Identification of Novel Protein Biomarkers and Drug Targets for Acne Vulgaris by Integrating Human Plasma Proteome with Genome-Wide Association Data.

Background: Despite the availability of numerous therapies, the treatment of acne vulgaris remains challenging. Novel drug targets for acne vulgaris are still needed. Methods: We conducted a Mendelian randomization analysis to explore possible drug targets for acne vulgaris. We utilized summary statistics obtained from the dataset of acne vulgaris, including 399,413 individuals of European ancestry. We gathered genetic instruments for 566 plasma proteins from genome-wide association studies. In order to strengthen the findings from Mendelian randomization, various methods were employed, including bidirectional Mendelian randomization analysis, Bayesian co-localization, phenotype scanning, and single-cell analysis. These methods facilitated the identification of reverse causality, the search for reported variant-trait associations, and the determination of the cell types that is the primary source of protein. Furthermore, using the plasma proteins in the deCODE cohort, we conducted a replication of the Mendelian randomization analysis as an external validation. Results: At the significance level of Bonferroni (P < 8.83×10-5), a protein-acne pair was discovered through Mendelian randomization analysis. In plasma, increasing TIMP4 (OR = 1.15; 95% CI, 1.09-1.21; P = 1.01×10-7) increased the risk of acne vulgaris. The absence of reverse causality was observed in the TIMP4 protein. According to Bayesian co-localization analysis, TIMP4 shared the same variant with acne vulgaris (PPH4 = 0.93). TIMP4 was replicated in deCODE cohort (OR = 1.17; 95% CI, 1.10-1.24; P = 1.48×10-7). Single-cell analysis revealed that TIMP4 was predominantly detected in myeloid cells in blood, and was detected in almost all cell types in skin tissue. Conclusion: The integrative analysis revealed that the level of plasma TIMP4 has a direct influence on the risk of developing acne vulgaris. This implies that TIMP4 protein could serve as a potential target for the development of drugs aimed at treating acne vulgaris.

The Relationship between Chocolate Consumption and the Severity of Acne Lesions-A Crossover Study.

The aim of this study was to assess the relationship between the daily consumption of 50 g of chocolate with 85% cocoa content and the severity of acne lesions. METHODS: The study involved 92 participants with acne who were divided into two groups, A (n = 51) and B (n = 41). In the first week, both groups had to follow an anti-inflammatory diet (AID), then for the next 4 weeks, group A continued on with the AID, and group B followed an AID with chocolate. After this time, group B started a 4-week AID without chocolate, and group A started a 4-week AID with chocolate. The severity of acne lesions was assessed using the Investigator's Static Global Assessment scale, where zero points indicated no lesions and five points indicated severe acne. RESULTS: As a result of the consumption of 50 g of chocolate, a statistically significant intensification of acne lesions was observed in both groups. After 4 weeks of following the chocolate diet, the severity of acne lesions increased from 2.5 ± 0.7 to 3.4 ± 0.8 points (p < 0.0001) in group A, and from 2.4 ± 0.7 to 3.5 ± 0.6 points (p < 0.0001) in group B. Overall, chocolate intake contributed to the exacerbation of acne lesions by one point in 65 participants, by two points in 13 participants and by three points in one participant. CONCLUSIONS: The obtained results suggest that daily consumption of 50 g of chocolate with 85% cocoa content, even with an anti-inflammatory diet, may intensify acne lesions in this study group. However, it remains unclear which chocolate components may lead to the exacerbation of acne.

Investigating Propionibacterium acnes antibiotic susceptibility and response to bacteriophage in vitro and in vivo.

