1.Ozonated triglyceride protects against septic lethality via preventing the activation of NLRP3 inflammasome.
Dan WANG ; Yuanhong LIU ; Xiule ZONG ; Siyu YAN ; Jianyun LU
Journal of Central South University(Medical Sciences) 2023;48(6):809-820
OBJECTIVES:
Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism.
METHODS:
Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting.
RESULTS:
Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD.
CONCLUSIONS
Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.
Animals
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Humans
;
Mice
;
Caspase 1
;
Cytokines
;
Disease Models, Animal
;
Inflammasomes
;
Lung Injury
;
NLR Family, Pyrin Domain-Containing 3 Protein
;
Ozone/therapeutic use*
;
Sepsis/drug therapy*
2.Effect of ozone oil for prevention and treatment of sorafenib-induced hand-foot skin reactions: a randomized controlled trial.
Xiaowei CHEN ; Yiyue JIANG ; Ying ZHANG ; Wencong DAI ; Rong FAN ; Xie WENG ; Peng HE ; Feifei YAN ; Yabing GUO
Journal of Southern Medical University 2020;40(10):1488-1492
OBJECTIVE:
To compare the effects of medical ozone oil and urea ointment for prevention and treatment of hand-foot skin reaction (HFSR) caused by sorafenib in patients with hepatocellular carcinoma (HCC).
METHODS:
A total of 99 patients diagnosed with advanced HCC according to National Comprehensive Cancer Network (NCCN) who were scheduled to receive sorafenib treatment for the first time were enrolled in this study between April, 2018 and January, 2020. The patients were randomized into medical ozone oil group (
RESULTS:
Eight patients were excluded for poor compliance or protocol violations, leaving a total of 91 patients for analysis, including 44 in medical ozone oil group and 47 in urea ointment group. Sixteen (36.4%) of patients in ozone oil group developed HFSR, a rate significantly lower than that in urea ointment group (57.4%;
CONCLUSIONS
Medical ozone oil can significantly reduce the incidence and severity of HFSR to improve the quality of life of HCC patients receiving sorafenib treatment.
Antineoplastic Agents/therapeutic use*
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Carcinoma, Hepatocellular/drug therapy*
;
Hand-Foot Syndrome/prevention & control*
;
Humans
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Liver Neoplasms/drug therapy*
;
Niacinamide/therapeutic use*
;
Ozone/therapeutic use*
;
Phenylurea Compounds/adverse effects*
;
Quality of Life
;
Sorafenib/therapeutic use*
3.Emerging roles of ozone in skin diseases.
Journal of Central South University(Medical Sciences) 2018;43(2):114-123
Ozone was discovered in the mid-nineteenth century and is proven to have many therapeutic effects, including its common application as a disinfectant to kill microorganisms in various conditions. Ozone therapies have been utilized for various purposes ever since it was discovered. Extensive studies over a century have verified its therapeutic effects, consistency, and safety with minimal and preventable side effects in medical care. Emerging evidence revealed that ozone also plays important roles in the management and prevention of various skin disorders including infectious skin diseases, skin related allergic diseases, erythema scaly diseases, wound healing and ulcer recovery. Herein, the author now summarizes the recent clinical applications of ozone therapy in dermatology and provide commentary on what we have learned in our practice. Our focuses are the efficacy and safety of ozone therapies as well as the application prospects of ozone on various skin disorders. In addition, the author discusses the potential mechanisms involved in ozone therapy and the efforts we should make for.
Humans
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Ozone
;
therapeutic use
;
Skin Diseases
;
therapy
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Skin Ulcer
;
therapy
;
Wound Healing
4.Diffusion-Weighted Imaging for Pretreatment Evaluation and Prediction of Treatment Effect in Patients Undergoing CT-Guided Injection for Lumbar Disc Herniation.
Xiang Ke NIU ; Anup BHETUWAL ; Han Feng YANG
Korean Journal of Radiology 2015;16(4):874-880
OBJECTIVE: To determine whether a change in apparent diffusion coefficient (ADC) value could predict early response to CT-guided Oxygen-Ozone (O2-O3) injection therapy in patients with unilateral mono-radiculopathy due to lumbar disc herniation. MATERIALS AND METHODS: A total of 52 patients with unilateral mono-radiculopathy received a single intradiscal (3 mL) and periganglionic (5 mL) injection of an O2-O3 mixture. An ADC index of the involved side to the intact side was calculated using the following formula: pre-treatment ADC index = ([ADC involved side - ADC intact side] / ADC intact side) x 100. We analyzed the relationship between the pre-treatment Oswestry Disability Index (ODI) and the ADC index. In addition, the correlation between ODI recovery ratio and ADC index was investigated. The sensitivity and specificity of the ADC index for predicting response in O2-O3 therapy was determined. RESULTS: Oswestry Disability Index and the ADC index was not significantly correlated (r = -0.125, p = 0.093). The ADC index and ODI recovery ratio was significantly correlated (r = 0.819, p < 0.001). When using 7.10 as the cut-off value, the ADC index obtained a sensitivity of 86.3% and a specificity of 82.9% for predicting successful response to therapy around the first month of follow-up. CONCLUSION: This preliminary study demonstrates that the patients with decreased ADC index tend to show poor improvement of clinical symptoms. The ADC index may be a useful indicator to predict early response to CT-guided O2-O3 injection therapy in patients with unilateral mono-radiculopathy due to lumbar disc herniation.
