Search Results (144)

Background: Chronic pelvic toxicity induced by radiotherapy and/or chemotherapy (R/CIPT) is a debilitating sequela in gynecological cancer survivors, often refractory to conventional treatments and potentially linked to gut microbiota dysbiosis. Ozone therapy (OT), particularly rectal insufflation, demonstrates anti-inflammatory and redox-modulating effects through hormetic mechanisms (Nrf2 activation/NF-κB inhibition). We hypothesize that its clinical benefit is mediated, in part, by restoring gut microbial homeostasis. Objective: This manuscript proposes a clinical study to evaluate the impact of rectal OT on the gut microbiota of patients with gynecological cancers and chronic R/CIPT. Proposed Methods: A prospective, observational study of 38 patients is outlined: 19 with CTCAE v5.0 Grade ≥2 chronic R/CIPT receiving compassionate rectal OT (~40 sessions over 4 months), and 19 matched controls without toxicity. Stool samples for 16S rRNA sequencing will be collected from the OT group pre- and post-intervention and once from controls. Primary endpoints are changes in microbiota composition/diversity and pelvic toxicity scores (CTCAE v5.0, EORTC QLQ-CX24). Secondary endpoints include quality of life (EORTC QLQ-C30, EQ-5D-5L), anxiety/depression (HADS), and serum inflammatory/oxidative stress biomarker analysis. Anticipated Results and Conclusion: This will be the first study to prospectively investigate whether rectal OT’s effect correlates with a beneficial shift in the gut microbiota, specifically an increase in commensals (e.g., short-chain fatty acids producers) and a decrease in pathobionts. If successful, OT could be assessed as a novel, microbiota-targeting intervention for R/CIPT. The findings from this pilot study will provide the necessary groundwork for a future randomized controlled trial to definitively establish causality and efficacy. Full article

Depression is becoming more common in the face of modern life’s obstacles. Antidepressants are a fast-expanding pharmaceutical category. Antidepressant residues in water must be closely monitored and kept at levels that do not endanger human health, just like those of other psychotropic medications. Additionally, research has shown that these pollutants severely hinder aquatic life’s ability to migrate, reproduce, and interact with one another when they enter natural ecosystems. Antidepressants released into the natural environment can therefore be expected to have an impact on exposed fish and other aquatic species. There is a lot of information available about how exposure affects fish, but much of it is for exposure levels higher than those seen in their natural habitats. Antidepressants can bioaccumulate in fish tissues, and some behavioral effects have been documented for exposures that are relevant to the environment. As a result, antidepressant residue removal methods must be incorporated into contemporary wastewater treatment plant technology. In addition to covering a wide range of suggested treatment options and their ecotoxicological consequences on non-target organisms, this study discusses recent efforts to accomplish this goal. First, a thorough analysis of the harmful impacts on non-target people is provided. This work describes a variety of adsorptive methods that can make use of modern materials like molecularly imprinted polymers or ion-exchange resins or can rely on well-known and efficient adsorbents like silicates or activated carbon. Although extractive methods are also taken into consideration, they are now impractical due to the lack of reasonably priced and ecologically suitable solvents. Lastly, sophisticated oxidation methods are discussed, such as electrochemical alternatives, UV and gamma radiation, and ozone therapy. Notably, some of these techniques could totally mineralize antidepressant toxicants, either alone or in combination. Lastly, the topic of biological treatment with microorganisms is covered. This method can be very specific, but it usually prevents full mineralization. Full article

