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 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.

[Effect of ozone on Staphylococcus aureus colonization in patients with atopic dermatitis].

OBJECTIVE: To verify the effect of ozone on Staphylococcus aureus (S. aureus) colonization in patients with atopic dermatitis (AD) and its correlation with the patient's status.
 Methods: A total of 12 patients with moderate or severe AD, aged from 6 to 65 years, were recruited from outpatient of the Third Xiangya Hospital. The treatment sides were showered with ozonated water and smeared with ozonated oil for 7 days (twice a day), while the control sides were washed with warm running water and smeared with base oil. At different time points, the severity scoring of atopic dermatitis (SCORAD) scores, sleep and pruritus scores were assessed and compared between the two sides. Meanwhile, plate cultivation was used to quantitatively detect the changes of S. aureus colonization in skin lesions.
 Results: After 7 days treatment, erythema and pimples were decreased in the treatment sides. The clear skin texture, smooth skin, improved skin lesions were also observed by dermoscopic examination. The results of reflectance confocal microscopy (RCM) demonstrated that the parakeratosis was improved, the structures were clearer, and the inflammatory cells infiltration was reduced after ozone treatment for 7 days. After ozone treatment for 3 and 7 days, the S. aureus colonization in the treatment sides decreased by (75.55±21.81)% and (97.24±2.64)% respectively. Compared to that of control sides, the percentage of S. aureus colony after ozone treatment for 7 days decreased significantly (P<0.01). After ozone treatment for 7 days, the SCORAD scores, sleep and pruritus scores were significantly decreased (all P<0.01). There was a linear correlation between the decreasing percentage of S. aureus colony and the declining percentage of SCORAD scores in AD patients.
 Conclusion: Topical ozone therapy can effectively reduce S. aureus colony in skin lesions and alleviate the severity of AD patients with moderate to severe degree.