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1.
Yakugaku Zasshi ; 144(5): 497-501, 2024.
Article Ja | MEDLINE | ID: mdl-38692923

Signal-transducing adaptor protein-2 (STAP-2) is a unique scaffold protein that regulates several immunological signaling pathways, including LIF/LIF receptor and LPS/TLR4 signals. STAP-2 is required for Fas/FasL-dependent T cell apoptosis and SDF-1α-induced T cell migration. Conversely, STAP-2 modulates integrin-mediated T cell adhesion, suggesting that STAP-2 is essential for several negative and positive T cell functions. However, whether STAP-2 is involved in T cell-antigen receptor (TCR)-mediated T cell activation is unknown. STAP-2 deficiency was recently reported to suppress TCR-mediated T cell activation by inhibiting LCK-mediated CD3ζ and ZAP-70 activation. Using STAP-2 deficient mice, it was demonstrated that STAP-2 is required for the pathogenesis of Propionibacterium acnes-induced granuloma formation and experimental autoimmune encephalomyelitis. Here, detailed functions of STAP-2 in TCR-mediated T cell activation, and how STAP-2 affects the pathogenesis of T cell-mediated inflammation and immune diseases, are reviewed.


Adaptor Proteins, Signal Transducing , Lymphocyte Activation , Receptors, Antigen, T-Cell , Signal Transduction , T-Lymphocytes , ZAP-70 Protein-Tyrosine Kinase , Animals , Receptors, Antigen, T-Cell/physiology , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/immunology , Humans , Adaptor Proteins, Signal Transducing/physiology , Adaptor Proteins, Signal Transducing/metabolism , Mice , ZAP-70 Protein-Tyrosine Kinase/metabolism , ZAP-70 Protein-Tyrosine Kinase/physiology , Propionibacterium acnes/physiology , Propionibacterium acnes/immunology , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/etiology , Inflammation/immunology , Apoptosis , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/physiology , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism , Cell Movement , Cell Adhesion , CD3 Complex , Chemokine CXCL12/physiology , Chemokine CXCL12/metabolism
2.
Int J Mol Sci ; 25(9)2024 Apr 27.
Article En | MEDLINE | ID: mdl-38731983

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 µg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin's bioactivity mirrored the extract's effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low µM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract's biological activities. This study is the first to explore ellagitannins' potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.


Acne Vulgaris , Fagaceae , Hydrolyzable Tannins , Plant Extracts , Plant Leaves , Humans , Hydrolyzable Tannins/pharmacology , Fagaceae/chemistry , Acne Vulgaris/microbiology , Acne Vulgaris/drug therapy , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Leaves/chemistry , Keratinocytes/drug effects , Keratinocytes/metabolism , NF-kappa B/metabolism , HaCaT Cells , Propionibacterium acnes/drug effects , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Interleukin-8/metabolism
3.
Medicine (Baltimore) ; 103(21): e37657, 2024 May 24.
Article En | MEDLINE | ID: mdl-38788015

BACKGROUND: Acne is a prevalent inflammatory condition of the pilosebaceous unit, which seriously affects the appearance and mental health of patients. Bibliometrics is the statistical analysis of academic literature in a certain field. We aimed to characterize the 100 most cited articles on acne from a bibliometric perspective, as well as explore the frontier hotspots and trends of acne. METHODS: A search was conducted on the Web of Science database on August 8, 2023. we employed the terms "acne," "acne Vulgaris," and "common acne" in our search. The top 100 articles with the most citations throughout the time frame of 2014 to 2023 were discovered and assessed. The visualization study was carried out using bibliometric tools such as CiteSpace 6.2.R4, VOSviewer 1.6.18, and MapChart. RESULTS: The top 100 most cited articles were published between 2014 and 2021, originated from a diverse range of 48 countries, with a predominant focus on the United States of America (USA) and Germany. The top 100 papers were cited between 50 and 712 times. Dreno B, from Nantes University, was the most frequently nominated author. With 12 papers, the Journal of the European Academy of Dermatology and Venereology contributed the most to the top 100 list. Alongside the term "acne", the following terms or phrases were observed frequency in the top 100 articles, Cutibacterium acnes, sebaceous, western diet, antibiotic resistance, staphylococcus-epidermidis, insulinlike growth factor 1, benzoyl peroxide, and polyunsaturated fatty acids. Alongside the term "acne", terms or phrases such as Cutibacterium acnes, sebaceous, western diet, antibiotic resistance, staphylococcus-epidermidis, insulinlike growth factor 1, benzoyl peroxide, and polyunsaturated fatty acids, etc also have a high frequency in the top 100 articles. CONCLUSION: This analysis summarizes the shifting trends of acne research over the last decades. Research on acne is currently flourishing. The related pathogenesis and therapeutic strategies have been the focus of current research and developmental trends in future research.