Introduction: A total of 94 Propionibacterium acnes (P. acnes) isolates were obtained from a hospital in Beijing to evaluate their susceptibility to erythromycin, clarithromycin, doxycycline, and minocycline. As well as the determination of the effectiveness of P. acnes phages in vitro and in P. acnes-induced lesions mouse model. Methods: Patients with acne vulgaris (AV) were enrolled from August 2021 to October 2022. Standard methods were employed for specimen collection, culture, and identification of P. acnes. Susceptibility testing was conducted using E-strips for erythromycin, clarithromycin, minocycline, and doxycycline. Phage culture and identification followed standard procedures. A mouse model with P. acnes-induced skin lesions was established, and data was analyzed using χ 2 test. Results: The results showed that all isolates were susceptible to minocycline and doxycycline, while 53 (56.4%) and 52 (55.3%) isolates were susceptible to erythromycin and clarithromycin, respectively. Interestingly, younger patients and those with lower acne severity exhibited reduced resistance. Phage cleavage rates ranged from 88.30 to 93.60%. Multilocus sequence typing (MLST) analysis was conducted on eight randomly selected P. acnes isolates, and the IA-2 subtype was used in experiments to address P. acnes-induced lesions in mice. Phage therapy proved effective in this model. Discussion: This study highlights the high susceptibility of P. acnes to doxycycline and tetracycline, while erythromycin and clarithromycin exhibited elevated resistance. Additionally, P. acnes phages demonstrated high cleavage rates and potential effectiveness in treating P. acnes-induced lesions. These findings suggest promising avenues for further exploration of phage therapy in acne treatment.

Microchanneling and ultrasonic delivery of gold and platinum nanoparticles for selective photothermolysis of sebaceous follicles in the treatment of acne: a pilot study using porcine skin.

PURPOSE: Several treatment options for acne vulgaris are limited by their associated adverse effects. An innovative approach involves introducing light-absorbing nanoparticles into sebaceous follicles before destroying the follicles using selective photothermolysis. We aimed to investigate efficient methods for introducing gold and platinum nanoparticles into sebaceous follicles and to identify suitable laser equipment and parameters for the effective destruction of these follicles. METHODS: We used porcine skin as the experimental model. We compared the efficacies of a thulium laser, ultrasound, and manual massage and evaluated the optimal method for delivering nanoparticles in close proximity to sebaceous follicles. Subsequently, a 1064-nm-wavelength neodymium-doped yttrium aluminum garnet (Nd: YAG) laser was employed to induce selective photothermolysis. We compared different parameters to identify the optimal pulse duration and fluence of the Nd: YAG laser. The extent of penetration and destruction of sebaceous follicles was assessed using hematoxylin and eosin (H&E) staining, and a numerical evaluation was conducted. RESULTS: H&E staining showed that irradiation with a long-pulsed Nd: YAG laser following a combination of thulium laser and sonophoresis effectively destroyed sebaceous follicles, with destruction rates exceeding 50%. These results were valid with a long pulse duration and a high fluence of the Nd: YAG laser. CONCLUSION: This study demonstrated that sebaceous follicles can be effectively destroyed through a mixture of gold and platinum nanoparticle delivery by a combination of microchanneling and sonophoresis, followed by selective thermal damage induced by a 1064-nm long-pulsed high-fluence Nd: YAG laser.

Egg white hydrolysate peptides act as antimicrobial and anti-inflammatory agents for acne.

A simple method to generate antibacterial peptides by alkaline hydrolysis of hen egg whites is reported. The method reproducibly generates short peptides with molecular weight of less than 14.4 kDa that exhibit low to no cytotoxicity on RAW 264.7 macrophage cells, but do inhibit the bacterial growth of Cutibacterium acnes (C. acnes), Staphylococcus aureus (S. aureus) and antibiotic-resistant S. aureus (MRSA), while also reducing nitric oxide production from heat-killed C. acnes-treated RAW 264.7 cells. Peptidomics revealed at least thirty peptides within the complex mixture, of which eight were evaluated individually. Three peptides (PK8, EE9 and RP8) were potent anti-inflammation and antibacterial agents, but notably the complex egg white hydrolysate (EWH) was more effective than the individual peptides. Electron microscopy suggests the antibacterial mechanism of both the hydrolysate and the selected peptides is through disruption of the cell membrane of C. acnes. These findings suggest that EWH and EWH-derived peptides are promising candidates for infection and inflammation treatment, particularly in managing acne and combating antibiotic-resistant bacteria like MRSA.

