Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on () biofilm. biofilms were constructed on a cell slide and treated with ALA-PDT.According to different light doses,the biofilms were divided into six groups:ALA-PDT group [ALA-PDT1 (50 J/cm),ALA-PDT2 group (100 J/cm),ALA-PDT3 group (200 J/cm)],ALA-only group (ALA group),light-only group (LED),and a negative control group (ALA-PDT-group).The biofilm structure and the ratio of the dead bacteria/live bacteria were observed using a laser confocal microscope (CLSM).Biofilm viability was measured using the XTT assay. CLSM showed that the biofilm structures of ALA group and LED group were not significantly different from that of ALA-PDT-group,whereas the biofilm structure was more seriously damaged in ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group than in the ALA-PDT-group.The ratios of the dead/live bacteria in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group were 0.350±0.033, 0.305±0.046, 0.330±0.032, 1.525±0.439, 2.293±0.148 and 3.092±0.189,respectively.ALA group(=0.003, =1.000)and LED group(=-0.025, =1.000)did not significantly differ from the ALA-PDT-group.However,the ratio of dead/live bacteria in ALA-PDT-group was significantly lower than those in ALA-PDT1 group (=-0.162, <0.001),ALA-PDT2 group (=-0.254, <0.001),and ALA-PDT3 group (=-0.352, <0.001).The values of the XTT assay were were 0.462±0.028,0.465±0.044,0.437±0.047,0.301±0.040,0.207±0.001,and 0.110±0.007,respectively,in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group.Although the values of XTT assay in ALA(=-0.044, =1.000)and LED groups (=-0.020, =1.000)did not significantly differ from that in ALA-PDT-group,it was significantly higher in ALA-PDT-group than in ALA-PDT1 group (=1.175, <0.001),ALA-PDT2 group (=1.942, <0.001),and ALA-PDT3 group (=-0.352, =2.742, <0.001). ALA-PDT has an inhibitory effect on biofilm.ALA-PDT destroys biofilm structure and inhibits biofilm viability.
Aminolevulinic Acid ; Biofilms ; Photochemotherapy ; Photosensitizing Agents ; Propionibacterium acnes

To investigate the pathogenesis of acne vulgaris, and to provide new ideas for non-antibiotic therapy for acne vulgaris.
 Methods: Normal human epidermal keratinocyte (NHEK) was exposed to Propionibacterium acnes (P. acnes) [multiplicity of infection (MOI)=10, 20, 30] for 12, 24, or 36 hours. The enzyme-linked immunosorbent assay (ELISA) and real-time PCR were used to detect the protein and mRNA of IL-1β in NHEK. Three groups were set up as follows: A negative control group (no NHEK pretreatment), a positive control group (P. acnes was used to stimulate NHEK), and a siRNA group (pretreated NHEK with siRNA). ELISA, real-time PCR, and Western blotting were used to detect the protein, mRNA of IL-1β and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) in NHEK.
 Results: IL-1β of NHEK in the positive control group was significantly increased in a time and dose-dependent manner compared with the negative control group (P<0.05). After pretreating NHEK with siRNA, IL-1β level was decreased compared with the positive control group, but it was higher than that in the negative control group (P<0.05).
 Conclusion: P. ances can stimulate NHEK to secrete IL-1β, and the process is possibly involved in NLRP3. The inflammatory response induced by P. ances could be inhibited by suppressing the activity of NLRP3.
Acne Vulgaris ; Humans ; Inflammasomes ; Interleukin-1beta ; Keratinocytes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Propionibacterium acnes

Propionibacterium acnes is one of the commensals living on the human skin and glands, implicated mainly in acnes, but seldom in deep infection. Pleural empyema is rarely complicated with closed thoracostomy. We experienced 1 case of empyema caused by P. acnes after pleural biopsy and closed thoracostomy through a percutaneous pigtail catheter. A 79-year-old man was admitted for cough, purulent sputum and shortness of breath. Three weeks ago, closed thoracostomy and pleural biopsy were performed to confirm a diagnosis for his recurrent pleural effusion. He had increased amount of right pleural effusion. Through the pigtail catheter, pleural effusion was removed. Gram-positive rods were observed in Gram stain, but not cultured. By 16S rRNA analysis, P. acnes was confirmed as the pathogen. His empyema was repeatedly treated with antibiotics, fibrolysis and irrigation. Pleural decortication was recommended. We report the first case of empyema with P. acnes in Korea, possibly complicated with closed thoracostomy procedures.
Aged ; Anti-Bacterial Agents ; Biopsy ; Catheters ; Cough ; Diagnosis ; Dyspnea ; Empyema ; Empyema, Pleural* ; Gram-Positive Rods ; Humans ; Korea ; Pleural Effusion ; Propionibacterium acnes* ; Propionibacterium* ; Skin ; Sputum ; Thoracostomy ; Thoracotomy