Acne Vulgaris , Bibliometrics , Acne Vulgaris/drug therapy , Humans , Biomedical Research/trends , Biomedical Research/statistics & numerical data , Propionibacterium acnes
4.
Acta Neurochir (Wien) ; 166(1): 224, 2024 May 21.
Article En | MEDLINE | ID: mdl-38771556

PURPOSE: Surgical site infection (SSI) is a serious complication after cranioplasty. Due to the relatively frequent occurrence of post-cranioplasty SSI, the utility of autologous bone flap swab cultures surrounding cryopreservation as a reliable predictor has been the subject of an ongoing debate. This bicentric study aims to contribute to this topic by conducting an in-depth analysis of bone flaps obtained via decompressive craniectomies. This study had three major aims: assessments of 1) bacterial contamination of bone flaps after decompressive craniotomy, 2) impact of cryoconservation on contamination rates and 3) potential effectiveness of anti-infective treatment to reduce the germ load prior to cranioplasty. METHODS: Cryopreserved bone flaps from two centers were used. Microbiological cultivations of swabs prior to and after cryopreservation were taken and assessed for aerobic and anaerobic growth over a 14-day incubation period. Additionally, in a subset of bone flaps, swab testing was repeated after thorough rinsing with an anti-infectant (octenidine-phenoxyethanol) followed by saline. RESULTS: All 63 bone flaps (patients median age at surgery: 59 years) were obtained via decompressive craniectomies. Swabs done prior to cryopreservation revealed a 54% infection rate with Propionibacterium acnes being the most common microorganism in 65% of those cases. After thorough disinfection of the preserved bone flaps, all but one case showed no bacterial growth in swab testing. Furthermore, no relevant risk factors for bacterial contamination could be identified. CONCLUSION: This retrospective study showed the common presence of bacterial growth in cryopreserved bone flaps before and after freezing. Rinsing with octenidine-phenoxyethanol and saline effectively prevented bacterial growth in a notable percentage of cases, suggesting a potential strategy to reduce contamination. However, persistent bacterial growth in some cases underscores the need for further research to optimize antiseptic measures during autologous cranioplasty.


Cryopreservation , Decompressive Craniectomy , Surgical Flaps , Surgical Wound Infection , Humans , Cryopreservation/methods , Middle Aged , Male , Female , Surgical Wound Infection/microbiology , Surgical Wound Infection/prevention & control , Decompressive Craniectomy/methods , Decompressive Craniectomy/adverse effects , Adult , Aged , Propionibacterium acnes/isolation & purification
5.
ACS Appl Mater Interfaces ; 16(17): 21595-21609, 2024 May 01.
Article En | MEDLINE | ID: mdl-38635857

A microneedle transdermal drug delivery system simultaneously avoids systemic toxicity of oral administration and low efficiency of traditional transdermal administration, which is of great significance for acne vulgaris therapy. Herein, eugenol-loaded hyaluronic acid-based dissolving microneedles (E@P-EO-HA MNs) with antibacterial and anti-inflammatory activities are developed for acne vulgaris therapy via eugenol transdermal delivery integrated with photothermal therapy. E@P-EO-HA MNs are pyramid-shaped with a sharp tip and a hollow cavity structure, which possess sufficient mechanical strength to penetrate the stratum corneum of the skin and achieve transdermal delivery, in addition to excellent in vivo biocompatibility. Significantly, E@P-EO-HA MNs show effective photothermal therapy to destroy sebaceous glands and achieve antibacterial activity against deep-seated Propionibacterium acnes (P. acnes) under near-infrared-light irradiation. Moreover, cavity-loaded eugenol is released from rapidly dissolved microneedle bodies to play a sustained antibacterial and anti-inflammatory therapy on the P. acnes infectious wound. E@P-EO-HA MNs based on a synergistic therapeutic strategy combining photothermal therapy and eugenol transdermal administration can significantly alleviate inflammatory response and ultimately facilitate the repair of acne vulgaris. Overall, E@P-EO-HA MNs are expected to be clinically applied as a functional minimally invasive transdermal delivery strategy for superficial skin diseases therapy in skin tissue engineering.