Updates on Topical Dyad and Triple Combination Therapies Approved for Acne Vulgaris.

Acne vulgaris is a multifaceted disease characterized by inflammatory and noninflammatory lesions. Topical combination therapies offer a multifaceted approach to acne treatment, with synergistic effects and a broad spectrum of action against multiple factors in acne pathogenesis in one single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene, a combination therapy consisting of clindamycin phosphate 1.2%, benzoyl peroxide (BPO) 3.1%, and adapalene 0.15%, is a novel treatment, the only FDA-approved triple combination drug that offers effective treatment of acne vulgaris. This review aims to provide information on clindamycin phosphate/benzoyl peroxide/adapalene and review the literature on combination topical acne medications approved in the United States. This search was conducted on topical combination therapies for acne, their efficacy, adverse effects, and impacts on quality of life with a specific focus on the newly approved clindamycin phosphate/benzoyl peroxide/adapalene and its sub-component dyads, along with other combinations. PubMed, SCOPUS, Embase, Cochrane, and Web of Science databases were searched for publications in 2018-2023. Primary sources were given priority, and secondary sources such as other reviews were considered to supplement any missing information. It was found that various topical dyad and triad combinations exist for acne vulgaris, including adapalene/BPO, tazarotene/clindamycin, clindamycin/BPO, adapalene/clindamycin, topical tretinoin/azelaic acid, topical tretinoin/BPO, and clindamycin phosphate/benzoyl peroxide/adapalene. Dyad and triple combinations represent a promising, convenient solution for acne management, potentially improving patient adherence due to its single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene exhibited significantly high efficacy in treating both inflammatory and noninflammatory lesions, a minimal side effect profile, although no significant changes in quality-of-life measures. Further research is indicated to assess its long-term efficacy and impact on other acne metrics such as cost, scarring, psychosocial implications, and impact on diverse patient populations.

Social media use as a source of information by acne vulgaris patients.

BACKGROUND: Social media and internet usage is undeniably high. Misinformation obtained from the internet and wrong treatment methods can cause serious problems in patients with acne vulgaris (AV). In this study, the sociodemographic data of AV patients, their frequency of using the internet as an information source, the relationship between them, and their attitudes and behaviors regarding their disease due to these programs were examined. METHODS: 481 patients aged 14 and over diagnosed with AV were included in the study. It was conducted in a descriptive cross-sectional type. Acne severity of all patients included in the study was determined using the Global Acne Grading System. RESULTS: 78.3 percent of participants use social media to get information about AV. It was determined that men and single people used social media about their illnesses at a statistically significantly higher rate than women and married people (p = 0.004). In addition, patients aged 13-18 and high school graduates use social media as a source of information about their diseases, and this rate is statistically significantly higher (p < 0.001). CONCLUSION: Especially in the last decade, the use of social media tools to spread health messages has increased significantly. Because it has a chronic course and can cause cosmetic problems, AV patients may frequently resort to communication sources such as social media. Considering the possibility of social media misinforming patients, physicians should be aware that their patients with AV frequently use social media and should improve themselves in creating correct awareness on this issue.

Evaluation of Depression, Self-esteem, Anxiety, and Dermatological Quality of Life Index in Adolescent Acne Patients: A Case-Control Study.

