Ozone therapy for skin diseases: Cellular and molecular mechanisms.

Ozone is a highly reactive oxidant molecule consisting of triatomic oxygen atoms. Ozone therapy can be achieved using ozonated hydrotherapy, ozonated oil, ozone autohemotherapy, and other innovative dosage forms of ozone products. Ozone is frequently used as a complementary therapy for various cutaneous diseases, including infectious skin diseases, wound healing, eczema, dermatitis, psoriasis, axillary osmidrosis, diabetic foot, and pressure ulcers. In addition, several studies have reported the superior potential of ozone therapy for improving skin and gut microbiomes, as well as antitumour and antiaging treatment. Ozone therapy is an emerging treatment strategy that acts via complex mechanisms, including antioxidant effects, immunomodulatory capacity, and modulation of local microcirculation. Studies assessing the mechanism of ozone have gradually expanded in recent years. This review article aims to summarise and explore the possible molecular biological mechanisms of ozone in cutaneous diseases and provide compelling theoretical evidence for the application of ozone in cutaneous diseases.

Mechanisms of ultraviolet-induced melasma formation: A review.

Melasma, a pigmentation disorder, commonly occurs in exposed skin areas and can be attributed to several factors. Ultraviolet radiation (UVR) is the primary factor that induces and aggravates melasma. Considering gene expression, exposed skin areas experience abnormal gene expression, involving melanin metabolism, oxidative stress, impaired skin barrier function, and abnormal composition of nerve factors. From a histological perspective, UVR can cause basement membrane collapse, melanocyte sinking, and disorders of skin lipid metabolism. Emerging therapies have focused on these pathological alterations in melasma, including platelet-rich plasma, mesotherapy, and phytochemicals. Understanding the role of UVR in the development of melasma can facilitate early prevention and highlight the future direction of melasma treatment.

Downregulated Serum Exosomal miR-451a Expression Correlates With Renal Damage and Its Intercellular Communication Role in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.

Ozonated autohemotherapy elevates PPAR-γ expression in CD4+ T cells and serum HDL-C levels, a potential immunomodulatory mechanism for treatment of psoriasis.

Psoriasis is widely accepted as a metabolic syndrome with significantly abnormal lipid metabolism and high level of blood lipids that induce a persistent low level of inflammatory condition in patients. T cell mediated immune response plays a critical role in the occurrence and persistence of psoriasis lesions. Hyperlipidemia and associated inflammatory reaction are believed to be the major risk factors for the onset and recurrence of psoriasis. Peroxisome proliferator activated receptor-gamma (PPAR-γ) is known to effectively regulate the blood lipid level and inhibit inflammatory reaction. In this study, we examined the efficacy of ozonated autohemotherapy (OAHT) treatment on psoriatic patients by evaluating the Psoriasis Area and Severity Index (PASI) score and blood lipid level. In addition, PPAR-γ expression level and the correlation of PASI scores or blood lipid level with the PPAR-γ expression were also assessed to determine the psoriasis-associate targets of OAHT. We found that OAHT significantly decreased patients' PASI scores and increased blood HDL-C level. Furthermore, we found that PPAR-γ expression in CD4+ T cells from psoriasis patients was significantly lower than healthy controls, and OAHT treatment increased the expression of PPAR-γ. In conclusion, OAHT attenuates the psoriatic severity in patients and increased blood HDL-C level, which may be associated with increased PPAR-γ expression. Our data suggests that OAHT is an effective treatment in psoriasis and deserves further evaluations in clinical applications.

Ozone Therapy Attenuates NF-κB-Mediated Local Inflammatory Response and Activation of Th17 Cells in Treatment for Psoriasis.

Ozone therapy has been widely used to treat many skin diseases, including infections, allergic dermatosis, and skin ulcers. However, its efficacy as a treatment for psoriasis is unclear. In this study, we explored the clinical efficacy and the underlying molecular mechanisms of ozone therapy on psoriasis. We found that topical ozone treatment significantly decreased patients' psoriasis area and severity index (PASI) scores and the expression of psoriasis-associated cytokines in their peripheral blood CD4+ T cells. In the IMQ-induced psoriasis mouse model, topical ozone treatment significantly inhibited the formation of IMQ-induced psoriasis-like lesions and the expression of psoriasis-associated inflammatory factors. High-throughput sequencing confirmed that IMQ-induced activation of toll-like receptor 2 (TLR2)/ nuclear factor-κB (NF-κB) signaling pathway was significantly suppressed in psoriasis-like lesions after topical ozone treatment. Furthermore, the activation of spleen T helper (Th) 17 cells was blocked in the mouse model; this was associated with the downregulation of cytokines and NF-κB pathways upon topical ozone treatment. Ozone therapy can attenuate local inflammatory reactions and the activation of Th17 cells in psoriasis by inhibiting the NF-κB pathway. Our results show that ozone therapy is effective in treating psoriasis. We recommend further evaluations for its clinical applications.

Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis.