Acne Vulgaris , Administration, Cutaneous , Anti-Bacterial Agents , Eugenol , Hyaluronic Acid , Needles , Photothermal Therapy , Propionibacterium acnes , Acne Vulgaris/therapy , Acne Vulgaris/drug therapy , Eugenol/chemistry , Eugenol/pharmacology , Hyaluronic Acid/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Propionibacterium acnes/drug effects , Mice , Drug Delivery Systems , Humans , Skin
6.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167195, 2024 Jun.
Article En | MEDLINE | ID: mdl-38648901

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.


Acne Vulgaris , Sebaceous Glands , TRPV Cation Channels , Toll-Like Receptor 2 , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 2/genetics , Animals , Acne Vulgaris/metabolism , Acne Vulgaris/pathology , Acne Vulgaris/genetics , Acne Vulgaris/immunology , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Humans , Mice , Sebaceous Glands/metabolism , Sebaceous Glands/pathology , Sebaceous Glands/immunology , Inflammation/metabolism , Inflammation/pathology , Inflammation/genetics , Propionibacterium acnes , Male , NF-kappa B/metabolism , Signal Transduction , Mice, Inbred C57BL , Female
7.
Sci Rep ; 14(1): 4529, 2024 02 24.
Article En | MEDLINE | ID: mdl-38402320

The increasing prevalence of antibiotic resistance in Cutibacterium acnes (C. acnes) requires the search for alternative therapeutic strategies. Antimicrobial peptides (AMPs) offer a promising avenue for the development of new treatments targeting C. acnes. In this study, to design peptides with the specific inhibitory activity against C. acnes, we employed a deep learning pipeline with generators and classifiers, using transfer learning and pretrained protein embeddings, trained on publicly available data. To enhance the training data specific to C. acnes inhibition, we constructed a phylogenetic tree. A panel of 42 novel generated linear peptides was then synthesized and experimentally evaluated for their antimicrobial selectivity and activity. Five of them demonstrated their high potency and selectivity against C. acnes with MIC of 2-4 µg/mL. Our findings highlight the potential of these designed peptides as promising candidates for anti-acne therapeutics and demonstrate the power of computational approaches for the rational design of targeted antimicrobial peptides.


Acne Vulgaris , Anti-Infective Agents , Deep Learning , Humans , Antimicrobial Peptides , Phylogeny , Anti-Infective Agents/pharmacology , Acne Vulgaris/microbiology , Propionibacterium acnes , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
8.
Microb Pathog ; 189: 106598, 2024 Apr.
Article En | MEDLINE | ID: mdl-38423403

Propionibacterium acnes (P. acnes) is an anaerobic and gram-positive bacterium involved in the pathogenesis and inflammation of acne vulgaris. This study particularly focuses on the antimicrobial effect of Lacticaseibacillus paracasei LPH01 against P. acnes, a bacterium that causes acne vulgaris. Fifty-seven Lactobacillus strains were tested for their ability to inhibit P. acnes growth employing the Oxford Cup and double dilution methods. The cell-free supernatant (CFS) of L. paracasei LPH01 demonstrated a strong inhibitory effect, with an inhibition zone diameter of 24.65 ± 0.27 mm and a minimum inhibitory concentration of 12.5 mg/mL. Among the CFS, the fraction over 10 kDa (CFS-10) revealed the best antibacterial effect. Confocal laser scanning microscopes and flow cytometry showed that CFS-10 could reduce cell metabolic activity and cell viability and destroy the integrity and permeability of the cell membrane. A scanning electron microscope revealed that bacterial cells exhibited obvious morphological and ultrastructural changes, which further confirmed the damage of CFS-10 to the cell membrane and cell wall. Findings demonstrated that CFS-10 inhibited the conversion of triglycerides, decreased the production of free fatty acids, and down-regulated the extracellular expression of the lipase gene. This study provides a theoretical basis for the metabolite of L. paracasei LPH01 as a potential antibiotic alternative in cosmeceutical skincare products.