Objectives: Acne vulgaris is a common skin condition that affects adolescents and can have a significant impact on their mental health. In this study, we aimed to evaluate the depression and anxiety symptoms, self-esteem and dermatological quality of life indexes of adolescent patients with acne vulgaris. Methods: A total of 160 patients aged between 10 and 19 years with acne vulgaris and 100 healthy controls were included in the study. All participants completed the Reynolds Adolescent Depression Scale (RADS), Beck Adolescent Anxiety Scale (BAAS), and Coopersmith Self-Esteem Survey Scale (CSES), alone and independently. The dermatologists evaluated the acne disease severity of the study group using the Global Acne Grading System, while the Children's Dermatological Quality of Life Index (CDLQI) was evaluated in the same group. Age, gender, and scale results of all participants were recorded on case report forms for further analysis. Results: The study group had significantly higher RADS (27.5% vs 12.5%, p=0.003) and BAAS scores (80% vs 64%, p=0.001) than the control group. The percentage of patients with CSES scores below 20 in the study group was significantly higher than the control group (p=0.001). Higher RADS and BAAS scores were associated with higher CDLQI scores (p=0.001, p=0.001, respectively), while higher CSES scores were associated with lower CDLQI scores (p=0.001). Conclusion: The study shows that acne vulgaris has a significant impact on the depression, anxiety, and self-esteem levels of adolescent patients. Dermatologists should pay attention to the psychological well-being of patients and provide psychiatric evaluation if necessary.

Ultrasonography of Facial and Submandibular Hidradenitis Suppurativa and Concomitance with Acne Vulgaris.

OBJECTIVES: To describe the ultrasound characteristics of facial and submandibular hidradenitis suppurativa (HS) and detect acne vulgaris (AV) concomitance in these cases. METHODS: We performed a retrospective study of the ultrasound images of patients with facial HS who had been clinically evaluated by dermatologists. The reported ultrasound diagnostic criteria, severity (mSOS-HS), and activity (US-HAS) staging of HS were used to categorize the patients. The finding of fragments of hair tracts within the key lesions (dilated hair follicles, pseudocysts, fluid collections, and tunnels) was considered a pivotal sign to discriminate HS from AV. Demographic and morphological analysis of the images were considered. RESULTS: Thirty-three patients met the criteria (78.8% male/21.2% female). Of these, the mSOS- HS scoring was stage I in 51.5%, stage II in 27.3%, and stage III in 21.2%. Dilation of the hair follicles and the presence of pseudocysts, fluid collections, and tunnels were detected in the HS cases; 63.1% of pseudocysts, 62.4% of tunnels, and 46.2% of fluid collections contained fragments of hair tracts. In all HS cases, there was a key lesion(s) with fragments of hair tracts. Four (12.1%) patients showed concomitant facial HS and acne ultrasound lesions. The acne lesions were pseudocysts without inner hair tract fragments in all cases, and the SOS-Acne scoring was stage II for all of them. CONCLUSION: Facial HS can be detected on ultrasound and shows a morphology similar to that of HS in other corporal regions. In some cases, facial HS could be concomitant with AV. The subclinical ultrasonographic information can support a better management of these cases.

The Effect of Isotretinoin on Insulin Resistance and Serum Adiponectin Levels in Acne Vulgaris Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Isotretinoin is the drug of choice for severe acne. We sought to examine the potential link between isotretinoin and insulin resistance. METHODS: We conducted a systematic review and meta-analysis in accordance with the PRISMA statement. A comprehensive search of the PubMed/MEDLINE, SCOPUS, and Cochrane databases was performed until 12 January 2022 utilizing the PICO (Patient, Intervention, Comparison, Outcome) tool. Fifteen English-language studies focusing on isotretinoin-treated acne patients were included. Serum levels of insulin, glucose, and adiponectin were evaluated before and after treatment, and insulin sensitivity was assessed using the HOMA-IR. A meta-analysis was conducted using RevMan 5.4.1 software, and a quality assessment was undertaken using the ROBINS-I tool. RESULTS: The meta-analysis unveiled a statistically significant rise in the post-treatment levels of adiponectin, an anti-inflammatory agent, which inhibits liver glucose production while enhancing insulin sensitivity (SMD = 0.86; 95% confidence interval (95% CI) = 0.48-1.25, p-value < 0.0001; I2 = 58%). Our subgroup analysis based on study type yielded consistent findings. However, no statistically significant outcomes were observed for insulin, glucose levels, and the HOMA-IR. CONCLUSIONS: There is not a clear association between isotretinoin and insulin resistance, but it appears to enhance the serum levels of adiponectin, which participates in glucose metabolism.

