Untargeted Lipidomics Analysis to Discover Lipid Profiles and Biomarkers of Rabbit Acne Model and Reveal Action Mechanism of Isotretinoin.

Background: Acne vulgaris (AV), a chronic inflammatory pilosebaceous disorder, affects 80-90% of teenagers. This study aimed to discover lipid profiles and biomarkers of the rabbit ear acne model, and investigate the mechanism of isotretinoin in treating acne at the lipid level. Methods: Untargeted lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was performed to identify skin lipid metabolites in blank control (groups C), model group (group M) and isotretinoin group (group T). Multivariate statistical analysis was used to process the lipidomics data. Results: A total of 43 lipid classes comprising 6989 lipid species were identified from the mass spectrometry data. The orthogonal partial least squares discriminant analysis (OPLS-DA) model demonstrated significant separation in skin lipidomic profiles between group M and group C. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 299 significantly different lipid metabolites were identified. These lipid metabolites consisted mainly of ceramides (Cer) (53.85%), phosphatidylethanolamines (PE) (9.03%), phosphatidylcholines (PC)(5.35%), and sphingomyelin (SM)(4.01%). Combining with AUC ≥ 0.9 as the elected criteria, Cer (d18;1_24:0), zymosterol (ZyE)(33:5), Cer (t43:1), ZyE (33:6), ZyE (24:7), and ZyE (35:6) have "high" accuracy. Isotretinoin treatment normalized 25 lipid metabolites in the acne model. Conclusion: Our findings provide new insights into the role of lipid metabolism in the pathogenesis of acne and the action mechanism of isotretinoin.

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.

The Features of Shared Genes among Transcriptomes Probed in Atopic Dermatitis, Psoriasis, and Inflammatory Acne: S100A9 Selection as the Target Gene.

BACKGROUND: Atopic dermatitis (AD), psoriasis (PS), and inflammatory acne (IA) are well-known as inflammatory skin diseases. Studies of the transcriptome with altered expression levels have reported a large number of dysregulated genes and gene clusters, particularly those involved in inflammatory skin diseases. OBJECTIVE: To identify genes commonly shared in AD, PS, and IA that are potential therapeutic targets, we have identified consistently dysregulated genes and disease modules that overlap with AD, PS, and IA. METHODS: Microarray data from AD, PS, and IA patients were downloaded from Gene Expression Omnibus (GEO), and identification of differentially expressed genes from microarrays of AD, PS, and IA was conducted. Subsequently, gene ontology and gene set enrichment analysis, detection of disease modules with known disease-associated genes, construction of the protein-protein interaction (PPI) network, and PPI sub-mapping analysis of shared genes were performed. Finally, the computational docking simulations between the selected target gene and inhibitors were conducted. RESULTS: We identified 50 shared genes (36 up-regulated and 14 down-regulated) and disease modules for each disease. Among the shared genes, 20 common genes in PPI network were detected such as LCK, DLGAP5, SELL, CEP55, CDC20, RRM2, S100A7, S100A9, MCM10, AURKA, CCNB1, CHEK1, BTC, IL1F7, AGTR1, HABP4, SERPINB13, RPS6KA4, GZMB, and TRIP13. Finally, S100A9 was selected as the target gene for therapeutics. Docking simulations between S100A9 and known inhibitors indicated several key binding residues, and based on this result, we suggested several cannabinoids such as WIN-55212-2, JZL184, GP1a, Nabilone, Ajulemic acid, and JWH-122 could be potential candidates for a clinical study for AD, PS, and IA via inhibition of S100A9-related pathway. CONCLUSION: Overall, our approach may become an effective strategy for discovering new disease candidate genes for inflammatory skin diseases with a reevaluation of clinical data.

TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne.

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.

Interrupting an IFN-γ-dependent feedback loop in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne.