Musculoskeletal disorders are a major cause of lameness in horses, often necessitating innovative regenerative strategies to restore joint function and improve quality of life. This study investigated the effects of platelet-rich plasma (PRP), ozonized PRP, hyaluronic acid, paracetamol, and polyacrylamide hydrogel (NOLTREX^®) on the behavior of mesenchymal stem cells (MSCs) derived from equine synovial fluid. Synovial fluid samples were collected under strict cytological criteria to ensure viability, followed by in vitro expansion and phenotypic characterization of MSCs. Cultures were supplemented with the tested preparations, and cellular proliferation and viability were evaluated at 24 h, 72 h, and 7 days. PRP significantly promoted MSC proliferation in a time- and dose-dependent manner, with maximal effect at 10%. Hyaluronic acid stimulated growth, most pronounced at 1 mg/mL, while paracetamol induced a concentration-dependent proliferative response, strongest at 100 μg/mL. NOLTREX displayed a biphasic effect, initially inhibitory at high concentrations but stimulatory at 7 days. Ozonized PRP showed concentration-dependent redox activity, with lower doses maintaining viability and higher doses producing an initial suppression followed by delayed stimulation. Collectively, these findings support the therapeutic potential of PRP and related biologic preparations as intra-articular regenerative therapies in equine medicine, while underscoring the importance of dose optimization and standardized protocols to facilitate clinical translation. Full article

Introduction: In clinical practice, the presence of abnormal physiological root resorption frequently results in the retention of deciduous teeth. Also, unilateral mastication may contribute to the altered physiological process of root resorption. This delayed exfoliation and retention of deciduous teeth may compromise the integrity of adjacent soft tissue. In recent years, ozone therapy can be considered a promising strategy in accelerating healing and reducing pain in both traumatic and autoimmune ulcers. Case Presentation: This case report describes a 12 year-old male patient with localized damaged gingival tissue resulting from chronic trauma due to the retention of a deciduous tooth. Following the application of gaseous ozone therapy, complete mucosal healing was achieved. Conclusions: This case supports the potential of ozone therapy in paediatric soft tissue management. Full article

Ozone (O₃) has re-emerged in periodontology for its antimicrobial, oxygenating, and immunomodulatory actions, yet its role in regeneration remains contentious. This narrative review synthesizes current evidence on adjunctive ozone use in periodontal therapy, delineates cellular constraints—especially in periodontal ligament fibroblasts (PDLFs)—and explores mitigation strategies using bioactive compounds and advanced delivery platforms. Two recent meta-analyses indicate that adjunctive ozone with scaling and root planing yields statistically significant reductions in probing depth and gingival inflammation, with no significant effects on bleeding on probing, plaque control, or clinical attachment level; interpretation is limited by heterogeneity of formulations, concentrations, and delivery methods. Mechanistically, ozone imposes a dose-dependent oxidative burden that depletes glutathione and inhibits glutathione peroxidase and superoxide dismutase, precipitating lipid peroxidation, mitochondrial dysfunction, ATP depletion, and PDLF apoptosis. Concurrent activation of NF-κB and upregulation of IL-6/TNF-α, together with matrix metalloproteinase-mediated extracellular matrix degradation and tissue dehydration (notably with gaseous applications), further impairs fibroblast migration, adhesion, and ECM remodeling, constraining regenerative potential. Emerging countermeasures include co-administration of polyphenols (epigallocatechin-3-gallate, resveratrol, curcumin, quercetin), coenzyme Q10, vitamin C, and hyaluronic acid to restore redox balance, stabilize mitochondria, down-modulate inflammatory cascades, and preserve ECM integrity. Nanocarrier-based platforms (nanoemulsions, polymeric nanoparticles, liposomes, hydrogels, bioadhesive films) offer controlled ozone release and co-delivery of protectants, potentially widening the therapeutic window while minimizing cytotoxicity. Overall, current evidence supports ozone as an experimental adjunct rather than a routine regenerative modality. Priority research needs include protocol standardization, dose–response definition, long-term safety, and rigorously powered randomized trials evaluating bioactive-ozone combinations and nanocarrier systems in clinically relevant periodontal endpoints. Full article