In severe acne vulgaris, TNF-α gene variants are connected to increased TNF-α gene expression and insulin resistance.

BACKGROUND: Acne vulgaris (AV) is a chronic inflammatory skin condition affecting the pilosebaceous unit, commonly presenting as comedones, papules, pustules, or nodules on the face, upper limbs, torso, and back, with comedones formation being the primary pathology leading to disfiguring inflammation, hyperpigmentation, scarring, and psychological impact. AIM: The purpose of this study was to investigate the significance of two genetic variants in the promoter region of the tumor necrosis factor-alpha (TNF-α) gene and their association with insulin resistance (IR) in acne patients. To understand how these variants contribute to AV and its associated IR. SUBJECTS AND METHODS: An analytical cross-sectional study with a case-control design and research evaluation was carried out on 87 AV patients and 73 healthy volunteers. The medical histories of both groups were obtained, as well as the severity and duration of inflammation among acne sufferers, as well as demographic data. Biochemical analysis was performed on both sets of participants, including fasting blood glucose levels, insulin levels while fasting, IR, and serum TNF-α. PCR-RFLP analysis identified -863 G > A (rs1800630) and -308 G > A (rs1800629) variations, and real-time PCR analysis evaluated TNF-α gene expression in both patients and healthy people. RESULTS: Acne patients exhibited significantly higher levels of IR, fasting glucose, fasting insulin, serum TNF-α, and TNF-α folding change, when compared to healthy controls. The co-dominant model for -863 G > A and -308 G > A variants exhibited significant variations between the two groups. Severe acne patients who had the A/A genotype for -308 variants exhibited higher levels of IR, serum TNF-α, and TNF-α folding change. Highly significant positive linear correlation between IR, serum TNF-α, and TNF-α folding change in severe AV. CONCLUSION: There is a correlation between AV, especially severe acne, and the -863 G > A and -308 G > A polymorphism, which influences TNF-α gene expression and serum TNF-α levels.

A novel H­tert immortalized human sebaceous gland cell line (XL-i-20) for the investigation of photodynamic therapy.

BACKGROUND: Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of acne vulgaris, primarily attributed to its cytotoxic properties; however, its regulatory mechanism remains largely unknown. OBJECTIVES: To establish an immortalized human sebocyte cell line derived from Chinese population and investigate the underlying mechanism of ALA-PDT. METHODS: Human primary sebocytes were transfected with the human tert gene (h­tert). The biological characteristics, including cell proliferation, cell markers, and sebum secretion function, were compared between primary sebocytes and the immortalized sebocytes (XL-i-20). Stimulations such as ALA-PDT, were applied respectively to both primary sebocytes and XL-i-20 cells to assess changes in their cellular functions. The transcriptome differences between primary sebocytes and XL-i-20 sebocytes were investigated using RNA-seq analysis. The XL-i-20 cell line was used to establish a sebaceous gland (SG) organoid culture, serving as a representative model of SG for the investigation of ALA-PDT. RESULTS: The h­tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebocyte markers such as epithelial membrane antigens (EMA, or MUC-1), Cytokeratin 7 (CK7) and adipose differentiation-related protein associated antigens (ADRP), and maintained sebum secretion function. The proliferative capacity of XL-i-20 was found to be significantly higher than that of primary sebocytes. The responses of XL-i-20 to ALA-PDT were indistinguishable from those elicited by primary sebocytes. Cell viability and sebum secretion were decreased after ALA-PDT in both two cell lines, and lipid-related proteins (SREBP-1/PPARγ) were down-regulated. The transcriptome data consistently demonstrated upregulation of genes related to inflammatory responses and downregulation of genes involved in lipid metabolism in both cell types following PDT. The analysis of common differential genes of primary sebocytes and XL-i-20 sebocytes post ALA-PDT showed that TNF signaling pathways, MAPK signaling pathways and JAK-STAT signaling pathways were activated. The SG organoids were spherical, which expressed markers of FANS and PLET1. Ki-67 was down-regulated after ALA-PDT. CONCLUSIONS: We have developed an h­tert immortalized sebocyte cell line from an Asian population. The cell line, XL-i-20, maintains the essential characteristics of its parent primary sebocytes. Moreover, XL-i-20 sebocyte exhibited a significant respond to ALA-PDT, demonstrating comparable phenotypic and molecular changes to primary sebocytes. Therefore, XL-i-20 and its derived SG organoid serve as appropriate in vitro models for investigating the efficacy and mechanisms of ALA-PDT in SG-related diseases.