OBJECTIVES: To study the molecular pathogenesis of PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome, a debilitating hereditary autoinflammatory disease caused by dominant mutation in PSTPIP1. METHODS: Gene knock-out and knock-in mice were generated to develop an animal model. THP1 and retrovirally transduced U937 human myeloid leukaemia cell lines, peripheral blood mononuclear cells, small interfering RNA (siRNA) knock-down, site-directed mutagenesis, cytokine immunoassays, coimmunoprecipitation and immunoblotting were used to study inflammasome activation. Cytokine levels in the skin were evaluated by immunohistochemistry. Responsiveness to Janus kinase (JAK) inhibitors was evaluated ex vivo with peripheral blood mononuclear cells and in vivo in five treatment-refractory PAPA patients. RESULTS: The knock-in mouse model of PAPA did not recapitulate the human disease. In a human myeloid cell line model, PAPA-associated PSTPIP1 mutations activated the pyrin inflammasome, but not the NLRP3, NLRC4 or AIM2 inflammasomes. Pyrin inflammasome activation was independent of the canonical pathway of pyrin serine dephosphorylation and was blocked by the p.W232A PSTPIP1 mutation, which disrupts pyrin-PSTPIP1 interaction. IFN-γ priming of monocytes from PAPA patients led to IL-18 release in a pyrin-dependent manner. IFN-γ was abundant in the inflamed dermis of PAPA patients, but not patients with idiopathic pyoderma gangrenosum. Ex vivo JAK inhibitor treatment attenuated IFN-γ-mediated pyrin induction and IL-18 release. In 5/5 PAPA patients, the addition of JAK inhibitor therapy to IL-1 inhibition was associated with clinical improvement. CONCLUSION: PAPA-associated PSTPIP1 mutations trigger a pyrin-IL-18-IFN-γ positive feedback loop that drives PAPA disease activity and is a target for JAK inhibition.

Azithromycin-loaded liposomes and niosomes for the treatment of skin infections: Influence of excipients and preparative methods on the functional properties.

The aim of this study was to develop azithromycin (AZT)-loaded liposomes (LP) and niosomes (NS) useful for the treatment of bacterial skin infections and acne. LP based on phosphatidylcholine from egg yolk (EPC) or from soybean lecithin (SPC), and NS composed of sorbitan monopalmitate (Span 40) or sorbitan monostearate (Span 60) were prepared through the thin film hydration (TFH) and the ethanol injection (EI) methods. The formulations were subsequently characterized for their physico-chemical and functional properties. Vesicles prepared through TFH showed higher average sizes than the corresponding formulations obtained by EI. All the vesicles presented adequate encapsulation efficiency and a negative ζ potential, which assured good stability during the storage period (except for LP-SPC). Formulations prepared with TFH showed a more prolonged AZT release than those prepared through EI, due to their lower surface area and multilamellar structure, as confirmed by atomic force microscopy nanomechanical characterization. Finally, among all the formulations, NS-Span 40-TFH and LP-EPC-TFH allowed the highest drug accumulation in the skin, retained the antimicrobial activity and did not alter fibroblast metabolism and viability. Overall, they could ensure to minimize the dosing and the administration frequency, thus representing promising candidates for the treatment of bacterial skin infections and acne.

Lipidomic analysis of facial skin surface lipids in acne in young women.

BACKGROUND: Alterations in the secretion and composition of skin surface lipids (SSL) are closely associated with the development of acne. Lipidomics is a useful tool to analyse the SSL of different types of acne. Our previous study found that phosphatidylserine and triacylglycerols dominate SSL changes in male acne and infantile acne, respectively. However, skin surface lipids as well as specific lipids in female acne patients remain to be investigated. OBJECTIVES: To analyse and compare the SSL profile of acne women and healthy women and to discuss the involvement of differential lipids in acne development. METHODS: Systematic lipidomics approach (high-throughput UPLC-QTOF-MS technology in combination with multivariate data analysis methods) was used to analyse the variations of SSL between acne and healthy groups. RESULTS: Analysis revealed significant differences in lipid content and composition between the two groups. Further analysis showed that levels of 13 individual lipids were significantly different and followed the same trend as the main class and subclasses. The largest individual contributor to the subgroup was triglycerides (TG) and phosphatidylinositol (PI). In addition, female acne patients exhibited reduced ceramide chain length (CCL) and increased levels of unsaturated fatty acids (UFAs), The changes of CCL in female acne are identical to male acne. CONCLUSIONS: There was a significantly higher level of TG and PI in the SSL of female acne patients. A reduction in CCL and an increase in UFAs content might contribute to the reduced skin barrier function in acne patients. The results suggest that female acne may have different pathogenesis than male acne.

Unlocking the potential of cosmetic dermal delivery with ethosomes: A comprehensive review.