Acne Vulgaris , Lacticaseibacillus paracasei , Humans , Propionibacterium acnes , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Inflammation/drug therapy , Microbial Sensitivity Tests
9.
J Drugs Dermatol ; 23(2): SF37896s4-SF378969s10, 2024 Feb 01.
Article En | MEDLINE | ID: mdl-38306149

Antibiotics, topical and oral, are a cornerstone in the treatment of acnes vulgaris specifically by targeting the skin bacterium Cutibacterium acnes. Billions of individuals have received antibiotics as part of their treatment resulting in a worldwide pandemic of antibiotic resistance not only for C. acnes but also many other pathogens. With the increasing prevalence of acne and exponentially increasing utilization of antibiotics, prescribers must urgently embrace the notion of antibiotic stewardship to maintain the efficacy of acne treatments while attenuating the rise of resistance. This paper serves as an update on C. acnes resistance to antibiotics commonly employed in the treatment of acne and the necessity of implementing benzoyl peroxide in the treatment regimen as monotherapy or combination antibiotic therapies for overcoming and preventing resistance. J Drugs Dermatol. 2024;23:1(Suppl 2):s4-10.


Acne Vulgaris , Antimicrobial Stewardship , Humans , Drug Resistance, Bacterial , Acne Vulgaris/diagnosis , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Anti-Bacterial Agents , Benzoyl Peroxide/therapeutic use , Propionibacterium acnes
10.
J Cosmet Dermatol ; 23(6): 2156-2169, 2024 Jun.
Article En | MEDLINE | ID: mdl-38406887

BACKGROUND: Acne is a common skin issue that typically occurs during adolescence. It causes long-lasting redness and swelling in the skin. An alternative approach to treating acne could involve using a cosmetic facial mask containing herbal ingredients such as Curcumin and Rosa Damascena extract for its antibacterial properties. AIMS: This study aims to create and try out a peel-off mask gel made from Curcumin and R. Damascena extract. This gel is intended to have the ability to kill bacteria such as Staphylococcus aureus, Escherichia coli, and Propionibacterium acnes and remove dead cells from the skin surface. METHODS: The peel-off mask was made using polyvinyl alcohol (PVA) in 8% and 10% as solidifier. The evaluation of peel-off masks comprises the examination of physiochemical and mechanical aspects. Furthermore, their longevity, effectiveness, and antibacterial properties are also considered. RESULTS: The white color, pleasant smell, and soft texture were the defining features of the peel-off gel mask. The changes in PVA affect the pH level, thickness, and how quickly the peel-off mask dries. The stability test found that the peel-off mask had no significant physical changes when exposed to freezing and thawing. However, there were some differences in color and separation when using the real-time method. A prepared peel-off mask containing 10% PVA and curcumin works best against P. acne. The amount of PVA in the formula affected the physical and chemical qualities, but it did not impact on the antibacterial abilities of the peel-off mask gel. The best formula that gives the best results uses 10% PVA + curcumin. CONCLUSIONS: Using the Curcumin and R. Damascena extract in the creation of the peel-off mask gel ensures its efficacy and safety for skin application.


Acne Vulgaris , Anti-Bacterial Agents , Antioxidants , Curcumin , Plant Extracts , Rosa , Staphylococcus aureus , Curcumin/pharmacology , Curcumin/administration & dosage , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Rosa/chemistry , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Antioxidants/pharmacology , Antioxidants/administration & dosage , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Staphylococcus aureus/drug effects , Propionibacterium acnes/drug effects , Polyvinyl Alcohol/chemistry , Escherichia coli/drug effects , Skin Cream/administration & dosage , Skin/drug effects , Skin/microbiology , Microbial Sensitivity Tests
11.
Spine J ; 24(6): 1034-1045, 2024 Jun.
Article En | MEDLINE | ID: mdl-38365007

BACKGROUND: An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD. PURPOSE: This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut. RESULTS: Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD. CONCLUSIONS: Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age.