Combinations of Energy-based Devices plus isotretinoin for management of acne and acne scars: A systematic review.

BACKGROUND AND OBJECTIVE: A 6-month interval between systemic isotretinoin (ISO) and the initiation of energy-based interventions has been recommended, due to concerns about keloid formation and delayed wound healing. While this postponement goes against the current trend of early intervention for acne scarring. This systematic review evaluates the efficacy, safety, and patient satisfaction of combinations of ISO with energy-based devices (EBD). STUDY DESIGN/METHODS AND MATERIALS: PubMed, Embase, Web of Science, Cochrane Library, and Cochrane Central Register of Controlled Trials were comprehensively searched up to April 2023 according to PRISMA guidelines. Two independent reviewers screened the titles and abstracts to select articles. The quality of the literature was assessed for each study design. RESULTS: A total of 16 studies addressing the efficacy and safety of energy-based modalities combined with ISO were identified, including six randomized controlled trials (RCTs), two case series, seven cohort studies, and one case report. ISO combinations with intense pulsed light (IPL), fractional ablative CO2 laser, pulsed dye laser (PDL), non-ablative fractional laser (NAFL) and fractional microneedle radiofrequency (FMRF) have been tested for improving acne severity, acne scarring and erythema. CONCLUSION: The current evidence does not justify delaying the use of EBDs for patients who have recently undergone or are currently receiving ISO treatment. Evidence-based treatments such as PDL, NAFL, and FMRF etc. are suggested relatively safe and effective in treating acne and acne scarring.

Targeting sebaceous glands: a review of selective photothermolysis for Acne Vulgaris treatment.

Acne vulgaris (AV), characterized by excessive sebum production and Cutibacterium acnes proliferation in the sebaceous glands, significantly impacts physical and psychological health. Recent treatment advancements have focused on selective photothermolysis of sebaceous glands. This review evaluates two innovative therapies: the 1726-nm laser and nanoparticle-assisted laser treatments. We conducted a comprehensive search of PubMed and Embase using the primary terms "acne vulgaris" or "acne" AND "laser," "photothermal therapy," "nanoparticles," "treatment," or "1726 nm laser." Inclusion criteria were articles published in English in peer-reviewed journals that focused on treating AV through targeting the sebaceous glands, yielding 11 studies. Gold nanoparticles, used with 800-nm laser, 1064-nm Nd: YAG laser, or photopneumatic device, and platinum nanoparticles with 1450-nm diode laser, showed notable improvements in severity and number of acne lesions, safety, and patient satisfaction. The 1726-nm laser treatments also showed considerable lesion reduction and tolerability, with minimal side effects such as erythema and edema. Its efficiency is credited to its short, high-power pulses that effectively target sebaceous glands, offering precise treatment with fewer side effects compared to lower-power pulses. Selective photothermolysis using nanoparticle-assisted laser therapy or the 1726-nm laser offers a promising alternative to conventional AV treatments, showcasing efficacy and high patient satisfaction. The 1726-nm laser streamlines treatment but involves new equipment costs, while nanoparticle-assisted therapy integrates well into existing setups but relies on external agents and is unsuitable for certain allergies. Future research should include long-term studies and comparative analyses. The choice of treatment modality should consider patient preferences, cost implications, and availability of specific therapies.