Psoriasis is a chronic immune-mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL-17 and IL-22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down-regulated KRT6 mRNA and protein expression while up-regulated KRT10 mRNA and protein expression within IL-22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expression of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63-mediated transcription of KRT10, therefore improving psoriasis.

Topical ozone therapy restores microbiome diversity in atopic dermatitis.

BACKGROUND: Staphylococcus aureus (S. aureus) accounts for 90% of the microbiome in atopic dermatitis (AD) lesions and plays a role in disease flare-ups and worsens disease outcome. Ozone treatment can improve AD conditions by its bactericidal effect on S. aureus. OBJECTIVE: To study the effects of topical ozone therapy on microbiome diversity in AD lesions and explore potential probiotic pathogens correlated with AD progression. METHODS: Patients with moderate to severe bilateral skin lesions in AD were recruited. Randomized split sides were performed. One side was treated with ozone hydrotherapy followed by ozonated oil; while the contralateral side with tap water and basal oil. Patients' SCORAD scores and modified EASI were recorded before and after treatments. The microbiological compositions in targeting sites were determined using 16S rDNA sequencing. RESULTS: After three-day ozone therapy, patients showed a significant decrease in SCORAD scores and inflammatory cell infiltration in AD lesions. The micro-ecological diversity was higher in the non-lesional as compared with lesional areas (p < 0.05), which was also negatively correlated with the severity of AD (r = -0.499, p < 0.05). The proportion of S. aureus in AD lesions was positively correlated with the severity of AD (r = 0.564, p = 0.010), which was decreased after ozone treatment (p = 0.07). Ozone therapy showed an increase in microbiological diversity with a significant increase in the proportion of Acinetobacter (p < 0.05). CONCLUSION: Topical ozone therapy is highly effective for treatment for AD. It can change the proportional ratio of Staphylococcus and Acinetobacter, thereby restoring the microbiological diversity in AD lesions.

Microbiosis in pathogenesis and intervention of atopic dermatitis.

Atopic dermatitis (AD) is a chronic, non-contagious, inflammatory skin disorder characterized by relapsing eczematous lesions. Its pathogenesis remains incompletely understood. The current evidence has emerged to show that skin and gut microbiome play critical roles in the pathogenesis and progression of AD. Skin mircrobiome mainly refers to skin commensal organisms that promote normal immune system functions and prevent the colonization of pathogens; while gut microbiome can modulate immunologic, metabolic and neuroendocrine functions. With the current knowledge of microbiome effects on the onset of the disease, there are evolving multifarious interventions targeting microbiome for the treatment of AD. In this report, we have reviewed the critical roles of microbiosis in the pathogenesis of AD, summarized potential mechanisms mediated by microbiosis and aimed to enlighten a theoretical basis for its therapeutic applications in the treatment of AD.

Mechanisms of action involved in ozone-therapy in skin diseases.

Ozone-therapy initially applied in medicine by an empirical approach, has now reached a new stage where most of the biological mechanisms of ozone action have been clarified, that refers to antimicrobial effects, immunoregulation, antioxidant defenses and epigenetic modification. Current ozone medical preparation in dermatology mainly classified as ozone hydrotherapy, ozonated oil externally used and ozone autohemotherapy (OAHT). Admittedly, ozone is widely used in various fields against gram-negative and gram-positive bacteria, viruses, and fungi. More recently, great progress has been obtained in wound healing which is a multiphase process that consists of three overlapping but distinct stages: inflammation, tissue proliferation and remodeling. While the exact mechanisms of ozone-therapy still remain unclear. Therefore, more evidence is required before ozone can be presented as a promising method for the management and prevention of various skin diseases. In this review, we review the application status of ozone in dermatology and summarize possible mechanisms of ozone-therapy on skin diseases, aims to shed a light on providing a series of theoretical basis for its applications.

[Experimental study on the effect of ginkgo bioba extract on the expression of heme oxygenase-1 in bronchial asthma].

AIM: To explore the effect of the ginkgo bioba extract on the expression of heme oxygenase-1 (HO-1) in bronchial asthma. METHODS: 30 guinea pigs were randomly divided into 3 groups (n = 10): (1) Normal control group; (2) Asthmatic group; (3) Therapeutic group. Blood carbon monoxide Hb (COHb) percent value, Airway resistance and eosinophilic inflammation of airway wall were observed, the expression of HO-1 in lung tissue were observed by immunohistochemical staining. RESULTS: The expression of HO-1 was mainly located in airway epithelium in these 3 groups, the optical densities were 0.170 +/- 0.020, 0.707 +/- 0.058, 0.397 +/- 0.034, respectively. The asthmatic group showed higher optical densities than that of the normal control group (P < 0.01), and the therapeutic group showed lower optical density than asthmatic group (P < 0.01). CONCLUSION: The expression of HO-1 is inhibited significantly by the treatment of the ginkgo bioba extract, which may be one of the mechanism for treating asthma by ginkgo bioba extract.