Ozone (O₃) therapy has demonstrated antioxidant and anti-inflammatory properties, but the systemic administration of ozonated saline solution (O₃SS) remains underexplored. This study evaluates the cytotoxicity, antioxidant response, and immunomodulatory effects of O₃SS on murine microglial (BV2) and human endothelial (HUVEC) cells. Cells were exposed to increasing doses of O₃ (1, 5, or 10 μg/NmL) dissolved in saline. Viability assays showed that low doses (1 and 5 μg/NmL) enhanced cell proliferation without cytotoxicity, while the highest dose (10 μg/NmL) reduced viability and increased cell death. O₃SS treatment upregulated antioxidant genes, including Nrf2 and SOD1, and decreased reactive oxygen species in lipopolysaccharide (LPS)-stimulated microglia. Additionally, O₃SS modulated microglial phenotype by reducing pro-inflammatory markers (iNOS, IL-1β) and increasing anti-inflammatory markers (Arg-1, IL-10). Immunofluorescence confirmed enhanced Arg-1 protein expression, indicating a shift toward an anti-inflammatory state. These results suggest that low-dose O₃SS activates cellular antioxidant defenses and promotes an anti-inflammatory microglial phenotype, supporting its potential as a safe systemic O₃ therapy. Further studies are warranted to confirm in vivo efficacy and optimize clinical protocols. Full article

Background: Tendinopathy is a degenerative condition caused by mechanical overload, accounting for approximately 30% of musculoskeletal healthcare cases. It progresses through a process characterized by collagen disorganization, altered vascularization, and neuronal ingrowth. Traditional conservative treatments, such as therapeutic exercises, non-steroidal anti-inflammatory drugs, and physical therapies, are useful, but their effectiveness is sometimes only partial and there is a need to search for new potential solutions. Recent interest in oxygen–ozone (O₂-O₃) therapy stems from preliminary observations suggesting potential anti-inflammatory and regenerative effects. Nevertheless, its clinical role remains speculative and warrants thorough investigation beyond anecdotal evidence. Considering the heterogeneity of clinical presentations and treatment responses among patients, O₂-O₃ therapy has been proposed as a promising tool for tailoring personalized treatment strategies for tendinopathy. This review critically appraises the available literature concerning the mechanistic rationale and clinical applications of O₂-O₃ therapy in tendinopathy, with attention to both its theoretical underpinnings and the quality of empirical evidence. Methods: A literature search was conducted on O₂-O₃ therapy for tendinopathy using PubMed, Cochrane, and Embase, filtering for full-text articles published between 2004 and 2024. Recent clinical trials were included irrespective of evidence level, while excluding systematic reviews, duplicates, and irrelevant studies. Results: Ozone has been shown to modulate oxidative stress, promote neovascularization, and suppress pro-inflammatory cytokines. Both clinical and in vivo studies indicate that O₂-O₃ therapy relieves pain, enhances tendon healing, and improves biomechanical properties. Some comparative studies suggest that O₂-O₃ therapy might provide more sustained symptoms control than corticosteroids, but the heterogeneity of follow-up durations and outcome measures prevents definitive conclusions. Conclusions: O₂-O₃ therapy emerges as a potentially valuable adjunct in the management of chronic tendinopathy, particularly in cases unresponsive to conventional treatments. However, its clinical role remains to be clearly defined and its possible role in personalized medicine needs further exploration, particularly in relation to patient stratification and individualized treatment protocols. Further high-quality randomized controlled trials are warranted to validate its efficacy, determine long-term outcomes, and standardize treatment protocols to ensure safety and reproducibility. Full article

Background: Diabetes mellitus is a heterogeneous chronic disease with an increasing global prevalence. In Romania, 11.6% of the population is affected, yet only 6.46% receive treatment. Among diabetic patients, 15–25% develop skin lesions that may progress to ulceration and necrosis, significantly impairing quality of life and increasing the risk of complications. Methods: We conducted a prospective study including 28 patients (14 in the control group and 14 in the intervention group) with type I or II diabetes and chronic ulcers of the calf or foot (>4 cm²). The control group received standard therapy with debridement, dressings, antibiotics when indicated, and local and systemic ozone therapy. The intervention group was treated with an Integrative Therapeutic Protocol combining ozone therapy, pulsed electromagnetic field therapy (PEMF), colon hydrotherapy with probiotic supplementation, and an anti-inflammatory alkaline diet. Wound healing (reduction in ulcer surface area) was the primary endpoint; secondary endpoints included changes in glycemia and inflammatory biomarkers. Results: After 8 weeks, the intervention group achieved 86.2% re-epithelialization versus 58.2% in controls (p < 0.01). Significant improvements were also observed in blood glucose level (−38%), HbA1c (−25%), CRP (−26%), and fibrinogen (−28%) relative to baseline, with differences versus controls reaching statistical significance. Conclusions: The Integrative Therapeutic Protocol accelerated wound healing and improved glycemic and inflammatory profiles compared with ozone therapy alone. Although an alkaline diet was recommended, adherence and its specific contribution were not objectively monitored; therefore, this component should be interpreted with caution. Full article