Metformin Therapy for Acne Vulgaris: A Meta-Analysis.

Acne vulgaris is a common disease, which occurs in adolescents as well as adults and has a significant influence on the patient's quality of life (QoL) in every aspect. Due to resistance to standard therapies, it has become necessary to prospect for new treatment strategies. It is important to highlight that the diagnosis and treatment of the underlying cause of acne such as metabolic and hormonal disorders may significantly improve the effectiveness of acne treatment. The correlation between Insulin Resistance (IR) and acne has been proven. Both disorders share many common occurrence factors and activation pathways. Metformin, an antihyperglycemic agent, seems to be a possible therapy option, not only because of its insulin sensitizing ability but also via plenty of additional effects of this medicine. While the efficiency of metformin therapy in patients with acne and Polycystic Ovary Syndrome (PCOS) is well explored, it is still necessary to evaluate it in patients without any endocrinopathies. This meta-analysis aimed to estimate the effectiveness of oral metformin as a monotherapy in acne patients without PCOS or other endocrinopathies. Study selection was performed with included criteria such as no PCOS and other endocrinopathies diagnosed, oral administration of metformin, and metformin in monotherapy. Selected studies contained comparisons in the Global Acne Grading System (GAGS) before and after metformin therapy. Statistical analysis detected significant improvement in skin condition after treatment with metformin.

Analysis of Intracellular Communication Reveals Consistent Gene Changes Associated with Early-Stage Acne Skin.

A comprehensive understanding of the intricate cellular and molecular changes governing the complex interactions between cells within acne lesions is currently lacking. Herein, we analyzed early papules from six subjects with active acne vulgaris, utilizing single-cell and high-resolution spatial RNA sequencing. We observed significant changes in signaling pathways across seven different cell types when comparing lesional skin samples (LSS) to healthy skin samples (HSS). Using CellChat, we constructed an atlas of signaling pathways for the HSS, identifying key signal distributions and cell-specific genes within individual clusters. Further, our comparative analysis revealed changes in 49 signaling pathways across all cell clusters in the LSS- 4 exhibited decreased activity, whereas 45 were upregulated, suggesting that acne significantly alters cellular dynamics. We identified ten molecules, including GRN, IL-13RA1 and SDC1 that were consistently altered in all donors. Subsequently, we focused on the function of GRN and IL-13RA1 in TREM2 macrophages and keratinocytes as these cells participate in inflammation and hyperkeratinization in the early stages of acne development. We evaluated their function in TREM2 macrophages and the HaCaT cell line. We found that GRN increased the expression of proinflammatory cytokines and chemokines, including IL-18, CCL5, and CXCL2 in TREM2 macrophages. Additionally, the activation of IL-13RA1 by IL-13 in HaCaT cells promoted the dysregulation of genes associated with hyperkeratinization, including KRT17, KRT16, and FLG. These findings suggest that modulating the GRN-SORT1 and IL-13-IL-13RA1 signaling pathways could be a promising approach for developing new acne treatments.

Ocular surface changes in moderate-to-severe acne vulgaris.

AIM: To investigate ocular surface disorders and tear function changes in patients with acne vulgaris and explore the potential relationship between acne vulgaris and dry eye. METHODS: This cross-sectional study included right eyes of 53 patients with acne vulgaris and 54 healthy controls. The participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The following ocular surface-related parameters were measured: tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), Schirmer I test (SIT), lipid layer thickness (LLT) score of the tear film, meibum score, meibomian gland orifice obstruction score, the ratio of meibomian gland loss, conjunctival hyperemia score, and corneal fluorescein staining (CFS) score. RESULTS: The stability of the tear film decreased in acne vulgaris patients. In the acne group, the TMH and NIBUT were lower, whereas the OSDI, meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss, and conjunctival hyperemia score were higher compared with controls (P<0.05). There were no significant differences in the CFS score, SIT, or LLT score between the groups (P>0.05). In two dry eye groups, the TMH, NIBUT, and LLT score were lower in the acne with dry eye (acne-DE) group, and the meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss and conjunctival hyperemia score in the acne-DE group were higher (P<0.05). There were no significant differences between OSDI, SIT, and CFS score (P>0.05). CONCLUSION: Patients with moderate-to-severe acne vulgaris are more likely to experience dry eye than those without acne vulgaris. Reduced tear film stability and meibomian gland structure dysfunction are more pronounced in patients with moderate-to-severe acne and dry eye.