BACKGROUND: In a world where hair loss, acne, and skin whitening are common concerns, ethosomes emerge as a captivating breakthrough in cosmetic drug delivery. METHOD: This review provides a comprehensive overview of the ethosomal system and assesses its potential as an effective nanocarrier for delivering active ingredients to the skin. The focus is on exploring their applications in various pathologies, particularly skin disorders such as acne, hair loss, and skin pigmentation. RESULTS: Ethosomes are a novel type of vesicular nanocarrier composed of high concentrations of ethanol (20-45%) and phospholipids. Their unique structure and composition make them an ideal choice for transporting active ingredients through the skin, offering targeted and effective treatment. The inclusion of ethanol in ethosomes' composition gives them distinctive properties, including flexibility, deformability, and stability, facilitating deep penetration into the skin and enhancing medication deposition. Moreover, ethosomes improved theoverall drug-loading capacity, and specificity of target treatment CONCLUSION: Ethosomes represent a unique and suitable approach for delivering active cosmetic ingredients in the treatment of hair loss, acne, and skin whitening, presenting a versatile alternative to traditional dermal delivery systems. Despite the challenges associated with their complex preparation and sensitivity to temperature and humidity, the remarkable potential benefits of ethosomes cannot be ignored. Further research is crucial to unlock their full potential, understand their limitations, and refine their formulations and administration methods. Ethosomes hold the promise of transforming the way we address these cosmetic concerns, offering an exciting glimpse into the future of advanced skincare solutions.

In vitro acne disease model from inertial focusing effect for studying the interactions between sebocyte glands and macrophages.

Acne is one of the most widespread skin diseases. The acne mechanism is intricate, involving interactions between different types of cells (i.e., sebocytes and macrophages). One of the challenges in studying the mechanism of acne is that current in vitro culture methods cannot reflect the 3D cellular environment in the tissue, including inflammatory stimuli and cellular interactions especially the interactions between sebocytes and immune cells. To solve this issue, we generated an in vitro acne disease model consisting of 3D artificial sebocyte glands and macrophages through the inertial focusing effect method. Using this model, we produced a controllable inflammatory environment similar to the acne pathogenetic process in the skin. The 3D artificial sebocyte glands and macrophages can be separated for analyzing each cell type, assisting the in-depth understanding of the acne mechanism. This study indicates that proinflammatory macrophages promote lipid accumulation and induce oxidative stress in sebocyte glands. Additionally, in an inflammatory environment, sebocyte glands induce macrophage polarization into the M1 phenotype. Employing this model for drug screening, we also demonstrated that, cannabidiol (CBD), a clinically investigated drug, is effective in restoring lipid accumulation, oxidative stress, inflammatory cytokines and macrophage polarization in the acne disease.

Systematic Study of Paeonol/Madecassoside Co-Delivery Nanoemulsion Transdermal Delivery System for Enhancing Barrier Repair and Anti-Inflammatory Efficacy.

Sensitive skin is defined as skin with low tolerance and high reactivity. Natural products, such as paeoniflorin and madecassoside, have unique skin care functionality. However, because they are hampered by the skin barrier, paeoniflorin and madecassoside have difficulty penetrating the stratum corneum, resulting in weakened skin barrier repair and anti-inflammatory effects. In addition, there is a lack of detailed studies on the efficacy of paeonol and madecassic in human skin, especially in 3D skin models and clinical trials. To overcome the low transdermal delivery issue, we developed nanoemulsions (PM-NEs) loaded with paeonol and madecassoside to improve their delivery efficiency and promote sensitive skin repair and anti-inflammation effects. Furthermore, systematic evaluations of the efficacy in cell line models, 3D skin models, and clinical trials were conducted. The PM-NEs effectively improved the efficacy of paeonol and madecassoside glucoside transdermal penetration and retention and enhanced cellular uptake. Cellular assays and 3D epidermal models showed that the PM-NEs significantly promoted the secretion of filamentous protein, aquaporin 3, Claudin-1, and hyaluronic acid, and considerably inhibited the secretion of interleukin 1α, interleukin 6, tumor necrosis factor-α, and prostaglandin E2 compared to free components. Notably, clinical trial data showed that the PM-NEs significantly reduced transepidermal water loss, a* values, erythropoietin, the amount of non-inflammatory acne, and the amount of inflammatory acne in the facial skin. Three levels of systematic studies suggest that co-delivery of paeoniflorin and madecassoside via nanoemulsions is a promising strategy to improve topical delivery efficiency and anti-inflammatory repair efficacy in sensitive skin.

The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis.