Non-thermal plasma has attracted strong interest in medicine and agriculture due to its ability to generate reactive oxygen and nitrogen species (RONS). These species can stimulate wound healing and seed germination, but at higher levels they induce DNA damage—useful in cancer therapy but harmful when healthy cells must be preserved. Direct study of DNA damage in cells is difficult because of repair processes and protective barriers. To address this, we applied a dual-model system combining plasmid DNA and human lymphocytes exposed to plasma from the RPS40 device. Using selective scavengers, we identified hydroxyl radicals, ozone, and reactive nitrogen species as key mediators of DNA strand breaks and structural changes. Our results support a mechanistic model in which long-lived plasma-derived species (NOx, ozone, acids) dissolve in water and subsequently generate short-lived radicals such as hydroxyl radicals and peroxynitrite. These reactive molecules then directly attack DNA. This integrated approach—linking plasmid and cellular assays with scavenger-based identification of RONS—offers a novel and cost-effective method for dissecting plasma–DNA interactions. The findings provide mechanistic insight into how plasma-activated water damages DNA, guiding the safer and more effective application of plasma technologies in biomedical and agricultural contexts. Full article

The chemotherapeutic combination of bleomycin, etoposide, and cisplatin (BEP) is well-documented to exert gonadotoxic effects, ultimately leading to impaired fertility. This experimental rat study investigated the potential protective role of repeated medical ozone therapy in mitigating the deleterious effects of BEP treatment in male rats. Thirty-two adult male Sprague Dawley rats were randomly assigned to four groups: (i) a healthy control group, (ii) a group receiving injections of the BEP regimen over nine weeks, (iii) a group receiving the same BEP regimen plus medical ozone (1 mg/kg IP) twice weekly, and (iv) a group receiving only ozone therapy. BEP treatment significantly reduced sperm concentration and increased morphological abnormalities, both of which were partially restored by ozone co-administration. Ozone therapy also elevated testosterone and thyroid-stimulating hormone (TSH) levels when co-administered with BEP compared to BEP treatment alone. Oxidative stress analysis demonstrated that total oxidative status (TOS) and total antioxidant status (TAS) levels were significantly improved in the BEP + ozone group. Histopathological analysis revealed that ozone treatment ameliorated BEP-induced testicular damage, as evidenced by improved Johnsen scores and increased thickness of the seminiferous tubule epithelium. In conclusion, repeated medical ozone therapy appears to mitigate BEP-induced reproductive toxicity by preserving sperm quality, endocrine function, and redox homeostasis. Full article

The therapeutic management of extensive skin wounds in cats can be time-consuming and require multiple therapeutic interventions, which can have significant financial implications for pet owners. Reconstructive surgery is often necessary to close skin defects with tissue loss to provide a quicker patient recovery. Conventional therapies like systemic antibiotics, anti-inflammatories, and local dressings are not always successful due to antibiotic resistance or a poor response, such as no or delayed healing. For more than a century, ozone has been utilized as an excellent disinfectant, but caution should be taken due to its oxidizing properties. Only in the past decade have numerous studies established therapeutic dose ranges for a wider medical use of ozone. The objective of this study was to clinically evaluate ozone therapy as a complementary treatment supporting and completing plastic and reconstructive surgery in 4 cats with extensive skin defects. The results obtained, following the local application of ozone therapy before and after skin reconstruction in our patients, encourage the use of ozone as a complementary therapy in the management of extensive skin wounds treated surgically by different reconstructive techniques. Full article

Ozone (O₃) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O₃ dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O₃ doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O₃ make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O₃ is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O₃. In recent years, novel O₃ formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O₃, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O₃ and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O₃ through nanocarriers is a just-started challenge, and multiple prospects may be foreseen. Full article