PURPOSE: The microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV composition METHODS: Twenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively. RESULTS: The proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level. CONCLUSIONS: We suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation.
Alicyclobacillus ; Animals ; Bacteria ; Cell Survival ; Dermatitis, Atopic* ; DNA, Ribosomal ; Extracellular Vesicles* ; Healthy Volunteers ; Humans ; In Vitro Techniques ; Inflammation ; Interleukin-4 ; Interleukins ; Keratinocytes ; Lactic Acid ; Lactobacillus* ; Lactococcus ; Leuconostoc ; Macrophages ; Metagenomics ; Mice ; Microbiota ; Probiotics ; Propionibacterium ; Skin ; Staphylococcus* ; Therapeutic Uses

Acne vulgaris is a very common condition affecting up of about 80% to 90% of adolescents. The patients with acne have been shown to be adversely impacted by the effect of acne on their quality of life. Four factors are believed to play a key role in the development of acne lesions: excess sebum production, disturbed keratinization within the follicle, colonization of the pilosebaceous duct by Propionibacterium acnes, and the release of inflammatory mediators into the skin. Consequently, the target for acne therapy is these well-known pathogenic factors responsible for this disease state. Topical retinoids correct abnormal keratinization, but it should be applied cautiously because of irritation. Benzoyl peroxide is an effective bactericidal agent against P. acnes. Main topical antibiotics are erythromycin and clindamycin. Fixed combination topical products with retinoids, benzoyl peroxide and antibiotics have been introduced. Use of systemic antibiotics, including tetracyclines and macrolides rapidly improves inflammatory acne lesions. Oral isotretinoin is effective against all of the main pathogenic features of acne but is contraindicated in pregnant women and has been associated with cheilitis and dry skin. Hormonal therapy has been found to improve acne in some selective patients and should be considered for appropriate candidates. This review will present the general aspects of the pharmacological treatments for acne.
Acne Vulgaris ; Adolescent ; Anti-Bacterial Agents ; Benzoyl Peroxide ; Cheilitis ; Clindamycin ; Colon ; Drug Therapy ; Erythromycin ; Female ; Humans ; Isotretinoin ; Macrolides ; Pregnant Women ; Propionibacterium acnes ; Quality of Life ; Retinoids ; Sebum ; Skin ; Tetracyclines

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, and bacterial infection plays a role in its pathogenesis. Bacteria secrete nanometer-sized extracellular vesicles (EVs), which may induce more immune dysfunction and inflammation than the bacteria themselves. We hypothesized that the microbiome of lung EVs might have distinct characteristics depending on the presence of COPD and smoking status. We analyzed and compared the microbiomes of 13 nonsmokers with normal spirometry, 13 smokers with normal spirometry (healthy smokers) and 13 patients with COPD by using 16S ribosomal RNA gene sequencing of surgical lung tissue and lung EVs. Subjects were matched for age and sex in all groups and for smoking levels in the COPD and healthy smoker groups. Each group included 12 men and 1 woman with the same mean age of 65.5 years. In all groups, EVs consistently showed more operational taxonomic units (OTUs) than lung tissue. In the healthy smoker and COPD groups, EVs had a higher Shannon index and a lower Simpson index than lung tissue and this trend was more prominent in the COPD group. Principal component analysis (PCA) showed clusters based on sample type rather than participants' clinical characteristics. Stenotrophomonas, Propionibacterium and Alicyclobacillus were the most commonly found genera. Firmicutes were highly present in the EVs of the COPD group compared with other samples or groups. Our analysis of the lung microbiome revealed that the bacterial communities present in the EVs and in the COPD group possessed distinct characteristics with differences in the OTUs, diversity indexes and PCA clustering.
Alicyclobacillus ; Bacteria ; Bacterial Infections ; Extracellular Vesicles* ; Female ; Firmicutes ; Humans ; Inflammation ; Lung* ; Male ; Microbiota* ; Passive Cutaneous Anaphylaxis ; Principal Component Analysis ; Propionibacterium ; Pulmonary Disease, Chronic Obstructive* ; RNA, Ribosomal, 16S ; Smoke ; Smoking ; Spirometry ; Stenotrophomonas

