The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production of pro-inflammatory interleukin (IL)-6 cytokine. Topical application of butyric acid alone or S. epidermidis with glycerol remarkably ameliorated the UVB-induced IL-6 production. In vivo knockdown of short-chain fatty acid receptor 2 (FFAR2) in mouse skin considerably blocked the probiotic effect of S. epidermidis on suppression of UVB-induced IL-6 production. These results demonstrate that butyric acid in the metabolites of fermenting skin probiotic bacteria mediates FFAR2 to modulate the production of pro-inflammatory cytokines induced by UVB.
Collagen type I is a key structural component of dermis tissue and is produced by fibroblasts and the extracellular matrix. The skin aging process, which is caused by intrinsic or extrinsic factors, such as natural aging or free radical exposure, greatly reduces collagen expression, thereby leading to obstructed skin elasticity. We investigated the effective fermentation of Cetearyl isononanoate (CIN), a polyethylene glycol (PEG) analog, as a carbon source with the skin probiotic bacterium Staphylococcus epidermidis (S.epidermidis) or butyrate, as their fermentation metabolites could noticeably restore collagen expression through phosphorylated extracellular signal regulated kinase (p-ERK) activation in mouse fibroblast cells and skin. Both the in vitro and in vivo knockdown of short-chain fatty acid (SCFA) or free fatty acid receptor 2 (FFaR2) considerably blocked the probiotic effect of S. epidermidis on p-ERK-induced collagen type I induction. These results demonstrate that butyric acid (BA) in the metabolites of fermenting skin probiotic bacteria mediates FFaR2 to induce the synthesis of collagen through p-ERK activation. We hereby imply that metabolites from the probiotic S. epidermidis fermentation of CIN as a potential carbon source could restore impaired collagen in the dermal extracellular matrix (ECM), providing integrity and elasticity to skin.
The global COVID-19 pandemic has highlighted the critical role of vaccines in controlling infectious diseases, with liposome-based formulations emerging as a pivotal advancement in vaccine technology. Liposomes are spherical vesicles composed of lipid bilayers that serve as drug delivery systems and versatile adjuvants, enhancing vaccine efficacy through improved antigen stability, targeted delivery, and immunogenicity. This review explores the potential of liposomes as adjuvants in both mRNA and protein subunit SARS-CoV-2 vaccines, detailing their composition and dual impact on innate and adaptive immune responses. Notably, liposome-based mRNA vaccines, such as those developed by Pfizer and Moderna, have demonstrated high efficacy by utilizing lipid nanoparticles to encapsulate mRNA and stimulate antigen-presenting cells, thereby inducing robust immune responses. Despite their advantages, challenges remain, including the optimization of lipid compositions and the mitigation of adverse immune effects. This review also examines the broad applications of liposomes in nanomedicine — from cancer therapy to antifungal treatments — and their potential for future vaccine development. By bridging the gap between engineering and immunology, the study of liposomes underscores their transformative potential in addressing current and emerging global health challenges.
Background: Limited attention paid to acne vulgaris has hindered progress in studying its pathological mechanisms and developing new treatments. While direct evidence confirming Cutibacterium acnes (C. acnes) as the initial trigger of acne vulgaris is scarce, the bacterium clearly drives inflammation within acne lesions. Material and methods: Mass spectrometric analysis demonstrated that C. acnes lipase digested triglycerides into various fatty acids, which increased sebum production in sebocytes. The secretory lipase was selected as an immunogenic antigen to generate antibodies in mice. Serum from mice vaccinated with C. acnes lipase was used to assess antibody titers via test strips. Pro-inflammatory interleukin-6 (IL-6) and macrophage inflammatory protein-2 (MIP-2) expression were measured by enzyme-linked immunosorbent assay. Passive immunization with neutralization antibodies to lipase was conducted by administering anti-lipase serum co-cultured with C. acnes. Results: Palmitic acid, a lipase-derived fatty acid, was identified as a major pro-inflammatory stimulus in sebocytes, confirming the central role of lipase in acne inflammation. Mice vaccinated with C. acnes lipase showed protection against C. acnes-induced inflammation in an ear model. Therefore, neutralization antibodies to lipase significantly reduced C. acnes-induced production of pro-inflammatory IL-6 and MIP-2. Conclusions: The C. acnes secretory lipase is a key virulence factor contributing to acne inflammation. Vaccination with C. acnes lipase significantly reduced bacterial colonization and the production of pro-inflammatory IL-6 and MIP-2. These findings support the potential of C. acnes lipase-targeted vaccines as a novel, antigen-specific strategy for both the treatment and prevention of acne vulgaris.
Background: The Coronavirus Disease 2019 (COVID-19) pandemic has highlighted the need to upgrade vaccine strategies. DNA vaccines are advantageous because of their stability and ease of large-scale production; however, they often require adjuvants to boost immune response. Liposomal adjuvants have emerged as effective immune response enhancers, offering efficient delivery and compatibility with biological systems. This study evaluated the immune response induced by a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike protein-encoding DNA vaccine formulated with various liposome adjuvants in mice. Material and methods: The interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-a) mRNA expression levels were analyzed by reverse transcription-quantitative polymerase chain reaction. Flow cytometry was conducted to characterize leukocyte populations and assess immune activation status. Five target cell surface markers were analyzed in this study: CD4+ T, CD8+ T, CD11b+, CD14+, and CD45+ leukocytes, along with their corresponding detected cell types. Results: Among the tested formulations, the PEI25k : DOTAP : cholesterol (2 : 1 : 1) combination showed the most significant immunostimulatory effect. This formulation induced the lowest expression levels of IL-6 (0.17 ± 0.01) and TNF-a (0.25 ± 0.01) mRNAs in the treatment groups; furthermore, flow cytometry revealed robust activation of both adaptive and innate immune subsets, with an increase in CD4+ (44.00 ± 1.00), CD8+ (40.00 ± 1.00), CD11b+ (50.00 ± 2.00), CD14+ (42.00 ± 2.000), and CD45+ (29.00 ± 1.00) T cell populations. These results demonstrate an integrated immune response characterized by strong T cell activation, myeloid engagement, and recruitment of a broad leukocyte population, indicating balanced immunity with reduced inflammation risk. Conclusions: The PEI25k : DOTAP : cholesterol (2 : 1 : 1) formulation has high potential as a liposome-based adjuvant for enhancing the immunogenicity of DNA vaccines. The findings of this study support its suitability for further development as a potential adjuvant candidate, particularly for improving DNA vaccine delivery and immunogenicity against SARS-CoV-2.