyl-CoA Synthetase Long-Chain Family Member 4 (Acsl4) has been identified as a critical target, with Au-Ag-PDA@MSCM demonstrating enhanced ferroptotic effects., Conclusion: These findings significantly advance our understanding of how PTT mediated by Au-Ag-PDA@MSCM nanoparticles reduces sebum secretion and underscore the pivotal role of MSCM in inducing ferroptosis in sebaceous glands, thus providing a robust theoretical foundation for employing PTT via specific molecular pathways in acne treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Li, Tian, Song, Zhao, Tian, Zouboulis, Jiang and Zhu.)

Background: Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa., Methods: BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at ClinicalTrials.gov, NCT04242446 and NCT04242498, and both are completed., Findings: Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16-4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22-4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 vs 24 [32%] of 74 with placebo; 2·42 [1·22-4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed., Interpretation: Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa., Funding: UCB Pharma., Competing Interests: Declaration of interests ABK reports grants paid to the institution from AbbVie, Admirx, Anapyts Bio, Aristea, Bristol Myers Squibb, Eli Lilly and Company, Incyte, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Prometheus, Sonoma Bio, and UCB Pharma; consulting fees from AbbVie, Alumis, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Priovant, Sonoma Bio, Sanofi, Target RWE, UCB Pharma, Union, and Ventyx; and serves on the board of directors of Almirall. GBEJ reports honoraria for participation on advisory boards from AbbVie, Boehringer Ingelheim, Chemocentryx, Incyte, Janssen-Cilag, LEO Pharma, Novartis, and UCB Pharma; and acted as an investigator for AbbVie, CJSL, InflaRx, Janssen-Cilag, LEO Pharma, Novartis, Regeneron, Sanofi, and UCB Pharma. CJS acted as an investigator for AbbVie, Chemocentryx, GSK, Incyte, InflaRx, Novartis, and UCB Pharma; reports consultancy fees from AbbVie, Alumis, InflaRx, Incyte, Logical Images, Sonoma Biotherapeutics, and UCB Pharma; and acted as a speaker for AbbVie and Novartis. JSK reports personal fees from AbbVie, ChemoCentryx, CJSL Behring, DermTech, Incyte, Insmed, Janssen, MoonLake, Novartis, and UCB Pharma; personal fees and grants from Incyte; is a co-copyright holder of HiSQOL; has been a consultant for and received honoraria from AbbVie, Alumis, DermTech, Incyte, Insmed, Janssen, MoonLake Immunotherapeutics, Novartis, and UCB Pharma; and has been a speaker for AbbVie, Janssen, Novartis, and UCB Pharma. EP has been a consultant, advisory board member, speaker for, and received honoraria from Almirall, Janssen-Cilag, GSK, MoonLake Immunotherapeutics, Novartis, and UCB Pharma; and his department received investigator-initiated grant support from AbbVie, Celgene, CHDR, Citryll, Kymera, Janssen-Cilag, and UCB Pharma. JRI receives a stipend as Editor‑in‑Chief of the British Journal of Dermatology and an authorship honorarium from UpToDate; has been a consultant for AbbVie, Boehringer Ingelheim, ChemoCentryx, Citryll, MoonLake Immunotherapeutics, Novartis, UCB Pharma, and Union Therapeutics, and has served on advisory boards for Insmed, Kymera Therapeutics, and Viela Bio; is a co‑copyright holder of the Hidradenitis Suppurativa Quality of Life score (HiSQOL) and hidradenitis suppurativa-Investigator Global Assessment; and his department receives income from copyright of the Dermatology Life Quality Instrument and related instruments. AG has been a consultant and receives honoraria from AbbVie, Aclaris Therapeutics, AnaptysBio, Aristea Therapeutics, Bristol Myers Squibb, Boehringer Ingelheim, Incyte, Insmed, Janssen, Novartis, Pfizer, Sonoma Biotherapeutics, UCB Pharma, Union Therapeutics, Ventyx Biosciences, and Viela Biosciences; has received research grants from AbbVie, C3, National Psoriasis Foundation, and UCB Pharma; and is a co-copyright holder of HiSQOL and hidradenitis suppurativa-IGA. ABG reports honoraria as an advisory board member and consultant for Amgen, Almirall, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapeutics, Eli Lilly and Company, Janssen, Novartis, Sanofi, UCB Pharma, and Xbiotech; and research or educational grants from AnaptysBio, Bristol Myers Squibb, MoonLake Immunotherapeutics, Novartis, and UCB Pharma (all paid to Mount Sinai School of Medicine). JCJS has acted as a consultant and advisory board member of AbbVie, LEO Pharma, Novartis, Pierre Fabre, Sanofi Genzyme, and Trevi Therapeutics; acted as a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Novartis, Pfizer, Pierre-Fabre, Sanofi, and UCB Pharma; and has acted as an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InflaRX, Janssen, Kliniksa, Kymab Limited, Menlo Therapeutics, Merck, Novartis, Pfizer, Regereron Pharmaceuticals, Trevi Therapeutics, and UCB Pharma. FGB reports honoraria for participation in advisory boards, in clinical trials, and as a speaker from AbbVie, AbbVie Deutschland, Boehringer Ingelheim, Celltrion, Dr. Wolff, Incyte, Janssen, Mölnlycke, MoonLake Immunotherapeutics, Novartis, and UCB Pharma. EJG-B reports honoraria from Abbott Products Operations, bioMérieux, Brahms, GSK, InflaRX, Sobi and XBiotech; independent educational grants from Abbott Products Operations, AxisShield, bioMérieux, InflaRx, Johnson & Johnson, MSD, Novartis, Sobi, and XBiotech; and funding from the Horizon2020 Marie Skłodowska-Curie International