BACKGROUND: Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. METHODS: Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins' expression and localization was detected by western blot and immunofluorescence. RESULTS: NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes' transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. CONCLUSIONS: Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs' function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation.

Comparison of clinical outcomes between intense pulsed light therapy using two different filters in meibomian gland dysfunction: prospective randomized study.

Our study compared treatment efficacy between cut-off and notch filters in intense pulsed light (IPL) therapy for meibomian gland dysfunction (MGD) through a prospective, randomized paired-eye trial. Additionally, the efficacy of IPL treatment alone was investigated by restricting other conventional treatments. One eye was randomly selected for an acne filter and the other for a 590-nm filter. Identical four regimens of IPL treatments were administered. The tear break-up time (TBUT), Oxford scale, Sjögren's International Clinical Collaborative Alliance (SICCA) staining score, tear matrix metalloproteinase-9 (MMP-9) expression, tear osmolarity, and Ocular Surface Disease Index (OSDI) questionnaires were evaluated before and after IPL. Meibomian gland (MG) parameters were measured. When combining the results from both filters, the TBUT, SICCA staining score, OSDI score, and upper and lower lid meibum expressibility were improved after IPL. No significant differences were found between the two filters in the TBUT, Oxford scale, SICCA staining score, MMP-9 expression, tear osmolarity, and MG parameters. Although not significant, the acne filter showed better treatment efficacy than that in the 590-nm filter. IPL alone is efficacious in terms of ocular surface parameters, MG function, and subjective symptoms. Regarding filter selection, both acne and 590-nm filters are promising options for MGD treatment.

Barrier function-related genes and proteins have an altered expression in acne-involved skin.

BACKGROUND: Acne vulgaris provides a unique disease setting in which a prominent skin inflammation is coupled with the overproduction of lipid-rich sebum. OBJECTIVES: Our goal was to evaluate the expression of barrier molecules in papular acne skin samples obtained from untreated patients and compare those to the results of healthy and of papulopustular rosacea-involved ones at the mRNA and protein levels. In addition, we aimed to assess the effects of various sebum composing lipids on the expression of proteins involved in barrier formation in keratinocytes. METHODS: Available microarray data sets of papular acne and papulopustular rosacea-affected skin samples were re-analysed with a focus on epidermal barrier-related pathways. Immunohistochemistry was performed to detect barrier molecules in the interfollicular regions of human acne and healthy skin samples. Protein levels of barrier-related genes were measured by western blot in samples of HaCaT keratinocytes treated with selected lipids. RESULTS: Meta-analysis of whole transcriptome data sets revealed that barrier-related pathways are significantly affected in acne vulgaris skin samples. While an altered expression of key molecules in maintaining barrier functions such as filaggrin, keratin 1, involucrin, desmoglein 1, kallikrein 5 and 7, was also observed at the protein levels, our data demonstrated that sebum composing lipids may selectively modify the levels of epidermal barrier-related molecules. CONCLUSIONS: Our results suggest that although not as prominently as in the dry papulopustular rosacea skin, the epidermal barrier in the interfollicular region may be damaged also in the lipid-rich skin samples of papular acne. Furthermore, our findings indicating diverse regulatory effects of various sebum lipids on the expression of barrier molecules in keratinocytes suggest, that they may influence the moisturization of the skin as well. Altogether, our findings could have implications in the development of sebum-modulating anti-acne therapies and even in the care of symptom-free skin.

Viaminate ameliorates Propionibacterium acnes-induced acne via inhibition of the TLR2/NF-κB and MAPK pathways in rats.

Viaminate, a retinoic acid derivative developed in China, has been clinically used for acne treatment to regulate and control keratinocyte cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and regulate immune and anti-inflammatory functions; however, its potential molecular mechanism has not yet been elucidated. Therefore, we induced ear acne in rats using Propionibacterium acnes and sebum application. Symptoms of ear redness, epidermal thickening, inflammatory reaction, keratin overproduction, subcutaneous oil, and triglyceride (TG) accumulation improved significantly in acne model rats treated with viaminate for 30 days. Transcriptome analysis of rat skin tissues suggested that viaminate had significant regulatory effects on fatty acid metabolism and cellular keratinization pathways. Molecular target prediction suggested that toll-like receptor 2 (TLR2) may be a key target of viaminate's therapeutic mechanism. Western blotting results confirmed that viaminate inhibited the TLR2 and its downstream pathways, nuclear factor-kappa B (NF-κB) [NF-κB inhibitor alpha (IκBα)/NF-κB-p65] and mitogen-activated protein kinases (MAPKs) [MAPK p38/c-Jun N-terminal kinase (JNK)/extracellular regulated kinase 1/2 (ERK1/2)] in acne vulgaris rats. In vitro studies revealed that viaminate treatment attenuated P. acnes proliferation and P. acnes-induced inflammatory response in human keratinocytes and has an inhibitory effect on the activation of NF-κB and MAPKs, while overexpression of TLR2 attenuated these effects. In conclusion, viaminate ameliorates P. acnes-induced acne by inhibiting the proliferation and inflammatory response of keratinocytes, ascribed to the deactivation of the TLR2-mediated NF-κB and MAPK pathways.

