The apoptotic effect of ozone therapy on mitochondrial activity of highly metastatic breast cancer cell line MDA-MB-231 using in vitro approaches

Ozone(O) gas is the triatomic state of oxygen and it is used as a disinfection agent due to its strong oxidizing effect, since its discovery in the mid-nineteenth century. Ozone therapy is also an alternative therapeutic approach for some diseases like circulatory disorders, AIDS, asthma, cardiovascular diseases, and certain types of cancer by increasing the oxygen levels in the blood by external addition of ozone to the body. In this study, the therapeutic potential of ozone therapy was examined by inhibiting the growth of breast cancer cells in a dose-dependent procedure. Ozone concentrations varying from 5 to 20 μg/ml were applied to the MDA-MB-231, human breast adenocarcinoma and HUVEC, human umbilical vein endothelium, cell lines, and MDA cells demonstrated an increased rate of death while its migration potential decreases. RT-PCR analysis showed mRNA expression levels of pro-apoptotic genes demonstrated higher folds in MDA cells after 10 μg/ml treatment. In the same context,Annexin V/PI and cell cycle analysis also concluded that ozone therapy causes apoptotic cell death on breast tumor cells. The use of ozone therapy for cancer treatment requires further and extensive research. However, this research has shown that ozone therapy is a promising source for cancer treatment in a way by inhibiting the proliferation of breast tumor cells.

Fundamentals of the Use of Ozone Therapy in the Treatment of Aesthetic Disorders: A Review

Considering the great interest of many professionals in the foundation that guides the effective use of ozone therapy in the treatment of aesthetic disorders, this study aims to define the physiological and practical aspects of using the oxygen-ozone mixture to solve aesthetic problems. Exploratory research was carried out, presented in a narrative review, to highlight the action of ozone therapy in the treatment of aesthetic affections. The review explored scientific articles, books, theses, and dissertations published and available in the following databases: MEDLINE (Medical Literature Analysis and Retrieval System Online), PubMed (National Library of Medicine), SCIELO (Scientific Electronic Library Online), and LILACS (Latin Literature American and the Caribbean in Health Sciences). In addition, elements that characterize the authors’ clinical experience on ozone therapy in various aesthetic treatment protocols were added. We found several reports in the literature that justify the use of ozone and its different therapeutic modalities in various aesthetic affections, mainly in the treatment of localized fat, cellulite, rejuvenation, skin tissue repair, acne, dyschromia, and others. Through its various therapeutic modalities, we conclude that ozone therapy has added a lot to aesthetic procedures, mainly for its effective supporting action or as the main agent of critical physiological changes to enhance clinical results when treating aesthetic conditions.

Medical ozone alleviates acute lung injury by enhancing phagocytosis targeting NETs via AMPK/SR-A1 axis

Acute lung injury(ALI)linked to sepsis has a high mortality rate,with limited treatment options available.In recent studies,medical ozone has shown the potential to alleviate inflammation and infection.Here,we aimed to evaluate therapeutic potential of medical ozone in a mouse model of the sepsis-induced ALI by measuring behavioral assessments,lung function,and blood flow.Protein levels were quantified by Western blotting.In vitro,we performed experiments on bone marrow-derived macrophages(BMDMs)to investigate the effect of adenosine monophosphate(AMP)-activated protein kinase(AMPK)inhibitors and agonists on their phagocytic activity.The results showed that medical ozone significantly improved the survival rate,ameliorated lung injury,and enhanced lung function and limb microcirculation in mice with ALI.Notably,medical ozone inhibited the formation of neutrophil extracellular traps(NETs),a crucial factor in the ALI development.Additionally,medical ozone counteracted the elevated levels of tissue factor,matrix metalloproteinase-9,and interleukin-1β.In the ALI mice,the effects of ozone were abolished,and BMDMs showed an impaired capacity to engulf NETs following the Sr-a1 knockout.Under normal physiological conditions,the administration of an AMPK antagonist showed similar effects on the Sr-a1 knockout,significantly inhibiting the phagocytosis of NETs by BMDMs.In contrast,AMPK agonists enhanced this phagocytic process.In conclusion,medical ozone may alleviate the sepsis-induced lung injury through the AMPK/SR-A1 pathway,thereby enhancing the phagocytosis of NETs by macrophages.

Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study

AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haemato- chemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS: The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O3-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (P <0.05 at 12 months). None of the treated patients experienced a loss in visual acuity in their study eye at 6 and 12 months, compared to 16% and 40 % of patients in the control group who lost 2 lines or more at 6 months and 12 months respectively (P <0.05 treated vs control group)). Major ozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, P <0.05) and an increase in Biological Antioxidant Potential plasma values (2100±34.8 micromoles/ C vitamin after 12 months compared to the baseline value of 1610±36.2, P <0.05) in the treated patients when compared to the control group. This data suggests that major ozonated autohaemotherapy may exert a role in reducing oxidative stress by endogenously stimulating the production of antioxidant molecules. CONCLUSION: The results of this study suggests that major ozonated autohaemotherapy could be a safe and effective therapeutic option for high-risk patients with dry AMD, and that a series of such treatments could improve the natural course of AMD.

