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.

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.

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.

Correlation between depression scores and serum NF-ĸB/NLRP3 axis, biotinidase, and HMGB1 after treatment with isotretinoin in patients with acne vulgaris.

BACKGROUND: Acne vulgaris (AV) is an inflammatory skin disorder leading to scars and discomfort, its intensity has major psychological consequences such as depression. AIM: To investigate the effect of isotretinoin (ISO) on NF-κB/NLRP3, biotinidase, and HMGB and correlation with depression. PATIENTS AND METHODS: This was a case-control study that involved two groups. Group 1 is 20 healthy control, and group 2 is 20 patients diagnosed with AV according to Global Acne Grading System (GAGS) and received 20 mg ISO for 2 months. Before and after therapy, the Hamilton Depression Rating Scale (HDRS) was applied to assess each participant's level of depression. Nuclear factor kappa B (NF-ĸB), biotinidase, high mobility group box protein (HMGB1), nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP-3) were measured in serum samples. RESULTS: There was no significant difference in all measured markers of healthy group before and after 2 months. Regarding group 2, there was a statistically significant decrease in all measured markers after 2 months of treatment and significant correlations between GAGS, NF-ĸB, HMGB1, NLRP3, biotinidase, and depression score. CONCLUSION: Increased GAGS, HMGB1, NLRP3, and biotinidase were associated with depression severity in AV patients and ISO treatment significantly reduced these parameters and reduced depressive symptoms.

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.

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.

Hair Follicle-Targeted Delivery of Azelaic Acid Micro/Nanocrystals Promote the Treatment of Acne Vulgaris.

Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.

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.

Poly­d,l­lactic acid­enhanced atrophic scar treatment via transdermal microjet drug delivery in Asians.

BACKGROUND: Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and impact on patients' quality of life. Various treatment options exist, including the use of poly-d,l-lactic acid delivered via different methods. OBJECTIVE: This study aimed to assess the efficacy and safety of poly-d,l-lactic acid delivered via laser-assisted needle-free microjet injection for treating atrophic scars. METHODS: Five Korean participants with atrophic facial scars were recruited. Poly-d,l-lactic acid solution was administered via the Mirajet system in five sessions, with clinical assessments conducted at baseline, before each session, and at 12-week and 22-week follow-ups. Outcome measures included the Global Aesthetic Improvement Scale and patient satisfaction scores. RESULTS: Positive results were observed at the 12-week and 22-week follow-ups, with high patient satisfaction and improvements in atrophic scars and skin texture. Mild discomfort and transient side effects were reported, with no adverse events observed during the follow-up period. CONCLUSION: Poly-d,l-lactic acid delivered by a laser-assisted needle-free microjet injector was judged to be effective for improving atrophic the facial area. Further research, particularly through randomized controlled trials, is needed to validate these findings and assess the longer-term safety and sustainability of outcomes.

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.

A Seven-week, Open-label Trial Evaluating the Safety and Efficacy of a Photopneumatic Device for Mitigating Mild-to-Moderate Acne in Healthy Adolescents and Young Adults.