Intervertebral Disc Degeneration , Propionibacterium acnes , Humans , Intervertebral Disc Degeneration/epidemiology , Intervertebral Disc Degeneration/microbiology , Risk Factors , Propionibacterium acnes/isolation & purification , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/complications , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Bacterial Infections/complications
13.
Microbiol Spectr ; 12(2): e0283823, 2024 Feb 06.
Article En | MEDLINE | ID: mdl-38197658

Acne vulgaris caused by antibiotic-resistant Cutibacterium acnes (C. acnes) infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the mechanism of phage treatment is inadequate. This research investigates the underlying molecular mechanisms of phage φPaP11-13 attenuating C. acnes-induced inflammation in rat models. We found that rats infected with C. acnes had higher average ear thickness, greater enrichment of inflammatory cells as shown by hematoxylin-eosin (HE) staining, and fewer TUNEL (TdT-mediated dUTP Nick-End Labeling)-positive keratinocytes visualized by IF staining. Moreover, an increase of IGF-1 and IGF-1 receptor (IGF-1r) was detected using the immunohistochemical (IHC) staining method, Western blot (WB), and quantitative real-time PCR (qRT-PCR) when infected with C. acnes, which was decreased after the application of phage φPaP11-13. By applying the IGF-1 antibody, it was demonstrated that the severity of C. acnes-induced inflammation was relevant to the expression of IGF-1. Through WB and qRT-PCR, activation of the PI3K/Akt pathway and a down-regulation of the BAD-mediated apoptosis pathway were discovered after C. acnes infection. Subsequently, it was shown that the activation of the PI3K/Akt pathway against BAD-mediated apoptosis pathway was alleviated after applying phage φPaP11-13. Furthermore, applying the IGF-1r inhibitor, Pan-PI3K inhibitor, and Akt inhibitor reversed the changing trends of BAD induced by C. acnes and phage φPaP11-13. This study demonstrates that one of the critical mechanisms underlying the attenuation of acne vulgaris by phage φPaP11-13 is lysing C. acnes and regulating keratinocyte apoptosis via the PI3K/Akt signaling pathway.IMPORTANCECutibacterium acnes infection-induced acne vulgaris may cause severe physical and psychological prognosis. However, the overuse of antibiotics develops drug resistance, bringing challenges in treating Cutibacterium acnes. Bacteriophages are currently proven effective in MDR (multiple drug-resistant) Cutibacterium acnes, but there is a significant lack of understanding of phage therapy. This study demonstrated a novel way of curing acne vulgaris by using phages through promoting cell death of excessive keratinocytes in acne lesions by lysing Cutibacterium acnes. However, the regulation of this cell cycle has not been proven to be directly mediated by phages. The hint of ternary relation among "phage-bacteria-host" inspires huge interest in future phage therapy studies.


Acne Vulgaris , Bacteriophages , Animals , Rats , Insulin-Like Growth Factor I/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Keratinocytes/metabolism , Keratinocytes/pathology , Acne Vulgaris/microbiology , Propionibacterium acnes/metabolism , Inflammation/metabolism , Apoptosis
14.
Sci Rep ; 14(1): 1521, 2024 01 17.
Article En | MEDLINE | ID: mdl-38233540

Acne vulgaris is a type of chronic skin disorder caused by Propionibacterium acnes (P. acnes). Neutrophil extrinsic traps (NETs) play key role in many types of inflammatory skin diseases. Adipose-derived stem cells (ADSCs) was reported modulate immune responses and neutrophil activity. Here, we explored the potential role of ADSCs and the potential mechanism associated with neutrophil extracellular traps (NETs) in relieving acne vulgaris. In the P. acnes-infected ear skin model, histological staining was used to evaluate the inflammatory infiltration and NET formation in control, P. acnes, and P. acnes + ADSCs groups. Besides, western blot was used to detect the expression levels of cit-H3, MPO, and Nrf2 in ear tissue. In vitro, the immunofluorescence staining of MPO and cit-H3, and SYTOX green staining were performed to measure the NET formation. CCK-8 assay, EdU staining, and wound healing assay were used to detect the proliferation and migration abilities of keratinocytes. ELISA assay was utilized to detect the secretion of inflammatory cytokines. In P. acnes-infected ear skin, ADSC treatment significantly attenuated inflammation and NET formation via activating Nrf2 signaling pathway. In vitro, the conditioned medium of ADSCs reduced the formation of P. acne-induced NETs. Besides, ADSCs could inhibit that the NETs efficiently promoted the proliferation, migration, and inflammatory cytokine secretion of keratinocytes. Our study suggested that ADSCs could attenuate P. acne-related inflammation by inhibiting NET formation. This study provides a novel therapeutic perspective of ADSCs in combating acne vulgaris.