Background: Additional therapies (e.g., laser, photodynamic therapy, and ozone) have been reported to improve mechanical instrumentation and immune response in non-surgical periodontal therapy (NSPT). With this systematic review we evaluated the effectiveness of ozone therapy in reducing inflammation and progression of periodontal disease. Methods: Three electronic databases (PubMed, Scopus, and Cochrane Library) were searched for randomized and clinical trials on ozone therapy (gas, liquid, gel/oil) combined with NSPT. The study design followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and the risk of bias was assessed using the RoB-2 tool. Results: Eight of the twenty-two studies reviewed reported on gaseous ozone, nine on ozone water, and five on ozonated oil/gel as an adjunct to mechanical periodontal instrumentation, often with scaling and root planing (SRP). Ozone was found to be more effective than SRP alone in treating inflammation, as measured with the gingival index (VMD −0.32; 95% confidence interval (CI) (−0.41; −0.24); p < 0.00001) and compared to chlorhexidine (CHX) (ozone gel; VMD −0.10; 95% CI (−0.20; −0.01); p = 0.03). The study findings were inconsistent, however, with several reporting clinical and microbiological benefit while others observed no marked improvement with the addition of ozone therapy to NSPT. Conclusions: While ozone therapy may represent a useful adjunct to NSPT, further research with larger study groups is warranted to determine its effectiveness. Full article

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have increased the number of patients living with CIPN. The only evidence-based treatment for CIPN-related pain, duloxetine, provides only modest clinical benefit, and there is no effective clinical management option for numbness and tingling. Several experimental studies and clinical reports suggest that adjuvant ozone treatment may be beneficial in managing CIPN. Methods: This narrative review aims to provide an overview of current knowledge regarding CIPN and ozone therapy. Specifically, it summarizes experimental studies (18) and clinical reports (27) published between 1995 and 2025 that offer preliminary evidence supporting the potential role of ozone treatment in managing CIPN, highlighting the need for ongoing randomized clinical trials to establish its efficacy. Additionally, this review highlights existing gaps in the literature and proposes directions for future research. Results: The hypothesized mechanisms of action and experimental findings suggest that ozone therapy may be a valuable intervention for CIPN, a concept supported by preliminary clinical observations. Conclusions: Clinically relevant approaches for established CIPN are currently unavailable. While preliminary data suggest a potential role of ozone therapy, clinical evidence remains limited. Further high-quality randomized controlled trials are needed to confirm its efficacy and safety in this context; several trials are currently ongoing. Full article

Background/Objectives: Surgery is the treatment of choice for symptomatic disc herniation after unsuccessful conservative management. This prospective study compared the impact on clinical and hospital outcomes of intradiscal ozone treatment vs. surgery (microdiscectomy/discectomy) in our clinical practice. Methods: Intradiscal ozone treatment was offered to 70 patients with scheduled surgery because of lumbar disc herniation. Initial treatment was surgery in 38 patients and ozone infiltration in 32 patients: lumbar and sciatic pain (Visual Analog Scale), Roland-Morris Disability Questionnaire score, days of hospital admission, and direct hospital costs were recorded during 24 months of follow-up. Results: At 12 and 24 months, lumbar pain, sciatic pain, and Roland-Morris score decreased significantly within both groups (p < 0.001). At 24 months, compared to the initial surgery, the initial intradiscal ozone treatment showed similar clinical outcomes with significantly lower requirements of surgery (100% versus 47%, p < 0.001) and lower hospital stay [median 2.5 (2–3) versus 0.5 (0–2) days, p < 0.001]. Direct hospital costs were significantly lower with initial ozone treatment at 12 months (p = 0.040). Conclusions: In our real-world prospective study, after 24 months of follow-up, initial intradiscal ozone treatment avoided surgery in more than half of patients and provided similar clinical outcomes with lower hospitalization requirements. In patients with lumbar disc herniation requiring surgery (microdiscectomy/discectomy), initial intradiscal ozone treatment could offer benefits for patients and healthcare service providers (NCT00566007). Full article