Objective: Photopneumatic devices combine gentle vacuum with pulsed broadband light to treat acne. This seven-week, open-label, single-group study evaluated the efficacy and safety of a photopneumatic device as acne monotherapy. Methods: Male and female subjects between the ages of 12 and 40 years with any Fitzpatrick Skin Phototype were enrolled (N=30). Subjects had facial acne and a baseline Investigator's Global Assessment (IGA) score of 2 (mild) or 3 (moderate), with ≥10 to ≤50 inflammatory lesions, ≥10 but ≤100 non-inflammatory lesions, and ≤1 facial nodule. The primary efficacy endpoints were change in baseline lesion counts and the percentage of subjects achieving a ≥1-grade reduction IGA Score at Day 49. Secondary efficacy endpoints included changes in Acne Quality of Life, self-assessment, and satisfaction scores. Adverse events and tolerability were assessed. Results: Inflammatory and non-inflammatory lesion counts significantly decreased at all time points versus baseline (for each, p<0.001); IGA scores were improved from baseline at most timepoints and 66.7 percent (20/30) achieved ≥1-grade IGA reduction at Day 49 (p<0.001). Consistent improvements in Acne Self-assessment, Acne-specific Quality of Life, and Treatment Satisfaction Questionnaires were reported. All subjects had favorable investigator and subject tolerability assessments. Limitations: This study was limited by its small sample size and open-label study design. Conclusion: Photopneumatic monotherapy significantly reduced acne lesions and resulted in clearer skin in all Fitzpatrick skin types. Adverse events were minor and subject satisfaction was favorable. Customizable energy and vacuum device settings makes the photopneumatic therapy device unique, allowing for a tailored individual approach to treating mild-to-moderate acne. Clinical Trial Idenifier Number: NCT06043102 (clinicaltrials.gov).

Pharmacological Management and Potentially Inappropriate Prescriptions for Patients with Acne.

Objective: Acne is a chronic inflammatory disease that involves the pilosebaceous follicle. Its pharmacological treatment involves topical and systemic medications, but a heterogeneous group of drugs may exacerbate or induce skin lesions. The aim of this study was to identify the pharmacological management and medications related to the exacerbation of skin lesions in patients diagnosed with acne. Methods: This was a cross-sectional study that identified the outpatient medication prescription patterns of patients with acne from a dispensing database of 8.5 million members of the Colombian Health System. Sociodemographic and pharmacological variables and the identification of prescriptions that were potentially inappropriate due to the risk of worsening acne were considered. Results: A total of 21,604 patients with acne were identified. Median age was 20.8 years (interquartile range: 17.3-27.3 years), and 60.7 percent were female. Treatment mainly involved antibiotics (79.9% of patients), especially doxycycline (66.0%), and retinoids (55.7%). A total of 17.2 percent of patients had potentially inappropriate prescriptions, predominantly progestogens with androgenic properties (8.9%). Female patients (odds ratio [OR]: 3.55; 95% confidence interval [CI]:3.24-3.90) and patients with pathologies such as systemic lupus erythematosus (OR: 18.61; 95% CI: 7.23-47.93) and rheumatoid arthritis (OR: 10.80; 95% CI: 5.02-23.23) were more likely to receive inappropriate prescriptions, and the risk increased with each year of life (OR: 1.02; 95% CI: 1.02-1.03). Limitations: Access to medical records was not obtained to verify clinical characteristics of acne. Conclusion: Patients with acne are excessively treated with systemic antibiotics, counter to clinical practice guidelines. Approximately one-fifth of these patients received some potentially inappropriate medication that could exacerbate their skin lesions.

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.

A Novel H-tert 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 the Chinese population and investigate the underlying mechanism of ALA-PDT. METHODS: Human primary sebocytes were transfected with the human tert gene (h-tert). 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 h-tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebaceous marker, 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 response 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 h-tert immortalized sebocyte cell line from an Asian firstly, which 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.

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.

Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin.

Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we demonstrate individual and niche heterogeneity of C. acnes from 1,234 isolate genomes. Skin disease (atopic dermatitis and acne) and body site shape genomic differences of C. acnes, stemming from horizontal gene transfer and selection pressure. C. acnes harbors characteristic metabolic functions, fewer antibiotic resistance genes and virulence factors, and a more stable genome compared with Staphylococcus epidermidis. Integrated genome, transcriptome, and metabolome analysis at the strain level unveils the functional characteristics of C. acnes. Consistent with the transcriptome signature, C. acnes in a sebum-rich environment induces toxic and pro-inflammatory effects on keratinocytes. L-carnosine, an anti-oxidative stress metabolite, is up-regulated in the C. acnes metabolome from atopic dermatitis and attenuates skin inflammation. Collectively, our study reveals the joint impact of genes and the microenvironment on C. acnes function.

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.

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.

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.