Lactoferrin regulates sebogenesis and inflammation in SZ95 human sebocytes and mouse model of acne.

BACKGROUND: The aim of this study was to explore the anti-inflammatory and anti-lipid effects of lactoferrin on SZ95 human sebaceous gland cells and mouse model of acne. METHODS: SZ95 cells were co-cultured with different concentrations of lactoferrin, and cell viability was determined using the 2,5-diphenyl-2H-tetrazolium bromide method. Oil red O and Nile red staining were performed to determine the lipid content. The mRNA expression of genes related to lipid metabolism (sterol regulatory element-binding protein-1 [SREBP-1], fatty acid synthase [FAS], stearoyl-CoA desaturase-1 [SCD-1], fatty acid desaturase 2 [FADS2]) and inflammation (interleukin-8 [IL-8]) was determined by reverse transcription-polymerase chain reaction. An acne mouse model was established using injection of P. acnes on the backs of mice. The proliferation and apoptosis of sebaceous gland cells were examined by immunohistochemistry against proliferating cell nuclear antigen (PCNA) and TUNEL staining, respectively. Western blotting was used to detect FADS2 and CXCL15 protein expression. RESULTS: Lactoferrin treatment at 10-500 µg/ml significantly decreased the lipid content, as revealed by the oil red O and Nile red staining. It also attenuated the increase of mRNA expression of SREBP-1, FAS, SCD-1, FADS2, and IL-8 in insulin-treated SZ95 cells. Moreover, lactoferrin treatment at the doses of 1-50 mg/mouse significantly reduced the inflammation and lipid production in the mouse model of acne. Also, the number of sebaceous gland cells was significantly reduced, and apoptosis was significantly increased by lactoferrin treatment in the mice. Mechanically, the levels of FADS2 and CXCL15 proteins in tissues were significantly decreased after lactoferrin treatment in the model mice. CONCLUSION: Our results demonstrate the potential of lactoferrin against sebogenesis, sebaceous gland inflammation in acne.

Red Light-Mediated Photoredox Catalysis Triggers Nitric Oxide Release for Treatment of Cutibacterium Acne Induced Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) has been known as a highly prevalent and disabling disease, which is one of the main causes of low back pain and disability. Unfortunately, there is no effective cure to treat this formidable disease, and surgical interventions are typically applied. Herein, we report that the local administration of nitric oxide (NO)-releasing micellar nanoparticles can efficiently treat IVDD associated with Modic changes in a rat model established by infection with Cutibacterium acnes (C. acnes). By covalent incorporation of palladium(II) meso-tetraphenyltetrabenzoporphyrin photocatalyst and coumarin-based NO donors into the core of micellar nanoparticles, we demonstrate that the activation of the UV-absorbing coumarin-based NO donors can be achieved under red light irradiation via photoredox catalysis, although it remains a great challenge to implement photoredox catalysis reactions in biological conditions due to the complex microenvironments. Notably, the local delivery of NO can not only efficiently eradicate C. acnes pathogens but also inhibit the inflammatory response and osteoclast differentiation in the intervertebral disc tissues, exerting antibacterial, anti-inflammatory, and antiosteoclastogenesis effects. This work provides a feasible means to efficiently treat IVDD by the local administration of NO signaling molecules without resorting to a surgical approach.

Particulate matter increases Cutibacterium acnes-induced inflammation in human epidermal keratinocytes via the TLR4/NF-κB pathway.