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study.

INTRODUCTION: Prior research has explored the relationship between inflammatory skin disorders and breast cancer (BC), yet the causality of this association remains uncertain. METHODS: Utilizing a bidirectional two-sample Mendelian randomization (MR) approach, this study aimed to elucidate the causal dynamics between various inflammatory skin conditions-namely acne, atopic dermatitis, psoriasis vulgaris, urticaria, and rosacea-and BC. Genetic variants implicated in these disorders were sourced from comprehensive genome-wide association studies representative of European ancestry. In the forward MR, BC was posited as the exposure, while the reverse MR treated each inflammatory skin disease as the exposure. A suite of analytical methodologies, including random effects inverse variance weighted (IVW), weighted median (WME), and MR-Egger, were employed to probe the causative links between inflammatory skin diseases and BC. Sensitivity analyses, alongside evaluations for heterogeneity and pleiotropy, were conducted to substantiate the findings. RESULTS: The MR analysis revealed an increased risk of acne associated with BC (IVW: OR = 1.063, 95% CI = 1.011-1.117, p = 0.016), while noting a decreased risk of atopic dermatitis (AD) in BC patients (IVW: OR = 0.941, 95% CI = 0.886-0.999, p = 0.047). No significant associations were observed between BC and psoriasis vulgaris, urticaria, or rosacea. Conversely, reverse MR analyses detected no effect of BC on the incidence of inflammatory skin diseases. The absence of pleiotropy and the consistency of these outcomes strengthen the study's conclusions. CONCLUSION: Findings indicate an elevated incidence of acne and a reduced incidence of AD in individuals with BC within the European population.

Repurposing lipid-lowering drugs as potential treatment for acne vulgaris: a Mendelian randomization study.

Background: Acne vulgaris, a chronic inflammatory skin condition predominantly seen in teenagers, impacts more than 640 million people worldwide. The potential use of lipid-lowering medications as a treatment for acne vulgaris remains underexplored. This study seeks to investigate the impact of lipid-lowering therapies on the risk of developing acne vulgaris using two-sample Mendelian randomization (MR) analysis. Method: The two-sample MR method was employed for analysis, and information on lipid-lowering drugs was obtained from the DrugBank and ChEMBL databases. The summary data for blood low-density lipoprotein (LDL) and triglycerides were sourced from the Global Lipids Genetics Consortium, while genome-wide association studies (GWAS) summary data for acne vulgaris were obtained from the FinnGen database. Heterogeneity was examined using the Q-test, horizontal pleiotropy was assessed using MR-Presso, and the robustness of analysis results was evaluated using leave-one-out analysis. Results: The MR analysis provided robust evidence for an association between lowering LDL cholesterol through two drug targets and acne vulgaris, with PCSK9 showing an odds ratio (OR) of 1.782 (95%CI: 1.129-2.812, p = 0.013) and LDL receptor (LDLR) with an OR of 1.581 (95%CI: 1.071-2.334, p = 0.021). Similarly, targeting the lowering of triglycerides through lipoprotein lipase (LPL) was significantly associated with an increased risk of acne vulgaris, indicated by an OR of 1.607 (95%CI: 1.124-2.299, p = 0.009). Conclusion: The current MR study presented suggestive evidence of a positive association between drugs targeting three genes (PCSK9, LDLR, and LPL) to lower lipids and a reduced risk of acne vulgaris.