The Usage of Laser Doppler Flowmetry for Evaluation of the Efficiency of Ozone-Containing Drugs for External Use

Ozone-containing drugs for external use are the new trend in applying of medical ozone-oxygen mixture. For the last few years the majority of manufacturer countries have produced wide lines of ozone-containing cosmetics, which were presented in various ozone therapeutic congresses. Its properties are used in dermato-cosmetology for correction of the changes associated with aging, promoting regeneration, shortening the recovery period after surgeries or chemical peelings. The article presents the results of LDF （laser Doppler flowmetry） study of skin＇s blood dynamics in response to applying cosmetic gels containing different amounts of active oxygen in the form of ozonides, Comparative analysis of the three-patient groups allowed us to draw a conclusion about the accumulating stimulating effect of the ＂Ozodermis＂ 10% cream on skin＇s microcirculation, which makes it perspective for use as in healthy people for improving one＇s skin condition, as well as in people suffering from diseases, the key roles in pathogenesis of which are disorders in the skin＇s microcirculation （exampli gratia： vasculitis, severe forms of atopic dermatitis）.

Condition Metabolic Balance Disturbance in Patients with Cor Pulmonale： Prevalence, Diagnosis, Risk Factors

To study the risk factors for the development of cor pulmonale （CP） in patients with chronic pulmonary diseases in the Republic of Uzbekistan, the disbalance in parameters of stable metabolites oxides of the nitrogen （SMNO）, of blood oxygen saturation （SaO2）, of respiratory function and on lipid peroxidation of cell membrane were measured. The authors evaluated the effect of base therapy and ozone therapy （OT） in patients with CP. Basis therapy and OT resulted in good parameters of SMNo, SaO2 and metabolic activeness of cell, significant positiveness of hypoxemia and parameters of pulmonary ventilation ability and hemodynamics of pulmonary arteria.

AMPK activation by peri-sciatic nerve administration of ozone attenuates CCl-induced neuropathic pain in rats

Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeu- tics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical aUodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C y, N-methyI-D-aspartate receptor, and extracellular signal-regulated kinase in a chronic constriction injury （CCI） model in rat sciatic nerve. Meanwhile, ozone significantly suppressed CCI-induced activation of spinal microgUa. More importantly, the anti-nociceptive effect of ozone depended on the activation of 5＇-adenosine monophosphate （AMP）-activated protein kinase （AMPK）, which was proved by the fact that the phosphorylated AMPK level increased during the ozone therapy and AMPK antagonist abolished the effect of ozone in vivo and in vitro. In addition, direct injection of AMPK agonist could replicate the anti-nociceptive effect of ozone in CCI rats. In conclusion, our observations indicate that peri-sciatic nerve injection of ozone activates AMPK to attenuate CCI-induced neuropathic pain.

醒脑开窍针法对急性缺血性脑卒中患者的临床疗效及预后预警模型建立

ObjectiveTo explore the clinical effectiveness of xingnao kaiqiao (regaining consciousness and opening orifice) acupuncture therapy for patients with acute ischemic stroke, and establish a prediction model for prognosis for the target population through Logistic regression analysis.MethodsNinety-six patients with acute ischemic stroke were randomly assigned to either an ozone therapy group or an ozone therapy plus xingnao kaiqiao acupuncture group (OA group) with a 1:1 ratio. The patients in the ozone group was treated with ozone therapy, and those in the OA group were treated with acupuncture at Nèiguān (内关PC6), Shuĭgōu (水沟GV26), Sānyīnjiāo (三阴交SP6), lower Jíquán (下极泉Extra, lower HT1), Wĕizhōng (委中BL40) and Chĭzé (尺泽LU5) on the basis of the treatment as the ozone therapy group. The treatment was given once daily for 7 days as a session and 3 consecutive sessions were required. Before treatment and 48 h after treatment, the serological indicators (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α] and hypersensitive C-reactive protein [hs-CRP]) were tested. Using the National Institute of Health stroke scale (NIHSS) score and Montreal cognitive assessment (MoCA) score, the neurological and cognitive functions of patients were assessed. The clinical efficacy was evaluated with the modified Rankin scale, and the incidence of adverse effects was analyzed statistically in two groups. The multivariate Logistic regression analysis was adopted to detect the risk factors of the prognosis in patients and the nomographic prediction model was established.Results(1) clinical therapeutic effect: after treatment, the levels of IL-6, TNF-α and Hs-CRP in the OA group were significantly lower than that in the ozone group (all P < 0.05). After treatment, compared with the ozone therapy group, NIHSS score was lower and the scores of BI and MoCA were significantly higher in the OA group (all P < 0.05). The total effective rate of the OA group was 91.67%, higher than that of the ozone therapy group (62.50%, P < 0.05). The incidence of adverse effects in the OA group was lower when compared with that in the ozone group (P < 0.05);(2) establishment of prediction model for prognosis: age, history of diabetes, cardiogenic cerebral embolism, high density lipoprotein-cholesterol (HDL-C), white blood cell (WBC) and treatment methods were independent risk factors of the unfavorable prognosis for the patients with acute stroke. The established model had sound accuracy for prediction of prognosis.ConclusionXingnao kaiqiao acupuncture was effective on acute ischemic stroke, and the prognosis of this therapy was increased significantly when combined with the ozone therapy. The preventive measures should be set up for patients with risk factors, e.g. advanced age, diabetes, cardiogenic cerebral embolism, low HDL-C and abnormal WBC, in order to further reduce the risk of unfavorable prognosis in patients with acute stroke.