Recent studies have demonstrated that particulate matter (PM) can induce oxidative stress and inflammatory responses that are related to the development or exacerbation of several inflammatory dermatoses. However, the effect of PM on acne vulgaris has yet to be determined. In this study, we induced acne-like inflammation in HEKn cells with several concentrations of Cutibacterium acnes (C. acnes) and Staphylococcus aureus peptidoglycan (PGN) to investigate whether PM exposure exacerbates acne-like inflammation and elucidate the underlying mechanisms. To confirm whether PM increases the messenger ribonucleic acid (mRNA) and protein levels of proinflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-8, and TNF-α) and cyclooxygenase (COX)-2 expression in C. acnes- or PGN-treated HEKn cells, we used quantitative real-time polymerase chain reactions, enzyme-linked immunosorbent assays, and western blot assays. The results demonstrated that C. acnes, PGN, and PM induced the expression of proinflammatory cytokines in a time- and dose-dependent manner at the mRNA and protein levels, respectively. Moreover, PM further increased the expression of proinflammatory cytokines, COX2, TLR4, and the phosphorylation of NF-κB in C. acnes- and PGN-treated HEKn cells. In conclusion, our results suggest that PM may exacerbate acne symptoms by increasing the inflammatory response.

Preventative effects of antioxidants on changes in sebocytes, outer root sheath cells, and Cutibacterium acnes-pretreated mice by particulate matter: No significant difference among antioxidants.

OBJECTIVES: Particulate matter (PM) is an air pollutant that can damage human skin; antioxidants have shown some efficacy in alleviating PM-induced skin inflammation. We investigated the antioxidant effects of punicalagin, epigallocatechin-3-gallate (EGCG), and resveratrol on PM-induced changes in cultured human sebocytes, outer root sheath (ORS) cells, and Cutibacterium acnes-pretreated mice. METHODS: Sebocytes and ORS cells were cultured with 100 µg/mL PM10 and 5 µM punicalagin, 1 µM EGCG, or 1 µM resveratrol for 24 h. In C. acnes-pretreated mice, inflammatory nodules were treated with 100 µg/mL PM10 and 5 µM punicalagin, 1 µM EGCG, or 1 µM resveratrol. Cell viability was measured using an MTT assay. Antioxidant effects were analyzed according to RNA expression, using real-time PCR, as well as reactive oxygen species (ROS) and sebum measurements. RESULTS: Antioxidants inhibited the upregulation of inflammatory cytokines, matrix metalloproteinase, aryl hydrocarbon receptor, and NF-kB as well as the production of ROS induced by PM10 in cultured sebocytes and ORS cells. The preventative effects of punicalagin and EGCG on biomarker expression in cultured sebocytes and ORS cells were slightly greater than those of resveratrol, though the difference was not significant. In C. acnes-pretreated mice, the antioxidants inhibited inflammatory cytokine and matrix metalloproteinase expression as well as sebum production. CONCLUSIONS: Antioxidants effectively reduced the expression of inflammatory biomarkers and sebum production in cultured sebocytes, ORS cells, and C. acnes-pretreated mice.

Clinical and metagenomic profiling of hormonal acne-prone skin in different populations.

INTRODUCTION: Acne is one of the most common skin concerns of unknown etiology, often connected to the menstrual cycle in women, and possibly to the microbial profile and function. OBJECTIVE: We aimed to investigate how hormonal fluctuation affects hormonal acne-prone skin in different populations in relation to skin clinical parameters and microbial profiles. METHODS: We evaluated skin features by using biophysical and topographical tools. For microbial profiling, we sequenced facial skin microbiota and associated the findings with the skin clinical parameters during the different phases of the menstrual cycle. RESULTS: We identified differences between and within hormonal phases in women of Chinese and Caucasian origin. Changes were discovered in transepidermal water loss (TEWL), sebum level, hydration level, and pore volume. The most abundant identifiable genera in both ethnicities were Cutibacterium, Staphylococcus, and Streptococcus, without any significant abundant differences within the menstrual cycle. Interestingly, 11 bacterial metabolic pathways were downregulated in Chinese compared to Caucasian skin during the follicular phase. The majority of these pathways were associated with skin redox balance, perhaps indicating a weaker oxidative stress response in Chinese versus Caucasian skin. Novosphingobium taxa were increased in the Chinese skin microbiome, which has been reported to protect skin from pollution-mediated oxidative stress. CONCLUSION: Thus, this pilot study explored some of the clinical and metagenomic changes in acne-prone skin, and provide guidance to tailor-personalized skin care regimes during the menstrual cycle. Also, the skin redox status in acne-prone skin, provides more opportunity to tailor-personalized skin care regimes.