Adult
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Aged
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Diffusion Magnetic Resonance Imaging/*methods
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Female
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Humans
;
Intervertebral Disc Displacement/*diagnosis/*therapy
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Lumbar Vertebrae/*pathology
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Male
;
Middle Aged
;
Oxygen/therapeutic use
;
Ozone/therapeutic use
;
Sensitivity and Specificity
;
Tomography, X-Ray Computed/*methods
;
Treatment Outcome
;
Young Adult
5.Treatment of middle-aged and aged patients with knee osteoarthritis of yang-deficiency induced cold-damp syndrome by ozone combined Chinese materia medica: a clinical research.
Juan-Hong LI ; Li-Xia ZHOU ; Gui-Ying LI ; Bin CHENG
Chinese Journal of Integrated Traditional and Western Medicine 2013;33(4):471-475
OBJECTIVETo observe the clinical efficacy of treating middle-aged and aged patients with knee osteoarthritis (KOA) of yang-deficiency induced cold-damp syndrome (YDICDS) by ozone combined Fugui Gutong Granule (FGG).
METHODSUsing a prospective, randomized controlled clinical trial, 200 KOA patients of YDICDS were randomly assigned to four groups. i.e., the control group (Group A), the Chinese medicine treatment group (Group B), the ozone group (Group C), and the Chinese-r medicine treatment plus ozone group (Group D).Patients in Group A took Voltaren Tablet. Those in Group B took FGG. Those in Group C received ozone injection (10 -18 mL) from knee joint cavity at 25 mg/L, once weekly for 4 weeks in total. Those in Group D received injection from knee joint cavity and took FGG. The therapeutic course for all was one month. The efficacy was assessed using visual analogue scale (VAS) and Western Ontario MacMaster University Osteoarthritis index (WOMAC).
RESULTSThe VAS score was obviously lower in Group D than in Group B and Group A at 24 h and 1 week (P <0. 05). After one month of treatment, the VAS score was obviously lower in Group D than in Group A, B, and C (P < 0.05). After treatment the total integral of WOMAC was 25.34 +/- 2.12 in Group D, obviously lower than that in Group A (44.72 +/- 6.57), Group B (40.58 +/- 5.98), and Group C (38.53 +/- 5. 13), showing statistical difference (P <0.05). The pain score, the joint stiffness score, the score for daily activities were lower in Group D than in Group A (P <0.05). The cured and markedly effective rate was 76.0% in Group D, higher than that of Group A (25. 0%), Group B (25. 0%), and Group C (43.8%), respectively (P < 0.05).
CONCLUSIONOzone combined FGG had advantages in alleviating joint pain, and improving joint stiffness and daily activities of middle-aged and aged patients with KOA of YDICDS.
Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; therapy ; Ozone ; therapeutic use ; Pain Measurement ; Phytotherapy ; Prospective Studies ; Treatment Outcome ; Yang Deficiency ; therapy
6.Effect of intra-articular ozone injection on serum and synovial TNF-α, TNFR I, and TNFR II contents in rats with rheumatoid arthritis.
Bin YU ; Hui-qiang CHEN ; Chang-huai LU ; Qing-rong LIN ; Bo-wei WANG ; Cheng-he QIN
Journal of Southern Medical University 2011;31(6):1055-1058
OBJECTIVETo observe the effects of intra-articular ozone injection at different concentrations on the contents of tumor necrosis factor-α (TNF-α), TNF receptor I (TNFR I), and TNFR II in the serum and synovium of rats with rheumatoid arthritis (RA) and explore the therapeutic mechanism of ozone in RA treatment.
METHODSForty-eight Wistar rats were randomized into 8 groups, including 5 ozone groups receiving intra-articular injection of 10, 20, 30, 40 or 50 µg/ml ozone, a blank control group, an oxygen group and a RA model group. All the rats, except for those in the blank control group, were subjected to hypodermic injection of bovine collagen II and complete Freunds adjuvant to induce RA. Ozone treatment was administered once weekly for 3 weeks starting at 21 days after the modeling. The swelling and thickness of the hind paws were observed, and the serum and synovial contents of TNF-α, TNFR I, and TNFR II were detected.