Acne Vulgaris , Extracellular Traps , Humans , Extracellular Traps/metabolism , NF-E2-Related Factor 2/metabolism , Acne Vulgaris/microbiology , Inflammation , Stem Cells/metabolism , Propionibacterium acnes/metabolism
16.
Arthritis Res Ther ; 26(1): 41, 2024 01 31.
Article En | MEDLINE | ID: mdl-38297365

BACKGROUND: Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain. METHODS: Cervical IVD degeneration and discitis was induced in 8-week-old male rats in C3-C6 IVDs through the anterior intervertebral puncture with intradiscal injections of low and high concentrations of P. acnes (P. acnes-L, n = 20 and P. acnes-H, n = 15) or Staphylococcus aureus (S. aureus, n = 15), compared to control (injection with PBS, n = 20). The structural changes in the cervical IVD using micro-CT, histological evaluation, and gene expression assays after MRI scans at 2 and 6 weeks post-modeling. The P. acnes-L induced IVD degeneration model was assessed for cervical spine MRI, histological degeneration, pain-like behaviors (guarding behavior and forepaw von Frey), nerve fiber growth in the IVD endplate region, and DRG TNF-α and CGRP. RESULTS: IVD injection with P. acnes-L induced IVD degeneration with decreased IVD height and MRI T2 values. IVD injection with P. acnes-H and S. aureus both lead to discitis-like changes on T2-weighted MRI, trabecular bone remodeling on micro-CT, and osseous fusion after damage in the cartilage endplate adjacent to the injected IVD. Eventually, rats in the P. acnes-L group exhibited significant nociceptive hypersensitivity, nerve fiber ingrowth was observed in the IVD endplate region, inflammatory activity in the DRG was significantly increased compared to the control group, and the expression of the pain neurotransmitter CGRP was significantly upregulated. CONCLUSION: P. acnes-L was validated to induce cervical IVD degeneration and discogenic pain phenotype, while P. acnes-H induced was identified to resemble septic discitis comparable to those caused by S. aureus infection.


Discitis , Intervertebral Disc Degeneration , Intervertebral Disc , Male , Rats , Animals , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/metabolism , Propionibacterium acnes/metabolism , Discitis/metabolism , Discitis/pathology , Neck Pain/metabolism , Neck Pain/pathology , Calcitonin Gene-Related Peptide/metabolism , Staphylococcus aureus , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/metabolism , Disease Models, Animal
17.
J Cosmet Dermatol ; 23(5): 1777-1799, 2024 May.
Article En | MEDLINE | ID: mdl-38268224