BACKGROUND: Acne vulgaris is a disease of the pilosebaceous unit characterized by increased sebum production, hyperkeratinization, and immune responses to Propionibacterium acnes (PA). Here, we explore a possible mechanism by which a lipid receptor, G2A, regulates immune responses to a commensal bacterium. OBJECTIVE: To elucidate the inflammatory properties of G2A in monocytes in response to PA stimulation. Furthermore, our study sought to investigate pathways by which lipids modulate immune responses in response to PA. METHODS: Our studies focused on monocytes collected from human peripheral blood mononuclear cells, the monocytic cell line THP-1, and a lab strain of PA. Our studies involved the use of enzyme-linked immunosorbent, Western blot, reverse transcription polymerase chain reaction, small interfering RNA (siRNA), and microarray analysis of human acne lesions in the measurements of inflammatory markers. RESULTS: G2A gene expression is higher in acne lesions compared to normal skin and is inducible by the acne therapeutic, 13-cis-retinoic acid. In vitro, PA induces both the Toll-like receptor 2-dependent expression of G2A as well as the production of the G2A ligand, 9-hydroxyoctadecadienoic acid, from human monocytes. G2A gene knockdown through siRNA enhances PA stimulation of interleukin (IL)-6, IL-8, and IL-1β possibly through increased activation of the ERK1/2 MAP kinase and nuclear factor kappa B p65 pathways. CONCLUSION: G2A may play a role in quelling inflammatory cytokine response to PA, revealing G2A as a potential attenuator of inflammatory response in a disease associated with a commensal bacterium.
Acne Vulgaris ; Blotting, Western ; Cell Line ; Cytokines* ; Gene Expression ; Gene Knockdown Techniques ; Humans* ; In Vitro Techniques ; Interleukin-8 ; Interleukins ; Isotretinoin ; Microarray Analysis ; Monocytes* ; NF-kappa B ; Phosphotransferases ; Polymerase Chain Reaction ; Propionibacterium acnes* ; Propionibacterium* ; Reverse Transcription ; RNA, Small Interfering ; Sebum ; Skin ; Toll-Like Receptors

Purpose of this study was to evaluate the influence of a lotion on the bacterial community in the human forearm skin. The chemical- and natural-based lotions were applied on the left and right inner forearm skins, respectively, of 14 participants, who cleansed forearm skin using sterilized cotton swabs. The germs on cotton swabs were analyzed using libraries of PCR amplicons. The genetic diversity of the bacterial communities detected on the natural-based lotion-applied skin (NLS) was significantly higher than that of the bacterial communities on the chemical-based lotion-applied skin (CLS) in all participants, except two. The diversity was estimated based on operational taxonomic unit (OTU), Chao1, Shannon, and Simpson indices. Bacterial communities obtained from the CLS and NLS were phylogenetically separated into 5 and 3 monophyletic groups, respectively, based on lotion types. The taxonomic distribution of the bacterial communities, which were composed of 198 genera in 14 phyla in the CLS and NLS, respectively, was irregularly and biasedly separated into 2 groups based on the lotion types. Among the 14 phyla, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria were found to be relatively dominant, and 15 of the 198 genera, including Methylobacterium, Propionibacterium, Pseudomonas, Staphylococcus, Streptococcus, and Bacillus were relatively dominant (>0.5%). The taxonomic distribution of dominant bacterial communities from CLS and NLS was irregularly and biasedly separated without relation to the lotion types. In conclusion, the chemical- and natural-based lotions were responsible for changing or influencing the genetic diversity, phylogenetic separation, and taxonomic distribution of skin bacterial communities.
Actinobacteria ; Bacillus ; Bacteroidetes ; Firmicutes ; Forearm* ; Genetic Variation ; Humans* ; Methylobacterium ; Polymerase Chain Reaction ; Propionibacterium ; Proteobacteria ; Pseudomonas ; Skin* ; Staphylococcus ; Streptococcus

BACKGROUND: Although recent metagenomic approaches have characterized the distinguished microbial compositions in airways of asthmatics, these results did not reach a consensus due to the small sample size, non-standardization of specimens and medication status. We conducted a metagenomics approach by using terminal restriction fragment length polymorphism (T-RFLP) analysis of the induced whole sputum representing both the cellular and fluid phases in a relative large number of steroid naïve asthmatics. METHODS: Induced whole sputum samples obtained from 36 healthy subjects and 89 steroid-naїve asthma patients were analyzed through T-RFLP analysis. RESULTS: In contrast to previous reports about microbiota in the asthmatic airways, the diversity of microbial composition was not significantly different between the controls and asthma patients (p=0.937). In an analysis of similarities, the global R-value showed a statistically significant difference but a very low separation (0.148, p=0.002). The dissimilarity in the bacterial communities between groups was 28.74%, and operational taxonomic units (OTUs) contributing to this difference were as follows: OTU 789 (Lachnospiraceae), 517 (Comamonadaceae, Acetobacteraceae , and Chloroplast), 633 (Prevotella), 645 (Actinobacteria and Propionibacterium acnes), 607 (Lactobacillus buchneri, Lactobacillus otakiensis, Lactobacillus sunkii, and Rhodobacteraceae), and 661 (Acinetobacter, Pseudomonas, and Leptotrichiaceae), and they were significantly more prevalent in the sputum of asthma patients than in the sputum of the controls. CONCLUSION: Before starting anti-asthmatic treatment, the microbiota in the whole sputum of patients with asthma showed a marginal difference from the microbiota in the whole sputum of the controls.
Acetobacteraceae ; Asthma* ; Consensus ; Healthy Volunteers ; Humans ; Lactobacillus ; Lung* ; Metagenomics ; Microbiota* ; Polymorphism, Restriction Fragment Length ; Propionibacterium ; Pseudomonas ; RNA, Ribosomal, 16S ; Sample Size ; Sputum*