RESULTSAt the end of treatment, the paw thickness was reduced significantly in rats with 40 µg/ml ozone injection compared with that in the model RA group (P<0.01). The serum contents of TNF-α, TNFR I and TNFR II showed no significant difference between the RA model group, oxygen group and the ozone groups, but their synovial contents showed significant reductions in rats with 40 and 50 µg/ml ozone injection (P<0.01); the synovial TNFR I was significantly higher in 40 µg/ml ozone group than in the model group (P<0.05).
CONCLUSIONIntra-articular injection of 40 µg/ml ozone can attenuate synovitis in rats with RA, the mechanism of which may involve the inhibition of TNF-α and TNFR II activity and enhancement of TNFR I activity in the synovium.
Animals ; Arthritis, Rheumatoid ; metabolism ; therapy ; Injections, Intra-Articular ; Male ; Ozone ; administration & dosage ; therapeutic use ; Rats ; Rats, Wistar ; Receptors, Tumor Necrosis Factor, Type I ; metabolism ; Receptors, Tumor Necrosis Factor, Type II ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism
7.Application of ozone concentration detection in the medical aspects and its development.
Hailong JIN ; Shaoyan CHENG ; Junjie SONG ; Wenxue HONG
Journal of Biomedical Engineering 2011;28(2):429-432
This article introduces some commonly used methods of ozone concentration detection, including chemical method, UV absorption method, and electrochemical method etc., introduces the latest four ozone concentration sensors, and summarizes the advantages and disadvantages of each method. In addition, the article emphatically introduces the ozone's applications and development in the medical aspects. Prospects for the use of ozone concentration detection, ozone treatment and ozone therapy instrument are also demonstrated in it. The literature collected and reviewed on ozone concentration detection and ozone therapy includes 37 papers in English, and 50 papers in Chinese, but only 30 articles among them are included in this review (19 in Chinese and 11 in English), according to the principle of eliminating the old information and repetitive contents. The present paper selects only those on ozone, ozone concentration, ozone therapy and ozone therapy instrument.
Hepatitis
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drug therapy
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Humans
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Mouth Diseases
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drug therapy
;
Ozone
;
analysis
;
therapeutic use
8.Effect of medical ozone therapy on renal blood flow and renal function of patients with chronic severe hepatitis.
Xi-bing GU ; Xiao-juan YANG ; Hong-ying ZHU ; Yue-qin XU ; Xia-ying LIU
Chinese Medical Journal 2010;123(18):2510-2513
BACKGROUNDMedical ozone therapy system was reported to have certain effects on the treatment of severe hepatitis, but its mechanism is not very clear. One of the causes of death of severe hepatitis is complication of renal damage or hepatorenal syndrome. The present study aimed to observe effects of medical ozone therapy system on plasma renin activity (PRA), angiotensin II (AII), aldosterone (ALD), renal blood flow and renal function of patients with chronic severe hepatitis and explore mechanisms of medical ozone therapy in the treatment of severe hepatitis.
METHODSEighty-five cases with chronic severe hepatitis were randomly divided into ozone therapy group (43 cases) and control group (42 cases). The patients in the ozone therapy group were treated with basic treatments plus ozone therapy system. Basic autohemotherapy was used. One hundred milliliter venous blood was drawn from each patient, and was mixed with 100 ml (35 µg/ml) medical ozone and then was returned the blood to the patient intravenously, once every other day for 20 days. Only the basic treatments were given to the control group. PRA, AII, ALD, renal blood flow and damage to renal function of the two groups before treatment and 20 days after treatment were compared. Survival rates were also compared.
RESULTSTwenty days after the treatment, in ozone therapy group, PRA was (1.31 ± 0.12) ng·ml⁻¹·h⁻¹, AII (111.25 ± 17.35) pg/ml, ALD (251.31 ± 22.60) pg/ml, which decreased significantly compared with those before treatment (PRA (2.23 ± 0.13) ng·ml⁻¹·h⁻¹, AII (155.18 ± 19.13) pg/ml, ALD (405.31 ± 29.88) pg/ml, t = 4.67 - 14.23, P < 0.01), also lower than those of control group 20 days after the treatment (PRA (2.02 ± 0.11) ng·ml⁻¹·h⁻¹, AII (162.21 ± 15.32) pg/ml, ALD (401.20 ± 35.02) pg/ml, t = 4.97 - 15.61, P < 0.01); renal blood flow was (175.15 ± 28.20) ml/min, which increased compared with that before the treatment ((125.68 ± 21.25) ml/min) and was higher than that of control group 20 days after the treatment ((128.59 ± 23.15) ml/min, t = 4.78, 4.61, P < 0.01). Renal damage occurred in 2 cases (5%) in ozone therapy group, less than that in control group (9 cases, 21%) (χ² = 5.295, P < 0.05). Thirty-three cases (77%) in ozone therapy group vs. 16 cases (38%) in control group survived (χ² = 12.993, P < 0.01).