Training Network the European Sepsis Academy (granted to the National and Kapodistrian University of Athens), the Horizon 2020 European Grants ImmunoSep and RISCinCOVID (granted to the Hellenic Institute for the Study of Sepsis) and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). HF reports honoraria or fees for serving on advisory boards, as a speaker, and as a consultant; and grants as an investigator from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly and Company, Janssen, Japan Blood Products Organization, JMEC, Kaken Pharmaceutical, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nihon Pharmaceutical, Novartis, Otsuka Pharmaceutical, Sanofi, Sato Pharmaceutical, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Pharma, and Ushio. RR, PJ, PD, EM, and LP are employees and shareholders of UCB Pharma. CM is a former employee and shareholder of UCB Pharma. MB is an employee of UCB Pharma. CCZ reports grants paid to the institution from AstraZeneca, Boehringer Ingelheim, GSK, InflaRx, Novartis, Relaxera, and UCB Pharma for participation as a clinical and research investigator; consultant honoraria from AccureAcne, Almirall, Boehringer Ingelheim, Incyte, InflaRx, Janssen, L'Oréal, Luvos, NAOS-BIODERMA, Novartis, PPM, Sanofi, UCB Pharma, and Viatris; lecture fees from Almirall, Biogen, Novartis, Sobi, and UCB Pharma; and is the president of the European Hidradenitis Suppurativa Foundation, coordinator of the ALLOCATE Skin group of the European Reference Network for rare skin diseases, and chair of the Acne, Rosacea and Hidradenitis Suppurativa Task Force group of the European Academy of Dermatology and Venereology (EADV); is the editor of the EADV News; and co-copyright holder of the International Hidradenitis Suppurativa Severity Score System on behalf of the European Hidradenitis Supurativa Foundation., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The S2k guideline on hidradenitis suppurativa/acne inversa (HS/AI) aims to provide an accepted decision aid for the selection/implementation of appropriate/sufficient therapy. HS/AI is a chronic recurrent, inflammatory, potentially mutilating skin disease of the terminal hair follicle-glandular apparatus, with painful, inflammatory lesions in the apocrine gland-rich regions of the body. Its point prevalence in Germany is 0.3%, it is diagnosed with a delay of 10.0 ± 9.6 years. Abnormal differentiation of the keratinocytes of the hair follicle-gland apparatus and accompanying inflammation form the central pathogenetic basis. Primary HS/AI lesions are inflammatory nodules, abscesses and draining tunnels. Recurrences in the last 6 months with at least 2 lesions at the predilection sites point to HS/AI with a 97% accuracy. HS/AI patients suffer from a significant reduction in quality of life. For correct treatment decisions, classification and activity assessment should be done with a validated tool, such as the International Hidradenitis Suppurativa Severity Scoring System (IHS4). HS/AI is classified into two forms according to the degree of detectable inflammation: active, inflammatory (mild, moderate, and severe according to IHS4) and predominantly inactive, non-inflammatory (Hurley grade I, II and III) HS/AI. Oral tetracyclines or 5-day intravenous therapy with clindamycin are equal to the effectiveness of clindamycin/rifampicin. Subcutaneously administered adalimumab, secukinumab and bimekizumab are approved for the therapy of HS/AI. Various surgical procedures are available for the predominantly non-inflammatory disease form. Drug/surgical combinations are considered a holistic therapy method., (© 2024 Deutsche Dermatologische Gesellschaft (DDG).)

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christos C. Zouboulis has patent #The immortalized human sebaceous gland cell line SZ95 (WO0046353) licensed to Christos C. Zouboulis. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sebocyte regeneration after injury is considered a key element of functional skin repair. Exosomes from adipose-derived stem cells (ADSCs-EXO) accelerate wound healing by promoting the proliferation of fibroblasts. However, the effects of ADSCs-EXO on sebocytes are largely unknown. In this study, the effects of ADSCs-EXO on sebocyte proliferation and migration were evaluated. The levels of phosphorylated AKT (p-AKT), AKT, sterol regulatory-element binding protein (SREBP), and perilipin-1 (PLIN-1) were detected with immunofluorescence, quantitative PCR, and western blot analysis. RNA-Seq was used to analyze the differential gene expression between the ADSCs-EXO group and the control group under anaerobic conditions. Lipogenesis was assessed with Nile red staining. In animal studies, full-thickness skin wounds in BALB/c mice were treated with gelatin methacrylate (GelMA) hydrogel-loaded sebocytes alone or in combination with ADSCs-EXO. Histopathological assessments of the wound tissues were performed Masson Trichrome staining, Immunohistochemical staining and so on. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway blocker LY294002 inhibited the effects of ADSCs-EXO on p-AKT and sebocytes proliferation. ADSCs-EXO also regulated the expression of SREBP-1 and PLIN-1 through the PI3K/AKT pathway in an oxygen level-dependent manner. In BALB/c mice, ADSCs-EXO accelerated sebocyte-assisted wound healing and regeneration. These in vitro and in vivo results supported that ADSCs-EXO can promote the regeneration of fully functional skin after injury through the PI3K/AKT-dependent activation of sebocytes., (© 2024. The Author(s).)