BACKGROUND: Acne vulgaris is a widespread chronic inflammatory dermatological condition. The precise molecular and genetic mechanisms of its pathogenesis remain incompletely understood. This research synthesizes existing databases, targeting a comprehensive exploration of core genetic markers. METHODS: Gene expression datasets (GSE6475, GSE108110, and GSE53795) were retrieved from the GEO. Differentially expressed genes (DEGs) were identified using the limma package. Enrichment analyses were conducted using GSVA for pathway assessment and clusterProfiler for GO and KEGG analyses. PPI networks and immune cell infiltration were analyzed using the STRING database and ssGSEA, respectively. We investigated the correlation between hub gene biomarkers and immune cell infiltration using Spearman's rank analysis. ROC curve analysis validated the hub genes' diagnostic accuracy. miRNet, TarBase v8.0, and ChEA3 identified miRNA/transcription factor-gene interactions, while DrugBank delineated drug-gene interactions. Experiments utilized HaCaT cells stimulated with Propionibacterium acnes, treated with retinoic acid and methotrexate, and evaluated using RT-qPCR, ELISA, western blot, lentiviral transduction, CCK-8, wound-healing, and transwell assays. RESULTS: There were 104 genes with consistent differences across the three datasets of paired acne and normal skin. Functional analyses emphasized the significant enrichment of these DEGs in immune-related pathways. PPI network analysis pinpointed hub genes PTPRC, CXCL8, ITGB2, and MMP9 as central players in acne pathogenesis. Elevated levels of specific immune cell infiltration in acne lesions corroborated the inflammatory nature of the disease. ROC curve analysis identified the acne diagnostic potential of four hub genes. Key miRNAs, particularly hsa-mir-124-3p, and central transcription factors like TFEC were noted as significant regulators. In vitro validation using HaCaT cells confirmed the upregulation of hub genes following Propionibacterium acnes exposure, while CXCL8 knockdown reduced pro-inflammatory cytokines, cell proliferation, and migration. DrugBank insights led to the exploration of retinoic acid and methotrexate, both of which mitigated gene expression upsurge and inflammatory mediator secretion. CONCLUSION: This comprehensive study elucidated pivotal genes associated with acne pathogenesis, notably PTPRC, CXCL8, ITGB2, and MMP9. The findings underscore potential biomarkers, therapeutic targets, and the therapeutic potential of agents like retinoic acid and methotrexate. The congruence between bioinformatics and experimental validations suggests promising avenues for personalized acne treatments.


Acne Vulgaris , Computational Biology , Humans , Acne Vulgaris/genetics , Acne Vulgaris/drug therapy , Acne Vulgaris/diagnosis , Acne Vulgaris/immunology , Genetic Markers , Gene Regulatory Networks , Protein Interaction Maps/genetics , Gene Expression Profiling , Precision Medicine , Methotrexate/therapeutic use , Tretinoin/administration & dosage , MicroRNAs/genetics , MicroRNAs/metabolism , Propionibacterium acnes , HaCaT Cells , Databases, Genetic
18.
Photodiagnosis Photodyn Ther ; 45: 103928, 2024 Feb.
Article En | MEDLINE | ID: mdl-38070633

BACKGROUND: The treatment of acne vulgaris is often challenging due to the antibiotic resistance frequently observed in Cutibacterium acnes (C.acnes), a prevalent bacterium linked to this condition. OBJECTIVE: The objective of this research was to examine the impact of curcumin photodynamic therapy (PDT) on the survival of C.acnes and activity of biofilms produced by this microorganism. METHODS: Following the Clinical and Laboratory Standards Institute (CLSI) guidelines, we assessed the drug sensitivity of 25 clinical C.acnes strains to five antibiotics (erythromycin, clindamycin, tetracycline, doxycycline, minocycline) and curcumin by implementing the broth microdilution technique. In addition, we established C.acnes biofilms in a laboratory setting and subjected them to curcumin-PDT(curcumin combined with blue light of 180 J/cm2). Afterwards, we evaluated their viability using the XTT assay and observed them using confocal laser scanning microscopy. RESULTS: The result revealed varying resistance rates among the tested antibiotics and curcumin, with erythromycin, clindamycin, tetracycline, doxycycline, minocycline, and curcumin exhibiting resistance rates of 72 %, 44 %, 36 %, 28 %, 0 %, and 100 %, respectively. In the curcumin-PDT inhibition tests against four representative antibiotic-resistant strains, it was found that the survival rate of all strains of planktonic C. acnes was reduced, and the higher the concentration of curcumin, the lower the survival rate. Furthermore, in the biofilm inhibition tests, the vitality and three-dimensional structure of the biofilms were disrupted, and the inhibitory effect became more significant with higher concentrations of curcumin. CONCLUSION: The results emphasize the possibility of using curcumin PDT as an alternative approach for the treatment of C.acnes, especially in instances of antibiotic-resistant variations and infections related to biofilms.