CONCLUSIONSBasic treatment plus medical ozone therapy for patients with chronic severe hepatitis could decrease PRA, AII and ALD levels significantly increase renal blood flow, prevent renal damage to certain extent and improve survival rate of the patients.
Adult ; Female ; Hepatitis, Chronic ; drug therapy ; Humans ; Kidney ; blood supply ; drug effects ; metabolism ; Male ; Middle Aged ; Ozone ; therapeutic use ; Renal Circulation ; drug effects
9.Electrophysiologial evaluation of ozone in treating of lumbar disc herniation with curving sheath-needle multi-direction rotating injection.
Qun-Wei QU ; Shao-Ming ZHU ; Jian-Bo ZHENG ; Xiu-Jian LIU ; Ming-Chun WANG ; Xiao-Ying XUE
China Journal of Orthopaedics and Traumatology 2010;23(10):765-768
OBJECTIVETo compare electrophysiological changes in treating lumbar disc herniation (LDH) with ozone by curving sheath-needle multi-direction rotating injection (CSNMRI) and conventional injection method.
METHODSFrom May 2005 to June 2009,100 patients with LDH were studied, included 68 males and 32 females, ranging in age from 25 to 58 years with an average of 44 years, in course of disease from 3 months to 8 years with an average of 8.8 months. All patients were numbered according to sequence of visit, and were completely randomly divided into group A and group B with DPS software, 50 cases in each group. All patients were injected ozone into lesion of intervertebral disc, in group A with CSNMRI and in group B with conventional method. The electrophysiologic study of all patients was performed respectively before treatment and at the 3 month after treatment. The electromyogram (EMG) of the main muscle groups of involved lower limb and the corresponding segments of sacrospinal muscle was tested; the duration and multiphase-wave rate of MUP were calculated. H-reflex of tibial nerve in both lower limbs was observed and the number of abnormal H-reflex and the H-wave latency were recorded.
RESULTSAfter treatment, the number of muscles with abnormal EMG was reduced to different degrees in each group, but there was more significant reduction in group A (P < 0.05 or 0.01); the duration and multiphase-wave rate of MUP in the two groups were both reduced and close to the normal level (P < 0.01), yet the changes in group A was more than that of group B (P < 0.05 or 0.01). There was no significant difference in the number of abnormal H-reflex before treatment between two groups, whereas was markedly lower in group A than that of group B after treatment (P < 0.05). After treatment, H-wave latency in two groups was shortened and become close to normal, but group B was more statistically significant than group B (P < 0.05).
CONCLUSIONThe neural electrophysiological abnormalities can reflect the degree of nerve root compression and damage, and is one of the objective indicators to estimate neuromuscular function. It can better meliorate abnormal electrophysiology to inject ozone to treat LDH with CSNMRI than conventional method.
Adult ; Aged ; Electrophysiological Phenomena ; Encephalocele ; drug therapy ; Female ; Humans ; Injections ; Intervertebral Disc Displacement ; drug therapy ; Lumbar Vertebrae ; Lumbosacral Region ; abnormalities ; Male ; Meningocele ; Middle Aged ; Ozone ; administration & dosage ; therapeutic use ; Young Adult
10.Effect of ozone water on the inflammation and repair in infected wounds.
Hua-jun HUANG ; Bin YU ; Qing-rong LIN ; Bo-wei WANG ; Hui-qiang CHEN
Journal of Southern Medical University 2010;30(3):515-518
OBJECTIVETo study the effect of ozone water in promoting the healing of infected wounds.
METHODSFifty Wistar rats were randomly divided into 5 groups, namely chlorhexidine treatment group, 5, 10, and 20 mg/L ozone water treatment groups, and the control group without any treatment. Infected wounds were induced on the back of the rats, and at 48 h of infection, chlorhexidine or ozone water was applied once daily for 9 days. Before and at days 3, 6, and 9 of the treatment, the wound changes were observed. The WBC in the tail venous blood was detected and the incised skin and muscular tissues were pathologically examined. RESULTS AMD CONCLUSION: Ozone water showed better effects in promoting the healing of the infected wound, especially at higher doses of 10 and 20 mg/L.
Animals ; Female ; Inflammation ; drug therapy ; Male ; Ozone ; therapeutic use ; Random Allocation ; Rats ; Rats, Wistar ; Wound Healing ; drug effects ; Wound Infection ; drug therapy

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