Acne Vulgaris , Curcumin , Photochemotherapy , Humans , Clindamycin/pharmacology , Clindamycin/therapeutic use , Doxycycline/pharmacology , Doxycycline/therapeutic use , Curcumin/pharmacology , Curcumin/therapeutic use , Minocycline/pharmacology , Minocycline/therapeutic use , Microbial Sensitivity Tests , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Acne Vulgaris/drug therapy , Anti-Bacterial Agents/therapeutic use , Erythromycin/pharmacology , Erythromycin/therapeutic use , Tetracycline/pharmacology , Tetracycline/therapeutic use , Biofilms , Propionibacterium acnes
19.
J Shoulder Elbow Surg ; 33(3): 618-627, 2024 Mar.
Article En | MEDLINE | ID: mdl-38072031

BACKGROUND: Periprosthetic joint infections occur in 1%-4% of primary total shoulder arthroplasties (TSAs). Cutibacterium acnes is the most commonly implicated organism and has been shown to persist in the dermis despite use of preoperative antibiotics and standard skin preparations. Studies have shown decreased rates of cultures positive for C acnes with use of preoperative benzoyl peroxide or hydrogen peroxide (H2O2), but even with this positive deep cultures remain common. We sought to determine whether an additional application of H2O2 directly to the dermis following skin incision would further decrease deep culture positivity rates. METHODS: We performed a randomized controlled trial comparing tissue culture results in primary TSA in patients who received a standard skin preparation with H2O2, ethanol, and ChloraPrep (CareFusion, Leawood, KS, USA) vs. an additional application of H2O2 to the dermis immediately after skin incision. Given the sexual dimorphism seen in the shoulder microbiome regarding C acnes colonization rates, only male patients were included. Bivariable and multivariable analyses were performed to compare rates of positive cultures based on demographic and surgical factors. RESULTS: Dermal cultures were found to be positive for C acnes at similar rates between the experimental and control cohorts for the initial (22% vs. 28%, P = .600) and final (61% vs. 50%, P > .999) dermal swabs. On bivariable analysis, the rate of positive deep cultures for C acnes was lower in the experimental group, but this difference was not statistically significant (28% vs. 44%, P = .130). However, patients who underwent anatomic TSA were found to have a significantly greater rate of deep cultures positive for C acnes (57% vs. 28%, P = .048); when controlling for this on multivariable analysis, the experimental cohort was found to be associated with significantly lower odds of having positive deep cultures (odds ratio, 0.37 [95% confidence interval, 0.16-0.90], P = .023). There were no wound complications in either cohort. CONCLUSIONS: An additional H2O2 application directly to the dermis following skin incision resulted in a small but statistically significant decrease in the odds of having deep cultures positive for C acnes without any obvious adverse effects on wound healing. Given its cost-effectiveness, use of a post-incisional dermal decontamination protocol may be considered as an adjuvant to preoperative use of benzoyl peroxide or H2O2 to decrease C acnes contamination.


Arthroplasty, Replacement, Shoulder , Gram-Positive Bacterial Infections , Shoulder Joint , Surgical Wound , Humans , Male , Hydrogen Peroxide , Arthroplasty, Replacement, Shoulder/adverse effects , Surgical Wound/complications , Shoulder Joint/surgery , Shoulder Joint/microbiology , Gram-Positive Bacterial Infections/microbiology , Skin/microbiology , Benzoyl Peroxide/therapeutic use , Shoulder/surgery , Propionibacterium acnes , Dermis/microbiology
20.
Intern Med ; 63(2): 299-304, 2024 Jan 15.
Article En | MEDLINE | ID: mdl-37258161

A 77-year-old Japanese woman with mediastinal lymphadenopathy and uveitis was diagnosed with sarcoidosis. The bacterial flora in biopsied samples from mediastinal lymph nodes was analyzed using a clone library method with Sanger sequencing of the 16S rRNA gene, and Streptococcus gordonii (52 of 71 clones) and Cutibacterium acnes (19 of 71 clones) were detected. No previous study has conducted a bacterial floral analysis using the Sanger method for the mediastinal lymph node in sarcoidosis, making this case report the first to document the presence of S. gordonii and C. acnes in the mediastinal lymph node of a patient with sarcoidosis.


Lymphadenopathy , Sarcoidosis , Female , Humans , Aged , Streptococcus gordonii/genetics , RNA, Ribosomal, 16S/genetics , Lymph Nodes/pathology , Sarcoidosis/complications , Sarcoidosis/diagnosis , Lymphadenopathy/pathology , Propionibacterium acnes/genetics , Clone Cells/pathology
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